A novel MEFV gene mutation (A511V) in a Chilean FMF patient

Familial Mediterranean fever (FMF) is an autosomal recessive disease which is characterized by recurrent fever and inflammation of serous membranes. A Chilean FMF patient was investigated for MEFV mutations. After DNA extraction, exons 3, 5, 10 and 30UTR region of MEFV gene were analyzed by DNA sequencing while E148Q and R202Q mutations of exon 2 weredetected by RFLP. A novel missense mutation, A511V (c.1532C>T, p.Ala511Val), was found in a heterozygous state in exon 5 of MEFV gene. Also, R202Q (c.605G>A, p.Arg202Gln) was detected in heterozygous state. R202Q was of clinical value in the diagnosis of FMF when combined with adisease causing mutation. In this patient, A511V was detected in compound heterozygous state with R202Q and this association may play an important role in FMF

Converting a series in \lambda to a series in \lambda^{-1}

We introduce a transformation for converting a series in a parameter, \lambda, to a series in the inverse of the parameter \lambda^{-1}. By applying the transform on simple examples, it becomes apparent that there exist relations between convergent and divergent series, and also between large- and small-coupling expansions. The method is also applied to the divergent series expansion of Euler-Heisenberg-Schwinger result for the one-loop effective action for constant background magnetic (or electric) field. The transform may help us gain some insight about the nature of both divergent (Borel or non-Borel summable series) and convergent series and their relationship, and how both could be used for analytical and numerical calculations.Comment: 7 pages, Latex, 3 figures; Typos corrected. To appear in Journal of Physics A: Math and Ge

Autophosphorylation of DNA-PKCS regulates its dynamics at DNA double-strand breaks

The DNA-dependent protein kinase catalytic subunit (DNA-PKCS) plays an important role during the repair of DNA double-strand breaks (DSBs). It is recruited to DNA ends in the early stages of the nonhomologous end-joining (NHEJ) process, which mediates DSB repair. To study DNA-PKCS recruitment in vivo, we used a laser system to introduce DSBs in a specified region of the cell nucleus. We show that DNA-PKCS accumulates at DSB sites in a Ku80-dependent manner, and that neither the kinase activity nor the phosphorylation status of DNA-PKCS influences its initial accumulation. However, impairment of both of these functions results in deficient DSB repair and the maintained presence of DNA-PKCS at unrepaired DSBs. The use of photobleaching techniques allowed us to determine that the kinase activity and phosphorylation status of DNA-PKCS influence the stability of its binding to DNA ends. We suggest a model in which DNA-PKCS phosphorylation/autophosphorylation facilitates NHEJ by destabilizing the interaction of DNA-PKCS with the DNA ends

HER2 testing in breast cancer: Opportunities and challenges

Human epidermal growth factor receptor 2 (HER2) is overexpressed in 15-25% of breast cancers, usually as a result of HER2 gene amplification. Positive HER2 status is considered to be an adverse prognostic factor. Recognition of the role of HER2 in breast cancer growth has led to the development of anti-HER2 directed therapy, with the humanized monoclonal antibody trastuzumab (Herceptin (R)) having been approved for the therapy of HER2-positive metastatic breast cancer. Clinical studies have further suggested that HER2 status can provide important information regarding success or failure of certain hormonal therapies or chemotherapies. As a result of these developments, there has been increasing demand to perform HER2 testing on current and archived breast cancer specimens. This article reviews the molecular background of HER2 function, activation and inhibition as well as current opinions concerning its role in chemosensitivity and interaction with estrogen receptor biology. The different tissue-based assays used to detect HER2 amplification and overexpression are discussed with respect to their advantages and disadvantages, when to test (at initial diagnosis or pre-treatment), where to test (locally or centralized) and the need for quality assurance to ensure accurate and valid testing results