Cytotoxicity of CD56bright NK Cells towards Autologous Activated CD4+ T Cells Is Mediated through NKG2D, LFA-1 and TRAIL and Dampened via CD94/NKG2A

In mouse models of chronic inflammatory diseases, Natural Killer (NK) cells can play an immunoregulatory role by eliminating chronically activated leukocytes. Indirect evidence suggests that NK cells may also be immunoregulatory in humans. Two subsets of human NK cells can be phenotypically distinguished as CD16+CD56dim and CD16dim/−CD56bright. An expansion in the CD56bright NK cell subset has been associated with clinical responses to therapy in various autoimmune diseases, suggesting an immunoregulatory role for this subset in vivo. Here we compared the regulation of activated human CD4+ T cells by CD56dim and CD56bright autologous NK cells in vitro. Both subsets efficiently killed activated, but not resting, CD4+ T cells. The activating receptor NKG2D, as well as the integrin LFA-1 and the TRAIL pathway, played important roles in this process. Degranulation by NK cells towards activated CD4+ T cells was enhanced by IL-2, IL-15, IL-12+IL-18 and IFN-α. Interestingly, IL-7 and IL-21 stimulated degranulation by CD56bright NK cells but not by CD56dim NK cells. NK cell killing of activated CD4+ T cells was suppressed by HLA-E on CD4+ T cells, as blocking the interaction between HLA-E and the inhibitory CD94/NKG2A NK cell receptor enhanced NK cell degranulation. This study provides new insight into CD56dim and CD56bright NK cell-mediated elimination of activated autologous CD4+ T cells, which potentially may provide an opportunity for therapeutic treatment of chronic inflammation

The Glasgow Outcome Scale -- 40 years of application and refinement

The Glasgow Outcome Scale (GOS) was first published in 1975 by Bryan Jennett and Michael Bond. With over 4,000 citations to the original paper, it is the most highly cited outcome measure in studies of brain injury and the second most-cited paper in clinical neurosurgery. The original GOS and the subsequently developed extended GOS (GOSE) are recommended by several national bodies as the outcome measure for major trauma and for head injury. The enduring appeal of the GOS is linked to its simplicity, short administration time, reliability and validity, stability, flexibility of administration (face-to-face, over the telephone and by post), cost-free availability and ease of access. These benefits apply to other derivatives of the scale, including the Glasgow Outcome at Discharge Scale (GODS) and the GOS paediatric revision. The GOS was devised to provide an overview of outcome and to focus on social recovery. Since the initial development of the GOS, there has been an increasing focus on the multidimensional nature of outcome after head injury. This Review charts the development of the GOS, its refinement and usage over the past 40 years, and considers its current and future roles in developing an understanding of brain injury

NK cells and cancer: you can teach innate cells new tricks

Natural killer (NK) cells are the prototype innate lymphoid cells endowed with potent cytolytic function that provide host defence against microbial infection and tumours. Here, we review evidence for the role of NK cells in immune surveillance against cancer and highlight new therapeutic approaches for targeting NK cells in the treatment of cancer

Developing a Maturity Model for Digital Servitization in Manufacturing Firms

In today’s rapidly changing markets, manufacturing firms are increasingly challenged by the convergence of digital technologies and servitization, which is defined as Digital Servitization. Enterprises struggle to grasp this phenomenon’s vision, constantly facing pressures to obtain and retain competitive advantage, inventing and reinventing new products and services, reducing costs and time to market, and enhancing quality at the same time. They need to define improvement actions to be taken to navigate through the transformation process and prioritize between different activities. Prior research has highlighted the importance of how to proceed into this transformation, however less emphasis has been put on suggesting suitable activities that fit the organization’s current status and future goals. To overcome this challenge, we propose a maturity model for digital servitization that serves as an assessment tool. The design of our maturity model is grounded in literature and expert interviews. During its evolutionary development, we gathered, structured and organized several critical requirements for digital servitization. We could also explore and highlight important attributes that must be examined by companies during the transformational process. We contribute by our proposed maturity model that serves companies not only as a diagnostics tool to assess the current situation, but also as a guideline for continuous improvement

The Rhyolitic Plateau of the Marifil Formation (Jurassic): A Gondwana Paleosurface in the Southeastern Portion of the Northern Patagonian Massif

Along the southeastern border of the Northern Patagonian Massif of the provinces of Río Negro and Chubut, an extensive surface is presently called the “Rhyolitic” or “Ignimbritic Plateau.” This large geomorphological unit has a geographical extension which exceeds 50,000 km2 and it is located between 40°30′ and 44° lat. S and between the Atlantic Ocean coast and 67°30′ long. W. It is characterized by a smooth topography of low and rounded hills, shallow endorheic basins, and a poorly integrated drainage network. The drainage network is mostly nonfunctional and roughly coincident with the bedrock fracture system. Bedrock is almost exclusively composed of the acid volcanic and pyroclastic rocks of the Marifil Formation of Early to Middle Jurassic age. A significant proportion of the identified positive landforms present form and nature very similar to that of “bornhardts,” as defined by Twidale (Revista de la Asociación Geológica Argentina 62(1):139–153, 2007), basically for granites. Bornhardts are uncovered dome hills (Twidale, Revista de la Asociación Geológica Argentina 62(1):139–153, 2007) which are usually frequent in Gondwana landscapes (Fairbridge, Encyclopedia of geomorphology. Ronald, New York, 1968). Furthermore, the ubiquitous presence of “corestones” (isolated, large, rounded boulders), which are taken as indicators of an ancient, deep weathering front, supports the hypothesis that these paleosurfaces were generated by long-term, intense chemical weathering processes. The deep weathering would have occurred over at least 25 Ma, between the Middle and Late Jurassic, under a hot and moist paleoenvironment and under extremely stable tectonic conditions. The mobilization, denudation, and later sedimentation of the regolith/saprolite formed under such conditions would have taken place during several erosion episodes, mostly under tectonic forcing, between the Late Jurassic and the Late Cretaceous. The important clay and other secondary mineral accumulations (some of them significant sources of uranium) in the region would have a direct genetic relationship with the development of these paleosurfaces. From the Late Miocene onwards, the colder and drier conditions that were imposed in the region by the uprising Andes and the establishment of mountain glaciers and ice caps during numerous glaciations allowed the modification of this landscape by hydro-eolian processes which generated the widely distributed endorheic depressions (locally known as “bajos sin salida”) by deflation and occasionally reworked the surviving rocky hills by abrasion.Fil: Martinez, Oscar A.. Universidad Nacional de la Patagonia "San Juan Bosco"; ArgentinaFil: Rabassa, Jorge Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; Argentin