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CA 92121; J. Craig Venter Institute[Aff... Publications | LitMetric

6,436 results match your criteria: "CA 92121; J. Craig Venter Institute[Affiliation]"

Pegfilgrastim, a 40 kDa PEGylated form of recombinant human granulocyte colony-stimulating factor (rhG-CSF), is a biotherapeutic protein used to treat chemotherapy-induced neutropenia. To ensure the product is safe and effective, stringent monitoring of product-related impurities, particularly those arising from oxidative degradation, is necessary. This study focuses on the isolation and characterization of oxidized variants in pegfilgrastim using a multi-step approach that includes method transfer to semi-preparative High-Performance Liquid Chromatography (HPLC), mass spectrometry, and an in vitro cell-based potency assay (CBPA).

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A multidonor class of highly glycan-dependent HIV-1 gp120-gp41 interface-targeting broadly neutralizing antibodies.

Cell Rep

December 2024

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Division of Viral Products, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD 20993, USA. Electronic address:

Antibodies that target the gp120-gp41 interface of the HIV-1 envelope (Env) trimer comprise a commonly elicited category of broadly neutralizing antibodies (bNAbs). Here, we isolate and characterize VRC44, a bNAb lineage with up to 52% neutralization breadth. The cryoelectron microscopy (cryo-EM) structure of antibody VRC44.

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Article Synopsis
  • - This study explores how measuring fecal indicators in sewage can be combined with microbial risk assessments to establish safety thresholds for recreational waters potentially contaminated by sewage.
  • - Researchers examined the levels of norovirus (a reference pathogen) and HF183 (a fecal indicator) across various sewage system samples, finding differences in their concentrations depending on the sample location.
  • - The findings helped create risk-based thresholds for HF183, revealing that the safety levels vary depending on the type of sewage discharge, key for evaluating water quality for recreational use.
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Background: Obstructive sleep apnea (OSA) is very common in obese patients. However, why some obese patients have severe OSA while others do not is unclear. Research is limited regarding which structures contribute to upper airway narrowing, especially in Asian patients where bony restrictions is thought to be important.

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GPR6 is an orphan G protein-coupled receptor with high constitutive activity found in D2-type dopamine receptor-expressing medium spiny neurons of the striatopallidal pathway, which is aberrantly hyperactivated in Parkinson's disease. Here, we solved crystal structures of GPR6 without the addition of a ligand (a pseudo-apo state) and in complex with two inverse agonists, including CVN424, which improved motor symptoms in patients with Parkinson's disease in clinical trials. In addition, we obtained a cryo-electron microscopy structure of the signaling complex between GPR6 and its cognate G heterotrimer.

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Adeno-associated virus serotype 2 capsids with proteolytic cuts by trypsin remain intact and potent.

Gene Ther

November 2024

Analytical Development & Operations, Novartis Pharmaceuticals, 10210 Campus Point Drive, San Diego, 92121, CA, USA.

Recombinant adeno-associated viral (AAV) vectors have emerged as prominent gene delivery vehicles for gene therapy. In the journey of an AAV vector, AAV vectors can be exposed to different proteolytic environments inside the production cells, during the cell lysis step, within the endosome, and finally inside the cell nucleus. The stability of a modified AAV serotype 2 (AAV2) capsid was evaluated via a proteolytic approach using trypsin and other proteases and both denaturing and non-denaturing analytical methods.

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RNA Interference Applied to Crustacean Aquaculture.

Biomolecules

October 2024

Interdisciplinary Centre of Marine and Environmental Research, The University of Porto (CIIMAR), 4450-208 Matosinhos, Portugal.

Article Synopsis
  • * While RNAi was first described in shrimp in the mid-2000s, practical applications in shrimp farms are limited due to challenges with cost-effective and easy synthesis and administration of dsRNA.
  • * The review discusses the current understanding of dsRNA mechanisms, design, and administration methods for shrimp, as well as challenges that may impede the widespread adoption of RNAi in crustacean aquaculture.
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In this study, we present a novel 3D perfused skin-on-a-chip model fabricated using micro-precision 3D printing, which offers a streamlined and reproducible approach for incorporating perfusion. Perfused skin models are well-regarded for their advantages, such as improved nutrient supply, enhanced barrier function, and prolonged tissue viability. However, current models often require complex setups, such as self-assembled endothelial cells or sacrificial rods, which are prone to variability and time-consuming.

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Although immune checkpoint inhibitors (ICIs) have become predominant therapies for cancer, the safety and efficacy of combining ICIs with vaccinations remain areas of needed investigation. As ICIs gain broader clinical application, the relevance of current vaccination guidelines for cancer patients-largely developed in the context of cytotoxic therapies-becomes increasingly uncertain. Although data support the safety of combining inactivated influenza and mRNA SARS-CoV-2 vaccines with ICI therapy, comprehensive data on other infectious disease vaccines remain scarce.

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Immuno-oncology has revolutionized cancer treatment, with NKG2A emerging as a novel target for immunotherapy. The blockade of NKG2A using the immune checkpoint inhibitor (ICI) monalizumab has been shown to enhance the responses of both NK cells and CD8+ T cells. However, monalizumab has demonstrated limited efficacy in in vitro cytotoxic assays and clinical trials.

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High-affinity agonists reveal recognition motifs for the MRGPRD GPCR.

Cell Rep

November 2024

Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC, USA; National Institute of Mental Health Psychoactive Drug Screening Program, University of North Carolina School of Medicine, Chapel Hill, NC, USA; Division of Chemical Biology and Medicinal Chemistry, University of North Carolina School of Medicine, Chapel Hill, NC, USA. Electronic address:

Article Synopsis
  • The human MRGPRD protein is part of a family of receptors that play a key role in detecting pain and itch, but it's not well-researched and has few known activating compounds.
  • The study identifies two new potent agonists, EP-2825 and EP-3945, that are about 100 times more effective than the previously known agonist, β-alanine.
  • The researchers also explored the structures of MRGPRD bound to these agonists, revealing unique binding interactions and flexibility in the receptor, which could help in creating new drugs targeting MRGPRD.
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The amyloid clock: mapping Alzheimer's disease in Down syndrome.

Lancet Neurol

December 2024

Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego, CA 92121, USA. Electronic address:

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Ensemble-function relationships: From qualitative to quantitative relationships between protein structure and function.

J Struct Biol

December 2024

Protein Homeostasis Structural Biology Group, Bristol Myers Squibb, San Diego, CA 92121, United States. Electronic address:

Structure-function relationships are deeply rooted in modern biochemistry and structural biology and have provided the basis for our understanding of how protein structure defines function. While structure-function relationships continue to provide invaluable qualitative information, they cannot, in principle, provide the quantitative information ultimately needed to fully understand how proteins function and to make quantitative predictions about changes in activity from changes in sequence and structure. These limitations appear to arise from fundamental principles of physics, which dictate that proteins exist as interchanging ensembles of conformations, rather than as static structures that underly conventional structure-function relationships.

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Mesenchymal stem cells (MSCs) are recognized for their immunomodulatory capabilities, tumor-homing abilities, and capacity to serve as carriers for therapeutic agents. This review delves into the role of adoptively transferred MSCs in tumor progression, their interactions with the tumor microenvironment, and their use in delivering anti-cancer drugs, oncolytic viruses, and genetic material. It also addresses the challenges and limitations associated with MSC therapy, such as variability in MSC preparations and potential tumorigenic effects emphasizing the need for advanced genetic engineering and personalized approaches to enhance therapeutic efficacy.

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Lipoprotein(a), or Lp(a), is encoded by the LPA gene and is a causal genetic risk factor for cardiovascular disease. Individuals with high Lp(a) are at risk for cardiovascular morbidity and are refractory to standard lipid-lowering agents. Lp(a)-lowering therapies currently in clinical development require repetitive dosing, while a gene editing approach presents an opportunity for a single-dose treatment.

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The Immune Epitope Database (IEDB): 2024 update.

Nucleic Acids Res

November 2024

Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.

Over the past 20 years, the Immune Epitope Database (IEDB, iedb.org) has established itself as the foremost resource for immune epitope data. The IEDB catalogs published epitopes and their contextual experimental data in a freely searchable public resource.

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Objective: To report 52-week safety and efficacy of ianalumab from phase 2b dose-finding study in patients with Sjögren's disease (SjD).

Methods: Patients randomly received (1:1:1:1) ianalumab (5, 50, or 300 mg) or placebo subcutaneously every 4 weeks till week 24 (treatment period [TP]1). At week 24, patients on 300 mg were re-randomized to continue 300 mg or receive placebo till week 52 (TP2), patients on placebo were switched to ianalumab 150 mg, while patients on 5 and 50 mg directly entered post treatment safety follow-up.

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Skeletal muscle tissue self-repair occurs through the finely timed activation of resident muscle stem cells (MuSC). Following perturbation, MuSC exit quiescence, undergo myogenic commitment, and differentiate to regenerate the injured muscle. This process is coordinated by signals present in the tissue microenvironment, however the precise mechanisms by which the microenvironment regulates MuSC activation are still poorly understood.

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The current state of the quality of homeopathic clinical research.

Complement Ther Med

November 2024

RAND, 1776 Main Street, PO Box 2138, Santa Monica, CA 90407-2138, USA. Electronic address:

Article Synopsis
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Hemodynamic microenvironment of coronary stent strut malapposition.

Comput Biol Med

January 2025

Center for Digital Cardiovascular Innovations, Cardiovascular Division, Miller School of Medicine, Miami, FL, USA. Electronic address:

Objective: This study aims to investigate the micro-hemodynamic effects of strut malapposition in patient-specific stented coronary bifurcations.

Methods: Using the mapping-back technique, three-dimensional reconstructions of clinical post-stenting artery bifurcations with strut malapposition were accurately generated from optical coherence tomography scans of 9 patients. Computational fluid dynamics (CFD) simulations were then conducted with these models to examine the impact of strut malapposition on various fluid dynamic parameters, including flow patterns, vorticity, strain rates, viscosity, and wall shear stress (WSS).

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Analysis and Prediction of Chymotrypsin Substrate Preferences through Large Data Acquisition with Target-Free mRNA Display.

Chembiochem

November 2024

Screening and Compound Profiling, Quantitative Biosciences, Merck & Co., Inc., Rahway, New Jersey, 07065, USA.

Oral delivery of peptide therapeutics is limited by degradation by gut proteases like chymotrypsin. Existing databases of peptidases are limited in size and do not enable systematic analyses of protease substrate preferences, especially for non-natural amino acids. Thus, stability optimization of hit compounds is time and resource intensive.

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Single cell and TCR analysis of immune cells from AAV gene therapy-dosed Duchenne muscular dystrophy patients.

Mol Ther Methods Clin Dev

December 2024

Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Clinical trials for Duchenne muscular dystrophy (DMD) are assessing the therapeutic efficacy of systemically delivered adeno-associated virus (AAV) carrying a modified transgene. High vector doses (>1E14 vg/kg) are needed to globally transduce skeletal muscles; however, such doses trigger immune-related adverse events. Mitigating these immune responses is crucial for widespread application of AAV-based therapies.

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A cyclin-dependent kinase 4/6 (CDK4/6) inhibitor combined with endocrine therapy is the standard-of-care for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer. However, not all patients respond to the treatment, resistance often occurs and efficacy outcomes from early breast cancer trials have been mixed. To identify biomarkers associated with CDK4/6 inhibitor response or resistance, we combined bioinformatic-database analyses, artificial intelligence-assisted literature review, and manual literature review (Embase and OVID Medline; search window: January 2012-October 2022) to compile data to comprehensively describe the CDK4/6 inhibitor biomarker landscape.

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