Utilizing osteocyte derived factors to enhance cell viability and osteogenic matrix deposition within IPN hydrogels

Many bone defects arising due to traumatic injury, disease, or surgery are unable to regenerate, requiring intervention. More than four million graft procedures are performed each year to treat these defects making bone the second most commonly transplanted tissue worldwide. However, these types of graft suffer from a limited supply, a second surgical site, donor site morbidity, and pain. Due to the unmet clinical need for new materials to promote skeletal repair, this study aimed to produce novel biomimetic materials to enhance stem/stromal cell osteogenesis and bone repair by recapitulating aspects of the biophysical and biochemical cues found within the bone microenvironment. Utilizing a collagen type I-alginate interpenetrating polymer network we fabricated a material which mirrors the mechanical and structural properties of unmineralized bone, consisting of a porous fibrous matrix with a young's modulus of 64 kPa, both of which have been shown to enhance mesenchymal stromal/stem cell (MSC) osteogenesis. Moreover, by combining this material with biochemical paracrine factors released by statically cultured and mechanically stimulated osteocytes, we further mirrored the biochemical environment of the bone niche, enhancing stromal/stem cell viability, differentiation, and matrix deposition. Therefore, this biomimetic material represents a novel approach to promote skeletal repair

Porcine innate and adaptative immune responses to influenza and coronavirus infections

Both innate and adaptative immune responses contribute to the control of infectious diseases, including by limiting the spreading of zoonotic diseases from animal reservoirs to humans. Pigs represent an important animal reservoir for influenza virus infection of human populations and are also naturally infected by coronaviruses, an important group of viruses, which includes the recently emerged severe acute respiratory syndrome (SARS) virus. Studies on both innate and adaptative immune responses of pigs to influenza virus and coronaviruses contribute, therefore, to a better control of these infections in their natural hosts and will be briefly reviewed in this article. Pro-inflammatory cytokines, including type I interferon (IFN), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6), were found in lung secretions of influenza virus infected pigs, and correlated with the intensity of clinical signs, whereas prior vaccination against influenza strongly reduced the production of infectious virus and cytokines in the lungs upon challenge, which was associated with clinical protection. An early type I IFN production was also found in coronavirus infected pigs, including at mucosal sites. IFN induction by coronavirus is shown to involve interaction between a viral glycoprotein and a leukocyte subset, likely equivalent to plasmacytoid dendritic cells, present in the mucosae and associated lymphoid tissues. Given the IFN mediated antiviral and immunomodulatory effects, the use of IFN or IFN inducers may prove an efficient strategy for a better control of influenza virus and coronavirus infections in pigs. Because influenza and coronaviruses target mucosal surfaces, adaptative immune responses have to be characterized at mucosal sites. Thus, nasal and pulmonary antibody responses were analyzed in influenza virus infected or vaccinated pigs showing short-lived, but potentially protective local IgA and IgG antibody (Ab) responses. Interestingly, primary influenza virus infection induced long-lived increase of lung CD8(+) T cells and local lymphoproliferative responses. Pigs infected by a respiratory coronavirus (PRCV) showed virus-specific IgG Ab-secreting cells in the bronchial lymph nodes, whereas the transmissible gastroenteritis coronavirus (TGEV) induced more IgA Ab-secreting cells in gut tissues, which illustrates the importance of the route of antigen administration for inducing local immune effector mechanisms. Porcine viral infections provide, therefore, valuable models for evaluating the immune parameters that are important for controlling transmission of important viral zoonotic infections

Tough on Scholarship

This series of three articles (that\u27s why it\u27s a trilogy, duh-h-h) chronicles the legal-academic career of one S. Breckinridge Tushingham ( Breck for short). As the trilogy unfolds, Breck works his way up (or maybe it\u27s down) from his first academic position to an established professorship to dean of the South Soybean (Soso) State University law school. In the process of recording his professional history, and thus memorializing it for the ages, Breck provides (probably defamatory) insights into the American legal academy

Proteic nanostructures and their use in veterinary vaccinology

Breakthroughs in the understanding and manipulation of viral genomes have allowed the emergence of a new generation of subunit vaccines: the viral nanoparticles. Such particles are formed with recombinant surface proteins that can self-assemble into virus-like particles or with internal proteins that mimic the viral nucleocapsid. These nanostructures display characteristics valuable for vaccination purposes: they are inert which exclude risk of dissemination; they are highly immunogenic due to their repeated organization and due to their nanometric size that facilitates uptake by antigen-presenting cells; they can be used as a platform to anchor heterologous antigens and make multivalent vaccine. Within our research department, we have created nanoparticles with the nucleoprotein (N) of the respiratory syncytial virus, one of the main agents causing calves pneumonia. These particles have a ring shape and have about ten nanometers diameters. N-rings have the ability to interact with dendritic cells and make them mature. We have also shown that N-rings can stimulate protective immunity against infection, especially following mucosal delivery, which is a major challenge for subunit vaccinesLes avancées dans le décryptage et la manipulation des génomes viraux ont permis de concevoir une nouvelle génération de vaccins sous-unitaires: les nanoparticules virales. Ces assemblages sont formés soit par les protéines de surface du virus (VLP pour « virus-like particles ») ou de protéines internes comme celles de la nucléocapside. Ces nanostructures possèdent des qualités utiles en vaccination : elles sont inertes et donc sans danger de dissémination ; elles sont fortement immunogènes de par leur structure répétée et de par leur taille nanométrique adaptée à une prise en charge par les cellules présentatrices d’antigène ; elles peuvent servir de plate-forme pour ancrer des antigènes hétérologues et être la base de vaccins multivalents. Au sein de notre unité, nous avons généré des nanoparticules avec la nucléoprotéine du virus respiratoire syncytial, agent majeur des broncho-pneumonies chez les veaux. Ces particules se présentent sous la forme d’anneaux d’une dizaine de nanomètres de diamètre. Nous avons mis en évidence leur capacité à interagir avec les cellules dendritiques et à les activer. Nous avons également démontré leur capacité à stimuler des défenses immunitaires protectrices, y compris après administration mucosale ce qui est un défi majeur pour les vaccins non réplicatif

A new subunit vaccine based on nucleoprotein nanoparticles confers partial clinical and virological protection in calves against bovine respiratory syncytial virus

Human and bovine respiratory syncytial viruses (HRSV and BRSV) are two closely related, worldwide prevalent viruses that are the leading cause of severe airway disease in children and calves, respectively. Efficacy of commercial bovine vaccines needs improvement and no human vaccine is licensed yet. We reported that nasal vaccination with the HRSV nucleoprotein produced as recombinant ringshaped nanoparticles (NSRS) protects mice against a viral challenge with HRSV. The aim of this work was to evaluate this new vaccine that uses a conserved viral antigen, in calves, natural hosts for BRSV. Calves, free of colostral or natural anti-BRSV antibodies, were vaccinated with NSRS either intramuscularly, or both intramuscularly and intranasally using MontanideTM ISA71 and IMS4132 as adjuvants and challenged with BRSV. All vaccinated calves developed anti-N antibodies in blood and nasal secretions and N-specific cellular immunity in local lymph nodes. Clinical monitoring post-challenge demonstrated moderate respiratory pathology with local lung tissue consolidations for the non vaccinated calves that were significantly reduced in the vaccinated calves. Vaccinated calves had lower viral loads than the nonvaccinated control calves. Thus NSRS vaccination in calves provided cross-protective immunity against BRSV infection without adverse inflammatory reaction

Kinetics and Mechanism of the Reaction of Cl Atoms with HO 2 Radicals

ABSTRACT: The kinetics and mechanism of the reaction Cl ϩ HO 2 : products (1) have been studied in the temperature range 230-360 K and at total pressure of 1 Torr of helium using the discharge-flow mass spectrometric method. The following Arrhenius expression for the total rate constant was obtained either from the kinetics of HO 2 consumption in excess of Cl atoms or from the kinetics of Cl in excess of HO 2 : , where uncertainties are 95% confidence limits. The temperature-independent value of k 1 ϭ (4.4 Ϯ 0.6) ϫ 10 Ϫ11 cm 3 molecule Ϫ1 s Ϫ1 at T ϭ 230-360 K, which can be recommended from this study, agrees well with most recent studies and current recommendations. Both OH and ClO were detected as the products of reaction (1) and the rate constant for the channel forming these species, Cl ϩ HO 2 : OH ϩ ClO (1b), has been determined: k 1b ϭ (8.6 Ϯ 3.2) ϫ 10 Ϫ11 exp[Ϫ(660 Ϯ 100)/T] cm 3 molecule Ϫ1 s Ϫ1 (with k 1b ϭ (9.4 Ϯ 1.9) ϫ 10 Ϫ12 cm 3 molecule Ϫ1 s Ϫ1 at T ϭ 298 K), where uncertainties represent 95% confidence limits