- The C-terminal domain of Fcj1 is required for formation of crista junctions and interacts with the TOB/SAM complex in mitochondria (2012)
- Crista junctions (CJs) are tubular invaginations of the inner membrane of mitochondria that connect the inner boundary with the cristae membrane. These architectural elements are critical for mitochondrial function. The yeast inner membrane protein Fcj1, called mitofilin in mammals, was reported to be preferentially located at CJs and crucial for their formation. Here we investigate the functional roles of individual domains of Fcj1. The most conserved part of Fcj1, the C-terminal domain, is essential for Fcj1 function. In its absence, formation of CJ is strongly impaired and irregular, and stacked cristae are present. This domain interacts with full-length Fcj1, suggesting a role in oligomer formation. It also interacts with Tob55 of the translocase of outer membrane β-barrel proteins (TOB)/sorting and assembly machinery (SAM) complex, which is required for the insertion of β-barrel proteins into the outer membrane. The association of the TOB/SAM complex with contact sites depends on the presence of Fcj1. The biogenesis of β-barrel proteins is not significantly affected in the absence of Fcj1. However, down-regulation of the TOB/SAM complex leads to altered cristae morphology and a moderate reduction in the number of CJs. We propose that the C-terminal domain of Fcj1 is critical for the interaction of Fcj1 with the TOB/SAM complex and thereby for stabilizing CJs in close proximity to the outer membrane. These results assign novel functions to both the C-terminal domain of Fcj1 and the TOB/SAM complex.
- SchussenAktivplus: reduction of micropollutants and of potentially pathogenic bacteria for further water quality improvement of the river Schussen, a tributary of Lake Constance, Germany (2013)
- The project focuses on the efficiency of combined technologies to reduce the release of micropollutants and bacteria into surface waters via sewage treatment plants of different size and via stormwater overflow basins of different types. As a model river in a highly populated catchment area, the river Schussen and, as a control, the river Argen, two tributaries of Lake Constance, Southern Germany, are under investigation in this project. The efficiency of the different cleaning technologies is monitored by a wide range of exposure and effect analyses including chemical and microbiological techniques as well as effect studies ranging from molecules to communities.
- Delayed Wound Repair in Sepsis Is Associated with Reduced Local Pro-Inflammatory Cytokine Expression (2013)
- Sepsis is one of the main causes for morbidity and mortality in hospitalized patients. Moreover, sepsis associated complications involving impaired wound healing are common. Septic patients often require surgical interventions that in-turn may lead to further complications caused by impaired wound healing. We established a mouse model to the study delayed wound healing during sepsis distant to the septic focus point. For this reason cecal ligation and puncture (CLP) was combined with the creation of a superficial wound on the mouse ear. Control animals received the same procedure without CPL. Epithelialization was measured every second day by direct microscopic visualization up to complete closure of the wound. As interplay of TNF-α, TGF-β, matrix metalloproteinases (MMP), and tissue inhibitors of metalloproteinases (TIMP) is important in wound healing in general, TNF-α, TGF-β, MMP7, and TIMP1 were assessed immunohistochemical in samples of wounded ears harvested on days 2, 6, 10 and 16 after wounding. After induction of sepsis, animals showed a significant delay in wound epithelialization from day 2 to 12 compared to control animals. Complete wound healing was attained after mean 12.2± standard deviation (SD) 3.0 days in septic animals compared to 8.7± SD 1.7 days in the control group. Septic animals showed a significant reduction in local pro-inflammatory cytokine level of TNF-α on day 2 and day 6 as well as a reduced expression of TGF-β on day 2 in wounds. A significant lower expression of MMP7 as well as TIMP1 was also observed on day 2 after wounding. The induction of sepsis impairs wound healing distant to the septic focus point. We could demonstrate that expression of important cytokines for wound repair is deregulated after induction of sepsis. Thus restoring normal cytokine response locally in wounds could be a good strategy to enhance wound repair in sepsis.
- A range-wide synthesis and timeline for phylogeographic events in the red fox (Vulpes vulpes) (2013)
- Background: Many boreo-temperate mammals have a Pleistocene fossil record throughout Eurasia and North America, but only few have a contemporary distribution that spans this large area. Examples of Holarctic-distributed carnivores are the brown bear, grey wolf, and red fox, all three ecological generalists with large dispersal capacity and a high adaptive flexibility. While the two former have been examined extensively across their ranges, no phylogeographic study of the red fox has been conducted across its entire Holarctic range. Moreover, no study included samples from central Asia, leaving a large sampling gap in the middle of the Eurasian landmass. Results: Here we provide the first mitochondrial DNA sequence data of red foxes from central Asia (Siberia), and new sequences from several European populations. In a range-wide synthesis of 729 red fox mitochondrial control region sequences, including 677 previously published and 52 newly obtained sequences, this manuscript describes the pattern and timing of major phylogeographic events in red foxes, using a Bayesian coalescence approach with multiple fossil tip and root calibration points. In a 335 bp alignment we found in total 175 unique haplotypes. All newly sequenced individuals belonged to the previously described Holarctic lineage. Our analyses confirmed the presence of three Nearctic- and two Japan-restricted lineages that were formed since the Mid/Late Pleistocene. Conclusions: The phylogeographic history of red foxes is highly similar to that previously described for grey wolves and brown bears, indicating that climatic fluctuations and habitat changes since the Pleistocene had similar effects on these highly mobile generalist species. All three species originally diversified in Eurasia and later colonized North America and Japan. North American lineages persisted through the last glacial maximum south of the ice sheets, meeting more recent colonizers from Beringia during postglacial expansion into the northern Nearctic. Both brown bears and red foxes colonized Japan’s northern island Hokkaido at least three times, all lineages being most closely related to different mainland lineages. Red foxes, grey wolves, and brown bears thus represent an interesting case where species that occupy similar ecological niches also exhibit similar phylogeographic histories.