Recreating a road traffic accident scheme is a task of current importance. There are several main problems when drawing up a plan of accident: a long-term collection of all information about an accident, inaccuracies, and errors during manual data fixation. All these disadvantages affect further decision-making during a detailed analysis of an accident.
View Article and Find Full Text PDFCD8 T cell differentiation into effector cells is initiated early after antigen encounter by signals from the T cell antigen receptor and costimulatory molecules. The molecular mechanisms that establish the timing and rate of differentiation however are not defined. Here we show that the RNA binding proteins (RBP) ZFP36 and ZFP36L1 limit the rate of differentiation of activated naïve CD8 T cells and the potency of the resulting cytotoxic lymphocytes.
View Article and Find Full Text PDFTo identify roles of RNA binding proteins (RBPs) in the differentiation or survival of antibody secreting plasma cells we performed a CRISPR/Cas9 knockout screen of 1213 mouse RBPs for their ability to affect proliferation and/or survival, and the abundance of differentiated CD138 + cells in vitro. We validated the binding partners CSDE1 and STRAP as well as the mA binding protein YTHDF2 as promoting the accumulation of CD138 + cells in vitro. We validated the EIF3 subunits EIF3K and EIF3L and components of the CCR4-NOT complex as inhibitors of CD138 + cell accumulation in vitro.
View Article and Find Full Text PDFThe aim of this study was to test the steepness of body size variation in males and females in the widespread ground beetle in geographical gradients. Beetles were sampled in 15 regions of Europe and Asia, and sampling territories differed 17° in latitude and 121° in longitude. We measured six linear traits in every captured beetle and formed a data set that included 2154 individuals.
View Article and Find Full Text PDFMotivation: The annotation of small open reading frames (smORFs) of <100 codons (<300 nucleotides) is challenging due to the large number of such sequences in the genome.
Results: In this study, we developed a computational pipeline, which we have named ORFLine, that stringently identifies smORFs and classifies them according to their position within transcripts. We identified a total of 5744 unique smORFs in datasets from mouse B and T lymphocytes and systematically characterized them using ORFLine.
Assessment of spatial patterns of potentially toxic metals is one of the most urgent tasks in soil chemistry. In this study, descriptive statistics and three methods of multivariate statistical analysis, such as the hierarchical cluster analysis (HCA), correlation analysis, and conditional inference tree (CIT), were used to identify patterns and potential sources of heavy metals (Co, Ni, Cu, Cr, Pb, MnO, and Zn). The investigation was carried out on 81 sample points, using 20 testing parameters.
View Article and Find Full Text PDFCell migration relies on coordinated activity of chemotactic and guidance receptors. Here, we report a specific role for the RNA-binding protein ZFP36L1 in limiting the abundance of molecules involved in the homing of antibody-secreting cells (ASCs) to the bone marrow (BM). In the absence of ZFP36L1, ASCs build up in the spleen and the liver and show diminished accumulation in the BM.
View Article and Find Full Text PDFGround beetles in multiple species vary greatly in the expression of the shape on sexual traits, resulting in a sexual shape dimorphism as a consequence of sexual selection differences. The present research focuses on the study of inter and intrasexual sexual shape dimorphism of two generalist genera of ground beetles and . Geometric morphometric methods were applied to five generalist species of ground beetles , , , , and and several multivariate analyses were applied for two different traits, abdomen and elytra.
View Article and Find Full Text PDFWe present a method of minimally invasive transcutaneous insertion of screws using a prefabricated extracorporeal navigation system using additive technologies (based on primary data obtained from the DICOM package in multi-detector computed tomography of the affected spine segment) according to the principle of personalized medicine. The method was tested on 10 dogs of different breeds with generally similar mechanism of trauma and typical consequences that led to fracture and dislocation of one of the lumbar vertebrae. In all animals, a positive treatment outcome of different degrees was achieved.
View Article and Find Full Text PDFEmission characteristics of heat recirculating porous burners with high temperature heat extraction are studied numerically. Two types of burners are considered: counterflow porous burner (CFB) and reciprocal counterflow porous burner (RCFB). The combustion of methane-air mixtures flowing through the porous media is modeled by solving steady state governing equations to obtain the flame temperature and species profiles.
View Article and Find Full Text PDFOrnithine transcarbamylase (OTC) deficiency is an X-linked urea cycle disorder associated with high mortality. Although a promising treatment for late-onset OTC deficiency, adeno-associated virus (AAV) neonatal gene therapy would only provide short-term therapeutic effects as the non-integrated genome gets lost during hepatocyte proliferation. CRISPR-Cas9-mediated homology-directed repair can correct a G-to-A mutation in 10% of OTC alleles in the livers of newborn OTC mice.
View Article and Find Full Text PDFPrimordial magnetic fields (PMFs), being present before the epoch of cosmic recombination, induce small-scale baryonic density fluctuations. These inhomogeneities lead to an inhomogeneous recombination process that alters the peaks and heights of the large-scale anisotropies of the cosmic microwave background (CMB) radiation. Utilizing numerical compressible MHD calculations and a Monte Carlo Markov chain analysis, which compares calculated CMB anisotropies with those observed by the WMAP and Planck satellites, we derive limits on the magnitude of putative PMFs.
View Article and Find Full Text PDFCoal-fired power stations are significant sources of soil contamination with heavy metals and a source of hazard to human health. The soil samples (n = 25) selected in the area around Novocherkassk Power Station (Rostov Region, Russia) within a radius of up to 20 km revealed the enrichment with Pb, Cu and Zn. The heavy metals (HM) content in soil is reduced in the following sequence: Mn > Cr > Zn > Ni > Cu > Pb > Co.
View Article and Find Full Text PDFMany genetic diseases, including hemophilia, require long-term therapeutic effects. Despite the initial success of liver-directed adeno-associated virus (AAV) gene therapy for hemophilia in clinical trials, long-term sustained therapeutic effects have yet to be seen. One explanation for the gradual decline of efficacy over time is that the nonintegrating AAV vector genome could be lost during cell division during hepatocyte turnover, albeit at a slow pace in adults.
View Article and Find Full Text PDFIn the original HTML version of this Article, the order of authors within the author list was incorrect. The consortium VRS Castricum was incorrectly listed after Theunis Piersma and should have been listed after Cornelis J. Camphuysen.
View Article and Find Full Text PDFUnder climate warming, migratory birds should align reproduction dates with advancing plant and arthropod phenology. To arrive on the breeding grounds earlier, migrants may speed up spring migration by curtailing the time spent en route, possibly at the cost of decreased survival rates. Based on a decades-long series of observations along an entire flyway, we show that when refuelling time is limited, variation in food abundance in the spring staging area affects fitness.
View Article and Find Full Text PDFModern portable and hand-held Raman spectrometers that recently have become widespread in drug quality screening have good reproducibility and are able to detect small concentrations of substances in mixtures of several components or distinguish compounds similar in structure and having minimal differences in spectrum with appropriate mathematical processing methods. Among other spectrum comparison approaches, the peak search at their location is the most important task of spectral imaging of the studied samples. In this work, the Raman spectra of liquid drugs involved in the governmental non-destructive quality screening program performed by 8 mobile laboratories equipped with Raman spectrometers with uncooled detector and a 532 nm laser were compared with reference sample spectra using the peak windows correlation (PWC) algorithm developed in this work by authors.
View Article and Find Full Text PDFSequence validation of plasmid DNA is a crucial quality control step that must occur prior to adeno-associated virus (AAV) vector packaging through plasmid transfection. AAV cis-plasmids present unique challenges to sequence analysis, as they contain inverted terminal repeats and are prone to sequence rearrangements. An accurate and rapid next-generation sequencing approach has been established to analyze full-length sequences of AAV cis-plasmids within 3.
View Article and Find Full Text PDFClinical translation of in vivo genome editing to treat human genetic diseases requires thorough preclinical studies in relevant animal models to assess safety and efficacy. A promising approach to treat hypercholesterolemia is inactivating the secreted protein PCSK9, an antagonist of the LDL receptor. Here we show that single infusions in six non-human primates of adeno-associated virus vector expressing an engineered meganuclease targeting PCSK9 results in dose-dependent disruption of PCSK9 in liver, as well as a stable reduction in circulating PCSK9 and serum cholesterol.
View Article and Find Full Text PDFThere is much interest in effective copper chelators to correct copper dyshomeostasis in neurodegenerative and oncological diseases. In this study, a recombinant fusion protein for expression in cells was constructed from glutathione-S-transferase (GST) and the N-terminal domain (ectodomain) of human high affinity copper transporter CTR1 (hNdCTR1), which has three metal-bound motifs. Several biological properties of the GST-hNdCTR1 fusion protein were assessed.
View Article and Find Full Text PDFComposting is viewed as one of the primary methods to treat organic wastes. Co-composting may improve the efficiency of this treatment by establishing the most suitable conditions for decomposers than those present in the individual wastes. Given that bacteria and fungi are the driving agents of composting, information about the composition of their communities and dynamics during composting may improve reproducibility, performance and quality of the final compost as well as help to evaluate the potential human health risk and the choice of the most appropriate application procedure.
View Article and Find Full Text PDFRNA-binding proteins of the ZFP36 family are best known for inhibiting the expression of cytokines through binding to AU-rich elements in the 3' untranslated region and promoting mRNA decay. Here we identified an indispensable role for ZFP36L1 as the regulator of a post-transcriptional hub that determined the identity of marginal-zone B cells by promoting their proper localization and survival. ZFP36L1 controlled a gene-expression program related to signaling, cell adhesion and locomotion; it achieved this in part by limiting expression of the transcription factors KLF2 and IRF8, which are known to enforce the follicular B cell phenotype.
View Article and Find Full Text PDFProgression through the stages of lymphocyte development requires coordination of the cell cycle. Such coordination ensures genomic integrity while cells somatically rearrange their antigen receptor genes [in a process called variable-diversity-joining (VDJ) recombination] and, upon successful rearrangement, expands the pools of progenitor lymphocytes. Here we show that in developing B lymphocytes, the RNA-binding proteins (RBPs) ZFP36L1 and ZFP36L2 are critical for maintaining quiescence before precursor B cell receptor (pre-BCR) expression and for reestablishing quiescence after pre-BCR-induced expansion.
View Article and Find Full Text PDFBackground: Solar archival tags (henceforth called geolocators) are tracking devices deployed on animals to reconstruct their long-distance movements on the basis of locations inferred post hoc with reference to the geographical and seasonal variations in the timing and speeds of sunrise and sunset. The increased use of geolocators has created a need for analytical tools to produce accurate and objective estimates of migration routes that are explicit in their uncertainty about the position estimates.
Results: We developed a hidden Markov chain model for the analysis of geolocator data.