Unlike for Human Monocytes after LPS Activation, Release of TNF-α by THP-1 Cells Is Produced by a TACE Catalytically Different from Constitutive TACE

Tumor necrosis factor-alpha (TNF-α) is a pro-inflammatory cytokine today identified as a key mediator of several chronic inflammatory diseases. TNF-α, initially synthesized as a membrane-anchored precursor (pro-TNF-α), is processed by proteolytic cleavage to generate the secreted mature form. TNF-α converting enzyme (TACE) is currently the first and single protease described as responsible for the inducible release of soluble TNF-α.Here, we demonstrated the presence on THP-1 cells as on human monocytes of a constitutive proteolytical activity able to cleave pro-TNF-α. Revelation of the cell surface TACE protein expression confirmed that the observed catalytic activity is due to TACE. However, further studies using effective and innovative TNF-α inhibitors, as well as a highly selective TACE inhibitor, support the presence of a catalytically different sheddase activity on LPS activated THP-1 cells. It appears that this catalytically different TACE protease activity might have a significant contribution to TNF-α release in LPS activated THP-1 cells, by contrast to human monocytes where the TACE activity remains catalytically unchanged even after LPS activation.On the surface of LPS activated THP-1 cells we identified a releasing TNF-α activity, catalytically different from the sheddase activity observed on human monocytes from healthy donors. This catalytically-modified TACE activity is different from the constitutive shedding activity and appears only upon stimulation by LPS

An intestinal epithelial defect conferring ER stress results in inflammation involving both innate and adaptive immunity

We recently characterized Winnie mice carrying a missense mutation in Muc2, leading to severe endoplasmic reticulum stress in intestinal goblet cells and spontaneous colitis. In this study, we characterized the immune responses due to this intestinal epithelial dysfunction. In Winnie, there was a fourfold increase in activated dendritic cells (DCs; CD11c+ major histocompatibility complex (MHC) class IIhi) in the colonic lamina propria accompanied by decreased colonic secretion of an inhibitor of DC activation, thymic stromal lymphopoietin (TSLP). Winnie also displayed a significant increase in mRNA expression of the mucosal TH17 signature genes Il17a, IL17f, Tgfb, and Ccr6, particularly in the distal colon. Winnie mesenteric lymph node leukocytes secreted multiple TH1, TH2, and TH17 cytokines on activation, with a large increase in interleukin-17A (IL-17A) progressively with age. A major source of mucosal IL-17A in Winnie was CD4+ T lymphocytes. Loss of T and B lymphocytes in Rag1-/- × Winnie (RaW) crosses did not prevent spontaneous inflammation but did prevent progression with age in the colon but not the cecum. Adoptive transfer of naive T cells into RaW mice caused more rapid and severe colitis than in Rag1-/-, indicating that the epithelial defect results in an intestinal microenvironment conducive to T-cell activation. Thus, the Winnie primary epithelial defect results in complex multicytokine-mediated colitis involving both innate and adaptive immune components with a prominent IL-23/TH17 response, similar to that of human ulcerative colitis

Similar estimates of temperature impacts on global wheat yield by three independent methods

The potential impact of global temperature change on global crop yield has recently been assessed with different methods. Here we show that grid-based and point-based simulations and statistical regressions (from historic records), without deliberate adaptation or CO2 fertilization effects, produce similar estimates of temperature impact on wheat yields at global and national scales. With a 1 °C global temperature increase, global wheat yield is projected to decline between 4.1% and 6.4%. Projected relative temperature impacts from different methods were similar for major wheat-producing countries China, India, USA and France, but less so for Russia. Point-based and grid-based simulations, and to some extent the statistical regressions, were consistent in projecting that warmer regions are likely to suffer more yield loss with increasing temperature than cooler regions. By forming a multi-method ensemble, it was possible to quantify ‘method uncertainty’ in addition to model uncertainty. This significantly improves confidence in estimates of climate impacts on global food security.<br/

Piezobasiertes System erhöht Präzision der Werkzeug-Feinpositionierung

The adaptive spindle support is a piezo-based system, which can improve the properties of the cutting process for certain purposes, that is hard to realize by using conventional systems. The system has a good dynamic behavior and concurrently a high positioning accuracy. The process stability will be reached by moving small masses and the use of the structure-integrated piezo-based drives

The Pecan Shelling and Processing Industry: Practices, Problems, Prospects

Excerpt from the report preface: Pecan shelling and processing on a large-scale commercial basis is relatively new. Little information has been published concerning the industry--its size, location, and marketing practices and problems. Those who produce and market pecans long have been interested in the composition of the pecan-marketing complex and in how its efficiency might be improved. This study is part of a broad program of research aimed at improving market efficiency and expanding markets for farm products, including pecans

Aktive lagekorrektur einer HSC-Hauptspindel

Bei der Eigenschaftsverbesserung von Werkzeugmaschinen stehen die konkurrierenden Forderungen nach einer hohen Produktivität und gleichzeitig hoher Fertigungsqualität im Fokus der Entwicklungen. Die Kombination konventioneller Antriebe für die Hauptbewegungen mit hochdynamischen Zusatzantrieben für einzelne Baugruppen der Maschinenstruktur kann die Gesamtqualität der Positionierung deutlich verbessern und den konstruktiven Auslegungskonflikt reduzieren. Für die aktive Lagekorrektur eines Werkzeuges sind elektromechanische, elektromagnetische und piezoelektrische Verstellmechanismen bekannt. Kommerzielle Lösungen sind bisher nur für die einachsige Bewegung von Werkzeugen verfügbar. Im Auftrag eines Spindel-Herstellers wurde deshalb ein Mechanismus zur mehrachsigen Feinpositionierung einer HSC-Spindel (Leistung 20 kW) entwickelt. Im konkreten Fall werden fünf zusätzliche Bewegungsachsen realisiert

Effects and limits of adiabatic cutting in comparison to the conventional shear cutting process: Presentation held at STAHL 2009, 12. November 2009, CCD Congress Center Düsseldorf. Stahldialog - Innovationen für die Bearbeitung und Verarbeitung von Stahl.

In den vergangenen Jahren sind Anstrengungen unternommen worden, die Geschwindigkeit als wesentlichen Parameter auch für Schneid- und Trennprozesse zu nutzen. Das sogenannte Hochgeschwindigkeitsscherschneiden (HGSS) erfährt gegenwärtig und wohl auch in Zukunft einen Bedeutungszuwachs im Bereich der Blechbearbeitung. Bei dieser Technologie wird sich das frühzeitiges Scherversagen im Werkstoff durch die Erzeugung von Scherbändern zu Nutze gemacht, um eine besonders hohe Qualität der Trennflächen, d. h. gratarme, plane Trennschnitte, zu erzielen

FACTORS AFFECTING STRUCTURAL CHANGE IN AGRICULTURAL SUBSECTORS: IMPLICATIONS FOR RESEARCH

Industrial Organization,