BMP signals: Mediated by stroma or thymocytes?

This is an invited comment on the paper by Hager-Theodorides AL, et al. Cell Cycle 2014; 13:324–33; PMID:24240189; http://dx.doi.org/10.4161/cc.27118 which is published in the same journa

The transcriptional activator Gli2 modulates T-cell receptor signalling through attenuation of AP-1 and NFκB activity

Different tissues contain diverse and dynamic cellular niches, providing distinct signals to tissue-resident or migratory infiltrating immune cells. Hedgehog (Hh) proteins are secreted inter-cellular signalling molecules, which are essential during development and are important in cancer, post-natal tissue homeostasis and repair. Hh signalling mediated by the Hh-responsive transcription factor Gli2 also has multiple roles in T-lymphocyte development and differentiation.Here, we investigate the function of Gli2 in T-cell signalling and activation. Gene transcription driven by the Gli2 transcriptional activator isoform (Gli2A) attenuated T-cell activation and proliferation following T-cell receptor (TCR) stimulation. Expression of Gli2A in T-cells altered gene expression profiles, impaired the TCR-induced Ca2+ flux and nuclear expression of NFAT2, suppressed upregulation of molecules essential for activation, and attenuated signalling pathways upstream of the AP-1 and NFκB complexes, leading to reduced activation of these important transcription factors. Inhibition of physiological Hh-dependent transcription increased NFκB activity upon TCR ligation. These data are important for nderstanding the molecular mechanisms of immunomodulation, particularly in tissues where Hh proteins or other Gli-activating ligands such as TGFβ are upregulated, including during inflammation, tissue damage and repair, and in tumour microenvironments

Direct BMP2/4 signaling through BMP receptor IA regulates fetal thymocyte progenitor homeostasis and differentiation to CD4+CD8+double-positive cell

BMP2/4 signaling is required for embryogenesis and involved in thymus morphogenesis and T-lineage differentiation. In vitro experiments have shown that treatment of thymus explants with exogenous BMP4 negatively regulated differentiation of early thymocyte progenitors and the transition from CD4−CD8− (DN) to CD4+CD8+ (DP). Here we show that in vivo BMP2/4 signaling is required for fetal thymocyte progenitor homeostasis and expansion, but negatively regulates differentiation from DN to DP cell. Unexpectedly, conditional deletion of BMPRIA from fetal thymocytes (using the Cre-loxP system and directing excision to hematopoietic lineage cells with the Vav promoter) demonstrated that physiological levels of BMP2/4 signaling directly to thymocytes through BMPRIA are required for normal differentiation and expansion of early fetal DN thymocytes. In contrast, the arrest in early thymocyte progenitor differentiation caused by exogenous BMP4 treatment of thymus explants is induced in part by direct signaling to thymocytes through BMPRIA, and in part by indirect signaling through non-hematopoietic cells. Analysis of the transition from fetal DN to DP cell, both by ex vivo analysis of conditional BMPRIA-deficient thymocytes and by treatment of thymus explants with the BMP4-inhibitor Noggin demonstrated that BMP2/4 signaling is a negative regulator at this stage. We showed that at this stage of fetal T-cell development BMP2/4 signals directly to thymocytes through BMPRIA

Highway construction and maintenance equipment with machine and automotive repair shops for the reconstruction of the highways of the IV division, Ankara, Turkey

With the rapid advancements being made in travel and communication facilities today, the world is steadily growing smaller and people in the far places of the world are no longer strangers. There is no doubting the importance of tractors, dozers, scrapers, power shovels, graders, bituminus construction equipment, aggregate handling, etc., in the present-day world, in aiding the progress of civilization and bringing to all people the good things of life. It must be remembered that money expended for highways is not wasted, and can be classified as an asset. In substance, this is a general project for the reconstruction and improvement of the highways of the IVth Division, Ankara, Turkey, on a four year program, which will cover approximately 1,400 miles of modern roads. The project will consist mainly of: I. a) The type and size of roads that will be constructed. b) An approximate estimation of the amount of earth to be moved per average mile in order to bring the highways to grade. c) An approximate estimation of the quantity of materials necessary for the basing and surfacing of the roads. d) Selection of type, size, and quantity of road construction and maintenance equipment. e) Detail technical specifications of the forgone equipment. II. General outfits of machine and automotive repair shops for the maintenance and repairs of the above equipment, giving locations, general plans, tools and machinery. III. a) Initial cost of the road equipment. b) Initial cost of the shops (Hangars), tools and machinery --Preface, pages iv-v

Culture and chemotherapy of intestinal trichomonads of the Golden Hamster

Thesis (M.A.)--Boston UniversitySeveral culture media were tested. The trichomonads multiplied only in gastric mucin-Loeffler's dried blood serum dissolved in a slight modification of Drbohlav's modified Ringer's solution. Among the species of intestinal trichomonads of the golden hamster that were studied only T. microti and T. wenyoni grew in the artificial culture medium. Several techniques of determining whether or not the hamsters were infected with trichomonads, methods of obtaining population counts, and several staining methods were presented. Protozoa other than T. microti and T. wenyoni were successfully cultured in the modified culture medium. Bacteria-free cultures of trichomonads were assured by adding to the culture medium penicillin and streptomycin in combination, and also terramycin. Cysts induced artificially and those found in the animal's feces were activated by placing them in a warm place or by using aqueous pancreatin solution. These cysts multiplied in the modified culture medium. The resistance of the intestinal trichomonads of the golden hamster to physical and chemical agents was discussed. Many antiseptics, ultraviolet light, high temperatures and low temperatures are lethal for the trichomonads. The trichomonads are resistant to X-rays. Hypotonic or hypertonic solutions of sodium chloride are destructive for these trichomonads. Experiments in vitro, with penicillin, streptomycin, terramycin, aureomycin, ahloromycetin, Carbarsone, Chiniofon, copper sulfate, Phenothiazine were described. Experiments in vivo, with Carbarsone, Chinifon, Phenothiazine, copper sulfate, Vioform, terramycin, and aureomycin were described. Carbarsone showed the best trichomonadicidal action per os. The hamsters are extremely resistant to high doses of Carbarsone. Prolonged administration of Carbarsone is harmful to animals. The pathogenicity of the intestinal trichomonads of the golden hamster was examined. These trichomonads are not pathogenic for man or for the hamsters. The author swallowed a mixed culture of T. microti and T. wenyoni, but no digestive abnormalities were observed subsequently

The Effect of Developer-Specified Explanations for Permission Requests on Smartphone User Behavior

In Apple’s iOS 6, when an app requires access to a protected resource (e.g., location or photos), the user is prompted with a permission request that she can allow or deny. These permission request dialogs include space for developers to optionally include strings of text to explain to the user why access to the resource is needed. We examine how app developers are using this mechanism and the effect that it has on user behavior. Through an online survey of 772 smartphone users, we show that permission requests that include explanations are significantly more likely to be approved. At the same time, our analysis of 4,400 iOS apps shows that the adoption rate of this feature by developers is relatively small: around 19 % of permission requests include developer-specified explanations. Finally, we surveyed 30 iOS developers to better understand why they do or do not use this feature

The Greek people in America

Thesis (M.A.)--Boston Universit

Socialist influences on John Stuart Mill

Thesis (M.A.)--Boston Universit

The morphology & physiology of trichomonas gallinarum Martin and Robertson, 1911, with special reference to electron microscopy and sugar fermentation

Thesis (Ph.D.)--Boston UniversityThis study was undertaken with the aim of describing some aspects of the biology of T. gallinarum, a parasite widely spread among gallinaceous birds, with special emphasis on its fine structure and sugar fermentation. The morphology of T. gallinarum was studied with both conventional and electron microscopy [TRUNCATED