Basement membrane proteoglycans: modulators Par Excellence of cancer growth and angiogenesis.

Proteoglycans located in basement membranes, the nanostructures underling epithelial and endothelial layers, are unique in several respects. They are usually large, elongated molecules with a collage of domains that share structural and functional homology with numerous extracellular matrix proteins, growth factors and surface receptors. They mainly carry heparan sulfate side chains and these contribute not only to storing and preserving the biological activity of various heparan sulfate-binding cytokines and growth factors, but also in presenting them in a more active configuration to their cognate receptors. Abnormal expression or deregulated function of these proteoglycans affect cancer and angiogenesis, and are critical for the evolution of the tumor microenvironment. This review will focus on the functional roles of the major heparan sulfate proteoglycans from basement membrane zones: perlecan, agrin and collagen XVIII, and on their roles in modulating cancer growth and angiogenesis

A review of implant provision for hypodontia patients within a Scottish referral centre

Background: Implant treatment to replace congenitally missing teeth often involves multidisciplinary input in a secondary care environment. High quality patient care requires an in-depth knowledge of treatment requirements. Aim: This service review aimed to determine treatment needs, efficiency of service and outcomes achieved in hypodontia patients. It also aimed to determine any specific difficulties encountered in service provision, and suggest methods to overcome these. Methods: Hypodontia patients in the Unit of Periodontics of the Scottish referral centre under consideration, who had implant placement and fixed restoration, or review completed over a 31 month period, were included. A standardised data collection form was developed and completed with reference to the patient's clinical record. Information was collected with regard to: the indication for implant treatment and its extent; the need for, complexity and duration of orthodontic treatment; the need for bone grafting and the techniques employed and indicators of implant success. Conclusion: Implant survival and success rates were high for those patients reviewed. Incidence of biological complications compared very favourably with the literature

Green's functions for parabolic systems of second order in time-varying domains

We construct Green's functions for divergence form, second order parabolic systems in non-smooth time-varying domains whose boundaries are locally represented as graph of functions that are Lipschitz continuous in the spatial variables and 1/2-H\"older continuous in the time variable, under the assumption that weak solutions of the system satisfy an interior H\"older continuity estimate. We also derive global pointwise estimates for Green's function in such time-varying domains under the assumption that weak solutions of the system vanishing on a portion of the boundary satisfy a certain local boundedness estimate and a local H\"older continuity estimate. In particular, our results apply to complex perturbations of a single real equation.Comment: 25 pages, 0 figur

Sleep patterns are associated with cardiometabolic risk factors in nine-year-old Swedish children

Aim: Sleep duration and bedtime may play a role in children's cardiometabolic health, but research is lacking. This study examined associations between sleep patterns and cardiometabolic risk factors in Swedish nine-year-olds. Methods: This cross-sectional study used data from three studies, where identical outcome measures were conducted in 411 nine-year-olds, 51% boys, between 2016 and 2020. Sleep was assessed with wrist-worn accelerometers and sleep journals. Children were grouped based on meeting the sleep guidelines of 9–11 h and going to bed early or late based on the median bedtime. Analysis of covariance was used to examine associations between sleep patterns and cardiometabolic risk factors. Results: Meeting sleep guidelines and going to bed early were associated with lower metabolic syndrome score (−0.15 vs. 0.42, p = 0.029), insulin resistance (0.30 vs. 0.60, p = 0.025) and insulin levels (6.80 vs. 8.87 mIU/L, p = 0.034), compared with their peers who did not meet the guidelines and went to bed later. When adjusting for total sleep time, analyses still showed associations with the metabolic syndrome score (−0.19 vs. 0.50, p = 0.011). Conclusion: The findings indicate that good sleep patterns could help mediate positive overall cardiometabolic health in children

Fixational eye movements predict visual sensitivity

© 2015 The Author(s) Published by the Royal Society. All rights reserved. During steady fixation, observers make small fixational saccades at a rate of around 1–2 per second. Presentation of a visual stimulus triggers a biphasic modulation in fixational saccade rate—an initial inhibition followed by a period of elevated rate and a subsequent return to baseline. Here we show that, during passive viewing, this rate signature is highly sensitive to small changes in stimulus contrast. By training a linear support vector machine to classify trials in which a stimulus is either present or absent, we directly compared the contrast sensitivity of fixational eye movements with individuals’ psychophysical judgements. Classification accuracy closely matched psychophysical performance, and predicted individuals’ threshold estimates with less bias and overall error than those obtained using specific features of the signature. Performance of the classifier was robust to changes in the training set (novel subjects and/or contrasts) and good prediction accuracy was obtained with a practicable number of trials. Our results indicate a tight coupling between the sensitivity of visual perceptual judgements and fixational eye control mechanisms. This raises the possibility that fixational saccades could provide a novel and objective means of estimating visual contrast sensitivity without the need for observers to make any explicit judgement

Activating transcription factor 3 is a positive regulator of human IFNG gene expression

IL-12 and IL-18 are essential for Th1 differentiation, whereas the role of IFN-α in Th1 development is less understood. In this microarray-based study, we searched for genes that are regulated by IFN-α, IL-12, or the combination of IL-12 plus IL-18 during the early differentiation of human umbilical cord blood CD4+ Th cells. Twenty-six genes were similarly regulated in response to treatment with IL-12, IFN-α, or the combination of IL-12 plus IL-18. These genes could therefore play a role in Th1 lineage decision. Transcription factor activating transcription factor (ATF) 3 was upregulated by these cytokines and selected for further study. Ectopic expression of ATF3 in CD4+ T cells enhanced the production of IFN-α, the hallmark cytokine of Th1 cells, whereas small interfering RNA knockdown of ATF3 reduced IFN-γ production. Furthermore, ATF3 formed an endogenous complex with JUN in CD4+ T cells induced to Th1. Chromatin immunoprecipitation and luciferase reporter assays showed that both ATF3 and JUN are recruited to and transactivate the IFNG promoter during early Th1 differentiation. Collectively, these data indicate that ATF3 promotes human Th1 differentiation

Dental age in patients with neurofibromatosis 1

Neurofibromatosis type 1 (NF1) is a common, hereditary, neurocutaneous skeletal condition with a variety of osseous manifestations. Although NF1 also affects craniofacial structures, the literature has only limited information related to the effect of NF1 on dental development. In this study the dental age of 34 Finnish NF1 patients, 817 yr of age, was estimated using the Demirjian & Goldstein method. The dental age of children with NF1 was similar to that of a Finnish control population. The findings suggest that NF1 does not affect the timing of tooth development.</p

Quantum Fluctuations around the Electroweak Sphaleron

We present an analysis of the quantum fluctuations around the electroweak sphaleron and calculate the associated determinant which gives the 1--loop correction to the sphaleron transition rate. The calculation differs in various technical aspects from a previous analysis by Carson et al. so that it can be considered as independent. The numerical results differ also -- by several orders of magnitude -- from those of this previous analysis; we find that the sphaleron transition rate is much less suppressed than found previously.Comment: DO-TH-93/19 39 pages, 5 figures (available on request as Postscript files or via Fax or mail), LaTeX, no macros neede

On the microscopic foundation of dissipative particle dynamics

Mesoscopic particle based fluid models, such as dissipative particle dynamics, are usually assumed to be coarse-grained representations of an underlying microscopic fluid. A fundamental question is whether there exists a map from microscopic particles in these systems to the corresponding coarse-grained particles, such that the coarse-grained system has the same bulk and transport properties as the underlying system. In this letter, we investigate the coarse-graining of microscopic fluids using a Voronoi type projection that has been suggested in several studies. The simulations show that the projection fails in defining coarse-grained particles that have a physically meaningful connection to the microscopic fluid. In particular, the Voronoi projection produces identical coarse-grained equilibrium properties when applied to systems with different microscopic interactions and different bulk properties.Comment: First revisio

The Goblet Cell Protein Clca1 (Alias mClca3 or Gob-5) Is Not Required for Intestinal Mucus Synthesis, Structure and Barrier Function in Naive or DSS- Challenged Mice

The secreted, goblet cell-derived protein Clca1 (chloride channel regulator, calcium-activated-1) has been linked to diseases with mucus overproduction, including asthma and cystic fibrosis. In the intestine Clca1 is found in the mucus with an abundance and expression pattern similar to Muc2, the major structural mucus component. We hypothesized that Clca1 is required for the synthesis, structure or barrier function of intestinal mucus and therefore compared wild type and Clca1-deficient mice under naive and at various time points of DSS (dextran sodium sulfate)-challenged conditions. The mucus phenotype in Clca1-deficient compared to wild type mice was systematically characterized by assessment of the mucus protein composition using proteomics, immunofluorescence and expression analysis of selected mucin genes on mRNA level. Mucus barrier integrity was assessed in-vivo by analysis of bacterial penetration into the mucus and translocation into sentinel organs combined analysis of the fecal microbiota and ex-vivo by assessment of mucus penetrability using beads. All of these assays revealed no relevant differences between wild type and Clca1-deficient mice under steady state or DSS-challenged conditions in mouse colon. Clca1 is not required for mucus synthesis, structure and barrier function in the murine colon