Subcellular Localization of Beta Catenin in Colorectal Non Neoplastic and Neoplastic Lesions

Loss of adenomatous polyposis coli (APC) function is typically an early event  in sporadic colorectal cancer (CRC) pathogenesis. The key tumor suppressor function of the APC  protein lies in its ability to destabilize free cytoplasmic beta catenin. This lead to the accumulation of nuclear beta catenin, and together with the DNA binding protein Tcf-4, function as a transcriptional activator. Accumulation of stabilized free  β-catenin is considered as an early event and perhaps initiating the process in intestinal tumorigenesis. Neoplastic transformation in the CRC associated chronic colitis is considered similar to the adenoma-carcinoma sequence in sporadic CRC. The distinguish feature from the CRC-related colitis is the difference in time and frequency changes. Loss of APC function, regarded as the beginning of a very common event in sporadic CRC, but the CRC associated chronic colitis generally occurs at the end of the dysplasia-carcinoma sequence. This research was conducted to determine the subcellular location of beta catenin expression in chronic colitis, colorectal adenomas and carcinomas that were evaluated by immunohistochemical staining. It can be concluded that beta-catenin is a component that plays a role in the development of the CRC and the subcellular location of beta-catenin can describe its oncogenic activity.&nbsp

An Empirical Assessment of Alternative Models of Risky Decision Making

In this paper, we assess the degree to which four of the most commonly used models of risky decision making can explain the choices individuals make when faced with risky prospects. To make this assessment, we use experimental evidence for two random samples of young adults. Using a robust, nonlinear least squares procedure, we estimate a model that is general enough to approximate Kahnenman and Tversky's prospect theory and that for certain parametric values will yield the expected utility model, a subjective expected utility model and a probability-transform model. We find that the four models considered explain the decision-making behavior of the majority of our subjects. Surprisingly, we find that the choice behavior of the largest number of subjects is consistent with a probability-transform model. Such models have only been developed recently and have not been used in applied settings. We find least support for the expected utility model -- the most widely used model of risky decision making.

AN INTRODUCTION TO VIRGINIA ISSUES: INFORMATION AND ANALYSIS: SPECIAL REPORT FOR VIRGINIA COOPERATIVE EXTENSION

Community/Rural/Urban Development, Labor and Human Capital, Land Economics/Use,

Chromatin Immunoprecipitation (ChIP): Revisiting the Efficacy of Sample Preparation, Sonication, Quantification of Sheared DNA, and Analysis via PCR

The “quantitative” ChIP, a tool commonly used to study protein-DNA interactions in cells and tissue, is a difficult assay often plagued with technical error. We present, herein, the process required to merge multiple protocols into a quick, reliable and easy method and an approach to accurately quantify ChIP DNA prior to performing PCR. We demonstrate that high intensity sonication for at least 30 min is required for full cellular disruption and maximum DNA recovery because ChIP lysis buffers fail to lyse formaldehyde-fixed cells. In addition, extracting ChIP DNA with chelex-100 yields samples that are too dilute for evaluation of shearing efficiency or quantification via nanospectrophotometry. However, DNA extracted from the Mock-ChIP supernatant via the phenol-chloroform-isoamyl alcohol (PCIA) method can be used to evaluate DNA shearing efficiency and used as the standard in a fluorescence-based microplate assay. This enabled accurate quantification of DNA in chelex-extracted ChIP samples and normalization to total DNA concentration prior to performing real-time PCR (rtPCR). Thus, a quick ChIP assay that can be completed in nine bench hours over two days has been validated along with a rapid, accurate and repeatable way to quantify ChIP DNA. The resulting rtPCR data more accurately depicts treatment effects on protein-DNA interactions of interest

The practical, ethical and legal reasons why patients should not be transferred between NHS trusts for phage therapy

Bacteriophages (phages) are naturally occurring viruses of bacteria that have a long history of use as antimicrobials, known as phage therapy. The antibiotic resistance crisis has driven renewed interest in phage therapy, which has been used on an unlicensed compassionate basis in various Western contexts. The option to use unlicensed medicines exists to allow clinicians to respond to genuine clinical needs arising in their own patients. However, in the UK some clinicians may, in the absence of suitable patients of their own, seek to transfer patients from other NHS trusts into their own Trust. This article sets out why patient transfer is not necessary and the practical, ethical and legal reasons why patients should not be transferred between NHS Trusts for phage therapy. Phage preparations should always be transported to the patient and the patient treated in the Trust in which they would have received care in the absence of phage. We enclose suggested best practice guidelines for adoption across the UK that will protect patient safety and safeguard clinicians and Trusts from potential litigation

Alteration of Subcellular Beta Catenin Expression in Normal Mucosa Adenoma and Carcinoma in Relation to Colorectal Carcinogenesis

Background: Adenomatous polyposis coli (APC) gene mutation was found in up to 80% of cases of sporadic colorectal cancers and adenomas. Loss of APC protein function has been known as one of the early process in colorectal carcinogenesis. This event leads to the accumulation of beta catenin in the cytoplasm and nucleus and subsequently activates target genes that regulate cell proliferation and apoptosis. The aim of this study was to investigate the alteration of subcellular beta catenin expression in the progression of colorectal cancer. Method: This cross-sectional study was conducted with 30 paraffin-embedded tissue sections each of normal colorectal mucosa, adenomas and carcinomas. Alteration of beta catenin expression in membranous, cytoplasmic, and nuclear compartments were evaluated by immunohistochemical staining. Results: Beta catenin immunoreactivity was detected in all cases, of which 87 (96.7%) cases showed membranous expression, 78 (86.7%) cases had cytoplasmic and 51 cases (56.7%) had nuclear expression. Such results were statistically significant (p < 0.000). All normal colorectal epithelium showed membranous beta catenin expression with 18 (60.0%) cases showed cytoplasmic and no nuclear beta catenin expression was found. Strong cytoplasmic expression was found in 17 (56.7%) adenomas and 25 (83.3%) carcinomas; while strong nuclear expression was found in 12 (40.0%) adenomas and 17 (56.7%) carcinomas. There was no statistical significant association between beta catenin expression in the membranous, cytoplasmic and nuclear compartment with the degree of dysplasia or differentiation of tumor (p > 0.05). Conclusion: Altered subcellular expression of beta catenin occurs as the oncogenic process develops from adenoma into carcinoma. Such finding reflects the importance of beta-catenin in colorectal carcinogenesis

A Digital Neuromorphic Architecture Efficiently Facilitating Complex Synaptic Response Functions Applied to Liquid State Machines

Information in neural networks is represented as weighted connections, or synapses, between neurons. This poses a problem as the primary computational bottleneck for neural networks is the vector-matrix multiply when inputs are multiplied by the neural network weights. Conventional processing architectures are not well suited for simulating neural networks, often requiring large amounts of energy and time. Additionally, synapses in biological neural networks are not binary connections, but exhibit a nonlinear response function as neurotransmitters are emitted and diffuse between neurons. Inspired by neuroscience principles, we present a digital neuromorphic architecture, the Spiking Temporal Processing Unit (STPU), capable of modeling arbitrary complex synaptic response functions without requiring additional hardware components. We consider the paradigm of spiking neurons with temporally coded information as opposed to non-spiking rate coded neurons used in most neural networks. In this paradigm we examine liquid state machines applied to speech recognition and show how a liquid state machine with temporal dynamics maps onto the STPU-demonstrating the flexibility and efficiency of the STPU for instantiating neural algorithms.Comment: 8 pages, 4 Figures, Preprint of 2017 IJCN

Natriuretic peptide receptor-C is up-regulated in the intima of advanced carotid artery atherosclerosis

OBJECTIVE: Natriuretic peptide receptor-C (NPR-C/NPR-3) is a cell surface protein involved in vascular remodelling that is up-regulated in atherosclerosis. NPR-C expression has not been well characterized in human carotid artery occlusive lesions. We hypothesized that NPR-C expression correlates with intimal features of vulnerable atherosclerotic carotid artery plaque. METHODS: To test this hypothesis, we evaluated NPR-C expression by immunohistochemistry (IHC) in carotid endarterectomy (CEA) specimens isolated from 18 patients. The grade, location, and co-localization of NPR-C in CEA specimens were evaluated using two tissue analysis techniques. RESULTS: Relative to minimally diseased CEA specimens, we observed avid NPR-C tissue staining in the intima of maximally diseased CEA specimens (65%; p=0.06). Specifically, maximally diseased CEA specimens demonstrated increased NPR-C expression in the superficial intima (61%, p=0.17), and deep intima (138% increase; p=0.05). In the superficial intima, NPR-C expression significantly co-localized with vascular smooth muscle cells (VSMCs) and macrophages. The intensity of NPR-C expression was also higher in the superficial intima plaque shoulder and cap regions, and significantly correlated with atheroma and fibroatheroma vulnerable plaque regions (β=1.04, 95% CI=0.46, 1.64). CONCLUSION: These findings demonstrate significant NPR-C expression in the intima of advanced carotid artery plaques. Furthermore, NPR-C expression was higher in vulnerable carotid plaque intimal regions, and correlate with features of advanced disease. Our findings suggest that NPR-C may serve as a potential biomarker for carotid plaque vulnerability and progression, in patients with advanced carotid artery occlusive disease

Cloud fragmentation and proplyd-like features in HII regions imaged by HST

We have analyzed HST ACS and WFPC2 new and archival images of eight HII regions to look for new proto-planetary disks (proplyds) similar to those found in the Orion Nebula. We find a wealth of features similar in size (though many are larger) to the bright cusps around the Orion Nebula proplyds. None of them, however, contains a definitive central star. From this, we deduce that the new cusps may not be proplyds, but instead are fragments of molecular cloud material. Out of all the features found in the eight HII regions examined, only one, an apparent edge-on silhouette in M17, may have a central star. This feature might join the small number of bona fide proplyds found outside the Orion Nebula, in M8, M20 and possibly in M16. In line with the results found recently by Smith et al. (2005), the paucity of proplyds outside the Orion Nebula, may be explained by their transient nature as well as by the specific environmental conditions under whichthey can be observed.Comment: 51 pages; 19 figures; 5 tables. Accepted by A

Teaching Nonsexist Language to College Students

Although psychologists have noted the importance of avoiding sexist language because of its potential role in transmitting sexism, little attention has been given to methods of teaching students of psychology to use nonsexist language. Two experiments were conducted to measure the effectiveness of teaching general Psychology students to use nonsexist language. In a pilot study (Experiment 1), undergraduates were exposed to a 20-minute lecture either on use of nonsexist language (experimental group) or on an unrelated topic (control group). No changes in use of sexist language in short essay responses were noted on the posttest or in a 2-week follow-up. In Experiment 2, the method of measuring sexist language was expanded by using three essay responses, and the procedure was repeated except that a second independent variable was added: Students were instructed either in lecture format or with an interactive computer program. The method of presentation showed no effect, but the group receiving training about nonsexist language used less sexist language on one of the three essay questions. Interpretations and implications of the findings are discussed