Cell fate decisions require appropriate regulation of key genes.
, a direct target of SRY, is pivotal in mammalian sex determination. In vivo high-throughput chromatin accessibility techniques, ...transgenic assays, and genome editing revealed several novel gonadal regulatory elements in the 2-megabase gene desert upstream of
Although others are redundant, enhancer 13 (Enh13), a 557-base pair element located 565 kilobases 5' from the transcriptional start site, is essential to initiate mouse testis development; its deletion results in XY females with
transcript levels equivalent to those in XX gonads. Our data are consistent with the time-sensitive activity of SRY and indicate a strict order of enhancer usage. Enh13 is conserved and embedded within a 32.5-kilobase region whose deletion in humans is associated with XY sex reversal, suggesting that it is also critical in humans.
► The metabolic footprint of bacterivore nematodes was enhanced by winter cover crops. ► The structure footprint of the soil food web increased over years of organic production. ► Functional ...connectance of predators and target prey was strongly related to that of predators and amplifiable prey. ► Organic resources transferred to higher trophic links increase top-down regulatory pressure. ► Crop plant growth was positively correlated with nematode-based measures of soil health.
The abundance and metabolic footprints of soil nematodes were quantified during four of eight years of an intensive organic vegetable production system. Treatment variables included cover crop mixtures and compost application rates. The abundances of bacterivore and fungivore nematodes were enhanced by the annual use of winter cover crops but showed no relationship to the level of residual soil organic matter. Metabolic footprints, based on biomass and respiratory activity, were calculated for functional guilds and ecosystem services of the nematode assemblage. The enrichment footprint, representing the ecosystem service of nutrient mineralization, was related to the level of soil organic carbon. It was strongly related to the metabolic footprint of bacterivore nematodes and both were enhanced in treatments that were cover cropped annually. Cover-cropped treatments also had a slightly higher herbivore footprint, suggesting support of some taxa of plant-feeding nematodes. The structure footprint, reflecting the metabolic activity of higher trophic level nematodes, including the predators of opportunistic species, did not differ among cover crop and compost amendment treatments. However, enrichment footprints were correlated with bacterivore footprints, which represented the predominantly bacterivore resources available to predators. Abundance of predators increased as a function of the abundance of those nematode prey that can be amplified by organic inputs. The functional connectance, represented by spatial co-location, between predators and amplifiable prey was greater in treatments with a greater abundance of predators. The functional connectance between predators and herbivore prey, representing a management target, was strongly related to the functional connectance between predators and amplifiable prey. We conclude that cover crops not only affect organisms at the entry level of the web but that resources are also transferred to higher trophic links which increases top-down pressure on plant-parasitic nematodes.
XX and XY fetal gonads are initially bipotential, poised between the ovary and testis fate. Multiple lines of evidence suggest that commitment to testis fate requires the repression of genes ...associated with ovary fate. It was previously shown that loss of CBX2, the subunit of the Polycomb Repressive Complex 1 (PRC1) that binds H3K27me3 and mediates silencing, leads to ovary development in XY mice and humans. While it had been proposed that CBX2 is an activator of the testis-determining gene Sry, we investigated the alternative possibility that CBX2 has a direct role as a repressor of the antagonistic ovary-promoting pathway. To investigate this possibility, we developed a quantitative genome-wide profile of the repressive histone mark H3K27me3 and its active counterpart H3K4me3 in isolated XY and XX gonadal supporting cells before and after sex determination. We show that testis and ovary sex-determining (SD) genes are bivalent before sex determination, providing insight into how the bipotential state of the gonad is established at the epigenetic level. After sex determination, many SD genes of the alternate pathway remain bivalent, possibly contributing to the ability of these cells to transdifferentiate even in adults. The finding that many genes in the Wnt signaling pathway were targeted for H3K27me3-mediated repression in Sertoli cells led us to test whether deletion of Wnt4 could rescue testis development in Cbx2 mutants. We show that Sry expression and testis development were rescued in XY Cbx2-/-;Wnt4-/- mice. Furthermore, we show that CBX2 directly binds the downstream Wnt signaler Lef1, an ovary-promoting gene that remains bivalent in Sertoli cells. Our results suggest that stabilization of the testis fate requires CBX2-mediated repression of bivalent ovary-determining genes, which would otherwise block testis development.
We analyze the role of megathrust geometry on slip estimation using the 1960 Chile earthquake (MW = 9.5) as an example. A variable slip distribution for this earthquake has been derived by Barrientos ...and Ward (1990) applying an elastic dislocation model with a planar fault geometry. Their model shows slip patches at 80–110 km depth, isolated from the seismogenic zone, interpreted as aseismic slip. We invert the same geodetic data set using a finite element model (FEM) with precise geometry derived from geophysical data. Isoparametric FEM is implemented to constrain the slip distribution of curve‐shaped elements. Slip resolved by our precise geometry model is limited to the shallow region of the plate interface suggesting that the deep patches of moment were most likely an artifact of the planar geometry. Our study emphasizes the importance of fault geometry on slip estimation of large earthquakes.
At present, selected patients with resectable colorectal peritoneal metastases (CRC-PM) are increasingly treated with a combination therapy of cytoreductive surgery (CRS) and hyperthermic ...intraperitoneal chemotherapy (HIPEC). The aim of this study was to investigate the current worldwide practice.
HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning their personal expertise and current hospital and countrywide practice.
It is estimated that currently more than 3800 patients with CRC-PM (synchronous and metachronous) are annually treated with CRS and HIPEC in 430 centers. Integration of CRS and HIPEC in national guidelines varies, resulting in large treatment disparities between countries. Amongst the experts, there was general agreement on issues related to indication, surgical technique and follow up but less on systemic chemotherapy or proactive strategies.
This international survey demonstrates that CRS and HIPEC is now performed on a large scale for CRC-PM patients. Variation in treatment may result in heterogeneity in surgical and oncological outcomes, emphasising the necessity to reach consensus on several issues of this comprehensive procedure. Future initiatives directed at achieving an international consensus statement are needed.
Shallow nearshore coastal waters provide a wealth of societal, economic and ecosystem services, yet their topographic structure is poorly mapped due to a reliance upon expensive and time intensive ...methods. Space‐borne bathymetric mapping has helped address these issues, but has remained largely dependent upon in situ measurements. Here we fuse ICESat‐2 lidar data with Sentinel‐2 optical imagery, within the Google Earth Engine cloud platform, to create openly available spatially continuous high‐resolution bathymetric maps at regional‐to‐national scales in Florida, Crete and Bermuda. ICESat‐2 bathymetric classified photons are used to train three Satellite Derived Bathymetry (SDB) methods, including Lyzenga, Stumpf and Support Vector Regression algorithms. For each study site the Lyzenga algorithm yielded the lowest RMSE (approx. 10‐15%) when compared with validation data. We demonstrate a means of using ICESat‐2 for both model calibration and validation, thus cementing a pathway for fully space‐borne estimates of nearshore bathymetry in shallow, clear water environments.
The spatiotemporal evolution of both U and Th isotopes in a mine effluent highly polluted by acid mine drainage (AMD) was evaluated. The acidic tributary, which born from the outflows of an abandoned ...sulfide mine, flows into the Odiel River. AMD comprises an important source of natural radionuclides, presenting concentrations of 238U and 232Th, two and four orders of magnitude higher, respectively, than the background values of surface continental waters. These natural radionuclides behave conservatively along the mine effluent (pH < 2.5) throughout the hydrological year. Under AMD conditions uranium is in the hexavalent state U(VI) and the main dissolved species are uranyl sulfate complexes. The polluted tributary has a significant impact on the Odiel River acidifying its waters during the low flow season and increasing up to one order of magnitude the activity concentrations of U and Th isotopes. U presented a conservative behavior in the Odiel River during the low flow season (pH ≈ 3), however it is removed from the liquid phase in the wet season (pH ≈ 6), probably due its coprecipitation/adsorption onto Al-phases. Th shows a high sensitivity to small increases of pH, and it is strongly coprecipitated/adsorbed with or onto Fe-oxyhydroxydizes in the river.
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•Acid mine drainage comprises an important source of natural radionuclides.•Conservative behaviour of U and Th isotopes in the mine effluent.•Uranium is in the hexavalent state U(VI) in the form of uranyl sulphate complexes.•Coprecipitation/adsorption of uranium with/onto Al-phases.•Coprecipitation/adsorption of thorium with/onto Fe-oxyhydroxides.
Phosphogypsum (PG) is disposed worldwide in large stacks usually placed in coastal zones, as in the case of Huelva (SW of Spain), where around 100 Mt of PG are stored on the salt marshes of the Tinto ...River estuary covering a surface of about 1000 ha. This management generates the weathering of PG, and due to its high acidity (pH ≈ 2) and pollutant load can provoke significant emissions into their surroundings. In this work were evaluated by laboratory experiments the effects of pH increase in the behaviour of heavy metals and natural radionuclides during the mixing of phosphogypsum leachates with seawater.
The acidic phosphogypsum leachates showed concentrations of heavy metals from two to three orders of magnitude higher than natural continental waters, and natural radionuclides (U-isotopes and 210Po) from four to five orders of magnitude higher than unperturbed aquatic systems. Major elements and some heavy metals as Mn, Ni, Cd, As, Sb and Co showed a conservative behaviour during the neutralisation of the leachates with seawater, remaining in the liquid phase, while other ones as Al, Fe, Cr, Zn, Cu, Pb precipitated and/or were adsorbed onto the solid phase. The U-isotopes and 210Po showed a clear non-conservative behaviour probably due to coprecipitation/adsorption processes onto the formed precipitates, but while 210Po reached a total removal at pH ≈ 7, U- isotopes after a total removal at pH ≈ 5 returned into the liquid phase due to redissolution/desorption processes at near neutral pH.
The formed precipitates, mainly composed by iron phosphates particles, showed heavy metal and natural radionuclide concentrations from one to three orders of magnitude higher than unperturbed soils. All these facts demonstrate the serious environmental impact produced by the PG stacks into their surroundings and the urgency of effective restoration measures.
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•Mixing of acidic phosphogypsum leachates with seawater.•Effects of pH increase in the behaviour of heavy metals and natural radionuclides.•Precipitation and/or adsorption onto the solid phase of Al, Fe, Cr, Zn, Cu, Pb.•Coprecipitation/adsorption of U-isotopes and 210Po.•Highly polluted precipitates by heavy metals and natural radionuclides.
Findings: The main finding is the evaluation of heavy metals and natural radionuclides behaviour during the mixing of PG leachates with seawater and the environmental impact due to the enrichment of these pollutants in the particulate phase.
Lactobacilli have been shown to promote health functions. In this study, we analyzed the mechanism by which four different strains of probiotics affected innate immunity, such as regulation of ROS, ...cytokines, phagocytosis, bactericidal activity, signaling by NF-κB pp65, and TLR2 activation. The production of ROS was dependent on the concentration and species of Lactobacillus. The results obtained from the tested strains (Lactobacillus rhamnosus GG, L. rhamnosus KLSD, L. helveticus IMAU70129, and L. casei IMAU60214) showed that strains induced early proinflammatory cytokines such as IL-8,TNF-α, IL-12p70, and IL-6. However, IL-1β expression was induced only by L. helveticus and L. casei strains (after 24 h stimulation). Phagocytosis and bactericidal activity of macrophages against various pathogens, such as S. aureus, S. typhimurium, and E. coli, were increased by pretreatment with Lactobacillus. The nuclear translocation NF-κB pp65 and TLR2-dependent signaling were also increased by treatment with the probiotics. Taken together, the experiments demonstrate that probiotic strains of Lactobacillus exert early immunostimulatory effects that may be directly linked to the initial inflammation of the response of human macrophages.
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