Shrews as Reservoir Hosts of Borna Disease Virus

Borna disease virus (BDV) is the causative agent of severe T-cell–mediated meningoencephalitis in horses, sheep, and other animal species in central Europe. Here we report the first unequivocal detection of a BDV reservoir species, the bicolored white-toothed shrew, Crocidura leucodon, in an area in Switzerland with endemic Borna disease

IL-27 supports germinal center function by enhancing IL-21 production and the function of T follicular helper cells

IL-27 signaling directly into T cells is needed for follicular T helper cell survival, germinal center formation, and the production of T cell–dependent high-affinity antibodies in mice

Helminth immunomodulation in autoimmune disease

Helminths have evolved to become experts at subverting immune surveillance. Through potent and persistent immune tempering, helminths can remain undetected in human tissues for decades. Redirecting the immunomodulating "talents" of helminths to treat inflammatory human diseases is receiving intensive interest. Here, we review therapies using live parasitic worms, worm secretions, and worm-derived synthetic molecules to treat autoimmune disease. We review helminth therapy in both mouse models and clinical trials and discuss what is known on mechanisms of action. We also highlight current progress in characterizing promising new immunomodulatory molecules found in excretory/secretory products of helminths and their potential use as immunotherapies for acute and chronic inflammatory diseases

Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) No 2016/429):Koi herpes virus disease (KHV)

Abstract Koi herpes virus (KHV) disease has been assessed according to the criteria of the Animal Health Law (AHL), in particular criteria of Article 7 on disease profile and impacts, Article 5 on the eligibility of KHV disease to be listed, Article 9 for the categorisation of KHV disease according to disease prevention and control rules as in Annex IV and Article 8 on the list of animal species related to KHV disease. The assessment has been performed following a methodology composed of information collection and compilation, expert judgement on each criterion at individual and, if no consensus was reached before, also at collective level. The output is composed of the categorical answer, and for the questions where no consensus was reached, the different supporting views are reported. Details on the methodology used for this assessment are explained in a separate opinion. According to the assessment performed, it is inconclusive whether KHV disease can be considered eligible to be listed for Union intervention as laid down in Article 5(3) of the AHL because there was no full consensus on the criterion 5 A(v). Consequently, the assessment on compliance of KHV disease with the criteria as in Annex IV of the AHL, for the application of the disease prevention and control rules referred to in Article 9(1) is also inconclusive, as well as which animal species can be considered to be listed for KHV disease according to Article 8(3) of the AHL

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

The Importance of Richard Lionheart in the Third Crusade

The impact that King Richard III of England had on the third crusade is apparent through his limited strategic victories on the battlefield. Richard III did well with his limited resources, but ultimately failed to retake Jerusalem. Due to unforeseeable events, Richard III lost his military support before embarking on much of the campaign to regain the Holy Land. These events proved detrimental to his task. While he was an excellent strategist and fearsome leader, Richard III simply lacked the resources and troops to succeed. This paper argues that with more military support, Richard “The Lionheart” would have retaken the Holy Land from the Muslims

The Interconnection Between Law and Christianity in Medieval England

In England, the influence of Christian morals and beliefs grew rapidly during the medieval era. Religious beliefs were evident in literature, laws, as well as social hierarchy. The extent of religious influence on medieval English law is undeniable, however historians have yet to attain a full understanding of religious reach because of institutionalized relativism -- the concept that varying environments affect how social regulations are established in their area. This paper discusses two of the most prominent ways Christianity influenced medieval English law -- through direct influence on laws themselves as well as religious impact on the individual administrators of law -- while taking into consideration the undermined concept of institutionalized relativism

Schutz vor ethnisch-kultureller Diskriminierung in der Arbeitswelt trotz Vertragsfreiheit : ein Diskussionsbeitrag zur Frage der Notwendigkeit, Nützlichkeit und der inhaltlichen Ausgestaltung eines verstärkten Schutzes vor und bei ethnisch-kultureller Diskriminierung in der Arbeitswelt

Ethnisch-kulturelle Diskriminierung in der Arbeitswelt ist eine Realität. Auf der Suche nach Rechtsschutz sind die Opfer oft hilflos. Die juristischen, strukturellen, ökonomischen und psychischen Hürden sind meist zu hoch. Die Autorin und der Autor des folgenden Beitrags sind der Meinung, dass die Stärkung des Rechtsschutzes eine grund- und menschenrechtliche Pflicht ist, für die Opfer eine Dringlichkeit darstellt und der Gesamtgesellschaft von grossem Nutzen sein kann. Die Autoren plädieren – nebst weiteren Ansätzen – für ein Rahmengesetz zum Schutze vor und bei ethnisch-kultureller Diskriminierung. Sie diskutieren einzelne inhaltliche Aspekte eines solchen Gesetzes

A critical assessment of a new approach to identify pregnancy signals based on irregular incremental lines in the tooth cementum of recent and archaeological teeth

There is evidence from previous research that pregnancies and diseases are recorded in the human tooth cementum. This study aims to assess the degree of concordance between signals based on irregular incremental lines (ILs) in the tooth cementum and reported pregnancies in recent and archaeological human teeth. This research assessed a novel methodology to identify pregnancy signals based on irregular IL width and irregular appearance in terms of brightness and contrast. 156 histological sections of 24 recent teeth and 32 archaeological teeth from the skeleton series Basel-Spitalfriedhof (timeframe: 1845-1868) with known birth history were assessed microscopically blinded for any pregnancy history. As part of a pilot study non-invasive conventional micro computed tomography (µCT) and synchrotron radiation-based micro computed tomography (SRµCT) techniques have been explored in seven archaeological teeth from the Basel-Spitalfriedhof collection to display the tooth cementum. This work showed that pregnancies leave signals in the tooth cementum identifiable by the applied methodology in recent and also archaeological human teeth. More irregular ILs were observed in the archaeological sample, a group predominantly including women from the lower class in particular exposed to demanding life conditions. Not all pregnancies were identifiable and there are some hints that more demanding ones lead to identifiable signals. The SRµCT imaging technique allowed to display the ILs in a 3D view and to identify irregular ILs showing the potential of this technique to identify signals in the tooth cementum in a non-invasive manner. The results added to the evidence that the tooth cementum is a rich source of information able to support the reconstruction of life history events