Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome).

We report an allelic series of eight mutations in GATA2 underlying Emberger syndrome, an autosomal dominant primary lymphedema associated with a predisposition to acute myeloid leukemia. GATA2 is a transcription factor that plays an essential role in gene regulation during vascular development and hematopoietic differentiation. Our findings indicate that haploinsufficiency of GATA2 underlies primary lymphedema and predisposes to acute myeloid leukemia in this syndrome

Gata3 Acts Downstream of β-Catenin Signaling to Prevent Ectopic Metanephric Kidney Induction

Metanephric kidney induction critically depends on mesenchymal–epithelial interactions in the caudal region of the nephric (or Wolffian) duct. Central to this process, GDNF secreted from the metanephric mesenchyme induces ureter budding by activating the Ret receptor expressed in the nephric duct epithelium. A failure to regulate this pathway is believed to be responsible for a large proportion of the developmental anomalies affecting the urogenital system. Here, we show that the nephric duct-specific inactivation of the transcription factor gene Gata3 leads to massive ectopic ureter budding. This results in a spectrum of urogenital malformations including kidney adysplasia, duplex systems, and hydroureter, as well as vas deferens hyperplasia and uterine agenesis. The variability of developmental defects is reminiscent of the congenital anomalies of the kidney and urinary tract (CAKUT) observed in human. We show that Gata3 inactivation causes premature nephric duct cell differentiation and loss of Ret receptor gene expression. These changes ultimately affect nephric duct epithelium homeostasis, leading to ectopic budding of interspersed cells still expressing the Ret receptor. Importantly, the formation of these ectopic buds requires both GDNF/Ret and Fgf signaling activities. We further identify Gata3 as a central mediator of β-catenin function in the nephric duct and demonstrate that the β-catenin/Gata3 pathway prevents premature cell differentiation independently of its role in regulating Ret expression. Together, these results establish a genetic cascade in which Gata3 acts downstream of β-catenin, but upstream of Ret, to prevent ectopic ureter budding and premature cell differentiation in the nephric duct

Indian Monsoon variability in a global warming scenario

The Intergovernmental Panel on Climate Change (IPCC) constituted by the World Meteorological Organisation provides expert guidance regarding scientific and technical aspects of the climate problem. Since 1990 IPCC has, at five-yearly intervals, assessed and reported on the current state of knowledge and understanding of the climate issue. These reports have projected the behaviour of the Asian monsoon in the warming world. While the IPCC Second Assessment Report (IPCC, 1996) on climate model projections of Asian/Indian monsoon stated "Most climate models produce more rainfall over South Asia in a warmer climate with increasing CO2", the recent IPCC (2001) Third Assessment Report states "It is likely that the warming associated with increasing greenhouse gas concentrations will cause an increase in Asian summer monsoon variability and changes in monsoon strength." Climate model projections (IPCC, 2001) also suggest more El Nino - like events in the tropical Pacific, increase in surface temperatures and decrease in the northern hemisphere snow cover. The Indian Monsoon is an important component of the Asian monsoon and its links with the El Nino Southern Oscillation (ENSO) phenomenon, northern hemisphere surface temperature and Eurasian snow are well documented. In the light of the IPCC global warming projections on the Asian monsoon, the interannual and decadal variability in summer monsoon rainfall over India and its teleconnections have been examined by using observed data for the 131-year (1871-2001) period. While the interannual variations show year-to-year random fluctuations, the decadal variations reveal distinct alternate epochs of above and below normal rainfall. The epochs tend to last for about three decades. There is no clear evidence to suggest that the strength and variability of the Indian Monsoon Rainfall (IMR) nor the epochal changes are affected by the global warming. Though the 1990s have been the warmest decade of the millennium (IPCC, 2001), the IMR variability has decreased drastically. Connections between the ENSO phenomenon, Northern Hemisphere surface temperature and the Eurasian snow with IMR reveal that the correlations are not only weak but have changed signs in the early 1990s suggesting that the IMR has delinked not only with the Pacific but with the Northern Hemisphere/Eurasian continent also. The fact that temperature/snow relationships with IMR are weak further suggests that global warming need not be a cause for the recent ENSO-Monsoon weakening. Observed snow depth over the Eurasian continent has been increasing, which could be a result of enhanced precipitation due to the global warming

Adiposity and cancer risk: new mechanistic insights from epidemiology

Excess body adiposity, commonly expressed as body mass index (BMI), is a risk factor for many common adult cancers. Over the past decade, epidemiological data have shown that adiposity-cancer risk associations are specific for gender, site, geographical population, histological subtype and molecular phenotype. The biological mechanisms underpinning these associations are incompletely understood but need to take account of the specificities observed in epidemiology to better inform future prevention strategies