Langolsson2390
The advent of massively parallel sequencing (MPS) applications focused on the generation of forensic-quality full mitochondrial genome sequences led to a popularization of the technique on a global scale. However, the lack of forensic-graded population databases has refrained a wider adoption of full genome sequences as the industry standard, despite its better discrimination capacity of individual maternal lineages.
This work describes a forensic-oriented full mtDNA genome database comprised of 480 samples from a Southern Brazilian population.
A collection of mitochondrial sequences were obtained from low-pass, full genome DNA sequencing results. The complete sample set was evaluated regarding haplotype composition and distribution. Summary statistics and forensic parameters were calculated and are presented for the database, with detailed information concerning the impact of removing genetic information in the form of specific variants or increasingly larger genomic regions. Interpopulational analysisan integrated, representative, national database comprising most of the genetic diversity of maternal lineages in the country.
The proposed database provides a basis for statistical calculation and frequency estimation of full mitochondrial genomes, and can be part of an integrated, representative, national database comprising most of the genetic diversity of maternal lineages in the country.
Although several studies provide data for reference dosimetry, the SNC600c and SNC125c ionization chambers (Sun Nuclear Corporation, Melbourne, FL) are in clinical use worldwide for which no beam quality correction factors k
are available. The goal of this study was to calculate beam quality correction factors k
for these ionization chambers according to dosimetry protocols TG-51, TRS 398 and DIN 6800-2.
Monte Carlo simulations using EGSnrc have been performed to calculate the absorbed dose to water and the dose to air within the active volume of ionization chamber models. Both spectra and simulations of beam transport through linear accelerator head models were used as radiation sources for the Monte Carlo calculations.
k
values as a function of the respective beam quality specifier Q were fitted against recommended equations for photon beam dosimetry in the range of 4 MV to 25 MV. The fitting curves through the calculated values showed a root mean square deviation between 0.0010 and 0.0017.
The investigated ionization chamber models (SNC600c, SNC125c) are not included in above mentioned dosimetry protocols, but are in clinical use worldwide. This study covered this knowledge gap and compared the calculated results with published k
values for similar ionization chambers. Agreements with published data were observed in the 95% confidence interval, confirming the use of data for similar ionization chambers, when there are no k
values available for a given ionization chamber.
The investigated ionization chamber models (SNC600c, SNC125c) are not included in above mentioned dosimetry protocols, but are in clinical use worldwide. This study covered this knowledge gap and compared the calculated results with published kQ values for similar ionization chambers. Agreements with published data were observed in the 95% confidence interval, confirming the use of data for similar ionization chambers, when there are no kQ values available for a given ionization chamber.A sensitive, accurate, simple, and rapid analytical UHPLC-MS/MS method was developed for identification and quantification of koumine, gelsemine, and gelsenicine in human hair. Approximately 10 mg of hair was extracted with methanol by cryogenic grinding. The limits of detection (LODs) ranged from 1 to 5 pg/mg, and the limits of quantitation (LOQs) ranged from 2 to 10 pg/mg. The method was linear over a concentration range from the LOQs to 1000 pg/mg, and the linear correlation (R2) of the calibration curves was above 0.998 for all three analytes. The bias varied from -6.5-13.1%, while the intra- and inter-day precision relative standard deviation (RSD) values were 4.3-12.4% and 3.7-13.2%, respectively. Recoveries ranged from 79.3% to 103.5%, and matrix effects ranged from 74.3% to 105.5%. The described method was used for the quantitative determination of koumine, gelsemine, and gelsenicine in a human hair sample from a Gelsemium elegans poisoning case. The highest concentrations of koumine, gelsemine, and gelsenicine were 27.2, 18.1, and 4.2 pg/mg, respectively, and corresponded to the segment associated with the ingestion period. To our knowledge, this is the first study to describe hair analysis in a G. elegans poisoning case and to provide quantitative toxicological findings.Immunotherapy has been developing at an unprecedented speed with promising therapeutic outcomes in the wide spectrum of cancers. Up until now, most immunotherapies have focused on adaptive immunity; however, investigating the potential of macrophage phagocytosis and consequent adaptive immune cross-priming has led to a growing interest in exploiting macrophages in cancer therapy. In light of the positive evidence from preclinical studies and early clinical data, targeting macrophage phagocytosis has become a promising therapeutic strategy. Here, we review therapies based on harnessing and amplifying macrophage phagocytosis, such as blocking phagocytosis checkpoints and exploiting nanoparticles as efficient approaches in elevating macrophages-mediated phagocytosis. The present study introduces CAR-macrophage as the state-of-the-art modality serving as the bridge between the innate and adaptive immune system to mount a superior anti-tumor response in the treatment of cancer. We also take a look at the recent reports of therapies based on CAR-engineered macrophages with the hope of providing a future research direction for expanding the application of CAR-macrophage therapy.The mechanisms that control B cell terminal differentiation remain undefined. Here, we investigate the role of bromodomain-containing protein 4 (Brd4) in regulating B cell differentiation and its therapeutic potential for B cell-mediated autoimmune diseases including systemic lupus erythematosus (SLE). We showed that Brd4 inhibitor PFI-1 suppressed plasmablast-mediated plasma cell differentiation in healthy human CD19+ B cells. PFI-1 reduced IgG and IgM secretion in costimulation-induced human B cells. We also observed a reduced percentage of plasma cells in mice with B cell-specific deletion of the Brd4 gene (Brd4flox/floxCD19-cre+). Mechanistically, using the luciferase reporter assay and the chromatin immunoprecipitation, we explored that Brd4 regulates the expression of B lymphocyte-induced maturation protein 1 (BLIMP1), an important transcript factor that is involved in modulation of plasma cell differentiation. Interestingly, PFI-1 decreased the percentages of plasmablasts and plasma cells from patients with SLE. PFI-1 administration reduced the percentages of plasma cells, hypergammaglobulinemia, and attenuated nephritis in MRL/lpr lupus mice. Pristane-injected Brd4flox/floxCD19-cre+ mice exhibited improved nephritis and reduced percentages of plasma cells. These findings suggest an essential factor of Brd4 in regulating plasma cell differentiation. Brd4 inhibition may be a potential strategy for the treatment of B cell-associated autoimmune disorders.
Fetal growth and development depend on metabolic energy from placental mitochondria. However, the impact of placental mitochondria on the occurrence of macrosomia remains unclear. We aimed to explore the association between macrosomia without gestational diabetes mellitus (non-GDM) and changes in placental mitochondrial DNA (mtDNA) copy number and methylation.
Fifty-four newborns with macrosomia and 54 normal birthweight controls were enrolled in this study. Placental mtDNA copy number and mRNA expression of nuclear genes related to mitochondrial replication or ATP synthesis-related genes were measured by real-time quantitative polymerase chain reaction (qPCR). Methylation levels of the non-coding regulatory region D-loop and ATP synthesis-related genes were detected by targeted bisulfite sequencing.
Newborns with macrosomia had lower placental mtDNA copy number and higher methylation rates of the CpG15 site in the D-loop region (D-CpG15) and CpG6 site in the cytochrome C oxidase III (COX3) gene (COX3-CpG6) than normal birth weight newborns. After adjusting for potential covariates (gestational age, prepregnancy BMI, and infant sex), decreased placental mtDNA copy number (adjusted odds ratio [aOR]=2.09, 95% confidence interval [CI] 1.03-4.25), elevated methylation rate of D-CpG15 (aOR=2.06, 95% CI 1.03-4.09) and COX3-CpG6 (aOR=2.13, 95% CI 1.08-4.20) remained significantly associated with a higher risk of macrosomia.
Reduced mtDNA copy number and increased methylation levels of specific loci at mtDNA would increase the risk of macrosomia. However, the detailed molecular mechanism needs further identification.
Reduced mtDNA copy number and increased methylation levels of specific loci at mtDNA would increase the risk of macrosomia. However, the detailed molecular mechanism needs further identification.A selective method for preconcentration and determination of methylmercury (MeHg) and inorganic mercury (iHg) in natural water samples at the ng L-1 level has been developed. The method involves adsorption of Hg species into a 3D printed metal scavenger and sequential elution with acidic thiourea solutions before ICP-MS determination. Experimental parameters affecting the preconcentration of MeHg and iHg such as the sample matrix, effect of the flow rate on adsorption, eluent composition, and elution mode have been studied in detail. The obtained method detection limits, considering the preconcentration factors of 42 and 93, were found to be 0.05 ng L-1 and 0.08 ng L-1 for MeHg and iHg, respectively. The accuracy of the method was assessed with a certified groundwater reference material ERM-CA615 (certified total iHg concentration 37 ± 4 ng L-1). The determined MeHg concentration was below MDL while iHg concentration was determined to be 41.2 ± 0.5 ng L-1. Both MeHg and iHg were also spiked to natural water samples at 5 ng L-1 concentration and favorable spiking recoveries of 88-97% were obtained. The speciation procedure was successfully applied to two lake water samples where MeHg and iHg concentrations ranged from 0.18 to 0.24 ng L-1 and 0.50-0.62 ng L-1, respectively. The results obtained demonstrate that the developed 3D printed metal scavenger-based method for preconcentration and speciation of Hg is simple and sensitive for the determination of Hg species at an ultra-trace level in water samples.GUMBOS (Group of Uniform Materials Based on Organic Salts) have recently emerged as interesting materials for protein analysis due to their unique features and high tunability. In this regard, four novel erythrosin B (EB)-based GUMBOS were synthesized and their potential to discriminate among proteins with distinct properties (e.g., size, charge, and hydrophobicity) was assessed. These solid-phase materials were prepared using a single-step metathesis reaction between EB and various phosphonium and ammonium cations, namely tetrabutylphosphonium (P4444+), tributylhexadecylphosphonium (P44416+), tetrabutylammonium (N4444+), and benzyldimethylhexadecylammonium (BDHA+). Subsequently, the effect of pH (3.0, 4.5, and 6.0) and reaction time (5, 10, and 15 min) on the discriminatory power of synthesized GUMBOS was evaluated. Absorption spectra resulting from the interaction between EB-based GUMBOS and proteins were analyzed using partial least squares discriminant analysis (PLSDA). selleck chemicals Unlike time, the pH value was determined to have influence over GUMBOS discrimination potential.
