In vivo Hypoxia and a Fungal Alcohol Dehydrogenase Influence the Pathogenesis of Invasive Pulmonary Aspergillosis

Currently, our knowledge of how pathogenic fungi grow in mammalian host environments is limited. Using a chemotherapeutic murine model of invasive pulmonary aspergillosis (IPA) and 1H-NMR metabolomics, we detected ethanol in the lungs of mice infected with Aspergillus fumigatus. This result suggests that A. fumigatus is exposed to oxygen depleted microenvironments during infection. To test this hypothesis, we utilized a chemical hypoxia detection agent, pimonidazole hydrochloride, in three immunologically distinct murine models of IPA (chemotherapeutic, X-CGD, and corticosteroid). In all three IPA murine models, hypoxia was observed during the course of infection. We next tested the hypothesis that production of ethanol in vivo by the fungus is involved in hypoxia adaptation and fungal pathogenesis. Ethanol deficient A. fumigatus strains showed no growth defects in hypoxia and were able to cause wild type levels of mortality in all 3 murine models. However, lung immunohistopathology and flow cytometry analyses revealed an increase in the inflammatory response in mice infected with an alcohol dehydrogenase null mutant strain that corresponded with a reduction in fungal burden. Consequently, in this study we present the first in vivo observations that hypoxic microenvironments occur during a pulmonary invasive fungal infection and observe that a fungal alcohol dehydrogenase influences fungal pathogenesis in the lung. Thus, environmental conditions encountered by invading pathogenic fungi may result in substantial fungal metabolism changes that influence subsequent host immune responses

ICAR: endoscopic skull‐base surgery

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Studies on the Chemical Stabilisation of Digestate from Mechanically Recovered Organic Fraction of Municipal Solid Waste

This study aims to explore an innovative approach consisting of the Fenton's process to stabilise organic wastes as an alternative to the traditional aerobic decomposition (composting). Digestate from the anaerobic digestion of the organic fraction of municipal solid wastes was taken from a mechanical-biological treatment plant and was thoroughly characterised regarding physical, chemical and biological properties. This sludge contained around 7.8 g Fe kg TS-1, which can be beneficial to the chemical oxidation. However, the use of zero-valent iron nanoparticles or iron(II) salt revealed treatment can be improved by adding extra iron into the system. The response surface methodology determined that the best peroxidation conditions were 35.6 g H2O2 kg TS-1 and 33.1 g Fe2+ kg TS-1, while maintaining constant pH 3, L/S 5 and room temperature. The chemical treatment enhanced the stability, reducing the oxygen uptake rate from 4.63 to 2.57 g O-2 kg VS-1 h(-1). Moreover, the germination index increased from 37 to 99.9 %, which means the treatment yielded a non-phytotoxic product. The outcomes of the present study are promising and open a new pathway for the Fenton peroxidation in semi-solid processes since this fast method can be very competitive when compared with the slow composting technology

Mapping the physiological and molecular markers of stress and SSRI antidepressant treatment in S100a10 corticostriatal neurons

In mood disorders, psychomotor and sensory abnormalities are prevalent, disabling, and intertwined with emotional and cognitive symptoms. Corticostriatal neurons in motor and somatosensory cortex are implicated in these symptoms, yet mechanisms of their vulnerability are unknown. Here, we demonstrate that S100a10 corticostriatal neurons exhibit distinct serotonin responses and have increased excitability, compared with S100a10-negative neurons. We reveal that prolonged social isolation disrupts the specific serotonin response which gets restored by chronic antidepressant treatment. We identify cell-type-specific transcriptional signatures in S100a10 neurons that contribute to serotonin responses and strongly associate with psychomotor and somatosensory function. Our studies provide a strong framework to understand the pathogenesis and create new avenues for the treatment of mood disorders

Cell death in the skin

The skin is the largest organ of the body and protects the organism against external physical, chemical and biological insults, such as wounding, ultraviolet radiation and micro-organisms. The epidermis is the upper part of the skin that is continuously renewed. The keratinocytes are the major cell type in the epidermis and undergo a specialized form of programmed cell death, called cornification, which is different from classical apoptosis. In keep with this view, several lines of evidence indicate that NF-kB is an important factor providing protection against keratinocyte apoptosis in homeostatic and inflammatory conditions. In contrast, the hair follicle is an epidermal appendage that shows cyclic apoptosis-driven involution, as part of the normal hair cycle. The different cell death programs need to be well orchestrated to maintain skin homeostasis. One of the major environmental insults to the skin is UVB radiation, causing the occurrence of apoptotic sunburn cells. Deregulation of cell death mechanisms in the skin can lead to diseases such as cancer, necrolysis and graft-versus-host disease. Here we review the apoptotic and the anti-apoptotic mechanisms in skin homeostasis and disease