Elevation of methylated DNA in KILLIN/PTEN in the plasma of patients with thyroid and/or breast cancer

© 2014 Ng et al. Around 80% of mutations in the PTEN gene have been reported to be associated with diseases such as Cowden syndrome, which is an autosomal dominant disorder associated with an increased risk of developing breast, thyroid, and endometrial neoplasms. Recent studies have also demonstrated that KILLIN, which is located proximally to PTEN, shares the same transcription start site, and is assumed to be regulated by the same promoter, but is transcribed in the opposite direction. In this regard, we postulate that there may be a connection between KILLIN/PTEN genes and breast and thyroid cancers. Using real-time quantitative polymerase chain reaction (qPCR), we found that expression of KILLIN, but not PTEN, was significantly decreased in 23 Chinese women with a personal history of breast and thyroid cancer or a personal history of breast cancer and a family history of thyroid cancer, or vice versa, and at least two persons in the family with thyroid cancer or at a young age ,40 years, when compared with healthy controls (P<0.0001). No PTEN mutations were found in these 23 patients. We then developed a simple methylation-sensitive restriction enzyme digestion followed by real-time quantitative assay to quantify plasma methylated KILLIN/PTEN DNA in these patients. Plasma levels of methylated KILLIN/PTEN DNA were significantly increased in these patients when compared with healthy controls (P<0.05). This study shows that plasma methylated KILLIN/PTEN DNA was significantly elevated, suggesting hypermethylation of the KILLIN/PTEN promoter in breast and thyroid cancer patients.published_or_final_versio

The building stones and slates of Killin : an investigation of stone for the built heritage

The village of Killin lies in an area of dramatic landscape and mountain scenery. The use of local stone in the buildings gives a direct connection to this landscape and reflects the local geology, comprising mostly metamorphic rocks of Precambrian age –dominantly limestone, meta-sandstone, mica schist and meta-igneous rocks. All of these (with the exception of the Loch Tay Limestone which was used for soil improvement) were used in buildings and structures within the Killin Conservation Area. The stone masonry in the village is classified into five categories; (1) cottages (mostly harled) built of random rubble from field and river boulders and surface rock outcrops, (2) two storey buildings with irregular coursed rubble walls of meta-sandstone and mica schist with large dressings of silver-grey slabs of actinolite schist, (3) and (4) larger late 19th century buildings with dressings of Central Belt sandstone used in combination with squared rubble walling of local actinolite schist and metasandstone. The 5th masonry category represents relatively late buildings constructed using distinctive imported stone types (e.g. whinstone, granite, red sandstone). These categories are broadly chronological in order and reflect the development of architectural form along with improving transportation of materials over time

Just Rewards

Anti-poaching efforts pay off to protect wildlife from illegal killin

Vignette: The Simple Delights Of Hog Killin\u27 Day

The Simple Delights Of Hog Killin\u27 Day Walter Darrell Hade

Will It Ever Be 50/50?: Diversity and Gender in the Law Firm and on Corporate Boards

Today, women account for 50% of graduates from university programs in Canada and abroad. Traditional gender roles are a growing “thing of the past” with women taking on more responsibility and leadership positions within law and business. However, a gap still remains between the sexes in partner track and directorships. This paper explores regulatory bodies, both in law and finance, which have voiced for change and sparked conversation to bridge this gap. As one will find, major successes have occurred in recent years, however a commitment must be maintained in order to continue to advance gender diversity in law and business

Will It Ever Be 50/50?: Diversity and Gender in the Law Firm and on Corporate Boards

Today, women account for 50% of graduates from university programs in Canada and abroad. Traditional gender roles are a growing “thing of the past” with women taking on more responsibility and leadership positions within law and business. However, a gap still remains between the sexes in partner track and directorships. This paper explores regulatory bodies, both in law and finance, which have voiced for change and sparked conversation to bridge this gap. As one will find, major successes have occurred in recent years, however a commitment must be maintained in order to continue to advance gender diversity in law and business

March 6th 2017

Latinas Killin\u27 it Three Latina Yotes share their narratives p.5 Super Senior \u27Til death to students and education part p.

Teaching Body Image to EFL Teenagers

An extract of an Upper-Intermediate EFL coursebook for teenage learners I designed in partial requirement for MA Applied Linguistics & English Language Teaching.\ud \ud The material is centred about the topic of 'Body Image' and includes a focus on learner training; infinitives & gerunds; skimming and scanning reading tasks; intensive listening practice; giving opinions/speculating; rhyming words

XTEN as Biological Alternative to PEGylation Allows Complete Expression of a Protease-Activatable Killin-Based Cytostatic

Increased effectiveness and reduced side effects are general goals in drug research, especially important in cancer therapy. The aim of this study was to design a long-circulating, activatable cytostatic drug that is completely producible in E. coli. Crucial for this goal was the novel unstructured polypeptide XTEN, which acts like polyethylene glycol (PEG) but has many important advantages. Most importantly, it can be produced in E. coli, is less immunogenic, and is biodegradable. We tested constructs containing a fragment of Killin as cytostatic/cytotoxic element, a cell-penetrating peptide, an MMP-2 cleavage site for specific activation, and XTEN for long blood circulation and deactivation of Killin. One of three sequence variants was efficiently expressed in E. coli. As typical for XTEN, it allowed efficient purification of the E. coli lysate by a heat step (10 min 75°C) and subsequent anion exchange chromatography using XTEN as purification tag. After 24 h XTEN- Killin reduced the number of viable cells of HT-1080 tumor cell line to 3.8 ±2.0% (p<0.001) compared to untreated controls. In contrast, liver derived non-tumor cells (BRL3A) did not show significant changes in viability. Our results demonstrate the feasibility of completely producing a complex protease-activatable, potentially long-circulating cytostatic/cytotoxic prodrug in E. coli—a concept that could lead to efficient production of highly multifunctional drugs in the future