86 results match your criteria 2020 serendipitously


Making HSP90 Inhibitors Great Again? Unite for Better Cancer Immunotherapy.

Authors:
Michael W Graner

Cell Chem Biol 2021 Feb;28(2):118-120

Department of Neurosurgery, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address:

HSP90 inhibitors are in numerous cancer clinical trials, but treatments often induce toxicity at effective dosages. In this issue of Cell Chemical Biology, Zavareh et al. (2020) serendipitously found that HSP90 inhibitors, at manageable doses, can reduce target cell expression of immune checkpoint molecules, potentially enabling improved anti-cancer immunotherapy. Read More

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February 2021

Machine Gaze: Self-Identification Through Play With a computer Vision-Based Projection and Robotics System.

Front Robot AI 2020 17;7:580835. Epub 2020 Dec 17.

Department of Art, Queens College City University of New York, New York, NY, United States.

Children begin to develop self-awareness when they associate images and abilities with themselves. Such "construction of self" continues throughout adult life as we constantly cycle through different forms of self-awareness, seeking, to redefine ourselves. Modern technologies like screens and artificial intelligence threaten to alter our development of self-awareness, because children and adults are exposed to machines, tele-presences, and displays that increasingly become part of human identity. Read More

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December 2020

Radiofrequency Ablation of the Splanchnic Nerve and Superior Hypogastric Plexus for Chronic Abdominal Pain Status Post-Abdominal Surgery.

Cureus 2020 Dec 20;12(12):e12189. Epub 2020 Dec 20.

Anesthesiology, Louisiana State University Health Sciences Center, Shreveport, USA.

Gastrointestinal cancers, such as malignant carcinoid tumor and pancreatic cancer, are responsible for excruciating and debilitating abdominal pain. Too often, patients are placed on chronic high-dose opioids, but the pain remains poorly controlled. It is incumbent on the medical team to approach the patient's debilitating pain in a thorough multi-modal fashion. Read More

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December 2020

Topoisomerase 2B Decrease Results in Diastolic Dysfunction p53 and Akt: A Novel Pathway.

Front Cardiovasc Med 2020 6;7:594123. Epub 2020 Nov 6.

Department of Cardiology, Division of Internal Medicine MD Anderson Cancer Center, Houston, TX, United States.

Diastolic dysfunction is condition of a stiff ventricle and a function of aging. It causes significant cardiovascular mortality and morbidity, and in fact, three million Americans are currently suffering from this condition. To date, all the pharmacological clinical trials have been negative. Read More

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November 2020

An Alternative HIV-1 Non-Nucleoside Reverse Transcriptase Inhibition Mechanism: Targeting the p51 Subunit.

Molecules 2020 Dec 13;25(24). Epub 2020 Dec 13.

Bioinformatics Institute, A*STAR, 30 Biopolis Street, #07-01 Matrix, Singapore 138671, Singapore.

The ongoing development of drug resistance in HIV continues to push for the need of alternative drug targets in inhibiting HIV. One such target is the Reverse transcriptase (RT) enzyme which is unique and critical in the viral life cycle-a rational target that is likely to have less off-target effects in humans. Serendipitously, we found two chemical scaffolds from the National Cancer Institute (NCI) Diversity Set V that inhibited HIV-1 RT catalytic activity. Read More

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December 2020

A Comprehensive Experimental Guide to Studying Cross-Presentation in Dendritic Cells In Vitro.

Curr Protoc Immunol 2020 12;131(1):e115

The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, New York.

Cross-presentation was first observed serendipitously in the 1970s. The importance of it was quickly realized and subsequently attracted great attention from immunologists. Since then, our knowledge of the ability of certain antigen presenting cells to internalize, process, and load exogenous antigens onto MHC-I molecules to cross-prime CD8 T cells has increased significantly. Read More

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December 2020

Syndecan-1 Promotes Streptococcus pneumoniae Corneal Infection by Facilitating the Assembly of Adhesive Fibronectin Fibrils.

mBio 2020 12 8;11(6). Epub 2020 Dec 8.

Department of Medicine, Boston Children's Hospital, Boston, Massachusetts, USA

Subversion of heparan sulfate proteoglycans (HSPGs) is thought to be a common virulence mechanism shared by many microbial pathogens. The prevailing assumption is that pathogens co-opt HSPGs as cell surface attachment receptors or as inhibitors of innate host defense. However, there are few data that clearly support this idea We found that deletion of syndecan-1 (Sdc1), a major cell surface HSPG of epithelial cells, causes a gain of function in a mouse model of scarified corneal infection, where corneas were significantly less susceptible to infection. Read More

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December 2020

Reactivity-Based Screening for Citrulline-Containing Natural Products Reveals a Family of Bacterial Peptidyl Arginine Deiminases.

ACS Chem Biol 2020 12 29;15(12):3167-3175. Epub 2020 Nov 29.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a family of natural products defined by a genetically encoded precursor peptide that is processed by associated biosynthetic enzymes to form the mature product. Lasso peptides are a class of RiPP defined by an isopeptide linkage between the N-terminal amine and an internal Asp/Glu residue with the C-terminal sequence threaded through the macrocycle. This unique lariat topology, which typically provides considerable stability toward heat and proteases, has stimulated interest in lasso peptides as potential therapeutics. Read More

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December 2020

Validation of Omega Subunit of RNA Polymerase as a Functional Entity.

Biomolecules 2020 11 23;10(11). Epub 2020 Nov 23.

Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India.

The bacterial RNA polymerase (RNAP) is a multi-subunit protein complex (α2ββ'ω σ) containing the smallest subunit, ω. Although identified early in RNAP research, its function remained ambiguous and shrouded with controversy for a considerable period. It was shown before that the protein has a structural role in maintaining the conformation of the largest subunit, β', and its recruitment in the enzyme assembly. Read More

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November 2020

Isocaloric low protein diet in a mouse model for vanishing white matter does not impact ISR deregulation in brain, but reveals ISR deregulation in liver.

Nutr Neurosci 2020 Nov 25:1-12. Epub 2020 Nov 25.

Child Neurology, Emma Children's Hospital, Amsterdam University Medical Centers, Vrije Universiteit and Amsterdam Neuroscience, Amsterdam, the Netherlands.

Vanishing white matter (VWM) is a genetic brain white matter disorder caused by mutations in eIF2B. eIF2B is central in the integrated stress response (ISR), during which its activity is inhibited by various cellular stresses. VWM is a chronic progressive disease with episodes of rapid neurological deterioration provoked by stresses. Read More

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November 2020

Long-Term Observation of a Man With Severe Obesity and Undiagnosed Monogenic Diabetes Serendipitously Treated With Metabolic Surgery.

J Investig Med High Impact Case Rep 2020 Jan-Dec;8:2324709620974871

Khoo Teck Puat Hospital, Singapore, Singapore.

A 43-year-old man, with severe obesity (43 kg/m) and diabetes (presumed as type 2 diabetes [T2D]), underwent vertical sleeve gastrectomy in 2009 and Roux-en-Y gastric bypass in 2013. Recently, whole exome sequencing (conducted to search for monogenic obesity) serendipitously revealed that the individual harbored a heterozygous glucokinase () variant p.(Arg422Leu) that was bioinformatically strongly predicted to be likely pathogenic. Read More

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November 2020

ALICE: a hybrid AI paradigm with enhanced connectivity and cybersecurity for a serendipitous encounter with circulating hybrid cells.

Theranostics 2020 2;10(24):11026-11048. Epub 2020 Sep 2.

College of Engineering, Peking University, Beijing 100871, China.

A fully automated and accurate assay of rare cell phenotypes in densely-packed fluorescently-labeled liquid biopsy images remains elusive. Employing a hybrid artificial intelligence (AI) paradigm that combines traditional rule-based morphological manipulations with modern statistical machine learning, we deployed a next generation software, ALICE (Automated Liquid Biopsy Cell Enumerator) to identify and enumerate minute amounts of tumor cell phenotypes bestrewed in massive populations of leukocytes. As a code designed for futurity, ALICE is armed with internet of things (IOT) connectivity to promote pedagogy and continuing education and also, an advanced cybersecurity system to safeguard against digital attacks from malicious data tampering. Read More

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September 2020

Discovery and characterization of ACE2 - a 20-year journey of surprises from vasopeptidase to COVID-19.

Clin Sci (Lond) 2020 09;134(18):2489-2501

School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT,U.K.

Angiotensin-converting enzyme (ACE) is a zinc membrane metallopeptidase that plays a key role in regulating vasoactive peptide levels and hence cardiovascular activity through its conversion of angiotensin I (Ang I) to Ang II and its metabolism of bradykinin. The discovery of its homologue, ACE2, 20 years ago has led to intensive comparisons of these two enzymes revealing surprising structural, catalytic and functional distinctions between them. ACE2 plays multiple roles not only as a vasopeptidase but also as a regulator of amino acid transport and serendipitously as a viral receptor, mediating the cellular entry of the coronaviruses causing severe acute respiratory syndrome (SARS) and, very recently, COVID-19. Read More

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September 2020

XMU-MP-1 induces growth arrest in a model human mini-organ and antagonises cell cycle-dependent paclitaxel cytotoxicity.

Cell Div 2020 17;15:11. Epub 2020 Sep 17.

Centre for Dermatology Research, University of Manchester & NIHR Biomedical Research Centre, Manchester, M13 9PT UK.

Background: XMU-MP-1 is an inhibitor of the Hippo pathway kinases MST1/2 and has been shown to promote the downstream activation of the pro-proliferative, pro-regenerative and anti-apoptotic transcriptional regulator YAP1. We tested whether XMU-MP-1 can activate YAP1 in a model human mini-organ, namely the hair follicle, to determine whether it can be pharmacologically exploited to promote regeneration in the hair follicle as a novel strategy to treat pathological hair loss disorders.

Results: XMU-MP-1 treatment inhibited MOB1 phosphorylation but did not increase active YAP1 in the hair follicle. Read More

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September 2020

Self-assembling peptides: From a discovery in a yeast protein to diverse uses and beyond.

Authors:
Shuguang Zhang

Protein Sci 2020 11 10;29(11):2281-2303. Epub 2020 Oct 10.

Laboratory of Molecular Architecture, Media Lab, Massachusetts Institute of Technology, 77 Massachusetts Avenue E15-391, Cambridge, Massachusetts, 02139-4306, USA.

Well-defined nanofiber scaffold hydrogels made of self-assembling peptides have found their way into various 3D tissue culture and clinical products. I reflect initial puzzlement of the unexpected discovery, gradual understanding of how these peptides undergo self-assembly, to eventually translating designer biological scaffolds into commercial products. Peptides are ubiquitous in nature and useful in many fields. Read More

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November 2020

Boranes: The Boron Subhydride BH with a Distorted β-Boron Crystal Structure.

Inorg Chem 2020 Sep 3;59(18):13295-13300. Epub 2020 Sep 3.

Mineralogisch-Petrographisches Institut, Universität Hamburg, 20146 Hamburg, Germany.

A single crystal of the boron subhydride BH was serendipitously obtained while attempting to synthesize β-boron. An accurate crystal structure analysis revealed a distorted β-boron framework with the noncentrosymmetric space group 3. We have found one interstitial site occupied by boron. Read More

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September 2020

Induced ferroelectric phases in SrTiO by a nanocomposite approach.

Nanoscale 2020 Sep 28;12(35):18193-18199. Epub 2020 Aug 28.

Center for Integrated Nanotechnologies (CINT), Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA.

Inducing new phases in thick films via vertical lattice strain is one of the critical advantages of vertically aligned nanocomposites (VANs). In SrTiO (STO), the ground state is ferroelastic, and the ferroelectricity in STO is suppressed by the orthorhombic transition. Here, we explore whether vertical lattice strain in three-dimensional VANs can be used to induce new ferroelectric phases in SrTiO:MgO (STO:MgO) VAN thin films. Read More

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September 2020

Directed evolution of the B. subtilis nitroreductase YfkO improves activation of the PET-capable probe SN33623 and CB1954 prodrug.

Biotechnol Lett 2021 Jan 26;43(1):203-211. Epub 2020 Aug 26.

School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.

Objectives: To use directed evolution to improve YfkO-mediated reduction of the 5-nitroimidazole PET-capable probe SN33623 without impairing conversion of the anti-cancer prodrug CB1954.

Results: Two iterations of error-prone PCR, purifying selection, and FACS sorting in a DNA damage quantifying GFP reporter strain were used to identify three YfkO variants able to sensitize E. coli host cells to at least 2. Read More

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January 2021

Enhancing intracellular accumulation and target engagement of PROTACs with reversible covalent chemistry.

Nat Commun 2020 08 26;11(1):4268. Epub 2020 Aug 26.

Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX, 77030, USA.

Current efforts in the proteolysis targeting chimera (PROTAC) field mostly focus on choosing an appropriate E3 ligase for the target protein, improving the binding affinities towards the target protein and the E3 ligase, and optimizing the PROTAC linker. However, due to the large molecular weights of PROTACs, their cellular uptake remains an issue. Through comparing how different warhead chemistry, reversible noncovalent (RNC), reversible covalent (RC), and irreversible covalent (IRC) binders, affects the degradation of Bruton's Tyrosine Kinase (BTK), we serendipitously discover that cyano-acrylamide-based reversible covalent chemistry can significantly enhance the intracellular accumulation and target engagement of PROTACs and develop RC-1 as a reversible covalent BTK PROTAC with a high target occupancy as its corresponding kinase inhibitor and effectiveness as a dual functional inhibitor and degrader, a different mechanism-of-action for PROTACs. Read More

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A Serendipitous One-Pot Cyanation/Hydrolysis/Enamide Formation: Direct Access to 3-Methyleneisoindolin-1-ones.

Chemistry 2021 Jan 3;27(2):628-633. Epub 2020 Dec 3.

Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai, 400076, India.

A direct, one-pot conversion of 2'-haloacetophenones to 3-methyleneisoindolin-1-one scaffolds using CuCN as the sole reagent without the need for moisture-free or anaerobic conditions is reported. This serendipitously discovered transformation with a broad substrate scope provides a significantly different route towards these important scaffolds. The scope of the method has also been further extended towards the synthesis of three special scaffolds, which are analogous to various bio-active drugs. Read More

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January 2021

Processable dispersions of photocatalytically active nanosheets derived from titanium diboride: self assembly into hydrogels and paper-like macrostructures.

Nanoscale 2020 Aug 12;12(32):17121-17131. Epub 2020 Aug 12.

Discipline of Chemical Engineering, Indian Institute of Technology Gandhinagar, Palaj, Gujarat 382355, India.

Titanium diboride (TiB), a layered ceramic material, is well-known for its ultrahigh strength, wear resistance, and chemical inertness. In this work, we present a simple one-pot chemical approach that yields sheet-like nanostructures from TiB. We serendipitously found that TiB crystals can undergo complete dissolution in a mild aqueous solution of HO under ambient conditions. Read More

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20 Years of Medicinal Chemistry - Always Look at the Bright Side (of Life).

Authors:
Christoph Boss

Chimia (Aarau) 2020 Aug;74(7):549-560

Idorsia Pharmaceuticals, Ltd., Hegenheimermattweg 91, CH-4123 Allschwil, Switzerland;, Email:

This paper summarizes a personal perspective on key learnings from projects the author was involved in over the last 20 years. For example, the discovery of , the most successful molecule to date from this personal collection, marketed by J&J for the treatment of pulmonary arterial hypertension (PAH). [1] Then the discovery of , a dual orexin receptor antagonist for the treatment of insomnia disorder with a serendipitously short story from the screening hit to the drug [2] followed by the identification of , another dual orexin receptor antagonist. Read More

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MALAT1 as a Versatile Regulator of Cancer: Overview of the updates from Predatory role as Competitive Endogenous RNA to Mechanistic Insights

Curr Cancer Drug Targets 2020 07 30. Epub 2020 Jul 30.

Clinica Oncologica, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I -GM Lancisi -G Salesi di Ancona, Via Conca 71, 60126 Ancona. Italy.

The central dogma of molecular biology, has remained a cornerstone of classical molecular biology. However, serendipitously discovered microRNAs (miRNAs) in nematodes paradigmatically shifted our current knowledge of the intricate mechanisms during transitions from transcription to translation. The discovery of miRNA captured considerable attention and appreciation, and we had witnessed an explosion in the field of non-coding RNAs. Read More

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Two dimensional speckle tracking echocardiography detects cardiac allograft stage III vasculopathy in recipients of heart transplants with preserved systolic function.

Acta Cardiol 2020 Jul 31:1-11. Epub 2020 Jul 31.

CNN Headquarters, New York, NY, USA.

Facile identification of cardiac allograft vasculopathy (CAV), extensively prevalently identifiable across recipients of cardiac explanted allografts, has proven challenging using non-invasive modalities exclusively. We consequently sought to evaluate diagnostic precision and accuracy of two-dimensional speckle tracking echocardiography (2D-STE) to the end of detecting international society heart & lung transplantation stage III graft vasculopathy (ISHLT-CAV) in individuals having received cardiac allografts by the meritorious pre-mortem scripted or verbalised indication of a benevolent benefactor personally or impersonally to a consanguineous Beloved to permit a sequential series of cuts to be made upon one's true corporal remnant successive to the terminal micro-epoch concluding viable organ perfusion possessing dynamic contractility of the myocardium failing to recede approximately a standard deviation from the central tendency metrically corresponding with the fraction of residual blood remaining within the chambered confines of the left ventricular muscle (LVEF). We successively sought to evaluate 39 individuals having unfortunately succumbed to the undesired incipient inaugural development of ISHLTCAV and two receding the quantal equivalent of the triplicate of fortnight beneficiaries of explanted cardiac allografts failing to manifest findings correlatively indicating abnormal patterns of -expressive contraction or -receptive relaxation of the myocardial wall identifiable by inspection, auscultation, palpation, and percussion of the integumental or mucosal surfaces of the patient or non-invasive static and dynamic visualisation of organ function. Read More

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Interdependent YpsA- and YfhS-Mediated Cell Division and Cell Size Phenotypes in .

mSphere 2020 07 22;5(4). Epub 2020 Jul 22.

Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, Florida, USA

Although many bacterial cell division factors have been uncovered over the years, evidence from recent studies points to the existence of yet-to-be-discovered factors involved in cell division regulation. Thus, it is important to identify factors and conditions that regulate cell division to obtain a better understanding of this fundamental biological process. We recently reported that in the Gram-positive organisms and , increased production of YpsA resulted in cell division inhibition. Read More

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Mosaic Analysis with Double Markers reveals IGF1R function in granule cell progenitors during cerebellar development.

Dev Biol 2020 09 19;465(2):130-143. Epub 2020 Jul 19.

Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, USA. Electronic address:

During cerebellar development, granule cell progenitors (GCPs) proliferate exponentially for a fixed period, promoted by paracrine mitogenic factor Sonic Hedgehog (Shh) secreted from Purkinje cells (PCs). Dysregulation of Shh signaling leads to uncontrolled GCP proliferation and medulloblastoma. Serendipitously our previous work discovered insulin-like growth factor 1 (IGF1) as another key driver for medulloblastoma, which led to the current investigation into the role of IGF1 in GCPs during normal development. Read More

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September 2020

Crystal structure of SrCo(OH)(PO), a new hy-droxy-phosphate.

Acta Crystallogr E Crystallogr Commun 2020 Jul 5;76(Pt 7):1022-1026. Epub 2020 Jun 5.

Laboratoire de Chimie Appliquée des Matériaux, Centre des Sciences des Matériaux, Faculty of Science, Mohammed V University in Rabat, Avenue Ibn Batouta, BP 1014, Rabat, Morocco.

Single crystals of strontium tetra-cobalt tris-(orthophosphate) hydroxide, SrCo(OH)(PO), were grown serendipitously under hydro-thermal conditions at 473 K. The crystal structure consists of undulating chains of edge-sharing [CoO] octa-hedra that are linked into (010) layers by common vertices between chains. Adjacent layers are linked along [010] into a framework structure by tetra-hedral [CoO] units and by PO tetra-hedra. Read More

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Dual-Functionalisation of Fluorophores for the Preparation of Targeted and Selective Probes.

Angew Chem Int Ed Engl 2020 11 2;59(46):20290-20301. Epub 2020 Sep 2.

School of Chemistry, The University of Sydney, NSW, 2006, Sydney, Australia.

A key current challenge in biological research is the elucidation of the that roles chemicals and chemical reactions play in cellular function and dysfunction. Of the available cellular imaging techniques, fluorescence imaging offers a balance between sensitivity and resolution, enabling the cost-effective and rapid visualisation of model biological systems. Importantly, the use of responsive fluorescent probes in conjunction with ever-advancing microscopy and flow cytometry techniques enables the visualisation, with high spatiotemporal resolution, of both specific chemical species and chemical reactions in living cells. Read More

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November 2020

Repeat percutaneous recanalizations of a discontinuous pulmonary artery: A very "lucky" vessel.

Ann Pediatr Cardiol 2020 Apr-Jun;13(2):163-166. Epub 2020 Mar 20.

Pediatric Cardiology and GUCH Unit, Heart Hospital "G. Pasquinucci", Tuscany-National Council of Research Foundation "G. Monasterio", Massa, Italy.

Pulmonary artery (PA) discontinuity with ductal origin of a major pulmonary branch is a rare congenital anomaly that can be diagnosed as an isolated lesion or in association with major cardiac malformations. Arterial duct (AD) closure results in complete disappearance of the dependent PA, thus leading to the misdiagnosis of "congenital PA absence." Neonatal AD transcatheter recanalization is considered a cost-effective approach in view of later, lower-risk surgical recruitment of the disconnected PA. Read More

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