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"Jonas, E."
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A History of Malaria and Conflict
It is supposed that in all armed conflicts until World War II more humans died of infectious diseases than of the actual violence. Especially malaria left a crucial imprint on wars throughout history. The disease aggravates wartime conditions, is thus responsible for significant morbidity and mortality in conflict zones, and is at the same time more commonly found in these areas. Malaria has halted many military campaigns in the past, with prominent examples ranging from antiquity through the medieval period and into the modern era. The parasitosis still continues to play an important role in the outcome of warfare and follow-up events today and is of special public health importance in areas of the Global South, where most of its endemicity and some of the most brutal conflicts of our time are located. Vice versa, wars and ensuing population movements increase malaria transmission and morbidity as well as impede control efforts. Awareness of this and the development of strategies to overcome both malaria and wars will massively improve the well-being of the population affected.
Journal Article
Methylotrophy in the thermophilic Bacillus methanolicus, basic insights and application for commodity production from methanol
Using methanol as an alternative non-food feedstock for biotechnological production offers several advantages in line with a methanol-based bioeconomy. The Gram-positive, facultative methylotrophic and thermophilic bacterium Bacillus methanolicus is one of the few described microbial candidates with a potential for the conversion of methanol to value-added products. Its capabilities of producing and secreting the commercially important amino acids L-glutamate and L-lysine to high concentrations at 50 °C have been demonstrated and make B. methanolicus a promising target to develop cell factories for industrial-scale production processes. B. methanolicus uses the ribulose monophosphate cycle for methanol assimilation and represents the first example of plasmid-dependent methylotrophy. Recent genome sequencing of two physiologically different wild-type B. methanolicus strains, MGA3 and PB1, accompanied with transcriptome and proteome analyses has generated fundamental new insight into the metabolism of the species. In addition, multiple key enzymes representing methylotrophic and biosynthetic pathways have been biochemically characterized. All this, together with establishment of improved tools for gene expression, has opened opportunities for systems-level metabolic engineering of B. methanolicus. Here, we summarize the current status of its metabolism and biochemistry, available genetic tools, and its potential use in respect to overproduction of amino acids.
Journal Article
High-level production of ethylmalonyl-CoA pathway-derived dicarboxylic acids by Methylobacterium extorquens under cobalt-deficient conditions and by polyhydroxybutyrate negative strains
Bio-based production of dicarboxylic acids is an emerging research field with remarkable progress during the last decades. The recently established synthesis of the ethylmalonyl-CoA pathway (EMCP)-derived dicarboxylic acids, mesaconic acid and (2S)-methylsuccinic acid, from the alternative carbon source methanol (Sonntag et al., Appl Microbiol Biotechnol 98:4533–4544, 2014) gave a proof of concept for the sustainable production of hitherto biotechnologically inaccessible monomers. In this study, substantial optimizations of the process by different approaches are presented. Abolishment of mesaconic and (2S)-methylsuccinic acid reuptake from culture supernatant and a productivity increase were achieved by 30-fold decreased sodium ion availability in culture medium. Undesired flux from EMCP into polyhydroxybutyrate (PHB) cycle was hindered by the knockout of polyhydroxyalkanoate synthase phaC which was concomitant with 5-fold increased product concentrations. However, frequently occurring suppressors of strain ΔphaC lost their beneficial properties probably due to redirected channeling of acetyl-CoA. Pool sizes of the product precursors were increased by exploiting the presence of two cobalt-dependent mutases in the EMCP: Fine-tuned growth-limiting cobalt concentrations led to 16-fold accumulation of mesaconyl- and (2S)-methylsuccinyl-CoA which in turn resulted in 6-fold increased concentrations of mesaconic and (2S)-methylsuccinic acids, with a combined titer of 0.65 g/l, representing a yield of 0.17 g/g methanol. This work represents an important step toward an industrially relevant production of ethylmalonyl-CoA pathway-derived dicarboxylic acids and the generation of a stable PHB synthesis negative Methylobacterium extorquens strain.
Journal Article
Is serotonin transporter brain binding associated with the cortisol awakening response? An independent non-replication
Serotonergic brain signaling is considered critical for an appropriate and dynamic adaptation to stress, seemingly through modulating limbic system functions, such as the hypothalamic-pituitary-adrenal (HPA)-axis. This interplay is of great interest since it holds promise as a target for preventing stress-related brain disorders, e.g., major depression. Our group has previously observed that prefrontal serotonin transporter (5-HTT) binding, imaged with positron emission tomography (PET), is positively associated with the cortisol awakening response (CAR), an index of HPA axis stress hormone dynamics. The aim of this cross-sectional study was to replicate the previous finding in a larger independent group of healthy individuals. Molecular imaging and cortisol data were available for 90 healthy individuals. Prefrontal 5-HTT binding was imaged with [.sup.11 C]DASB brain PET. Non-displaceable 5-HTT binding potential (BP.sub.ND) was quantified using the Multilinear Reference Tissue Model 2 (MRTM2) with cerebellum as the reference region. CAR was based on five serial salivary cortisol samples within the first hour upon awakening. The association between CAR and prefrontal 5-HTT BP.sub.ND was evaluated using a multiple linear regression model adjusted for age and sex. Further, we tested for sex differences in the association. Finally, an exploratory analysis of the association, was performed in 8 additional brain regions. We observed no statistically significant association between 5-HTT binding and CAR corrected for age and sex in the prefrontal cortex ([beta] = -0.28, p = 0.26). We saw no interaction with sex on the association (p = 0.99). We could not confirm a positive association between CAR and prefrontal 5-HTT BP.sub.ND in this independent dataset. Also, sex differences in the association were not apparent. Our data do not exclude that the serotonin transporter system is involved in the regulation of stress responses in at-risk or manifest depressed states.
Journal Article
Deposition of carbon from methane on manganese sources
Carbon has been deposited on HCFeMn slag from methane-containing gas with and without CO
2
, creating C-MnO composites and giving a hydrogen-rich off-gas as a by-product. The maximum deposited amount corresponds to 38 ± 6% of the carbon required for reduction of all manganese in the slag to metallic Mn. This was achieved at 1100 °C with a H
2
-concentration in the off gas of 76%. Temperature was an important parameter. At 790 °C, no deposited carbon was detected, at temperatures ≥ 1000 °C, deposition increased with temperature. A lower gas-flow leads to more methane decomposition. Experiments with CO
2
in the process gas gave less deposited carbon than other experiments. This could be caused by dilution of methane or chemical reactions involving CO
2
, or a combination. Investigations of fines formation indicate that the deposited carbon sticks well to the HCFeMn-slag, and would not fall off easily during transport and handling. This demonstrates that biogas can potentially be a non-fossil source of carbon in manganese production.
Journal Article
INFERENCE BASED ON STRUCTURAL VECTOR AUTOREGRESSIONS IDENTIFIED WITH SIGN AND ZERO RESTRICTIONS: THEORY AND APPLICATIONS
In this paper, we develop algorithms to independently draw from a family of conjugate posterior distributions over the structural parameterization when sign and zero restrictions are used to identify structural vector autoregressions (SVARs). We call this family of conjugate posteriors normal-generalized-normal. Our algorithms draw from a conjugate uniform-normal-inverse-Wishart posterior over the orthogonal reduced-form parameterization and transform the draws into the structural parameterization; this transformation induces a normal-generalized-normal posterior over the structural parameterization. The uniform-normal-inverse-Wishart posterior over the orthogonal reduced-form parameterization has been prominent after the work of Uhlig (2005). We use Beaudry, Nam, and Wang's (2011) work on the relevance of optimism shocks to show the dangers of using alternative approaches to implementing sign and zero restrictions to identify SVARs like the penalty function approach. In particular, we analytically show that the penalty function approach adds restrictions to the ones described in the identification scheme.
Journal Article
Methylotrophic Bacillus methanolicus Encodes Two Chromosomal and One Plasmid Born NAD+ Dependent Methanol Dehydrogenase Paralogs with Different Catalytic and Biochemical Properties
Bacillus methanolicus can utilize methanol as the sole carbon source for growth and it encodes an NAD(+)-dependent methanol dehydrogenase (Mdh), catalyzing the oxidation of methanol to formaldehyde. Recently, the genomes of the B. methanolicus strains MGA3 (ATCC53907) and PB1 (NCIMB13113) were sequenced and found to harbor three different putative Mdh encoding genes, each belonging to the type III Fe-NAD(+)-dependent alcohol dehydrogenases. In each strain, two of these genes are encoded on the chromosome and one on a plasmid; only one chromosomal act gene encoding the previously described activator protein ACT was found. The six Mdhs and the ACT proteins were produced recombinantly in Escherichia coli, purified, and characterized. All Mdhs required NAD(+) as cosubstrate, were catalytically stimulated by ACT, exhibited a broad and different substrate specificity range and displayed both dehydrogenase and reductase activities. All Mdhs catalyzed the oxidation of methanol; however the catalytic activity for methanol was considerably lower than for most other alcohols tested, suggesting that these enzymes represent a novel class of alcohol dehydrogenases. The kinetic constants for the Mdhs were comparable when acting as pure enzymes, but together with ACT the differences were more pronounced. Quantitative PCR experiments revealed major differences with respect to transcriptional regulation of the paralogous genes. Taken together our data indicate that the repertoire of methanol oxidizing enzymes in thermotolerant bacilli is larger than expected with complex mechanisms involved in their regulation.
Journal Article
Automatic ploidy prediction and quality assessment of human blastocysts using time-lapse imaging
Assessing fertilized human embryos is crucial for in vitro fertilization, a task being revolutionized by artificial intelligence. Existing models used for embryo quality assessment and ploidy detection could be significantly improved by effectively utilizing time-lapse imaging to identify critical developmental time points for maximizing prediction accuracy. Addressing this, we develop and compare various embryo ploidy status prediction models across distinct embryo development stages. We present BELA, a state-of-the-art ploidy prediction model that surpasses previous image- and video-based models without necessitating input from embryologists. BELA uses multitask learning to predict quality scores that are thereafter used to predict ploidy status. By achieving an area under the receiver operating characteristic curve of 0.76 for discriminating between euploidy and aneuploidy embryos on the Weill Cornell dataset, BELA matches the performance of models trained on embryologists’ manual scores. While not a replacement for preimplantation genetic testing for aneuploidy, BELA exemplifies how such models can streamline the embryo evaluation process.
Assessing human embryos is crucial for in vitro fertilization, a task being revolutionized by artificial intelligence. Here, the authors introduce BELA, an automated AI model for predicting embryo ploidy status and quality using time-lapse imaging.
Journal Article
Prediction of brain age using structural magnetic resonance imaging: A comparison of accuracy and test–retest reliability of publicly available software packages
Brain age prediction algorithms using structural magnetic resonance imaging (MRI) aim to assess the biological age of the human brain. The difference between a person's chronological age and the estimated brain age is thought to reflect deviations from a normal aging trajectory, indicating a slower or accelerated biological aging process. Several pre‐trained software packages for predicting brain age are publicly available. In this study, we perform a comparison of such packages with respect to (1) predictive accuracy, (2) test–retest reliability, and (3) the ability to track age progression over time. We evaluated the six brain age prediction packages: brainageR, DeepBrainNet, brainage, ENIGMA, pyment, and mccqrnn. The accuracy and test–retest reliability were assessed on MRI data from 372 healthy people aged between 18.4 and 86.2 years (mean 38.7 ± 17.5 years). All packages showed significant correlations between predicted brain age and chronological age ( r = 0.66–0.97, p < 0.001), with pyment displaying the strongest correlation. The mean absolute error was between 3.56 (pyment) and 9.54 years (ENIGMA). brainageR, pyment, and mccqrnn were superior in terms of reliability (ICC values between 0.94–0.98), as well as predicting age progression over a longer time span. Of the six packages, pyment and brainageR consistently showed the highest accuracy and test–retest reliability.
Journal Article