Cap mesenchyme cell swarming during kidney development is influenced by attraction, repulsion, and adhesion to the ureteric tip

Morphogenesis of the mammalian kidney requires reciprocal interactions between two cellular domains at the periphery of the developing organ: the tips of the epithelial ureteric tree and adjacent regions of cap mesenchyme. While the presence of the cap mesenchyme is essential for ureteric branching, how it is specifically maintained at the tips is unclear. Using ex vivo timelapse imaging we show that cells of the cap mesenchyme are highly motile. Individual cap mesenchyme cells move within and between cap domains. They also attach and detach from the ureteric tip across time. Timelapse tracks collected for >800 cells showed evidence that this movement was largely stochastic, with cell autonomous migration influenced by opposing attractive, repulsive and cell adhesion cues. The resulting swarming behaviour maintains a distinct cap mesenchyme domain while facilitating dynamic remodelling in response to underlying changes in the tip

Dynamics and Excitation of Radio Galaxy Emission-Line Regions - I. PKS 2356-61

Results are presented from a programme of detailed longslit spectroscopic observations of the extended emission-line region (EELR) associated with the powerful radio galaxy PKS 2356-61. The observations have been used to construct spectroscopic datacubes, which yield detailed information on the spatial variations of emission-line ratios across the EELR, together with its kinematic structure. We present an extensive comparison between the data and results obtained from the MAPPINGS II shock ionization code, and show that the physical properties of the line-emitting gas, including its ionization, excitation, dynamics and overall energy budget, are entirely consistent with a scenario involving auto-ionizing shocks as the dominant ionization mechanism. This has the advantage of accounting for the observed EELR properties by means of a single physical process, thereby requiring less free parameters than the alternative scheme involving photoionization by radiation from the active nucleus. Finally, possible mechanisms of shock formation are considered in the context of the dynamics and origin of the gas, specifically scenarios involving infall or accretion of gas during an interaction between the host radio galaxy and a companion galaxy.Comment: 35 pages, LaTeX, uses aas2pp4.sty file, includes 9 PostScript figures. Two additional colour plates are available from the authors upon request. Accepted for publication in the Astrophysical Journa

Self-organisation after embryonic kidney dissociation is driven via selective adhesion of ureteric epithelial cells

Human pluripotent stem cells, after directed differentiation in vitro, can spontaneously generate complex tissues via self-organisation of the component cells. Self-organisation can also reform embryonic organ structure after tissue disruption. It has previously been demonstrated that dissociated embryonic kidneys can recreate component epithelial and mesenchymal relationships sufficient to allow continued kidney morphogenesis. Here, we investigate the timing and underlying mechanisms driving self-organisation after dissociation of the embryonic kidney using time-lapse imaging, high-resolution confocal analyses and mathematical modelling. Organotypic self-organisation sufficient for nephron initiation was observed within a 24 h period. This involved cell movement, with structure emerging after the clustering of ureteric epithelial cells, a process consistent with models of random cell movement with preferential cell adhesion. Ureteric epithelialisation rapidly followed the formation of ureteric cell clusters with the reformation of nephron-forming niches representing a later event. Disruption of P-cadherin interactions was seen to impair this ureteric epithelial cell clustering without affecting epithelial maturation. This understanding could facilitate improved regulation of patterning within organoids and facilitate kidney engineering approaches guided by cell-cell self-organisation

Constraining fundamental constants of physics with quasar absorption line systems

We summarize the attempts by our group and others to derive constraints on variations of fundamental constants over cosmic time using quasar absorption lines. Most upper limits reside in the range 0.5-1.5x10-5 at the 3sigma level over a redshift range of approximately 0.5-2.5 for the fine-structure constant, alpha, the proton-to-electron mass ratio, mu, and a combination of the proton gyromagnetic factor and the two previous constants, gp(alpha^2/mu)^nu, for only one claimed variation of alpha. It is therefore very important to perform new measurements to improve the sensitivity of the numerous methods to at least <0.1x10-5 which should be possible in the next few years. Future instrumentations on ELTs in the optical and/or ALMA, EVLA and SKA pathfinders in the radio will undoutedly boost this field by allowing to reach much better signal-to-noise ratios at higher spectral resolution and to perform measurements on molecules in the ISM of high redshift galaxies.Comment: 11 pages, 3 figure

Spatially Resolved Transcriptomes of Mammalian Kidneys Illustrate the Molecular Complexity and Interactions of Functional Nephron Segments

Available transcriptomes of the mammalian kidney provide limited information on the spatial interplay between different functional nephron structures due to the required dissociation of tissue with traditional transcriptome-based methodologies. A deeper understanding of the complexity of functional nephron structures requires a non-dissociative transcriptomics approach, such as spatial transcriptomics sequencing (ST-seq). We hypothesize that the application of ST-seq in normal mammalian kidneys will give transcriptomic insights within and across species of physiology at the functional structure level and cellular communication at the cell level. Here, we applied ST-seq in six mice and four human kidneys that were histologically absent of any overt pathology. We defined the location of specific nephron structures in the captured ST-seq datasets using three lines of evidence: pathologist's annotation, marker gene expression, and integration with public single-cell and/or single-nucleus RNA-sequencing datasets. We compared the mouse and human cortical kidney regions. In the human ST-seq datasets, we further investigated the cellular communication within glomeruli and regions of proximal tubules–peritubular capillaries by screening for co-expression of ligand–receptor gene pairs. Gene expression signatures of distinct nephron structures and microvascular regions were spatially resolved within the mouse and human ST-seq datasets. We identified 7,370 differentially expressed genes (padj < 0.05) distinguishing species, suggesting changes in energy production and metabolism in mouse cortical regions relative to human kidneys. Hundreds of potential ligand–receptor interactions were identified within glomeruli and regions of proximal tubules–peritubular capillaries, including known and novel interactions relevant to kidney physiology. Our application of ST-seq to normal human and murine kidneys confirms current knowledge and localization of transcripts within the kidney. Furthermore, the generated ST-seq datasets provide a valuable resource for the kidney community that can be used to inform future research into this complex organ

Millimeter imaging of submillimeter galaxies in the COSMOS field: Redshift distribution

We present new IRAM PdBI 1.3mm continuum observations at ~1.5" resolution of 28 SMGs previously discovered with the 870um bolometer LABOCA at APEX within the central 0.7deg2 of the COSMOS field. 19 out of the 28 LABOCA sources were detected with the PdBI at a >~3sigma level of ~1.4mJy/b. A combined analysis of this new sample with existing interferometrically identified SMGs in the COSMOS field yields the following results: 1) >~15%, and possibly up to ~40% of single-dish detected SMGs consist of multiple sources, 2) statistical identifications of multi-wavelength counterparts to the single-dish SMGs yield that only ~50% of these single-dish SMGs have real radio or IR counterparts, 3) ~18% of interferometric SMGs have only radio or even no multi-wavelength counterpart at all, and 4) ~50-70% of z>~3 SMGs have no radio counterparts down to an rms of 7-12uJy at 1.4GHz. Using the exact interferometric positions to identify proper multi-wavelength counterparts allows us to determine accurate photometric redshifts for these sources. The redshift distributions of the combined and the individual 1.1mm and 870um selected samples have a higher mean and broader width than the redshift distributions derived in previous studies. Our sample supports the previous tentative trend that on average brighter and/or mm-selected SMGs are located at higher redshifts. There is a tentative offset between the mean redshift for the 1.1mm (=3.1+/-0.4) and 870um (=2.6+/-0.4) selected samples, with the 1.1mm sources lying on average at higher redshifts. Based on our nearly complete sample of AzTEC 1.1mm SMGs within a uniform 0.15deg2 area we infer a higher surface density of z>~4 SMGs than predicted by current cosmological models. In summary, our findings imply that (sub-)millimeter interferometric identifications are crucial to build statistically complete and unbiased samples of SMGs.Comment: 35 pages, 18 figures, 10 tables; accepted for publication in A&

The Single-Particle density of States, Bound States, Phase-Shift Flip, and a Resonance in the Presence of an Aharonov-Bohm Potential

Both the nonrelativistic scattering and the spectrum in the presence of the Aharonov-Bohm potential are analyzed. The single-particle density of states (DOS) for different self-adjoint extensions is calculated. The DOS provides a link between different physical quantities and is a natural starting point for their calculation. The consequences of an asymmetry of the S matrix for the generic self-adjoint extension are examined. I. Introduction II. Impenetrable flux tube and the density of states III. Penetrable flux tube and self-adjoint extensions IV. The S matrix and scattering cross sections V. The Krein-Friedel formula and the resonance VI. Regularization VII. The R --> 0 limit and the interpretation of self-adjoint extensions VIII. Energy calculations IX. The Hall effect in the dilute vortex limit X. Persistent current of free electrons in the plane pierced by a flux tube XI. The 2nd virial coefficient of nonrelativistic interacting anyons XII. Discussion of the results and open questionsComment: 68 pages, plain latex, 7 figures, 3 references and one figure added plus a few minor text correction

Obscured Activity: AGN, Quasars, Starbursts and ULIGs observed by the Infrared Space Observatory

Some of the most active galaxies in the Universe are obscured by large quantities of dust and emit a substantial fraction of their bolometric luminosity in the infrared. Observations of these infrared luminous galaxies with the Infrared Space Observatory (ISO) have provided a relatively unabsorbed view to the sources fuelling this active emission. The improved sensitivity, spatial resolution and spectroscopic capability of ISO over its predecessor Infrared Astronomical Satellite (IRAS), has enabled significant advances in the understanding of the infrared properties of active galaxies. ISO surveyed a wide range of active galaxies which, in the context of this review, includes those powered by intense bursts of star-formation as well as those containing a dominant active galactic nucleus (AGN). Mid infrared imaging resolved for the first time the dust enshrouded nuclei in many nearby galaxies, while a new era in infrared spectroscopy was opened by probing a wealth of atomic, ionic and molecular lines as well as broad band features in the mid and far infrared. This was particularly useful since it resulted in the understanding of the power production, excitation and fuelling mechanisms in the nuclei of active galaxies including the intriguing but so far elusive ultraluminous infrared galaxies. Detailed studies of various classes of AGN and quasars greatly improved our understanding of the unification scenario. Far-infrared imaging and photometry also revealed the presence of a new very cold dust component in galaxies and furthered our knowledge of the far-infrared properties of faint starbursts, ULIGs and quasars. We summarise almost nine years of key results based upon ISO data spanning the full range of luminosity and type of active galaxies.Comment: Accepted for publication in 'ISO science legacy - a compact review of ISO major achievements', Space Science Reviews - dedicated ISO issue. To be published by Springer in 2005. 62 pages (low resolution figures version). Higher resolution PDFs available from http://users.physics.uoc.gr/~vassilis/papers/VermaA.pdf or http://www.iso.vilspa.esa.es/science/SSR/Verma.pd

Present-day scaling relations of submm galaxies: origin of spheroidal sytems

We analyse the spectral energy distributions (SEDs) of 23 submm galaxies and 3 ISO-detected EROs, all of which have the spectroscopic redshifts, by using an evolutionary SED model of starbursts. This SED model allows us to investigate intrinsic properties of starbursts, such as the starburst age and the mean stellar metallicity, as it takes into account the chemical evolution. Also, the intrinsic size of the starburst region is estimated from observed SEDs. Using this SED model, we predict colour, magnitude, and size of present-day descendants of submm galaxies, and derive scaling relations, such as the present-day colour-magnitude and size-magnitude relations. We argue that submm galaxies are the progenitors of present-day elliptical galaxies, provided that the initial mass function (IMF) of submm galaxies is slightly flatter than the Salpeter IMF. In this case, we find that 1) the mean present-day magnitude of submm galaxies is similar to that of L* elliptical galaxies, 2) the present-day colour-magnitude relation is consistent with that of elliptical galaxies, 3) the present-day size-magnitude relation of elliptical galaxies can be reproduced if massive submm galaxies consist of multiple starburst regions. We estimate the effect of feedback in submm galaxies as a function of starburst age. It is found that starburst regions in submm galaxies are likely to be self-regulated; i.e. the effect of feedback is nearly balanced with the self-gravity of starburst regions.Comment: 27 pages, submitted to MNRA

Polarity, cell division, and out-of-equilibrium dynamics control the growth of epithelial structures

The growth of a well-formed epithelial structure is governed by mechanical constraints, cellular apico-basal polarity, and spatially controlled cell division. Here we compared the predictions of a mathematical model of epithelial growth with the morphological analysis of 3D epithelial structures. In both in vitro cyst models and in developing epithelial structures in vivo, epithelial growth could take place close to or far from mechanical equilibrium, and was determined by the hierarchy of time-scales of cell division, cell-cell rearrangements, and lumen dynamics. Equilibrium properties could be inferred by the analysis of cell-cell contact topologies, and the nonequilibrium phenotype was altered by inhibiting ROCK activity. The occurrence of an aberrant multilumen phenotype was linked to fast nonequilibrium growth, even when geometric control of cell division was correctly enforced. We predicted and verified experimentally that slowing down cell division partially rescued a multilumen phenotype induced by altered polarity. These results improve our understanding of the development of epithelial organs and, ultimately, of carcinogenesi