Circadian clocks drive rhythmic behaviour in animals and are regulated by transcriptional feedback loops. For example, the Drosophila proteins Clock (Clk) and Cycle (Cyc) activate transcription of ...period (per) and timeless (tim). Per and Tim then associate, translocate to the nucleus, and repress the activity of Clk and Cyc. However, post-translational modifications are also critical to proper timing. Per and Tim undergo rhythmic changes in phosphorylation, and evidence supports roles for two kinases in this process: Doubletime (Dbt) phosphorylates Per, whereas Shaggy (Sgg) phosphorylates Tim. Yet Sgg and Dbt often require a phosphoserine in their target site, and analysis of Per phosphorylation in dbt mutants suggests a role for other kinases. Here we show that the catalytic subunit of Drosophila casein kinase 2 (CK2alpha) is expressed predominantly in the cytoplasm of key circadian pacemaker neurons. CK2alpha mutant flies show lengthened circadian period, decreased CK2 activity, and delayed nuclear entry of Per. These effects are probably direct, as CK2alpha specifically phosphorylates Per in vitro. We propose that CK2 is an evolutionary link between the divergent circadian systems of animals, plants and fungi.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We established criteria for appropriate use of the prostate-specific antigen (PSA) assay and used them to evaluate PSA test utilization at 1 tertiary care institution. During a 6-month period, 2,330 ...PSA results were reported for outpatients and 95 for inpatients. We reviewed medical records for a random sample of 338 outpatient results (14.51%) and all 95 inpatient results, of which 21% (71/338) of outpatient and 17% (16/95) of inpatient results were inappropriate according to our test utilization criteria. Among outpatients, 52% of tests were done for screening and 19% for monitoring for cancer recurrence. For inpatients, workup for cancer (53/95 56%) was the most frequent indication for testing and screening the second (24/95 25%). Of tests failing the criteria, 66 (76%) of 87 resulted from excessively frequent and age-inappropriate screening. We assessed the potential effect on clinical outcome if these tests were not performed. Of the 87 tests considered inappropriate, only 1 test result influenced clinical management for patients younger than 75 years. By instituting simple limits on age and frequency, we estimate that 74% (64/87) of the inappropriate tests could have been eliminated.
Genetic control of root development in rice is complex and the underlying mechanisms (constitutive and adaptive) are poorly understood. Lowland and upland varieties of indica and japonica rice with ...contrasting root development characteristics have been crossed, mapping populations developed and a number of QTLs in different chromosomes were identified. As these studies have used different sets of markers and many of the QTLs identified are long, it is difficult to exploit the varietal difference for improved root traits by marker assisted selection and for identification of concerned alleles. Intensive data mining of literature resulted in the identification 861 root development QTLs and associated microsatellite markers located on different chromosomes. The QTL and marker data generated and the genome sequence of rice were used for construction of a relational database, Rootbrowse, using MySQL relational database management system and Bio::DB::GFF schema. The data is viewed using GBrowse visualization tool. It graphically displays a section of the genome and all features annotated on it including the QTLs. The QTLs can be displayed along with SSR markers, protein coding genes and/or known root development genes for prediction of probable candidate genes.
Rootbrowse is freely available at http://www.ricebrowse.org.
The T lymphocyte glycoprotein CD2 appears to have an important role in human T cell development and activation. A novel anti-CD2 monoclonal antibody, designed UMCD2, was shown to block E rosetting, ...and therefore was defined as recognizing the Tll1 ligand-binding epitope. Binding of UMCD2 to T cells and thymocytes was blocked by several, but not all, anti-Tll1 antibodies, suggesting that the Tll1 epitope consists of more than one subepitope. In functional studies, the combination of UMCD2 plus anti-Tll3 was mitogenic for T cells; in some individuals, the level of activation was as high as that seen for the combination of anti-Tll2 plus anti-Tll3. However, when UMCD2 was added to other stimuli mitogenic for T lymphocytes, such as IL-2 or anti-CD3-Sepharose, it inhibited T cell responses. Although the combination of UMCD2 and anti-Tll3 induced an increase in cytoplasmic free calcium, the inhibitory activities of UMCD2 were not accompanied by effects on calcium fluxes. A panel of previously characterized CD2 mutants was then analyzed for binding of UMCD2 and other anti-CD2 monoclonals. Surprisingly, UMCD2 bound to all mutants tested, although the other anti-CD2 antibodies with specificity for the ligand-binding region of CD2 each failed to bind to one or more mutants. These data suggest that binding of antibody to a particular CD2 epitope can have opposite effects on the state of T cell activation, depending on the costimulus. Moreover, inhibitory effects mediated through CD2 may use a signaling mechanism distinct from that used in CD2 pathway activation. Of particular interest, the portion of the CD2 ligand-binding region recognized by UMCD2 is distinct from areas of the CD2 molecule that have previously been studied.
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