3,046 results match your criteria: "USA M.Z.; University of North Texas System College of Pharmacy[Affiliation]"

Diagnostic utility of N-terminal TMPP labels for unambiguous identification of clipped sites in therapeutic proteins.

Sci Rep

October 2023

Janssen Research and Development LLC, The Janssen Pharmaceutical Companies of Johnson & Johnson, Spring House, PA, USA.

Protein therapeutics are susceptible to clipping via enzymatic and nonenzymatic mechanisms that create neo-N-termini. Typically, neo-N-termini are identified by chemical derivatization of the N-terminal amine with (N-Succinimidyloxycarbonylmethyl)tris(2,4,6-trimethoxyphenyl)phosphonium bromide (TMPP) followed by proteolysis and mass spectrometric analysis. Detection of the TMPP-labeled peptide is achieved by mapping the peptide sequence to the product ion spectrum derived from collisional activation.

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Article Synopsis
  • * Our study included tandem mass spectrometry to map out the relationships between precursor and fragment ions, allowing us to assign structures to major fragments resulting from the dissociation.
  • * We proposed a benzyl migration mechanism based on computational analysis, offering insights into sparsentan's fragmentation pathways that could aid future research on similar molecules and their degradation products.
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Background: Isovitexin-2"-O-D-glucopyranoside (IVG) has been known to exhibit sedative and hypnotic effects. However, there is little understanding of the in vivo pharmacokinetics and tissue distribution of IVG.

Objective: This study aimed to investigate the pharmacokinetics and tissue distribution of IVG.

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We present a rare case of hydatidiform molar pregnancy, which led to the development of thyroid storm, followed by a rare complication of takotsubo cardiomyopathy in the setting of a COVID-19 infection. A 21-year-old female of 22 weeks gestational age presented with heavy vaginal blood loss, brown emesis, tachycardia, and lethargy. Through clinical presentation and ultrasound confirmation, a molar pregnancy was diagnosed.

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Transporter-mediated drug-drug interactions (DDIs) are assessed using probe drugs and in vitro and in vivo models during drug development. The utility of endogenous metabolites as transporter biomarkers is emerging for prediction of DDIs during early phases of clinical trials. Endogenous metabolites such as pyridoxic acid and kynurenic acid have shown potential to predict DDIs mediated by organic anion transporters (OAT1 and OAT3).

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Article Synopsis
  • - The study analyzed data from the POLARIX trial to evaluate the pharmacokinetics (PKs) of polatuzumab vedotin in Asian and non-Asian patients with untreated diffuse large B-cell lymphoma.
  • - Results showed that the drug exposures (both antibody-conjugated and unconjugated forms) were largely comparable between Asian and non-Asian patients, with minor variations in some concentrations.
  • - The findings indicate that the PKs of polatuzumab vedotin do not differ significantly by ethnicity, suggesting that Asian patients do not require dose adjustments for effective and safe treatment.
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Oxygen stable isotopes (i.e., O, O, O) of nitrite (NO) are useful for investigating chemical processes and sources contributing to this important environmental contaminant and nutrient.

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Angiotensin and kinin metabolic pathways are reported to be altered by many diseases, including COVID-19. Monitoring levels of these peptide metabolites is important for understanding mechanisms of disease processes. In this paper, we report dimethyl labeling of amines in peptides by addition of formaldehyde to samples and deutero-formaldehyde to internal standards to generate nearly identical isotopic standards with 4 / units larger per amine group than the corresponding analyte.

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Equilibrated Gas and Carbonate Standard-Derived Dual (Δ47 and Δ48) Clumped Isotope Values.

Geochem Geophys Geosyst

February 2023

Department of Earth, Planetary, and Space Sciences, Department of Atmospheric and Oceanic Sciences, Center for Diverse Leadership in Science, Institute of the Environment and Sustainability, UCLA, Los Angeles, CA, USA.

Carbonate clumped isotope geochemistry has primarily focused on mass spectrometric determination of 47 CO for geothermometry, but theoretical calculations and recent experiments indicate paired analysis of the 47 (COO) and 48 (COO) isotopologues (referred to as and ) can be used to study non-equilibrium isotope fractionations and refine temperature estimates. We utilize 5,448 and 3,400 replicate measurements of carbonate samples and standards, and 183 and 195 replicate measurements of gas standards from 2015 to 2021 from a multi-year and multi-instrument data set to constrain and values for 27 samples and standards, including Devils Hole cave calcite, and study equilibrium -, -temperature, and -temperature relationships. We compare results to previously published findings and calculate equilibrium regressions based on data from multiple laboratories.

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Stable sound decoding despite modulated sound representation in the auditory cortex.

Curr Biol

October 2023

Cold Spring Harbor Laboratory, 1 Bungtown Rd, Cold Spring Harbor, NY 11724, USA.

The activity of neurons in the auditory cortex is driven by both sounds and non-sensory context. To investigate the neuronal correlates of non-sensory context, we trained head-fixed mice to perform a two-alternative-choice auditory task in which either reward or stimulus expectation (prior) was manipulated in blocks. Using two-photon calcium imaging to record populations of single neurons in the auditory cortex, we found that both stimulus and reward expectation modulated the activity of these neurons.

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Biogenic alkenes, such as isoprene and α-pinene, are the predominant source of volatile organic compounds (VOCs) emitted into the atmosphere. Atmospheric processing of alkenes reaction with ozone leads to formation of zwitterionic reactive intermediates with a carbonyl oxide functional group, known as Criegee intermediates (CIs). CIs are known to exhibit a strong absorption (π* ← π) in the near ultraviolet and visible (UV-vis) region due to the carbonyl oxide moiety.

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Comparative urine metabolomics of mice treated with non-toxic and toxic oral doses of (-)-epigallocatechin-3-gallate.

Food Funct

October 2023

Department of Food Science, The Pennsylvania State University, 332 Food Science Building, University Park, PA 16802, USA.

The green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), has been studied for its potential positive health effects, but human and animal model studies have reported potential toxicity at high oral bolus doses. This study used liquid chromatography-mass spectrometry-based metabolomics to compare the urinary EGCG metabolite profile after administration of a single non-toxic (100 mg kg) or toxic (750 mg kg) oral bolus dose to male C57BL6/J mice to better understand how EGCG metabolism varies with dose. EGCG metabolites, including methyl, glucuronide, sulfate, and glucoside conjugates, were tentatively identified based on their mass to charge (/) ratio and fragment ion patterns.

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Article Synopsis
  • A billion tons of carbon is stored in deep soils of the Southeastern Coastal Plain, referred to as deep podzolized carbon (DPC), but its stabilization mechanisms are not well understood.
  • The main idea is that water table fluctuations slow down microbial degradation, helping carbon accumulate, although this hypothesis hasn’t been thoroughly tested yet.
  • Research methods included various analyses that showed DPC organic matter is more resistant to breakdown than surface soil, influenced by persistent water saturation and low redox conditions which help it stabilize over time.
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Tracking cell-type-specific temporal dynamics in human and mouse brains.

Cell

September 2023

Laboratory of Single Cell Genomics and Population Dynamics, The Rockefeller University, New York, NY, USA. Electronic address:

Progenitor cells are critical in preserving organismal homeostasis, yet their diversity and dynamics in the aged brain remain underexplored. We introduced TrackerSci, a single-cell genomic method that combines newborn cell labeling and combinatorial indexing to characterize the transcriptome and chromatin landscape of proliferating progenitor cells in vivo. Using TrackerSci, we investigated the dynamics of newborn cells in mouse brains across various ages and in a mouse model of Alzheimer's disease.

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Lavender ( Miller or Chaix) is an ethnopharmacological plant commonly known as English lavender. Linalool and linalyl acetate are putative phytoactives in lavender essential oil (LEO) derived from the flower heads. LEO has been used in aroma or massage therapy to reduce sleep disturbance and to mitigate anxiety.

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Rapid detection of carbapenemase (KPC) in the species is desirable. The MALDI Biotyper MBT Subtyping Module (Bruker Daltonics) uses an algorithm that detects a peak at ~11,109 m/z corresponding to a protein encoded by the gene to detect KPC simultaneously with organism identification by a matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-ToF MS). Here, the subtyping module was evaluated using 795 clinical isolates, with whole genome sequences used to assess for and .

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Recent advances have rekindled the interest in ion mobility as an additional dimension of separation in mass spectrometry (MS)-based proteomics. Ion mobility separates ions according to their size and shape in the gas phase. Here, we set out to investigate the effect of 22 different post-translational modifications (PTMs) on the collision cross section (CCS) of peptides.

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Introduction: It is critical to develop more inclusive Alzheimer's disease (AD) research protocols to ensure that historically excluded groups are included in preclinical research and have access to timely diagnosis and treatment. If validated in racialized groups, plasma AD biomarkers and measures of subtle cognitive dysfunction could provide avenues to expand diversity in preclinical AD research. We sought to evaluate the utility of two easily obtained, low-burden disease markers, plasma amyloid beta (Aβ)42/40, and intra-individual cognitive variability (IICV), to predict concurrent and longitudinal cognitive performance in a sample of Black adults.

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Despite aggressive treatment approaches, the overall survival of glioblastoma (GBM) patients remained poor with a strong need for more effective chemotherapeutic agents. A previous study has shown that ARN14988 is more cytotoxic to GBM cells compared to US Food and Drug Administration-approved temozolomide. This finding makes ARN14988 a desirable candidate for further pharmacological assessment.

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Stable sound decoding despite modulated sound representation in the auditory cortex.

bioRxiv

September 2023

Cold Spring Harbor Laboratory, 1 Bungtown Rd, Cold Spring Harbor, NY 11724, USA.

The activity of neurons in the auditory cortex is driven by both sounds and non-sensory context. To investigate the neuronal correlates of non-sensory context, we trained head-fixed mice to perform a two-alternative choice auditory task in which either reward or stimulus expectation (prior) was manipulated in blocks. Using two-photon calcium imaging to record populations of single neurons in auditory cortex, we found that both stimulus and reward expectation modulated the activity of these neurons.

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Anaerobic bioreactors are an efficient technology for the biodegradation of emerging contaminants in environmental matrices. In this work, a horizontal-flow anaerobic immobilized biomass (HAIB) bioreactor was used to remove caffeine (CAF), which is frequently found in various aqueous matrices. The acrylic bench top bioreactor, with dimensions of 100 × 5.

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Background: High-resolution metabolomics (HRM) is an innovative tool to study challenging infectious diseases like leprosy, where the pathogen cannot be grown with standard methods. Here, we use HRM to better understand associations between disease manifestations, nutrition, and host metabolism.

Methods: From 2018 to 2019, adults with leprosy and controls were recruited in Minas Gerais, Brazil.

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Pituitary crosstalk with bone, adipose tissue and brain.

Nat Rev Endocrinol

December 2023

Center for Translational Medicine and Pharmacology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Traditional textbook physiology has ascribed unitary functions to hormones from the anterior and posterior pituitary gland, mainly in the regulation of effector hormone secretion from endocrine organs. However, the evolutionary biology of pituitary hormones and their receptors provides evidence for a broad range of functions in vertebrate physiology. Over the past decade, we and others have discovered that thyroid-stimulating hormone, follicle-stimulating hormone, adrenocorticotropic hormone, prolactin, oxytocin and arginine vasopressin act directly on somatic organs, including bone, adipose tissue and liver.

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Forensic laboratories are faced with an ever-expanding seized drug landscape including the increasing prevalence of novel psychoactive substances (NPS), such as synthetic cathinones, that have varying potencies and scheduling. This study demonstrates a combined gas chromatography-electron ionization-mass spectrometry (GC-EI-MS) and nuclear magnetic resonance (NMR) spectroscopy approach for the differentiation of N-butyl pentylone isomers based on distinct retention times, characteristic EI mass spectra, and NMR characterization. Retention time reproducibility was assessed from 60 replicate measurements for each isomer over the course of a month.

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Article Synopsis
  • Left ventricular ejection fraction (LVEF) alone is not sufficient for predicting sudden cardiac death (SCD), prompting a study to enhance risk assessment for ICD implantation using machine learning (ML) with clinical data and ECG features.
  • A multicentric analysis involved 1010 patients with serious heart conditions (average age 65, mostly male) who had LVEF ≤ 35% and received ICDs for SCD prevention, collecting both clinical info and ECG data before implantation.
  • Machine learning models demonstrated high reliability in predicting non-arrhythmic mortality, achieving an impressive AUROC of 0.90 in a development cohort and 0.79 in an external validation cohort, indicating strong potential for personalized risk stratification.
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