The role of Tribbles 1 and Tribbles 3 in cartilage turnover

PhD ThesisArthritis is a term which encompasses a number of diseases characterised by cartilage degradation and joint destruction which represents an enormous and growing healthcare burden. Matrix metalloproteinases (MMPs) are a family of enzymes involved in cleavage of extracellular matrix proteins. They have many roles in both development and normal tissue homeostasis. As well as this they have been shown to be important in a number of diseases, including arthritis. MMP-1 and -13 in particular have been shown to be important in arthritis, due to their ability to cleave type II collagen, a key component of cartilage. A greater understanding of the regulation of these MMPs could lead to the potential for new therapeutic arthritis treatments. Tribbles (Trb) 1-3 are a group of proteins linked with diseases including diabetes, multiple sclerosis and cancer. Trb 1-3 are reported to play a role in regulating many cellular signalling pathways, such as mitogen-activated protein kinase (MAPK), phosphoinositide-3-kinase/Akt (PI3K/Akt) and nuclear factor kappa B (NFκB). These pathways are considered important in mediating gene expression changes, including MMPs. Both Trb1 and Trb3 were shown to regulate MMPs in chondrocytes, with a greater effect being on MMP-13 regulation. Trb1 and Trb3 were both shown to regulate the major MMP transcription factor AP-1, as well as the ATF3 and NFκB transcription factors. Both Trb1 and Trb3 interacted with MAP2Ks MEK1, MKK4, MKK6 and MKK7, and in addition were shown to regulate MAPK activation, with Trb3 protein levels appearing to be affected by MAP2K levels. Trb3 also had the ability to affect both Akt and STAT activation. These data demonstrate that Trb1 and Trb3 can regulate signalling pathways that have the ability to alter MMP expression and transcription factors within chondrocytes. This would suggest that Trb1 and Trb3 have the ability to affect cartilage degradation. This greater understanding of MMP regulation by Trb1 and Trb3 may help in the development of potential future therapeutic targets for arthritic disease.Oliver Bird and Nuffield foundatio

Evidence-Based Indications of Cone Beam Computed Tomography in Children with maxillary impacted canines - A literary review

Prosjektoppgåve/masteroppgåveOD3PROSJMAOD-ODON

The effectiveness of functional family therapy in substance-involved family preservation clients

Abuse and neglect of children has been a recognized problem in America for many years. Recent developments in the child welfare system have introduced intensive, family-based services, otherwise known as family preservation services. The aim is to preserve the family and provide reasonable efforts to avoid out of home placement. State and private family preservation programs across the country have been faced with the challenge of evaluating program effectiveness and to better meet the needs of client populations by enhancing treatment models and programs; The Nevada State Division of Child and Family Services (DCFS) has utilized valuable resources to evaluate their Intensive Family Preservation (IFP) service program to discover its effectiveness. The program has been the subject of a longitudinal study. Research data from the 1999 fiscal year was used to examine the effectiveness of the Functional Family Therapy (FFT) model on substance-involved families. This secondary analysis discovered that the preservation services in Las Vegas are effective but that substance involved families have significantly lower outcome scores. The data revealed that substance-involved families also have larger households and less income than non-substance users

Triclinic polymorph of bis­(triphenyl­sil­yl) oxide toluene disolvate

A new polymorph of the title compound, C36H30OSi2·2C7H8, is reported, which is triclinic (P-1) instead of possessing the previously reported rhombohedral symmetry [Hönle et al. (1990). Acta Cryst. C46, 1982–1984]. Each of the –SiPh3 units are related by the inversion center. The Si—O—Si moiety is linear with the O atom sitting on an inversion center, and the O—Si—(toluene ring centroid) angle is 3.69 (15)°. Each toluene mol­ecule is 5.622 (2) Å from the Si atom and has its closest contacts with the phenyl rings outside of the van der Waals radii

Free field auditory localization and perception

viii, 61 leaves : ill. ; 29 cmWe have designed a system suitable for auditory electroencephalographic (EEG) experiments, with the objective of enabling studies of auditory motion. This thesis details the perceptual cues involved in spatial auditory experiments, and compares a number of spatial panning algorithms while examining their suitability to this purpose. A behavioural experiment involving perception of static auditory objects was used in an attempt to differentiate these panning algorithms. This study was used to inform the panner choice used in an auditory EEG experiment. This auditory EEG experiment involved the effects of discontinuity in velocity and position, and their affects on object perception. A new event related potential (ERP) component – the lateralized object related negativity (LORN) – was identified, and we consider its significance. libnetstation, a library for connecting with the NetStation (EEG) system has been developed, and released as open source software

Groundwater in Cretaceous carbonates: KG@B field trip 21st June 2015

The Upper Cretaceous Chalk of southern England is the UK’s most important aquifer, providing more than 75% of the public supply for southeast England, including London. The aquifer also sustains rivers and wetlands, and their associated groundwater dependent ecosystems. However, the aquifer is facing a multitude of threats including over-abstraction, nitrate pollution, and climate change. The Chalk is a complex aquifer in which groundwater flow is through the matrix, fractures and karstic dissolutional voids. The Chalk matrix has a porosity of around 35% (Bloomfield et al., 1995). The matrix is thought to provide an important contribution to storage, although the size of the pore throats is very small, and therefore the permeability is very low (Price et al., 1993). The average permeability of 977 core samples was only 6.3 x 10-4 m/day (Allen et al., 1997). The matrix is particularly important in solute transport, because solutes move between the matrix and the more permeable parts of the aquifer via diffusion (Foster 1975). The unmodified fracture network provides an important contribution to storage and flow, and has a hydraulic conductivity of about 0.1 m/d, and a transmissivity of about 20 m2/day (Price, 1987). However, it is the dissolutionally enlarged fissures and conduits that make the Chalk such a good aquifer. The median transmissivity from 2100 pumping tests is 540 m2/day, and the 25th and 75th percentiles are 190 and 1500 m2/day respectively (MacDonald and Allen, 2001). Borehole packer testing, logging and imaging have shown that most of this transmissivity comes from a small number of dissolutional voids (e.g. Tate et al., 1970; Schurch and Buckley, 2002). Laterally extensive lithostratigraphical horizons including marl seams, bedding planes, sheet and tabular flint bands, and hard-grounds have an important influence on these groundwater flows. They are all horizons where downward percolation of water may be impeded. Dissolution often occurs where flow is concentrated along these horizons, creating conduits or fissures, especially where they are intersected by joint sets

Little Island Comics Goes to University!

DOI: 10.1353/jeu.2014.002