LAMP-2 is required for incorporating syntaxin-17 into autophagosomes and for their fusion with lysosomes

Autophagy is an evolutionarily conserved process used for removing surplus and damaged proteins and organelles from the cytoplasm. The unwanted material is incorporated into autophagosomes that eventually fuse with lysosomes leading to the degradation of their cargo. The fusion event is mediated by the interaction between the Qa-SNARE syntaxin-17 (STX17) on autophagosomes and the R-SNARE VAMP8 on lysosomes. Cells deficient in lysosome membrane-associated protein-2 (LAMP-2) have increased numbers of autophagosomes but the underlying mechanism is poorly understood. By transfecting LAMP-2 deficient and LAMP-1/2 doubly deficient mouse embryonic fibroblast (MEF) with a tandem fluorescent-tagged LC3 we observed a failure of fusion between the autophagosomes and the lysosomes that could be rescued by complementation with LAMP-2A. Although we observed no change in expression and localization of VAMP8, its interacting partner STX17 was absent from autophagosomes of LAMP-2 deficient cells. Thus LAMP-2 is essential for STX17 expression by the autophagosomes and this absence is sufficient to explain their failure to fuse with lysosomes. The results have clear implications for situations associated with a reduction of LAMP-2 expression

Development and Application of the Owner-Bird Relationship Scale (OBRS) to Assess the Relation of Humans to Their Pet Birds

Only a few birds besides domestic pigeons and poultry can be described as domesticated. Therefore, keeping a pet bird can be challenging, and the human-avian relationship will have a major influence on the quality of this cohabitation. Studies that focus on characterizing the owner-bird relationship generally use adapted cat/dog scales which may not identify its specific features. Following a sociological approach, a concept of human-animal relationship was developed leading to three types of human-animal relationship (impersonal, personal, and close personal). This concept was used to develop a 21-item owner-bird-relationship scale (OBRS). This scale was applied to measure the relationship between pet bird owners (or keepers) (n = 1,444) and their birds in an online survey performed in Germany. Factor analysis revealed that the relationship between owner and bird consisted of four dimensions: the tendency of the owner to anthropomorphize the bird;the social support the bird provides for the owner;the empathy, attentiveness, and respect of the owner toward the bird;and the relationship of the bird toward the owner. More than one quarter of the German bird owners of this sample showed an impersonal, half a personal, and less than a quarter a close personal relationship to their bird. The relationship varied with the socio-demographic characteristics of the owners, such as gender, marital status, and education. This scale supports more comprehensive quantitative research into the human-bird relationship in the broad field of human-animal studies including the psychology and sociology of animals as well as animal welfare and veterinary medicine

Activation of Hypoxia Inducible Factor 1 Is a General Phenomenon in Infections with Human Pathogens

BACKGROUND: Hypoxia inducible factor (HIF)-1 is the key transcriptional factor involved in the adaptation process of cells and organisms to hypoxia. Recent findings suggest that HIF-1 plays also a crucial role in inflammatory and infectious diseases. METHODOLOGY/PRINCIPAL FINDINGS: Using patient skin biopsies, cell culture and murine infection models, HIF-1 activation was determined by immunohistochemistry, immunoblotting and reporter gene assays and was linked to cellular oxygen consumption. The course of a S. aureus peritonitis was determined upon pharmacological HIF-1 inhibition. Activation of HIF-1 was detectable (i) in all ex vivo in biopsies of patients suffering from skin infections, (ii) in vitro using cell culture infection models and (iii) in vivo using murine intravenous and peritoneal S. aureus infection models. HIF-1 activation by human pathogens was induced by oxygen-dependent mechanisms. Small colony variants (SCVs) of S. aureus known to cause chronic infections did not result in cellular hypoxia nor in HIF-1 activation. Pharmaceutical inhibition of HIF-1 activation resulted in increased survival rates of mice suffering from a S. aureus peritonitis. CONCLUSIONS/SIGNIFICANCE: Activation of HIF-1 is a general phenomenon in infections with human pathogenic bacteria, viruses, fungi and protozoa. HIF-1-regulated pathways might be an attractive target to modulate the course of life-threatening infections

A contour for the entanglement entropies in harmonic lattices

We construct a contour function for the entanglement entropies in generic harmonic lattices. In one spatial dimension, numerical analysis are performed by considering harmonic chains with either periodic or Dirichlet boundary conditions. In the massless regime and for some configurations where the subsystem is a single interval, the numerical results for the contour function are compared to the inverse of the local weight function which multiplies the energy-momentum tensor in the corresponding entanglement hamiltonian, found through conformal field theory methods, and a good agreement is observed. A numerical analysis of the contour function for the entanglement entropy is performed also in a massless harmonic chain for a subsystem made by two disjoint intervals

Die Mensch-Tier-Beziehung in der tierärztlichen Praxis

Welche Relevanz hat die Beziehung des Besitzers zu seinem Tier für die Tätigkeit einer tierärztlichen Praxis? Es kann von einem Interaktionsdreieck gesprochen werden, in dem sich Besitzer, Tier und Tierarzt/Tierärztin gegenseitig beeinflussen (Taubert 2015). Diverse Studien konnten einen Zusammenhang zwischen dem Einfluss des Menschen auf das Wohlbefinden des Tieres und der Mensch-Tier-Beziehung zeigen (Bergler et al. 2011; Klaphake und Smith 2002; Kurdek 2008; Lue et al. 2008; Patronek et al. 1996). Für die vorliegende Studie wurde die Mensch-Tier-Beziehung aus der Perspektive der tierärztlichen Untersuchung und Behandlung von Heimtieren in den Blick genommen. Mittels der Dimensionen: „Serie von Interaktionen“, „personale Entität, Du-Evidenz“, „Gegenseitigkeit“, „Emotionales Band“ und „Empathie“ wurden drei Konzepte der Mensch-Tier-Beziehung vorgeschlagen (unpersönliche, persönliche sowie enge persönliche Mensch-Tier-Beziehung). In einem interdisziplinären Ansatz zwischen Tiermedizin und Soziologie wurde eine psychometrische Skala („Owner-Bird-Relationship-Scale“) als Instrument zur Erfassung der Mensch-Vogel-Beziehung entwickelt und getestet. Dieses Messinstrument wurde in einem standardisierten Online-Fragebogen an Vogelhalter in Deutschland verbreitet. Die Auswertung der Befragung von 1458 Vogelhaltern erfolgte mittels multivariater Analyseverfahren. Die Beziehung zwischen Vogelhaltern und ihren Vögeln ließ sich im Rahmen von Faktorenanalysen mittels vier Beziehungsdimensionen beschreiben und war spezifisch für die jeweilige Besitzer-Vogel-Konstellation. Anhand der Ausprägungen der Beziehungsdimensionen konnten mit Hilfe clusteranalytischer Verfahren fünf verschiedene Typen von Vogelhaltern identifiziert werden. Es konnte mittels multivariater linearer und logistischer Regressionsverfahren gezeigt werden, dass die Beziehung des Halters zu seinem Vogel Einfluss auf das Verhalten des Besitzers in der tierärztlichen Untersuchung und Behandlung hat. Es bestand ein Zusammenhang zwischen der Mensch-Vogel-Beziehung und jeweils der Bereitschaft hohe Tierarztkosten zu tragen, dem Informationsverhalten des Halters, dem Verhalten im Erkrankungsfall sowie der Bedeutung der Spezialisierung eines Tierarztes für den Vogelhalter

Entanglement negativity in a two dimensional harmonic lattice: Area law and corner contributions

We study the logarithmic negativity and the moments of the partial transpose in the ground state of a two dimensional massless harmonic square lattice with nearest neighbour interactions for various configurations of adjacent domains. At leading order for large domains, the logarithmic negativity and the logarithm of the ratio between the generic moment of the partial transpose and the moment of the reduced density matrix at the same order satisfy an area law in terms of the length of the curve shared by the adjacent regions. We give numerical evidence that the coefficient of the area law term in these quantities is related to the coefficient of the area law term in the R\ue9nyi entropies. Whenever the curve shared by the adjacent domains contains vertices, a subleading logarithmic term occurs in these quantities and the numerical values of the corner function for some pairs of angles are obtained. In the special case of vertices corresponding to explementary angles, we provide numerical evidence that the corner function of the logarithmic negativity is given by the corner function of the R\ue9nyi entropy of order 1/2

On R\ue9nyi entropies of disjoint intervals in conformal field theory

We study the R\ue9nyi entropies of N disjoint intervals in the conformal field theories describing the free compactified boson and the Ising model. They are computed as the 2N-point function of twist fields, by employing the partition function of the model on a particular class of Riemann surfaces. The results are written in terms of Riemann theta functions. The prediction for the free boson in the decompactification regime is checked against exact results for the harmonic chain. For the Ising model, matrix product state computations agree with the conformal field theory result once the finite size corrections have been taken into account. \ua9 2014 IOP Publishing Ltd and SISSA Medialab srl

Partial transpose of two disjoint blocks in XY spin chains

We consider the partial transpose of the spin reduced density matrix of two disjoint blocks in spin chains admitting a representation in terms of free fermions, such as XY chains. We exploit the solution of the model in terms of Majorana fermions and show that such partial transpose in the spin variables is a linear combination of four Gaussian fermionic operators. This representation allows to explicitly construct and evaluate the integer moments of the partial transpose. We numerically study critical XX and Ising chains and we show that the asymptotic results for large blocks agree with conformal field theory predictions if corrections to the scaling are properly taken into account

Entanglement negativity after a global quantum quench

We study the time evolution of the logarithmic negativity after a global quantum quench. In a 1+1-dimensional conformal invariant field theory, we consider the negativity between two intervals which can be either adjacent or disjoint. We show that the negativity follows the quasi-particle interpretation for the spreading of entanglement. We check and generalise our findings with a systematic analysis of the negativity after a quantum quench in the harmonic chain, highlighting two peculiar lattice effects: the late birth and the sudden death of entanglement

Orientia tsutsugamushi is highly susceptible to the RNA polymerase switch region inhibitor corallopyronin a In Vitro and In Vivo

Scrub typhus is a potentially lethal infection caused by the obligate intracellular bacterium; Orientia tsutsugamushi; Reports on the emergence of doxycycline-resistant strains highlight the urgent need to develop novel antiinfectives against scrub typhus. Corallopyronin A (CorA) is a novel α-pyrone compound synthesized by the myxobacterium; Corallococcus coralloides; that was characterized as a noncompetitive inhibitor of the switch region of the bacterial RNA polymerase (RNAP). We investigated the antimicrobial action of CorA against the human-pathogenic Karp strain of; O. tsutsugamushi; in vitro; and; in vivo; The MIC of CorA against; O. tsutsugamushi; was remarkably low (0.0078 μg/ml), 16-fold lower than that against; Rickettsia typhi; In the lethal intraperitoneal; O. tsutsugamushi; mouse infection model, a minimum daily dose of 100 μg CorA protected 100% of infected mice. Two days of treatment were sufficient to confer protection. In contrast to BALB/c mice, SCID mice succumbed to the infection despite treatment with CorA or tetracycline, suggesting that antimicrobial treatment required synergistic action of the adaptive immune response. Similar to tetracycline, CorA did not prevent latent infection of; O. tsutsugamushi; in vivo; However, latency was not caused by acquisition of antimicrobial resistance, since; O. tsutsugamushi; reisolated from latently infected BALB/c mice remained fully susceptible to CorA. No mutations were found in the CorA-binding regions of the β and β' RNAP subunit genes; rpoB; and; rpoC; Inhibition of the RNAP switch region of; O. tsutsugamushi; by CorA is therefore a novel and highly potent target for antimicrobial therapy for scrub typhus