Krabbeburt2511

We measured the concentrations of 205 polychlorinated biphenyl (PCB) congeners in 26 food items beef steak, butter, canned tuna, catfish, cheese, eggs, french fries, fried chicken, ground beef, ground pork, hamburger, hot dog, ice cream, liver, luncheon meat, margarine, meat-free dinner, milk, pizza, poultry, salmon, sausage, shrimp, sliced ham, tilapia, and vegetable oil. Using Diet History Questionnaire II, we calculated the PCB dietary exposure in mothers and children participating in the AESOP Study in East Chicago, Indiana, and Columbus Junction, Iowa. Salmon had the highest concentration followed by canned tuna, but fish is a minor contributor to exposure. Other animal proteins are more important sources of PCB dietary exposure in this study population. Despite the inclusion of few congeners and food types in previous studies, we found evidence of a decline in PCB concentrations over the last 20 years. We also found strong associations of PCB congener distributions with Aroclors in most foods and found manufacturing byproduct PCBs, including PCB11, in tilapia and catfish. The reduction in PCB levels in food indicates that dietary exposure is comparable to PCB inhalation exposures reported for the same study population.Demyelinating injuries and diseases, like multiple sclerosis, affect millions of people worldwide. Oligodendrocyte precursor cells (OPCs) have the potential to repair demyelinated tissues because they can both self-renew and differentiate into oligodendrocytes (OLs), the myelin producing cells of the central nervous system (CNS). Cell-matrix interactions impact OPC differentiation into OLs, but the process is not fully understood. Biomaterial hydrogel systems help to elucidate cell-matrix interactions because they can mimic specific properties of native CNS tissues in an in vitro setting. We investigated whether OPC maturation into OLs is influenced by interacting with a urokinase plasminogen activator (uPA) degradable extracellular matrix (ECM). uPA is a proteolytic enzyme that is transiently upregulated in the developing rat brain, with peak uPA expression correlating with an increase in myelin production in vivo. OPC-like cells isolated through the Mosaic Analysis with Double Marker technique (MADM OPCs) produced low-molecular-weight uPA in culture. MADM OPCs were encapsulated into two otherwise similar elastin-like protein (ELP) hydrogel systems one that was uPA degradable and one that was nondegradable. Encapsulated MADM OPCs had similar viability, proliferation, and metabolic activity in uPA degradable and nondegradable ELP hydrogels. Expression of OPC maturation-associated genes, however, indicated that uPA degradable ELP hydrogels promoted MADM OPC maturation although not sufficiently for these cells to differentiate into OLs.A pyridine/aniline appended unsymmetrical bidentate ligand N-(4-(4-aminobenzyl)phenyl)nicotinamide, investigated in this work has two well-separated coordination sites. Combination of the ligand with cis-protected palladium(II) (i.e., PdL') and palladium(II) in separate reactions produced the corresponding Pd2L'2Lun2 and extremely rare Pd2Lun4 type self-assembled binuclear complexes, respectively. Notably, both varieties of complexes are prepared from a common ligand system. Two diastereomers (i.e., (2,0) and (1,1)-forms) are possible for Pd2L'2Lun2 type complex, whereas four diastereomers (i.e., (4,0), (3,1), trans(2,2), and cis(2,2)-forms) can be imagined for the Pd2Lun4 type complex. However, exclusive diastereoselectivity was observed, and the complexes formed belong to (1,1)-Pd2L'2Lun2 and cis(2,2)-Pd2Lun4 forms. The diastereomers are predicted from NMR study in solution and DFT calculations in gas-phase and implicit-solvent media; however, single-crystal structures of both the complexes provided unambiguous support. The rare Pd2Lun4 type complex is studied in further detail. Parameters like counteranion, concentration, temperature, and stoichiometry of metal to ligand did not influence the diastereoselectivity in complex formation. DFT calculations show the cis(2,2) form to be the most stable, followed by the (3,1) isomer. The lowest conformational strain in the bound ligand strands in the cis(2,2)-arrangement along with optimal intermolecular interactions makes it the energetically most stable of all the isomers. Molecular dynamics (MD) simulations were carried out to visualize the self-assembly process toward the formation of Pd2Lun4 type complex and the free energy difference between the cis(2,2) and (3,1) isomers. Snapshots of MD simulation elucidate the step-by-step progress of complexation leading to the cis(2,2)-isomer.Amyloidogenic peptides and proteins are rich sources of supramolecular assemblies. Sequences derived from well-known amyloids, including Aβ, human islet amyloid polypeptide, and tau have been found to assemble as fibrils, nanosheets, ribbons, and nanotubes. The supramolecular assembly of medin, a 50-amino acid peptide that forms fibrillary deposits in aging human vasculature, has not been heavily investigated. In this work, we present an X-ray crystallographic structure of a cyclic β-sheet peptide derived from the 19-36 region of medin that assembles to form interpenetrating cubes. The edge of each cube is composed of a single peptide, and each vertex is occupied by a divalent metal ion. This structure may be considered a metal-organic framework (MOF) containing a large peptide ligand. This work demonstrates that peptides containing Glu or Asp that are preorganized to adopt β-hairpin structures can serve as ligands and assemble with metal ions to form MOFs.Cancer immunotherapy can be augmented with toll-like receptor agonist (TLRa) adjuvants, which interact with immune cells to elicit potent immune activation. Despite their potential, use of many TLRa compounds has been limited clinically due to their extreme potency and lack of pharmacokinetic control, causing systemic toxicity from unregulated systemic cytokine release. Herein, we overcome these shortcomings by generating poly(ethylene glycol)-poly(lactic acid) (PEG-PLA) nanoparticles (NPs) presenting potent TLR7/8a moieties on their surface. The NP platform allows precise control of TLR7/8a valency and resulting surface presentation through self-assembly using nanoprecipitation. We hypothesize that the pharmacokinetic profile of the NPs minimizes systemic toxicity, localizing TLR7/8a presentation to the tumor bed and tumor-draining lymph nodes. In conjunction with antiprogrammed death-ligand 1 (anti-PD-L1) checkpoint blockade, peritumoral injection of TLR7/8a NPs slows tumor growth, extends survival, and decreases systemic toxicity in comparison to the free TLR7/8a in a murine colon adenocarcinoma model. These NPs constitute a modular platform for controlling pharmacokinetics of immunostimulatory molecules, resulting in increased potency and decreased toxicity.Fourier transform mass spectrometry (FTMS) applications require accurate analysis of extremely complex mixtures of species in wide mass and charge state ranges. To optimize the related FTMS data analysis accuracy, parameters for data acquisition and the allied data processing should be selected rationally, and their influence on the data analysis outcome is to be understood. To facilitate this selection process and to guide the experiment design and data processing workflows, we implemented the underlying algorithms in a software tool with a graphical user interface, FTMS Isotopic Simulator. This tool computes FTMS data via time-domain data (transient) simulations for user-defined molecular species of interest and FTMS instruments, including diverse Orbitrap FTMS models, followed by user-specified FT processing steps. BBI608 Herein, we describe implementation and benchmarking of this tool for analysis of a wide range of compounds as well as compare simulated and experimentally generated FTMS data. In particular, we discuss the use of this simulation tool for narrowband, broadband, and low- and high-resolution analysis of small molecules, peptides, and proteins, up to the level of their isotopic fine structures. By demonstrating the allied FT processing artifacts, we raise awareness of a proper selection of FT processing parameters for modern applications of FTMS, including intact mass analysis of proteoforms and top-down proteomics. Overall, the described transient-mediated approach to simulate FTMS data has proven useful for supporting contemporary FTMS applications. We also find its utility in fundamental FTMS studies and creating didactic materials for FTMS teaching.The control of layer thickness and phase structure in two-dimensional transition metal dichalcogenides (2D TMDCs) like MoTe2 has recently gained much attention due to their broad applications in nanoelectronics and nanophotonics. Continuous-wave laser-based thermal treatment has been demonstrated to realize layer thinning and phase engineering in MoTe2, but requires long heating time and is largely influenced by the thermal dissipation of the substrate. The ultrafast laser produces a different response but is yet to be explored. In this work, we report the nonlinear optical interactions between MoTe2 crystals and femtosecond (fs) laser, where we have realized the nonlinear optical characterization, precise layer thinning, and phase transition in MoTe2 using a single fs laser platform. By using the fs laser with a low fluence as an excitation light source, we observe the strong nonlinear optical signals of second-harmonic generation and four-wave mixing in MoTe2, which can be used to identify the odd-even layers and layer numbers, respectively. With increasing the laser fluence to the ablation threshold (Fth), we achieve layer-by-layer removal of MoTe2, while 2H-to-1T' phase transition occurs with a higher laser fluence (2Fth to 3Fth). Moreover, we obtain highly ordered subwavelength nanoripples on both the thick and few-layer MoTe2 with a controlled fluence, which can be attributed to the fs laser-induced reorganization of the molten plasma. Our study provides a simple and efficient ultrafast laser-based approach capable of characterizing the structures and modifying the physical properties of 2D TMDCs.Protein misfolding and aggregation is the pathological hallmark of Alzheimer's disease (AD). The etiopathogenesis of AD involves the accumulation of amyloid-β (Aβ) plaques in the brain, which disrupt the neuronal network and communication, causing neuronal death and severe cognitive impairment. Modulation of Aβ aggregation by exogenous therapeutic agents is considered an effective strategy to treat AD. Frequent failure of drug candidates in various phases of clinical trials reiterates the need for alternative therapeutic strategies for AD treatment. Polyampholytes with cationic and anionic segments are considered as artificial protein mimics capable of modulating the protein misfolding and aggregation. We report a diblock copolymer of tryptophan-functionalized methacrylic acid (PTMA) polyampholyte synthesized through reversible addition-fragmentation chain transfer (RAFT) polymerization. Investigation revealed that PTMA acts as a synthetic chaperone to protect the native structure of the lysozyme under heat-induced aggregation conditions.