Signal transduction around thymic stromal lymphopoietin (TSLP) in atopic asthma

Thymic stromal lymphopoietin (TSLP), a novel interleukin-7-like cytokine, triggers dendritic cell-mediated inflammatory responses ultimately executed by T helper cells of the Th2 subtype. TSLP emerged as a central player in the development of allergic symptoms, especially in the airways, and is a prime regulatory cytokine at the interface of virus- or antigen-exposed epithelial cells and dendritic cells (DCs). DCs activated by epithelium-derived TSLP can promote naïve CD4+ T cells to adopt a Th2 phenotype, which in turn recruite eosinophilic and basophilic granulocytes as well as mast cells into the airway mucosa. These different cells secrete inflammatory cytokines and chemokines operative in inducing an allergic inflammation and atopic asthma. TSLP is, thus, involved in the control of both an innate and an adaptive immune response. Since TSLP links contact of allergen with the airway epithelium to the onset and maintainance of the asthmatic syndrome, defining the signal transduction underlying TSLP expression and function is of profound interest for a better understandimg of the disease and for the development of new therapeutics

Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study

Objective To determine whether use of cannabis in adolescence increases the risk for psychotic outcomes by affecting the incidence and persistence of subclinical expression of psychosis in the general population (that is, expression of psychosis below the level required for a clinical diagnosis)

Cosmopolitan geographic distribution of Phaeosaccion multiseriatum (Phaeosacciaceae, Phaeosacciophyceae), and description of P. westermeieri sp. nov. from Chile

Author Contributions: Conceptualization, A.F.P.; methodology, A.F.P.; software, A.F.P., N.J. and L.A.M.; validation, A.F.P.; formal analysis, L.A.M., A.F.P.; investigation, A.F.P., G.Y.C., A.R. and N.J.; resources, A.F.P, G.Y.C. and F.C.K.; data curation, A.F.P.; writing—original draft preparation, A.F.P.; writing—review and editing, A.F.P., M.D.G and all co-authors; visualization, A.F.P.; supervision, A.F.P.; project administration, A.F.P.; funding acquisition, A.F.P, G.Y.C. and F.C.K. The authors have accepted responsibility for the entire content of this manuscript and approved its submission. Persons: We appreciated assistance in the field by A. Montecinos, M.-L. Guillemin, S. Faugeron, E. Kytinou, Steve Cartwright and K.J. Yoon, and in the laboratory by H. Weitz.Peer reviewe

Metal-free syn-dioxygenation of alkenes

Reactions employing inexpensive reagents from sustainable sources and with low toxicity are becoming increasingly desirable from an academic and industrial perspective. A fascinating example of a synthetic transformation that requires development of alternative procedures is the osmium catalysed dihydroxylation. Recently there has been considerable interest in achieving this reaction through metal-free procedures. This review describes the methods available for metal-free syn-dioxygenation of alkenes

Therapeutic inhibition of FcgammaRIIb signaling targets leukemic stem cells in chronic myeloid leukemia

Despite the successes achieved with molecular targeted inhibition of the oncogenic driver Bcr-Abl in chronic myeloid leukemia (CML), the majority of patients still require lifelong tyrosine kinase inhibitor (TKI) therapy. This is primarily caused by resisting leukemic stem cells (LSCs), which prevent achievement of treatment-free remission in all patients. Here we describe the ITIM (immunoreceptor tyrosine-based inhibition motif)-containing Fc gamma receptor IIb (FcgammaRIIb, CD32b) for being critical in LSC resistance and show that targeting FcgammaRIIb downstream signaling, by using a Food and Drug Administration-approved BTK inhibitor, provides a successful therapeutic approach. First, we identified FcgammaRIIb upregulation in primary CML stem cells. FcgammaRIIb depletion caused reduced serial re-plaiting efficiency and cell proliferation in malignant cells. FcgammaRIIb targeting in both a transgenic and retroviral CML mouse model provided in vivo evidence for successful LSC reduction. Subsequently, we identified BTK as a main downstream mediator and targeting the Bcr-Abl-FcgammaRIIb-BTK axis in primary CML CD34(+) cells using ibrutinib, in combination with standard TKI therapy, significantly increased apoptosis in quiescent CML stem cells thereby contributing to the eradication of LSCs.. As a potential curative therapeutic approach, we therefore suggest combining Bcr-Abl TKI therapy along with BTK inhibition

Advanced location-based services

This special issue of Computer Communications presents state-of-the-art research and applications in the area of location-based services (LBS). Initial location-based services entered the market around the turn of the millennium and for the greater part appeared in the form of restaurant finders and tourist guides, which never gained widespread user acceptance. The reasons for this were numerous and ranged from inaccurate localization mechanisms like Cell-ID, little creativity in the design and functions of such services, to a generally low acceptance of data services. However, in recent years, there has been an increasing market penetration of GPS-capable mobile phones and devices, which not only support high-accuracy positioning, but also allow for the execution of sophisticated location-based applications due to fast mobile data services, remarkable computational power and high-resolution color displays. Furthermore, the popularity of these devices is accompanied by the emergence of new players in the LBS market, which offer real-time mapping, points-of-interest content, navigation support, and supplementary services. LBS have also received a significant boost by federal government agency mandates in emergency services, such as in the United States of America

Regulation of high mobility group box protein 1 expression following mechanical loading by orthodontic forces in vitro and in vivo

INTRODUCTION: The chromatin-binding protein high mobility group box protein 1 (HMGB1) can be released into the extracellular milieu by necrotic and damaged cells and functions as an alarmin that is recognized by the innate immune system to initiate and modulate tissue repair. However, little is known about the function of HMGB1 within orthodontic tooth movement. Therefore, it was the aim of the present study to investigate HMGB1 expression by periodontal ligament (PDL) cells challenged by mechanical loading similar to force levels being applied in orthodontic treatment in vitro and to transfer these findings to an in vivo microenvironment in an animal model of tooth movement in rats. In addition, we addressed the question of whether the regulation of HMGB1 expression is modulated in a time-dependent manner in zones of compressive forces. METHODS AND RESULTS: Protein analysis revealed a basal HMGB1 expression in PDL cell cultures and an increased expression when orthodontic forces were applied. In a rat model of tooth movement including 25 animals that received orthodontic tooth movement for 3, 6, 9, and 12 days, HMGB1 protein expression was demonstrated to be regulated in a time-dependent manner as determined by means of immunohistochemistry and histomorphometrical analyses. CONCLUSION: These data indicate a potential role for HMGB1 protein originating from PDL cells in the regulation of orthodontic tooth movement and the periodontal remodelling process by modifying the local microenvironment