Genomic Description of ‘Candidatus Abyssubacteria,’ a Novel Subsurface Lineage Within the Candidate Phylum Hydrogenedentes

The subsurface biosphere is a massive repository of fixed carbon, harboring approximately 90% of Earth’s microbial biomass. These microbial communities drive transformations central to Earth’s biogeochemical cycles. However, there is still much we do not understand about how complex subterranean microbial communities survive and how they interact with these cycles. Recent metagenomic investigation of deeply circulating terrestrial subsurface fluids revealed the presence of several novel lineages of bacteria. In one particular example, phylogenomic analyses do not converge on any one previously identified taxon; here we describe the first full genomic sequences of a new bacterial lineage within the candidate phylum Hydrogenedentes, ‘Candidatus Abyssubacteria.’ A global survey revealed that members of this proposed lineage are widely distributed in both marine and terrestrial subsurface environments, but their physiological and ecological roles have remained unexplored. Two high quality metagenome assembled genomes (SURF_5: 97%, 4%; SURF_17: 91% and 4% completeness and contamination, respectively) were reconstructed from fluids collected 1.5 kilometers below surface in the former Homestake gold mine—now the Sanford Underground Research Facility (SURF)—in Lead, South Dakota, United States. Metabolic reconstruction suggests versatile metabolic capability, including possible nitrogen reduction, sulfite oxidation, sulfate reduction and homoacetogenesis. This first glimpse into the metabolic capabilities of these cosmopolitan bacteria suggests that they are involved in key geochemical processes, including sulfur, nitrogen, and carbon cycling, and that they are adapted to survival in the dark, often anoxic, subsurface biosphere

Kinetic Control over Self-Assembly of Semiconductor Nanoplatelets

Semiconductor nanoplatelets exhibit spectrally pure, directional fluorescence. To make polarized light emission accessible and the charge transport effective, nanoplatelets have to be collectively oriented in the solid state. We discovered that the collective nanoplatelets orientation in monolayers can be controlled kinetically by exploiting the solvent evaporation rate in self-assembly at liquid interfaces. Our method avoids insulating additives such as surfactants, making it ideally suited for optoelectronics. The monolayer films with controlled nanoplatelets orientation (edge-up or face-down) exhibit long-range ordering of transition dipole moments and macroscopically polarized light emission. Furthermore, we unveil that the substantial in-plane electronic coupling between nanoplatelets enables charge transport through a single nanoplatelets monolayer, with an efficiency that strongly depends on the orientation of the nanoplatelets. The ability to kinetically control the assembly of nanoplatelets into ordered monolayers with tunable optical and electronic properties paves the way for new applications in optoelectronic devices

Kinetic Control over Self-Assembly of Semiconductor Nanoplatelets

Semiconductor nanoplatelets exhibit spectrally pure, directional fluorescence. To make polarized light emission accessible and the charge transport effective, nanoplatelets have to be collectively oriented in the solid state. We discovered that the collective nanoplatelets orientation in monolayers can be controlled kinetically by exploiting the solvent evaporation rate in self-assembly at liquid interfaces. Our method avoids insulating additives such as surfactants, making it ideally suited for optoelectronics. The monolayer films with controlled nanoplatelets orientation (edge-up or face-down) exhibit long-range ordering of transition dipole moments and macroscopically polarized light emission. Furthermore, we unveil that the substantial in-plane electronic coupling between nanoplatelets enables charge transport through a single nanoplatelets monolayer, with an efficiency that strongly depends on the orientation of the nanoplatelets. The ability to kinetically control the assembly of nanoplatelets into ordered monolayers with tunable optical and electronic properties paves the way for new applications in optoelectronic devices

Lead Optimization of 3,5-Disubstituted-7-Azaindoles for the Treatment of Human African Trypanosomiasis.

Neglected tropical diseases such as human African trypanosomiasis (HAT) are prevalent primarily in tropical climates and among populations living in poverty. Historically, the lack of economic incentive to develop new treatments for these diseases has meant that existing therapeutics have serious shortcomings in terms of safety, efficacy, and administration, and better therapeutics are needed. We now report a series of 3,5-disubstituted-7-azaindoles identified as growth inhibitors of Trypanosoma brucei, the parasite that causes HAT, through a high-throughput screen. We describe the hit-to-lead optimization of this series and the development and preclinical investigation of 29d, a potent antitrypanosomal compound with promising pharmacokinetic (PK) parameters. This compound was ultimately not progressed beyond in vivo PK studies due to its inability to penetrate the blood-brain barrier (BBB), critical for stage 2 HAT treatments.The authors acknowledge funding from the National Institute of Allergy and Infectious Diseases (M.P.P. and M.N., R01AI114685; M.P.P., 1R21AI127594, R01AI124046; C.R.C., R21AI126296; https://www.niaid.nih.gov/), the Spanish Ministerio de Economí a, Industria y Competitividad (M.N., SAF2015-71444-P; D.G.-P., SAF2016-79957-R; http://www.mineco.gob.es), Subdireccion General de Redes ́ y Centros de Investigacion Cooperativa (RICET, https://www.ricet.es/) (M.N., RD16/0027/0019; D.G.P., RD16/ 0027/0014), and RTI2018-097210-B-I00 (MINCIU-FEDER) to F.G. An ACS MEDI Predoctoral Fellowship for D.M.K. is gratefully acknowledged, as is support from the National Science Foundation for K.F. (CHE-1262734). We thank AstraZeneca, Charles River Laboratories, and GlaxoSmithKline for the provision of the in vitro ADME and physicochemical properties data. The use of JChem/ChemAxon software is acknowledged

Directed evolution unlocks oxygen reactivity for a nicotine-degrading flavoenzyme

The flavoenzyme nicotine oxidoreductase (NicA2) is a promising injectable treatment to aid in the cessation of smoking, a behavior responsible for one in ten deaths worldwide. NicA2 acts by degrading nicotine in the bloodstream before it reaches the brain. Clinical use of NicA2 is limited by its poor catalytic activity in the absence of its natural electron acceptor CycN. Without CycN, NicA2 is instead oxidized slowly by dioxygen (O2), necessitating unfeasibly large doses in a therapeutic setting. Here, we report a genetic selection strategy that directly links CycN-independent activity of NicA2 to growth of Pseudomonas putida S16. This selection enabled us to evolve NicA2 variants with substantial improvement in their rate of oxidation by O2. The encoded mutations cluster around a putative O2 tunnel, increasing flexibility and accessibility to O2 in this region. These mutations further confer desirable clinical properties. A variant form of NicA2 is tenfold more effective than the wild type at degrading nicotine in the bloodstream of rats

Treatment Seeking Problem Gamblers: Characteristics of Individuals who Offend to Finance Gambling

The relationship between Crime and gambling is well established, however few studies have examined offending specifically to finance gambling within a UK gambling treatment-seeking population. 1226 treatment-seeking gamblers completed the Problem Gambling Severity Index (PGSI), Patient Health Questionnaire, and the Generalized Anxiety Disorder 7 item scale, and were asked whether they had committed any illegal behaviours to finance gambling. 42.5 % reported offending behaviour. A greater proportion of the offending group were single or married/ cohabiting, had a lower-level qualifications, lower income, had experienced childhood abuse, family mental health problems and gambling related harms compared to the non-offending group. Offenders reported higher anxiety, depression and disordered gambling scores. Disordered gamblers who offend make up a discrete and complex subgroup with distinct vulnerabilities. Findings will be useful to clinicians involved in the assessment and management of problematic gambling. Gamblers who offend to finance gambling may have different treatment needs and treatment providers should administer appropriate clinical interventions to address vulnerabilities

A genomic catalog of Earth’s microbiomes

The reconstruction of bacterial and archaeal genomes from shotgun metagenomes has enabled insights into the ecology and evolution of environmental and host-associated microbiomes. Here we applied this approach to >10,000 metagenomes collected from diverse habitats covering all of Earth’s continents and oceans, including metagenomes from human and animal hosts, engineered environments, and natural and agricultural soils, to capture extant microbial, metabolic and functional potential. This comprehensive catalog includes 52,515 metagenome-assembled genomes representing 12,556 novel candidate species-level operational taxonomic units spanning 135 phyla. The catalog expands the known phylogenetic diversity of bacteria and archaea by 44% and is broadly available for streamlined comparative analyses, interactive exploration, metabolic modeling and bulk download. We demonstrate the utility of this collection for understanding secondary-metabolite biosynthetic potential and for resolving thousands of new host linkages to uncultivated viruses. This resource underscores the value of genome-centric approaches for revealing genomic properties of uncultivated microorganisms that affect ecosystem processes

3D visualization of additive occlusion and tunable full-spectrum fluorescence in calcite

From biomineralization to synthesis, organic additives provide an effective means of controlling crystallization processes. There is growing evidence that these additives are often occluded within the crystal lattice. This promises an elegant means of creating nanocomposites and tuning physical properties. Here we use the incorporation of sulfonated fluorescent dyes to gain new understanding of additive occlusion in calcite (CaCO3), and to link morphological changes to occlusion mechanisms. We demonstrate that these additives are incorporated within specific zones, as defined by the growth conditions, and show how occlusion can govern changes in crystal shape. Fluorescence spectroscopy and lifetime imaging microscopy also show that the dyes experience unique local environments within different zones. Our strategy is then extended to simultaneously incorporate mixtures of dyes, whose fluorescence cascade creates calcite nanoparticles that fluoresce white. This offers a simple strategy for generating biocompatible and stable fluorescent nanoparticles whose output can be tuned as required