Martin Luther University of Halle-Wittenberg

About: Martin Luther University of Halle-Wittenberg is a education organization based out in Halle, Germany. It is known for research contribution in the topics: Population & Liquid crystal. The organization has 20232 authors who have published 38773 publications receiving 965004 citations. The organization is also known as: MLU & University of Wittenberg.

Intra-aortic balloon counterpulsation in patients with acute myocardial infarction complicated by cardiogenic shock: the prospective, randomized IABP SHOCK Trial for attenuation of multiorgan dysfunction syndrome.

Abstract: Objective: Patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction with cardiogenic shock (CS) are often treated with intra-aortic balloon pump counterpulsation (IABP), even though the evidence to support this is limited. We determined whether IABP as an addition to PCIcentered therapy ameliorates multiorgan dysfunction syndrome (MODS) in patients with acute myocardial infarction complicated by CS. Design: A prospective, randomized, controlled, open-label clinical trial recruiting patients between March 2003 and June 2004 (ClinicalTrials.gov ID NCT00469248). Setting: Tertiary care university hospital. Patients and Interventions: Forty-five consecutive patients with AMI and CS undergoing PCI were randomized to treatment with or without IABP. Measurements and Main Results: Acute Physiology and Chronic Health Evaluation (APACHE) II scores (primary outcome measure), hemodynamic values, inflammatory markers, and plasma brain natriuretic peptide (BNP) levels (secondary outcomes) were collected over 4 days from randomization. The prospective hypothesis was that adding IABP therapy to “standard care” would improve CS-triggered MODS. The addition of IABP to standard therapy did not result in a significant improvement in MODS (measured by serial APACHE II scoring over 4 days). IABP use had no significant effect on cardiac index or systemic inflammatory activation, although BNP levels were significantly lower in IABP-treated patients. Initial and serial APACHE II scoring correlated with mortality better than cardiac index, systemic inflammatory state, and BNP levels in this group of patients. Nonsurvivors had significantly higher initial APACHE II scores (29.9 2.88) than survivors (18.1 1.66, p < 0.05). Nevertheless, discrepancies among patients within the groups cannot be ruled out and might interfere with our results. Conclusions: In this randomized trial addressing addition of IABP in CS patients, mechanical support was associated only with modest effects on reduction of APACHE II score as a marker of severity of disease, improvement of cardiac index, reduction of inflammatory state, or reduction of BNP biomarker status compared with medical therapy alone. However, the limitations of our present trial preclude any definitive conclusion, but request for a larger prospective, randomized, multicentered trial with mortality as primary end point. (Crit Care Med 2010; 38:000‐000)

Structure of the human MHC-I peptide-loading complex

Abstract: The peptide-loading complex (PLC) is a transient, multisubunit membrane complex in the endoplasmic reticulum that is essential for establishing a hierarchical immune response. The PLC coordinates peptide translocation into the endoplasmic reticulum with loading and editing of major histocompatibility complex class I (MHC-I) molecules. After final proofreading in the PLC, stable peptide-MHC-I complexes are released to the cell surface to evoke a T-cell response against infected or malignant cells. Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin. The molecular organization of and mechanistic events that take place in the PLC are unknown owing to the heterogeneous composition and intrinsically dynamic nature of the complex. Here, we isolate human PLC from Burkitt's lymphoma cells using an engineered viral inhibitor as bait and determine the structure of native PLC by electron cryo-microscopy. Two endoplasmic reticulum-resident editing modules composed of tapasin, calreticulin, ERp57, and MHC-I are centred around TAP in a pseudo-symmetric orientation. A multivalent chaperone network within and across the editing modules establishes the proofreading function at two lateral binding platforms for MHC-I molecules. The lectin-like domain of calreticulin senses the MHC-I glycan, whereas the P domain reaches over the MHC-I peptide-binding pocket towards ERp57. This arrangement allows tapasin to facilitate peptide editing by clamping MHC-I. The translocation pathway of TAP opens out into a large endoplasmic reticulum lumenal cavity, confined by the membrane entry points of tapasin and MHC-I. Two lateral windows channel the antigenic peptides to MHC-I. Structures of PLC captured at distinct assembly states provide mechanistic insight into the recruitment and release of MHC-I. Our work defines the molecular symbiosis of an ABC transporter and an endoplasmic reticulum chaperone network in MHC-I assembly and provides insight into the onset of the adaptive immune response.

The fungal collaboration gradient dominates the root economics space in plants.

Abstract: Plant economics run on carbon and nutrients instead of money. Leaf strategies aboveground span an economic spectrum from "live fast and die young" to "slow and steady," but the economy defined by root strategies belowground remains unclear. Here, we take a holistic view of the belowground economy and show that root-mycorrhizal collaboration can short circuit a one-dimensional economic spectrum, providing an entire space of economic possibilities. Root trait data from 1810 species across the globe confirm a classical fast-slow "conservation" gradient but show that most variation is explained by an orthogonal "collaboration" gradient, ranging from "do-it-yourself" resource uptake to "outsourcing" of resource uptake to mycorrhizal fungi. This broadened "root economics space" provides a solid foundation for predictive understanding of belowground responses to changing environmental conditions.