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Gut microbiota and the immune system are in constant exchange shaping both host immunity and microbial communities. Here, improper immune regulation can cause inflammatory bowel disease (IBD) and colitis. Antibody therapies blocking signaling through the CD40-CD40L axis showed promising results as these molecules are deregulated in certain IBD patients. To better understand the mechanism, we used transgenic DC-LMP1/CD40 animals with a constitutive CD40-signal in CD11c + cells, causing a lack of intestinal CD103 + dendritic cells (DCs) and failure to induce regulatory T (iTreg) cells. These mice rapidly develop spontaneous fatal colitis, accompanied by dysbiosis and increased inflammatory IL-17 + IFN-γ + Th17/Th1 and IFN-γ + Th1 cells. In the present study, we analyzed the impact of the microbiota on disease development and detected elevated IgA- and IgG-levels in sera from DC-LMP1/CD40 animals. Their serum antibodies specifically bound intestinal bacteria, and by proteome analysis, we identified a 60 kDa chaperonin GroEL (Hsp60) from Helicobacter hepaticus ( Hh ) as the main specific antigen targeted in the absence of iTregs. When re-derived to a different Hh -free specific-pathogen-free (SPF) microbiota, mice showed few signs of disease, normal microbiota, and no fatality. Upon recolonization of mice with Hh , the disease developed rapidly. Thus, the present work identifies GroEL/Hsp60 as a major Hh -antigen and its role in disease onset, progression, and outcome in this colitis model. Our results highlight the importance of CD103 + DC- and iTreg-mediated immune tolerance to specific pathobionts to maintain healthy intestinal balance.

An increasing number of microorganisms are classified as 'pathobionts' (i.e., organisms that can cause harm under certain circumstances) but there exist no universally used criteria for this definition. In particular, the term is often used for categorizing disease-associated taxa without proof of 'causality'. This creates confusion and distracts from explicitly searching for beneficial functions of these organisms that they may in fact have. Here, we discuss why this term in its current use, and its apparent simplicity, may obscure the complexity of microbe-host and microbe-microbe interactions that define (the status of) the gut ecosystem., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The naturally occurring nitrogen (N) isotopes, 15 N and 14 N, exhibit different reaction rates during many microbial N transformation processes, which results in N isotope fractionation. Such isotope effects are critical parameters for interpreting natural stable isotope abundances as proxies for biological process rates in the environment across scales. The kinetic isotope effect of ammonia oxidation (AO) to nitrite (NO 2 - ), performed by ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB), is generally ascribed to the enzyme ammonia monooxygenase (AMO), which catalyzes the first step in this process. However, the kinetic isotope effect of AMO, or ε A M O , has been typically determined based on isotope kinetics during product formation (cumulative product, NO 2 - ) alone, which may have overestimated ε A M O due to possible accumulation of chemical intermediates and alternative sinks of ammonia/ammonium (NH 3 /NH 4 + ). Here, we analyzed 15 N isotope fractionation during archaeal ammonia oxidation based on both isotopic changes in residual substrate (RS, NH 4 + ) and cumulative product (CP, NO 2 - ) pools in pure cultures of the soil strain Nitrososphaera viennensis EN76 and in highly enriched cultures of the marine strain Nitrosopumilus adriaticus NF5, under non-limiting substrate conditions. We obtained ε A M O values of 31.9-33.1‰ for both strains based on RS (δ 15 NH 4 + ) and showed that estimates based on CP (δ 15 NO 2 - ) give larger isotope fractionation factors by 6-8‰. Complementary analyses showed that, at the end of the growth period, microbial biomass was 15 N-enriched (10.1‰), whereas nitrous oxide (N 2 O) was highly 15 N depleted (-38.1‰) relative to the initial substrate. Although we did not determine the isotope effect of NH 4 + assimilation (biomass formation) and N 2 O production by AOA, our results nevertheless show that the discrepancy between ε A M O estimates based on RS and CP might have derived from the incorporation of 15 N-enriched residual NH 4 + after AMO reaction into microbial biomass and that N 2 O production did not affect isotope fractionation estimates significantly., (Copyright © 2020 Mooshammer, Alves, Bayer, Melcher, Stieglmeier, Jochum, Rittmann, Watzka, Schleper, Herndl and Wanek.)

Background: Key insights into the role of platelets in acute myocardial infarction (AMI) and unstable angina have led to the development of the polymer-coated stent, Camouflage(R). Coating of stents is an elegant method to minimize interactions between platelets and the stent surface and the vascular response following stent implantation., Methods: This single-center prospective registry was performed to estimate the in-hospital, 30-day and 180-day event rate (death, revascularization, reinfarction and pathological stress test at 180 days) in an everyday patient population with AMI with immediate percutaneous coronary intervention. There were 44 males (65.7%) and 23 females (34.3%); 53 patients (79.1%) had hypertension, 11 (16.4%) were diabetic, and 32 (47.8%) had elevated LDL cholesterol. The mean age was 60.7 +/- 11.6 years., Results: Sixty-seven patients with AMI (STEMI: 56.7%, NSTEMI: 43.3%) were included. Clinical data at the 30-day and 180-day follow up were available for all but 1 of the patients. Overall, there were 3 (4.5%) deaths, 1 (1.5%) death at 30 days and 2 (3.0%) at 180 days (1 cardiogenic shock 3, 1 sudden cardiac death and 1 AMI). Three (4.5%) patients experienced subacute closure of the target vessel. At 180 days, 1 (1.5%) patient had a pathological stress test and 5 patients (7.5%) underwent target vessel revascularization., Conclusion: The registry with this passive-coated stent showed good results in patients with AMI, consistent with earlier studies. Data are now available both for the development of hypotheses and for a data-based estimation of the number of cases for a comparative clinical study versus other coronary stents.

Image formation with partially coherent radiation is evaluated with the Hopkins formula and then applied to x-ray microscopy. Image characteristics expected from instruments with circular and annular pupils in partially coherent conditions are considered for two-point objects and a knife-edge object. The theoretically expected values for image characteristics that are easy accessible by an experiment, such as the width of a knife edge, are given for various x-ray microscopes.

In collaboration with the IBM (Basel) a computer program was developed for the analysis of data from cytology, colposcopy and histopathology. Due to the general way of formulation the program-system is applicabel for every kind of problem in natural sciences as well as economics. It is written in FORTRAN. Until now 15 parametric and non-parametric statistical tests are available for the analysis of descriptive or analytical statistical questions. The amount of data to be analyzed is nearly unlimited. Several plot-routines incorporated in the program serve for graphical presentation of distributions of different variables, of scatter-diagrams and computed functions. The internal control of the statistical monitor including the report card-system and the syntax of the input orders (with generation of error messages) are shortly explained. In a sample of 251 random selected patients showing pathological signes of the portio uteri from the department of gynecology of the university Basel the way of working of some subroutines is demonstrated and some general principles of data-acquisition and data-management in medicine are outlined.

Since the Swiss Gynecological Society suggests that cervical smears be taken only from patients age 25 years or over, we have investigated the validity of an age limitation. Analyzing the patients at our dysplasia clinic, the following statistics emerged: of the 4255 patients in the period 1970-1980, 897 or 21.08% were under 25 years of age; 190 or 4.46% were under 20. Of these women, 153 had or developed (cytologically at least) serious dysplasia or carcinoma in situ. On the basis of the data presented and the literature we are obliged to concluded that an age limit is not medically meaningful and that every sexually active woman, regardless of age, should be accepted into the preventive examination program.

In order to more effectively monitor women with dysplasia of the uterine cervix, a dysplasia clinic was established at the University Women's Hospital, Basel, in 1970. From 1970 to 1978, 3,570 women were examined in the clinic. The mean age of the patients was 36.4 +/- 13.3 years. Since in most cases we administer therapy to women whose cervical smear reports indicate at least severe dysplasia, we devoted our attention to those patients with smears showing mild-to-moderate dysplasia. Of the 2,528 women who had such smears, 111 were not followed up in our clinic. Mild-to-moderate dysplasia was demonstrated only once in 1,110 patients and was found at least twice in 1,051 women. Progression to a cervical smear showing at least severe dysplasia occurred in 256 patients (10%). This progression, however, was demonstrated in 87% of the 256 patients as early as the first two years of monitoring. Our observations make it clear that strict surveillance of patients with dysplasia even in the mild or moderate stage is necessary. With strict monitoring, the anticipated progression in 10% of the patients can be detected early; as a result, we can achieve successful secondary prophylaxis of cervical carcinoma.