Transcriptome and Network Changes in Climbers at Extreme Altitudes

Extreme altitude can induce a range of cellular and systemic responses. Although it is known that hypoxia underlies the major changes and that the physiological responses include hemodynamic changes and erythropoiesis, the molecular mechanisms and signaling pathways mediating such changes are largely unknown. To obtain a more complete picture of the transcriptional regulatory landscape and networks involved in extreme altitude response, we followed four climbers on an expedition up Mount Xixiabangma (8,012 m), and collected blood samples at four stages during the climb for mRNA and miRNA expression assays. By analyzing dynamic changes of gene networks in response to extreme altitudes, we uncovered a highly modular network with 7 modules of various functions that changed in response to extreme altitudes. The erythrocyte differentiation module is the most prominently up-regulated, reflecting increased erythrocyte differentiation from hematopoietic stem cells, probably at the expense of differentiation into other cell lineages. These changes are accompanied by coordinated down-regulation of general translation. Network topology and flow analyses also uncovered regulators known to modulate hypoxia responses and erythrocyte development, as well as unknown regulators, such as the OCT4 gene, an important regulator in stem cells and assumed to only function in stem cells. We predicted computationally and validated experimentally that increased OCT4 expression at extreme altitude can directly elevate the expression of hemoglobin genes. Our approach established a new framework for analyzing the transcriptional regulatory network from a very limited number of samples

The oyster genome reveals stress adaptation and complexity of shell formation

The Pacific oyster Crassostrea gigas belongs to one of the most species-rich but genomically poorly explored phyla, the Mollusca. Here we report the sequencing and assembly of the oyster genome using short reads and a fosmid-pooling strategy, along with transcriptomes of development and stress response and the proteome of the shell. The oyster genome is highly polymorphic and rich in repetitive sequences, with some transposable elements still actively shaping variation. Transcriptome studies reveal an extensive set of genes responding to environmental stress. The expansion of genes coding for heat shock protein 70 and inhibitors of apoptosis is probably central to the oyster's adaptation to sessile life in the highly stressful intertidal zone. Our analyses also show that shell formation in molluscs is more complex than currently understood and involves extensive participation of cells and their exosomes. The oyster genome sequence fills a void in our understanding of the Lophotrochozoa. © 2012 Macmillan Publishers Limited. All rights reserved

A time-varying causality formalism based on the Liang-Kleeman information flow for analyzing directed interactions in nonstationary climate systems

The interaction between the land surface and the atmosphere is of significant importance in the climate system because it is a key driver of the exchanges of energy and water. Several important relations to heat waves, floods, and droughts exist that are based on the interaction of soil moisture and, for instance, air temperature and humidity. Our ability to separate the elements of this coupling, identify the exact locations where they are strongest, and quantify their strengths is, therefore, of paramount importance to their predictability. A recent rigorous causality formalism based on the Liang-Kleeman (LK) information flow theory has been shown, both theoretically and in real-world applications, to have the necessary asymmetry to infer the directionality and magnitude within geophysical interactions. However, the formalism assumes stationarity in time, whereas the interactions within the land surface and atmosphere are generally nonstationary; furthermore, it requires a sufficiently long time series to ensure statistical sufficiency. In this study, we remedy this difficulty by using the square root Kalman filter to estimate the causality based on the LK formalism to derive a time-varying form. Results show that the new formalism has similar properties compared to its timeinvariant form. It is shown that it is also able to capture the time-varying causality structure within soil moisture-air temperature coupling. An advantage is that it does not require very long time series to make an accurate estimation. Applying a wavelet transform to the results also reveals the full range of temporal scales of the interactions