Rivers of the Anthropocene Phase 1: A Comparative Study of the Tyne and Ohio River Valleys

poster abstractThe Rivers of the Anthropocene project is an international effort. Our part is an attempt to determine flood frequency and land use by American Indian tribes of the Mississippian Culture along the Ohio River. Methodologically, we will measure the physical and geochemical properties of lacustrine sediments recovered from Hovey Lake, a flood plane lake located on the Ohio River in southwestern Indiana. Sediment cores taken from Hovey Lake are being measured for bulk density and loss-on-ignition tests to determine organic composition by weight. Magnetic susceptibility is also being measured to determine variations in the delivery of terrestrial material (e.g. from flooding/land erosion) to the lake. Land use will be evaluated by measuring variations in the elemental abundance and isotopic composition of nitrogen and organic carbon, which has been used in the past to identify prehistoric land use. Here we present the initial results of our ongoing work, including sedimentological and chronological data. Ultimately, these data will help bring together historical records, geochemical records, and other contributions from scientists around the world in our attempt to better understand mankind’s impact on our environment

Integrative analysis of genomic and exposomic influences on youth mental health

Background: Understanding complex influences on mental health problems in young people is needed to inform early prevention strategies. Both genetic and environmental factors are known to influence youth mental health, but a more comprehensive picture of their interplay, including wide-ranging environmental exposures – that is, the exposome – is needed. We perform an integrative analysis of genomic and exposomic data in relation to internalizing and externalizing symptoms in a cohort of 4,314 unrelated youth from the Adolescent Brain and Cognitive Development (ABCD) Study. / Methods: Using novel GREML-based approaches, we model the variance in internalizing and externalizing symptoms explained by additive and interactive influences from the genome (G) and modeled exposome (E) consisting of up to 133 variables at the family, peer, school, neighborhood, life event, and broader environmental levels, including genome-by-exposome (G × E) and exposome-by-exposome (E × E) effects. / Results: A best-fitting integrative model with G, E, and G × E components explained 35% and 63% of variance in youth internalizing and externalizing symptoms, respectively. Youth in the top quintile of model-predicted risk accounted for the majority of individuals with clinically elevated symptoms at follow-up (60% for internalizing; 72% for externalizing). Of note, different domains of environmental exposures were most impactful for internalizing (life events) and externalizing (contextual including family, school, and peer-level factors) symptoms. In addition, variance explained by G × E contributions was substantially larger for externalizing (33%) than internalizing (13%) symptoms. / Conclusions: Advanced statistical genetic methods in a longitudinal cohort of youth can be leveraged to address fundamental questions about the role of ‘nature and nurture’ in developmental psychopathology

Rigs and Reefs: A Comparison of the Fish Communities at Two Artificial Reefs, a Production Platform, and a Natural Reef in the Northern Gulf of Mexico

Final report comparing the fish populations of two artificial reefs, an operating oil and gas platform, and a natural reef in the northern Gulf of Mexico. Data regarding fish species, density of species, factors effecting biomass, and configuration of reef structures is gathered using visual survey and hydro-acoustics and then statistically analyzed

Biogenesis of Influenza A Virus Hemagglutinin Cross-Protective Stem Epitopes

Antigenic variation in the globular domain of influenza A virus (IAV) hemagglutinin (HA) precludes effective immunity to this major human pathogen. Although the HA stem is highly conserved between influenza virus strains, HA stem-reactive antibodies (StRAbs) were long considered biologically inert. It is now clear, however, that StRAbs reduce viral replication in animal models and protect against pathogenicity and death, supporting the potential of HA stem-based immunogens as drift-resistant vaccines. Optimally designing StRAb-inducing immunogens and understanding StRAb effector functions require thorough comprehension of HA stem structure and antigenicity. Here, we study the biogenesis of HA stem epitopes recognized in cells infected with various drifted IAV H1N1 strains using mouse and human StRAbs. Using a novel immunofluorescence (IF)-based assay, we find that human StRAbs bind monomeric HA in the endoplasmic reticulum (ER) and trimerized HA in the Golgi complex (GC) with similar high avidity, potentially good news for producing effective monomeric HA stem immunogens. Though HA stem epitopes are nestled among several N-linked oligosaccharides, glycosylation is not required for full antigenicity. Rather, as N-linked glycans increase in size during intracellular transport of HA through the GC, StRAb binding becomes temperature-sensitive, binding poorly to HA at 4°C and well at 37°C. A de novo designed, 65-residue protein binds the mature HA stem independently of temperature, consistent with a lack of N-linked oligosaccharide steric hindrance due to its small size. Likewise, StRAbs bind recombinant HA carrying simple N-linked glycans in a temperature-independent manner. Chemical cross-linking experiments show that N-linked oligosaccharides likely influence StRAb binding by direct local effects rather than by globally modifying the conformational flexibility of HA. Our findings indicate that StRAb binding to HA is precarious, raising the possibility that sufficient immune pressure on the HA stem region could select for viral escape mutants with increased steric hindrance from N-linked glycans.</p

Iridium Corroles

This work reports the synthesis and full characterization of 5,10,15-tris-pentafluorophenylcorrolato-iridium(III) bis-trimethylamine 1 and its octabromo derivative 2. The corrole is planar in both cases (the mean deviation from the plane is as low as 0.0371 Å for 1 and 0.0325 Å for 2), the UV−vis spectra display a split Soret band with a shoulder attributable to an MLCT transition, and cyclic voltammetry reveals that the iridium(II) oxidation state cannot be accessed, while the oxidation to formal iridium(IV) complexes is achieved at much lower potentials than in other coordination environments

Design Specification for a Thrust-Vectoring, Actuated-Nose-Strake Flight Control Law for the High-Alpha Research Vehicle

Specifications for a flight control law are delineated in sufficient detail to support coding the control law in flight software. This control law was designed for implementation and flight test on the High-Alpha Research Vehicle (HARV), which is an F/A-18 aircraft modified to include an experimental multi-axis thrust-vectoring system and actuated nose strakes for enhanced rolling (ANSER). The control law, known as the HARV ANSER Control Law, was designed to utilize a blend of conventional aerodynamic control effectors, thrust vectoring, and actuated nose strakes to provide increased agility and good handling qualities throughout the HARV flight envelope, including angles of attack up to 70 degrees

Solvent-controlled self-assembly of Fmoc protected aliphatic amino acids

Self-assembly of modified amino acids facilitate the formation of various structures that have unique properties and therefore serve as excellent bio-organic scaffolds for diverse applications. Self-assembly of Fmoc protected single amino acids has attracted great interest owing to their ease of synthesis and applications as functional materials. Smaller assembly units enable synthetic convenience and potentially broader adoption. Herein, we demonstrate the ability to control the morphologies resulting from self-assembly of Fmoc modified aliphatic single amino acids (Fmoc-SAAs) namely, Alanine, Valine, Leucine, Isoleucine, and Proline. Controlled morphological transitions were observed through solvent variation and the mechanism that allows this control was investigated using coarse-grained molecular dynamics simulations. These show that FmocA can form well defined crystalline structures through uniform parallel Fmoc stacking and the optimization of ion concentrations, which is not observed for the other Fmoc-SAAs. We demonstrate that Fmoc protected aliphatic single amino acids are novel scaffolds for the design of distinct micro/nanostructures through a bottom-up approach that can be tuned by control of the environmental parameters

A practical, bioinformatic workflow system for large data sets generated by next-generation sequencing

Transcriptomics (at the level of single cells, tissues and/or whole organisms) underpins many fields of biomedical science, from understanding the basic cellular function in model organisms, to the elucidation of the biological events that govern the development and progression of human diseases, and the exploration of the mechanisms of survival, drug-resistance and virulence of pathogens. Next-generation sequencing (NGS) technologies are contributing to a massive expansion of transcriptomics in all fields and are reducing the cost, time and performance barriers presented by conventional approaches. However, bioinformatic tools for the analysis of the sequence data sets produced by these technologies can be daunting to researchers with limited or no expertise in bioinformatics. Here, we constructed a semi-automated, bioinformatic workflow system, and critically evaluated it for the analysis and annotation of large-scale sequence data sets generated by NGS. We demonstrated its utility for the exploration of differences in the transcriptomes among various stages and both sexes of an economically important parasitic worm (Oesophagostomum dentatum) as well as the prediction and prioritization of essential molecules (including GTPases, protein kinases and phosphatases) as novel drug target candidates. This workflow system provides a practical tool for the assembly, annotation and analysis of NGS data sets, also to researchers with a limited bioinformatic expertise. The custom-written Perl, Python and Unix shell computer scripts used can be readily modified or adapted to suit many different applications. This system is now utilized routinely for the analysis of data sets from pathogens of major socio-economic importance and can, in principle, be applied to transcriptomics data sets from any organism