Cetaceans (whales, dolphins, and porpoises) are a group of mammals adapted to various aquatic habitats, from oceans to freshwater rivers. We report the sequencing, de novo assembly and analysis of a finless porpoise genome, and the re-sequencing of an additional 48 finless porpoise individuals. We use these data to reconstruct the demographic history of finless porpoises from their origin to the occupation into the Yangtze River. Analyses of selection between marine and freshwater porpoises identify genes associated with renal water homeostasis and urea cycle, such as urea transporter 2 and angiotensin I-converting enzyme 2, which are likely adaptations associated with the difference in osmotic stress between ocean and rivers. Our results strongly suggest that the critically endangered Yangtze finless porpoises are reproductively isolated from other porpoise populations and harbor unique genetic adaptations, supporting that they should be considered a unique incipient species.
Telomerase consists of the catalytic protein TERT and the RNA TERC . Mutations in TERC are linked to human diseases, but the underlying mechanisms are poorly understood. Here we report that the RNA-binding protein HuR associates with TERC and promotes the assembly of the TERC /TERT complex by facilitating TERC C106 methylation. Dyskeratosis congenita (DC)-related TERC U100A mutation impair the association of HuR with TERC , thereby reducing C106 methylation. Two other TERC mutations linked to aplastic anemia and autosomal dominant DC, G107U, and GC107/108AG, likewise disrupt methylation at C106. Loss-of-HuR binding and hence lower TERC methylation leads to decreased telomerase activity and telomere shortening. Furthermore, HuR deficiency or mutation of mTERC HuR binding or methylation sites impair the renewal of mouse hematopoietic stem cells, recapitulating the bone marrow failure seen in DC. Collectively, our findings reveal a novel function of HuR, linking HuR to telomerase function and TERC -associated DC.
The low-cost room-temperature sodium-sulfur battery system is arousing extensive interest owing to its promise for large-scale applications. Although significant efforts have been made, resolving low sulfur reaction activity and severe polysulfide dissolution remains challenging. Here, a sulfur host comprised of atomic cobalt-decorated hollow carbon nanospheres is synthesized to enhance sulfur reactivity and to electrocatalytically reduce polysulfide into the final product, sodium sulfide. The constructed sulfur cathode delivers an initial reversible capacity of 1081 mA h g −1 with 64.7% sulfur utilization rate; significantly, the cell retained a high reversible capacity of 508 mA h g −1 at 100 mA g −1 after 600 cycles. An excellent rate capability is achieved with an average capacity of 220.3 mA h g −1 at the high current density of 5 A g −1 . Moreover, the electrocatalytic effects of atomic cobalt are clearly evidenced by operando Raman spectroscopy, synchrotron X-ray diffraction, and density functional theory.
As the black cesium lead iodide (CsPbI 3 ) tends to transit into a yellow δ-phase at ambient, it is imperative to develop a stabilized black phase for photovoltaic applications. Herein, we report a distorted black CsPbI 3 film by exploiting the synergistic effect of hydroiodic acid (HI) and phenylethylammonium iodide (PEAI) additives. It is found that the HI induces formation of hydrogen lead iodide (HPbI 3+x ), an intermediate to the distorted black phase with appropriate band gap of 1.69 eV; while PEAI provides nucleation for optimized crystallization. More importantly, it stabilizes the distorted black phase by hindering phase transition via its steric effects. Upon optimization, we have attained solar cell efficiency as high as 15.07%. Specifically, the bare cell without any encapsulation shows negligible efficiency loss after 300 h of light soaking. The device keeps 92% of its initial cell efficiency after being stored for 2 months under ambient conditions.
To balance immunity and tolerance, the endogenous pool of Foxp3 + regulatory T (T reg ) cells is tightly controlled, but the underlying mechanisms of this control remain poorly understood. Here we show that the number of T reg cells is negatively regulated by the kinase Lkb1 in dendritic cells (DCs). Conditional knockout of the Lkb1 gene in DCs leads to excessive T reg cell expansion in multiple organs and dampens antigen-specific T cell immunity. Lkb1-deficient DCs are capable of enhancing, compared with wild-type DCs, T reg cell proliferation via cell-cell contact involving the IKK/IKBα-independent activation of the NF-κB/OX40L pathway. Intriguingly, treating wild-type mice with lipopolysaccharide selectively depletes Lkb1 protein in DCs, resulting in T reg cell expansion and suppressed inflammatory injury upon subsequent challenge. Loss of Lkb1 does not obviously upregulate proinflammatory molecules expression on DCs. We thus identify Lkb1 as a regulatory switch in DCs for controlling T reg cell homeostasis, immune response and tolerance.
Basal-like breast cancer (BLBC) is an aggressive subtype with a strong tendency to metastasize. Due to the lack of effective chemotherapy, BLBC has a poor prognosis compared with luminal subtype breast cancer. MicroRNA-221 and -222 (miR-221/222) are overexpressed in BLBC and associate with metastasis as well as poor prognosis; however, the mechanisms by which miR-221/222 function as oncomiRs remain unknown. Here, we report that miR-221/222 expression is inversely correlated with Notch3 expression in breast cancer cell lines. Notch3 is known to be overexpressed in luminal breast cancer cells and inhibits epithelial to mesenchymal transition (EMT). We demonstrate that miR-221/222 target Notch3 by binding to its 3′ untranslated region and suppressing protein translation. Ectopic expression of miR-221/222 significantly promotes EMT, whereas overexpression of Notch3 intracellular domain attenuates the oncogenic function of miR-221/222, suggesting that miR-221/222 exerts its oncogenic role by negatively regulating Notch3. Taken together, our results elucidated that miR-221/222 promote EMT via targeting Notch3 in breast cancer cell lines suggesting that miR-221/222 can serve as a potential therapeutic target in BLBC.
Nonclassical state is an essential resource for quantum-enhancedcommunication, computing and metrology to outperform their classicalcounterpart. The nonclassical states that can operate at high bandwidth androom temperature while being compatible with quantum memory are highlydesirable to enable the scalability of quantum technologies. Here, we present adirect observation of broadband nonclasscal states in a room-temperaturelight-matter interface, where the atoms can also be controlled to store andinterfere with photons. With a single coupling pulse and far off-resonanceconfiguration, we are able to induce a multi-field interference between lightand atoms to create the desired nonclassical states by spectrally selecting thetwo correlated photons out of seven possible emissions. We explicitly confirmthe nonclassicality by observing a cross correlation up to 17 and a violationof Cauchy-Schwarz inequality with 568 standard deviations. Our resultsdemonstrate the potential of a state-built-in, broadband and room-temperaturelight-matter interface for scalable quantum information networks.