Allogeneic Stem Cells Alter Gene Expression and Improve Healing of Distal Limb Wounds in Horses.

Distal extremity wounds are a significant clinical problem in horses and humans and may benefit from mesenchymal stem cell (MSC) therapy. This study evaluated the effects of direct wound treatment with allogeneic stem cells, in terms of gross, histologic, and transcriptional features of healing. Three full-thickness cutaneous wounds were created on each distal forelimb in six healthy horses, for a total of six wounds per horse. Umbilical cord-blood derived equine MSCs were applied to each wound 1 day after wound creation, in one of four forms: (a) normoxic- or (b) hypoxic-preconditioned cells injected into wound margins, or (c) normoxic- or (d) hypoxic-preconditioned cells embedded in an autologous fibrin gel and applied topically to the wound bed. Controls were one blank (saline) injected wound and one blank fibrin gel-treated wound per horse. Data were collected weekly for 6 weeks and included wound surface area, thermography, gene expression, and histologic scoring. Results indicated that MSC treatment by either delivery method was safe and improved histologic outcomes and wound area. Hypoxic-preconditioning did not offer an advantage. MSC treatment by injection resulted in statistically significant increases in transforming growth factor beta and cyclooxygenase-2 expression at week 1. Histologically, significantly more MSC-treated wounds were categorized as pro-healing than pro-inflammatory. Wound area was significantly affected by treatment: MSC-injected wounds were consistently smaller than gel-treated or control wounds. In conclusion, MSC therapy shows promise for distal extremity wounds in horses, particularly when applied by direct injection into the wound margin. Stem Cells Translational Medicine 2018;7:98-108

Respiratory Francisella tularensis Live Vaccine Strain Infection Induces Th17 Cells and Prostaglandin E2, Which Inhibits Generation of Gamma Interferon-Positive T Cells

Two key routes of Francisella tularensis infection are through the skin and airway. We wished to understand how the route of inoculation influenced the primary acute adaptive immune response. We show that an intranasal inoculation of the F. tularensis live vaccine strain (LVS) with a 1,000-fold-smaller dose than an intradermal dose results in similar growth kinetics and peak bacterial burdens. In spite of similar bacterial burdens, we demonstrate a difference in the quality, magnitude, and kinetics of the primary acute T-cell response depending on the route of inoculation. Further, we show that prostaglandin E2 secretion in the lung is responsible for the difference in the gamma interferon (IFN-γ) response. Intradermal inoculation led to a large number of IFN-γ+ T cells 7 days after infection in both the spleen and the lung. In contrast, intranasal inoculation induced a lower number of IFN-γ+ T cells in the spleen and lung but an increased number of Th17 cells in the lung. Intranasal infection also led to a significant increase of prostaglandin E2 (PGE2) in the bronchoalveolar lavage fluid. Inhibition of PGE2 production with indomethacin treatment resulted in increased numbers of IFN-γ+ T cells and decreased bacteremia in the lungs of intranasally inoculated mice. This research illuminates critical differences in acute adaptive immune responses between inhalational and dermal infection with F. tularensis LVS mediated by the innate immune system and PGE2

Fast detector of the ellipticity of infrared and terahertz radiation based on HgTe quantum well structures

We report a fast, room temperature detection scheme for the polarization ellipticity of laser radiation, with a bandwidth that stretches from the infrared to the terahertz range. The device consists of two elements, one in front of the other, that detect the polarization ellipticity and the azimuthal angle of the ellipse. The elements respectively utilise the circular photogalvanic effect in a narrow gap semiconductor and the linear photogalvanic effect in a bulk piezoelectric semiconductor. For the former we characterized both a HgTe quantum well and bulk Te, and for the latter, bulk GaAs. In contrast with optical methods our device is an easy to handle all-electric approach, which we demonstrated by applying a large number of different lasers from low power, continuous wave systems to high power, pulsed sources.Comment: 7 pages, 5 figure

Performance evaluation of a lossy transmission lines based diode detector at cryogenic temperature

This work is focused on the design, fabrication, and performance analysis of a square-law Schottky diodedetector based on lossy transmission lines working under cryogenic temperature (15 K). The design analysis of a microwave detector, based on a planar gallium-arsenide low effective Schottky barrier height diode, is reported, which is aimed for achieving large input return loss as well as flat sensitivity versus frequency. The designed circuit demonstrates good sensitivity, as well as a good return loss in a wide bandwidth at Ka-band, at both room (300 K) and cryogenic (15 K) temperatures. A good sensitivity of 1000 mV/mW and input return loss better than 12 dB have been achieved when it works as a zero-bias Schottky diodedetector at room temperature, increasing the sensitivity up to a minimum of 2200 mV/mW, with the need of a DC bias current, at cryogenic temperature.This work has been funded by the Spanish Ministry for Economy and Competitiveness under the CONSOLIDER-INGENIO 2010 programme under the Reference No. CSD2010-00064. The authors would like to thank Eva Cuerno and Ana Pérez for the assistance in the assembly of the circuit

Identification of a dominant CD4 T cell epitope in the membrane lipoprotein Tul4 from Francisella tularensis LVS

Francisella tularensis is a Gram-negative intracellular bacterium that is the causative agent of tularemia. Small mammals such as rodents and rabbits, as well as some biting arthropods, serve as the main vectors for environmental reservoirs of F. tularensis. The low infectious dose, ability to aerosolize the organism, and the possibility of generating antibiotic resistant strains make F. tularensis a prime organism for use in bioterrorism. As a result, some strains of F. tularensis have been placed on the CDC category A select agent list. T cell immune responses are thought to be a critical component in protective immunity to this organism. However, investigation into the immune responses to F. tularensis has been hampered by the lack of molecularly defined epitopes. Here we report the identification of a major CD4+ T cell epitope in C57Bl/6 (B6) mice. The murine model of F. tularensis infection is relevant as mice are a natural host for F. tularensis LVS and exhibit many of the same features of tularemia seen in humans. Using T cell hybridomas derived from B6 mice that had either been inoculated with F. tularensis and allowed to clear the infection or which had been immunized by conventional means using purified recombinant protein in adjuvant, we have identified amino acids 86–99 of the lipoprotein Tul4 (RLQWQAPEGSKCHD) as an immunodominant CD4 T cell epitope in B6 mice. This epitope is a major component of both the acute and memory responses to F. tularensis infection and can constitute as much as 20% of the responding CD4 T cells in an acute infection. Reactive T cells can also effectively enter the long-term memory T cell pool. The identification of this epitope will greatly aid in monitoring the course of F. tularensis infection and will also aid in the development of effective vaccine strategies for F. tularensis

Ovarian VEGF165b expression regulates follicular development, corpus luteum function and fertility

Angiogenesis and vascular regression are critical for the female ovulatory cycle. They enable progression and regression of follicular development, and corpora lutea formation and regression. Angiogenesis in the ovary occurs under the control of the vascular endothelial growth factor-A (VEGFA) family of proteins, which are generated as both pro-(VEGF165) and anti(VEGF165b)-angiogenic isoforms by alternative splicing. To determine the role of the VEGF165b isoforms in the ovulatory cycle, we measured VEGF165b expression in marmoset ovaries by immunohistochemistry and ELISA, and used transgenic mice over-expressing VEGF165b in the ovary. VEGF165b was expressed in the marmoset ovaries in granulosa cells and theca, and the balance of VEGF165b:VEGF165 was regulated during luteogenesis. Mice over-expressing VEGF165b in the ovary were less fertile than wild-type littermates, had reduced secondary and tertiary follicles after mating, increased atretic follicles, fewer corpora lutea and generated fewer embryos in the oviduct after mating, and these were more likely not to retain the corona radiata. These results indicate that the balance of VEGFA isoforms controls follicle progression and luteogenesis, and that control of isoform expression may regulate fertility in mammals, including in primates

Type-II GaAsSb/InP DHBTs with Record f T = 670 GHz and Simultaneous f T , f MAX > 400 GHz

For over 3 decades, the output power performance and power efficiencies of the leading solid-state source technology within the terahertz (THz) gap have been very low Permeable base transistors (PBT), which include almost all the salient yet favorable features of HBT and HEMT, were first proposed and demonstrated in GaAs in 1980 The performance of PBT can be enhanced in several ways. The most obvious method is to reduce the channel length to attain ballistic carrier transport with velocity overshoot. Unlike their HEMT counterparts, the deeply scaled PBT could still maintain very good short-channel integrity thanks to their multiple base finger electrode architecture. An exceedingly thin base electrode layer, however, would introduce a prohibitively large base resistance and degrade f max . An alternative approach is the introduction of high mobility semiconductor in the channel region. With the recent advancements in their growth technology, highest f T transistor demonstration, and higher saturation and overshoot velocity, high In content InGaAs-based compound semiconductors [3]-[5] could be employed to fabricate the PBT layer structures (and especially the base layer). These high mobility compound semiconductors have nonetheless relatively small bandgap energies that in turn induce a substantial base leakage current across the embedded electrode metal and emitter/channel/collector semiconductor Schottky junctions. In this work, a novel PBT structure with suppressed base current is proposed and evaluated. By wrapping the base finger electrode metal with an insulator, the low bandgap high mobility semiconductor in both the emitter and collector regions no longer makes Schottky contacts with the base electrodes that yield high leakage. Alternatively, the resultant insulator-semiconductor interfaces need to be carefully engineered to avoid Fermilevel pinning Reference