Transgenic up-regulation of alpha-CaMKII in forebrain leads to increased anxiety-like behaviors and aggression

<p>Abstract</p> <p>Background</p> <p>Previous studies have demonstrated essential roles for alpha-calcium/calmodulin-dependent protein kinase II (alpha-CaMKII) in learning, memory and long-term potentiation (LTP). However, previous studies have also shown that alpha-CaMKII (+/-) heterozygous knockout mice display a dramatic decrease in anxiety-like and fearful behaviors, and an increase in defensive aggression. These findings indicated that alpha-CaMKII is important not only for learning and memory but also for emotional behaviors. In this study, to understand the roles of alpha-CaMKII in emotional behavior, we generated transgenic mice overexpressing alpha-CaMKII in the forebrain and analyzed their behavioral phenotypes.</p> <p>Results</p> <p>We generated transgenic mice overexpressing alpha-CaMKII in the forebrain under the control of the alpha-CaMKII promoter. In contrast to alpha-CaMKII (+/-) heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in anxiety-like behaviors in open field, elevated zero maze, light-dark transition and social interaction tests, and a decrease in locomotor activity in their home cages and novel environments; these phenotypes were the opposite to those observed in alpha-CaMKII (+/-) heterozygous knockout mice. In addition, similarly with alpha-CaMKII (+/-) heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in aggression. However, in contrast to the increase in defensive aggression observed in alpha-CaMKII (+/-) heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in offensive aggression.</p> <p>Conclusion</p> <p>Up-regulation of alpha-CaMKII expression in the forebrain leads to an increase in anxiety-like behaviors and offensive aggression. From the comparisons with previous findings, we suggest that the expression levels of alpha-CaMKII are associated with the state of emotion; the expression level of alpha-CaMKII positively correlates with the anxiety state and strongly affects aggressive behavior.</p

Mechanical guidance of self-condensation patterns of differentiating progeny

Spatially controlled self-organization represents a major challenge for organoid engineering. We have developed a mechanically patterned hydrogel for controlling self-condensation process to generate multi-cellular organoids. We first found that local stiffening with intrinsic mechanical gradient (IG > 0.008) induced single condensates of mesenchymal myoblasts, whereas the local softening led to stochastic aggregation. Besides, we revealed the cellular mechanism of two-step self-condensation: (1) cellular adhesion and migration at the mechanical boundary and (2) cell-cell contraction driven by intercellular actin-myosin networks. Finally, human pluripotent stem cell-derived hepatic progenitors with mesenchymal/endothelial cells (i.e., liver bud organoids) experienced collective migration toward locally stiffened regions generating condensates of the concave to spherical shapes. The underlying mechanism can be explained by force competition of cell-cell and cell-hydrogel biomechanical interactions between stiff and soft regions. These insights will facilitate the rational design of culture substrates inducing symmetry breaking in self-condensation of differentiating progeny toward future organoid engineering.Matsuzaki T., Shimokawa Y., Koike H., et al. Mechanical guidance of self-condensation patterns of differentiating progeny. iScience 25, 105109 (2022); https://doi.org/10.1016/j.isci.2022.105109

Preparation of mechanically patterned hydrogels for controlling the self-condensation of cells

Synthetic protocols providing mechanical patterns to culture substrate are essential to control the self-condensation of cells for organoid engineering. Here, we present a protocol for preparing hydrogels with mechanical patterns. We describe steps for hydrogel synthesis, mechanical evaluation of the substrate, and time-lapse imaging of cell self-organization. This protocol will facilitate the rational design of culture substrates with mechanical patterns for the engineering of various functional organoids. For complete details on the use and execution of this protocol, please refer to Takebe et al. (2015) and Matsuzaki et al. (2014, 2022).Matsuzaki T., Kawano Y., Horikiri M., et al. Preparation of mechanically patterned hydrogels for controlling the self-condensation of cells. STAR Protocols 4, 102471 (2023); https://doi.org/10.1016/j.xpro.2023.102471

Discharge and suspended sediment transport in the Ayeyarwady River, Myanmar: Centennial and decadal changes

Among the large rivers rising on the Tibetan Plateau and adjacent high mountains, the discharge and suspended sediment load of the Ayeyarwady (Irrawaddy) River are the least well known. Data collected between 1969 and 1996 at Pyay (Prome) are analysed t

Mapping Land Use/Land Cover Changes and Forest Disturbances in Vietnam Using a Landsat Temporal Segmentation Algorithm

Accurately mapping land use/land cover changes (LULCC) and forest disturbances provides valuable information for understanding the influence of anthropogenic activities on the environment at regional and global scales. Many approaches using satellite remote sensing data have been proposed for characterizing these long-term changes. However, a spatially and temporally consistent mapping of both LULCC and forest disturbances at medium spatial resolution is still limited despite their critical contributions to the carbon cycle. In this study, we examined the applicability of Landsat time series temporal segmentation and random forest classifiers to mapping LULCC and forest disturbances in Vietnam. We used the LandTrendr temporal segmentation algorithm to derive key features of land use/land cover transitions and forest disturbances from annual Landsat time series data. We developed separate random forest models for classifying land use/land cover and detecting forest disturbances at each segment and then derived LULCC and forest disturbances that coincided with each other during the period of 1988–2019. The results showed that both LULCC classification and forest disturbance detection achieved low accuracy in several classes (e.g., producer’s and user’s accuracies of 23.7% and 78.8%, respectively, for forest disturbance class); however, the level of accuracy was comparable to that of existing datasets using the same reference samples in the study area. We found relatively high confusion between several land use/land cover classes (e.g., grass/shrub, forest, and cropland) that can explain the lower overall accuracies of 67.6% and 68.4% in 1988 and 2019, respectively. The mapping of forest disturbances and LULCC suggested that most forest disturbances were followed by forest recovery, not by transitions to other land use/land cover classes. The landscape complexity and ephemeral forest disturbances contributed to the lower classification and detection accuracies in this study area. Nevertheless, temporal segmentation and derived features from LandTrendr were useful for the consistent mapping of LULCC and forest disturbances. We recommend that future studies focus on improving the accuracy of forest disturbance detection, especially in areas with subtle landscape changes, as well as land use/land cover classification in ambiguous and complex landscapes. Using more training samples and effective variables would potentially improve the classification and detection accuracies

Complex sediment deposition history on a wide continental shelf: implications for the calculation of accumulation rates on the Great Barrier Reef

Understanding the key processes controlling the delivery, deposition and fate of sediments on continental shelves is critical to appreciate the evolution of coasts and estuaries and to interpret geological sequences. This study presents radiocarbon and Optically Stimulated Luminescence (OSL) ages of sediment cores collected from key locations offshore from the Burdekin River, Australia, the largest single source of sediment delivered to the Great Barrier Reef (GBR) lagoon. The ages show variable sediment accumulation rates at the different locations that coincide with the Holocene avulsion history of the Burdekin River. Our data show that most fine sediment (<63 μm) delivered from the Burdekin River is retained within 50 km of the mouth, a finding that contrasts previous studies which postulated that fine sediments are advected northwards via longshore drift processes. The pairing of radiocarbon and OSL ages provides insights on resuspension regimes operating on the inner shelf of the GBR. It was thought that turbidity on inshore GBR coral reefs and seagrass meadows has increased as a result of increased erosion in the adjacent catchment from agricultural development. Our data show that the age of the sediments in Cleveland Bay (derived from the radiocarbon ages from shell and organic material) can be several thousand years older than when the sediment was last deposited (OSL ages). However, the increased turbidity could conceivably be caused from 'new biologically-produced sediment' (i.e. particulate organic matter) as a result of increased nutrient export to the GBR. We suggest that the composition of sediment in resuspension events before and after the wet season be analysed to examine whether newly delivered organic-rich sediment can affect coral reefs and seagrass meadows

Paired geochemical tracing and load monitoring analysis for identifying sediment sources in a large catchment draining into the Great Barrier Reef Lagoon

While sediment tracing has been typically applied to identify sediment sources that are difficult to measure by gauging (monitoring), it can also be useful in estimating relative sediment yields from gauged river catchments. The major and trace element composition of river sediments from eleven locations in the 130000 km2 Burdekin River catchment, northeastern Australia was analysed to examine relative contributions from upstream source areas in the 2011/12water year. Sediment tracing results are compared against estimates derived fromsediment load monitoring at three locations. Comparisons show that there is good agreement between tracing results and monitoring data at one of the tributary confluences. At the second site, notable contrastswere found between the load estimates from the monitoring and tracing data. At this site a large impoundment occurs between the upstream sampling/gauging sites for source sediments and the downstream sampling/gauging sites for target sediments. The contrast is likely caused by temporal variations in particle size distributions of suspended sediment fromeach river and differential trapping efficiencies in the impoundment for sediment derived fromthe different tributaries. In the absence of the detailed particle size data and trapping efficiency estimates, sediment tracing provides the unique opportunity to elucidate source contributions of the finer fractions of suspended sediment. At a third site, where there were recognised measurement gaps in the monitoring data during large discharge events, the relative load estimates fromthe tracing data provided a means of constraining the recognized uncertainty of monitored load estimates.We conclude that sediment tracing can be used as a valuable adjunct to monitoring data particularly in remote, large and data-sparse catchments. Both tracing results and monitoring data showthat the Upper Burdekin River and Bowen-Bogie Riverswere the dominant source of the b10 μm sediments being delivered to the GBR lagoon from the Burdekin River catchment in the 2011/12 water year. More substantial contribution from the Belyando-Suttor Rivers indicated by the tracing results than the monitoring data is attributed to preferential delivery of the 1–10 μm sediments through the impoundment and has uncovered a knowledge gap in sediment budgets in the catchment