Methyl 6-bromo-7-meth­oxy-1,3-benzodioxole-5-carboxyl­ate

The non-H atoms of the title compound, C10H9BrO5, are essentially coplanar, with the exception of the ester group [the O=C—O—C torsion angle is −143.4 (3)°]

Efficient Commitment to Functional CD34+ Progenitor Cells from Human Bone Marrow Mesenchymal Stem-Cell-Derived Induced Pluripotent Stem Cells

The efficient commitment of a specialized cell type from induced pluripotent stem cells (iPSCs) without contamination from unknown substances is crucial to their use in clinical applications. Here, we propose that CD34+ progenitor cells, which retain hematopoietic and endothelial cell potential, could be efficiently obtained from iPSCs derived from human bone marrow mesenchymal stem cells (hBMMSC-iPSCs) with defined factors. By treatment with a cocktail containing mesodermal, hematopoietic, and endothelial inducers (BMP4, SCF, and VEGF, respectively) for 5 days, hBMMSC-iPSCs expressed the mesodermal transcription factors Brachyury and GATA-2 at higher levels than untreated groups (P<0.05). After culturing with another hematopoietic and endothelial inducer cocktail, including SCF, Flt3L, VEGF and IL-3, for an additional 7–9 days, CD34+ progenitor cells, which were undetectable in the initial iPSC cultures, reached nearly 20% of the total culture. This was greater than the relative number of progenitor cells produced from human-skin-fibroblast-derived iPSCs (hFib-iPSCs) or from the spontaneous differentiation groups (P<0.05), as assessed by flow cytometry analysis. These induced cells expressed hematopoietic transcription factors TAL-1 and SCL. They developed into various hematopoietic colonies when exposed to semisolid media with hematopoietic cytokines such as EPO and G-CSF. Hematopoietic cell lineages were identified by phenotype analysis with Wright-Giemsa staining. The endothelial potential of the cells was also verified by the confirmation of the formation of vascular tube-like structures and the expression of endothelial-specific markers CD31 and VE-CADHERIN. Efficient induction of CD34+ progenitor cells, which retain hematopoietic and endothelial cell potential with defined factors, provides an opportunity to obtain patient-specific cells for iPSC therapy and a useful model for the study of the mechanisms of hematopoiesis and drug screening

Synthesis and Characterization of Monodispersed Copper Colloids in Polar Solvents

A chemical reduction method for preparing monodispersed pure-phase copper colloids in water and ethylene glycol has been reported. Owing to the reduction property of ethylene glycol, the reaction rate in ethylene glycol is higher than that in water. In addition, the amount of reducing agent can be reduced largely. Ascorbic acid plays roles as reducing agent and antioxidant of colloidal copper, due to its ability to scavenge free radicals and reactive oxygen molecules. Thermogravimetric results reveal that the as-prepared copper nanoparticles have good stability, and they begin to be oxidized at above 210 °C. Polyvinyl pyrrolidone works both as size controller and polymeric capping agents, because it hinders the nuclei from aggregation through the polar groups, which strongly absorb the copper particles on the surface with coordination bonds

The Identification of Lymphocyte-Like Cells and Lymphoid-Related Genes in Amphioxus Indicates the Twilight for the Emergency of Adaptive Immune System

To seek evidence of a primitive adaptive immune system (AIS) before vertebrate, we examined whether lymphocytes or lymphocyte-like cells and the related molecules participating in the lymphocyte function existed in amphioxus. Anatomical analysis by electron microscopy revealed the presence of lymphocyte-like cells in gills, and these cells underwent morphological changes in response to microbial pathogens that are reminiscent of those of mammalian lymphocytes executing immune response to microbial challenge. In addition, a systematic comparative analysis of our cDNA database of amphioxus identified a large number of genes whose vertebrate counterparts are involved in lymphocyte function. Among these genes, several genes were found to be expressed in the vicinity of the lymphocyte-like cells by in situ hybridization and up-regulated after exposure to microbial pathogens. Our findings in the amphioxus indicate the twilight for the emergency of AIS before the invertebrate-vertebrate transition during evolution

Thermoelectric effects induced dendrite branching dynamics in pure substances: An insight from morphological theory

Insights on the mechanical behavior in materials highly depend upon sufficiently characterizing microstructure details at the relevant length scales. In this study, the side-branching dynamics of dendritic structures formation in pure substances is studied upon the phase-field simulations of crystallization with applied direct currents. The effect of heat diffusion (including thermoelectric effect and undercooling) on the dendritic development is investigated, and the characteristics of the primary arms and side-branches are identified by implementing the image recognition technique. Results indicate that increasing the latent heat release would firstly enhance the side-branching and then cause the side-branches re-melting with large heat extraction form the solid. The side-branching could be tailored by rationally controlling the applied electric filed as well the heat treatment, which could be a potential way to improve the mechanical properties in metallic materials via optimizing the microstructure

Petrology and zircon U-Pb dating of well-preserved eclogites from the Thongmon area in central Himalaya and their tectonic implications

The discovery of eclogites is reported within the Great Himalayan Crystalline Complexin the Thongmön area, central Himalaya, and their metamorphic evolution is deci-phered by petrographic studies, pseudosection modelling, and zircon dating. For thefirst time, omphacite has been found in the matrix of eclogites taken from a metamor-phic mafic lens. Two groups of garnet have been identified in the Thongmön eclogiteson the basis of major and rare earth elements and mineral inclusions. Core and interme-diate sections of garnet represent Grt I, in which the major elements (Ca, Mg, and Fe)show a nearly homogenous distribution with little or weak zonation. This Grt I displaysan almost flat chondrite‐normalized HREE pattern, and the main inclusions are amphi-bole, apatite, quartz, and abundant omphacite. Grt II, forms thin rims on large garnetgrains, and is characterized by rim‐ward Ca decrease and Mg increase and MREEenrichment relative to HREE and LREE. No amphibole inclusions are found in Grt II,indicating the decomposition of amphibole contributed to its MREE enrichment. Twometamorphic stages, recorded by matrix minerals and inclusions in garnet and zircon,outline the burial of the Thongmön eclogites and progressive metamorphic processesto the pressure peak: (a) the assemblage of amphibole–garnet–omphacite–phengite–ru-tile–quartz, with the phengite interpreted as having been replaced by Bt+Pl symplec-tites, represents the prograde amphibole eclogite facies stage M1(1), (b) in the peakeclogite facies [stage M1(2)], amphibole was lost and melting started. Based on thecompositions of garnet and omphacite inclusions, M1(1)is constrained to 19–20 kbarand 640–660°C and M1(2)occurred at >21 kbar, >750°C, with appearance of meltand its entrapment in metamorphic zircon. SHRIMP U–Pb dating of zircon from twoeclogite samples yielded consistent metamorphic ages of 16.7 ± 0.6 Ma and17.1 ± 0.4 Ma respectively. The metamorphic zircon grew concurrently with Grt II inthe peak eclogite facies. Thongmön eclogites characterized by the prograde metamor-phism from amphibolite facies to eclogite facies were formed by the continuing conti-nental subduction of Indian plate beneath the Euro‐Asian continent in the Miocene.National Natural Science Foundation of China, Grant/Award Number: 91755206, 4112106

Structural changes in the extracellular loop 2 of the murine KCC2 potassium chloride cotransporter modulate ion transport

K+-Cl- cotransporters (KCCs) play important roles in physiological processes such as inhibitory neurotransmission and cell-volume regulation. KCCs exhibit significant variations in K+ affinities, yet recent atomic structures demonstrated that K+- and Cl--binding sites are highly conserved, raising the question of whether additional structural elements may contribute to ion coordination. The termini and the large extracellular domain (ECD) of KCCs exhibit only low sequence identity and were already discussed as modulators of transport activity. Here, we used the extracellular loop 2 (EL2) that links transmembrane helices (TMs) 3 and 4, as a mechanism to modulate ECD folding. We compared consequences of point mutations in the K+-binding site on the function of WT KCC2 and in a KCC2 variant, in which EL2 was structurally altered by insertion of a IFYPYDVPDYAGYPYDVPDYAGSY-PYDVPDYAAHAAA (3xHA) tag (36 amino acids). In WT KCC2, individual mutations of five residues in the K+-binding site resulted in a 2- to 3-fold decreased transport rate. However, the same mutations in the KCC2 variant with EL2 structurally altered by insertion of a 3xHA tag had no effect on transport activity. Homology models of mouse KCC2 with the 3xHA tag inserted into EL2 using ab initio prediction were generated. The models suggest subtle conformational changes occur in the ECD upon EL2 modification. These data suggest that a conformational change in the ECD, for example, by interaction with EL2, might be an elegant way to modulate the K+ affinity of the different isoforms in the KCC subfamily

The early exhumation history of the Western Tianshan UHP metamorphic belt, China: New constraints from titanite U-Pb geochronology and thermobarometry

The Chinese Western Tianshan terrane is a well-known ultrahigh-pressure (UHP) metamorphic belt that mainly consists of subducted oceanic crustal materials. While two uplift stages have been recognized, the early exhumation history has not been fully constrained. We conducted U-Th-Pb and trace element microanalysis of titanite as well as zircon from UHP eclogites. Apart from several inclusions in garnet, three types of retrograde titanite have been identified based on their petrographic occurrences: (a) in matrix enclosing relict rutile; (b) as coarse-grained coronas around garnet; and (c) in veins coexisting with epidote and/or apatite. The three types of titanite are homogeneous in chemical composition, low in Al, enriched in middle rare earth elements (REEs), and depleted in light REEs and heavy REEs, suggesting their growth during retrograde decompression. Sensitive high-resolution ion microprobe (SHRIMP) and LA-ICP-MS U-Pb dating of titanite from four samples, regardless of their textural occurrences, gave consistent ages of c. 306Ma. Phase equilibria modelling and Zr-in-titanite thermometry indicate that titanite replaced rutile at similar to 14kbar and similar to 570 degrees C, following a nearly isothermal decompression from the UHP peak conditions of 30kbar and 550-570 degrees C. SHRIMP zircon U-Pb dating yields two age groups: c. 320Ma and c.305Ma. The former is generally interpreted to be the age of UHP stage. The latter, overlapping the titanite ages, represents the timing of titanite growth during exhumation. Thus, we estimate that the near-isothermal exhumation from the UHP peak conditions to the epidote-amphibolite facies retrogression (14kbar) lasted c.15Ma, corresponding to an average exhumation rate of 3.4 +/- 2.5mm/yr (2 sigma). This exhumation rate lies within the range of oceanic LT-HP belts in the absence of continental subduction, suggesting a similar slab exhumation mechanism that operates in the UHP regime. The consistent retrograde metamorphic ages recorded by titanite from different localities, and the general agreement among P-T paths in the adjacent area, suggest that the UHP unit of Western Tianshan metamorphic belt was likely exhumed as a coherent unit.the National Natural Science Foundation, Grant/Award Number: 41330210, 41702052; China Postdoctoral Science Foundation Funded Project, Grant/Award Number: 820140076

A hospital-associated measles outbreak in health workers in Beijing: Implications for measles elimination in China, 2018

Background: Since the National Action Plan for Measles Elimination 2006–2012 was released in 2006, China has entered into an era of accelerated measles elimination. Despite substantial decline, measles outbreak continued to occur mainly in a non-targeted population, in particular health workers due to occupational exposure. We investigated a measles outbreak in a Chinese medicine hospital, Beijing, in March 2018. Methods: Descriptive analysis was performed on epidemiology of the outbreak, clinical and laboratory evaluations, vaccination status of cases, and public health response. A case-control study was also conducted to identify the associated risk factors for measles. Results: From March 13, 2018, through March 27, 2018, a total of 11 measles cases in health workers were reported in Hospital X, Beijing. The median age of cases was 26 years (range, 21–53) and 4 (36.4%) were male. Of the 11 cases, ten had not been vaccinated or had unknown vaccination status; two occurred in emergency departments. No inpatients became infected, 141 (83.9%) of whom in affected departments were 55 years of age or older. The outbreak was confirmed by laboratory testing; the virus strain was genotype H1. The response activities included isolation of cases, and enhanced health surveillance of health workers and inpatients, particularly in affected departments. A total of 2234 doses of measles-containing vaccines (MCVs) were administered, covering 93.3% of susceptible health workers, in addition to 973 doses to the susceptible individuals in household and community. Lack of documentation of MCV vaccination before the outbreak was identified as a risk factor for measles (odd ratio: 3.333, 95% confidence interval: 1.295–8.621). Conclusions: High coverage of outbreak response immunization activities contributed largely to limit the spread of measles and might provide an indirect protection for inpatients. 2-Dose measles-containing vaccination of personnel in healthcare settings is warranted to prevent potential nosocomial transmission of measles. Keywords: Measles, Outbreak, Health workers, Vaccination, Measles eliminatio