37,713 results match your criteria full-length human

Comparative studies on the substrate specificity and defucosylation activity of three α-l-fucosidases using synthetic fucosylated glycopeptides and glycoproteins as substrates.

Bioorg Med Chem 2021 Jun 7;42:116243. Epub 2021 Jun 7.

Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA. Electronic address:

Core fucosylation is the attachment of an α-1,6-fucose moiety to the innermost N-acetyl glucosamine (GlcNAc) in N-glycans in mammalian systems. It plays a pivotal role in modulating the structural and biological functions of glycoproteins including therapeutic antibodies. Yet, few α-l-fucosidases appear to be capable of removing core fucose from intact glycoproteins. Read More

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Long read transcript profiling of ion channel splice isoforms.

Methods Enzymol 2021 7;654:345-364. Epub 2021 Apr 7.

Department of Psychiatry, University of Oxford, Oxford, United Kingdom; Oxford Health NHS Foundation Trust, Oxford, United Kingdom. Electronic address:

Alternative splicing of RNA transcripts allows a single gene to generate multiple products and is a key means of generating functionally diverse voltage-gated ion channels. Splicing can be regulated according to cell type, cell state, and stage of development to produce a bespoke complement of protein isoforms. Characterizing the identities of full-length transcript isoforms is essential in order to fully understand a gene's expression and function. Read More

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Sequences in the stalk domain regulate autoinhibition and ciliary tip localization of the immotile kinesin-4 KIF7.

J Cell Sci 2021 06 10. Epub 2021 Jun 10.

Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.

The kinesin-4 member KIF7 plays critical roles in Hedgehog signaling in vertebrate cells. KIF7 is an atypical kinesin as it binds to microtubules but is immotile. We demonstrate that, like conventional kinesins, KIF7 is regulated by autoinhibition as the full-length protein is inactive for microtubule binding in cells. Read More

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The mechanism of full activation of tumor suppressor PTEN at the phosphoinositide-enriched membrane.

iScience 2021 May 17;24(5):102438. Epub 2021 Apr 17.

Computational Structural Biology Section, Frederick National Laboratory for Cancer Research in the Laboratory of Cancer Immunometabolism, National Cancer Institute, Frederick, MD 21702, USA.

Tumor suppressor PTEN, the second most highly mutated protein in cancer, dephosphorylates signaling lipid PIP produced by PI3Ks. Excess PIP promotes cell proliferation. The mechanism at the membrane of this pivotal phosphatase is unknown hindering drug discovery. Read More

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Origins and Evolution of the Primate Hepatitis B Virus.

Front Microbiol 2021 24;12:653684. Epub 2021 May 24.

Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.

Recent interest in the origins and subsequent evolution of the hepatitis B virus (HBV) has strengthened with the discovery of ancient HBV sequences in fossilized remains of humans dating back to the Neolithic period around 7,000 years ago. Metagenomic analysis identified a number of African non-human primate HBV sequences in the oldest samples collected, indicating that human HBV may have at some stage, evolved in Africa following zoonotic transmissions from higher primates. Ancestral genotype A and D isolates were also discovered from the Bronze Age, not in Africa but rather Eurasia, implying a more complex evolutionary and migratory history for HBV than previously recognized. Read More

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Structural analysis of the full-length human LRRK2.

Cell 2021 Jun 3. Epub 2021 Jun 3.

Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address:

Mutations in leucine-rich repeat kinase 2 (LRRK2) are commonly implicated in the pathogenesis of both familial and sporadic Parkinson's disease (PD). LRRK2 regulates critical cellular processes at membranous organelles and forms microtubule-based pathogenic filaments, yet the molecular basis underlying these biological roles of LRRK2 remains largely enigmatic. Here, we determined high-resolution structures of full-length human LRRK2, revealing its architecture and key interdomain scaffolding elements for rationalizing disease-causing mutations. Read More

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A new method to determine the optimal orientation of Slim Modiolar cochlear implant electrode array insertion.

Ideggyogy Sz 2021 May;74(5-6):191-195

University of Szeged, Department of Oto-Rhino-Laryngology and Head-Neck Surgery, Szeged.

Background And Purpose: Our goal was to determine the optimal orientation of insertion of the Slim Modiolar electrode and develop an easy-to-use method to aid implantation surgery. In some instances, the electrode arrays cannot be inserted in their full length. This can lead to buckling, interscalar dislocation or tip fold-over. Read More

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Association of KCTD15 gene with fat deposition in pigs.

J Anim Physiol Anim Nutr (Berl) 2021 Jun 9. Epub 2021 Jun 9.

National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing, China.

KCTD15 is associated with body mass index and fat deposition in humans, mice and chickens. However, the function of KCTD15 in pig fat deposition remains unclear. In this study, we cloned and analysed the cDNA sequence of porcine KCTD15. Read More

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Efficacy of behavioral audiological tests in identifying cochlear synaptopathy: a systematic review.

Eur Arch Otorhinolaryngol 2021 Jun 9. Epub 2021 Jun 9.

Department of Audiology, All India Institute of Speech and Hearing, Mysore, Karnataka, 570006, India.

Purpose: Cochlear synaptopathy or hidden hearing loss is difficult to assess due to the lack of sensitivity with standard audiological tests. Poor speech perception, especially in the presence of noise or tinnitus, is the most common complaint of these patients. The purpose of this systematic review is to identify articles in peer-reviewed journals that used behavioral measures in the effective assessment of cochlear synaptopathy or hidden hearing loss. Read More

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A versatile reverse genetics platform for SARS-CoV-2 and other positive-strand RNA viruses.

Nat Commun 2021 06 8;12(1):3431. Epub 2021 Jun 8.

School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, QLD, Australia.

The current COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We demonstrate that despite the large size of the viral RNA genome (~30 kb), infectious full-length cDNA is readily assembled in vitro by a circular polymerase extension reaction (CPER) methodology without the need for technically demanding intermediate steps. Overlapping cDNA fragments are generated from viral RNA and assembled together with a linker fragment containing CMV promoter into a circular full-length viral cDNA in a single reaction. Read More

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Dynamic, Variable Oligomerization and the Trafficking of Variant Surface Glycoproteins of Trypanosoma brucei.

Traffic 2021 Jun 7. Epub 2021 Jun 7.

Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo (SUNY), Buffalo, New York, USA.

African trypanosomes cause disease in humans and livestock, avoiding host immunity by changing the expression of variant surface glycoproteins (VSGs), the major glycosylphosphatidylinositol (GPI) anchored antigens coating the surface of the bloodstream stage. Proper trafficking of VSGs is therefore critical to pathogen survival. The Valence Model argues that GPI anchors regulate progression and fate in the secretory pathway and that, specifically, a valence of two (VSGs are dimers) is critical for stable cell surface association. Read More

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RNA structure probing reveals the structural basis of Dicer binding and cleavage.

Nat Commun 2021 06 7;12(1):3397. Epub 2021 Jun 7.

Ministry of Education Key Laboratory of Bioinformatics, Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing, China.

It is known that an RNA's structure determines its biological function, yet current RNA structure probing methods only capture partial structure information. The ability to measure intact (i.e. Read More

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Safety and immunogenicity of an HIV-1 gp120-CD4 chimeric subunit vaccine in a phase 1a randomized controlled trial.

Vaccine 2021 Jun 4. Epub 2021 Jun 4.

Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA; Intralytix, Columbia, MD, USA. Electronic address:

A major challenge for HIV vaccine development is to raise anti-envelope antibodies capable of recognizing and neutralizing diverse strains of HIV-1. Accordingly, a full length single chain (FLSC) of gp120-CD4 chimeric vaccine construct was designed to present a highly conserved CD4-induced (CD4i) HIV-1 envelope structure that elicits cross-reactive anti-envelope humoral responses and protective immunity in animal models of HIV infection. IHV01 is the FLSC formulated in aluminum phosphate adjuvant. Read More

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LEO1 is a partner for Cockayne syndrome protein B (CSB) in response to transcription-blocking DNA damage.

Nucleic Acids Res 2021 Jun 7. Epub 2021 Jun 7.

Section on DNA repair, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.

Cockayne syndrome (CS) is an autosomal recessive genetic disorder characterized by photosensitivity, developmental defects, neurological abnormalities, and premature aging. Mutations in CSA (ERCC8), CSB (ERCC6), XPB, XPD, XPG, XPF (ERCC4) and ERCC1 can give rise to clinical phenotypes resembling classic CS. Using a yeast two-hybrid (Y2H) screening approach, we identified LEO1 (Phe381-Ser568 region) as an interacting protein partner of full-length and C-terminal (Pro1010-Cys1493) CSB in two independent screens. Read More

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Analysis of RAGE Proteome and Interactome in Lung Adenocarcinoma Using PANTHER and STRING Databases.

Charles A Downs

Biol Res Nurs 2021 Jun 7:10998004211021496. Epub 2021 Jun 7.

School of Nursing and Health Studies, University of Miami, Coral Gables, FL, USA.

Adenocarcinoma accounts for about 40% of all lung cancers. Histological studies indicate a loss of expression of the Receptor for Advanced Glycation End-products (RAGE) in lung adenocarcinoma cells compared to neighboring non-malignant tissue. Gene silencing of RAGE in human lung adenocarcinoma cells was performed and then cells were subjected to LC-MS/MS ( = 3, FDR < 1%). Read More

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Large-Scale Multiplexing Permits Full-Length Transcriptome Annotation of 32 Bovine Tissues From a Single Nanopore Flow Cell.

Front Genet 2021 20;12:664260. Epub 2021 May 20.

Department of Animal Science, University of California, Davis, Davis, CA, United States.

A comprehensive annotation of transcript isoforms in domesticated species is lacking. Especially considering that transcriptome complexity and splicing patterns are not well-conserved between species, this presents a substantial obstacle to genomic selection programs that seek to improve production, disease resistance, and reproduction. Recent advances in long-read sequencing technology have made it possible to directly extrapolate the structure of full-length transcripts without the need for transcript reconstruction. Read More

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Metabolism of oral turinabol by human brain cholesterol 24-hydroxylase CYP46A1.

J Steroid Biochem Mol Biol 2021 Jun 2:105927. Epub 2021 Jun 2.

Institute of Biochemistry, Saarland University, D-66123, Saarbruecken, Germany. Electronic address:

The human microsomal cytochrome P450 enzyme CYP46A1 plays a crucial role in cholesterol elimination from the brain. It performs a 24-hydroxylation of cholesterol and is of outstanding significance for memory and cognition. This study demonstrates the catalytic activity of human CYP46A1 towards an anabolic androgenic steroid, oral turinabol (dehydrochloromethyltestosterone, 4-chloro-17β-dihydroxy,17α-methylandrosta-1,4-dien-3-one), which is a doping substance. Read More

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Generation and characterization of HLA-A2 transgenic mice expressing the human TCR 1G4 specific for the HLA-A2 restricted NY-ESO-1 tumor-specific peptide.

J Immunother Cancer 2021 Jun;9(6)

MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, Oxford, UK.

Background: NY-ESO-1 is a tumor-specific, highly immunogenic, human germ cell antigen of the MAGE-1 family that is a promising vaccine and cell therapy candidate in clinical trial development. The mouse genome does not encode an NY-ESO-1 homolog thereby not subjecting transgenic T-cells to thymic tolerance mechanisms that might impair in-vivo studies. We hypothesized that an NY-ESO-1 T cell receptor (TCR) transgenic mouse would provide the unique opportunity to study avidity of TCR response against NY-ESO-1 for tumor vaccine and cellular therapy development against this clinically relevant and physiological human antigen. Read More

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Effect of Recombinant Human Parathyroid Hormone (1-84) on Resolution of Active Charcot Neuro-osteoarthropathy in Diabetes: A Randomized, Double-Blind, Placebo-Controlled Study.

Diabetes Care 2021 Jun 4. Epub 2021 Jun 4.

Diabetic Foot Clinic, King's College Hospital NHS Foundation Trust, London, U.K.

Objective: Fractures in Charcot neuro-osteoarthropathy (CN) often fail to heal despite prolonged immobilization with below-knee casting. The aim of the study was to assess the efficacy of recombinant human parathyroid hormone (PTH) in reducing time to resolution of CN and healing of fractures.

Research Design And Methods: People with diabetes and acute (active) Charcot foot were randomized (double-blind) to either full-length PTH (1-84) or placebo therapy, both in addition to below-knee casting and calcium and vitamin D3 supplementation. Read More

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Synergistic sequence contributions bias glycation outcomes.

Nat Commun 2021 06 3;12(1):3316. Epub 2021 Jun 3.

Department of Chemistry, Tufts University, Medford, MA, USA.

The methylglyoxal-derived hydroimidazolone isomer, MGH-1, is an abundant advanced glycation end-product (AGE) associated with disease and age-related disorders. As AGE formation occurs spontaneously and without an enzyme, it remains unknown why certain sites on distinct proteins become modified with specific AGEs. Here, we use a combinatorial peptide library to determine the chemical features that favor MGH-1. Read More

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State of the art of clinical applications of Tissue Engineering in 2021.

Tissue Eng Part B Rev 2021 Jun 3. Epub 2021 Jun 3.

Universitaire Ziekenhuizen Leuven, 60182, Plastic and Reconstructive Surgery, Leuven, Belgium;

Tissue engineering (TE) was introduced almost 30 years ago as a potential technique for regenerating human tissues. However, despite promising laboratory findings, the complexity of the human body, scientific hurdles, and lack of persistent long-term funding still hamper its translation towards clinical applications. In this report, we compile an inventory of clinically applied TE medical products relevant to surgery. Read More

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Serological profiles of pan-coronavirus-specific responses in COVID-19 patients using a multiplexed electro-chemiluminescence-based testing platform.

PLoS One 2021 3;16(6):e0252628. Epub 2021 Jun 3.

Immunology Core, Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.

Serological assessment of SARS-CoV-2 specific responses are an essential tool for determining the prevalence of past SARS-CoV-2 infections in the population especially when testing occurs after symptoms have developed and limited contact tracing is in place. The goal of our study was to test a new 10-plex electro-chemiluminescence-based assay to measure IgM and IgG responses to the spike proteins from multiple human coronaviruses including SARS-CoV-2, assess the epitope specificity of the SARS-CoV-2 antibody response against full-length spike protein, receptor-binding domain and N-terminal domain of the spike protein, and the nucleocapsid protein. We carried out the assay on samples collected from three sample groups: subjects diagnosed with COVID-19 from the U. Read More

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Allosteric Antagonist Modulation of TRPV2 by Piperlongumine Impairs Glioblastoma Progression.

ACS Cent Sci 2021 May 14;7(5):868-881. Epub 2021 Apr 14.

Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal.

The use of computational tools to identify biological targets of natural products with anticancer properties and unknown modes of action is gaining momentum. We employed self-organizing maps to deconvolute the phenotypic effects of piperlongumine (PL) and establish a link to modulation of the human transient receptor potential vanilloid 2 (hTRPV2) channel. The structure of the PL-bound full-length rat TRPV2 channel was determined by cryo-EM. Read More

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Biochemical properties of VGLL4 from Homo sapiens and Tgi from Drosophila melanogaster and possible biological implications.

Protein Sci 2021 Jun 1. Epub 2021 Jun 1.

Disease Area Oncology, Novartis Institutes for Biomedical Research, Basel, Switzerland.

The TEAD (Sd in drosophila) transcription factors are essential for the Hippo pathway. Human VGLL4 and drosophila Tgi bind to TEAD/Sd via two distinct binding sites. These two regions are separated by few amino acids in VGLL4 but they are very distant from each other in Tgi. Read More

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Immunotherapeutic Efficacy of IgY Antibodies Targeting the Full-Length Spike Protein in an Animal Model of Middle East Respiratory Syndrome Coronavirus Infection.

Pharmaceuticals (Basel) 2021 May 26;14(6). Epub 2021 May 26.

Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

Identified in 2012, the Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe and often fatal acute respiratory illness in humans. No approved prophylactic or therapeutic interventions are currently available. In this study, we developed chicken egg yolk antibodies (IgY Abs) specific to the MERS-CoV spike (S) protein and evaluated their neutralizing efficiency against MERS-CoV infection. Read More

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Epidemiology, Genetic Characterization, and Evolution of Carried by and : The First Epidemiological Evidence from Southern China.

Pathogens 2021 May 28;10(6). Epub 2021 May 28.

Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou 510515, China.

is a novel member of the family . A single species, , is currently described. However, there is limited information on the identification of to date, and thereby the circulation of is not fully understood. Read More

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Analysis of Pembrolizumab in Human Plasma by LC-MS/HRMS. Method Validation and Comparison with Elisa.

Biomedicines 2021 May 30;9(6). Epub 2021 May 30.

Biochemistry and Pharmacology-Toxicology Laboratory, Lyon-Sud Hospital, Hospices Civils de Lyon, F-69495 Pierre Bénite, France.

Pembrolizumab is a humanized immunoglobulin G4-kappa anti-PD1 antibody used in the treatment of different solid tumors or haematological malignancies. A liquid chromatography coupled with a high resolution mass spectrometry (orbitrap technology) method was fully developed, optimized, and validated for quantitative analysis of pembrolizumab in human plasma. A mass spectrometry assay was used for the first time a full-length stable isotope-labelled pembrolizumab-like (Arginine C-N and Lysine C-N) as an internal standard; the sample preparation was based on albumin depletion and trypsin digestion and, finally, one surrogate peptide was quantified in positive mode. Read More

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Structural Plasticity of LL-37 Indicates Elaborate Functional Adaptation Mechanisms to Bacterial Target Structures.

Int J Mol Sci 2021 May 14;22(10). Epub 2021 May 14.

Institute of Microbiology and Infection, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.

The human cathelicidin LL-37 is a multifunctional peptide of the human innate immune system. Among the various functions of LL-37, its antimicrobial activity is important in controlling the microorganisms of the human body. The target molecules of LL-37 in bacteria include membrane lipids, lipopolysaccharides (LPS), lipoteichoic acid (LTA), proteins, DNA and RNA. Read More

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High Levels of the Cleaved Form of Galectin-9 and Osteopontin in the Plasma Are Associated with Inflammatory Markers That Reflect the Severity of COVID-19 Pneumonia.

Int J Mol Sci 2021 May 7;22(9). Epub 2021 May 7.

Department of Respiratory Medicine, Sendai City Hospital, Miyagi 982-8502, Japan.

Numbers of patients with coronavirus disease 2019 (COVID-19) have increased rapidly worldwide. Plasma levels of full-length galectin-9 (FL-Gal9) and osteopontin (FL-OPN) as well as their truncated forms (Tr-Gal9, Ud-OPN, respectively), are representative inflammatory biomarkers. Here, we measured FL-Gal9, FL-OPN, Tr-Gal9, and Ud-OPN in 94 plasma samples obtained from 23 COVID-19-infected patients with mild clinical symptoms (CV), 25 COVID-19 patients associated with pneumonia (CP), and 14 patients with bacterial infection (ID). Read More

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PARP Power: A Structural Perspective on PARP1, PARP2, and PARP3 in DNA Damage Repair and Nucleosome Remodelling.

Int J Mol Sci 2021 May 12;22(10). Epub 2021 May 12.

Structure and Biophysics, Discovery Sciences, R&D, AstraZeneca, Cambridge CB4 0WG, UK.

Poly (ADP-ribose) polymerases (PARP) 1-3 are well-known multi-domain enzymes, catalysing the covalent modification of proteins, DNA, and themselves. They attach mono- or poly-ADP-ribose to targets using NAD as a substrate. Poly-ADP-ribosylation (PARylation) is central to the important functions of PARP enzymes in the DNA damage response and nucleosome remodelling. Read More

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