Properties and expression of Na+/K+-ATPase α-subunit isoforms in the brain of the swamp eel, Monopterus albus, which has unusually high brain ammonia tolerance

10.1371/journal.pone.0084298PLoS ONE812-POLN

The use of dynamic elastomeric fabric orthosis suits as an orthotic intervention in the management of children with neuropathic onset scoliosis: A retrospective audit of routine clinical case notes

BACKGROUND: To date the main treatment approach for neuropathic onset scoliosis has utilised thoracic lumbar sacral orthoses (TLSO) to stabilize the spine and enable stable sitting. Dynamic elastomeric fabric orthoses (DEFOs) may achieve both of these aims if used as an early intervention. Due to a lack of evidence in this area, a retrospective audit of case notes was undertaken to understand current orthotic practice investigating the usage, outcomes and clinical characteristics of treated children with neuropathic onset scoliosis. Clinical notes of 180 children at risk for, or identified with, scoliosis were audited using a search matrix to identify diagnostic group, spinal muscle tone, Gross Motor Functional Classification Scale (GMFCS) level, orthotic treatment modalities, scoliosis specific data, surgical interventions, adaptive technologies used, and outcome measurements reported. RESULTS: Of the 180 notes examined, 85 were male; mean age nine years one month [SD four years seven months]. Spinal muscle tone was reported in 137 cases: 122/137 presented as low tone, 4/137 high tone, 6/137 fluctuating tone and 5/137 typical tone. Scoliosis was confirmed in (77/180) of whom (39/77) used a DEFO. Another (43/180) had a spinal curve developing, of whom (22/43) used a DEFO. The remaining (60/180) had no report of spinal curvature, but used a DEFO as a preventative measure. GMFCS scores were reported for 49 children of whom 14/49 were graded as level 4 and 17/49 level 5. Of the children with scoliosis who had spinal curve shapes reported, 48/60 had a C-shape presentation and 12/60 had an S-shape. CONCLUSIONS: The findings confirm previously reported papers in children with neuropathic onset scoliosis in relation to curve shape and GMFCS levels. It provides some evidence of the role DEFOs may have in the management of these children, and highlights the need for further research in this area due to the lack of peer-reviewed publications

Transcriptome-Wide Prediction of miRNA Targets in Human and Mouse Using FASTH

Transcriptional regulation by microRNAs (miRNAs) involves complementary base-pairing at target sites on mRNAs, yielding complex secondary structures. Here we introduce an efficient computational approach and software (FASTH) for genome-scale prediction of miRNA target sites based on minimizing the free energy of duplex structure. We apply our approach to identify miRNA target sites in the human and mouse transcriptomes. Our results show that short sequence motifs in the 5′ end of miRNAs frequently match mRNAs perfectly, not only at validated target sites but additionally at many other, energetically favourable sites. High-quality matching regions are abundant and occur at similar frequencies in all mRNA regions, not only the 3′UTR. About one-third of potential miRNA target sites are reassigned to different mRNA regions, or gained or lost altogether, among different transcript isoforms from the same gene. Many potential miRNA target sites predicted in human are not found in mouse, and vice-versa, but among those that do occur in orthologous human and mouse mRNAs most are situated in corresponding mRNA regions, i.e. these sites are themselves orthologous. Using a luciferase assay in HEK293 cells, we validate four of six predicted miRNA-mRNA interactions, with the mRNA level reduced by an average of 73%. We demonstrate that a thermodynamically based computational approach to prediction of miRNA binding sites on mRNAs can be scaled to analyse complete mammalian transcriptome datasets. These results confirm and extend the scope of miRNA-mediated species- and transcript-specific regulation in different cell types, tissues and developmental conditions

Oncogenic Pathway Combinations Predict Clinical Prognosis in Gastric Cancer

Many solid cancers are known to exhibit a high degree of heterogeneity in their deregulation of different oncogenic pathways. We sought to identify major oncogenic pathways in gastric cancer (GC) with significant relationships to patient survival. Using gene expression signatures, we devised an in silico strategy to map patterns of oncogenic pathway activation in 301 primary gastric cancers, the second highest cause of global cancer mortality. We identified three oncogenic pathways (proliferation/stem cell, NF-κB, and Wnt/β-catenin) deregulated in the majority (>70%) of gastric cancers. We functionally validated these pathway predictions in a panel of gastric cancer cell lines. Patient stratification by oncogenic pathway combinations showed reproducible and significant survival differences in multiple cohorts, suggesting that pathway interactions may play an important role in influencing disease behavior. Individual GCs can be successfully taxonomized by oncogenic pathway activity into biologically and clinically relevant subgroups. Predicting pathway activity by expression signatures thus permits the study of multiple cancer-related pathways interacting simultaneously in primary cancers, at a scale not currently achievable by other platforms

A Sub-Cellular Viscoelastic Model for Cell Population Mechanics

Understanding the biomechanical properties and the effect of biomechanical force on epithelial cells is key to understanding how epithelial cells form uniquely shaped structures in two or three-dimensional space. Nevertheless, with the limitations and challenges posed by biological experiments at this scale, it becomes advantageous to use mathematical and ‘in silico’ (computational) models as an alternate solution. This paper introduces a single-cell-based model representing the cross section of a typical tissue. Each cell in this model is an individual unit containing several sub-cellular elements, such as the elastic plasma membrane, enclosed viscoelastic elements that play the role of cytoskeleton, and the viscoelastic elements of the cell nucleus. The cell membrane is divided into segments where each segment (or point) incorporates the cell's interaction and communication with other cells and its environment. The model is capable of simulating how cells cooperate and contribute to the overall structure and function of a particular tissue; it mimics many aspects of cellular behavior such as cell growth, division, apoptosis and polarization. The model allows for investigation of the biomechanical properties of cells, cell-cell interactions, effect of environment on cellular clusters, and how individual cells work together and contribute to the structure and function of a particular tissue. To evaluate the current approach in modeling different topologies of growing tissues in distinct biochemical conditions of the surrounding media, we model several key cellular phenomena, namely monolayer cell culture, effects of adhesion intensity, growth of epithelial cell through interaction with extra-cellular matrix (ECM), effects of a gap in the ECM, tensegrity and tissue morphogenesis and formation of hollow epithelial acini. The proposed computational model enables one to isolate the effects of biomechanical properties of individual cells and the communication between cells and their microenvironment while simultaneously allowing for the formation of clusters or sheets of cells that act together as one complex tissue

Review of Matrix Metalloproteinases’ Effect on the Hybrid Dentin Bond Layer Stability and Chlorhexidine Clinical Use to Prevent Bond Failure

This review describes the relationship between dentin collagen hybrid bond layer degradation and the Matrix Metalloproteinases (MMPs) after their release by acid etch and rinse adhesives and self etching bonding adhesives that can reduce the bond stability over time. MMP-2, MMP-8 and MMP-9 are indicated as the active proteases that breakdown the collagen fibrils in the hybrid bond layer. Phosphoric acid in the acid etch and rinse bonding process and acid primers in the self etch process are implicated in the release of these proteases and their activation by several non-collagen proteins also released from dentin by the etching. MMPs are released in saliva by salivary glands, by cells in the gingival crevices to crevicular fluid and by pulpal odontoblasts cells to the dentinal fluids. These sources may affect the hybrid layer also. Evidence of the bond strength deterioration over time and the ability of Chlorhexidine to prevent bond deterioration by inhibiting MMP action are discussed. Dentin Bonding procedure utilizing Chlorhexidine for different application times and concentrations are being developed. The application of 2% Chlorhexidine to the phosphoric acid etch surface after rinsing off the acid is the only procedure that has been clinically tested for a longer period of time and shown to prevent bond strength degradation so far. The adoption of this procedure is recommended as means of improving bond stability at this time

Genetic instability and anti-HPV immune response as drivers of infertility associated with HPV infection

Funding Information: RFBR grant 17–54-30002, Ministry of Science and Higher Education of the Russian Federation (Agreement No. 075–15–2019-1660) to Olga Smirnova. Publisher Copyright: © 2021, The Author(s).Human papillomavirus (HPV) is a sexually transmitted infection common among men and women of reproductive age worldwide. HPV viruses are associated with epithelial lesions and cancers. HPV infections have been shown to be significantly associated with many adverse effects in reproductive function. Infection with HPVs, specifically of high-oncogenic risk types (HR HPVs), affects different stages of human reproduction, resulting in a series of adverse outcomes: 1) reduction of male fertility (male infertility), characterized by qualitative and quantitative semen alterations; 2) impairment of couple fertility with increase of blastocyst apoptosis and reduction of endometrial implantation of trophoblastic cells; 3) defects of embryos and fetal development, with increase of spontaneous abortion and spontaneous preterm birth. The actual molecular mechanism(s) by which HPV infection is involved remain unclear. HPV-associated infertility as Janus, has two faces: one reflecting anti-HPV immunity, and the other, direct pathogenic effects of HPVs, specifically, of HR HPVs on the infected/HPV-replicating cells. Adverse effects observed for HR HPVs differ depending on the genotype of infecting virus, reflecting differential response of the host immune system as well as functional differences between HPVs and their individual proteins/antigens, including their ability to induce genetic instability/DNA damage. Review summarizes HPV involvement in all reproductive stages, evaluate the adverse role(s) played by HPVs, and identifies mechanisms of viral pathogenicity, common as well as specific for each stage of the reproduction process.publishersversionPeer reviewe