Shulamit an Ancient Love-Drama. Known as the "Song of Songs," and attributed to Solomon, King of Israel

Gershon Katz

Fritta Brod, Rollenbild, in: Rabindranath Tagore: The King of the dark chamber

Signatur des Originals: S 36/F03237

Post-biblical history of the Jews : from the close of the Old Testament, about the year 420 B.C.E. till the destruction of the second temple, in the year 70 C.E. ; in two volumes

by Morris J. Raphall

The role of ATM in the cell cycle control of V(D)J recombination

Lymphocyte development requires the assembly of diversified antigen receptor complexes generated by the genetically programmed V(D)J recombination event. Because germline DNA is cut, introducing potentially dangerous double-stranded breaks (DSBs) and rearranged prior to repair, its activity is limited to the non-cycling stages of the cell cycle, G0/G1. The potential involvement of a key mediator, Ataxia Telangiectasia Mutated or ATM, in the DNA damage response (DDR) and cell cycle checkpoints has been implicated in recombination, but its role is not fully understood. Thymic lymphomas from ATM deficient mice contain clonal chromosomal translocations involving the T-cell antigen receptor (TCR). A previous report found ATM and its downstream target p53 associated with V(D)J intermediates, suggesting the DDR senses recombination. In this study, we sought to understand the role of ATM in V(D)J recombination. Developing thymocytes from ATM deficient mice were analyzed according to the cell cycle to detect V(D)J intermediates. Examination of all TCR loci in the non-cycling (G0/G1) and cycling (S/G2/M) fractions revealed the persistence of intermediates in ATM deficient thymocytes, contrary to the wild-type in which intermediates are found only during G0/G1. Further analysis found no defect in end-joining of intermediates, nor were they detected in developed T-cells. Based upon the presence of persisting intermediates, the recombination initiating nuclease Rag-2 was examined; strict regulation limits it to G 0/G1. Rag-2 regulation was not affected by an ATM deficiency as Rag-2 expression remained contained within G0/G 1, indicating recombination is not continuous. To determine if an ATM deficiency affects recognition of V(D)J breaks, sites of recombination identified by a TCR locus or Rag expression were analyzed according to co-localization with a DDR factor phosphorylated immediately after DNA damage, phosphorylated H2AX (γH2AX). No differences in co-localization were found between the wild-type and ATM deficiency, demonstrating ATM deficient lymphocytes retain the ability to recognize DSBs. Together, these results suggest ATM is necessary in the cell cycle regulation of recombination but not essential for the identification of V(D)J breaks. ATM ensures the containment of intermediates within G0/G1 and maintains genomic stability of developing lymphocytes, emphasizing its fundamental role in preventing tumorigenesis.^

Molecular studies of human high grade B cell non -Hodgkin's lymphomas

The non-Hodgkin's B cell lymphomas are a diverse group of neoplastic diseases. The incidence rate of the malignant tumors has been rising rapidly over the past twenty years in the United States and worldwide. The lack of insight to pathogenesis of the disease poses a significant problem in the early detection and effective treatment of the human malignancies. These studies attempted to investigate the molecular basis of pathogenesis of the human high grade B cell non-Hodgkin's lymphomas with a reverse genetic approach. The specific objective was to clone gene(s) which may play roles in development and progression of human high grade B cell non-Hodgkin's lymphomas.^ The messenger RNAs from two high grade B cell lymphoma lines, CJ and RR, were used for construction of cDNA libraries. Differential screening of the derived cDNA libraries yielded a 1.4 kb cDNA clone. The gene, designated as NHL-B1.4, was shown to be highly amplified and over-expressed in the high grade B cell lymphoma lines. It was not expressed in the peripheral blood lymphoid cells from normal donors. However, it was inducible in peripheral blood T lymphocytes by a T cell mitogen, PHA, but could not be activated in normal B cells by B cell mitogen PMA. Further molecular characterization revealed that the gene may have been rearranged in the RR and some other B cell lymphoma lines. The coding capacity of the cDNA has been confirmed by a rabbit reticulocyte lysate and wheat germ protein synthesis system. A recombinant protein with a molecular weight of approximate 30 kDa was visualized in autoradiogram. Polyclonal antisera have been generated by immunization of two rabbits with the NHL-B1.4 recombinant protein produced in the E. coli JM109. The derived antibody can recognize a natural protein with molecular weight of 49 kDa in cell lysate of activated peripheral T lymphocytes of normal donors and both the cell lysate and supernatant of RR B cell lymphoma lines. The possible biologic functions of the molecule has been tested preliminarily in a B lymphocyte proliferation assay. It was found that the Q-sepharose chromatograph purified supernatant of COS cell transfection could increase tritiated thymidine uptake by B lymphocytes but not by T lymphocytes. The B cell stimulatory activity of the supernatant of COS cell tranfection could be neutralized by the polyclonal antisera, indicating that the NHL-B1.4 gene product may be a molecule with BCGF-like activity.^ The expression profiles of NHL-B1.4 in normal and neoplastic lymphoid cells were consistent with the current B lymphocyte activation model and autocrine hypothesis of high grade B cell lymphomagenesis. These results suggested that the NHL-B1.4 cDNA may be a disease-related gene of human high grade B cell lymphomas, which may codes for a postulated B cell autocrine growth factor. ^

PML tumor suppressor potentiates cell death through inhibition of the NF -kappa B survival pathway

The promyelocytic leukemia protein PML is a growth suppressor essential for induction of apoptosis by diverse apoptotic stimuli. The mechanism by which PML regulates cell death remains unclear. In this study we found that ectopic expression of PML potentiates cell death in the TNFα-resistant tumor line U2OS and significantly sensitized these cells to apoptosis induced by TNFα in a p53-independent manner. Our study demonstrated that both PML and PML/TNFα-induced cell death are associated with DNA fragmentation, activation of caspase-3, -7, -8, and degradation of DFF/ICAD. Furthermore, we found that PML-induced and PML/TNFα-induced cell death could be blocked by the caspase-8 inhibitors crmA and c-FLIP, but not by Bcl-2, the inhibitor of mitochondria-mediated apoptotic pathway. These findings indicate that this cell death event is initiated through the death receptor-dependent apoptosis pathway. Our study further showed that PML recruits NF-kappa B (NF-κB) to the PML nuclear body, blocks NF-κB binding to its cognate enhancer, and represses its transactivation function with the C-terminal region. Therefore PML inhibits the NF-κB survival pathway. Overexpression of NF-κB rescued cell death induced by PML and PML/TNFκ. These results imply that PML is a functional repressor of NF-κB. This notion was further supported by the finding that the PML−/− mouse embryo fibroblasts (MEFs) are more resistant than the wild-type MEFs to TNFκ-induced apoptosis. In conclusion, our studies convincingly demonstrated that PML potentiates cell death through inhibition of the NF-κB survival pathway. Activation of NF-κB frequently occurs during oncogenesis. Our study here suggests that a loss of PML function enhances the NF-κB survival pathway and this event may contribute to tumorigenesis. ^

Net primary productivity, POC export, Th234 and U238 activities and abundance of autotrophs during U.S.C.G.C. Healy cruises HLY0802 and HLY0803

Seasonal patterns in the partitioning of phytoplankton carbon during receding sea ice conditions in the eastern Bering Sea water column are presented using rates of 14C net primary productivity (NPP), phototrophic plankton carbon content, and POC export fluxes from shelf and slope waters in the spring (March 30-May 6) and summer (July 3-30) of 2008. At ice-covered and marginal ice zone (MIZ) stations on the inner and middle shelf in spring, NPP averaged 76 ± 93 mmol C/m**2/d, and in ice-free waters on the outer shelf NPP averaged 102 ± 137 mmol C/m**2/d. In summer, rates of NPP were more uniform across the entire shelf and averaged 43 ± 23 mmol C/m**2/d over the entire shelf. A concomitant shift was observed in the phototrophic pico-, nano-, and microplankton community in the chlorophyll maximum, from a diatom dominated system (80 ± 12% autotrophic C) in ice covered and MIZ waters in spring, to a microflagellate dominated system (71 ± 31% autotrophic C) in summer. Sediment trap POC fluxes near the 1% PAR depth in ice-free slope waters increased by 70% from spring to summer, from 10 ± 7 mmol C/m**2/d to 17 ± 5 mmol C/m**2/d, respectively. Over the shelf, under-ice trap fluxes at 20 m were higher, averaging 43 ± 17 mmol C/m**2/d POC export over the shelf and slope estimated from 234Th deficits averaged 11 ± 5 mmol C/m**2/d in spring and 10 ± 2 mmol C/m**2/d in summer. Average e-ratios calculated on a station-by-station basis decreased by ~ 30% from spring to summer, from 0.46 ± 0.48 in ice-covered and MIZ waters, to 0.33 ± 0.26 in summer, though the high uncertainty prevents a statistical differentiation of these data.

(Table 2) Layer-by-layer chemical composition of barite crusts from the Atlantis II Deep of the Red Sea rift zone

Results of studies of hydrothermal sulfide-sulfate rocks occurring in the Atlantis II Deep of the Red Sea are reported in the paper.

Description of two mass species of Pacific copepods in terms of two polymorphic loci

Population genetics of two species of mass copepods Undinula darwini and Calanus australis, with different range types, is investigated. Both species exhibit considerable genetic diversity, especially C. australis (observed heterozygoticity = 0.36), which inhabits a variable biotope in the zone of the Peru current. Samples of both species exhibited highly significant genetic heterogeneity as well as heterozygote deficiency compared with the situation expected from the Hardy-Weinberg law. Contribution of distance isolation to genetic differentiation of populations is estimated. Gene drift is discussed as a source of heterogeneity in populations of planktic copepods. Possible aspects of population genetic research on marine plank-tic crustaceans are discussed.

Seawater carbonate chemistry and photosystem II photoinactivation of the coastal diatom Thalassiosira pseudonana in a laboratory experiment

We studied the interactive effects of pCO2 and growth light on the coastal marine diatom Thalassiosira pseudonana CCMP 1335 growing under ambient and expected end-of-the-century pCO2 (750 ppmv), and a range of growth light from 30 to 380 µmol photons/m**2/s. Elevated pCO2 significantly stimulated the growth of T. pseudonana under sub-saturating growth light, but not under saturating to super-saturating growth light. Under ambient pCO2 susceptibility to photoinactivation of photosystem II (sigma i) increased with increasing growth rate, but cells growing under elevated pCO2 showed no dependence between growth rate and sigma i, so under high growth light cells under elevated pCO2 were less susceptible to photoinactivation of photosystem II, and thus incurred a lower running cost to maintain photosystem II function. Growth light altered the contents of RbcL (RUBISCO) and PsaC (PSI) protein subunits, and the ratios among the subunits, but there were only limited effects on these and other protein pools between cells grown under ambient and elevated pCO2.