We report here the synthesis of nucleoside and oligonucleotide analogs containing selenium, which serves as an anomalous scattering center to enable MAD phase determination in nucleotide X-ray crystallography. We have developed a phase transfer approach to introduce the selenium functionality in A, C, G, T, and U nucleosides at 5'-positions. In the incorporation of the selenium functionality, the leaving groups (bromide, mesyl, and tosyl) were readily displaced by sodium selenide, sodium diselenide, and sodium methyl selenide with yields higher than 90%. Selenium-derivatized oligonucleotides have been synthesized via phosphoramidite chemistry.

UV light, a paradigmatic initiator of cell stress, invokes responses that include signal transduction, activation of transcription factors, and changes in gene expression. Consequently, in epidermal keratinocytes, its principal and frequent natural target, UV regulates transcription of a distinctive set of genes. Hypothesizing that UV activates distinctive epidermal signal transduction pathways, we compared the UV-responsive activation of the JNK and NFkappaB pathways in keratinocytes, with the activation of the same pathways by other agents and in other cell types. Using of inhibitors and antisense oligonucleotides, we found that in keratinocytes only UVB/UVC activate JNK, while in other cell types UVA, heat shock, and oxidative stress do as well. Keratinocytes express JNK-1 and JNK-3, which is unexpected because JNK-3 expression is considered brain-specific. In keratinocytes, ERK1, ERK2, and p38 are activated by growth factors, but not by UV. UVB/UVC in keratinocytes activates Elk1 and AP1 exclusively through the JNK pathway. JNKK1 is essential for UVB/UVC activation of JNK in keratinocytes in vitro and in human skin in vivo. In contrast, in HeLa cells, used as a control, crosstalk among signal transduction pathways allows considerable laxity. In parallel, UVB/UVC and TNFalpha activate the NFkappaB pathway via distinct mechanisms, as shown using antisense oligonucleotides targeted against IKKbeta, the active subunit of IKK. This implies a specific UVB/UVC responsive signal transduction pathway independent from other pathways. Our results suggest that in epidermal keratinocytes specific signal transduction pathways respond to UV light. Based on these findings, we propose that the UV light is not a genetic stress response inducer in these cells, but a specific agent to which epidermis developed highly specialized responses.

The calculation of the Earth's age, based on ascribing approximately 40 years to each generation mentioned in the Talmud, results in a total of 5,740 years from the "birth" of Adam. For modern scientists holding traditional viewpoints, this "dating" has led to conflicts which have been explained by various semantic gymnastics. The most common of these is that the Biblical "six days of creation" refers not to days as we know them, but to vast periods of time. However, an examination of the writings of Rabbi Abbahu, Rabbi Abbaye, in the Talmud and Midrash, suggest a concept more akin to our present knowledge. Simon Hahasid in the Talmud estimated the Earth's age as 40,000 years. Based on these early sages, many writers of Jewish religious philosophy in the 10th-12th centuries give ages of the Earth from 50,000 to 100,000 years. Certain Kabbalists from Spain in the 12-13 centuries calculated the Earth's age at 900,000 to 2.5 billion years. A continuation of these concepts are expressed throughout Jewish traditional literature from the Middle Ages to the present by Jewish philosophers and Rabbis such as Maimonides, Rabbi Judah Halevi, Rabbi Israel Lipschitz and others.

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