Description: Thermodynamic arguments imply that global mean rainfall increases in a warmer atmosphere; however, dynamical effects may result in more significant diversity of regional precipitation change. Here we investigate rainfall changes in the mid-Pliocene Warm Period (~ 3 Ma), a time when temperatures were 2–3ºC warmer than the pre-industrial era, using output from the Pliocene Model Intercomparison Projects phases 1 and 2 and sensitivity climate model experiments. In the Mid-Pliocene simulations, the higher rates of warming in the northern hemisphere create an interhemispheric temperature gradient that enhances the southward cross-equatorial energy flux by up to 48%. This intensified energy flux reorganizes the atmospheric circulation leading to a northward shift of the Inter-Tropical Convergence Zone and a weakened and poleward displaced Southern Hemisphere Subtropical Convergences Zones. These changes result in drier-than-normal Southern Hemisphere tropics and subtropics. The evaluation of the mid-Pliocene adds a constraint to possible future warmer scenarios associated with differing rates of warming between hemispheres.

Description: Numerical modeling enables a comprehensive understanding not only of the Earth's system today, but also of the past. To date, a significant amount of time and effort has been devoted to paleoclimate modeling and analysis, which involves the latest and most advanced Paleoclimate Modelling Intercomparison Project phase 4 (PMIP4). The definition of seasonality, which is influenced by slow variations in the Earth's orbital parameters, plays a key role in determining the calculated seasonal cycle of the climate. In contrast to the classical calendar used today, where the lengths of the months and seasons are fixed, the angular calendar calculates the lengths of the months and seasons according to a fixed number of degrees along the Earth's orbit. When comparing simulation results for different time intervals, it is essential to account for the angular calendar to ensure that the data for comparison are from the same position along the Earth's orbit. Most models use the classical calendar, which can lead to strong distortions of the monthly and seasonal values, especially for the climate of the past. Here, by analyzing daily outputs from multiple PMIP4 model simulations, we examine calendar effects on surface air temperature and precipitation under mid-Holocene, Last Interglacial, and pre-industrial climate conditions. We came to the following conclusions. (a) The largest cooling bias occurs in boreal autumn when the classical calendar is applied for the mid-Holocene and Last Interglacial, due to the fact that the vernal equinox is fixed on 21 March. (b) The sign of the temperature anomalies between the Last Interglacial and pre-industrial in boreal autumn can be reversed after the switch from the classical to angular calendar, particularly over the Northern Hemisphere continents. (c) Precipitation over West Africa is overestimated in boreal summer and underestimated in boreal autumn when the classical seasonal cycle is applied. (d) Finally, month-length adjusted values for surface air temperature and precipitation are very similar to the day-length adjusted values, and therefore correcting the calendar based on the monthly model results can largely reduce the artificial bias. In addition, we examine the calendar effects in three transient simulations for 6–0 ka by AWI-ESM, MPI-ESM, and IPSL-CM. We find significant discrepancies between adjusted and unadjusted temperature values over continents for both hemispheres in boreal autumn, while for other seasons the deviations are relatively small. A drying bias can be found in the summer monsoon precipitation in Africa (in the classical calendar), whereby the magnitude of bias becomes smaller over time. Overall, our study underlines the importance of the application of calendar transformation in the analysis of climate simulations. Neglecting the calendar effects could lead to a profound artificial distortion of the calculated seasonal cycle of surface air temperature and precipitation.

Description: The Maritime Continent (MC) forms the western boundary of the tropical Pacific Ocean, and relatively small changes in this region can impact the climate locally and remotely. In the mid-Piacenzian warm period of the Pliocene (mPWP; 3.264 to 3.025 Ma) atmospheric CO2 concentrations were ∼ 400 ppm, and the subaerial Sunda and Sahul shelves made the land–sea distribution of the MC different to today. Topographic changes and elevated levels of CO2, combined with other forcings, are therefore expected to have driven a substantial climate signal in the MC region at this time. By using the results from the Pliocene Model Intercomparison Project Phase 2 (PlioMIP2), we study the mean climatic features of the MC in the mPWP and changes in Indonesian Throughflow (ITF) with respect to the preindustrial. Results show a warmer and wetter mPWP climate of the MC and lower sea surface salinity in the surrounding ocean compared with the preindustrial. Furthermore, we quantify the volume transfer through the ITF; although the ITF may be expected to be hindered by the subaerial shelves, 10 out of 15 models show an increased volume transport compared with the preindustrial. In order to avoid undue influence from closely related models that are present in the PlioMIP2 ensemble, we introduce a new metric, the multi-cluster mean (MCM), which is based on cluster analysis of the individual models. We study the effect that the choice of MCM versus the more traditional analysis of multi-model mean (MMM) and individual models has on the discrepancy between model results and data. We find that models, which reproduce modern MC climate well, are not always good at simulating the mPWP climate anomaly of the MC. By comparing with individual models, the MMM and MCM reproduce the preindustrial sea surface temperature (SST) of the reanalysis better than most individual models and produce less discrepancy with reconstructed sea surface temperature anomalies (SSTA) than most individual models in the MC. In addition, the clusters reveal spatial signals that are not captured by the MMM, so that the MCM provides us with a new way to explore the results from model ensembles that include similar models.

Description: 〈jats:p〉Abstract. The mid-Pliocene warm period (3.264–3.025 Ma) is the most recent geological period in which the atmospheric CO2 concentration was approximately equal to the concentration we measure today (ca. 400 ppm). Sea surface temperature (SST) proxies indicate above-average warming over the North Atlantic in the mid-Pliocene with respect to the pre-industrial period, which may be linked to an intensified Atlantic Meridional Overturning Circulation (AMOC). Earlier results from the Pliocene Model Intercomparison Project Phase 2 (PlioMIP2) show that the ensemble simulates a stronger AMOC in the mid-Pliocene than in the pre-industrial. However, no consistent relationship between the stronger mid-Pliocene AMOC and either the Atlantic northward ocean heat transport (OHT) or average North Atlantic SSTs has been found. In this study, we look further into the drivers and consequences of a stronger AMOC in mid-Pliocene compared to pre-industrial simulations in PlioMIP2. We find that all model simulations with a closed Bering Strait and Canadian Archipelago show reduced freshwater transport from the Arctic Ocean into the North Atlantic. This contributes to an increase in salinity in the subpolar North Atlantic and Labrador Sea that can be linked to the stronger AMOC in the mid-Pliocene. To investigate the dynamics behind the ensemble's variable response of the total Atlantic OHT to the stronger AMOC, we separate the Atlantic OHT into two components associated with either the overturning circulation or the wind-driven gyre circulation. While the ensemble mean of the overturning component is increased significantly in magnitude in the mid-Pliocene, it is partly compensated by a reduction in the gyre component in the northern subtropical gyre region. This indicates that the lack of relationship between the total OHT and AMOC is due to changes in OHT by the subtropical gyre. The overturning and gyre components should therefore be considered separately to gain a more complete understanding of the OHT response to a stronger mid-Pliocene AMOC. In addition, we show that the AMOC exerts a stronger influence on North Atlantic SSTs in the mid-Pliocene than in the pre-industrial, providing a possible explanation for the improved agreement of the PlioMIP2 ensemble mean SSTs with reconstructions in the North Atlantic. 〈/jats:p〉

Description: The Maritime Continent (MC) forms the western boundary of the tropical Pacific Ocean, and relatively small changes in this region can impact the climate locally and remotely. In the mid-Piacenzian warm period of the Pliocene (mPWP; 3.264 to 3.025 Ma) atmospheric CO2 concentrations were ∼ 400 ppm, and the subaerial Sunda and Sahul shelves made the land–sea distribution of the MC different to today. Topographic changes and elevated levels of CO2, combined with other forcings, are therefore expected to have driven a substantial climate signal in the MC region at this time. By using the results from the Pliocene Model Intercomparison Project Phase 2 (PlioMIP2), we study the mean climatic features of the MC in the mPWP and changes in Indonesian Throughflow (ITF) with respect to the preindustrial. Results show a warmer and wetter mPWP climate of the MC and lower sea surface salinity in the surrounding ocean compared with the preindustrial. Furthermore, we quantify the volume transfer through the ITF; although the ITF may be expected to be hindered by the subaerial shelves, 10 out of 15 models show an increased volume transport compared with the preindustrial. In order to avoid undue influence from closely related models that are present in the PlioMIP2 ensemble, we introduce a new metric, the multi-cluster mean (MCM), which is based on cluster analysis of the individual models. We study the effect that the choice of MCM versus the more traditional analysis of multi-model mean (MMM) and individual models has on the discrepancy between model results and data. We find that models, which reproduce modern MC climate well, are not always good at simulating the mPWP climate anomaly of the MC. By comparing with individual models, the MMM and MCM reproduce the preindustrial sea surface temperature (SST) of the reanalysis better than most individual models and produce less discrepancy with reconstructed sea surface temperature anomalies (SSTA) than most individual models in the MC. In addition, the clusters reveal spatial signals that are not captured by the MMM, so that the MCM provides us with a new way to explore the results from model ensembles that include similar models.

Description: Keratinocyte migration is an early event in the wound healing process. Although we previously found that CD9 downregulation is required for the keratinocyte migration during wound repair, the mechanism of how CD9 expression is regulated remains unclear. Here, we observed the effect of hypoxia (2% O2) on CD9 expression and keratinocyte migration. CD9 expression was downregulated and keratinocyte migration was increased under hypoxic conditions. In addition, CD9 overexpression reversed hypoxia-induced cell migration. We also found that hypoxia activated the p38/MAPK pathway. SB203580, a p38/MAPK inhibitor, increased CD9 expression and inhibited keratinocyte migration under hypoxia, while MKK6 (Glu) overexpression decreased CD9 expression and promoted hypoxic keratinocyte migration. Our results demonstrate that hypoxia regulates CD9 expression and CD9-mediated keratinocyte migration via the p38/MAPK pathway. Scientific Reports 4 doi: 10.1038/srep06304

Description: Article An increase in the concentration of atmospheric carbon dioxide and warmer temperatures can alter plant growth and development. Here the authors show that these conditions can also elicit significant changes in microRNAs expression, including some which might induce early flowering in Arabidopsis. Nature Communications doi: 10.1038/ncomms3145 Authors: Patrick May, Will Liao, Yijin Wu, Bin Shuai, W. Richard McCombie, Michael Q. Zhang, Qiong A. Liu

Description: The genome-wide variation of multiple epigenetic modifications in CpG islands (CGIs) and the interactions between them are of great interest. Here, we optimized an entropy-based strategy to quantify variation of epigenetic modifications and explored their interaction across mouse embryonic stem cells, neural precursor cells and brain. Our results showed that four epigenetic modifications (DNA methylation, H3K4me2, H3K4me3 and H3K27me3) of CGIs in the mouse genome undergo combinatorial variation during neuron differentiation. DNA methylation variation was positively correlated with H3K27me3 variation, and negatively correlated with H3K4me2/3 variation. We identified 5,194 CGIs differentially modified by epigenetic modifications (DEM-CGIs). Among them, the differentially DNA methylated CGIs overlapped significantly with the CGIs differentially modified by H3K27me3. Moreover, DEM-CGIs may contribute to co-regulation of related developmental genes including core transcription factors. Our entropy-based strategy provides an effective way of investigating dynamic cross-talk among epigenetic modifications in various biological processes at the macro scale. Scientific Reports 3 doi: 10.1038/srep02576

Description: KIAA1199 promotes metastasis of colorectal cancer cells via microtubule destabilization regulated by a PP2A/stathmin pathway KIAA1199 promotes metastasis of colorectal cancer cells via microtubule destabilization regulated by a PP2A/stathmin pathway, Published online: 10 September 2018; doi:10.1038/s41388-018-0493-8 KIAA1199 promotes metastasis of colorectal cancer cells via microtubule destabilization regulated by a PP2A/stathmin pathway

Description: Nature Medicine 20, 1187 (2014). doi:10.1038/nm.3611 Authors: Xiping Cheng, Xiaoli Zhang, Qiong Gao, Mohammad Ali Samie, Marlene Azar, Wai Lok Tsang, Libing Dong, Nirakar Sahoo, Xinran Li, Yue Zhuo, Abigail G Garrity, Xiang Wang, Marc Ferrer, James Dowling, Li Xu, Renzhi Han & Haoxing Xu The integrity of the plasma membrane is maintained through an active repair process, especially in skeletal and cardiac muscle cells, in which contraction-induced mechanical damage frequently occurs in vivo. Muscular dystrophies (MDs) are a group of muscle diseases characterized by skeletal muscle wasting and weakness. An important cause of these group of diseases is defective repair of sarcolemmal injuries, which normally requires Ca2+ sensor proteins and Ca2+-dependent delivery of intracellular vesicles to the sites of injury. MCOLN1 (also known as TRPML1, ML1) is an endosomal and lysosomal Ca2+ channel whose human mutations cause mucolipidosis IV (ML4), a neurodegenerative disease with motor disabilities. Here we report that ML1-null mice develop a primary, early-onset MD independent of neural degeneration. Although the dystrophin-glycoprotein complex and the known membrane repair proteins are expressed normally, membrane resealing was defective in ML1-null muscle fibers and also upon acute and pharmacological inhibition of ML1 channel activity or vesicular Ca2+ release. Injury facilitated the trafficking and exocytosis of vesicles by upmodulating ML1 channel activity. In the dystrophic mdx mouse model, overexpression of ML1 decreased muscle pathology. Collectively, our data have identified an intracellular Ca2+ channel that regulates membrane repair in skeletal muscle via Ca2+-dependent vesicle exocytosis.