[Hydrochemical Characteristics and Control Factors of Groundwater in the Northwest Salt Lake Basin].

Taking the Tugeligaole sub-basin of the Jilantai Salt Lake Basin in Inner Mongolia as the typical study area, the groundwater samples of 22 points were collected, and their main characteristic indexes were tested during the wet season and the dry season separately in 2021. Mathematical statistics, Piper triangular diagrams, a Gibbs plot, ionic relations, and factor analysis were used to analyze and discuss the hydrochemical characteristics and formation mechanism of groundwater in different periods. Based on the evaluation of the groundwater quality using the water quality index(WQI) method, the potential risks of groundwater Cr6+ and F- were evaluated using the health risk evaluation model. The results showed that the groundwater was overall weakly alkaline; the dominant anions and cations during the different periods were Cl- and Na+, and the water chemistry type was mainly Cl--Na+; the groundwater quality was generally good, and the difference in water quality between the wet season and the dry season was not significant; adults and children had higher carcinogenic health risks in the dry season than that in the wet season, and the health risks of children were significantly higher than those in adults. The maximum carcinogenic health risk of drinking water exposure to Cr6+ in adults and children was higher than the maximum acceptable risk level(5×10-5). The chemical evolution of groundwater was mainly affected by evaporative concentration, evaporative salt rock dissolution, and cation exchange, and the main control factors were evaporative concentration(contribution rate of 54.19%), native geological environment factors(contribution rate of 12.99%), and carbonate rock dissolution(contribution rate of 11.66%). The study results have significance to some degree to the sustainable exploitation and utilization of groundwater resources and environmental protection of the salt lake basin.

[Relationship Between Precipitation, River Water, and Groundwater Conversion in the Upper Reaches of Xilin River During the Rainy Season].

To deeply understand the hydrological cycle process and the transformation mechanism of different water bodies in the grassland inland river basin, the atmospheric precipitation, river water, and groundwater in the Xilin River Basin were taken as the research objects, the hydrogen and oxygen stable isotopes were analyzed, and the multi-scale spatio-temporal characteristics were analyzed to explore the quantitative transformation relationship between different water bodies in the basin. The results showed that:① the Xilin River Basin had an obvious inland semi-arid climate, the atmospheric precipitation was the main source of recharge for the river water and groundwater, and the groundwater and river water experienced different degrees of non-equilibrium evaporation at the same time. ② The isotopic composition of the river water showed the characteristics of depletion in spring and autumn and enrichment in summer and showed a trend of increasing from upstream to downstream in space. The variation in δ18O in shallow and deep groundwater during the growing season was basically the same, and the main difference between the two occurred at the end of the growing season, that is, the former tended to be stable, whereas the latter showed an upward trend, which reflected that the deep groundwater had a lagged response to the infiltration and recharge of atmospheric precipitation and surface water, and both of them were depleted gradually from southeast to northwest in space. ③ Based on the estimation results of the endmember mixing model, the average recharge ratio of atmospheric precipitation and shallow groundwater to river water in summer was 52.69% and 47.31%, respectively, indicating that shallow groundwater was an important recharge source of river water in the inland river basin even during the rainy season. The results of this study provide theoretical guidance for water resource regulation and ecological environment protection in a typical semi-arid grassland inland river basin.

[Risk Assessment of Heavy Metals in Dust Fall Around Reservoirs in Typical Ecologically Fragile Areas and Traceability Based on APCS-MLR Model].

To assess the health risk status and pollution sources of heavy metals in the atmosphere of ecologically vulnerable areas, the surrounding area of Dahekou Reservoir in Xilingol League was selected as the study area. From 2021 to 2022, 12 monitoring points for atmospheric dust fall were collected for a period of one year. A total of 144 samples were collected to determine the contents of eight types of heavy metals, namely Cr, Ni, Pb, Cu, Zn, Mn, As, and Cd. The potential ecological index (Eri) and health risk assessment model were used to assess the risk level of atmospheric heavy metals on ecological security and human health. The analysis of enrichment factors, principal components, and the model of absolute principal component multiple linear regression (APCS-MLR) receptor were used to analyze the sources of heavy metal pollution qualitatively in the atmosphere of the study area. The results showed that:① the mean value of the comprehensive potential ecological risk of heavy metals in the annual atmospheric dust fall in the study area was at a high ecological risk, and only the Cd value was at a very high risk level among the heavy metals, whereas the remaining were at a slight risk. ② The results of the health risk showed that intake by hand, mouth, and skin contact were the main exposure routes, which led to non-carcinogenic and carcinogenic risks. Children were under non-carcinogenic and acceptable carcinogenic risks in different months. During those months, the main source of the risks was As. ③ Through enrichment factor analysis, principal component analysis, and APCS-MLR receptor model calculation, the results revealed that the proportion of wind-blown sources was the largest, accounting for 37.82%, and the contribution rates of coal combustion and traffic sources to Cu, Cd, Pb, and Zn were 73.01%, 40.22%, 70.31%, and 32.82%, respectively. The contribution rate of mining activities to As was 42.59%, while that of industrial sources of Cd was 22.01%; the contributions of other human activity sources of Cd, As, Pb, and Zn were 21.12%, 34.40%, 23.04%, and 32.15%, respectively.

[Water Chemical Isotope Characteristics and Water Transformation Relationship in Mongolian Section of the Yellow River Basin].

The Yellow River in Inner Mongolia was selected as the study area in this study. In July (wet season) and October (dry season) of 2021, the acquisition of seasonal rivers, the Yellow River tributaries and precipitation, the Yellow River, Wuliangsuhai, Lake Hasuhai, Lake Daihai, an irrigation canal system, and underground water and sea water samples were collected to test the water chemical composition and hydrogen and oxygen isotopic values of different water types. Using the Piper triplot, Gibbs plot, ion ratio, and MixSIAR model methods, the evolution of water chemistry in the Mongolian section of the Yellow River Basin was analyzed, and the transformation relationship between precipitation, surface water, and groundwater was revealed. The results showed that both groundwater and surface water in the study area were slightly alkaline; the dominant anion in water was Cl-, and the dominant cation was Na+. The main hydrochemical types of surface water were Cl·SO4-Na·Mg and SO4·HCO3-Na·Mg, whereas those of groundwater were Cl·SO4-Na·Mg and SO4·HCO3-Na·Ca. Groundwater Ca2+ and Mg2+ were primarily derived from the dissolution of silicate and evaporite, and surface water Ca2+ and Mg2+ were primarily derived from carbonate karst dissolution and carbonate and sulfuric acid in water participating in the dissolution process of carbonate and sulfide minerals. Na+ and Cl- in different water bodies were all affected by anthropogenic pollution sources. Owing to the seasonal effect, δD and δ18O of surface water and groundwater were higher in the wet season than in the dry season. The results showed that surface water was affected by evaporative fractionation after receiving precipitation recharge, and the groundwater recharge sources were complex. The MixSIAR model revealed that surface water was the main recharge source of groundwater, accounting for 52.4%-62.2% of the total recharge, and atmospheric precipitation was the main recharge source of surface water, accounting for 85.4%-97.1% of the total recharge.

Spatiotemporal variations of ecosystem security pattern in Horqin sandy dune meadow alternating area, China.

The natural and geographical environment of ecologically fragile areas in northern China is complex. Due to heavy human disturbance and impacts of climate change, the sustainable development of ecosystems is facing serious challenges. Constructing ecological security pattern can provide decision-making basis for ecological environment protection in desertification areas. Based on land use change data of Horqin dune-meadow interphase area from 1985 to 2021, we identified ecological sources with the importance of ecosystem services and ecological sensitivity, and constructed the ecological security pattern using the minimum cumulative resistance model. We further analyzed the ecological security pattern and its development trend in 1985, 1995, 2005, 2015 and 2021, and explored the ecological spatial layout adjustment strategy. The results showed that the proportion of source area in the ecological security pattern of the study area was always small and scattered from 1985 to 2021, the network of ecological corridors was low, and the connectivity between ecological patches was lacking. The ecological security pattern had experienced a trend of deterioration first and then gradually improving. Ecological policies such as returning farmland to forest and grassland and afforestation had significantly improved the environmental security. We optimized the study area by combining the cultivated land suitability evaluation method. The ecological security pattern showed a spatial trend of 'dual-core, scattered and semi-surrounded'. The results could provide references for the construction of county-scale ecological security pattern in ecologically fragile areas and the ecological management of Horqin sands.

Forecasting groundwater level of karst aquifer in a large mining area using partial mutual information and NARX hybrid model.

Predicting the groundwater level of karst aquifers in North China Coalfield is essential for early warning of mine water hazards and regional water resources management. However, the dynamic changes of strata structure and hydrogeological parameters driven by coal mining activity cause challenges to the process-oriented groundwater model. In order to achieve accurate prediction of groundwater level in large mining areas, this study was the first to use the data-driven Nonlinear Autoregressive with External Input (NARX) model to predict the groundwater level of six karst aquifer observation wells in Pingshuo Mining Area. Three variable input scenarios were set up, solely considering meteorological factors, anthropogenic disturbance factors, and considering both meteorological and anthropogenic disturbance factors. The novel partial mutual information (PMI) screening algorithm was adopted to determine optimized input variables in each scenario. The input and feedback delay coefficients of NARX model were determined by using Seasonal-trend Decomposition Procedure Based on Loess (STL) algorithm and auto- and cross-correlation functions. The results showed that PMI algorithm can effectively screen out the optimal input variables for predicting groundwater level, the NSE coefficients of the PMI-NARX models under the three scenarios were 38.81%, 4.26% and 41.46% higher than those of the corresponding control experiments, respectively. In addition, the prediction performance of the PMI-NARX built on the basis of meteorological factors is poor (NSE <0.63). However, in scenarios which solely use anthropogenic disturbance factors and both use meteorological and anthropogenic disturbance factors, the PMI-NARX coupling models exhibit good prediction performance (NSE and R2 are all greater than 0.8). Especially under solely considering anthropogenic disturbance factors scenario, the model still exhibited good prediction accuracy with a negligible number of input variables. The results can provide technical and theoretical support for the prediction of groundwater level in other mining areas.

[Temporal and spatial variations of annual precipitation and meteorological drought in China during 1951-2018]. / 1951­2018年中国年降水量及气象干旱的时空变异.

Exploring the temporal and spatial variations of precipitation and drought is an important topic in hydro-logy. Based on the precipitation data of 619 meteorological stations in China from 1951 to 2018, we used anomaly percentage method and Morlet wavelet analysis to analyze the temporal and spatial variations of annual precipitation and drought. The results showed that annual precipitation in China showed a stepwise decreasing trend from southeast to northwest during the study period, and that the intensity of annual precipitation change was on the contrary. The precipitation near the boundary of the second and third steps showed a downward trend, and the abrupt change of precipitation occurred mainly in the 1960s and 1970s. The rest region was on the rise, with substantial changes in the 1990s. The main period of precipitation was short in the regions with temperate continental climate and temperate monsoon climate. From 1960s to 2010s, the area of arid land in China had decreased, while that of the semi-arid area and semi-humid area had increased gradually, especially in the recent decade. An aridity boundary was found between 30° N and 40° N, with drought frequency in its north being much more than the south. On the whole, the frequency and scope of drought events showed a decreasing trend and its interdecadal shift direction was from the central part of northwest China to the southern part of North China and then to the northern part of North China.

Selective and competitive functions of the AAR and UPR pathways in stress-induced angiogenesis.

The amino acid response (AAR) and unfolded protein response (UPR) pathways converge on eIF2α phosphorylation, which is catalyzed by Gcn2 and Perk, respectively, under different stresses. This close interconnection makes it difficult to specify different functions of AAR and UPR. Here, we generated a zebrafish model in which loss of threonyl-tRNA synthetase (Tars) induces angiogenesis dependent on Tars aminoacylation activity. Comparative transcriptome analysis of the tars-mutant and wild-type embryos with/without Gcn2- or Perk-inhibition reveals that only Gcn2-mediated AAR is activated in the tars-mutants, whereas Perk functions predominantly in normal development. Mechanistic analysis shows that, while a considerable amount of eIF2α is normally phosphorylated by Perk, the loss of Tars causes an accumulation of uncharged tRNAThr, which in turn activates Gcn2, leading to phosphorylation of an extra amount of eIF2α. The partial switchover of kinases for eIF2α largely overwhelms the functions of Perk in normal development. Interestingly, although inhibition of Gcn2 and Perk in this stress condition both can reduce the eIF2α phosphorylation levels, their functional consequences in the regulation of target genes and in the rescue of the angiogenic phenotypes are dramatically different. Indeed, genetic and pharmacological manipulations of these pathways validate that the Gcn2-mediated AAR, but not the Perk-mediated UPR, is required for tars-deficiency induced angiogenesis. Thus, the interconnected AAR and UPR pathways differentially regulate angiogenesis through selective functions and mutual competitions, reflecting the specificity and efficiency of multiple stress response pathways that evolve integrally to enable an organism to sense/respond precisely to various types of stresses.

Characteristics and environmental driving factors of water transformation in the Balaguer River watershed of Inner Mongolia steppe.

Inner Mongolian steppe is one of the ecological barriers in China. The variation of water resources is very important for the development of social-economy and the protection of eco-environment. We collected 254 water samples of precipitation, river, and shadow groundwater during wet-season and dry-season of 2018-2019 from Balaguer River watershed and meansured the physical-chemical indicators, δD and δ18O of water samples. The stable isotope technology, mathematical statistics, and the inverse distance weighting method were used to analyze the stable isotope composition, spatial-temporal variation, and impact factors. Moreover, the d-excess and the isotopic mixing ratio formula were used to analyze the conversion characteristics of different water and to identify their environment driving variables. The results showed that δD and δ18O of precipitation, river and shallow groundwater were higher in wet season than in dry season. The driving factors of different water transformation in the watershed were air temperature, altitude, and groundwater depth. Altitude was significantly negatively correlated with river δD, and the δD and δ18O of groundwater. δD and δ18O of groundwater fluctuated significantly in the area with groundwater depth less than 10 m, but were stable in other areas. There was a positive correlation between precipitation δ18O and air temperature. The d-excess in wet season was higher than that in dry season, with a decreasing distribution characteristic from southern to northern part in the study area. More than 50% river in upper stream came from precipitation, while more than half river water converted to groundwater, with different recharge-drainage relationships existed between surface water and groundwater in different river reaches.

[Characteristics of humidity and temperature variations and CO2 exchange of mobile dunes at different space-time scales in Horqin sandy land, China].

Terrestrial carbon cycle plays a key role in driving climate change and ecosystem carbon balance. Understanding the variations of humidity and temperature and CO2 exchanges are meaningful to reveal the law and mechanism of regional carbon cycles in deserts. We examined the near surface humidity, temperature variations, and CO2 exchanges by eddy covariance and Bowen ratio systems in a typical mobile dune of Horqin sandy land. We analyzed the relationships between water-heat and CO2 exchanges of 0 to 10 m vertical height at daily and seasonal scales were analyzed. The results showed that the vertical variations of near surface temperature ranged from 0.4 ℃ to 2 ℃ and decreased with the increases of height from April to September, but with an opposite pattern in other months. The seasonal variation of air relative humidity was greater than 40%. During the growing season of 2018, the averaged daily net ecosystem carbon exchange (NEE) was -0.02 mg·m-2·s-1. The annual averaged daily NEE was 0.003 mg·m-2·s-1, indicating that the mobile dunes were carbon sources at the whole year scale. The vertical differences of temperature and humidity well fitted the NEE. The inflexion points of the fitting curve were at 10% humidity and 0.5 ℃ temperature, respectively. At the scalem of the year, the NEE fitting result of temperature was better than that of humidity, with the inflexion points at 17 ℃ and 65% humidity, respectively. In the growing season, the near surface vertical temperature difference was negative, which would inhibit CO2 absorption of mobile dunes. The circumstances of high humidity would promote the absorption of atmospheric CO2. Across different time and vertical height, the variations of humidity and temperature were closely related to CO2 exchanges, which affected carbon sink and source of mobile dunes. Carbon budget was more sensitive to temperature than humidity.

[Deep water leakage from semi-mobile dunes in semi-arid regions and its response to rainfall patterns]. / åŠå¹²æ—±åœ°åŒºåŠæµåŠ¨æ²™ä¸˜æ°´åˆ†æ·±å±‚æ¸—æ¼é‡åŠå ¶å¯¹é™é›¨æ ¼å±€çš„å“åº”.

As the main source of soil moisture supply in desertified areas, rainfall has a profound impact on soil moisture changes and plays an important role in deep soil moisture replenishment. Based on the Hydrus-1D model with optimized parameters, we analyzed the dynamic change process of the leakage in the 200 cm deep layer of the semi-mobile dunes in Horqin Sandy Land and its response to the rainfall patterns. The results showed that the averaged leakage replenishment of semi-mobile dunes was 254.31 mm from April to October each year during 2016 to 2019, accoun-ting for 61.8% of the rainfall in the same period. Deep leakage mainly occurred from June to August, accounting for 72.8% of the total. The leakage rate was distributed between 0.03-2.70 mm·h-1, with the maximum leakage rate occurring under heavy rainfall and frequent rainfall events. The deep soil water supplied by rainfall infiltration was affected by the amount of rainfall, rainfall intensity, duration of precipitation and soil moisture content in the earlier period. Precipitation events with long duration and small rainfall intensity were more conducive to deep water lea-kage, with a significant positive correlation between the leakage and rainfall (R2=0.85). 16-18 mm rainfall was the threshold for the leakage of 200 cm soil depth. The high-frequency rainfall event usually reached peak after 17-38 hours, with the entire leakage process being more than 164 hours. Accurate estimation of deep leakage has theoretical and practical significance for water resource assessment and ecological construction in desertified areas.

[Characteristics of soil greenhouse gas flux and its driving factors in Horqin sand dune-mea-dow wetland cascade ecosystems.] / 科尔沁沙丘-è‰ç”¸æ¢¯çº§ç”Ÿæ€ç³»ç»ŸåœŸå£¤æ¸©å®¤æ°”ä½“é€šé‡ç‰¹å¾åŠå ¶å½±å“å› ç´ .

Using the static chamber-GC technique, greenhouse gas (CO2, CH4, N2O) fluxes of sand dunes and meadow wetlands were measured in a typical sand dune-meadow cascade ecological zone of Horqin. The dynamics of the greenhouse gas fluxes and driving factors were analyzed. The results showed that soil CH4 flux underwent absorption during the growing season, with average CH4 fluxes of semi-mobile dunes and meadow wetlands were -52.7 µg·m-2·h-1 and -34.7 µg·m-2·h-1, respectively, ranging from -176.1 to 49.8 µg·m-2·h-1. The peak of CH4 absorption in the growing season occurred at August 22nd, 2017. In August and September, the months with heavy rainfall, the CH4 flux in meadow wetlands showed continuous emission, being significantly different from that in semi-mobile dunes. The peak of N2O flux during the growing season was at July 21st. The monthly average N2O flux in semi-mobile dunes was following the order of July > August > September > June > May. Soil temperature and moisture were the key factors affecting CO2 and CH4 fluxes, whereas the N2O flux was mainly affected by soil temperature. The soil temperature sensitivity (Q10) showed the sequence of semi-mobile dune (1.009) < meadow wetland (1.474). The water stress rendered the greenhouse gas fluxes in semi-mobile dunes being less sensitive to soil temperature change than that in meadow wetlands.

Simulation of evapotranspiration for the mobile and semi-mobile dunes in the Horqin Sandy Land using the Shuttleworth-Wallace model.

Terrestrial evapotranspiration (ET) plays a crucial role in climate regulation and the maintenance of regional water balance. Quantitative estimation of ET and its partitioning are important for revealing the eco-hydrological processes in arid and semi-arid areas. Using the in situ data sampled by the meteorological monitoring system, the Shuttleworth-Wallace (S-W) model was applied to simulate and partition ET in the mobile and semi-mobile dunes of the Horqin sandy land during the growing season in 2017. The eddy covariance system was used to verify the simulated ET. The results were as follows: the simulated ET (308 mm) was very close to the eddy covariance observed ET (296 mm) during the whole growing season, indicating the applicability of the S-W model for ET estimation in this area. The ET rate at the vigorous growth stage (192 mm) was larger than those at the late and early growth stages (71 and 45 mm, respectively) which accounted for 62.3%, 23.1%, and 14.6% of the total, respectively. The simulated ET was close to the eddy covariance observed ET at the daily time-scale. The simulation performance of the S-W model for clear days was better than for cloudy or rainy days. The simulated ET rate was always smaller than the eddy covariance observed ET in the cloudy or rainy days. According to the model, the evaporation (E) from soil was 176 mm and the transpiration (T) from plants was 132 mm, accounting for 57.1% and 42.9% of the ET, respectively, suggesting that water use efficiency of the sand dune was low. The characteristics of ET varied substantially under the sustained drought and precipitation events. Compared to T from plants, E from soil was more sensitive to precipitation.

[Effects of temperature and moisture on net ecosystem CO2 exchange over a meadow wetland in the Horqin, China.] / 温度和水分对科尔沁草甸湿地净生态系统碳交换量的影响.

Using the eddy covariance technique, the Bowen-ratio meteorological and soil monitoring system, we analyzed the CO2 flux dynamics and its responses to temperature and moisture over a meadow wetland in the Horqin during the growing season (from May to September) in 2016. The results showed that the accumulated net ecosystem CO2 exchange (NEE) was -766.18 g CO2·m-2 during the growing season. The gross primary productivity (GPP) and ecosystem respiration (Re) were 3379.89 and 2613.71 g CO2·m-2, respectively. The ratio of Re to GPP was 77.3%, indicating that this ecosystem was an obvious carbon sink. The average diurnal variation of NEE exhibited a single peak U-shaped curve with an absorption of CO2 from May to mid August and a release of CO2 from late August to September. Daytime NEE well fitted with the photosynthetically active radiation (PAR) by a rectangular hyperbolic function. Meanwhile, the relationship was affected by the environmental factors, including vapor pressure deficit (VPD), soil water content (SWC) and air temperature (Ta). Regression analysis showed that the VPD and SWC for the maximum daytime NEE were 1.75 kPa and 35.5%, respectively. Daytime NEE increased with Ta, and with no inhibitory effect on the daytime NEE when it reached the maximum. Nighttime NEE had an exponential relationship with soil temperature (Ts). During the entire growing season, the temperature sensitivity of the ecosystem respiration (Q10) was 2.4, which was negatively related to SWC. The nighttime NEE was controlled by both Ts and SWC.

The histone demethylase Jmjd3 regulates zebrafish myeloid development by promoting spi1 expression.

The histone demethylase Jmjd3 plays a critical role in cell lineage specification and differentiation at various stages of development. However, its function during normal myeloid development remains poorly understood. Here, we carried out a systematic in vivo screen of epigenetic factors for their function in hematopoiesis and identified Jmjd3 as a new epigenetic factor that regulates myelopoiesis in zebrafish. We demonstrated that jmjd3 was essential for zebrafish primitive and definitive myelopoiesis, knockdown of jmjd3 suppressed the myeloid commitment and enhanced the erythroid commitment. Only overexpression of spi1 but not the other myeloid regulators rescued the myeloid development in jmjd3 morphants. Furthermore, preliminary mechanistic studies demonstrated that Jmjd3 could directly bind to the spi1 regulatory region to alleviate the repressive H3K27me3 modification and activate spi1 expression. Thus, our studies highlight that Jmjd3 is indispensable for early zebrafish myeloid development by promoting spi1 expression.

Vibsanin B preferentially targets HSP90ß, inhibits interstitial leukocyte migration, and ameliorates experimental autoimmune encephalomyelitis.

Interstitial leukocyte migration plays a critical role in inflammation and offers a therapeutic target for treating inflammation-associated diseases such as multiple sclerosis. Identifying small molecules to inhibit undesired leukocyte migration provides promise for the treatment of these disorders. In this study, we identified vibsanin B, a novel macrocyclic diterpenoid isolated from Viburnum odoratissimum Ker-Gawl, that inhibited zebrafish interstitial leukocyte migration using a transgenic zebrafish line (TG:zlyz-enhanced GFP). We found that vibsanin B preferentially binds to heat shock protein (HSP)90ß. At the molecular level, inactivation of HSP90 can mimic vibsanin B's effect of inhibiting interstitial leukocyte migration. Furthermore, we demonstrated that vibsanin B ameliorates experimental autoimmune encephalomyelitis in mice with pathological manifestation of decreased leukocyte infiltration into their CNS. In summary, vibsanin B is a novel lead compound that preferentially targets HSP90ß and inhibits interstitial leukocyte migration, offering a promising drug lead for treating inflammation-associated diseases.

miR-142-3p acts as an essential modulator of neutrophil development in zebrafish.

Neutrophils play critical roles in vertebrate innate immune responses. As an emerging regulator in normal myelopoiesis, the precise roles of microRNA in the development of neutrophils have yet to be clarified. Using zinc-finger nucleases, we have successfully generated heritable mutations in miR-142a and miR-142b and showed that hematopoietic-specific miR-142-3p is completely deleted in miR-142 double mutant zebrafish. The lack of miR-142-3p resulted in aberrant reduction and hypermaturation of neutrophils in definitive myelopoiesis, as well as impaired inflammatory migration of neutrophils in the fetal stage. Furthermore, the adult myelopoiesis in the miR-142-3p-deficient zebrafish was also affected, producing irregular hypermature neutrophils with increased cell size and a decreased nucleocytoplasmic ratio. Additionally, miR-142-3p-deficient zebrafish are expected to develop a chronic failure of myelopoiesis with age. Transcriptome analysis showed an aberrant activation of the interferon γ (IFN-γ) signaling pathway in myelomonocytes after miR-142-3p deletion. We found that the reduced number and hypermaturation of neutrophils caused by loss of miR-142-3p was mainly mediated by the abnormally activated IFN-γ signaling, especially the upregulation of stat1a and irf1b. Taken together, we uncovered a novel role of miR-142-3p in maintaining normal neutrophil development and maturation.

Setdb2 controls convergence and extension movements during zebrafish gastrulation by transcriptional regulation of dvr1.

As the primary driving forces of gastrulation, convergence and extension (C&E) movements lead to a medio-lateral narrowing and an anterior-posterior elongation of the embryonic body axis. Histone methylation as a post-translational modification plays a critical role in early embryonic development, but its functions in C&E movements remain largely unknown. Here, we show that the setdb2-dvr1 transcriptional cascade plays a critical role in C&E movements during zebrafish gastrulation. Knockdown of Setdb2, a SET domain-containing protein possessing a potential histone H3K9 methyltransferase activity, induced abnormal C&E movements, resulting in anterior-posterior shortening and medio-lateral expansion of the embryonic axis, as well as abnormal notochord cell polarity. Furthermore, we found that Setdb2 functions through fine-tuning the expression of dvr1, a ligand of the TGF-ß superfamily, to an appropriate level to ensure proper C&E movements in a non-cell-autonomous manner. In addition, both overexpression and knockdown of Dvr1 at the one-cell stage resulted in defects at epiboly and C&E. These data demonstrate that Setdb2 is a novel regulator for C&E movements and acts by modulating the expression level of dvr1, suggesting that Dvr1 acts as a direct and essential mediator for C&E cell movements.

Functional and molecular features of the calmodulin-interacting protein IQCG required for haematopoiesis in zebrafish.

We previously reported a fusion protein NUP98-IQCG in an acute leukaemia, which functions as an aberrant regulator of transcriptional expression, yet the structure and function of IQCG have not been characterized. Here we use zebrafish to investigate the role of iqcg in haematopoietic development, and find that the numbers of haematopoietic stem cells and multilineage-differentiated cells are reduced in iqcg-deficient embryos. Mechanistically, IQCG binds to calmodulin (CaM) and acts as a molecule upstream of CaM-dependent kinase IV (CaMKIV). Crystal structures of complexes between CaM and IQ domain of IQCG reveal dual CaM-binding footprints in this motif, and provide a structural basis for a higher CaM-IQCG affinity when deprived of calcium. The results collectively allow us to understand IQCG-mediated calcium signalling in haematopoiesis, and propose a model in which IQCG stores CaM at low cytoplasmic calcium concentrations, and releases CaM to activate CaMKIV when calcium level rises.

Pten regulates homeostasis and inflammation-induced migration of myelocytes in zebrafish.

BACKGROUND: Loss of the tumor suppressor phosphatase and tensin homolog (PTEN) is frequently observed in hematopoietic malignancies. Although PTEN has been implicated in maintaining the quiescence of hematopoietic stem cells (HSCs), its role in hematopoiesis during ontogeny remains largely unexplored. METHODS: The expression of hematopoietic marker genes was analyzed via whole mount in situ hybridization assay in ptena and ptenb double mutant zebrafish. The embryonic myelopoiesis was characterized by living imaging and whole mount in situ immunofluorescence with confocal microscopy, as well as cell-specific chemical staining for neutrophils and macrophages. Analyses of the involved signaling pathway were carried out by inhibitor treatment and mRNA injection. RESULTS: Pten-deficient zebrafish embryos exhibited a strikingly increased number of myeloid cells, which were further characterized as being immune deficient. In accordance with this finding, the inhibition of phosphoinositide 3-kinase (PI3K) or the mechanistic target of rapamycin (mTOR) corrected the expansive myelopoiesis in the pten-deficient embryos. Further mechanistic studies revealed that the expression of cebpa, a critical transcription factor in myeloid precursor cells, was downregulated in the pten-deficient myeloid cells, whereas the injection of cebpa mRNA markedly ameliorated the dysmyelopoiesis induced by the loss of pten. CONCLUSIONS: Our data provide in vivo evidence that definitive myelopoiesis in zebrafish is critically regulated by pten via the elevation of cebpa expression.