16 research outputs found
Supermassive black holes at high redshifts
MeV blazars are the most luminous persistent sources in the Universe and emit
most of their energy in the MeV band. These objects display very large jet
powers and accretion luminosities and are known to host black holes with a mass
often exceeding . An MeV survey, performed by a new generation
MeV telescope which will bridge the entire energy and sensitivity gap between
the current generation of hard X-ray and gamma-ray instruments, will detect
1000 MeV blazars up to a redshift of . Here we show that this would
allow us: 1) to probe the formation and growth mechanisms of supermassive black
holes at high redshifts, 2) to pinpoint the location of the emission region in
powerful blazars, 3) to determine how accretion and black hole spin interplay
to power the jet.Comment: 7 pages, 4 figure. Submitted to the Astro2020 call for Science White
Paper
A hydrogel platform that incorporates laminin isoforms for efficient presentation of growth factors â neural growth and osteogenesis
Laminins (LMs) are important structural proteins of the extracellular matrix (ECM). The abundance of every LM isoform is tissueâdependent, suggesting that LM has tissueâspecific roles. LM binds growth factors (GFs), which are powerful cytokines widely used in tissue engineering due to their ability to control stem cell differentiation. Currently, the most commonly used ECM mimetic material in vitro is Matrigel, a matrix of undefined composition containing LM and various GFs, but subjected to batch variability and lacking control of physicochemical properties. Inspired by Matrigel, a new and completely defined hydrogel platform based on hybrid LMâpoly(ethylene glycol) (PEG) hydrogels with controllable stiffness (1â25 kPa) and degradability is proposed. Different LM isoforms are used to bind and efficiently display GFs (here, bone morphogenetic protein (BMPâ2) and betaânerve growth factor (ÎČâNGF)), enabling their solidâphase presentation at ultralow doses to specifically target a range of tissues. The potential of this platform to trigger stem cell differentiation toward osteogenic lineages and stimulate neural cells growth in 3D, is demonstrated. These hydrogels enable 3D, synthetic, defined composition, and reproducible cell culture microenvironments reflecting the complexity of the native ECM, where GFs in combination with LM isoforms yield the full diversity of cellular processes
Residual cancer burden after neoadjuvant chemotherapy and long-term survival outcomes in breast cancer: a multicentre pooled analysis of 5161 patients
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Early divergence of central and peripheral neural retina precursors during vertebrate eye development
BackgroundDuring development of the vertebrate eye, optic tissue is progressively compartmentalized into functionally distinct tissues. From the central to the peripheral optic cup, the original optic neuroepithelial tissue compartmentalizes, forming retina, ciliary body, and iris. The retina can be further sub-divided into peripheral and central compartments, where the central domain is specialized for higher visual acuity, having a higher ratio and density of cone photoreceptors in most species.ResultsClassically, models depict a segregation of the early optic cup into only two domains, neural and non-neural. Recent studies, however, uncovered discrete precursors for central and peripheral retina in the optic vesicle, indicating that the neural retina cannot be considered as a single unit with homogeneous specification and development. Instead, central and peripheral retina may be subject to distinct developmental pathways that underlie their specialization.ConclusionsThis review focuses on lineage relationships in the retina and revisits the historical context for segregation of central and peripheral retina precursors before overt eye morphogenesis
Murine Retroviruses Re-engineered for Lineage Tracing and Expression of Toxic Genes in the Developing Chick Embryo
We describe two replication incompetent retroviral vectors that co-express green fluorescent protein (GFP) and beta-galactosidase. These vectors incorporate either the avian reticuloendotheliosis (spleen necrosis virus; SNV) promoter or the chick beta-actin promoter, into the backbone of the murine leukemia (MLV) viral vector. the additional promoters drive transgene expression in avian tissue. the remainder of the vector is MLV-like, allowing high titer viral particle production by means of transient transfection. the SNV promoter produces high and early expression of introduced genes, enabling detection of the single copy integrated GFP gene in infected cells and their progeny in vivo. Substitution of the LacZ coding DNA with a relevant gene of interest will enable its co-expression with GFP, thus allowing visualization of the effect of specific and stable changes in gene expression throughout development. As the VSV-G pseudotyped viral vector is replication incompetent, changes in gene expression can be controlled temporally, by altering the timing of introduction. Developmental Dynamics 237.3260-3269, 2008. Published 2008 Wiley-Liss, Inc.Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USAUniversidade Federal de SĂŁo Paulo, Escola Paulista Med, Dept Bioquim, SĂŁo Paulo, BrazilUniversidade Federal de SĂŁo Paulo, Escola Paulista Med, Dept Bioquim, SĂŁo Paulo, BrazilWeb of Scienc
Mapping Central and Peripheral Eye Domains.
<p>Schematic summary of optic vesicle fate mapping results. <b>A:</b> Three distinct optic cup domains can be defined in the dorsal optic vesicle at HH9/10; OCL at the distal OV (green), central RPE situated more proximally (yellow), and central NR at the posterior OV (red). <b>B:</b> Distribution of dye from OV labeling in a forming optic cup at E3. Distinct central NR (red) and RPE (yellow) zones are constrained to the optic cup dorsal to the optic stalk. Distal OV/OCL label (green) distributes equally to inner and outer layers at initial OC stages. <b>C</b>: Representation of labeling results correlated with fate domains of NR, RPE, and anterior inner and outer eye fates at E4.5. Central RPE and NR zones remain restricted to the central eye. An anterior bias is evident in the extent of OCL derived OC tissue, which traverses the boundary between NR and presumptive ciliary body/iris. A-anterior, P-posterior, D-dorsal, V-ventral, Cen-central, Per-peripheral, L-lens, RPE-retinal pigmented epithelium, NR-neural retina, OV-optic vesicle, OCL-optic cup lip, OC-optic cup, se-surface ectoderm, os-optic stalk.</p
Identification of Central Optic Cup Fields in the Optic Vesicle.
<p><b>A:</b> Schematic dorsal view of an optic vesicle at HH9/10 summarizing non-distal OV zones. <b>B:</b> Dye targeted to the posterior OV (arrow). <b>CâE:</b> Coronal sections of B following re-incubation. <b>C:</b> Low magnification. <b>DâE:</b> Higher magnification showing dye distributed in the central neural retina (red arrows). Dye is excluded from the OCL and posterior RPE. <b>F:</b> Dorsal view with DiI at the distal OV (red arrow) and DiO proximal (green arrows). <b>GâI:</b> Coronal section through the embryo in F following reincubation. <b>G:</b> DiI is distributed to the OCL. The central limit of DiI distribution is indicated (red arrow). <b>H:</b> DiO is distributed through the central RPE. The peripheral limit of DiO distribution is indicated (green arrow). <b>I:</b> Composite of G/H. DiI (red) in the OCL and DiO (green) in the central RPE do not overlap. <b>J:</b> Dorsal view of dye label proximal in the OV (red arrow). <b>K:</b> The same embryo following re-incubation. Dye is constrained towards the back of the eye (arrow). Pink line marks boundary between lens and OCL. <b>LâN:</b> Coronal sections through the embryo in J, K. <b>L:</b> DiI (red arrows) is in the central RPE and brain (red arrows) but absent from other eye domains. <b>M:</b> Higher magnification of the boxed area in L. DiI (red arrows) is distributed in the central RPE and in the brain. <b>N:</b> More temporally positioned section through the optic stalk. DiI is distributed from the central RPE through the optic stalk to the brain (red arrows). <b>OâR:</b> Optic vesicle labeling distributing in non-eye tissues. <b>O, Q:</b> Optic vesicle labeling in HH9 embryos. <b>P, R:</b> Distribution of dye in the CNS (arrows) following the labeling in O and Q respectively. No dye was distributed to the eye. <b>S</b>: Scheme summarizing dye distribution of OV dye labels into the central OC. Central RPE arose from the dorsal OV (yellow) and central NR from the posterior OV, adjacent to paraxial mesoderm (red). Proximal OV label distributed label to the CNS (grey). OV-optic vesicle, CNS-central nervous system, L-lens, NR-neural retina, RPE-retinal pigmented epithelium, A-anterior, P-posterior, Pr-proximal, Di-distal, D-dorsal, V-ventral, b-brain, L-lens. Scale barsâ=â100 ”m.</p
The Expression of Eye Field Transcription Factors subdivides the Optic Vesicle.
<p><b>AâH</b>: Coronal sections through HH10 optic vesicles immuno-labeled as indicated on panels. <b>A:</b> DAPI stained coronal section, to highlight the relevant tissues. Asterisk indicates the paraxial mesenchyme in contact with the posterior optic vesicle. Green arrow indicates the targeted site of injection for labeling the central neural retina in previous figures. <b>B:</b> Graphic representation of sections with axes labeled for orientation. <b>CâF:</b> Single immunostaining as indicated. <b>G, H:</b> Double immunostaining as indicated. Scale Bar in A applies to panels CâH. Scale barsâ=â100 ”m.</p
The Peripheral not Central Optic Cup Originates in the Distal Optic Vesicle.
<p><b>A:</b> Scheme of the predicted distribution of dye directed to the OV of an HH10 embryo. The distal-most tip (red) is predicted to generate central neural retina. Central RPE is predicted to arise from the dorsal OV (yellow dots). OCL (green dots) origin is not known <b>B:</b> Dorsal view of a 12-somite embryo after DiI targeted to the distal OV (red arrow). <b>C:</b> Lateral view of the embryo in B following re-incubation. Dye distributed to the dorsal eye, from the OCL towards the central eye (white bar). Asterisk marks dye in the ectoderm. Pink line marks boundary between lens and OCL. <b>DâG:</b> Coronal sections of the embryo in B, C. <b>D:</b> Lower magnification for orientation. <b>EâF:</b> Dye in the dorsal OCL. Dye is present in the OCL and adjacent inner and outer layers (arrows). <b>G:</b> Dye is absent in both central neural retinal and RPE. <b>H:</b> DiI (red) and DiO (green) targeted to anterior and posterior distal OV. <b>I:</b> The embryo in H following re-incubation. DiO is distributed around the temporal OCL (green arrows) and DiI around the nasal OCL (red arrows). <b>JâK:</b> Transverse section through an embryo targeted at the anterior distal OV. Dye is restricted to the OCL and into the peripheral inner and outer layers (arrow). <b>L:</b> Graph showing dye distribution in the optic cup following distal OV labeling. Most embryos showed dye distributed to the OCL and excluded from the central neural retina or RPE. <b>M:</b> Scheme of the measuring strategy to analyze dye distribution. <b>N:</b> Plot of the distribution of distal OV targets against the midpoint of dye distribution around the OCL. Targeting through the posterior to anterior of the distal OV trends from temporal to nasal OCL. NR-neural retina, RPE-retinal pigmented epithelium, OCL-optic cup lip, L-lens, A-anterior, P-posterior, Pr-proximal, Di-distal, D-dorsal, V-ventral, T-temporal, N-nasal, OV-optic vesicle, OCL-optic cup lip. Scale barsâ=â100 ”m.</p