Salmonella Typhimurium Strain ATCC14028 Requires H-2-Hydrogenases for Growth in the Gut, but Not at Systemic Sites

Salmonella enterica is a common cause of diarrhea. For eliciting disease, the pathogen has to colonize the gut lumen, a site colonized by the microbiota. This process/initial stage is incompletely understood. Recent work established that one particular strain, Salmonella enterica subspecies 1 serovar Typhimurium strain SL1344, employs the hyb H-2-hydrogenase for consuming microbiota-derived H-2 to support gut luminal pathogen growth: Protons from the H-2-splitting reaction contribute to the proton gradient across the outer bacterial membrane which can be harvested for ATP production or for import of carbon sources. However, it remained unclear, if other Salmonella strains would use the same strategy. In particular, earlier work had left unanswered if strain ATCC14028 might use H-2 for growth at systemic sites. To clarify the role of the hydrogenases, it seems important to establish if H-2 is used at systemic sites or in the gut and if Salmonella strains may differ with respect to the host sites where they require H-2 in vivo. In order to resolve this, we constructed a strain lacking all three H-2-hydrogenases of ATCC14028 (14028(hyd3)) and performed competitive infection experiments. Upon intragastric inoculation, 14028(hyd3) was present at 100-fold lower numbers than 14028(WT) in the stool and at systemic sites. In contrast, i.v. inoculation led to equivalent systemic loads of 14028(hyd3) and the wild type strain. However, the pathogen population spreading to the gut lumen featured again up to 100-fold attenuation of 14028(hyd3). Therefore, ATCC14028 requires H-2-hydrogenases for growth in the gut lumen and not at systemic sites. This extends previous work on ATCC14028 and supports the notion that H-2-utilization might be a general feature of S. Typhimurium gut colonization

Salmonella Typhimurium Strain ATCC14028 Requires H-2-Hydrogenases for Growth in the Gut, but Not at Systemic Sites

Salmonella enterica is a common cause of diarrhea. For eliciting disease, the pathogen has to colonize the gut lumen, a site colonized by the microbiota. This process/initial stage is incompletely understood. Recent work established that one particular strain, Salmonella enterica subspecies 1 serovar Typhimurium strain SL1344, employs the hyb H-2-hydrogenase for consuming microbiota-derived H-2 to support gut luminal pathogen growth: Protons from the H-2-splitting reaction contribute to the proton gradient across the outer bacterial membrane which can be harvested for ATP production or for import of carbon sources. However, it remained unclear, if other Salmonella strains would use the same strategy. In particular, earlier work had left unanswered if strain ATCC14028 might use H-2 for growth at systemic sites. To clarify the role of the hydrogenases, it seems important to establish if H-2 is used at systemic sites or in the gut and if Salmonella strains may differ with respect to the host sites where they require H-2 in vivo. In order to resolve this, we constructed a strain lacking all three H-2-hydrogenases of ATCC14028 (14028(hyd3)) and performed competitive infection experiments. Upon intragastric inoculation, 14028(hyd3) was present at 100-fold lower numbers than 14028(WT) in the stool and at systemic sites. In contrast, i.v. inoculation led to equivalent systemic loads of 14028(hyd3) and the wild type strain. However, the pathogen population spreading to the gut lumen featured again up to 100-fold attenuation of 14028(hyd3). Therefore, ATCC14028 requires H-2-hydrogenases for growth in the gut lumen and not at systemic sites. This extends previous work on ATCC14028 and supports the notion that H-2-utilization might be a general feature of S. Typhimurium gut colonization

Graft failure rate and complications after Descemet membrane endothelial keratoplasty in eyes with pre-existing glaucoma

Purpose: To evaluate the outcome of Descemet Membrane Endothelial Keratoplasty (DMEK) in eyes with pre-existing glaucoma. Design: In this retrospective, observational case series we included data of 150 consecutive DMEKs in eyes with pre-existing glaucoma of 150 patients after excluding data of the second treated eye of each patient and of re-DMEKs during follow-up. Cumulative incidences of IOP elevation (IOP > 21 mmHg or >= 10 mmHg increase in IOP from preoperative value), post-DMEK glaucoma (need of an additional intervention due to worsening of the IOP), graft rejection, and graft failure rate were analyzed using Kaplan-Meier survival analysis. COX regression analysis was used to evaluate independent risk factors. Results: The 36-month cumulative incidence of IOP elevation was 53.5% [95 CI 43.5-63.5%] and of post-DMEK glaucoma 36.3% [95 CI 26.3-46.3%]. Graft rejection occurred with a 36-month cumulative incidence of 9.2% [CI 95% 2.3-16.1]. None of the analyzed risk factors increased the risk for the development of graft rejection. The 36-month cumulative incidence of graft failure was 16.6% [CI 95% 8.4-24.8]. Independent risk factors for graft failure were the indication for DMEK "status after graft failure" (n = 16) compared to Fuchs' dystrophy (n = 74) (p = 0.045, HR 8.511 [CI 95% 1.054-68.756]) and pre-existing filtrating surgery via glaucoma drainage device (GDD) (n = 10) compared to no surgery/iridectomy (n = 109) (p = 0.014, HR 6.273 [CI 95% 1.456-27.031]). Conclusion: The risks of postoperative complications (IOP elevation, post-DMEK glaucoma, graft rejection, and graft failure) in patients with pre-existing glaucoma are high. In particular, pre-existing filtrating surgery via GDD implantation-but not trabeculectomy-and DMEK after graft failure increase the risk of graft failure

Alterations in Cerebrospinal Fluid in Patients with Bipolar Syndromes

Bipolar disorder (BD) is a severe and lifelong condition. Primary endogenic polygenetic forms are common. Secondary organic forms have received increasing interest recently due to the detection of immunological encephalopathies that mimic various psychiatric syndromes, including bipolar disorder. However, only limited data about routine findings of cerebrospinal fluid (CSF) analyses in bipolar disorder are available. Therefore, we investigated the frequency of alterations in the CSF in patients with BD and the association with autoantibodies, cerebral magnetic resonance imaging, and electroencephalography findings.CSF samples of patients with BD collected from January 1998 until December 2015 were analyzed retrospectively. Patients with preexisting causes for alterations in the CSF (e.g., patients with obvious past or current neurological disorders) were excluded. In total, 63 patients with BD fulfilled the inclusion criteria for the study. In 1.6% of the patients with BD, an increased white blood cell count was found in the CSF. Increased albumin quotients were found in 12.9% of the patients, oligoclonal bands (OCBs) in 1.6%, and increased immunoglobulin (Ig) G indices in 3.2% (OCBs were not measured in case of increased IgG indices). No significant differences in CSF findings were found between patients with manic and depressive episodes. The main findings of this open uncontrolled study are that alterations in the CSF may be found in a small but potentially relevant subgroup of patients with BD. These findings are discussed in light of the new concepts of mild encephalitis and immunological encephalopathy. The detection of patients with possibly secondary organic bipolar syndromes could open up new causal treatment options with immunomodulatory medication

Techno-Economic Analysis of a Flexible Process Concept for the Production of Transport Fuels and Heat from Biomass and Renewable Electricity

Different processes have been proposed to meet the global need for renewable fuel. The Biomass to Liquid process (BtL) converts biomass via the Fischer-Tropsch route to hydrocarbon chains that can be refined to transport fuel. With the addition of electrolytic hydrogen to the Power and Biomass to Liquid process (PBtL), the carbon efficiency can be increased relative to the BtL process. It was shown in previous studies that the PBtL concept has an economic edge over BtL when cheap electricity is available to maximize the fuel yield. In this study, a techno-economic analysis is conducted for a hybrid process concept which can switch operation modes from electrolysis enhanced to only biomass conversion. In case studies the effect of the Fischer-Tropsch conversion, H2/CO ratio of the Fischer-Tropsch feed and the biomass feed rate in the electrolysis enhanced mode are analyzed. Every process configuration is modeled based on experimentally validated unit models from literature in the commercial software Aspen Plus and analyzed using DLR’s software tool TEPET. For a 200 MWth biomass input plant, production costs of 1.08 €2019/L for the hybrid concept with a carbon efficiency of 53.3% compared to 0.66 €2019/L for BtL with 35.4% and 1 €2019/L for PBtL with 61.1% were found based on the Finnish day-ahead market for the base case. The net production cost for the hybrid concept can be decreased by 0.07 €2019/L when a Fischer-Tropsch H2/CO ratio of 1.6 instead of 2.05 is used

Opportunities and Challenges for Electro-Fuels in Future Aviation

1. Sustainable fuels are required to meet the aviation contribution towards Europe’s climate obligations 2. GHG abatement costs shall be the key decision criteria for large scale SAF deployment, PBtL: < 1.000 €/tCO2-eq. achievable 3. Europe can largely decarbonize its aviation utilizing biomass residues, investing in renewable power 4. PtX will only cover a minor portion of current crude oil consumption 5. Preventing + Shifting + Replacing of transport by REGULATION require