Clinico–anatomical characteristic of the traffic trauma in the megapolis environment.Second report: anatomical verification of injuries

Objective.Verification of clinic–anatomical characteristics of trauma as a consequence of traffic accident in the megapolis environment. Materials and methods. Retrospective analysis of the data obtained was conducted in 1159 injured persons, who were traumatized as a consequence of a traffic accident in megapolis. Results.There was established, that as a result of traffic accident in the megapolis environment, the injured persons most frequently obtained trauma of the head – 68.31%, of thoracic cage – 57.07%, and of the extremities – 53.99%. The majority of the injured persons survived have had the trauma of the head (67.13%), of the thoracic cage (55.74%) and extremities (53.63%), while mostly rare – pelvic trauma (15.70%). Among the injured persons, who died, the head injuries was noted in 94.0%, thoracic trauma – in 86.0%, and abdominal injuries – in 76.0%. Conclusion.Trauma as a consequence of traffic accident in the megapolis environment constitutes a multicomponent injury (2.4 damages in every injured person). The result of the traumatic process course depends on the injury composition (in the injured persons survived, the combination coefficient was 2.3, while in the dead – 3.8) and on damage of a certain anatomic–functional local site.The head, thoracic and pelvic sites have constituted the most dangerous localizations

Dense and accurate whole-chromosome haplotyping of individual genomes

The diploid nature of the human genome is neglected in many analyses done today, where a genome is perceived as a set of unphased variants with respect to a reference genome. This lack of haplotype-level analyses can be explained by a lack of methods that can produce dense and accurate chromosome-length haplotypes at reasonable costs. Here we introduce an integrative phasing strategy that combines global, but sparse haplotypes obtained from strand-specific single-cell sequencing (Strand-seq) with dense, yet local, haplotype information available through long-read or linked-read sequencing. We provide comprehensive guidance on the required sequencing depths and reliably assign more than 95% of alleles (NA12878) to their parental haplotypes using as few as 10 Strand-seq libraries in combination with 10-fold coverage PacBio data or, alternatively, 10X Genomics linked-read sequencing data. We conclude that the combination of Strand-seq with different technologies represents an attractive solution to chart the genetic variation of diploid genomes

Improvement of characterization accuracy of the nonlinear photonic crystals using finite elements-iterative method

We investigate nonlinear one- and two-dimensional photonic crystals by applying a finite element-iterative method.Numerical results show the essential influence of nonlinear elements embedded into a quarter-wave stack and the sharp photonic crystal waveguide bend on the spectral characteristics of these structures. We compare our results with those obtained in [21] from the discrete equation method for the case of a sharp waveguide bend. The comparison shows that neglecting the nonuniform field distribution inside the embedded nonlinear elements leads to overestimation of the waveguide bend transmissivity.Comment: 5 pages, 9 figure

Identification of Two Protein-Signaling States Delineating Transcriptionally Heterogeneous Human Medulloblastoma

Summary: The brain cancer medulloblastoma consists of different transcriptional subgroups. To characterize medulloblastoma at the phosphoprotein-signaling level, we performed high-throughput peptide phosphorylation profiling on a large cohort of SHH (Sonic Hedgehog), group 3, and group 4 medulloblastomas. We identified two major protein-signaling profiles. One profile was associated with rapid death post-recurrence and resembled MYC-like signaling for which MYC lesions are sufficient but not necessary. The second profile showed enrichment for DNA damage, as well as apoptotic and neuronal signaling. Integrative analysis demonstrated that heterogeneous transcriptional input converges on these protein-signaling profiles: all SHH and a subset of group 3 patients exhibited the MYC-like protein-signaling profile; the majority of the other group 3 subset and group 4 patients displayed the DNA damage/apoptotic/neuronal signaling profile. Functional analysis of enriched pathways highlighted cell-cycle progression and protein synthesis as therapeutic targets for MYC-like medulloblastoma. : Using peptide phosphorylation profiling, Zomerman et al. identify two medulloblastoma phosphoprotein-signaling profiles that have prognostic value and are potentially targetable. They find that these profiles extend across transcriptome-based subgroup borders. This suggests that diverse genetic information converges on common protein-signaling pathways and highlights protein-signaling as a unique information layer. Keywords: medulloblastoma, protein-signaling, protein synthesis, MYC, TP53, proteome, phosphoproteom

Whole-genome sequencing of 1,171 elderly admixed individuals from Brazil

As whole-genome sequencing (WGS) becomes the gold standard tool for studying population genomics and medical applications, data on diverse non-European and admixed individuals are still scarce. Here, we present a high-coverage WGS dataset of 1,171 highly admixed elderly Brazilians from a census-based cohort, providing over 76 million variants, of which ~2 million are absent from large public databases. WGS enables identification of ~2,000 previously undescribed mobile element insertions without previous description, nearly 5 Mb of genomic segments absent from the human genome reference, and over 140 alleles from HLA genes absent from public resources. We reclassify and curate pathogenicity assertions for nearly four hundred variants in genes associated with dominantly-inherited Mendelian disorders and calculate the incidence for selected recessive disorders, demonstrating the clinical usefulness of the present study. Finally, we observe that whole-genome and HLA imputation could be significantly improved compared to available datasets since rare variation represents the largest proportion of input from WGS. These results demonstrate that even smaller sample sizes of underrepresented populations bring relevant data for genomic studies, especially when exploring analyses allowed only by WGS

Monitoring the genomic stability of in vitro cultured rat bone-marrow-derived mesenchymal stem cells

Bone-marrow-derived mesenchymal stem cells (MSCs) are multipotent cells capable of self-renewal and differentiation into multiple cell types. Accumulating preclinical and clinical evidence indicates that MSCs are good candidates to use as cell therapy in many degenerative diseases. For MSC clinical applications, an adequate number of cells are necessary so an extensive expansion is required. However, spontaneous immortalization and malignant transformation of MSCs after culture expansion have been reported in human and mouse, while very few data are present for rat MSCs (rMSCs). In this study, we monitored the chromosomal status of rMSCs at several passages in vitro, also testing the influence of four different cell culture conditions. We first used the conventional traditional cytogenetic techniques, in order to have the opportunity to observe even minor structural abnormalities and to identify low-degree mosaic conditions. Then, a more detailed genomic analysis was conducted by array comparative genomic hybridization. We demonstrated that, irrespective of culture conditions, rMSCs manifested a markedly aneuploid karyotype and a progressive chromosomal instability in all the passages we analyzed and that they are anything but stable during in vitro culture. Despite the fact that the risk of neoplastic transformation associated with this genomic instability needs to be further addressed and considering the apparent genomic stability reported for in vitro cultured human MSCs (hMSCs), our findings underline the fact that rMSCs may not in fact be a good model for effectively exploring the full clinical therapeutic potential of hMSCs