To date, apoptosis has been characterized biochemically by the production of 180-200 bp internucleosomal DNA fragments resulting from the activation of an endonuclease(s). The principal morphological feature of apoptosis is the condensation of chromatin and it has been assumed that this may reflect the oligonucleosomal fragmentation pattern. We have re-examined this dogma by comparing the biochemical and morphological features of cell death in several epithelial cell types (HT-29-I1 colon adenocarcinoma, CC164 mink lung, DU-145 human prostatic carcinoma and MCF-7 human breast adenocarcinoma) and one mesenchymal cell line (Hllras-R3 ras-transformed rat fibroblasts). Cell death was induced either by serum deprivation, TGF-,B1 or etoposide, or by leaving cells to reach confluence. Cell death was assessed with respect to detachment from monolayers, morphological changes and DNA integrity. The DNA-binding fluorophore Hoechst 33258 revealed chromatin condensation patterns consistent with apoptotic cell death in all cell types except MCF-7 cells. Using field inversion gel electrophoresis in conjunction wih conventional 2% agarose gel electrophoresis, cleavage of DNA to 50 kbp fragments was observed in all cases except MCF-7 cells. This preceded the appearance of oligonucleosomal fragments in HT-29-I1, CC164 and Hllras-R3 cells. Although the DNA of DU-145 cells fragmented into 50 kbp units, and although the cells exhibited classical apoptotic morphology, no subsequent internucleosomal cleavage was observed. These results suggest that changes in the integrity of DNA indicative of the release of chromatin loop domains occur before cleavage at internucleosomal sites is initiated and that the latter is not an essential step in the apoptotic process.

Radar can produce detailed precipitation information for large areas from a single location in real time. Although radar has been used experimentally for nearly 30 years to measure rainfall, operational implementation has been slow. Today we find that data are underutilized and both confusion and misunderstanding exist about the inherent ability of radar to measure rainfall, about factors that contribute to errors, and about the importance of careful calibration and signal processing. Areal and point rainfall estimates are often in error by a factor of two or more. Error sources reside in measurement of radar reflectivity factor, evaporation and advection of precipitation before reaching the ground, and variations in the drop-size distribution and vertical air motions. Nevertheless, radar can be of lifesaving usefulness by alerting forecasters to the potential for flash flooding. The most successful technique for improving the radar rainfall estimates has been to "calibrate" the radar with rain gages. Simple techniques that combine sparse gage reports (one gage per 1000-2000 km 2) with radar produce smaller measurement errors (10-30%) than either system alone. When high accuracy rainfall measurements are needed (average error less than about 10-20%) the advantage of radar is diminished, since the number of gages required for calibration is itself sufficient to provide the desired accuracy.

Traditionally, the nowcasting of precipitation was conducted to a large extent by means of extrapolation of observations, especially of radar ref lectivity. In recent years, the blending of traditional extrapolation-based techniques with high-resolution numerical weather prediction (NWP) is gaining popularity in the nowcasting community. The increased need of NWP products in nowcasting applications poses great challenges to the NWP community because the nowcasting application of high-resolution NWP has higher requirements on the quality and content of the initial conditions compared to longer-range NWP. Considerable progress has been made in the use of NWP for nowcasting thanks to the increase in computational resources, advancement of high-resolution data assimilation techniques, and improvement of convective-permitting numerical modeling. This paper summarizes the recent progress and discusses some of the challenges for future advancement.

Oxygen is essential for the life of most multicellular organisms. Cells possess enzymes called molecular dioxygenases that depend on oxygen for activity. A subclass of molecular dioxygenases is the histone demethylase enzymes, which are characterized by the presence of a Jumanji-C (JmjC) domain. Hypoxia can alter chromatin, but whether this is a direct effect on JmjC-histone demethylases or due to other mechanisms is unknown. Here, we report that hypoxia induces a rapid and hypoxia-inducible factor–independent induction of histone methylation in a range of human cultured cells. Genomic locations of histone-3 lysine-4 trimethylation (H3K4me3) and H3K36me3 after a brief exposure of cultured cells to hypoxia predict the cell’s transcriptional response several hours later. We show that inactivation of one of the JmjC-containing enzymes, lysine demethylase 5A (KDM5A), mimics hypoxia-induced cellular responses. These results demonstrate that oxygen sensing by chromatin occurs via JmjC-histone demethylase inhibition.

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Data from the Convection and Precipitation/Electrification (CaPE) project, as well as results from numerical simulations, are used to study horizontal convective rolls. The environmental conditions necessary for sustaining rolls and for influencing the aspect ratio, ratio of roll wavelength to convective boundary layer (CBL) depth, and orientation are examined. Observations and numerical model simulations both suggest that a moderate surface sensible heat flux and some vertical wind shear are necessary for roll existence. Unlike some previous studies, however, it is shown that rolls occurred within very low CBL shear conditions (ϳ2 ϫ 10 Ϫ3 s Ϫ1). In addition, the low-level (i.e., ϳ200 m) shear seems to be more important than the shear through the depth of the CBL in roll sustenance. The aspect ratio is shown to be proportional to the CBL instability, measured in terms of the Monin-Obukhov length. The roll orientation is similar to the wind direction at 10 m AGL, the CBL wind direction, the inversion-level wind direction, and the CBL shear direction. This is not surprising since there was very little directional shear observed within the CBL during CaPE.

The molecular events that lead to the onset of labor in humans and in other mammalian species remain unclear. We propose that a decline in coactivators containing histone acetylase activity in myometrium may contribute to the onset of labor by impairing the function of the progesterone-progesterone receptor (PR) complex. As assessed by semiquantitative and real-time RT-PCR, immunohistochemistry, and immunoblotting, expression of the PR coactivators cAMP-response element-binding protein (CREB)-binding protein and steroid receptor coactivators 2 and 3 was decreased in fundal uterine tissue of women in labor. Using the mouse as an animal model, we also found decreased coactivator levels in uterine tissues at term. In both human and mouse, the levels of acetylated histone H3 were also decreased in uterine tissues at term. Administration of trichostatin A, a specific and potent histone deacetylase inhibitor, to pregnant mice late in gestation increased histone acetylation and delayed the initiation of parturition by 24 -48 h, suggesting the functional importance of the decline in histone acetylation in the initiation of labor. These findings suggest that the decline in PR coactivator expression and in histone acetylation in the uterus near term may impair PR function by causing a functional progesterone withdrawal. The resulting decrease in expression of PR-responsive genes should increase sensitivity of the uterus to contractile stimuli.pregnancy ͉ labor ͉ histone acetylation ͉ human ͉ mouse I n many species, progesterone withdrawal appears to be a critical event in the initiation of parturition, which is evidenced by the fact that a decline in progesterone levels precedes the onset of parturition and that progesterone administration delays the process (1). However, a role for progesterone withdrawal in the control of human labor has not been identified, because plasma progesterone levels do not decline before or during labor (2). Nevertheless, the fact that the progesterone receptor (PR) antagonist mifepristone can enhance cervical ripening and initiate labor (3) suggests some form of functional progesterone deprivation might be involved in the initiation of labor in women. Functional progesterone withdrawal could be mediated by a variety of mechanisms, including accelerated inactivation͞ metabolism of progesterone within target cells, formation of metabolites that antagonize binding of progesterone to its receptor, reduction in the amount of PR, and͞or impairment of the transcriptional activity of the progesterone-PR complex by alterations in the levels of essential coregulators. Because levels of uterine PR do not decline prior to or during labor (4), in the present study we analyzed the potential role of changes in coregulator levels in the initiation of labor.Nuclear receptors such as the PR interact with coregulators, coactivators, and corepressors, which increase and decrease their transcriptional activities, respectively. Coactivators likely function by bridging sequence-specific activators, such as ligandbo...

The data-rich International H2O Project (IHOP_2002) experiment is used to study convective storm initiation and subsequent evolution for all days of the experiment. Initiation episodes were almost evenly divided between those triggered along surface-based convergence lines and elevated initiation episodes that showed no associated surface convergence. The elevated episodes occurred mostly at night, and the surface-based episodes occurred during the afternoon and evening. Surface-based initiations were mostly associated with synoptic fronts and gust fronts and less so with drylines and bores. Elevated initiations were frequently associated with observable convergent or confluent features in the Rapid Update Cycle (RUC) wind analysis fields between 900 and 600 hPa. The RUC10 3-h forecast of the precipitation initiation episodes were correct 44% of the time, allowing a tolerance of 250 km in space and for the forecast being early by one period. However, the accuracy was closely tied to the scale of the initiation mechanism, being highest for synoptic frontal features and lowest for gust fronts. Gust fronts were a primary feature influencing the evolution of the initiated storms. Almost one-half of the storm complexes associated with initiation episodes did not produce surface gust fronts. Storm systems that did not produce gust fronts most often lived 2–6 h while those that did frequently lived at least 8 h. The largest and longest-lived storm complexes had well-developed intense gust fronts that influenced the propagation of the storm system. The RUC10 was generally not successful in forecasting the evolution and motion of the larger, more intense storm complexes; presumably this was because it did not produce strong gust fronts. Implications for forecasting convective storm initiation and evolution are discussed.