Spectral Shape as an Indicator of Molecular Weight in Chromophoric Dissolved Organic Matter

Spectral slope is a term used to parameterize featureless absorbance spectra according to their shape. Spectral slope is obtained by calculating the slope of the log-linearized absorption spectrum over a given range of wavelengths. Past studies have shown that spectral slope is related to molecular size in fulvic acids. A simple method of spectral analysis that compares spectral slopes obtained from two distinct regions of the UV spectra of aquatic dissolved organic matter is demonstrated. The ratio of these slopes (RS) shows considerable change during photo-oxidation, variation within estuaries, and substantial shifts with depth in the upper 1000 m of open ocean waters. Evidence is presented that these variations in RS are strongly related to molecular size shifts within dissolved organic matter (DOM) in a water sample. UV-visible spectrophotometric analysis of 0.2 μm filtered, estuarine waters coupled with stirred cell ultrafiltration and subsequent analysis of the size fractions show that the RS parameter exhibits significant correlation with shifts in molecular weight distribution that occur during photo-oxidation of DOM and during the mixing of high-molecular weight (HMW) terrigenous DOM and low-molecular weight (LMW) marine DOM. The RSparameter is applicable to natural waters as diverse as the Great Dismal Swamp and the Saragasso Sea, acting as a qualitative or semi-quantitative indicator of molecular weight and DOM source. In addition, RS is a faster and simpler tool than fluorescence excitation emission matrices (EEMs), which have been proposed as a means to determine the source of ballast water in ships from foreign ports. RS can serve as a quick screening step for determining which samples need to be examined using EEMs or other methods

Spectroscopic Characterization of Dissolved Organic Matter: Insights into Composition, Photochemical Transformation and Carbon Cycling

This dissertation explores processes affecting the composition of dissolved organic matter (DOM) and how DOM composition changes in sunlit surface waters and in the dark interior ocean. Simulated solar irradiations were used to investigate the impact of photochemistry on terrestrial waters and deep ocean DOM. The photochemically mediated processes observed in Dismal Swamp samples included (i) light induced flocculation of up to 12% of the organic matter and 84% of the dissolved iron originally present; (ii) 74-88% mineralization of dissolved organic carbon (DOC) and 95-99% bleaching of chromophoric DOM (CDOM) during 110 days of irradiation; and (iii) nearly complete loss of the biochemical markers for terrestrial DOM: lignin phenols, CDOM absorption and fluorescence, and aromaticity determined by nuclear magnetic resonance (NMR) spectroscopy. Extensively photo-degraded terrestrial DOM exhibited spectroscopic signatures similar to DOM isolated from ocean water (except that it lacked protein-like fluorescence and appeared to contain excess carboxyl carbon), and photo-degraded deep ocean DOM exhibited optical properties similar to surface ocean DOM. The heretofore-unexamined DOM removal process of light induced flocculation was further investigated using solid-state 13C NMR and infrared spectroscopy. Photochemical decarboxylation and production of alkyl functionality drives the initial phase of photochemical flocculation, while adsorption to iron flocculates is important during later phases of the process. Carboxyl amides appeared to resist mineralization, but were susceptible to photochemical flocculation. A fraction of the photodegraded DOM is more susceptible to mineral adsorption, which may be an important pathway for DOM export from surface waters to the sediments and subsequent preservation. Advanced solid-state 13C NMR characterization of DOM isolated by reverse osmosis — electrodialysis (RO/ED) from marine environments with varying biogeochemistries revealed new insights into the biodegradation of carbohydrates as well as preservation of carboxyl groups and condensed aromatic structures in the ocean\u27s interior. Quaternary anomeric carbons were identified as a potentially important structural component of the poorly characterized pool of bio-refractory carbohydrates. The present biogeochemical paradigm for ocean DOC cycling, the three-pool model, is re-examined along with the three-pool photoreactivity classification system. A new conceptual model is proposed, which incorporates both biological and photochemical reactivity of dissolved organic matter

α−α Cross-Links Increase Fibrin Fiber Elasticity and Stiffness

Fibrin fibers, which are ∼100 nm in diameter, are the major structural component of a blood clot. The mechanical properties of single fibrin fibers determine the behavior of a blood clot and, thus, have a critical influence on heart attacks, strokes, and embolisms. Cross-linking is thought to fortify blood clots; though, the role of α–α cross-links in fibrin fiber assembly and their effect on the mechanical properties of single fibrin fibers are poorly understood. To address this knowledge gap, we used a combined fluorescence and atomic force microscope technique to determine the stiffness (modulus), extensibility, and elasticity of individual, uncross-linked, exclusively α–α cross-linked (γQ398N/Q399N/K406R fibrinogen variant), and completely cross-linked fibrin fibers. Exclusive α–α cross-linking results in 2.5× stiffer and 1.5× more elastic fibers, whereas full cross-linking results in 3.75× stiffer, 1.2× more elastic, but 1.2× less extensible fibers, as compared to uncross-linked fibers. On the basis of these results and data from the literature, we propose a model in which the α-C region plays a significant role in inter- and intralinking of fibrin molecules and protofibrils, endowing fibrin fibers with increased stiffness and elasticity

Reconfigurable ferromagnetic liquid droplets.

Solid ferromagnetic materials are rigid in shape and cannot be reconfigured. Ferrofluids, although reconfigurable, are paramagnetic at room temperature and lose their magnetization when the applied magnetic field is removed. Here, we show a reversible paramagnetic-to-ferromagnetic transformation of ferrofluid droplets by the jamming of a monolayer of magnetic nanoparticles assembled at the water-oil interface. These ferromagnetic liquid droplets exhibit a finite coercivity and remanent magnetization. They can be easily reconfigured into different shapes while preserving the magnetic properties of solid ferromagnets with classic north-south dipole interactions. Their translational and rotational motions can be actuated remotely and precisely by an external magnetic field, inspiring studies on active matter, energy-dissipative assemblies, and programmable liquid constructs

Accuracy and Precision of Age Estimates for Pallid Sturgeon from Pectoral Fin Rays

Accurate age information is critical to the biological understanding and management of most fish species, but particularly for species of concern, such as the pallid sturgeon Scaphirhynchus albus. The accuracy and precision of pallid sturgeon age estimates from pectoral fin ray sections has never been established, yet all accumulated age information for the species was collected using this technique. To examine the accuracy and precision of age estimates, 16 pectoral fin ray samples from age-6 pallid sturgeon were obtained from Gavins Point National Fish Hatchery, South Dakota. The fin rays were sectioned, mounted, and independently examined twice by each of two readers. Only 28.1% of the age estimates accurately reflected the known age of the fish. Multiple readings of the same sample by the same reader (within-reader precision) only agreed 25% of the time, differences being as great as 5 years between the two estimates. Between-reader agreement was 46.9%, the two readers\u27 estimates of the same fish differing by as much as 2 years. Because of low accuracy and precision, estimated ages from pallid sturgeon pectoral fin rays should be viewed with caution

Dynamic properties of noise and Her6 levels are optimized by miR-9, allowing the decoding of the Her6 oscillator

This work was supported by a Wellcome Trust Senior Research Fellowship to NP (106185/Z/14/Z).Noise is prevalent in biology and has been widely quantified using snapshot measurements. This static view obscures our understanding of dynamic noise properties and how these affect gene expression and cell state transitions. Using a CRISPR/Cas9 Zebrafish her6::Venus reporter combined with mathematical and in vivo experimentation, we explore how noise affects the protein dynamics of Her6, a basic helix‐loop‐helix transcriptional repressor. During neurogenesis, Her6 expression transitions from fluctuating to oscillatory at single‐cell level. We identify that absence of miR‐9 input generates high‐frequency noise in Her6 traces, inhibits the transition to oscillatory protein expression and prevents the downregulation of Her6. Together, these impair the upregulation of downstream targets and cells accumulate in a normally transitory state where progenitor and early differentiation markers are co‐expressed. Computational modelling and double smFISH of her6 and the early neurogenesis marker, elavl3, suggest that the change in Her6 dynamics precedes the downregulation in Her6 levels. This sheds light onto the order of events at the moment of cell state transition and how this is influenced by the dynamic properties of noise. Our results suggest that Her/Hes oscillations, facilitated by dynamic noise optimization by miR‐9, endow progenitor cells with the ability to make a cell state transition.Publisher PDFPeer reviewe

Evaluating hybrid controls methodology in early-phase oncology trials: a simulation study based on the MORPHEUS-UC trial

Phase Ib/II oncology trials, despite their small sample sizes, aim to provide information for optimal internal company decision-making concerning novel drug development. Hybrid controls (a combination of the current control arm and controls from one or more sources of historical trial data [HTD]) can be used to increase the statistical precision. Here we assess combining two sources of Roche HTD to construct a hybrid control in targeted therapy for decision-making via an extensive simulation study. Our simulations are based on the real data of one of the experimental arms and the control arm of the MORPHEUS-UC Phase Ib/II study and two Roche HTD for atezolizumab monotherapy. We consider potential complications such as model misspecification, unmeasured confounding, different sample sizes of current treatment groups, and heterogeneity among the three trials. We evaluate two frequentist methods (with both Cox and Weibull accelerated failure time [AFT] models) and three different priors in Bayesian dynamic borrowing (with a Weibull AFT model), and modifications within each of those, when estimating the effect of treatment on survival outcomes and measures of effect such as marginal hazard ratios. We assess the performance of these methods in different settings and potential of generalizations to supplement decisions in early-phase oncology trials. The results show that the proposed joint frequentist methods and noninformative priors within Bayesian dynamic borrowing with no adjustment on covariates are preferred, especially when treatment effects across the three trials are heterogeneous. For generalization of hybrid control methods in such settings we recommend more simulation studies.Comment: 34 pages, 3 figures, 5 tables. To be appear in Pharmaceutical Statistic

Draft Aphaenogaster genomes expand our view of ant genome size variation across climate gradients

Given the abundance, broad distribution, and diversity of roles that ants play in many ecosystems, they are an ideal group to serve as ecosystem indicators of climatic change. At present, only a few whole-genome sequences of ants are available (19 of \u3e16,000 species), mostly from tropical and sub-tropical species. To address this limited sampling, we sequenced genomes of temperate-latitude species from the genus Aphaenogaster, a genus with important seed dispersers. In total, we sampled seven colonies of six species: Aphaenogaster ashmeadi, Aphaenogaster floridana, Aphaenogaster fulva, Aphaenogaster miamiana, Aphaenogaster picea, and Aphaenogaster rudis. The geographic ranges of these species collectively span eastern North America from southern Florida to southern Canada, which encompasses a latitudinal gradient in which many climatic variables are changing rapidly. For the six genomes, we assembled an average of 271,039 contigs into 47,337 scaffolds. The Aphaenogaster genomes displayed high levels of completeness with 96.1% to 97.6% of Hymenoptera BUSCOs completely represented, relative to currently sequenced ant genomes which ranged from 88.2% to 98.5%. Additionally, the mean genome size was 370.5 Mb, ranging from 310.3 to 429.7, which is comparable to that of other sequenced ant genomes (212.8-396.0 Mb) and flow cytometry estimates (210.7-690.4 Mb). In an analysis of currently sequenced ant genomes and the new Aphaenogaster sequences, we found that after controlling for both spatial autocorrelation and phylogenetics ant genome size was marginally correlated with sample site climate similarity. Of all examined climate variables, minimum temperature, and annual precipitation had the strongest correlations with genome size, with ants from locations with colder minimum temperatures and higher levels of precipitation having larger genomes. These results suggest that climate extremes could be a selective force acting on ant genomes and point to the need for more extensive sequencing of ant genomes