AG14361 is, to our knowledge, the first high-potency PARP-1 inhibitor with the specificity and in vivo activity to enhance chemotherapy and radiation therapy of human cancer.

The U.S. National Oceanic and Atmospheric Administration (NOAA) Coral Reef Watch (CRW) program has developed a daily global 5-km product suite based on satellite observations to monitor thermal stress on coral reefs. These products fulfill requests from coral reef managers and researchers for higher resolution products by taking advantage of new satellites, sensors and algorithms. Improvements of the 5-km products over CRW's heritage global 50-km products are derived from: (1) the higher resolution and greater data density of NOAA's next-generation operational daily global 5-km geo-polar blended sea surface temperature (SST) analysis; and (2) implementation of a new SST climatology derived from the Pathfinder SST climate data record. The new products increase near-shore coverage and now allow direct monitoring of 95% of coral reefs and significantly reduce data gaps caused by cloud cover. The 5-km product suite includes SST Anomaly, Coral Bleaching HotSpots, Degree Heating Weeks and Bleaching Alert Area, matching existing CRW products. When compared with the 50-km products and in situ bleaching observations for 2013-2014, the 5-km products identified known thermal stress events and matched bleaching observations. These near reef-scale products significantly advance the ability of coral reef researchers and managers to monitor coral thermal stress in near-real-time.

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M-phase promoting factor or maturation promoting factor, a key regulator of the G 2 3 M transition of the cell cycle, is a complex of cdc2 and a B-type cyclin. We have previously shown that Xenopus cyclin B1 has five sites of Ser phosphorylation, four of which map to a recently identified cytoplasmic retention signal (CRS). The CRS appears to be responsible for the cytoplasmic localization of B-type cyclins, although the underlying mechanism is still unclear. Phosphorylation of cyclin B1 is not required for cdc2 binding or cdc2 kinase activity. However, when all of the Ser phosphorylation sites in the CRS are mutated to Ala to abolish phosphorylation, the mutant cyclin B1 Ala is inactivated; activity can be enhanced by mutation of these residues to Glu to mimic phosphoserine, suggesting that phosphorylation of cyclin B1 is required for its biological activity. Here we show that biological activity can be restored to cyclin B1 Ala by appending either a nuclear localization signal (NLS), or a second CRS domain with the Ser phosphorylation sites mutated to Glu, while fusion of a second CRS domain with the Ser phosphorylation sites mutated to Ala inactivates wild-type cyclin B1. Nuclear histone H1 kinase activity was detected in association with cyclin B1 Ala targeted to the nucleus by a wild-type NLS, but not by a mutant NLS. These results demonstrate that nuclear translocation mediates the biological activity of cyclin B1 and suggest that phosphorylation within the CRS domain of cyclin B1 plays a regulatory role in this process. Furthermore, given the similar in vitro substrate specificity of cyclin-dependent kinases, this investigation provides direct evidence for the hypothesis that the control of subcellular localization of cyclins plays a key role in regulating the biological activity of cyclin-dependent kinase-cyclin complexes.M-phase promoting factor or maturation promoting factor (MPF), the key regulator of the G 2 3 M transition during the cell cycle (1, 2), is regulated by phosphorylation of both of its component proteins: the serine͞threonine protein kinase cdc2 and a B-type cyclin. Three phosphorylation sites govern the activity of cdc2: phosphorylation of Thr-14 and Tyr-15 inhibits cdc2 activity, while phosphorylation of Thr-161 acts as a positive regulatory signal (3-9).B-type cyclins are phosphorylated in a variety of cell types, including somatic cells, oocytes, and embryos (10-12). Phosphorylation of B-type cyclins temporally correlates with MPF activation (11,12). Five phosphorylation sites have been identified for Xenopus cyclin B1 at 14). Phosphorylation of cyclin B1 is required for its biological activity, as demonstrated by the fact that mutation of these five Ser phosphorylation sites to Ala inactivates cyclin B1, whereas mutation of the same residues to Glu to mimic phosphoserine enhances the activity of cyclin B1 (13). However, the precise role of phosphorylation in regulating cyclin activity has remained obscure. It is known that phosphorylation of cyclin B1 is not required for cdc...

BackgroundHypopharyngeal glands (HG) of honeybee workers play an important role in honeybee nutrition and caste differentiation. Previous research mainly focused on age-dependent morphological, physiological, biochemical and genomic characters of the HG. Here proteomics and biochemical network analysis were used to follow protein changes during the HG development.ResultsA total of 87, 76, 85, 74, 71, and 55 proteins were unambiguously identified on day 1, 3, 6, 12, 15 and 20, respectively. These proteins were major royal jelly proteins (MRJPs), metabolism of carbohydrates, lipids and proteins, cytoskeleton, development regulation, antioxidant, molecule transporter, regulation of transcription/translation, proteins with folding functions. The most interesting is that MRJP's that have been detected in the HG of the newly emerged worker bees. The MRJP's expression is at peak level from 6-12 days, was validated by western blot analysis of MRJP1, 2 and 3. Moreover, 35 key node proteins were found in the biochemical networks of the HG.ConclusionsHG secretes RJ at peak level within 6-12 days, but the worker bee can secrete royal jelly (RJ) since birth, which is a new finding. Several key node proteins play an important role in the biochemical networks of the developing HG. This provides us some target proteins when genetically manipulating honeybees.