Retrieving Soil Physical Properties by Assimilating SMAP Brightness Temperature Observations into the Community Land Model.

This paper coupled a unified passive and active microwave observation operator-namely, an enhanced, physically-based, discrete emission-scattering model-with the community land model (CLM) in a data assimilation (DA) system. By implementing the system default local ensemble transform Kalman filter (LETKF) algorithm, the Soil Moisture Active and Passive (SMAP) brightness temperature TBp (p = Horizontal or Vertical polarization) assimilations for only soil property retrieval and both soil properties and soil moisture estimates were investigated with the aid of in situ observations at the Maqu site. The results indicate improved estimates of soil properties of the topmost layer in comparison to measurements, as well as of the profile. Specifically, both assimilations of TBH lead to over a 48% reduction in root mean square errors (RMSEs) for the retrieved clay fraction from the background compared to the top layer measurements. Both assimilations of TBV reduce RMSEs by 36% for the sand fraction and by 28% for the clay fraction. However, the DA estimated soil moisture and land surface fluxes still exhibit discrepancies when compared to the measurements. The retrieved accurate soil properties alone are inadequate to improve those estimates. The discussed uncertainties (e.g., fixed PTF structures) in the CLM model structures should be mitigated.

The Importance of mTORC1-Autophagy Axis for Skeletal Muscle Diseases.

The mechanistic target of rapamycin (mTOR) complex 1, mTORC1, integrates nutrient and growth factor signals with cellular responses and plays critical roles in regulating cell growth, proliferation, and lifespan. mTORC1 signaling has been reported as a central regulator of autophagy by modulating almost all aspects of the autophagic process, including initiation, expansion, and termination. An increasing number of studies suggest that mTORC1 and autophagy are critical for the physiological function of skeletal muscle and are involved in diverse muscle diseases. Here, we review recent insights into the essential roles of mTORC1 and autophagy in skeletal muscles and their implications in human muscle diseases. Multiple inhibitors targeting mTORC1 or autophagy have already been clinically approved, while others are under development. These chemical modulators that target the mTORC1/autophagy pathways represent promising potentials to cure muscle diseases.

N-Cadherin Orchestrates Self-Organization of Neurons within a Columnar Unit in the Drosophila Medulla.

Columnar structure is a basic unit of the brain, but the mechanism underlying its development remains largely unknown. The medulla, the largest ganglion of the Drosophila melanogaster visual center, provides a unique opportunity to reveal the mechanisms of 3D organization of the columns. In this study, using N-cadherin (Ncad) as a marker, we reveal the donut-like columnar structures along the 2D layer in the larval medulla that evolves to form three distinct layers in pupal development. Column formation is initiated by three core neurons, R8, R7, and Mi1, which establish distinct concentric domains within a column. We demonstrate that Ncad-dependent relative adhesiveness of the core columnar neurons regulates their relative location within a column along a 2D layer in the larval medulla according to the differential adhesion hypothesis. We also propose the presence of mutual interactions among the three layers during formation of the 3D structures of the medulla columns.SIGNIFICANCE STATEMENT The columnar structure is a basic unit of the brain, but its developmental mechanism remains unknown. The medulla, the largest ganglion of the fly visual center, provides a unique opportunity to reveal the mechanisms of 3D organization of the columns. We reveal that column formation is initiated by three core neurons that establish distinct concentric domains within a column. We demonstrate the in vivo evidence of N-cadherin-dependent differential adhesion among the core columnar neurons within a column along a 2D layer in the larval medulla. The 2D larval columns evolve to form three distinct layers in the pupal medulla. We propose the presence of mutual interactions among the three layers during formation of the 3D structures of the medulla columns.

Land Use Change and Climate Variation in the Three Gorges Reservoir Catchment from 2000 to 2015 Based on the Google Earth Engine.

Possible environmental change and ecosystem degradation have received increasing attention since the construction of Three Gorges Reservoir Catchment (TGRC) in China. The advanced Google Earth Engine (GEE) cloud-based platform and the large number of Geosciences and Remote Sensing datasets archived in GEE were used to analyze the land use and land cover change (LULCC) and climate variation in TGRC. GlobeLand30 data were used to evaluate the spatial land dynamics from 2000 to 2010 and Landsat 8 Operational Land Imager (OLI) images were applied for land use in 2015. The interannual variations in the Land Surface Temperature (LST) and seasonally integrated normalized difference vegetation index (SINDVI) were estimated using Moderate Resolution Imaging Spectroradiometer (MODIS) products. The climate factors including air temperature, precipitation and evapotranspiration were investigated based on the data from the Global Land Data Assimilation System (GLDAS). The results indicated that from 2000 to 2015, the cultivated land and grassland decreased by 2.05% and 6.02%, while the forest, wetland, artificial surface, shrub land and waterbody increased by 3.64%, 0.94%, 0.87%, 1.17% and 1.45%, respectively. The SINDVI increased by 3.209 in the period of 2000-2015, while the LST decreased by 0.253 °C from 2001 to 2015. The LST showed an increasing trend primarily in urbanized area, with a decreasing trend mainly in forest area. In particular, Chongqing City had the highest LST during the research period. A marked decrease in SINDVI occurred primarily in urbanized areas. Good vegetation areas were primarily located in the eastern part of the TGRC, such as Wuxi County, Wushan County, and Xingshan County. During the 2000-2015 period, the air temperature, precipitation and evapotranspiration rose by 0.0678 °C/a, 1.0844 mm/a, and 0.4105 mm/a, respectively. The climate change in the TGRC was influenced by LULCC, but the effect was limited. What is more, the climate change was affected by regional climate change in Southwest China. Marked changes in land use have occurred in the TGRC, and they have resulted in changes in the LST and SINDVI. There was a significantly negative relationship between LST and SINDVI in most parts of the TGRC, especially in expanding urban areas and growing forest areas. Our study highlighted the importance of environmental protection, particularly proper management of land use, for sustainable development in the catchment.

Multiple timescale analysis of the urban heat island effect based on the Community Land Model: a case study of the city of Xi'an, China.

Urban heat islands (UHIs) are the phenomenon of urban regions usually being warmer than rural regions, which significantly impacts both the regional ecosystem and societal activities. Numerical simulation can provide spatially and temporally continuous datasets for UHI analysis. In this study, a spatially and temporally continuous ground temperature dataset of Xi'an, China was obtained through numerical simulation based on the Community Land Model version 4.5 (CLM4.5), at a temporal resolution of 30 min and a spatial resolution of 0.05∘× 0.05∘. Based on the ground temperature, the seasonal average UHI intensity (UHII) was calculated and the seasonal variation of the UHI effect was analyzed. The monthly variation tendency of the urban heat stress was also investigated. Based on the diurnal cycle of ground temperature and the UHI effect in each season, the variation tendencies of the maximum, minimum, and average UHII were analyzed. The results show that the urban heat stress in summer is the strongest among all four seasons. The heat stress in urban areas is very significant in July, and the UHII is the weakest in January. Regarding the diurnal cycle of UHII, the maximum always appears at 06:30 UTC to 07:30 UTC, while the minimum intensity of the UHI effect occurs at different times in the different seasons. The results of this study could provide a reference for policymakers about how to reduce the damage caused by heat stress.

Molecular cloning and sequence analysis of an extracellular protease from four Bacillus subtilis strains.

Four Bacillus subtilis strains were isolated from traditional fermented foods, and the sequences of their extracellular alkaline proteases (AprE) were analyzed and cloned. The recombinant enzymes synthesized by means of Escherichia coli exhibited high proteolytic activity. AprE CN2 showed hydrolytic activity 4-fold higher than that of AprE 168. This activity was also seen in the presence of relatively high NaCl concentrations.

Generation of Pmel-dependent conditional and inducible Cre-driver mouse line for melanocytic-targeted gene manipulation.

Conditional and inducible gene targeting using Cre/loxP-mediated recombination is a powerful reverse genetics approach used to study spatiotemporal gene functions in specified cell types. To enable temporal gene manipulation in the melanocyte lineage, we established a novel inducible Cre-driver mouse line by targeting an all-in-one tetracycline/doxycycline (Dox)-inducible Cre expression cassette into the Pmel locus (PmelP2A-TetON3G-TRE3G-iCre ), a gene locus preferentially expressed in pigment cells. By crossing these Cre-driver mice with a strong Cre-reporter mouse line, Gt(ROSA)26Sortm9(CAG-tdTomato)Hze , we show the effectiveness of the PmelP2A-TetON3G-TRE3G-iCre mouse line in facilitating Dox-inducible Cre/loxP recombination in a wide variety of pigment cell lineages including hair follicle melanocytes and their stem cells. Furthermore, to demonstrate proof of concept, we ablated Notch signaling postnatally in the PmelP2A-TetON3G-TRE3G-iCre mice. In agreement with the previously reported phenotype, induced ablation of Notch signaling in the melanocyte lineage resulted in premature hair graying, demonstrating the utility of the PmelP2A-TetON3G-TRE3G-iCre allele. Therefore, the PmelP2A-TetON3G-TRE3G-iCre mouse line is suitable for assessing gene functions in melanocytes using an in vivo inducible reverse genetics approach. Furthermore, we unexpectedly identified previously unrecognized PMEL-expressing cells in non-pigmentary organs in the mice, suggesting unanticipated functions of PMEL other than melanosome formation.

Multivariate and multiscale data assimilation in terrestrial systems: a review.

More and more terrestrial observational networks are being established to monitor climatic, hydrological and land-use changes in different regions of the World. In these networks, time series of states and fluxes are recorded in an automated manner, often with a high temporal resolution. These data are important for the understanding of water, energy, and/or matter fluxes, as well as their biological and physical drivers and interactions with and within the terrestrial system. Similarly, the number and accuracy of variables, which can be observed by spaceborne sensors, are increasing. Data assimilation (DA) methods utilize these observations in terrestrial models in order to increase process knowledge as well as to improve forecasts for the system being studied. The widely implemented automation in observing environmental states and fluxes makes an operational computation more and more feasible, and it opens the perspective of short-time forecasts of the state of terrestrial systems. In this paper, we review the state of the art with respect to DA focusing on the joint assimilation of observational data precedents from different spatial scales and different data types. An introduction is given to different DA methods, such as the Ensemble Kalman Filter (EnKF), Particle Filter (PF) and variational methods (3/4D-VAR). In this review, we distinguish between four major DA approaches: (1) univariate single-scale DA (UVSS), which is the approach used in the majority of published DA applications, (2) univariate multiscale DA (UVMS) referring to a methodology which acknowledges that at least some of the assimilated data are measured at a different scale than the computational grid scale, (3) multivariate single-scale DA (MVSS) dealing with the assimilation of at least two different data types, and (4) combined multivariate multiscale DA (MVMS). Finally, we conclude with a discussion on the advantages and disadvantages of the assimilation of multiple data types in a simulation model. Existing approaches can be used to simultaneously update several model states and model parameters if applicable. In other words, the basic principles for multivariate data assimilation are already available. We argue that a better understanding of the measurement errors for different observation types, improved estimates of observation bias and improved multiscale assimilation methods for data which scale nonlinearly is important to properly weight them in multiscale multivariate data assimilation. In this context, improved cross-validation of different data types, and increased ground truth verification of remote sensing products are required.

Intracellular trafficking of Notch orchestrates temporal dynamics of Notch activity in the fly brain.

While Delta non-autonomously activates Notch in neighboring cells, it autonomously inactivates Notch through cis-inhibition, the molecular mechanism and biological roles of which remain elusive. The wave of differentiation in the Drosophila brain, the 'proneural wave', is an excellent model for studying Notch signaling in vivo. Here, we show that strong nonlinearity in cis-inhibition reproduces the second peak of Notch activity behind the proneural wave in silico. Based on this, we demonstrate that Delta expression induces a quick degradation of Notch in late endosomes and the formation of the twin peaks of Notch activity in vivo. Indeed, the amount of Notch is upregulated and the twin peaks are fused forming a single peak when the function of Delta or late endosomes is compromised. Additionally, we show that the second Notch peak behind the wavefront controls neurogenesis. Thus, intracellular trafficking of Notch orchestrates the temporal dynamics of Notch activity and the temporal patterning of neurogenesis.

Dscam1 establishes the columnar units through lineage-dependent repulsion between sister neurons in the fly brain.

The brain is organized morphologically and functionally into a columnar structure. According to the radial unit hypothesis, neurons from the same lineage form a radial unit that contributes to column formation. However, the molecular mechanisms that link neuronal lineage and column formation remain elusive. Here, we show that neurons from the same lineage project to different columns under control of Down syndrome cell adhesion molecule (Dscam) in the fly brain. Dscam1 is temporally expressed in newly born neuroblasts and is inherited by their daughter neurons. The transient transcription of Dscam1 in neuroblasts enables the expression of the same Dscam1 splice isoform within cells of the same lineage, causing lineage-dependent repulsion. In the absence of Dscam1 function, neurons from the same lineage project to the same column. When the splice diversity of Dscam1 is reduced, column formation is significantly compromised. Thus, Dscam1 controls column formation through lineage-dependent repulsion.

DWnt4 and DWnt10 Regulate Morphogenesis and Arrangement of Columnar Units via Fz2/PCP Signaling in the Drosophila Brain.

Columns are structural and functional units of the brain. However, the mechanism of column formation remains unclear. The medulla of the fly visual center shares features with the mammalian cerebral cortex, such as columnar and layered structures, and provides a good opportunity to study the mechanisms of column formation. Column formation is initiated by three core neurons in the medulla, namely, Mi1, R8, and R7. The proper orientation of neurons is required for the orientation and arrangement of multiple columns. Their orientations may be under the control of planar cell polarity (PCP) signaling, because it is known to regulate the orientation of cells in two-dimensional tissue structures. In this study, we demonstrate that the ligands DWnt4 and DWnt10 expressed specifically in the ventral medulla and dorsal medulla, respectively, globally regulate the columnar arrangement and orientation of Mi1 and R8 terminals through Fz2/PCP signaling in a three-dimensional space.

Transient IGF-1R inhibition combined with osimertinib eradicates AXL-low expressing EGFR mutated lung cancer.

Drug tolerance is the basis for acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) including osimertinib, through mechanisms that still remain unclear. Here, we show that while AXL-low expressing EGFR mutated lung cancer (EGFRmut-LC) cells are more sensitive to osimertinib than AXL-high expressing EGFRmut-LC cells, a small population emerge osimertinib tolerance. The tolerance is mediated by the increased expression and phosphorylation of insulin-like growth factor-1 receptor (IGF-1R), caused by the induction of its transcription factor FOXA1. IGF-1R maintains association with EGFR and adaptor proteins, including Gab1 and IRS1, in the presence of osimertinib and restores the survival signal. In AXL-low-expressing EGFRmut-LC cell-derived xenograft and patient-derived xenograft models, transient IGF-1R inhibition combined with continuous osimertinib treatment could eradicate tumors and prevent regrowth even after the cessation of osimertinib. These results indicate that optimal inhibition of tolerant signals combined with osimertinib may dramatically improve the outcome of EGFRmut-LC.

Soil moisture estimation by assimilating L-band microwave brightness temperature with geostatistics and observation localization.

The observation could be used to reduce the model uncertainties with data assimilation. If the observation cannot cover the whole model area due to spatial availability or instrument ability, how to do data assimilation at locations not covered by observation? Two commonly used strategies were firstly described: One is covariance localization (CL); the other is observation localization (OL). Compared with CL, OL is easy to parallelize and more efficient for large-scale analysis. This paper evaluated OL in soil moisture profile characterizations, in which the geostatistical semivariogram was used to fit the spatial correlated characteristics of synthetic L-Band microwave brightness temperature measurement. The fitted semivariogram model and the local ensemble transform Kalman filter algorithm are combined together to weight and assimilate the observations within a local region surrounding the grid cell of land surface model to be analyzed. Six scenarios were compared: 1_Obs with one nearest observation assimilated, 5_Obs with no more than five nearest local observations assimilated, and 9_Obs with no more than nine nearest local observations assimilated. The scenarios with no more than 16, 25, and 36 local observations were also compared. From the results we can conclude that more local observations involved in assimilation will improve estimations with an upper bound of 9 observations in this case. This study demonstrates the potentials of geostatistical correlation representation in OL to improve data assimilation of catchment scale soil moisture using synthetic L-band microwave brightness temperature, which cannot cover the study area fully in space due to vegetation effects.