Petrophysical, Geochemical, and Hydrological Evidence for Extensive Fracture-Mediated Fluid and Heat Transport in the Alpine Fault's Hanging-Wall Damage Zone

International audienceFault rock assemblages reflect interaction between deformation, stress, temperature, fluid, and chemical regimes on distinct spatial and temporal scales at various positions in the crust. Here we interpret measurements made in the hanging‐wall of the Alpine Fault during the second stage of the Deep Fault Drilling Project (DFDP‐2). We present observational evidence for extensive fracturing and high hanging‐wall hydraulic conductivity (∼10−9 to 10−7 m/s, corresponding to permeability of ∼10−16 to 10−14 m2) extending several hundred meters from the fault's principal slip zone. Mud losses, gas chemistry anomalies, and petrophysical data indicate that a subset of fractures intersected by the borehole are capable of transmitting fluid volumes of several cubic meters on time scales of hours. DFDP‐2 observations and other data suggest that this hydrogeologically active portion of the fault zone in the hanging‐wall is several kilometers wide in the uppermost crust. This finding is consistent with numerical models of earthquake rupture and off‐fault damage. We conclude that the mechanically and hydrogeologically active part of the Alpine Fault is a more dynamic and extensive feature than commonly described in models based on exhumed faults. We propose that the hydrogeologically active damage zone of the Alpine Fault and other large active faults in areas of high topographic relief can be subdivided into an inner zone in which damage is controlled principally by earthquake rupture processes and an outer zone in which damage reflects coseismic shaking, strain accumulation and release on interseismic timescales, and inherited fracturing related to exhumation

Large-Scale Recombinant Production of the SARS-CoV-2 Proteome for High-Throughput and Structural Biology Applications

The highly infectious disease COVID-19 caused by the Betacoronavirus SARS-CoV-2 poses a severe threat to humanity and demands the redirection of scientific efforts and criteria to organized research projects. The international COVID19-NMR consortium seeks to provide such new approaches by gathering scientific expertise worldwide. In particular, making available viral proteins and RNAs will pave the way to understanding the SARS-CoV-2 molecular components in detail. The research in COVID19-NMR and the resources provided through the consortium are fully disclosed to accelerate access and exploitation. NMR investigations of the viral molecular components are designated to provide the essential basis for further work, including macromolecular interaction studies and high-throughput drug screening. Here, we present the extensive catalog of a holistic SARS-CoV-2 protein preparation approach based on the consortium’s collective efforts. We provide protocols for the large-scale production of more than 80% of all SARS-CoV-2 proteins or essential parts of them. Several of the proteins were produced in more than one laboratory, demonstrating the high interoperability between NMR groups worldwide. For the majority of proteins, we can produce isotope-labeled samples of HSQC-grade. Together with several NMR chemical shift assignments made publicly available on covid19-nmr.com, we here provide highly valuable resources for the production of SARS-CoV-2 proteins in isotope-labeled form

Can Health 2.0 Address Critical Healthcare Challenges? Insights from the Case of How Online Social Networks Can Assist in Combatting the Obesity Epidemic

One of the serious concerns in healthcare in this 21st century is obesity. While the causes of obesity are multifaceted, social networks have been identified as one of the most important dimensions of people's social environment that may influence the adoption of many behaviours, including health-promoting behaviours. In this article, we examine the possibility of harnessing the appeal of online social networks to address the obesity epidemic currently plaguing society. Specifically, a design science research methodology is adopted to design, implement and test the Health 2.0 application called “Calorie Cruncher”. The application is designed specifically to explore the influence of online social networks on individual’s health-related behaviour. In this regard, pilot data collected based on qualitative interviews indicate that online social networks may influence health-related behaviours in several ways. Firstly, they can influence people’s norms and value system that have an impact on their health-related behaviours. Secondly, social control and pressure of social connections may also shape health-related behaviours, and operate implicitly when people make food selection decisions. Thirdly, social relationships may provide emotional support. Our study has implications for research and practice. From a theoretical perspective, the article inductively identifies three factors that influence specific types of health outcomes in the context of obesity. From a practical perspective, the study underscores the benefits of adopting a design science methodology to design and implement a technology solution for a healthcare issue as well as the key role for online social media to assist with health and wellness management and maintenance

Which Factors Determine Our Online Social Capital? An Analysis Based on Structural Equation Modelling

The relationship between social network sites and social capital has received much research attention. However, two research gaps can be identified in the existing literature. First, only few studies have examined online social capital as a resource in online social networks. In this regard, it is not clear how to validly measure online social capital. Second, while the factors influencing social capital, among them properties of an individual’s social network, have been investigated in offline settings, such factors have not yet been investigated in terms of online social capital. Addressing these gaps, we asked 1000 Facebook users to provide information on their Facebook usage and online friendship network. Employing structural equation modelling for analysing the survey data, we show that Williams’ Internet Social Capital Scales, which are commonly used to assess social capital in offline settings, can be used to validly measure online social capital. Moreover, we find that some of the variables influencing offline social capital, among them similarity in terms of sociodemographic attributes, seem less important in an online setting

Kollaboratives Informationssuchverhalten von Personen unterschiedlicher Generationszugehörigkeit

Im vorliegenden Paper wird eine Studie dargestellt, in der das kollaborative Informationssucherverhalten (Collaborative Information Seeking, kurz: CIS) zwischen Generationen untersucht wurde. In Teams von zwei Personen sollten die Suchgruppen eine Reise planen und dafür im Internet nach Reiseinformation recherchieren. Anhand der Forschungsfrage: „Wie wird die kollaborative Informationssuche zwischen unterschiedlichen Generationen durchgeführt?“ fand eine qualitative Studie statt, in welcher die Organisation und das generelle Vorgehen bei der Suche beobachtet wurden. Im Fokus standen dabei das Rollenverhalten der Beteiligten und die Frage danach, ob eine Person eine leitende Position während der Suche einnimmt. Die Suche und Zusammenarbeit wurden zu diesem Zweck mittels Videos aufgenommen und nachfolgend analysiert. Im Anschluss partizipierten die Testpersonen in leitfadengestützten Gruppeninterviews. Die Ergebnisse deuten in allen Teams auf einen ähnlichen Ablauf der gemeinsamen Suche hin. Eine Leitungsfunktion war nur bedingt zu beobachten, wobei die Testpersonen jedoch spezifische Rollen während der Suche eingenommen haben

Neocarzilin A Is a Potent Inhibitor of Cancer Cell Motility Targeting VAT-1 Controlled Pathways

The natural product neocarzilin A (NCA) was discovered decades ago, and despite its potent cytotoxic effects no mode of action studies have been performed up to date. Synthesis of neocarzilins A, B, and C and a stereoisomer of NCA provided insights into structural preferences as well as access to probes for functional studies. NCA turned out to be the most active member and was not only effective against cell proliferation but also migration, a novel and so far overlooked activity. To decipher the molecular mode of action, we applied chemical proteomics for target discovery and revealed that NCA targets cancer cell migration via irreversible binding to the largely uncharacterized synaptic vesicle membrane protein VAT-1. A corresponding knockout of the protein confirmed the phenotype, and pull-down studies showed the interaction with an intricate network of key migration mediators such as Talin-1. Overall, we introduce VAT-1 as a promising novel target for the development of selective migration inhibitors with the perspective to limit toxicity in the absence of antiproliferative effects.ISSN:2374-795

Structure-based redesign of docking domain interactions modulates the product spectrum of a rhabdopeptide-synthesizing NRPS

Several peptides in clinical use are derived from non-ribosomal peptide synthetases (NRPS). In these systems multiple NRPS subunits interact with each other in a specific linear order mediated by specific docking domains (DDs), whose structures are not known yet, to synthesize well-defined peptide products. In contrast to classical NRPSs, single-module NRPS subunits responsible for the generation of rhabdopeptide/xenortide-like peptides (RXPs) can act in different order depending on subunit stoichiometry thereby producing peptide libraries. To define the basis for their unusual interaction patterns, we determine the structures of all N-terminal DDs ((N)DDs) as well as of an (DD)-D-N-(DD)-D-C complex and characterize all putative DD interactions thermodynamically for such a system. Key amino acid residues for DD interactions are identified that upon their exchange change the DD affinity and result in predictable changes in peptide production. Recognition rules for DD interactions are identified that also operate in other megasynthase complexes

The solution structure of the lantibiotic immunity protein NisI and its interactions with nisin

Many Gram-positive bacteria produce lantibiotics, genetically encoded and posttranslationally modified peptide antibiotics, which inhibit the growth of other Gram-positive bacteria. To protect themselves against their own lantibiotics these bacteria express a variety of immunity proteins including the LanI lipoproteins. The structural and mechanistic basis for LanI-mediated lantibiotic immunity is not yet understood. Lactococcus lactis produces the lantibiotic nisin, which is widely used as a food preservative. Its LanI protein NisI provides immunity against nisin but not against structurally very similar lantibiotics from other species such as subtilin from Bacillus subtilis. To understand the structural basis for LanI-mediated immunity and their specificity we investigated the structure of NisI. We found that NisI is a two-domain protein. Surprisingly, each of the two NisI domains has the same structure as the LanI protein from B. subtilis, SpaI, despite the lack of significant sequence homology. The two NisI domains and SpaI differ strongly in their surface properties and function. Additionally, SpaI-mediated lantibiotic immunity depends on the presence of a basic unstructured N-terminal region that tethers SpaI to the membrane. Such a region is absent from NisI. Instead, the N-terminal domain of NisI interacts with membranes but not with nisin. In contrast, the C-terminal domain specifically binds nisin and modulates the membrane affinity of the N-terminal domain. Thus, our results reveal an unexpected structural relationship between NisI and SpaI and shed light on the structural basis for LanI mediated lantibiotic immunity