[1] Data from the Global Precipitation Climatology Project (GPCP) covering the period 1979 -2007 are examined for changes of precipitation extremes as a function of global mean temperature by using a new method which focuses on interannual differences rather than time series. We find that the top 10% bin of precipitation intensity increases by about 95% for each degree Kelvin (K) increase in global mean temperature, while 30%-60% bins decrease by about 20% K À1 . The global average precipitation intensity increases by about 23% K À1, substantially greater than the increase of about 7% K À1 in atmospheric water-holding capacity estimated by the Clausius-Clapeyron equation. The large increase of precipitation intensity is qualitatively consistent with the hypothesis that the precipitation intensity should increase by more than 7% K À1 because of the additional latent heat released from the increased moisture. Our results also provide an independent evidence in support for significant increases in the number and/or size of strong global tropical cyclones. However an ensemble of 17 latest generation climate models estimates an increase of only about 2% K À1 in precipitation intensity, about one order of magnitude smaller than our value, suggesting that the risk of extreme precipitation events due to global warming is substantially greater than that estimated by the climate models.

Chromosome movements in mitosis are orchestrated by dynamic interactions between spindle microtubules and the kinetochore, a multiprotein complex assembled onto centromeric DNA of the chromosome. Here we show that phosphorylation of human HsMis13 by Aurora B kinase is required for functional kinetochore assembly in HeLa cells. Aurora B interacts with HsMis13 in vitro and in vivo. HsMis13 is a cognate substrate of Aurora B, and the phosphorylation sites were mapped to Ser-100 and Ser-109. Suppression of Aurora B kinase by either small interfering RNA or chemical inhibitors abrogates the localization of HsMis13 but not HsMis12 to the kinetochore. In addition, non-phosphorylatable but not wild type and phospho-mimicking HsMis13 failed to localize to the kinetochore, demonstrating the requirement of phosphorylation by Aurora B for the assembly of HsMis13 to kinetochore. In fact, localization of HsMis13 to the kinetochore is spatiotemporally regulated by Aurora B kinase, which is essential for recruiting outer kinetochore components such as Ndc80 components and CENP-E for functional kinetochore assembly. Importantly, phospho-mimicking mutant HsMis13 restores the assembly of CENP-E to the kinetochore, and tension developed across the sister kinetochores in Aurora B-inhibited cells. Thus, we reason that HsMis13 phosphorylation by Aurora B is required for organizing a stable bi-oriented microtubule kinetochore attachment that is essential for faithful chromosome segregation in mitosis.The kinetochore is a super-molecular complex assembled at each centromere in eukaryotes. It provides a chromosomal attachment point for the mitotic spindle, linking the chromosome to the microtubules and functions in initiating, controlling, and monitoring the movements of chromosomes during mitosis. The kinetochore of animal cells contains two functional domains; that is, the inner kinetochore, which is tightly and persistently associated with centromeric DNA sequences throughout the cell cycle and the outer kinetochore which is composed of many dynamic protein complexes that interact with microtubules only during mitosis. The stable propagation of eukaryotic cells requires each chromosome to be accurately duplicated and faithfully segregated. During mitosis, attaching, positioning, and bi-orientating kinetochores with the spindle microtubules play critical roles in chromosome segregation and genomic stability (see Refs. 1 and 2).Mitosis is orchestrated by signaling cascades that coordinate mitotic processes and ensure accurate chromosome segregation. The key switch for the onset of mitosis is the archetypal cyclin-dependent kinase Cdk1. In addition to the master mitotic kinase Cdk1, three other protein serine/threonine kinase families are also involved, including the Polo kinases, Aurora kinases, and the NEK 3 (NIMA-related kinases) (e.g. Refs. 3 and 4). Recent studies have demonstrated the involvement of NEK kinase in stabilization of the kinetochore-microtubule attachment (e.g. Ref. 5) and the critical role of Aurora B kinase in kineto...

Helicobacter pylori persistently colonize the human stomach and have been linked to atrophic gastritis and gastric carcinoma. Although it is well known that H. pylori infection can result in hypochlorhydria, the molecular mechanisms underlying this phenomenon remain poorly understood. Here we show that VacA permeabilizes the apical membrane of gastric parietal cells and induces hypochlorhydria. The functional consequences of VacA infection on parietal cell physiology were studied using freshly isolated rabbit gastric glands and cultured pari- Helicobacter pylori are Gram-negative bacteria that colonize the gastric mucosa in more than half of the world's human population and persist despite a vigorous host immune response. Infection with these organisms consistently results in gastric inflammation and is a risk factor for the development of peptic ulcer disease, distal gastric adenocarcinoma, and gastric lymphoma (1, 2). Some individuals who are persistently infected with H. pylori develop a body-predominant atrophic gastritis and profound suppression of gastric acid secretion (3, 4). Atrophic gastritis is considered a risk factor for the development of gastric adenocarcinoma (5). In addition to causing hypochlorhydria in the setting of chronic infection, H. pylori also can cause hypochlorhydria in the setting of acute infection (6). The molecular mechanisms underlying H. pylori-induced hypochlorhydria have remained incompletely understood.Acid secretion by the gastric parietal cell is regulated by paracrine, endocrine, and neural pathways. The physiological stimuli for acid secretion include histamine, acetylcholine, and gastrin, each of which binds to receptors located on the basolateral plasma membranes. Stimulation of acid secretion typically involves an activation of a cAMP-dependent protein kinase cascade that triggers the translocation and insertion of the proton pump enzyme, H,K-ATPase, into the apical plasma membrane of parietal cells (7). Ezrin is an actin-binding protein of the ezrin/radixin/moesin family of cytoskeleton-membrane linker proteins (8, 9) and, within the gastric epithelium, has been localized exclusively to parietal cells and primarily to the apical canalicular membrane of these cells (10). Our previous studies show that gastric ezrin is co-distributed with the ␤-actin isoform in vivo (11) and preferentially binds to the ␤-actin isoform in vitro (9). Based on the cytolocalization and observed stimulation-dependent phosphorylation of ezrin, it was postulated that ezrin couples the activation of protein kinase A to the apical membrane remodeling associated with parietal cell secretion (10, 12). Indeed, we have recently mapped the protein kinase A phosphorylation site on ezrin and elucidated the phosphoregulation of gastric acid secretion (13).