Assembling kidney tissues from cells: the long road from organoids to organs

The field of regenerative medicine has witnessed significant advances that can pave the way to creating de novo organs. Organoids of brain, heart, intestine, liver, lung and also kidney have been developed by directed differentiation of pluripotent stem cells. While the success in producing tissue-specific units and organoids has been remarkable, the maintenance of an aggregation of such units in vitro is still a major challenge. While cell cultures are maintained by diffusion of oxygen and nutrients, three- dimensional in vitro organoids are generally limited in lifespan, size, and maturation due to the lack of a vascular system. Several groups have attempted to improve vascularization of organoids. Upon transplantation into a host, ramification of blood supply of host origin was observed within these organoids. Moreover, sustained circulation allows cells of an in vitro established renal organoid to mature and gain functionality in terms of absorption, secretion and filtration. Thus, the coordination of tissue differentiation and vascularization within developing organoids is an impending necessity to ensure survival, maturation, and functionality in vitro and tissue integration in vivo. In this review, we inquire how the foundation of circulation is laid down during the course of organogenesis, with special focus on the kidney. We will discuss whether nature offers a clue to assist the generation of a nephro-vascular unit that can attain functionality even prior to receiving external blood supply from a host. We revisit the steps that have been taken to induce nephrons and provide vascularity in lab grown tissues. We also discuss the possibilities offered by advancements in the field of vascular biology and developmental nephrology in order to achieve the long-term goal of producing transplantable kidneys in vitro

Controlling fast transport of cold trapped ions

We realize fast transport of ions in a segmented micro-structured Paul trap. The ion is shuttled over a distance of more than 10^4 times its groundstate wavefunction size during only 5 motional cycles of the trap (280 micro meter in 3.6 micro seconds). Starting from a ground-state-cooled ion, we find an optimized transport such that the energy increase is as low as 0.10 $\pm$ 0.01 motional quanta. In addition, we demonstrate that quantum information stored in a spin-motion entangled state is preserved throughout the transport. Shuttling operations are concatenated, as a proof-of-principle for the shuttling-based architecture to scalable ion trap quantum computing.Comment: 5 pages, 4 figure

A tunable high-pass filter for simple and inexpensive size-segregation of sub-10-nm nanoparticles

© The Author(s) 2017. Recent advanced in the fields of nanotechnology and atmospheric sciences underline the increasing need for sizing sub-10-nm aerosol particles in a simple yet efficient way. In this article, we develop, experimentally test and model the performance of a High-Pass Electrical Mobility Filter (HP-EMF) that can be used for sizing nanoparticles suspended in gaseous media. Experimental measurements of the penetration of nanoparticles having diameters down to ca 1nm through the HP-EMF are compared with predictions by an analytic, a semi-empirical and a numerical model. The results show that the HPEMF effectively filters nanoparticles below a threshold diameter with an extremely high level of sizing performance, while it is easier to use compared to existing nanoparticle sizing techniques through design simplifications. What is more, the HP-EMF is an inexpensive and compact tool, making it an enabling technology for a variety of applications ranging from nanomaterial synthesis to distributed monitoring of atmospheric nanoparticles

Structural basis of gene regulation by the Grainyhead/CP2 transcription factor family

Grainyhead (Grh)/CP2 transcription factors are highly conserved in multicellular organisms as key regulators of epithelial differentiation, organ development and skin barrier formation. In addition, they have been implicated as being tumor suppressors in a variety of human cancers. Despite their physiological importance, little is known about their structure and DNA binding mode. Here, we report the first structural study of mammalian Grh/CP2 factors. Crystal structures of the DNA-binding domains of grainyhead-like (Grhl) 1 and Grhl2 reveal a closely similar conformation with immunoglobulin-like core. Both share a common fold with the tumor suppressor p53, but differ in important structural features. The Grhl1 DNA-binding domain binds duplex DNA containing the consensus recognition element in a dimeric arrangement, supporting parsimonious target-sequence selection through two conserved arginine residues. We elucidate the molecular basis of a cancer-related mutation in Grhl1 involving one of these arginines, which completely abrogates DNA binding in biochemical assays and transcriptional activation of a reporter gene in a human cell line. Thus, our studies establish the structural basis of DNA target-site recognition by Grh transcription factors and reveal how tumor-associated mutations inactivate Grhl proteins. They may serve as points of departure for the structure-based development of Grh/CP2 inhibitors for therapeutic applications

Quantitative system drift compensates for altered maternal inputs to the gap gene network of the scuttle fly Megaselia abdita.

Published onlineJournal ArticleThis is the final version of the article. Available from eLife Sciences Publications via the DOI in this record.The segmentation gene network in insects can produce equivalent phenotypic outputs despite differences in upstream regulatory inputs between species. We investigate the mechanistic basis of this phenomenon through a systems-level analysis of the gap gene network in the scuttle fly Megaselia abdita (Phoridae). It combines quantification of gene expression at high spatio-temporal resolution with systematic knock-downs by RNA interference (RNAi). Initiation and dynamics of gap gene expression differ markedly between M. abdita and Drosophila melanogaster, while the output of the system converges to equivalent patterns at the end of the blastoderm stage. Although the qualitative structure of the gap gene network is conserved, there are differences in the strength of regulatory interactions between species. We term such network rewiring 'quantitative system drift'. It provides a mechanistic explanation for the developmental hourglass model in the dipteran lineage. Quantitative system drift is likely to be a widespread mechanism for developmental evolution.Ministerio de Economía y Competitividad MEC/EMBL Agreement/ BFU2009-10184/ BFU2012-33775/ SEV-2012-0208 Agència de Gestió d'Ajuts Universitaris I de Recerca SGR Grant 406 European Commission FP7-KBBE-2011-5/289434 National Science Foundation IOS-0719445/IOS-112121

The IgCAM CLMP regulates expression of Connexin43 and Connexin45 in intestinal and ureteral smooth muscle contraction in mice

CAR-like membrane protein (CLMP), an immunoglobulin cell adhesion molecule (IgCAM), has been implicated in congenital short-bowel syndrome in humans, a condition with high mortality for which there is currently no cure. We therefore studied the function of CLMP in a Clmp-deficient mouse model. Although we found that the levels of mRNAs encoding Connexin43 or Connexin45 were not or were only marginally affected, respectively, by Clmp deficiency, the absence of CLMP caused a severe reduction of both proteins in smooth muscle cells of the intestine and of Connexin43 in the ureter. Analysis of calcium signaling revealed a disordered cell-cell communication between smooth muscle cells, which in turn induced an impaired and uncoordinated motility of the intestine and the ureter. Consequently, insufficient transport of chyme and urine caused a fatal delay to thrive, a high rate of mortality, and provoked a severe hydronephrosis in CLMP knockouts. Neurotransmission and the capability of smooth muscle cells to contract in ring preparations of the intestine were not altered. Physical obstructions were not detectable and an overall normal histology in the intestine as well as in the ureter was observed, except for a slight hypertrophy of smooth muscle layers. Deletion of Clmp did not lead to a reduced length of the intestine as shown for the human CLMP gene but resulted in gut malrotations. In sum, the absence of CLMP caused functional obstructions in the intestinal tract and ureter by impaired peristaltic contractions most likely due to a lack of gap-junctional communication between smooth muscle cells

The rp-process and new measurements of beta-delayed proton decay of light Ag and Cd isotopes

Recent network calculations suggest that a high temperature rp-process could explain the abundances of light Mo and Ru isotopes, which have long challenged models of p-process nuclide production. Important ingredients to network calculations involving unstable nuclei near and at the proton drip line are $\beta$-halflives and decay modes, i.e., whether or not $\beta$-delayed proton decay takes place. Of particular importance to these network calculation are the proton-rich isotopes $^{96}$Ag, $^{98}$Ag, $^{96}$Cd and $^{98}$Cd. We report on recent measurements of $\beta$-delayed proton branching ratios for $^{96}$Ag, $^{98}$Ag, and $^{98}$Cd at the on-line mass separator at GSI.Comment: 4 pages, uses espcrc1.sty. Proceedings of the 4th International Symposium Nuclei in the Cosmos, June 1996, Notre Dame/IN, USA, Ed. M. Wiescher, to be published in Nucl.Phys.A. Also available at ftp://ftp.physics.ohio-state.edu/pub/nucex/nic96-gs

Aerosol Route to Antibacterial Nanosilver Coating of Cotton Fabrics

The paper describes a gas phase process for the preparation of cotton fabrics coated with silver nanoparticles as antimicrobial agents. Silver nanoparticles are synthesized by means of atmospheric pressure electrical discharges (spark discharge and glow discharge) in pure inert gases, and the aerosols are passed through cotton fabric samples, where nanoparticles deposit. The particle size distribution of the aerosols is measured online during synthesis. Also, the cristallinity, size and morphology of the silver particles are analyzed. The mean size of the primary particles of silver varies from 4 nm to 18 nm, depending upon the type of discharge, the nature and flow rate of the gas. The bactericidal activity of the cotton samples doped with silver nanoparticles is assessed following the ISO 20743 method. All cotton samples show significant bactericidal property, although it degrades with increasing primary particle size and particle agglomeration. This purely physical aerosol route is a promising sustainable method for nanocoating of textiles