Plakoglobin: Role in Tumorigenesis and Metastasis

Plakoglobin (γ-catenin) is a member of the Armadillo family of proteins and a homolog of β-catenin. As a component of both the adherens junctions and desmosomes, plakoglobin plays a pivotal role in the regulation of cell-cell adhesion. Furthermore, similar to β-catenin, plakoglobin is capable of participating in cell signaling. However, unlike β-catenin that has well-documented oncogenic potential through its involvement in the Wnt signaling pathway, plakoglobin generally acts as a tumor/metastasis suppressor. The exact roles that plakoglobin plays during tumorigenesis and metastasis are not clear; however, recent evidence suggests that it may regulate gene expression, cell proliferation, apoptosis, invasion, and migration. In this paper, we describe plakoglobin, its discovery and characterization, its role in regulating cell-cell adhesion, and its signaling capabilities in regulation of tumorigenesis and metastasis

Subwavelength grating metamaterial waveguides and ring resonators on a silicon nitride platform

We propose and demonstrate subwavelength grating (SWG) metamaterial waveguides and ring resonators on a silicon nitride platform for the first time. The SWG waveguide is engineered such that a large overlap of 53% of the Bloch mode with the top cladding material is achieved, demonstrating excellent potential for applications in evanescent field sensing and light amplification. The devices, which have critical dimensions greater than 100 nm, are fabricated using a commercial rapid turn-around silicon nitride prototyping foundry process using electron beam lithography. Experimental characterization of the fabricated device reveals excellent ring resonator internal quality factor (2.11x10^5) and low propagation loss (~1.5 dB/cm) in the C-band, a significant improvement of both parameters compared to silicon based SWG ring resonators. These results demonstrate the promising prospects of SWG metamaterial structures for silicon nitride based photonic integrated circuits.Comment: 12 pages, 7 figures, submitted to Laser & Photonics Reviews for publicatio

Development of valve train rig for assessment of cam/follower tribochemistry.

Component bench tests are a crucial part of a tribology assessment experimental programme for most engines and subsystems. This is because they test the components under conditions simulating the operating characteristics of the system. These have become very important as they shed more light into the friction, wear, lubrication and importantly for this study, the tribochemistry of valve train systems. This work outlines the procedure for the development of a single cam rig (SCR) from a 1.25L FORD Zetec (SE) engine. Friction plots were used to validate the data obtained from the newly developed single cam rig with Mn-phosphate coated and polished follower against a cast iron camshaft. The tribofilm formed using normal and mid Sulphated Ash, Phosphorus and Sulphur (SAPS) 5W-30 oils were evaluated and correlated to the friction and wear properties of the tribopair.Raman and FIB-SEM/EDX investigations of the tribochemical films showed that the normal SAPS oil produced patchy, thick (80-100. nm) and well dispersed tribofilm with better wear prevention capabilities. It was observed that Mid SAPS oil had lower wear prevention due to loosely dispersed and thin tribofilms. Absence of tribofilms at the centre of the insert with this oil also suggests that formation and removal processes are an integral part of the wear mechanisms in highly loaded cam follower systems

A role for Dynlt3 in melanosome movement, distribution, acidity and transfer

Skin pigmentation is dependent on cellular processes including melanosome biogenesis, transport, maturation and transfer to keratinocytes. However, how the cells finely control these processes in space and time to ensure proper pigmentation remains unclear. Here, we show that a component of the cytoplasmic dynein complex, Dynlt3, is required for efficient melanosome transport, acidity and transfer. In Mus musculus melanocytes with decreased levels of Dynlt3, pigmented melanosomes undergo a more directional motion, leading to their peripheral location in the cell. Stage IV melanosomes are more acidic, but still heavily pigmented, resulting in a less efficient melanosome transfer. Finally, the level of Dynlt3 is dependent on beta -catenin activity, revealing a function of the Wnt/beta -catenin signalling pathway during melanocyte and skin pigmentation, by coupling the transport, positioning and acidity of melanosomes required for their transfer. Aktary et al. identify novel roles for the dynein light chain Dynlt3 in melanosome transport, maturation, and transfer to keratinocytes. They also find that the Wnt/beta catenin signalling pathway controls Dynlt3 levels and thus also contributes to the regulation of melanocyte transport and skin pigmentation

Tribological performance and tribochemical processes in a DLC/steel system when lubricated in a fully formulated oil and base oil

Diamond-like carbon (DLC) coatings show extremely good promise for a number of applications in automotive components as they exhibit excellent tribological properties such as low friction and good wear resistance. This can impact on improved fuel economy and durability of the engine components. Much work has been reported on the dry sliding of DLC coatings with less so in lubricated contacts and, as such, there is a need to further understand the tribochemistry of lubricated DLC contacts. Commercially-available oils are normally optimised to work on ferrous surfaces. Previous studies on DLC lubricated contacts have tended to use model oil systems rather than fully formulated lubricants and from this an interesting picture of lubrication mechanisms is emerging. Optimising compatibility between a surface and a set of lubricant additives may lead to excellent durability (wear) as well as increased fuel economy (low friction). In this work, the friction and wear properties of a DLC coating under boundary lubrication conditions have been investigated and the tribological performance compared with that of an uncoated steel system. A pin-on-plate tribotester was used to run the experiments using High speed steel (HSS) M2 grade plates coated with 15 at.% hydrogenated DLC (a-C:15H) sliding against cast iron pins. A Group III mineral base oil, fully synthetic Group IV PAO and four different fully formulated oils were used in this study. Furthermore optical and scanning electron microscopes (SEM) were used to observe the wear scar and to assess the durability of the coatings. Energy-Dispersive X-ray analysis (EDX), X-ray Photoelectron Spectroscopy (XPS) and Raman spectroscopy analyses were performed on the tribofilms to understand the tribochemical interactions between oil additives and the a-C:15H coating. This study show that the durability of the a-C:15H coating strongly depends on the selected additive package in the oils. In addition the effect of detergent, dispersant and antioxidants on the performance of the molybdenum-based friction modifier (Mo-FM) and ZDDP anti-wear additive was investigated and results are reported in this paper

Comparative genomics reveals that loss of lunatic fringe (LFNG) promotes melanoma metastasis

Metastasis is the leading cause of death of patients with advanced melanoma, yet the somatic alterations that aid tumour cell dissemination and colonization are poorly understood. Here we deploy comparative genomics to identify and validate clinically relevant drivers of melanoma metastasis. To do this we identified a set of 976 genes whose expression level was associated with a poor outcome in patients from two large melanoma cohorts. We next characterised the genomes and transcriptomes of mouse melanoma cell lines defined as weakly metastatic and their highly metastatic derivatives. By comparing expression data between species we identified Lunatic Fringe (LFNG), amongst 28 genes whose expression level is predictive of poor prognosis, and whose altered expression is associated with a pro-metastatic phenotype in mouse melanoma cells. CRISPR/Cas9 mediated knockout of Lfng dramatically enhanced the capability of weakly metastatic melanoma cells to metastasize in vivo, a phenotype that could be rescued with the Lfng cDNA. Notably, genomic alterations disrupting LFNG are found exclusively in human metastatic melanomas sequenced as part of The Cancer Genome Atlas. Using comparative genomics we show that LFNG expression plays a functional role in regulating melanoma metastasis

Development of a new mechano-chemical model in boundary lubrication

A newly developed tribochemical model based on thermodynamics of interfaces and kinetics of tribochemical reactions is implemented in a contact mechanics simulation and the results are validated against experimental results. The model considers both mechanical and thermal activation of tribochemical reactions instead of former thermal activation theories. The model considers tribofilm removal and is able to capture the tribofilm behaviour during the experiment. The aim of this work is to implement tribochemistry into deterministic modelling of boundary lubrication and study the effect of tribofilms in reducing friction or wear. A new contact mechanics model considering normal and tangential forces in boundary lubrication is developed for two real rough steel surfaces. The model is developed for real tribological systems and is flexible to different laboratory experiments. Tribochemistry (e.g. tribofilm formation and removal) and also mechanical properties are considered in this model. The amount of wear is calculated using a modified Archard’s wear equation accounting for local tribofilm thickness and its mechanical properties. This model can be used for monitoring the tribofilm growth on rough surfaces and also the real time surface roughness as well as changes in the λ ratio. This model enables the observation of in-situ tribofilm thickness and surface coverage and helps in better understanding the real mechanisms of wear