1,030 research outputs found

    Ligand-receptor interactions elucidate sex-specific pathways in the trajectory from primordial germ cells to gonia during human development

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    The human germ cell lineage originates from primordial germ cells (PGCs), which are specified at approximately the third week of development. Our understanding of the signaling pathways that control this event has significantly increased in recent years and that has enabled the generation of PGC-like cells (PGCLCs) from pluripotent stem cells in vitro. However, the signaling pathways that drive the transition of PGCs into gonia (prospermatogonia in males or premeiotic oogonia in females) remain unclear, and we are presently unable to mimic this step in vitro in the absence of gonadal tissue. Therefore, we have analyzed single-cell transcriptomics data of human fetal gonads to map the molecular interactions during the sex-specific transition from PGCs to gonia. The CellPhoneDB algorithm was used to identify significant ligand-receptor interactions between germ cells and their sex-specific neighboring gonadal somatic cells, focusing on four major signaling pathways WNT, NOTCH, TGF beta/BMP, and receptor tyrosine kinases (RTK). Subsequently, the expression and intracellular localization of key effectors for these pathways were validated in human fetal gonads by immunostaining. This approach provided a systematic analysis of the signaling environment in developing human gonads and revealed sex-specific signaling pathways during human premeiotic germ cell development. This work serves as a foundation to understand the transition from PGCs to premeiotic oogonia or prospermatogonia and identifies sex-specific signaling pathways that are of interest in the step-by-step reconstitution of human gametogenesis in vitro.Stem cells & developmental biolog

    Extensive remineralization of peatland‐derived dissolved organic carbon and ocean acidification in the Sunda Shelf Sea, Southeast Asia

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    Southeast Asia is a hotspot of riverine export of terrigenous organic carbon to the ocean, accounting for ∼10% of the global land-to-ocean riverine flux of terrigenous dissolved organic carbon (tDOC). While anthropogenic disturbance is thought to have increased the tDOC loss from peatlands in Southeast Asia, the fate of this tDOC in the marine environment and the potential impacts of its remineralization on coastal ecosystems remain poorly understood. We collected a multi-year biogeochemical time series in the central Sunda Shelf (Singapore Strait), where the seasonal reversal of ocean currents delivers water masses from the South China Sea first before (during Northeast Monsoon) and then after (during Southwest Monsoon) they have mixed with run-off from peatlands on Sumatra. The concentration and stable isotope composition of DOC, and colored dissolved organic matter spectra, reveal a large input of tDOC to our site during Southwest Monsoon. Using isotope mass balance calculations, we show that 60%–70% of the original tDOC input is remineralized in the coastal waters of the Sunda Shelf, causing seasonal acidification. The persistent CO2 oversaturation drives a CO2 efflux of 2.4–4.9 mol m−2 yr−1 from the Singapore Strait, suggesting that a large proportion of the remineralized peatland tDOC is ultimately emitted to the atmosphere. However, incubation experiments show that the remaining 30%–40% tDOC exhibits surprisingly low lability to microbial and photochemical degradation, suggesting that up to 20%–30% of peatland tDOC might be relatively refractory and exported to the open ocean

    Proteomic profiling of proteins associated with the rejuvenation of Sequoia sempervirens (D. Don) Endl

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    Background: Restoration of rooting competence is important for rejuvenation in Sequoia sempervirens (D. Don) Endl and is achieved by repeatedly grafting Sequoia shoots after 16 and 30 years of cultivation in vitro. Results: Mass spectrometry-based proteomic analysis revealed three proteins that differentially accumulated in different rejuvenation stages, including oxygen-evolving enhancer protein 2 (OEE2), glycine-rich RNA-binding protein (RNP), and a thaumatin-like protein. OEE2 was found to be phosphorylated and a phosphopeptide (YEDNFDGNSNVSVMVpTPpTDK) was identified. Specifically, the protein levels of OEE2 increased as a result of grafting and displayed a higher abundance in plants during the juvenile and rejuvenated stages. Additionally, SsOEE2 displayed the highest expression levels in Sequoia shoots during the juvenile stage and less expression during the adult stage. The expression levels also steadily increased during grafting. Conclusion: Our results indicate a positive correlation between the gene and protein expression patterns of SsOEE2 and the rejuvenation process, suggesting that this gene is involved in the rejuvenation of Sequoia sempervirens

    Does entropic force always imply the Newtonian force law?

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    We study the entropic force by introducing a bound SA3/4S \le A^{3/4} between entropy and area which was derived by imposing the non-gravitational collapse condition. In this case, applying a modified entropic force to this system does not lead to the Newtonian force law.Comment: 11 pages, version to appear in EPJ

    A CSF-1R-blocking antibody/IL-10 fusion protein increases anti-tumor immunity by effectuating tumor-resident CD8<sup>+</sup> T cells.

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    Strategies to increase intratumoral concentrations of an anticancer agent are desirable to optimize its therapeutic potential when said agent is efficacious primarily within a tumor but also have significant systemic side effects. Here, we generate a bifunctional protein by fusing interleukin-10 (IL-10) to a colony-stimulating factor-1 receptor (CSF-1R)-blocking antibody. The fusion protein demonstrates significant antitumor activity in multiple cancer models, especially head and neck cancer. Moreover, this bifunctional protein not only leads to the anticipated reduction in tumor-associated macrophages but also triggers proliferation, activation, and metabolic reprogramming of CD8 &lt;sup&gt;+&lt;/sup&gt; T cells. Furthermore, it extends the clonotype diversity of tumor-infiltrated T cells and shifts the tumor microenvironment (TME) to an immune-active state. This study suggests an efficient strategy for designing immunotherapeutic agents by fusing a potent immunostimulatory molecule to an antibody targeting TME-enriched factors

    Magnetic-field and temperature dependence of the energy gap in InN nanobelt

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    We present tunneling measurements on an InN nanobelt which shows signatures of superconductivity. Superconducting transition takes place at temperature of 1.3K and the critical magnetic field is measured to be about 5.5kGs. The energy gap extrapolated to absolute temperature is about 110 mu eV. As the magnetic field is decreased to cross the critical magnetic field, the device shows a huge zero-bias magnetoresistance ratio of about 400%. This is attributed to the suppression of quasiparticle subgap tunneling in the presence of superconductivity. The measured magnetic-field and temperature dependence of the superconducting gap agree well with the reported dependences for conventional metallic superconductors. Copyright 2012 Author(s). This article is distributed under a Creative Commons Attribution 3.0 Unported License. [http://dx.doi.org/10.1063/1.3691830

    Characterization of the human fetal gonad and reproductive tract by single-cell transcriptomics

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    During human fetal development, sex differentiation occurs not only in the gonads but also in the adjacent developing reproductive tract. However, while the cellular composition of male and female human fetal gonads is well described, that of the adjacent developing reproductive tract remains poorly characterized. Here, we performed single-cell transcriptomics on male and female human fetal gonads together with the adjacent developing reproductive tract from first and second trimesters, highlighting the morphological and molecular changes during sex differentiation. We validated different cell populations of the developing reproductive tract and gonads and compared the molecular signatures between the first and second trimesters, as well as between sexes, to identify conserved and sex-specific features. Together, our study provides insights into human fetal sex-specific gonadogenesis and development of the reproductive tract beyond the gonads.</p
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