A theoretical model for the formation of ultrasonic signals in metallic microcrystalline rods taking into account the metastable behavior of their defective states is proposed. The influence of ...metastable states of the defective structure of samples on the features of changes in their resonant frequencies in ultrasonic experiments of fast dynamics is analyzed. The decrease in Young’s modulus in such processes is explained. The correspondence between theoretical and experimental data is demonstrated for the example of resonant acoustic vibrations of rods made of aluminum alloy D16.
MicroRNA (miRNA) and other types of small regulatory RNAs play a crucial role in the regulation of gene expression in eukaryotes. Several distinct classes of small regulatory RNAs have been ...discovered in recent years. To extend the repertoire of small RNAs characterized in mammals and to examine relationship between host miRNA expression and viral infection we used Illumina's ultrahigh throughput sequencing approach. We sequenced three small RNA libraries prepared from cell line derived from the adult bovine kidney under normal conditions and upon infection of the cell line with Bovine herpesvirus 1. We used a bioinformatics approach to distinguish authentic mature miRNA sequences from other classes of small RNAs and short RNA fragments represented in the sequencing data. Using this approach we detected 219 out of 356 known bovine miRNAs and 115 respective miRNA* sequences. In addition we identified five new bovine orthologs of known mammalian miRNAs and discovered 268 new cow miRNAs many of which are not identifiable in other mammalian genomes and thus might be specific to the ruminant lineage. In addition we found seven new bovine mirtron candidates. We also discovered 10 small nucleolar RNA (snoRNA) loci that give rise to small RNA with possible miRNA-like function. Results presented in this study extend our knowledge of the biology and evolution of small regulatory RNAs in mammals and illuminate mechanisms of small RNA biogenesis and function. New miRNA sequences and the original sequencing data have been submitted to miRNA repository (miRBase) and NCBI GEO archive respectively. We envisage that these resources will facilitate functional annotation of the bovine genome and promote further functional and comparative genomics studies of small regulatory RNA in mammals.
Multicentric carpotarsal osteolysis (MCTO) is a rare skeletal dysplasia characterized by aggressive osteolysis, particularly affecting the carpal and tarsal bones, and is frequently associated with ...progressive renal failure. Using exome capture and next-generation sequencing in five unrelated simplex cases of MCTO, we identified previously unreported missense mutations clustering within a 51 base pair region of the single exon of MAFB, validated by Sanger sequencing. A further six unrelated simplex cases with MCTO were also heterozygous for previously unreported mutations within this same region, as were affected members of two families with autosomal-dominant MCTO. MAFB encodes a transcription factor that negatively regulates RANKL-induced osteoclastogenesis and is essential for normal renal development. Identification of this gene paves the way for development of novel therapeutic approaches for this crippling disease and provides insight into normal bone and kidney development.
The author’s method for calculating the brink depth taking into account the vacuum under the nappe is used to evaluate the effect of the vacuum on the brink depth. It should be taken it into account ...when determining the discharge of water by the end-depth method in channels with a free overfall.
The 3' untranslated regions (3'UTRs) of eukaryotic genes regulate mRNA stability, localization and translation. Here, we present evidence that large numbers of 3'UTRs in human, mouse and fly are also ...expressed separately from the associated protein-coding sequences to which they are normally linked, likely by post-transcriptional cleavage. Analysis of CAGE (capped analysis of gene expression), SAGE (serial analysis of gene expression) and cDNA libraries, as well as microarray expression profiles, demonstrate that the independent expression of 3'UTRs is a regulated and conserved genome-wide phenomenon. We characterize the expression of several 3'UTR-derived RNAs (uaRNAs) in detail in mouse embryos, showing by in situ hybridization that these transcripts are expressed in a cell- and subcellular-specific manner. Our results suggest that 3'UTR sequences can function not only in cis to regulate protein expression, but also intrinsically and independently in trans, likely as noncoding RNAs, a conclusion supported by a number of previous genetic studies. Our findings suggest novel functions for 3'UTRs, as well as caution in the use of 3'UTR sequence probes to analyze gene expression.
Recent advances in DNA sequencing have enabled mapping of genes for monogenic traits in families with small pedigrees and even in unrelated cases. We report the identification of disease-causing ...mutations in a rare, severe, skeletal dysplasia, studying a family of two healthy unrelated parents and two affected children using whole-exome sequencing. The two affected daughters have clinical and radiographic features suggestive of anauxetic dysplasia (OMIM 607095), a rare form of dwarfism caused by mutations of RMRP. However, mutations of RMRP were excluded in this family by direct sequencing. Our studies identified two novel compound heterozygous loss-of-function mutations in POP1, which encodes a core component of the RNase mitochondrial RNA processing (RNase MRP) complex that directly interacts with the RMRP RNA domains that are affected in anauxetic dysplasia. We demonstrate that these mutations impair the integrity and activity of this complex and that they impair cell proliferation, providing likely molecular and cellular mechanisms by which POP1 mutations cause this severe skeletal dysplasia.
The process of generating an acoustic signal during laser heating of metals and dielectrics is analyzed in the framework of the theory of thermoelasticity. A comparison of the experimental ...optoacoustic signal and the theoretical distribution of mechanical stresses for plates with a hole of aluminum alloy and silicon nitride is performed. It was found that the standard theory of thermoelasticity can qualitatively describe the dependence of the optoacoustic signal on the stress near the hole in the silicon nitride plate, but is not enough to correctly describe the dependence of the signal on the stress near the hole in the metal plate. It is noted that in order to achieve agreement between the obtained experimental and theoretical results for metals, in addition to the thermal effect of laser radiation on the lattice, it is necessary to take into account the additional effect of the electron system.
MicroRNAs (miRNAs) are a rapidly growing family of small regulatory RNAs modulating gene expression in plants and animals. In animals, most of the miRNAs discovered in early studies were found to be ...evolutionarily conserved across the whole kingdom. More recent studies, however, have identified many miRNAs that are specific to a particular group of organisms or even a single species. These present a question about evolution of the individual miRNAs and their role in establishing and maintaining lineage-specific functions and characteristics.
In this study, we describe a detailed analysis of the miRNA cluster (hereafter mir-379/mir-656 cluster) located within the imprinted DLK-DIO3 region on human chromosome 14. We show that orthologous miRNA clusters are present in all sequenced genomes of the placental (eutherian) mammals but not in the marsupial (metatherian), monotreme (prototherian), or any other vertebrate genomes. We provide evidence that the locus encompassing this cluster emerged in an early eutherian ancestor prior to the radiation of modern placental mammals by tandem duplication of the ancient precursor sequence. The original amplified cluster may have contained in excess of 250 miRNA precursor sequences, most of which now appear to be inactive. Examination of the eutherian genomes showed that the cluster has been maintained in evolution for approximately 100 Myr.
Analysis of genes that contain predicted evolutionarily conserved targets for miRNAs from this cluster revealed significant overrepresentation of the Gene Ontology terms associated with biological processes such as neurogenesis, embryonic development, transcriptional regulation, and RNA metabolism. Consistent with these findings, a survey of the miRNA expression data within the cluster demonstrates a strong bias toward brain and placenta samples from adult organisms and some embryonic tissues.
Our results suggest that emergence of the mir-379/mir-656 miRNA cluster was one of the factors that facilitated evolution of the placental mammals. Overrepresentation of genes involved in regulation of neurogenesis among predicted miRNAs targets indicates an important role of the mir-379/mir-656 cluster in this biological process in the placental mammals.
KLF1 (formerly known as EKLF) regulates the development of erythroid cells from bi-potent progenitor cells via the transcriptional activation of a diverse set of genes. Mice lacking Klf1 die in utero ...prior to E15 from severe anemia due to the inadequate expression of genes controlling hemoglobin production, cell membrane and cytoskeletal integrity, and the cell cycle. We have recently described the full repertoire of KLF1 binding sites in vivo by performing KLF1 ChIP-seq in primary erythroid tissue (E14.5 fetal liver). Here we describe the KLF1-dependent erythroid transcriptome by comparing mRNA-seq from Klf1(+/+) and Klf1(-/-) erythroid tissue. This has revealed novel target genes not previously obtainable by traditional microarray technology, and provided novel insights into the function of KLF1 as a transcriptional activator. We define a cis-regulatory module bound by KLF1, GATA1, TAL1, and EP300 that coordinates a core set of erythroid genes. We also describe a novel set of erythroid-specific promoters that drive high-level expression of otherwise ubiquitously expressed genes in erythroid cells. Our study has identified two novel lncRNAs that are dynamically expressed during erythroid differentiation, and discovered a role for KLF1 in directing apoptotic gene expression to drive the terminal stages of erythroid maturation.
Achieving the highest precision for theoretical predictions at the LHC requires the calculation of hard-scattering cross sections that include perturbative QCD corrections up to (N)NNLO and ...electroweak (EW) corrections up to NLO. Parton distribution functions (PDFs) need to be provided with matching accuracy, which in the case of QED effects involves introducing the photon parton distribution of the proton,
x
γ
(
x
,
Q
2
)
. In this work a determination of the photon PDF from fits to recent ATLAS measurements of high-mass Drell–Yan dilepton production at
s
=
8
TeV is presented. This analysis is based on the xFitter framework, and has required improvements both in the APFEL program, to account for NLO QED effects, and in the aMCfast interface to account for the photon-initiated contributions in the EW calculations within MadGraph5_aMC@NLO. The results are compared with other recent QED fits and determinations of the photon PDF, consistent results are found.
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