Myelopoiesis in spleen-producing distinct dendritic-like cells

Dendritic cells (DC) represent a heterogeneous class of antigen presenting cells (APC). Previously we reported a distinct myeloid dendritic-like cell present in spleen, as an 'in vivo' counterpart to cells produced in murine spleen long-term cultures (LTC-DC). These cells, named 'L-DC', were found to be functionally and phenotypically distinct from conventional (c)DC, plasmacytoid (p)DC and monocytes. These results suggested that spleen may represent a niche for development of L-DC from endogenous progenitors. Adult murine spleen has now been investigated for the presence of L-DC progenitors. Lineage-negative (Lin)(-) ckit(lo) and Lin(-) ckit(hi) progenitor subsets were identified as candidate populations, and tested for ability to produce L-DC; 'in vitro' upon co-culture with the spleen stromal line STX3, and 'in vivo' after adoptive therapy into mice. Both subsets colonized STX3 stroma 'in vitro' for L-DC production, indicating that they contained either a common or two distinct progenitors for L-DC. However, only the Lin(-) ckit(hi) subset gave progeny cells after adoptive transfer into lethally irradiated mice. 'In vivo' development was however multilineage and not restricted to L-DC development. Multilineage reconstitution reflects long-term reconstituting haematopoietic stem cells (LT-HSC), suggesting a close relationship between L-DC progenitors and LT-HSC. L-DC were however produced 'in vivo' in much higher number than monocytes/macrophages and cDC, indicating the presence of a specific L-DC progenitor within the Lin(-) ckit(hi) subset. A model is advanced for development of L-DC directly from haematopoietic progenitors in spleen and dependent on the spleen microenvironmentNHMRC (National Health and Medical Research Council of Australia

Spleen as a Site for Hematopoiesis of a Distinct Antigen Presenting Cell Type

While spleen and other secondary tissue sites contribute to hematopoiesis, the nature of cells produced and the environment under which this happens are not fully defined. Evidence is reviewed here for hematopoiesis occurring in the spleen microenvironment leading to the production of tissue-specific antigen presenting cells. The novel dendritic-like cell identified in spleen is phenotypically and functionally distinct from other described antigen presenting cells. In order to identify these cells as distinct, it has been necessary to show that their lineage origin and progenitors differ from that of other known dendritic and myeloid cell types. The spleen therefore represents a distinct microenvironment for hematopoiesis of a novel myeloid cell arising from self-renewing hematopoietic stem cells (HSC) or progenitors endogenous to spleen

A Semi-Empirical Model of the Infra-Red Universe

We present a simple model of the infra-red universe, based as much as possible on local observations. We model the luminosity and number evolution of disk and starburst galaxies, including the effects of dust, gas and spectral evolution. Although simple, our approach is able to reproduce observations of galaxy number counts and the infra-red and sub-millimeter extra-galactic backgrounds. It provides a useful probe of galaxy formation and evolution out to high redshift. The model demonstrates the significant role of the starburst population and predicts high star formation rates at redshifts 3 to 4, consistent with recent extinction-corrected observations of Lyman break galaxies. Starbursting galaxies are predicted to dominate the current SCUBA surveys. Their star formation is driven predominantly by strong tidal interactions and mergers of galaxies. This leads to the creation of spheroidal stellar systems, which may act as the seeds for disk formation as gas infalls. We predict the present-day baryonic mass in bulges and halos is comparable to that in disks. From observations of the extra-galactic background, the model predicts that the vast majority of star formation in the Universe occurs at z<5.Comment: 23 pages including 9 figures. To appear in ApJ. Model results available electronically at http://astro.berkeley.edu/~jt/irmodel.htm

Global Star Formation Rates in Disk Galaxies and Circumnuclear Starbursts from Cloud Collisions

We invoke star formation triggered by cloud-cloud collisions to explain global star formation rates of disk galaxies and circumnuclear starbursts. Previous theories based on the growth rate of gravitational perturbations ignore the dynamically important presence of magnetic fields. Theories based on triggering by spiral density waves fail to explain star formation in systems without such waves. Furthermore, observations suggest gas and stellar disk instabilities are decoupled. Following Gammie, Ostriker & Jog (1991), the cloud collision rate is set by the shear velocity of encounters with initial impact parameters of a few tidal radii, due to differential rotation in the disk. This, together with the effective confinement of cloud orbits to a two dimensional plane, enhances the collision rate above that for particles in a three dimensional box. We predict Sigma_{SFR}(R) proportional to Sigma_{gas} Omega (1-0.7 beta). For constant circular velocity (beta = 0), this is in agreement with recent observations (Kennicutt 1998). We predict a B-band Tully-Fisher relation: L_{B} proportional to v_{circ}^{7/3}, also consistent with observations. As additional tests, we predict enhanced star formation in regions with relatively high shear rates, and lower star formation efficiencies in clouds of higher mass.Comment: 27 pages including 3 figures and 2 tables. Accepted to ApJ. Expanded statistical analysis of cloud SF efficiency test. Stylistic changes. Data for figures available electronically at http://astro.berkeley.edu/~jt/disksfr.htm

Clinical heterogeneity associated with KCNA1 mutations include cataplexy and nonataxic presentations

Mutations in the KCNA1 gene are known to cause episodic ataxia/myokymia syndrome type 1 (EA1). Here, we describe two families with unique presentations who were enrolled in an IRB-approved study, extensively phenotyped, and whole exome sequencing (WES) performed. Family 1 had a diagnosis of isolated cataplexy triggered by sudden physical exertion in multiple affected individuals with heterogeneous neurological findings. All enrolled affected members carried a KCNA1 c.941T>C (p.I314T) mutation. Family 2 had an 8-year-old patient with muscle spasms with rigidity for whom WES revealed a previously reported heterozygous missense mutation in KCNA1 c.677C>G (p.T226R), confirming the diagnosis of EA1 without ataxia. WES identified variants in KCNA1 that explain both phenotypes expanding the phenotypic spectrum of diseases associated with mutations of this gene. KCNA1 mutations should be considered in patients of all ages with episodic neurological phenotypes, even when ataxia is not present. This is an example of the power of genomic approaches to identify pathogenic mutations in unsuspected genes responsible for heterogeneous diseases

Efficient light-emitting diodes based on nanocrystalline perovskite in a dielectric polymer matrix.

Electroluminescence in light-emitting devices relies on the encounter and radiative recombination of electrons and holes in the emissive layer. In organometal halide perovskite light-emitting diodes, poor film formation creates electrical shunting paths, where injected charge carriers bypass the perovskite emitter, leading to a loss in electroluminescence yield. Here, we report a solution-processing method to block electrical shunts and thereby enhance electroluminescence quantum efficiency in perovskite devices. In this method, a blend of perovskite and a polyimide precursor dielectric (PIP) is solution-deposited to form perovskite nanocrystals in a thin-film matrix of PIP. The PIP forms a pinhole-free charge-blocking layer, while still allowing the embedded perovskite crystals to form electrical contact with the electron- and hole-injection layers. This modified structure reduces nonradiative current losses and improves quantum efficiency by 2 orders of magnitude, giving an external quantum efficiency of 1.2%. This simple technique provides an alternative route to circumvent film formation problems in perovskite optoelectronics and offers the possibility of flexible and high-performance light-emitting displays.The authors acknowledge funding from the Gates Cambridge Trust, the Singapore National Research Foundation (Energy Innovation Programme Office), the KACST-Cambridge University Joint Centre of Excellence, the Royal Society/Sino-British Fellowship Trust, and the Engineering and Physical Sciences Research Council, UK. We also thank Dr. Alessandro Sepe for helpful discussions of the XRD data.This is the final version of the article. It first appeared from ACS via http://dx.doi.org/10.1021/acs.nanolett.5b0023

GMC Collisions as Triggers of Star Formation. II. 3D Turbulent, Magnetized Simulations

We investigate giant molecular cloud (GMCs) collisions and their ability to induce gravitational instability and thus star formation. This mechanism may be a major driver of star formation activity in galactic disks. We carry out a series of three dimensional, magnetohydrodynamics (MHD), adaptive mesh refinement (AMR) simulations to study how cloud collisions trigger formation of dense filaments and clumps. Heating and cooling functions are implemented based on photo-dissociation region (PDR) models that span the atomic to molecular transition and can return detailed diagnostic information. The clouds are initialized with supersonic turbulence and a range of magnetic field strengths and orientations. Collisions at various velocities and impact parameters are investigated. Comparing and contrasting colliding and non-colliding cases, we characterize morphologies of dense gas, magnetic field structure, cloud kinematic signatures, and cloud dynamics. We present key observational diagnostics of cloud collisions, especially: relative orientations between magnetic fields and density structures, like filaments; 13CO(J=2-1), 13CO(J=3-2), and 12CO(J=8-7) integrated intensity maps and spectra; and cloud virial parameters. We compare these results to observed Galactic clouds

XBP1, Downstream of Blimp-1, Expands the Secretory Apparatus and Other Organelles, and Increases Protein Synthesis in Plasma Cell Differentiation

AbstractThe differentiation of B cells into immunoglobulin-secreting plasma cells is controlled by two transcription factors, Blimp-1 and XBP1. By gene expression profiling, we defined a set of genes whose induction during mouse plasmacytic differentiation is dependent on Blimp-1 and/or XBP1. Blimp-1-deficient B cells failed to upregulate most plasma cell-specific genes, including xbp1. Differentiating xbp1-deficient B cells induced Blimp-1 normally but failed to upregulate genes encoding many secretory pathway components. Conversely, ectopic expression of XBP1 induced a wide spectrum of secretory pathway genes and physically expanded the endoplasmic reticulum. In addition, XBP1 increased cell size, lysosome content, mitochondrial mass and function, ribosome numbers, and total protein synthesis. Thus, XBP1 coordinates diverse changes in cellular structure and function resulting in the characteristic phenotype of professional secretory cells