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Endurance exercise training promotes a protective phenotype in skeletal muscle known as exercise preconditioning. Exercise preconditioning protects muscle fibers against a variety of threats including inactivity-induced muscle atrophy. The mechanism(s) responsible for exercise preconditioning remain unknown and are explored in these experiments. Specifically, we investigated the impact of endurance exercise training on key components of the renin-angiotensin system (RAS). The RAS was targeted because activation of the classical axis of the RAS pathway via angiotensin II type I receptors (AT1Rs) promotes muscle atrophy whereas activation of the non-classical RAS axis via Mas receptors (MasRs) inhibits the atrophic signaling of the classical RAS pathway. Guided by prior studies, we hypothesized that an exercise-induced decrease in AT1Rs and/or increases in MasRs in skeletal muscle fibers is a potential mechanism responsible for exercise preconditioning. Following endurance exercise training in rats, we examined the abundance of AT1Rs and MasRs in both locomotor and respiratory muscles. Our results indicate that endurance exercise training does not alter the protein abundance of AT1Rs or MasRs in muscle fibers from the diaphragm, plantaris, and soleus muscles compared to sedentary controls (p ​> ​0.05). Furthermore, fluorescent angiotensin II (AngII) binding analyses confirm our results that exercise preconditioning does not alter the protein abundance of AT1Rs in the diaphragm, plantaris, and soleus (p ​> ​0.05). This study confirms that exercise-induced changes in RAS receptors are not a key mechanism that contributes to the beneficial effects of exercise preconditioning in skeletal muscle fibers.

As next-generation imaging instruments and interferometers search for planets closer to their stars, they must contend with increasing orbital motion and longer integration times. These compounding effects make it difficult to detect faint planets but also present an opportunity. Increased orbital motion makes it possible to move the search for planets into the orbital domain, where direct images can be freely combined with the radial velocity and proper motion anomaly, even without a confirmed detection in any single epoch. In this paper, we present a fast and differentiable multimethod orbit-modeling and planet detection code called Octofitter. This code is designed to be highly modular and allows users to easily adjust priors, change parameterizations, and specify arbitrary function relations between the parameters of one or more planets. Octofitter further supplies tools for examining model outputs including prior and posterior predictive checks and simulation-based calibration. We demonstrate the capabilities of Octofitter on real and simulated data from different instruments and methods, including HD 91312, simulated JWST/NIRISS aperture masking interferometry observations, radial velocity curves, and grids of images from the Gemini Planet Imager. We show that Octofitter can reliably recover faint planets in long sequences of images with arbitrary orbital motion. This publicly available tool will enable the broad application of multiepoch and multimethod exoplanet detection, which could improve how future targeted ground- and space-based surveys are performed. Finally, its rapid convergence makes it a useful addition to the existing ecosystem of tools for modeling the orbits of directly imaged planets.

Manufacturing of optical coatings is about the precise deposition of material and its control on the nanometer scale. This has to be achieved for a stack of multiple layers with a total thickness that can reach several micrometer. In addition, this has to be maintained for the complete functional area. In this contribution we demonstrate a process capable of delivering these accuracies not only to flat but also to curved surfaces.

Daily rhythms of light/darkness, activity/rest and feeding/fasting are important in human physiology and their disruption (for example by frequent changes between day and night shifts) increases the risk of disease. Many of the diseases found to be associated with such disrupted circadian lifestyles, including cancer, cardiovascular diseases, metabolic disorders and neurological diseases, depend on pathological de-regulation of angiogenesis, suggesting that disrupting the circadian clock will impair the physiological regulation of angiogenesis leading to development and progression of these diseases. Today there is little known regarding circadian regulation of pathological angiogenesis but there is some evidence that supports both direct and indirect regulation of angiogenic factors by the cellular circadian clock machinery, as well as by circulating circadian factors, important for coordinating circadian rhythms in the organism. Through highlighting recent advances both in pre-clinical and clinical research on various diseases including cancer, cardiovascular disorders and obesity, we will here present an overview of the available knowledge on the importance of circadian regulation of angiogenesis and discuss how the circadian clock may provide alternative targets for pro- or anti-angiogenic therapy in the future.

Abstract Background Sulfonamide resistance is very common in Escherichia coli. The aim of this study was to characterize plasmids carrying sulfonamide resistance genes (sul1, sul2 and sul3) in E. coli isolated from pigs and humans with a specific objective to assess the genetic diversity of plasmids involved in the mobility of sul genes. Methods A total of 501 E. coli isolates from pig feces, pig carcasses and human stools were tested for their susceptibility to selected antimicrobial. Multiplex PCR was conducted to detect the presence of three sul genes among the sulfonamide-resistant E. coli isolates. Fifty-seven sulfonamide-resistant E. coli were selected based on presence of sul resistance genes and subjected to conjugation and/or transformation experiments. S1 nuclease digestion followed by pulsed-field gel electrophoresis was used to visualize and determine the size of plasmids. Plasmids carrying sul genes were characterized by PCR-based replicon typing to allow a comparison of the types of sul genes, the reservoir and plasmid present. Results A total of 109/501 isolates exhibited sulfonamide resistance. The relative prevalences of sul genes from the three reservoirs (pigs, pig carcasses and humans) were 65%, 45% and 12% for sul2, sul1, and sul3, respectively. Transfer of resistance through conjugation was observed in 42/57 isolates. Resistances to streptomycin, ampicillin and trimethoprim were co-transferred in most strains. Class 1 integrons were present in 80% of sul1-carrying plasmids and 100% of sul3-carrying plasmids, but only in 5% of sul2-carrying plasmids. The sul plasmids ranged from 33 to 160-kb in size and belonged to nine different incompatibility (Inc) groups: FII, FIB, I1, FIA, B/O, FIC, N, HI1 and X1. IncFII was the dominant type in sul2-carrying plasmids (52%), while IncI1 was the most common type in sul1 and sul3-carrying plasmids (33% and 45%, respectively). Multireplicons were found associated with all three sul genes. Conclusions Sul genes were distributed widely in E. coli isolated from pigs and humans with sul2 being most prevalent. Sul-carrying plasmids belonged to diverse replicon types, but most of detected plasmids were conjugative enabling horizontal transfer. IncFII seems to be the dominant replicon type in sul2-carrying plasmids from all three sources.

Abstract Background Screening and enumeration of antimicrobial resistant Escherichia coli directly from samples is needed to identify emerging resistant clones and obtain quantitative data for risk assessment. Aim of this study was to evaluate the performance of 3M™ Petrifilm™ Select E. coli Count Plate (SEC plate) supplemented with antimicrobials to discriminate antimicrobial-resistant and non-resistant E. coli. Method A range of E. coli isolates were tested by agar dilution method comparing the Minimal Inhibitory Concentration (MIC) for eight antimicrobials obtained by Mueller-Hinton II agar, MacConkey agar and SEC plates. Kappa statistics was used to assess the levels of agreement when classifying strains as resistant, intermediate or susceptible. Results SEC plate showed that 74% of all strains agreed within ± 1 log2 dilution when comparing MICs with Mueller-Hinton II media. High agreement levels were found for gentamicin, ampicillin, chloramphenicol and cefotaxime, resulting in a kappa value of 0.9 and 100% agreement within ± 1 log2 dilution. Significant variances were observed for oxytetracycline and sulphamethoxazole. Further tests showed that the observed discrepancy in classification of susceptibility to oxytetracycline by the two media could be overcome when a plate-dependent breakpoint of 64 mg/L was used for SEC plates. For sulphamethoxazole, SEC plates provided unacceptably high MICs. Conclusion SEC plates showed good agreement with Mueller-Hinton II agar in MIC studies and can be used to screen and discriminate resistant E. coli for ampicillin, cephalothin, streptomycin, chloramphenicol, cefotaxime and gentamicin using CLSI standardized breakpoints, but not for sulphamethoxazole. SEC plates can also be used to discriminate oxytetracycline-resistant E. coli if a plate-dependent breakpoint value of 64 mg/L is used.

Abstract Background Research in herd health management solely using a quantitative approach may present major challenges to the interpretation of the results, because the humans involved may have responded to their observations based on previous experiences and own beliefs. This challenge can be met through increased awareness and dialogue between researchers and farmers or other stakeholders about the background for data collection related to management and changes in management. By integrating quantitative and qualitative research methods in a mixed methods research approach, the researchers will improve their understanding of this potential bias of the observed data and farms, which will enable them to obtain more useful results of quantitative analyses. Case description An example is used to illustrate the potentials of combining quantitative and qualitative approaches to herd health related data analyses. The example is based on two studies on bovine metritis. The first study was a quantitative observational study of risk factors for metritis in Danish dairy cows based on data from the Danish Cattle Database. The other study was a semi-structured interview study involving 20 practicing veterinarians with the aim to gain insight into veterinarians' decision making when collecting and processing data related to metritis. Discussion and Evaluation The relations between risk factors and metritis in the first project supported the findings in several other quantitative observational studies; however, the herd incidence risk was highly skewed. There may be simple practical reasons for this, e.g. underreporting and differences in the veterinarians' decision making. Additionally, the interviews in the second project identified several problems with correctness and validity of data regarding the occurrence of metritis because of differences regarding case definitions and thresholds for treatments between veterinarians. Conclusion Studies where associations between specific herd health management routines and disease outcome variables are drawn based purely on quantitative observational studies may benefit greatly by adding a qualitative perspective to the quantitative approach as illustrated and discussed in this article. The combined approach requires, besides skills and interdisciplinary collaboration, also openness, reflection and scepticism from the involved scientists, but the benefits may be extended to various contexts both in advisory service and science.

Abstract Background For most sequenced prokaryotic genomes, about a third of the protein coding genes annotated are "orphan proteins", that is, they lack homology to known proteins. These hypothetical genes are typically short and randomly scattered throughout the genome. This trend is seen for most of the bacterial and archaeal genomes published to date. Results In contrast we have found that a large fraction of the genes coding for such orphan proteins in the Methanopyrus kandleri AV19 genome occur within two large regions. These genes have no known homologs except from other M. kandleri genes. However, analysis of their lengths, codon usage, and Ribosomal Binding Site (RBS) sequences shows that they are most likely true protein coding genes and not random open reading frames. Conclusions Although these regions can be considered as candidates for massive lateral gene transfer, our bioinformatics analysis suggests that this is not the case. We predict many of the organism specific proteins to be transmembrane and belong to protein families that are non-randomly distributed between the regions. Consistent with this, we suggest that the two regions are most likely unrelated, and that they may be integrated plasmids.