Notes: Abstract  We present an analysis of the seasonal precipitation associated with the African, Indian and the Australian-Indonesian monsoon and the interannual variation of the Indian monsoon simulated by 30 atmospheric general circulation models undertaken as a special diagnostic subproject of the Atmospheric Model Intercomparison Project (AMIP). The seasonal migration of the major rainbelt observed over the African region, is reasonably well simulated by almost all the models. The Asia West Pacific region is more complex because of the presence of warm oceans equatorward of heated continents. Whereas some models simulate the observed seasonal migration of the primary rainbelt, in several others this rainbelt remains over the equatorial oceans in all seasons. Thus, the models fall into two distinct classes on the basis of the seasonal variation of the major rainbelt over the Asia West Pacific sector, the first (class I) are models with a realistic simulation of the seasonal migration and the major rainbelt over the continent in the boreal summer; and the second (class II) are models with a smaller amplitude of seasonal migration than observed. The mean rainfall pattern over the Indian region for July-August (the peak monsoon months) is even more complex because, in addition to the primary rainbelt over the Indian monsoon zone (the monsoon rainbelt) and the secondary one over the equatorial Indian ocean, another zone with significant rainfall occurs over the foothills of Himalayas just north of the monsoon zone. Eleven models simulate the monsoon rainbelt reasonably realistically. Of these, in the simulations of five belonging to class I, the monsoon rainbelt over India in the summer is a manifestation of the seasonal migration of the planetary scale system. However in those belonging to class II it is associated with a more localised system. In several models, the oceanic rainbelt dominates the continental one. On the whole, the skill in simulation of excess/deficit summer monsoon rainfall over the Indian region is found to be much larger for models of class I than II, particularly for the ENSO associated seasons. Thus, the classification based on seasonal mean patterns is found to be useful for interpreting the simulation of interannual variation. The mean rainfall pattern of models of class I is closer to the observed and has a higher pattern correlation coefficient than that of class II. This supports Sperber and Palmer’s (1996) result of the association of better simulation of interannual variability with better simulation of the mean rainfall pattern. The hypothesis, that the skill of simulation of the interannual variation of the all-India monsoon rainfall in association with ENSO depends upon the skill of simulation of the seasonal variation over the Asia West Pacific sector, is supported by a case in which we have two versions of the model where NCEP1 is in class II and NCEP2 is in class I. The simulation of the interannual variation of the local response over the central Pacific as well as the all-India monsoon rainfall are good for NCEP2 and poor for NCEP1. Our results suggest that when the model climatology is reasonably close to observations, to achieve a realistic simulation of the interannual variation of all-India monsoon rainfall associated with ENSO, the focus should be on improvement of the simulation of the seasonal variation over the Asia West Pacific sector rather than further improvement of the simulation of the mean rainfall pattern over the Indian region.

Notes: Abstract Our previous studies have shown that MMP-9 levels are significantly elevated during the progression of human gliomas. In the current study, we examined the role of JNK- and ERK-dependent signaling modules in the regulation of MMP-9 production and the invasive behavior of the human glioblastoma cell line SNB19, in which JNK/ERK1 is constitutively activated. SNB19 cells that were transfected with dominant-negative JNK, MEKK, and ERK1 expression vectors showed reduced MMP-9 promoter activity. In addition, conditioned medium collected from SNB19 cells transfected with these expression vectors showed diminished MMP-9 activity in the presence of phorbol myristate acetate, as determined by gelatin zymography. The cotransfection of SNB19 cells with kinase-deficient c-raf also diminished MMP-9 promoter activity. Further, in the presence of a specific inhibitor of MEKK (PD098059), the Matrigel invasion assay showed the invasiveness of dominant-negative SNB19 cells transfected with dominant-negative JNK1 or ERK1 to be remarkably reduced. In conclusion, our studies showed for the first time that MMP-9 production and the invasive behavior of SNB19 cells are regulated by JNK- and ERK-dependent signaling modules and that interfering with either of the pathways reduces invasiveness.

Notes: Abstract Human tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type serine protease inhibitor that inhibits plasmin, trypsin, chymotrypsin, cathepsin G and plasma kallikrein but not urokinase (uPA) or tissue-type plasminogen activator and thrombin. Earlier studies from our and other laboratories have shown that the production of TFPI-2 is downregulated during the progression of various cancers. To investigate the role of TFPI-2 in the invasion and metastasis of lung tumors, the human lung cancer cell line A549, which produces high levels of TFPI-2, was stably transfected with a vector capable of expressing an antisense transcript complementary to the full-length TFPI-2 mRNA. Northern blot analysis was used to quantify the TFPI-2 mRNA transcript, and western blot analysis was used to measure TFPI-2 protein levels in parental cells and stably transfected (vector and antisense) clones. The levels of TFPI-2 mRNA and protein were significantly less in antisense clones than in the parental and vector controls. The invasive potential of the parental cells and stably transfected vector clones in vitro, as measured by the Matrigel invasion assay, was also markedly less than that of antisense clones. Further characterization of these clones showed that more cells migrated from antisense clones than from parental and vector clones. These data suggest that TFPI-2 is critical for the invasion and metastasis of lung cancer and that the downregulation of TFPI-2 production may be a feasible approach to increase invasiveness and metastasis.

Notes: Abstract We previously showed that downregulation of the urokinase-type plasminogen activator receptor (uPAR) in the SNB19 human glioblastoma cell line by the stable transfection of a plasmid expressing a 300 bp antisense sequence to the 5′ end of the uPAR gene produced a decrease in the amount of target mRNA. In a more recent study, we found that adenovirus-mediated transduction (Ad-uPAR) of the same uPAR antisense gene construct in SNB19 cells also downregulated uPAR protein levels. We report here that Ad-uPAR-transfected SNB19 cells produced the same amounts of target uPAR mRNA but significantly less protein by in vitro translation and by in situ [35S] labeling compared to Ad-CMV vector-transfected and mock-transfected cells. This antisense construct also inhibited glioblastoma cell invasion confirming previous results. We conclude that downregulation of uPAR by this antisense gene construct results from inhibition of protein translation.