Infusing concept directly into serious understanding regarding interpretable reactivity conjecture

The l-lysine-ϵ-dehydrogenase (LysEDH) from Geobacillus stearothermophilus naturally catalyzes the oxidative deamination of the ϵ-amino group of l-lysine. We previously engineered this enzyme to create amine dehydrogenase (AmDH) variants that possess a new hydrophobic cavity in their active site such that aromatic ketones can bind and be converted into α-chiral amines with excellent enantioselectivity. We also recently observed that LysEDH was capable of reducing aromatic aldehydes into primary alcohols. Herein, we harnessed the promiscuous alcohol dehydrogenase (ADH) activity of LysEDH to create new variants that exhibited enhanced catalytic activity for the reduction of substituted benzaldehydes and arylaliphatic aldehydes to primary alcohols. Notably, these novel engineered dehydrogenases also catalyzed the reductive amination of a variety of aldehydes and ketones with excellent enantioselectivity, thus exhibiting a dual AmDH/ADH activity. We envisioned that the catalytic bi-functionality of these enzymes could be applied for the direct conversion of alcohols into amines. As a proof-of-principle, we performed an unprecedented one-pot "hydrogen-borrowing" cascade to convert benzyl alcohol to benzylamine using a single enzyme. Conducting the same biocatalytic cascade in the presence of cofactor recycling enzymes (i.e., NADH-oxidase and formate dehydrogenase) increased the reaction yields. In summary, this work provides the first examples of enzymes showing "alcohol aminase" activity.Human embryonic stem cell (hESC)-derived midbrain dopamine (DA) neurons stand out as a cell source for transplantation with their sustainability and consistency superior to the formerly used fetal tissues. However, multiple studies of DA neurons in culture failed to register action potential (AP) generation upon synaptic input. To test whether this is due to deficiency of NMDA receptor (NMDAR) coagonists released from astroglia, we studied the functional properties of neural receptors in hESC-derived DA neuronal cultures. We find that, apart from an insufficient amount of coagonists, lack of interneuronal crosstalk is caused by hypofunction of synaptic NMDARs due to their direct inhibition by synaptically released DA. This inhibitory tone is independent of DA receptors and affects the NMDAR coagonist binding site.The 3D organization of our genome is an important determinant for the transcriptional output of a gene in (patho)physiological contexts. The spatial organization of linear chromosomes within nucleus is dominantly inferred using two distinct approaches, chromosome conformation capture (3C) and DNA fluorescent in situ hybridization (DNA-FISH). While 3C and its derivatives score genomic interaction frequencies based on proximity ligation events, DNA-FISH methods measure physical distances between genomic loci. Despite these approaches probe different characteristics of chromosomal topologies, they provide a coherent picture of how chromosomes are organized in higher-order structures encompassing chromosome territories, compartments, and topologically associating domains. Yet, at the finer topological level of promoter-enhancer communication, the imaging-centered and the 3C methods give more divergent and sometimes seemingly paradoxical results. Here, we compare and contrast observations made applying visual DNA-FISH and molecular 3C approaches. We emphasize that the 3C approach, due to its inherently competitive ligation step, measures only 'relative' proximities. A 3C interaction enriched between loci, therefore does not necessarily translates into a decrease in absolute spatial distance. Hence, we advocate caution when modeling chromosome conformations.The persistence of whole communities hinges on the presence of select interactions which act to stabilize communities making the identification of these keystone interactions critical. One potential candidate is omnivory, yet theoretical research on omnivory thus far has been dominated by a modular theory approach whereby an omnivore and consumer compete for a shared resource. Empirical research, however, has highlighted the presence of a broader suite of omnivory modules. Here, we integrate empirical data analysis and mathematical models to explore the influence of both omnivory module (including classic, multi-resource, higher level, mutual predation and cannibalism) and omnivore-resource interaction type on food web stability. We use six classic empirical food webs to examine the prevalence of the different types of omnivory, a multi-species consumer-resource model to determine the stability of these different kinds of omnivory within a module context, and finally extend these models to a 50 species, wholeivory acts less as a keystone interaction, rather, specific types of omnivory, particularly multi-resource omnivory, act as keystone modules. Future work integrating module and whole food web theory is critical for resolving the role of key interactions in food webs.The climate on our planet is changing and the range distributions of organisms are shifting in response. In aquatic environments, species might not be able to redistribute poleward or into deeper water when temperatures rise because of barriers, reduced light availability, altered water chemistry or any combination of these. How species respond to climate change may depend on physiological adaptability, but also on the population dynamics of the species. Density dependence is a ubiquitous force that governs population dynamics and regulates population growth, yet its connections to the impacts of climate change remain little known, especially in marine studies. Reductions in density below an environmental carrying capacity may cause compensatory increases in demographic parameters and population growth rate, hence masking the impacts of climate change on populations. On the other hand, climate-driven deterioration of conditions may reduce environmental carrying capacities, making compensation less likely and populations more susceptible to the effects of stochastic processes. Here we investigate the effects of climate change on Baltic blue mussels using a 17-year dataset on population density. selleck kinase inhibitor Using a Bayesian modelling framework, we investigate the impacts of climate change, assess the magnitude and effects of density dependence, and project the likelihood of population decline by the year 2030. Our findings show negative impacts of warmer and less saline waters, both outcomes of climate change. We also show that density dependence increases the likelihood of population decline by subjecting the population to the detrimental effects of stochastic processes (i.e. low densities where random bad years can cause local extinction, negating the possibility for random good years to offset bad years). We highlight the importance of understanding, and accounting for both density dependence and climate variation when predicting the impact of climate change on keystone species, such as the Baltic blue mussel.