Role of IL-33 and ST2 signalling pathway in multiple sclerosis: expression by oligodendrocytes and inhibition of myelination in central nervous system

Recent research findings have provided convincing evidence indicating a role for Interleukin-33 (IL-33) signalling pathway in a number of central nervous system (CNS) diseases including multiple sclerosis (MS) and Alzheimer’s disease. However, the exact function of IL-33 molecule within the CNS under normal and pathological conditions is currently unknown. In this study, we have mapped cellular expression of IL-33 and its receptor ST2 by immunohistochemistry in the brain tissues of MS patients and appropriate controls; and investigated the functional significance of these findings in vitro using a myelinating culture system. Our results demonstrate that IL-33 is expressed by neurons, astrocytes and microglia as well as oligodendrocytes, while ST2 is expressed in the lesions by oligodendrocytes and within and around axons. Furthermore, the expression levels and patterns of IL-33 and ST2 in the lesions of acute and chronic MS patient brain samples are enhanced compared with the healthy brain tissues. Finally, our data using rat myelinating co-cultures suggest that IL-33 may play an important role in MS development by inhibiting CNS myelination

Evolving small-world networks with geographical attachment preference

We introduce a minimal extended evolving model for small-world networks which is controlled by a parameter. In this model the network growth is determined by the attachment of new nodes to already existing nodes that are geographically close. We analyze several topological properties for our model both analytically and by numerical simulations. The resulting network shows some important characteristics of real-life networks such as the small-world effect and a high clustering.Comment: 11 pages, 4 figure

Spatiotemporal Fluctuation Induced Transition in a Tumor Model with Immune Surveillance

We report on a simple model of spatial extend anti-tumor system with a fluctuation in growth rate, which can undergo a nonequilibrium phase transition. Three states as excited, sub-excited and non-excited states of a tumor are defined to describe its growth. The multiplicative noise is found to be double-face: The positive effect on a non-excited tumor and the negative effect on an excited tumor.Comment: 8pages,5figure

Safety and efficacy of etomidate and propofol anesthesia in elderly patients undergoing gastroscopy: A double-blind randomized clinical study

The aim of the present study is to compare the safety, efficacy and cost effectiveness of anesthetic regimens by compound, using etomidate and propofol in elderly patients undergoing gastroscopy. A total of 200 volunteers (65–79 years of age) scheduled for gastroscopy under anesthesia were randomly divided into the following groups: P, propofol (1.5–2.0 mg/kg); E, etomidate (0.15-0.2 mg/kg); P+E, propofol (0.75–1 mg/kg) followed by etomidate (0.075-0.1 mg/kg); and E+P, etomidate (0.075-0.01 mg/kg) followed by propofol (0.75–1 mg/kg). Vital signs and bispectral index were monitored at different time points. Complications, induction and examination time, anesthesia duration, and recovery and discharge time were recorded. At the end of the procedure, the satisfaction of patients, endoscopists and the anesthetist were evaluated. The recovery (6.1±1.2 h) and discharge times (24.8±2.8 h) in group E were significantly longer compared with groups P, P+E and E+P (P<0.05). The occurrence of injection pain in group P+E was significantly higher compared with the other three groups (P<0.05). In addition, the incidence of myoclonus and post-operative nausea and vomiting were significantly higher in group P+E compared with the other three groups (P<0.05). There was no statistical difference among the four groups with regards to the patients' immediate, post-procedure satisfaction (P>0.05). Furthermore, there was no difference in the satisfaction of anesthesia, as evaluated by the anesthetist and endoscopist, among the four groups (P>0.05). The present study demonstrates that anesthesia for gastroscopy in elderly patients can be safely and effectively accomplished using a drug regimen that combines propofol with etomidate. The combined use of propofol and etomidate has unique characteristics which improve hemodynamic stability, cause minimal respiratory depression and less side effects, provide rapid return to full activity and result in high levels of satisfaction

High Dimensional Apollonian Networks

We propose a simple algorithm which produces high dimensional Apollonian networks with both small-world and scale-free characteristics. We derive analytical expressions for the degree distribution, the clustering coefficient and the diameter of the networks, which are determined by their dimension

Adult Gli2+/-;Gli3Δ699/+ Male and Female Mice Display a Spectrum of Genital Malformation.

Disorders of sexual development (DSD) encompass a broad spectrum of urogenital malformations and are amongst the most common congenital birth defects. Although key genetic factors such as the hedgehog (Hh) family have been identified, a unifying postnatally viable model displaying the spectrum of male and female urogenital malformations has not yet been reported. Since human cases are diagnosed and treated at various stages postnatally, equivalent mouse models enabling analysis at similar stages are of significant interest. Additionally, all non-Hh based genetic models investigating DSD display normal females, leaving female urogenital development largely unknown. Here, we generated compound mutant mice, Gli2+/-;Gli3Δ699/+, which exhibit a spectrum of urogenital malformations in both males and females upon birth, and also carried them well into adulthood. Analysis of embryonic day (E)18.5 and adult mice revealed shortened anogenital distance (AGD), open ventral urethral groove, incomplete fusion of scrotal sac, abnormal penile size and structure, and incomplete testicular descent with hypoplasia in male mice, whereas female mutant mice displayed reduced AGD, urinary incontinence, and a number of uterine anomalies such as vaginal duplication. Male and female fertility was also investigated via breeding cages, and it was identified that male mice were infertile while females were unable to deliver despite becoming impregnated. We propose that Gli2+/-;Gli3Δ699/+ mice can serve as a genetic mouse model for common DSD such as cryptorchidism, hypospadias, and incomplete fusion of the scrotal sac in males, and a spectrum of uterine and vaginal abnormalities along with urinary incontinence in females, which could prove essential in revealing new insights into their equivalent diseases in humans

Multi-Player and Multi-Choice Quantum Game

We investigate a multi-player and multi-choice quantum game. We start from two-player and two-choice game and the result is better than its classical version. Then we extend it to N-player and N-choice cases. In the quantum domain, we provide a strategy with which players can always avoid the worst outcome. Also, by changing the value of the parameter of the initial state, the probabilities for players to obtain the best payoff will be much higher that in its classical version.Comment: 4 pages, 1 figur

MicroRNAs in Diabetic Kidney Disease

Rapid growth of diabetes and diabetic kidney disease exerts a great burden on society. Owing to the lack of effective treatments for diabetic kidney disease, treatment relies on drugs that either reduces its progression or involve renal replacement therapies, such as dialysis and kidney transplantation. It is urgent to search for biomarkers for early diagnosis and effective therapy. The discovery of microRNAs had lead to a new era of post-transcriptional regulators of gene expression. Studies from cells, experimental animal models and patients under diabetic conditions demonstrate that expression patterns of microRNAs are altered during the progression of diabetic kidney disease. Functional studies indicate that the ability of microRNAs to bind 3′ untranslated region of messenger RNA not only shows their capability to regulate expression of target genes, but also their therapeutic potential to diabetic kidney disease. The presence of microRNAs in plasma, serum, and urine has been shown to be possible biomarkers in diabetic kidney disease. Therefore, identification of the pathogenic role of microRNAs possesses an important clinical impact in terms of prevention and treatment of progression in diabetic kidney disease because it allows us to design novel and specific therapies and diagnostic tools for diabetic kidney disease

High lubricity meets load capacity: cartilage mimicking bilayer structure by brushing up stiff hydrogels from subsurface

Natural articular cartilage has ultralow friction even at high squeezing pressure. Biomimicking cartilage with soft materials has been and remains a grand challenge in the fields of materials science and engineering. Inspired by the unique structural features of the articular cartilage, as well as by its remarkable lubrication mechanisms dictated by the properties of the superficial layers, a novel archetype of cartilage‐mimicking bilayer material by robustly entangling thick hydrophilic polyelectrolyte brushes into the subsurface of a stiff hydrogel substrate is developed. The topmost soft polymer layer provides effective aqueous lubrication, whereas the stiffer hydrogel layer used as a substrate delivers the load‐bearing capacity. Their synergy is capable of attaining low friction coefficients (order 0.010) under heavily loaded conditions (order 10 MPa contact pressure) in water environment, a performance incredibly close to that of natural articular cartilage. The bioinspired material can maintain low friction even when subjected to 50k reciprocating cycles under high contact pressure, with almost no wear observed on the sliding track. These findings are theoretically explained and compounded by multiscale simulations used to shed light on the mechanisms responsible for this remarkable performance. This work opens innovative technology routes for developing cartilage‐mimicking ultralow friction soft materials

Transcriptionally active HERV-H retrotransposons demarcate topologically associating domains in human pluripotent stem cells.

Chromatin architecture has been implicated in cell type-specific gene regulatory programs, yet how chromatin remodels during development remains to be fully elucidated. Here, by interrogating chromatin reorganization during human pluripotent stem cell (hPSC) differentiation, we discover a role for the primate-specific endogenous retrotransposon human endogenous retrovirus subfamily H (HERV-H) in creating topologically associating domains (TADs) in hPSCs. Deleting these HERV-H elements eliminates their corresponding TAD boundaries and reduces the transcription of upstream genes, while de novo insertion of HERV-H elements can introduce new TAD boundaries. The ability of HERV-H to create TAD boundaries depends on high transcription, as transcriptional repression of HERV-H elements prevents the formation of boundaries. This ability is not limited to hPSCs, as these actively transcribed HERV-H elements and their corresponding TAD boundaries also appear in pluripotent stem cells from other hominids but not in more distantly related species lacking HERV-H elements. Overall, our results provide direct evidence for retrotransposons in actively shaping cell type- and species-specific chromatin architecture