A Novel Acyl-CoA Beta-Transaminase Characterized from a Metagenome

BACKGROUND: Bacteria are key components in all ecosystems. However, our knowledge of bacterial metabolism is based solely on the study of cultivated organisms which represent just a tiny fraction of microbial diversity. To access new enzymatic reactions and new or alternative pathways, we investigated bacterial metabolism through analyses of uncultivated bacterial consortia. METHODOLOGY/PRINCIPAL FINDINGS: We applied the gene context approach to assembled sequences of the metagenome of the anaerobic digester of a municipal wastewater treatment plant, and identified a new gene which may participate in an alternative pathway of lysine fermentation. CONCLUSIONS: We characterized a novel, unique aminotransferase that acts exclusively on Coenzyme A (CoA) esters, and proposed a variant route for lysine fermentation. Results suggest that most of the lysine fermenting organisms use this new pathway in the digester. Its presence in organisms representative of two distinct bacterial divisions indicate that it may also be present in other organisms

Split Course Hyperfractionated Accelerated Radio-Chemotherapy (SCHARC) for patients with advanced head and neck cancer: Influence of protocol deviations and hemoglobin on overall survival, a retrospective analysis

BACKGROUND: The advantage of hyperfractionated accelerated radiation therapy for advanced head and neck cancer has been reported. Furthermore, randomized trials and meta-analyses have confirmed the survival benefit of additional chemotherapy to radiotherapy. We retrospectively analyzed the efficiency and toxicity of the Regensburg standard therapy protocol "SCHARC" and the overall survival of our patients. METHODS: From 1997 to 2004, 64 patients suffering from advanced head and neck cancer (88 % stage IV, 12 % stage III) were assigned to receive the SCHARC protocol. Around half of the patients were diagnosed with oro-hypopharynx carcinoma (52 %), one third with tongue and floor of mouth tumors (29 %) and one fifth (19 %) suffered from H & N cancer at other sites. The schedule consisted of one therapy block with 30 Gy in 20 fractions over a two week period with concomitant chemotherapy (d 1–5: 20 mg/m(2)/d DDP + 750–1000 mg/m(2)/d 5FU (cont. infusion). This therapy block was repeated after a fortnight break up to a cumulative dose of 60 Gy and followed by a boost up to 70 Gy (69–70.5 Gy). All patients assigned to this scheme were included in the survival evaluation. RESULTS: Forty patients (63 %) received both radiation and chemotherapy according to the protocol. The mean follow up was 2.3 years (829 d) and the median follow up was 1.9 years (678 d), respectively. The analysis of survival revealed an estimated 3 year overall survival rate of 57 %. No patient died of complications, 52 patients (80 %) had acute grade 2–3 mucositis, and 33 patients (58 %) suffered from acute grade 3 skin toxicity. Leucopenia was no major problem (mean nadir 3.4 g/nl, no patient < 1.0 g/nl) and the mean hemoglobin value decreased from 13.2 to 10.5 g/dl. Univariate analysis of survival showed a better outcome for patients with a hemoglobin nadir >10.5 g/dl and for patients who completed the protocol. CONCLUSION: The SCHARC protocol was effective in patients diagnosed with advanced head and neck cancer. It led to long-term disease control and survival in about 50 % of the patients with significant but acceptable toxicity. Most patients were not anemic at beginning of therapy. Therefore, we could assess the influence of pre-treatment hemoglobin on survival. However, a low hemoglobin nadir was associated with poor outcome. This result suggests an influence of anemia during therapy on prognosis

Comparative Analysis of Acinetobacters: Three Genomes for Three Lifestyles

Acinetobacter baumannii is the source of numerous nosocomial infections in humans and therefore deserves close attention as multidrug or even pandrug resistant strains are increasingly being identified worldwide. Here we report the comparison of two newly sequenced genomes of A. baumannii. The human isolate A. baumannii AYE is multidrug resistant whereas strain SDF, which was isolated from body lice, is antibiotic susceptible. As reference for comparison in this analysis, the genome of the soil-living bacterium A. baylyi strain ADP1 was used. The most interesting dissimilarities we observed were that i) whereas strain AYE and A. baylyi genomes harbored very few Insertion Sequence elements which could promote expression of downstream genes, strain SDF sequence contains several hundred of them that have played a crucial role in its genome reduction (gene disruptions and simple DNA loss); ii) strain SDF has low catabolic capacities compared to strain AYE. Interestingly, the latter has even higher catabolic capacities than A. baylyi which has already been reported as a very nutritionally versatile organism. This metabolic performance could explain the persistence of A. baumannii nosocomial strains in environments where nutrients are scarce; iii) several processes known to play a key role during host infection (biofilm formation, iron uptake, quorum sensing, virulence factors) were either different or absent, the best example of which is iron uptake. Indeed, strain AYE and A. baylyi use siderophore-based systems to scavenge iron from the environment whereas strain SDF uses an alternate system similar to the Haem Acquisition System (HAS). Taken together, all these observations suggest that the genome contents of the 3 Acinetobacters compared are partly shaped by life in distinct ecological niches: human (and more largely hospital environment), louse, soil

Semantic computational analysis of anticoagulation use in atrial fibrillation from real world data

Atrial fibrillation (AF) is the most common arrhythmia and significantly increases stroke risk. This risk is effectively managed by oral anticoagulation. Recent studies using national registry data indicate increased use of anticoagulation resulting from changes in guidelines and the availability of newer drugs. The aim of this study is to develop and validate an open source risk scoring pipeline for free-text electronic health record data using natural language processing. AF patients discharged from 1st January 2011 to 1st October 2017 were identified from discharge summaries (N = 10,030, 64.6% male, average age 75.3 ± 12.3 years). A natural language processing pipeline was developed to identify risk factors in clinical text and calculate risk for ischaemic stroke (CHA2DS2-VASc) and bleeding (HAS-BLED). Scores were validated vs two independent experts for 40 patients. Automatic risk scores were in strong agreement with the two independent experts for CHA2DS2-VASc (average kappa 0.78 vs experts, compared to 0.85 between experts). Agreement was lower for HAS-BLED (average kappa 0.54 vs experts, compared to 0.74 between experts). In high-risk patients (CHA2DS2-VASc ≥2) OAC use has increased significantly over the last 7 years, driven by the availability of DOACs and the transitioning of patients from AP medication alone to OAC. Factors independently associated with OAC use included components of the CHA2DS2-VASc and HAS-BLED scores as well as discharging specialty and frailty. OAC use was highest in patients discharged under cardiology (69%). Electronic health record text can be used for automatic calculation of clinical risk scores at scale. Open source tools are available today for this task but require further validation. Analysis of routinely collected EHR data can replicate findings from large-scale curated registries.info:eu-repo/semantics/publishedVersio

Designing Actuation Concepts for Adaptive Slabs with Integrated Fluidic Actuators Using Influence Matrices

Previous work has shown that floor slabs make up most of the material mass of building structures and are typically made of reinforced concrete. Considering the associated resource consumption and greenhouse gas emissions, new approaches are needed in order to reduce the built environment’s impact on the ongoing climate crisis. Various studies have demonstrated that adaptive building structures offer a potential solution for reducing material resource consumption and associated emissions. Adaptive structures have the ability to improve load-bearing performance by specifically reacting to external loads. This work applies the concept of adaptive structures to reinforced concrete slabs through the integration of fluidic actuators into the cross-section. The optimal integration of actuators in reinforced concrete slabs is a challenging interdisciplinary design problem that involves many parameters. In this work, actuation influence matrices are extended to slabs and used as an analysis and evaluation tool for deriving actuation concepts for adaptive slabs with integrated fluidic actuators. To define requirements for the actuator concept, a new procedure for the selection of actuation modes, actuator placement and the computation of actuation forces is developed. This method can also be employed to compute the required number of active elements for a given load case. The new method is highlighted in a case study of a 2 m × 2 m floor

A New Flavor-Coated Sachet Bait For Delivering Oral Rabies Vaccine To Raccoons And Coyotes

Research was conducted during 1996–2000 to develop baits for delivering an oral rabies vaccine to raccoons (Procyon lotor) and coyotes (Canis latrans). A bait was sought that: (1) was attractive to the target species, (2) could be distributed by aircraft, (3) was as effective (or more so) than the currently used fish meal polymer bait, and (4) could be produced in large numbers by automated procedures and could be purchased by user groups at substantially lower cost. Ten field trials were conducted to document raccoons’ bait flavor preferences, evaluate a new vaccine sachet bait coated with various attractants, and determine if the sachet bait would effectively deliver Raboral V-RG oral rabies vaccine (Merial Limited, Athens, Georgia, USA) to this species. Raccoons preferred fish and crustacean-based flavors over those derived from plant materials. Raccoon visits to tracking stations, frequency of bait removals, and percent of sachets discarded by this species that were emptied of placebo vaccine indicated efficacy of the new bait was equal or superior to the currently used fish meal polymer bait. A field trial conducted in fall 1998 compared aerially distributed vaccine-laden sachet and polymer baits and showed there was no difference between the percent of raccoons from the test and reference areas subsequently found positive for rabies antibody. Four bait trials to determine coyote response to sachet baits were conducted in 1997–98. The propensity for canids to gulp or bolt smaller food items is well known. Thus, a first trial involved offering fish-flavored sachet baits of different sizes to 30 captive coyotes to determine if smaller size baits were more frequently swallowed intact. Two field trials were also conducted in fall 1997 to determine if free-ranging coyotes discriminated among sachet baits coated with different attractants. Finally, Raboral V-RG-laden poultry-flavored sachet baits were aerially dropped and the percent of seropositive coyotes was compared with coyotes from surrounding areas where fish meal polymer vaccine baits had been distributed. Captive coyotes did not swallow sachet baits intact, regardless of size. Bait preference field trials indicated that coyotes preferred poultry, cheese/beef tallow, and fish-flavored sachet baits and that such baits were taken at the same rate as polymer baits. A sample of coyotes from the area baited with vaccine-laden sachet baits had a markedly higher (P = 0.01) seropositivity rate than coyotes from areas where vaccine was distributed in polymer baits. Sachet bait production could be facilitated by automated technology and sachet baits used either as an alternative vaccine delivery device or in combination with the fish meal polymer bait