Der fall wagner. Eine katamnese, zugleich ein beitrag zur lehre von der paranoia

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Mn valence instability in La2/3Ca1/3MnO3 thin films

A Mn valence instability on La2/3Ca1/3MnO3 thin films, grown on LaAlO3 (001)substrates is observed by x-ray absorption spectroscopy at the Mn L-edge and O K-edge. As-grown samples, in situ annealed at 800 C in oxygen, exhibit a Curie temperature well below that of the bulk material. Upon air exposure a reduction of the saturation magnetization, MS, of the films is detected. Simultaneously a Mn2+ spectral signature develops, in addition to the expected Mn3+ and Mn4+ contributions, which increases with time. The similarity of the spectral results obtained by total electron yield and fluorescence yield spectroscopy indicates that the location of the Mn valence anomalies is not confined to a narrow surface region of the film, but can extend throughout the whole thickness of the sample. High temperature annealing at 1000 C in air, immediately after growth, improves the magnetic and transport properties of such films towards the bulk values and the Mn2+ signature in the spectra does not appear. The Mn valence is then stable even to prolonged air exposure. We propose a mechanism for the Mn2+ ions formation and discuss the importance of these observations with respect to previous findings and production of thin films devices.Comment: Double space, 21 pages, 6 figure

Selective mitochondrial antioxidant MitoTEMPO reduces renal dysfunction and systemic inflammation in experimental sepsis in rats

BACKGROUND: Excess mitochondrial reactive oxygen species (mROS) in sepsis is associated with organ failure, in part by generating inflammation through the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome. We determined the impact of a mitochondrial-targeted antioxidant (MitoTEMPO) on mitochondrial dysfunction in renal proximal tubular epithelial cells, peritoneal immune cell function ex vivo, and organ dysfunction in a rat model of sepsis. METHODS: The effects of MitoTEMPO were assessed ex vivo using adenosine triphosphate and lipopolysaccharide-stimulated rat peritoneal immune cells and fresh rat kidney slices exposed to serum from septic rats. We assessed mROS production and phagocytotic capacity (flow cytometry), mitochondrial functionality (multiphoton imaging, respirometry), and NLRP3 inflammasome activation in cell culture. The effect of MitoTEMPO on organ dysfunction was evaluated in a rat model of faecal peritonitis. RESULTS: MitoTEMPO decreased septic serum-induced mROS (P0.05). In vivo, compared with untreated septic animals, MitoTEMPO reduced systemic IL-1β (P=0.01), reduced renal oxidative stress as determined by urine isoprostane levels (P=0.04), and ameliorated renal dysfunction (reduced serum urea (P<0.001) and creatinine (P=0.05). CONCLUSIONS: Reduction of mROS by a mitochondria-targeted antioxidant reduced IL-1β, and protected mitochondrial, cellular, and organ functionality after septic insults

\u3ci\u3eStaphylococcus aureus\u3c/i\u3e Metabolic Adaptations during the Transition from a Daptomycin Susceptibility Phenotype to a Daptomycin Nonsusceptibility Phenotype

Staphylococcus aureus is a major cause of nosocomial and community-acquired infections. The success of S. aureus as a pathogen is due in part to its many virulence determinants and resistance to antimicrobials. In particular, methicillin-resistant S. aureus has emerged as a major cause of infections and led to increased use of the antibiotics vancomycin and daptomycin, which has increased the isolation of vancomycin-intermediate S. aureus and daptomycin-nonsusceptible S. aureus strains. The most common mechanism by which S. aureus acquires intermediate resistance to antibiotics is by adapting its physiology and metabolism to permit growth in the presence of these antibiotics, a process known as adaptive resistance. To better understand the physiological and metabolic changes associated with adaptive resistance, six daptomycin-susceptible and -nonsusceptible isogenic strain pairs were examined for changes in growth, competitive fitness, and metabolic alterations. Interestingly, daptomycin nonsusceptibility coincides with a slightly delayed transition to the postexponential growth phase and alterations in metabolism. Specifically, daptomycin-nonsusceptible strains have decreased tricarboxylic acid cycle activity, which correlates with increased synthesis of pyrimidines and purines and increased carbon flow to pathways associated with wall teichoic acid and peptidoglycan biosynthesis. Importantly, these data provided an opportunity to alter the daptomycin nonsusceptibility phenotype by manipulating bacterial metabolism, a first step in developing compounds that target metabolic pathways that can be used in combination with daptomycin to reduce treatment failures

Early development of the malleus and incus in humans.

It is widely accepted by developmental biologists that the malleus and incus of the mammalian middle ear are first pharyngeal arch derivatives, a contention based originally on classical embryology that has now been backed up by molecular evidence from rodent models. However, it has been claimed in several studies of human ossicular development that the manubrium of the malleus and long process of the incus are actually derived from the second arch. This 'dual-arch' interpretation is commonly presented in otolaryngology textbooks, and it has been used by clinicians to explain the aetiology of certain congenital abnormalities of the human middle ear. In order to re-examine the origins of the human malleus and incus, we made three-dimensional reconstructions of the pharyngeal region of human embryos from 7 to 28 mm crown-rump length, based on serial histological sections from the Boyd Collection. We considered the positions of the developing ossicles relative to the pharyngeal pouches and clefts, and the facial and chorda tympani nerves. Confirming observations from previous studies, the primary union between first pharyngeal pouch and first cleft found in our youngest specimens was later lost, the external meatus developing rostroventral to this position. The mesenchyme of the first and second arches in these early embryos seemed to be continuous, but the boundaries of the developing ossicles proved to be very hard to determine at this stage. When first distinguishable, the indications were that both the manubrium of the malleus and the long process of the incus were emerging within the first pharyngeal arch. We therefore conclude that the histological evidence, on balance, favours the 'classical' notion that the human malleus and incus are first-arch structures. The embryological basis of congenital ossicular abnormalities should be reconsidered in this light.This is the author accepted manuscript. The final version is available from Wiley via https://doi.org/10.1111/joa.1252

Transport mode choice and body mass index: Cross-sectional and longitudinal evidence from a European-wide study.

BACKGROUND: In the fight against rising overweight and obesity levels, and unhealthy urban environments, the renaissance of active mobility (cycling and walking as a transport mode) is encouraging. Transport mode has been shown to be associated to body mass index (BMI), yet there is limited longitudinal evidence demonstrating causality. We aimed to associate transport mode and BMI cross-sectionally, but also prospectively in the first ever European-wide longitudinal study on transport and health. METHODS: Data were from the PASTA project that recruited adults in seven European cities (Antwerp, Barcelona, London, Oerebro, Rome, Vienna, Zurich) to complete a series of questionnaires on travel behavior, physical activity levels, and BMI. To assess the association between transport mode and BMI as well as change in BMI we performed crude and adjusted linear mixed-effects modeling for cross-sectional (n = 7380) and longitudinal (n = 2316) data, respectively. RESULTS: Cross-sectionally, BMI was 0.027 kg/m2 (95%CI 0.015 to 0.040) higher per additional day of car use per month. Inversely, BMI was -0.010 kg/m2 (95%CI -0.020 to -0.0002) lower per additional day of cycling per month. Changes in BMI were smaller in the longitudinal within-person assessment, however still statistically significant. BMI decreased in occasional (less than once per week) and non-cyclists who increased cycling (-0.303 kg/m2, 95%CI -0.530 to -0.077), while frequent (at least once per week) cyclists who stopped cycling increased their BMI (0.417 kg/m2, 95%CI 0.033 to 0.802). CONCLUSIONS: Our analyses showed that people lower their BMI when starting or increasing cycling, demonstrating the health benefits of active mobility

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition