Mutations in SELENBP1, encoding a novel human methanethiol oxidase, cause extraoral halitosis

Selenium-binding protein 1 (SELENBP1) has been associated with several cancers, although its exact role is unknown. We show that SELENBP1 is a methanethiol oxidase (MTO), related to the MTO in methylotrophic bacteria, that converts methanethiol to H2O2, formaldehyde, and H2S, an activity not previously known to exist in humans. We identified mutations in SELENBP1 in five patients with cabbage-like breath odor. The malodor was attributable to high levels of methanethiol and dimethylsulfide, the main odorous compounds in their breath. Elevated urinary excretion of dimethylsulfoxide was associated with MTO deficiency. Patient fibroblasts had low SELENBP1 protein levels and were deficient in MTO enzymatic activity; these effects were reversed by lentivirus-mediated expression of wild-type SELENBP1. Selenbp1-knockout mice showed biochemical characteristics similar to those in humans. Our data reveal a potentially frequent inborn error of metabolism that results from MTO deficiency and leads to a malodor syndrome.info:eu-repo/semantics/publishedVersio

A Simple Evolutionary Model of Social Differentiation

Der Artikel erklärt mittels moderner evolutionstheoretischer Konzepte einen Prozess der sozialen Differenzierung. Er analysiert die diesbezüglichen konzeptuellen Schwächen der evolutionären Theorien von Parsons und Luhmann, um dann ein einfaches, vierstufiges Modell sozialer Differenzierung vorzustellen, das zu empirischen Forschungen genutzt werden kann.This article utilizes contemporary evolutionary theory to explain the rise of social differentiation and the increase in social diversity. It provides a conceptual analysis of the evolutionary theories of Parsons and Luhmann with an eye to avoiding some of the fallacies their critics have revealed and proposes a simple four-tier model of social differentiation that may serve as a guide in empirical research

Design for Mass Adaptation of the Neurointerventional Training Model HANNES with Patient-Specific Aneurysm Models

A neurointerventional training model called HANNES (Hamburg ANatomical NEurointerventional Simulator) has been developed to replace animal models in catheter-based aneurysm treatment training. A methodical approach to design for mass adaptation is applied so that patient-specific aneurysm models can be designed recurrently based on real patient data to be integrated into the training system. HANNES’ modular product structure designed for mass adaptation consists of predefined and individualized modules that can be combined for various training scenarios. Additively manufactured, individualized aneurysm models enable high reproducibility of real patient anatomies. Due to the implementation of a standardized individualization process, order-related adaptation can be realized for each new patient anatomy with modest effort. The paper proves how the application of design for mass adaptation leads to a well-designed modular product structure of the neurointerventional training model HANNES, which supports quality treatment and provides an animal-free and patient-specific training environment

PARL mediates Smac proteolytic maturation in mitochondria to promote apoptosis

Mitochondria drive apoptosis by releasing pro-apoptotic proteins that promote caspase activation in the cytosol. The rhomboid protease PARL, an intramembrane cleaving peptidase in the inner membrane, regulates mitophagy and plays an ill-defined role in apoptosis. Here, we employed PARL-based proteomics to define its substrate spectrum. Our data identified the mitochondrial pro-apoptotic protein Smac (also known as DIABLO) as a PARL substrate. In apoptotic cells, Smac is released into the cytosol and promotes caspase activity by inhibiting inhibitors of apoptosis (IAPs). Intramembrane cleavage of Smac by PARL generates an amino-terminal IAP-binding motif, which is required for its apoptotic activity. Loss of PARL impairs proteolytic maturation of Smac, which fails to bind XIAP. Smac peptidomimetics, downregulation of XIAP or cytosolic expression of cleaved Smac restores apoptosis in PARL-deficient cells. Our results reveal a pro-apoptotic function of PARL and identify PARL-mediated Smac processing and cytochrome c release facilitated by OPA1-dependent cristae remodelling as two independent pro-apoptotic pathways in mitochondria