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Mutations in the TP53 tumor suppressor gene are the most abundant genetic occurrences in cancer. Some of these mutations lead to loss of function of p53 protein, some are gain of function, and some variants are hypomorphic (partially functional). Currently, there is no clinical distinction between different p53 mutations and cancer therapy or prognosis. Mutations in the oligomerization domain of p53 appear to be quite distinct in function, compared to mutations in the DNA binding domain. Here we show that, like other p53 oligomerization domain mutants, the Ashkenazi-specific G334R mutant accumulates to very high levels in cells and is significantly impaired for the transactivation of canonical p53 target genes. Surprisingly, we find that this mutant retains the ability to bind to consensus p53 target sites. A mouse model reveals that mice containing the G334R variant show increased predisposition to cancer, but only a fraction of these mice develop late-onset cancer. We show that the G334R variant retains the ability to interact with the SP1 transcription factor and contributes to the transactivation of joint SP1-p53 target genes. The combined evidence indicates that G334R is a unique oligomerization domain mutant that retains some tumor suppressor function. [ABSTRACT FROM AUTHOR]

In July 1950, Moroccan Rabbi Yahya Ben Harosh wrote a letter to his students chastising those exposed to ultraOrthodox anti-Zionist influences for disparaging and denigrating Zionist leaders and the founders of the State of Israel. This article discusses the historical background to the letter, including the ideological foundation of the rabbi's vigorous protest: from his position regarding the messianic concept to the religious affirmation of Zionism as a national-liberation movement. As such, Ben Harosh's stimulating letter is not an isolated episode but a reflection of the longstanding religious and ideological antecedents of Zionism, dating back to the 16th century, which contained the main elements of the would-be Zionist endeavour. So much so that it is arguable that the 16th century set in motion a fundamental process worthy of being the departure point of Zionist historiography. [ABSTRACT FROM AUTHOR]

The JAK2V617F mutation has emerged in recent years as a diagnostic as well as treatment target in patients with polycythemia vera (PV). We analyzed JAK2V617F allele burden (JAK2V617F) in a Jewish population with PV. Results were correlated with disease symptoms and complications. Median JAK2V617F was 48% and 54% in patients of Ashkenazi and non-Ashkenazi origin, respectively ( p =0.75). Higher JAK2V617F was seen in patients with imaging-proven splenomegaly ( p =0.01). A correlation between JAK2V617F and the weekly hydoxyurea dose needed for disease control was found ( p =0.043). In addition, a trend for higher allele burden in patients with longer disease duration ( p =0.064) and those treated with cytoreductive drugs other than hydroxyurea ( p =0.056) was noted. Higher JAK2V617F was seen in patients with transformation to myelofibosis ( p =0.0001), but not in patients with vascular complications. JAK2V617F may assist in prognostic stratification of patients with PV. [ABSTRACT FROM AUTHOR]

In the 100+ years between 1840 and 1945, Shanghai was home to a number of Jewish diaspora communities, not all of whom came, but all of whom left as refugees. Each of these communities maintained its own traditions and practices; in modern Shanghai only a few historic buildings and sites remain. In this report of my ethnomusicological "study at home", I use rare ephemera and other documents to reconstruct a now vanished musical world, assembling evidence of actual musical events, their purposes, participants and repertoire. I observe the many and varied ways in which music functioned as a (subjective) marker of cultural identity within a self-enclosed cultural enclave that was characterized more by its heterogeneity than by the commonality suggested by its Jewishness. [ABSTRACT FROM AUTHOR]