DNA methylation and developmental genes in lymphomagenesis--more questions than answers?

There is now considerable evidence suggesting that alterations in the DNA methylating machinery play an important role in tumorigenesis and tumour progression. For example, focal hypermethylation and generalised genomic demethylation are features of many different types of neoplasms. It is thought that tumorigenesis and tumour progression may be caused by hypermethylation induced mutational events and silencing of genes which control cellular proliferation and/or demethylation induced reactivation of genes which may only be required during embryological development. Consequently, we have begun to investigate the role of DNA methylation and developmental genes in malignant lymphoproliferative diseases. Previously, in all cases of non-Hodgkins lymphoma and leukemia studied, we have shown that the myogenic developmental gene Myf-3 is abnormally hypermethylated. In this review we discuss the possible significance of these findings since in vitro studies suggest that Myf-3 may play an important role in control of the cell cycle and therefore lymphomagenesis. In vitro and in vivo evidence suggests that PAX genes may also have oncogenic potential. The PAX family of developmental genes are involved in cellular differentiation, proliferation and cell migration. Expression of PAX3 in particular is associated with cellular mobility. Our previous studies have indicated that alternate regional expression of PAX genes may be controlled by DNA methylation. Therefore, we have proposed that abnormal methylation profiles of PAX3 may be associated with neoplastic transformation and/or metastatic potential. Results thus far reveal that the paired box of PAX3 is abnormally hypermethylated and the homeobox abnormally hypomethylated in lymphomas and leukemias. These new findings are consistent with our postulate and support the idea that inappropriate methylation induced activation or inactivation of developmental genes such as Myf-3 and PAX3 play an important role in lymphomagenesis and disease progression and that inspection of the methylation status of other developmental genes is warranted.     

Timing of reproductive life stages

We have investigated lysis of cultured human glial cells by non-major histocompatibility complex (MHC)-restricted or 'promiscuous' CD(4+)-T lymphocytes, activated either under relatively long-term limiting dilution culture conditions in the presence of phytohemagglutinin (PHA) and interleukin (IL)-2, or under short-term PHA-activated bulk culture conditions. Specific effector:target cell ratio-dependent lysis of oligodendrocytes (OGCs) by CD4+ T lymphocytes, generated under both of the above conditions, was observed in an 18-h 51Cr-release assay, but not in a 5-h assay. The extent of CD4 T-cell-mediated OGC lysis was less than for the tumor necrosis factor (TNF)-alpha-sensitive cell line U937, but greater than for TNF-resistant cell lines (K562, EL4). The effect could not be reproduced by T-cell culture supernatants or by high concentrations of recombinant TNF-alpha or beta. Anti-TNF-alpha antibody did not inhibit CD4-mediated lysis of OGC or U937 cells, but did inhibit U937 lysis induced by recombinant TNF-alpha, added in amounts exceeding those secreted by CD4 T cells. Human astrocytes and microglia were also susceptible to CD4+ T-cell-mediated lysis. Our results suggest that non-antigen non-MHC-restricted CD4+ T-cell-mediated injury of human glial cells can occur and may be dependent or enhanced by effector:target cell contact.     

Immune-Inspired Adaptable Error Detection for Automated Teller Machines

This paper presents an immune-inspired adaptable error detection (AED) framework for automated teller machines (ATMs). This framework has two levels: one is local to a single ATM, while the other is network-wide. The framework employs vaccination and adaptability analogies of the immune system. For discriminating between normal and erroneous states, an immune-inspired one-class supervised algorithm was employed, which supports continual learning and adaptation. The effectiveness of the proposed approach was confirmed in terms of classification performance and impact on availability. The overall results are encouraging as the downtime of ATMs can de reduced by anticipating the occurrence of failures before they actually occur.     

Recognizing, assessing, and intervening with problems of professional competence.

Working collaboratively, psychologist educators and trainers at the doctoral, internship, and postdoctoral levels; credentialers; practitioners; and students offer 8 proposals for psychologists to consider in recognizing, assessing, and intervening with problems of professional competence in students and practicing professionals. In the proposals, the authors address the following topics: definitions and categories; preparing the system; self-assessment; remediation; diversity; communication across various levels of the system; confidentiality; and ethical, regulatory, and legal underpinnings. They also propose future directions for the assessment of problems in professional competence in both students and practicing psychologists. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Palatability of prerigor cooked boar meat

Cooking reduces odor intensity in boar meat but also may induce lipid oxidation unless the meat pH is above approximately 6.0. This research was designed to determine the feasibility of cooking boar meat in the prerigor state to overcome boar odor and lipid oxidation problems. Prerigor and postrigor triceps brachii muscle samples from 40 boars (20 Duroc and 20 Yorkshire) were cooked to 60 degrees C, frozen and stored at -20 degrees C, reheated in a 60 degrees C water bath for 1 h, and then subjected to pH, thiobarbituric acid (TBA), and sensory analyses. Boar odor intensity and skatole concentration in backfat samples were determined by olfactory test and HPLC, respectively. Cooked (initial cooking) prerigor meat was found to have higher (P < .05) pH and lower (P < .05) TBA values than comparable postrigor meat (6.44 vs 6.09 and 2.15 vs 3.23, respectively). Regression analysis indicated an inverse relationship between pH and TBA values (r = -.52; P < .01). No appreciable changes in TBA values were noted after frozen storage for 14 to 98 d, but reheating increased TBA values (P < .05) in both prerigor and postrigor samples (3.45 vs 4.32, respectively). Sensory evaluation scores indicated that prerigor cooked meat was less tender with more pronounced rancid flavor than postrigor cooked meat (P < .05), but panelists may have allowed the toughness of the prerigor samples to adversely affect their flavor scores. No difference in boar odor was detected between rigor states or breeds. Mean skatole concentration in backfat was .12 micrograms/g and no difference was detected between breeds.(ABSTRACT TRUNCATED AT 250 WORDS)