River Network Patterns and Their Evolutionary Preconditions

Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchiv

Expression mapping of GREM1 and functional contribution of its-secreting-cells in the brain using transgenic mouse models

Gremlin 1 (Grem1) is a secreted protein that antagonizes bone morphogenetic proteins (BMPs). While abnormal Grem1 expression has been reported to cause behavioral defects in postpartum mice, the spatial and cellular distribution of GREM1 in the brain and the influence of the Grem1-secreating cells on brain function and behavior remain unclear. To address this, we designed a genetic cassette incorporating a 3 × Flag-TeV-HA-T2A-tdTomato sequence, resulting in the creation of a novel Grem1Tag mouse model, expressing an epitope tag (3 × Flag-TeV-HA-T2A) followed by a fluorescent reporter (tdTomato) under the control of the endogenous Grem1 promoter. This design facilitated precise tracking of the cell origin and distribution of GREM1 in the brain using tdTomato and Flag (or HA) markers, respectively. We confirmed that the Grem1Tag mouse exhibited normal motor, cognitive, and social behaviors at postnatal 60 days (P60), compared with C57BL/6 J controls. Through immunofluorescence staining, we comprehensively mapped the distribution of Grem1-secreting cells across the central nervous system. Pervasive Grem1 expression was observed in the cerebral cortex (Cx), medulla, pons, and cerebellum, with the highest levels in the Cx region. Notably, within the Cx, GREM1 was predominantly secreted by excitatory neurons, particularly those expressing calcium/calmodulin-dependent protein kinase II alpha (Camk2a), while inhibitory neurons (parvalbumin-positive, PV+) and glial cells (oligodendrocytes, astrocytes, and microglia) showed little or no Grem1 expression. To delineate the functional significance of Grem1-secreting cells, a selective ablation at P42 using a diphtheria toxin A (DTA) system resulted in increased anxiety-like behavior and impaired memory in mice. Altogether, our study harnessing the Grem1Tag mouse model reveals the spatial and cellular localization of GREM1 in the mouse brain, shedding light on the involvement of Grem1-secreting cell in modulating brain function and behavior. Our Grem1Tag mouse serves as a valuable tool for further exploring the precise role of Grem1 in brain development and disease

Comparative Study on Volatile Flavor of Chinese Acid-curd Cheese Using Sensory Evaluation, Gas Chromatography-Ion Mobility Spectrometry and Gas Chromatography-Mass Spectrometry

The difference in the volatile flavors of five different Chinese acid-curd cheeses including milk fan, milk cake, Qula (yak milk cheese), Hurood cheese and milk knot was analyzed by sensory evaluation, gas chromatography-ion mobility spectrometry (GC-IMS) and gas chromatography-mass spectrometry (GC-MS). The results of sensory evaluation showed that the five cheeses had a significant difference in flavor. Among them, dairy fan, with strong milky, fruity and bread-like aromas, had the best overall aroma performance and the highest preference score. The combination of GC-IMS and GC-MS expanded the detection range of volatile flavor compounds, and could more comprehensively reflect the volatile compounds in different Chinese acid-curd cheeses. The sensory evaluation results were verified by GC-IMS analysis. All five samples had their own characteristic peak areas, and the characteristic peak areas of dairy fan and Qula were significantly larger than those of the other samples. GC-MS analysis showed that the proportion of acids in dairy fan, Hurood cheese and Qula was the highest, the proportion of esters in milk cake was the highest, and the proportion of alcohols in milk knot was the highest. The calculation of odor activity value (OAV) combined with the results of principal component analysis (PCA) showed that ethanol, ethyl butyrate, ethyl caproate, 2-heptanone and δ-caprylactone were the major contributors to the flavor of dairy fan. Phenethyl formate, phenethyl acetate, caprylic acid, lauric acid and n-decanoic acid were the major contributors to the flavor of Qula. Dodecyl aldehyde was identified as the characteristic flavor compound of dairy cake. Partial least squares analysis (PLSA) revealed the correlation between aroma properties and volatile flavor compounds. Dairy fan has the potential to be developed and promoted in China because of its excellent flavor and consumer preference

Impact of a water-sediment regulation scheme on nutrient variations at the Lijin station of the Yellow River

The water-sediment regulation scheme (WSRS) imposed on dams throughout the Yellow River not only alleviates siltation in the downstream section but also alters the nutrient characteristics, which indirectly affects the enrichment of nutrients in the estuary. Nevertheless, the long-term changes in the nutrient contents and their causes in the lower Yellow River (LYR) remain unclear, and the nutrients characteristics during the years with and without WSRS have yet to be compared. Therefore, the purpose of this study was to explore the variations in the nutrient contents and limitations at the Lijin station on the LYR over the past decade, especially during the annual WSRS period, and to compare the water quality characteristics at Lijin between the years with and without WSRS. The results reveal that WSRS significantly changed the seasonal nutrient concentrations (nitrogen, phosphorus and silicon) at the Lijin station. The fluxes of these nutrients during WSRS (excluding 2016 and 2017) accounted for 11.64–40.63% of the total annual fluxes. The N concentration in the LYR was higher than that in some global rivers, while the concentrations of dissolved inorganic phosphorus (DIP) and dissolved silica (DSi) were lower than the average levels in other rivers. In addition, higher values of dissolved inorganic nitrogen (DIN), DSi and the Redfield ratio indicated that the growth of phytoplankton at the Lijin station was strongly restricted by P. However, during the 2 years without WSRS (2016 and 2017), the proportions of the nutrient fluxes in June were less than 66% of those in the WSRS period in other years. Additionally, there was a potential Si limitation in June in these 2 years. Furthermore, due to the occurrence of floods upstream of the Yellow River and the low-level operation of the Xiaolangdi Reservoir, the fluxes of nutrients during WSRS in 2018 were approximately 0.90–4.20 times those during the same period in 2009–2015 and 6.30–35.76 times those in June 2016 and June 2017. This study shows that WSRS effectively changes the nutrient balance in the LYR and provides a reference for the multi-objective collaborative optimization of WSRS to improve siltation and control flood in the LYR

Effects of Spur Dikes on Water Flow Diversity and Fish Aggregation

As a typical waterway modification, the spur dike narrows the water cross section, which increases the flow velocity and flushes the riverbed. Meanwhile, it also protects ecological diversity and improves river habitat. Different types of spur dikes could greatly impact the interaction between flow structure and local geomorphology, which in turn affects the evolution of river aquatic habitats. Four different types of spur dikes—including rock-fill, permeable, w-shaped rock-fill, and w-shaped permeable—were evaluated using flume experiments for spur dike hydrodynamics and fish aggregation effects. Based on Shannon’s entropy, an index for calculating water flow diversity is proposed. Additionally, the impact of the different spur dikes on water flow diversity and the relationship between water flow diversity and fish aggregation effects were studied. The water flow diversity index around the spur dike varied from 1.13 to 2.96. The average aggregation rate of test fish around the spur dike was 5% to 28%, and the attraction effect increased with increasing water flow diversity. Furthermore, we plotted the relationship between water flow diversity index and average fish aggregation rate. A fish hydroacoustic study conducted on the Laohutan fish-bone dike in the Dongliu reach of downstream Yangtze River showed that the fish aggregation effect of the permeable spur dike was greater than the rock-fill spur dike. These research results could provide theoretical support for habitat heterogeneity research and ecologically optimal design of spur dikes

Stability Assessment of Rubble Mound Breakwaters Using Extreme Learning Machine Models

The stability number of a breakwater can determine the armor unit’s weight, which is an important parameter in the breakwater design process. In this paper, a novel and simple machine learning approach is proposed to evaluate the stability of rubble-mound breakwaters by using Extreme Learning Machine (ELM) models. The data-driven stability assessment models were built based on a small size of training samples with a simple establishment procedure. By comparing them with other approaches, the simulation results showed that the proposed models had good assessment performances. The least user intervention and the good generalization ability could be seen as the advantages of using the stability assessment models

Courtyard-level sewer data-enhanced two-dimensional hydraulic model for urban flood hazard assessment in Kunming, China

This paper describes a study of urban flooding in downtown Kunming, China, simulating a major flood event that occurred in July 2008 using an improved two-dimensional (2D) hydraulic model enhanced with courtyard-level sewer data (CLSD). Although municipal authorities are not responsible for ‘private’ courtyard sewers, available records were specifically added to this model, enhancing its accuracy and usefulness. Geographic information system (GIS) flood maps, a mapping overlay approach and statistical method compared both predicted results and the recorded flood area. A statistical method also provided a measure of the correlation between the extent of the predicted flood areas and recorded flood areas (parameter ‘F’). Results of the improved 2D/CLSD model showed a correlation value for F of 51, 32.6% higher than the basic one-dimensional municipal-level sewer data (1D/MLSD) model; 26.2% higher than an interim version of the model that included a 2D ground surface (2D/MLSD). The 2D/CLSD model predicted flooding in 10 of the 12 courtyards with observed flooding. This was a major improvement over the 1D/MLSD model (three out of 12) and the 2D/MLSD model (five out of 12). Thus a CLSD-enhanced 2D hydraulic model potentially improves accuracy in predicting, mapping and understanding flood risk in urban areas.</jats:p

Association between Single Nucleotide Polymorphisms in Cardiovascular Developmental Critical Genes and Hypertension: A Propensity Score Matching Analysis

Cardiovascular development critical genes are key determinants in cardiovascular diseases. We hypothesize that SNPs in these genes may play critical roles in the development of hypertension. Therefore, we enrolled 516 paired hypertension patients and controls in a total of 2,742 subjects in a cross-sectional population study by the propensity score matching (PSM) method. Twenty-one SNPs from 5 cardiovascular developmental related genes were detected by the improved multiplex ligase detection reaction (iMLDR) method. Conditioned logistic regression under three different genetic models, namely, additive model, dominant model, and recessive model, was performed. The odds ratio (ORs) and 95% confidence intervals (95% CIs) were used to estimate the associations of SNPs with hypertension. We found that the distribution of genotypes at rs833061, rs3025010, and rs699947 within the VEGFA gene and the distribution of alleles at rs3025010 in hypertension subjects were different from those in controls. Both rs833061 and rs3025010 were associated with hypertension in crude models, but only rs3025010 remains associated with hypertension after adjusting with confounding factors in the additive model and the dominant model. We also found that hypertension subjects with C/T and C/C genotypes at rs3025010 had lower SBP and DBP levels. In addition, rs3025010 could interact with rs6784267 within the CCM3 gene in the association. In conclusion, our findings suggest that rs3025010 may play a role in the pathogenesis of hypertension, which may be a potential target for individualized prevention and treatment of hypertension

Resistance to allosteric SHP2 inhibition in FGFR-driven cancers through rapid feedback activation of FGFR

SHP2 mediates RAS activation downstream of multiple receptor tyrosine kinases (RTKs) and cancer cell lines dependent on RTKs are in general dependent on SHP2. Profiling of the allosteric SHP2 inhibitor SHP099 across cancer cell lines harboring various RTK dependencies reveals that FGFR-dependent cells are often insensitive to SHP099 when compared to EGFR-dependent cells. We find that FGFR-driven cells depend on SHP2 but exhibit resistance to SHP2 inhibitors in vitro and in vivo. Treatment of such models with SHP2 inhibitors results in an initial decrease in phosphorylated ERK1/2 (p-ERK) levels, however p-ERK levels rapidly rebound within two hours. This p-ERK rebound is blocked by FGFR inhibitors or high doses of SHP2 inhibitors. Mechanistically, compared with EGFR-driven cells, FGFR-driven cells tend to express high levels of RTK negative regulators such as the SPRY family proteins, which are rapidly downregulated upon ERK inhibition. Moreover, over-expression of SPRY4 in FGFR-driven cells prevents MAPK pathway reactivation and sensitizes them to SHP2 inhibitors. We also identified two novel combination approaches to enhance the efficacy of SHP2 inhibitors, either with a distinct site 2 allosteric SHP2 inhibitor or with a RAS-SOS1 interaction inhibitor. Our findings suggest the rapid FGFR feedback activation following initial pathway inhibition by SHP2 inhibitors may promote the open conformation of SHP2 and lead to resistance to SHP2 inhibitors. These findings may assist to refine patient selection and predict resistance mechanisms in the clinical development of SHP2 inhibitors and to suggest strategies for discovering SHP2 inhibitors that are more effective against upstream feedback activation