Erythroid-Specific Expression of β-globin from Sleeping Beauty-Transduced Human Hematopoietic Progenitor Cells

Gene therapy for sickle cell disease will require efficient delivery of a tightly regulated and stably expressed gene product to provide an effective therapy. In this study we utilized the non-viral Sleeping Beauty (SB) transposon system using the SB100X hyperactive transposase to transduce human cord blood CD34+ cells with DsRed and a hybrid IHK–β-globin transgene. IHK transduced cells were successfully differentiated into multiple lineages which all showed transgene integration. The mature erythroid cells had an increased β-globin to γ-globin ratio from 0.66±0.08 to 1.05±0.12 (p = 0.05), indicating expression of β-globin from the integrated SB transgene. IHK–β-globin mRNA was found in non-erythroid cell types, similar to native β-globin mRNA that was also expressed at low levels. Additional studies in the hematopoietic K562 cell line confirmed the ability of cHS4 insulator elements to protect DsRed and IHK–β-globin transgenes from silencing in long-term culture studies. Insulated transgenes had statistically significant improvement in the maintenance of long term expression, while preserving transgene regulation. These results support the use of Sleeping Beauty vectors in carrying an insulated IHK–β-globin transgene for gene therapy of sickle cell disease

Structure and dynamics of the shark assemblage off recife, northeastern Brazil

Understanding the ecological factors that regulate elasmobranch abundance in nearshore waters is essential to effectively manage coastal ecosystems and promote conservation. However, little is known about elasmobranch populations in the western South Atlantic Ocean. An 8-year, standardized longline and drumline survey conducted in nearshore waters off Recife, northeastern Brazil, allowed us to describe the shark assemblage and to monitor abundance dynamics using zero-inflated generalized additive models. This region is mostly used by several carcharhinids and one ginglymostomid, but sphyrnids are also present. Blacknose sharks, Carcharhinus acronotus, were mostly mature individuals and declined in abundance throughout the survey, contrasting with nurse sharks, Ginglymostoma cirratum, which proliferated possibly due to this species being prohibited from all harvest since 2004 in this region. Tiger sharks, Galeocerdo cuvier, were mostly juveniles smaller than 200 cm and seem to use nearshore waters off Recife between January and September. No long-term trend in tiger shark abundance was discernible. Spatial distribution was similar in true coastal species (i.e. blacknose and nurse sharks) whereas tiger sharks were most abundant at the middle continental shelf. The sea surface temperature, tidal amplitude, wind direction, water turbidity, and pluviosity were all selected to predict shark abundance off Recife. Interspecific variability in abundance dynamics across spatiotemporal and environmental gradients suggest that the ecological processes regulating shark abundance are generally independent between species, which could add complexity to multi-species fisheries management frameworks. Yet, further research is warranted to ascertain trends at population levels in the South Atlantic Ocean.State Government of Pernambuco, Brazil; Fundacao para a Ciencia e Tecnologia, Portugal [SFRH/BD/37065/2007]info:eu-repo/semantics/publishedVersio

Remineralization of particulate organic carbon in an ocean oxygen minimum zone

This work was funded by a NERC standard grant NE/E01559X/1

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

The synthesis and superconducting properties of the strontium copper oxy-fluoride SrCuO₂F_2+d

HIGH-PRESSURE synthesis has proved a useful technique for obtaining new, metastable copper oxide superconductors; for example, oxygen insertion into Sr2CuO3 at 6 GPa (ref. 1) yields superconducting Sr2CuO3.1, with transition temperature T(c) = 70 K, in which the superconducting CuO2 layers are generated by pressure-induced oxygen migration from apical to equatorial sites. Although the simple structure and high transition temperatures make this family (general formula Sr(n+1)Cu(n)O(2n+1+δ) of interest, the stringent synthesis conditions limit its value for applications. Here we report that fluorine insertion into Sr2CuO3 at ambient pressure causes related structural rearrangements to give superconducting Sr2CuO2F(2+δ) with a maximum T(c) of 46 K. In this synthesis, the structural changes previously initiated by the thermodynamic effects of high pressure are induced chemically under ambient conditions. The result is a superconducting oxy-fluoride in which fluorine plays a dominant structural role, rather than merely being an electronic dopant as in La2CuO4F(x) (ref. 2) and Nd2CuO(4- x)F(y) (ref. 3). | High-pressure synthesis has proved a useful technique for obtaining new, metastable copper oxide superconductors; for example, oxygen insertion into Sr2CuO3 at 6 GPa (ref. 1) yields superconducting Sr2CuO3.1, with transition temperature Tc = 70 K, in which the superconducting CuO2 layers are generated by pressure-induced oxygen migration from apical to equatorial sites. Although the simple structure and high transition temperatures make this family (general formula Srn+1CunO2n+1+δ) of interest, the stringent synthesis conditions limit its value for applications. Here we report that fluorine insertion into Sr2CuO3 at ambient pressure causes related structural rearrangements to give superconducting Sr2CuO2F2+δ with a maximum Tc of 46 K. In this synthesis, the structural changes previously initiated by the thermodynamic effects of high pressure are induced chemically under ambient conditions. The result is a superconducting oxy-fluoride in which fluorine plays a dominant structural role, rather than merely being an electronic dopant as in La2CuO4Fy (ref. 2) and Nd2CuO4-xFy (ref. 3)