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The hydrogen-dependent carbon dioxide reductase is a soluble enzyme complex that directly utilizes hydrogen (H2) for the reduction of carbon dioxide (CO2) to formate in the first step of the acetyl-coenzyme A- or Wood-Ljungdahl pathway (WLP). HDCR consists of 2 catalytic subunits, a hydrogenase and a formate dehydrogenase (FDH) and two small subunits carrying iron-sulfur clusters. The enzyme complex has been purified and characterized from two acetogenic bacteria, from the mesophile Acetobacterium woodii and, recently, from the thermophile Thermoanaerobacter kivui. Physiological studies toward the importance of the HDCR for growth and formate metabolism in acetogens have not been carried out yet, due to the lack of genetic tools. Here, we deleted the genes encoding HDCR in T. kivui taking advantage of the recently developed genetic system. As expected, the deletion mutant (strain TKV_MB013) did not grow with formate as single substrate or under autotrophic conditions with H2 + CO2. Surprisingly, the strain did also not grow on any other substrate (sugars, mannitol or pyruvate), except for when formate was added. Concentrated cell suspensions quickly consumed formate in the presence of glucose only. In conclusion, HDCR provides formate which was essential for growth of the T. kivui mutant. Alternatively, extracellularly added formate served as terminal electron acceptor in addition to CO2, complementing the growth deficiency. The results show a tight coupling of multi-carbon substrate oxidation to the WLP. The metabolism in the mutant can be viewed as a coupled formate + CO2 respiration, which may be an ancient metabolic trait.
We introduce Implied Volatility Duration (IVD) as a new measure for the timing of uncertainty resolution, with a high IVD corresponding to late resolution. Portfolio sorts on a large cross-section of stocks indicate that investors demand on average about seven percent return per year as a compensation for a late resolution of uncertainty. In a general equilibrium model, we show that `late' stocks can only have higher expected returns than `early' stocks if the investor exhibits a preference for early resolution of uncertainty. Our empirical analysis thus provides a purely market-based assessment of the timing preferences of the marginal investor.
In pathology, tissue images are evaluated using a light microscope, relying on the expertise and experience of pathologists. There is a great need for computational methods to quantify and standardize histological observations. Computational quantification methods become more and more essential to evaluate tissue images. In particular, the distribution of tumor cells and their microenvironment are of special interest. Here, we systematically investigated tumor cell properties and their spatial neighborhood relations by a new application of statistical analysis to whole slide images of Hodgkin lymphoma, a tumor arising in lymph nodes, and inflammation of lymph nodes called lymphadenitis. We considered properties of more than 400, 000 immunohistochemically stained, CD30-positive cells in 35 whole slide images of tissue sections from subtypes of the classical Hodgkin lymphoma, nodular sclerosis and mixed cellularity, as well as from lymphadenitis. We found that cells of specific morphology exhibited significant favored and unfavored spatial neighborhood relations of cells in dependence of their morphology. This information is important to evaluate differences between Hodgkin lymph nodes infiltrated by tumor cells (Hodgkin lymphoma) and inflamed lymph nodes, concerning the neighborhood relations of cells and the sizes of cells. The quantification of neighborhood relations revealed new insights of relations of CD30-positive cells in different diagnosis cases. The approach is general and can easily be applied to whole slide image analysis of other tumor types.
Dieser Beitrag betrachtet die Verwendung von Fotografien des Brandenburger Tors in Schulbüchern für die gymnasiale Oberstufe in Hessen. US-Präsident Ronald Reagan machte mit seiner Rede 1987 das Tor zum Symbol der deutschen Teilung:
"Mr. Gorbachev, open this gate! Mr. Gorbachev, tear down this wall!"
Untersucht wird die Frage: Werden Fotografien des Brandenburger Tors vornehmlich im Kontext der deutschen Teilung verwendet?
Background: Chronic autoimmune demyelinating polyneuropathies (CADP) result in impaired sensorimotor function. However, anecdotal clinical observations suggest the development of cognitive deficits during the course of disease.
Methods: We tested 16 patients with CADP (11 patients with chronic inflammatory demyelinating polyneuropathy, 4 patients with multifocal motor neuropathy and 1 patient with multifocal acquired demyelinating sensory and motor neuropathy) and 40 healthy controls (HC) with a neuropsychological test battery. Blood-brain-barrier dysfunction (BBBd) in patients was assessed retrospectively by analysing the cerebral spinal fluid (CSF) status at the time the diagnosis of CAPD was established.
Results: CADP patients failed on average in 1.7 out of 9 neuropsychological tests (SD ± 1.25, min. 0, max. 5). 50% of the CADP patients failed in at least two neuropsychological tests and 44.3% of the patients failed in at least two different cognitive domains. CADP patients exhibiting BBBd at the time of first diagnosis failed in more neuropsychological tests than patients with intact integrity of the BBB (p < 0.05). When compared directly with the HC group, CADP patients performed worse than HC in tests measuring information processing ability and speed as well as phonemic verbal fluency after adjusting for confounding covariates.
Conclusions: Our results suggest that mild to moderate cognitive deficits might be present in patients with CAPD. One possible tentative explanation, albeit strong evidence is still lacking for this pathophysiological mechanism, refers to the effect of autoimmune antibodies entering the CNS via the dysfunctional blood-brain barrier typically seen in some of the CADP patients.
Lyme disease (LD), which is caused by genospecies of the Borrelia burgdorferi sensu lato complex, is the most common vector-borne disease in the Northern hemisphere. Spirochetes are transmitted by Ixodes ticks and maintained in diverse vertebrate animal hosts. Following tick bite, spirochetes initially establish a localized infection in the skin. However, they may also disseminate hematogenously to several distal sites, including heart, joints, or the CNS. Because they need to survive in diverse microenvironments, from tick vector to mammalian hosts, spirochetes have developed multiple strategies to combat the numerous host defense mechanisms. One of these strategies includes the production of a number of complement-regulator acquiring surface proteins (CRASPs) which encompass CspA, CspZ, and OspE paralogs to blunt the complement pathway. These proteins are capable of preventing complement activation on the spirochete surface by binding to complement regulator Factor H. The genes encoding these CRASPs differ in their expression patterns during the tick-to-host infection cycle, implying that these proteins may exhibit different functions during infection. This review summarizes the recent published reports which investigated the roles that each of these molecules plays in conferring tick-borne transmission and dissemination in vertebrate hosts. These findings offer novel mechanistic insights into LD pathobiology and may facilitate the identification of new targets for preventive strategies against Lyme borreliosis.
Uni-Highlights Februar 2020 : Einladungen zu ausgewählten Veranstaltungen der Goethe-Universität
(2020)
Although immune checkpoint and targeted therapies offer remarkable benefits for lung cancer treatment, some patients do not qualify for these regimens or do not exhibit consistent benefit. Provided that lung cancer appears to be driven by transforming growth factor beta signaling, we investigated the single drug potency of Pirfenidone, an approved drug for the treatment of lung fibrosis. Five human lung cancer cell lines and one murine line were investigated for transforming growth factor beta inhibition via Pirfenidone by using flow cytometry, In-Cell western analysis, proliferation assays as well as comprehensive analyses of the transcriptome with subsequent bioinformatics analysis. Overall, Pirfenidone induced cell cycle arrest, down-regulated SMAD expression and reduced proliferation in lung cancer. Furthermore, cell stress pathways and pro-apoptotic signaling may be mediated by reduced expression of Survivin. A murine subcutaneous model was used to assess the in vivo drug efficacy of Pirfenidone and showed reduced tumor growth and increased infiltration of T cells and NK cells. This data warrant further clinical evaluation of Pirfenidone with advanced non-small cell lung cancer. The observed in vitro and in vivo effects point to a substantial benefit for using Pirfenidone to reactivate the local immune response and possible application in conjunction with current immunotherapies.