Graft immaturity and safety concerns in transplanted human kidney organoids

For chronic kidney disease, regeneration of lost nephrons with human kidney organoids derived from induced pluripotent stem (iPS) cells is proposed to be an attractive potential therapeutic option. It remains unclear, however, whether organoids transplanted into kidneys in vivo would be safe or functional. Here, we purified kidney organoids and transplanted them beneath the kidney capsules of immunodeficient mice to test their safety and maturity. Kidney organoid grafts survived for months after transplantation and became vascularized from host mouse endothelial cells. Nephron-like structures in grafts appeared more mature than kidney organoids in vitro, but remained immature compared with the neighboring mouse kidney tissue. Ultrastructural analysis revealed filtration barrier-like structures, capillary lumens, and tubules with brush border in the transplanted kidney organoids, which were more mature than those of the kidney organoids in vitro but not as organized as adult mammalian kidneys. Immaturity was a common feature of three separate differentiation protocols by immunofluorescence analysis and single cell RNA sequencing. Stroma of transplanted kidney organoid grafts were filled with vimentin-positive mesenchymal cells, and chondrogenesis, cystogenesis, and stromal expansion were observed in the long term. Transcription profiles showed that long-term maintenance after kidney organoid transplantation induced transcriptomic reprogramming with prominent suppression of cell-cycle-related genes and upregulation of extracellular matrix organization. Our data suggest that kidney organoids derived from iPS cells may be transplantable but strategies to improve nephron differentiation and purity are required before they can be applied in humans as a therapeutic option.11Ysciescopuskc

Synthesis, structure and magnetic properties ofβ-MnO2nanorods

We present synthesis, structure and magnetic properties of structurally well-ordered single-crystalline β-MnO2nanorods of 50–100 nm diameter and several µm length. Thorough structural characterization shows that the basic β-MnO2material is covered by a thin surface layer (∼2.5 nm) of α-Mn2O3phase with a reduced Mn valence that adds its own magnetic signal to the total magnetization of the β-MnO2nanorods. The relatively complicated temperature-dependent magnetism of the nanorods can be explained in terms of a superposition of bulk magnetic properties of spatially segregated β-MnO2and α-Mn2O3constituent phases and the soft ferromagnetism of the thin interface layer between these two phases

Cosmological distance indicators

We review three distance measurement techniques beyond the local universe: (1) gravitational lens time delays, (2) baryon acoustic oscillation (BAO), and (3) HI intensity mapping. We describe the principles and theory behind each method, the ingredients needed for measuring such distances, the current observational results, and future prospects. Time delays from strongly lensed quasars currently provide constraints on $H_0$ with < 4% uncertainty, and with 1% within reach from ongoing surveys and efforts. Recent exciting discoveries of strongly lensed supernovae hold great promise for time-delay cosmography. BAO features have been detected in redshift surveys up to z <~ 0.8 with galaxies and z ~ 2 with Ly-$\alpha$ forest, providing precise distance measurements and $H_0$ with < 2% uncertainty in flat $\Lambda$CDM. Future BAO surveys will probe the distance scale with percent-level precision. HI intensity mapping has great potential to map BAO distances at z ~ 0.8 and beyond with precisions of a few percent. The next years ahead will be exciting as various cosmological probes reach 1% uncertainty in determining $H_0$, to assess the current tension in $H_0$ measurements that could indicate new physics.Comment: Review article accepted for publication in Space Science Reviews (Springer), 45 pages, 10 figures. Chapter of a special collection resulting from the May 2016 ISSI-BJ workshop on Astronomical Distance Determination in the Space Ag

Recognition of the Phanerozoic “Young Granite Gneiss” in the central Yeongnam Massif

Up to now, all the high-grade gneisses of the Korean peninsula have been regarded as Precambrian basement rocks and presence of the Phanerozoic high-grade metamorphic rocks have remained unknown. However, such granite gneiss is discovered through this study from the central Yeongnam massif near Gimcheon. SHRIMP zircon U-Pb age determinations on the granite gneiss, having well-developed gneissic foliations and migmatitic textures, reveal concordant age of ca. 250 Ma indicating the Early Triassic emplacement of this pluton, which is in contradict to the previous belief that it is a Precambrian product. Even though the granite gneiss reveals well-developed gneissic foliations and some zircons show rather low Th/U ratios, the metamorphic age has not been determined successfully. However, the age of metamorphism can be constrained as middle Triassic considering the absence of any evidences of metamorphism from the nearby granitic plutons having emplacement ages of ca. 225 Ma. Early Triassic emplacement and subsequent Middle Triassic metamorphism of the granite gneiss from the Yeongnam massif bear a remarkable resemblance to the case of South China block. We suggest the possibility that Early to Middle Triassic metamorphism of the Korean peninsula might be products of the intracontinental collisional events not directly related with the Early Triassic continental collision event

Search for Neutral Q-balls in Super-Kamiokande II

A search for Q-balls induced groups of successive contained events has been carried out in Super-Kamiokande II with 541.7 days of live time. Neutral Q-balls would emit pions when colliding with nuclei, generating a signal of successive contained pion events along a track. No candidate for successive contained event groups has been found in Super-Kamiokande II, so upper limits on the possible flux of such Q-balls have been obtained.Comment: 5 pages, 5 figures, Submitted to Phys. Lett.

Structures of DPAGT1 explain glycosylation disease mechanisms and advance TB antibiotic design

Summary: Protein N-glycosylation is a widespread post-translational modification. The first committed step in this process is catalysed by dolichyl-phosphate N-acetylglucosamine-phosphotransferase DPAGT1 (GPT/E.C. 2.7.8.15). Missense DPAGT1 variants cause congenital myasthenic syndrome and disorders of glycosylation. In addition, naturally-occurring bactericidal nucleoside analogues such as tunicamycin are toxic to eukaryotes due to DPAGT1 inhibition, preventing their clinical use. Our structures of DPAGT1 with the substrate UDP-GlcNAc and tunicamycin reveal substrate binding modes, suggest a mechanism of catalysis, provide an understanding of how mutations modulate activity (thus causing disease) and allow design of non-toxic “lipid-altered” tunicamycins. The structure-tuned activity of these analogues against several bacterial targets allowed the design of potent antibiotics for Mycobacterium tuberculosis, enabling treatment in vitro, in cellulo and in vivo, providing a promising new class of antimicrobial drug

Two-pion Bose-Einstein correlations in central Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV

The first measurement of two-pion Bose-Einstein correlations in central Pb-Pb collisions at $\sqrt{s_{\rm NN}} = 2.76$ TeV at the Large Hadron Collider is presented. We observe a growing trend with energy now not only for the longitudinal and the outward but also for the sideward pion source radius. The pion homogeneity volume and the decoupling time are significantly larger than those measured at RHIC.Comment: 17 pages, 5 captioned figures, 1 table, authors from page 12, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/388

Suppression of charged particle production at large transverse momentum in central Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}} = 2.76 TeV

Inclusive transverse momentum spectra of primary charged particles in Pb-Pb collisions at $\sqrt{s_{_{\rm NN}}}$ = 2.76 TeV have been measured by the ALICE Collaboration at the LHC. The data are presented for central and peripheral collisions, corresponding to 0-5% and 70-80% of the hadronic Pb-Pb cross section. The measured charged particle spectra in $|\eta|<0.8$ and $0.3 < p_T < 20$ GeV/$c$ are compared to the expectation in pp collisions at the same $\sqrt{s_{\rm NN}}$, scaled by the number of underlying nucleon-nucleon collisions. The comparison is expressed in terms of the nuclear modification factor $R_{\rm AA}$. The result indicates only weak medium effects ($R_{\rm AA} \approx$ 0.7) in peripheral collisions. In central collisions, $R_{\rm AA}$ reaches a minimum of about 0.14 at $p_{\rm T}=6$-7GeV/$c$ and increases significantly at larger $p_{\rm T}$. The measured suppression of high-$p_{\rm T}$ particles is stronger than that observed at lower collision energies, indicating that a very dense medium is formed in central Pb-Pb collisions at the LHC.Comment: 15 pages, 5 captioned figures, 3 tables, authors from page 10, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/98

School-based prevention for adolescent Internet addiction: prevention is the key. A systematic literature review

Adolescents’ media use represents a normative need for information, communication, recreation and functionality, yet problematic Internet use has increased. Given the arguably alarming prevalence rates worldwide and the increasingly problematic use of gaming and social media, the need for an integration of prevention efforts appears to be timely. The aim of this systematic literature review is (i) to identify school-based prevention programmes or protocols for Internet Addiction targeting adolescents within the school context and to examine the programmes’ effectiveness, and (ii) to highlight strengths, limitations, and best practices to inform the design of new initiatives, by capitalizing on these studies’ recommendations. The findings of the reviewed studies to date presented mixed outcomes and are in need of further empirical evidence. The current review identified the following needs to be addressed in future designs to: (i) define the clinical status of Internet Addiction more precisely, (ii) use more current psychometrically robust assessment tools for the measurement of effectiveness (based on the most recent empirical developments), (iii) reconsider the main outcome of Internet time reduction as it appears to be problematic, (iv) build methodologically sound evidence-based prevention programmes, (v) focus on skill enhancement and the use of protective and harm-reducing factors, and (vi) include IA as one of the risk behaviours in multi-risk behaviour interventions. These appear to be crucial factors in addressing future research designs and the formulation of new prevention initiatives. Validated findings could then inform promising strategies for IA and gaming prevention in public policy and education