Stem cell research tools in human metabolic disorders: An overview

Metabolic disorders are very common in the population worldwide and are among the diseases with the highest health utilization and costs per person. Despite the ongoing efforts to de-velop new treatments, currently, for many of these disorders, there are no approved therapies, re-sulting in a huge economic hit and tension for society. In this review, we recapitulate the recent advancements in stem cell (gene) therapy as potential tools for the long-term treatment of both inherited (lysosomal storage diseases) and acquired (diabetes mellitus, obesity) metabolic disorders, focusing on the main promising results observed in human patients and discussing the critical hur-dles preventing the definitive jump of this approach from the bench to the clinic

Analysis of the Expression of Neurotrophins and Their Receptors in Adult Zebrafish Kidney

Neurotrophins and their receptors are involved in the development and maintenance of neuronal populations. Different reports have shown that all neurotrophin/receptor pathways can also play a role in several non-neuronal tissues in vertebrates, including the kidney. These signaling pathways are involved in different events to ensure the correct functioning of the kidney, such as growth, differentiation, and regulation of renal tubule transport. Previous studies in some fish species have identified the neurotrophins and receptors in the kidney. In this study, for the first time, we compare the expression profiles (mRNA and protein) of all neurotrophin/receptor pathways in the kidney of the adult zebrafish. We quantify the levels of mRNA by using qPCR and identify the expression pattern of each neurotrophin/receptor pathway by in situ hybridization. Next, we detect the proteins using Western blotting and immunohistochemistry. Our results show that among all neurotrophins analyzed, NT-3/TrkC is the most expressed in the glomerule and tubule and in the hematopoietic cells, similar to what has been reported in the mammalian kidney

Adult neurogenesis and regeneration in zebrafish brain: Are the neurotrophins involved in?

Lette

Synthesis and photophysical characteristics of polyfluorene polyrotaxanes

Two alternating polyfluorene polyrotaxanes (3·TM-βCD and 3·TM-γCD) have been synthesized by the coupling of 2,7-dibromofluorene encapsulated into 2,3,6-tri-O-methyl-β- or γ-cyclodextrin (TM-βCD, TM-γCD) cavities with 9,9-dioctylfluorene-2,7-diboronic acid bis(1,3-propanediol) ester. Their optical, electrochemical and morphological properties have been evaluated and compared to those of the non-rotaxane counterpart 3. The influence of TM-βCD or TM-γCD encapsulation on the thermal stability, solubility in common organic solvents, film forming ability was also investigated. Polyrotaxane 3·TM-βCD exhibits a hypsochromic shift, while 3·TM-γCD displays a bathochromic with respect to the non-rotaxane 3 counterpart. For the diluted CHCl3 solutions the fluorescence lifetimes of all compounds follow a mono-exponential decay with a time constant of ≈0.6 ns. At higher concentration the fluorescence decay remains mono-exponential for 3·TM-βCD and polymers 3, with a lifetime τ = 0.7 ns and 0.8 ns, whereas the 3·TM-γCD polyrotaxane shows a bi-exponential decay consisting of a main component (with a weight of 98% of the total luminescence) with a relatively short decay constant of τ1 = 0.7 ns and a minor component with a longer lifetime of τ2 = 5.4 ns (2%). The electrochemical band gap (ΔEg) of 3·TM-βCD polyrotaxane is smaller than that of 3·TM-γCD and 3, respectively. The lower ΔEg value for 3·TM-βCD suggests that the encapsulation has a greater effect on the reduction process, which affects the LUMO energy level value. Based on AFM analysis, 3·TM-βCD and 3·TM-γCD polyrotaxane compounds exhibit a granular morphology with lower dispersity and smaller roughness exponent of the film surfaces in comparison with those of the neat copolymer 3

Synergistic prostaglandin E synthesis by myeloid and endothelial cells promotes fetal hematopoietic stem cell expansion in vertebrates

During development, hematopoietic stem cells (HSCs) are produced from the hemogenic endothelium and will expand in a transient hematopoietic niche. Prostaglandin E2 (PGE2) is essential during vertebrate development and HSC specification, but its precise source in the embryo remains elusive. Here, we show that in the zebrafish embryo, PGE2 synthesis genes are expressed by distinct stromal cell populations, myeloid (neutrophils, macrophages), and endothelial cells of the caudal hematopoietic tissue. Ablation of myeloid cells, which produce the PGE2 precursor prostaglandin H2 (PGH2), results in loss of HSCs in the caudal hematopoietic tissue, which could be rescued by exogeneous PGE2 or PGH2 supplementation. Endothelial cells contribute by expressing the PGH2 import transporter slco2b1 and ptges3, the enzyme converting PGH2 into PGE2. Of note, differential niche cell expression of PGE2 biosynthesis enzymes is also observed in the mouse fetal liver. Taken altogether, our data suggest that the triad composed of neutrophils, macrophages, and endothelial cells sequentially and synergistically contributes to blood stem cell expansion during vertebrate development

A connexin/ifi30 pathway bridges HSCs with their niche to dampen oxidative stress

Reactive oxygen species (ROS) represent a by-product of metabolism and their excess is toxic for hematopoietic stem and progenitor cells (HSPCs). During embryogenesis, a small number of HSPCs are produced from the hemogenic endothelium, before they colonize a transient organ where they expand, for example the fetal liver in mammals. In this study, we use zebrafish to understand the molecular mechanisms that are important in the caudal hematopoietic tissue (equivalent to the mammalian fetal liver) to promote HSPC expansion. High levels of ROS are deleterious for HSPCs in this niche, however this is rescued by addition of antioxidants. We show that Cx41.8 is important to lower ROS levels in HSPCs. We also demonstrate a new role for ifi30, known to be involved in the immune response. In the hematopoietic niche, Ifi30 can recycle oxidized glutathione to allow HSPCs to dampen their levels of ROS, a role that could be conserved in human fetal liver

Triazolobenzothiadiazole-Based Copolymers for Polymer Light-Emitting Diodes: Pure Near-Infrared Emission via Optimized Energy and Charge Transfer

A series of new near-infrared (NIR) emitting copolymers, based on a low band gap 6-(2-butyloctyl)-4,8-di(thiophen-2-yl)-[1,2,3]triazolo[4′,5′:4,5]benzo[1,2-c]-[1,2,5]thiadiazole (TBTTT) fluorophore copolymerized into a high band gap poly[3,3′-ditetradecyl-2,2′-bithiophene-5,5′-diyl-alt-5-(2-ethylhexyl)-4H-thieno[3,4-c]pyrrole-4,6(5H)-dione-1,3-diyl] (P2TTPD) host backbone, for polymer light-emitting diode (PLED) applications is reported. PLEDs fabricated from the host polymer (P2TTPD-0) show external quantum efficiencies (EQEs) up to 0.49% at 690 nm, with turn-on voltage (Von) at only 2.4 V. By incorporating the TBTTT segments into the host polymer backbone, pure NIR emission peaking at ca. 900 nm is obtained with Von remaining below 5 V. This work demonstrates that such a low Von can be attributed to efficient intrachain energy and/or charge transfer to the TBTTT sites. When the NIR emitting copolymer (P2TTPD-10) is blended with P2TTPD-0, the TBTTT are confined to well-separated polymer chains. As a result, the EQE from the blend is lower and the Von higher than that obtained from the pure copolymer (P2TTPD-1.0) with equal content of TBTTT. An analogous copolymer (P4T-1.0), consisting of poly[3,3′-ditetradecyl-2,2′:5′,2′′:5′′,2′′′-quaterthiophene-5,5′′′-diyl] (P4T) as the host and 1% TBTTT as the NIR emitter, further demonstrates that pure NIR emission can be obtained only through optimized molecular orbital energy levels, as in P2TTPD-1.0, which minimizes chances for either charge trapping or exciton splitting

Hapln1b, a central organizer of the ECM, modulates kit signaling to control developmental hematopoiesis in zebrafish

During early vertebrate development, hematopoietic stem and progenitor cells (HSPCs) are produced in hemogenic endothelium located in the dorsal aorta, before they migrate to a transient niche where they expand to the fetal liver and the caudal hematopoietic tissue, in mammals and zebrafish, respectively. In zebrafish, previous studies have shown that the extracellular matrix (ECM) around the aorta must be degraded to enable HSPCs to leave the aortic floor and reach blood circulation. However, the role of the ECM components in HSPC specification has never been addressed. In this study, hapln1b, a key component of the ECM, was specifically expressed in hematopoietic sites in the zebrafish embryo. Gain- and loss-of-function experiments all resulted in the absence of HSPCs in the early embryo, showing that hapln1b is necessary, at the correct level, to specify HSPCs in the hemogenic endothelium. Furthermore, the expression of hapln1b was necessary to maintain the integrity of the ECM through its link domain. By combining functional analyses and computer modeling, we showed that kitlgb interacts with the ECM to specify HSPCs. The findings show that the ECM is an integral component of the microenvironment and mediates the cytokine signaling that is necessary for HSPC specification

Strategies for organic VLC: Effects of clipping on the performance of multi-band CAP modulation with polymer-based light-emitting diodes

We investigate, for the first time, the effect of signal clipping on multi-band carrier-less amplitude and phase (m-CAP) modulation in visible light communications based on PLEDs. We experimentally demonstrate a Q-factor improvement up to ~2.25 dB can be obtained with a clipping level of 50%

Efficient red electroluminescence from diketopyrrolopyrrole copolymerised with a polyfluorene

We thank the EC Seventh Framework Programme (FP7/2007-2013) under Grant Agreement No. 212311 (ONE-P), the RTN THREADMILL (EU-Contract No.: MRTN-CT-2006-036040), the ITNs SUPERIOR (PITN-CT-2009-238177), and CONTEST (PITN-CT-2012-317488) as well as the Royal Society, and EPSRC for funding