Publications by authors named "Harry Stern"

Article Synopsis
  • Cyclometalated iridium(III) complexes are being explored for use in G-quadruplex (GQ) nucleic acid biosensors, highlighting their potential in biochemistry.
  • Through NMR titrations, researchers discovered that the compound [Ir(ppy)(pizp)](PF) significantly affects specific GQ residues, suggesting it mainly binds via end-stacking at the 5' tetrad position.
  • Molecular docking and dynamics simulations not only corroborate these findings but also refine the understanding of the binding interactions, indicating their effectiveness in predicting binding sites for experimental contexts.
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Inference of gene regulatory networks from gene perturbation experiments is the most reliable approach for investigating interdependence between genes. Here, we describe the initial gene perturbations, expression measurements, and preparation steps, followed by network modeling using TopNet. Summarization and visualization of the estimated networks and optional genetic testing of dependencies revealed by the network model are demonstrated.

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Polar bears are susceptible to climate warming because of their dependence on sea ice, which is declining rapidly. We present the first evidence for a genetically distinct and functionally isolated group of polar bears in Southeast Greenland. These bears occupy sea-ice conditions resembling those projected for the High Arctic in the late 21st century, with an annual ice-free period that is >100 days longer than the estimated fasting threshold for the species.

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Malignant cell transformation and the underlying reprogramming of gene expression require the cooperation of multiple oncogenic mutations. This cooperation is reflected in the synergistic regulation of non-mutant downstream genes, so-called cooperation response genes (CRGs). CRGs affect diverse hallmark features of cancer cells and are not known to be functionally connected.

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Colloidal semiconductor quantum dots (QDs) have long established their versatility and utility for the visualization of biological interactions. On the single-particle level, QDs have demonstrated superior photophysical properties compared to organic dye molecules or fluorescent proteins, but it remains an open question as to which of these fundamental characteristics are most significant with respect to the performance of QDs for imaging beyond the diffraction limit. Here, we demonstrate significant enhancement in achievable localization precision in QD-labeled neurons compared to neurons labeled with an organic fluorophore.

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Kane Basin (KB) is one of the world's most northerly polar bear (Ursus maritimus) subpopulations, where bears have historically inhabited a mix of thick multiyear and annual sea ice year-round. Currently, KB is transitioning to a seasonally ice-free region because of climate change. This ecological shift has been hypothesized to benefit polar bears in the near-term due to thinner ice with increased biological production, although this has not been demonstrated empirically.

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Climate change has broad ecological implications for species that rely on sensitive habitats. For some top predators, loss of habitat is expected to lead to cascading behavioral, nutritional, and reproductive changes that ultimately accelerate population declines. In the case of the polar bear (Ursus maritimus), declining Arctic sea ice reduces access to prey and lengthens seasonal fasting periods.

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The fabled Northwest Passage and Northern Sea Route that were once the quests of early Western explorers are now increasingly sea ice-free, with routine vessel transits expected by midcentury. The potential impacts of this novel vessel traffic on endemic Arctic marine mammal (AMM) species are unknown despite their critical social and ecological roles in the ecosystem and widely recognized susceptibility to ice loss. We developed a vulnerability assessment of 80 subpopulations of seven AMM species to vessel traffic during the ice-free season.

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Background: The ease at which influenza virus sequence data can be used to estimate antigenic relationships between strains and the existence of databases containing sequence data for hundreds of thousands influenza strains make sequence-based antigenic distance estimates an attractive approach to researchers. Antigenic mismatch between circulating strains and vaccine strains results in significantly decreased vaccine effectiveness. Furthermore, antigenic relatedness between the vaccine strain and the strains an individual was originally primed with can affect the cross-reactivity of the antibody response.

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The conservation of many wildlife species requires understanding the demographic effects of climate change, including interactions between climate change and harvest, which can provide cultural, nutritional or economic value to humans.We present a demographic model that is based on the polar bear life cycle and includes density-dependent relationships linking vital rates to environmental carrying capacity (). Using this model, we develop a state-dependent management framework to calculate a harvest level that (i) maintains a population above its maximum net productivity level (MNPL; the population size that produces the greatest net increment in abundance) relative to a changing , and (ii) has a limited negative effect on population persistence.

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There has been extensive sea ice loss in the Chukchi and Beaufort seas where two beluga whale (Delphinapterus leucas) populations occur between July-November. Our goal was to develop population-specific beluga habitat selection models that quantify relative use of sea ice and bathymetric features related to oceanographic processes, which can provide context to the importance of changing sea ice conditions. We established habitat selection models that incorporated daily sea ice measures (sea ice concentration, proximity to ice edge and dense ice) and bathymetric features (slope, depth, proximity to the continental slope, Barrow Canyon, and shore) to establish quantitative estimates of habitat use for the Eastern Chukchi Sea ('Chukchi') and Eastern Beaufort Sea ('Beaufort') populations.

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The backbone dihedral parameters of the Amber RNA force field were improved by fitting using multiple linear regression to potential energies determined by quantum chemistry calculations. Five backbone and four glycosidic dihedral parameters were fit simultaneously to reproduce the potential energies determined by a high-level density functional theory calculation (B97D3 functional with the AUG-CC-PVTZ basis set). Umbrella sampling was used to determine conformational free energies along the dihedral angles, and these better agree with the population of conformations observed in the protein data bank for the new parameters than for the conventional parameters.

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Migrations are often influenced by seasonal environmental gradients that are increasingly being altered by climate change. The consequences of rapid changes in Arctic sea ice have the potential to affect migrations of a number of marine species whose timing is temporally matched to seasonal sea ice cover. This topic has not been investigated for Pacific Arctic beluga whales (Delphinapterus leucas) that follow matrilineally maintained autumn migrations in the waters around Alaska and Russia.

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Loss of Arctic sea ice owing to climate change is the primary threat to polar bears throughout their range. We evaluated the potential response of polar bears to sea-ice declines by (i) calculating generation length (GL) for the species, which determines the timeframe for conservation assessments; (ii) developing a standardized sea-ice metric representing important habitat; and (iii) using statistical models and computer simulation to project changes in the global population under three approaches relating polar bear abundance to sea ice. Mean GL was 11.

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Arctic marine mammals (AMMs) are icons of climate change, largely because of their close association with sea ice. However, neither a circumpolar assessment of AMM status nor a standardized metric of sea ice habitat change is available. We summarized available data on abundance and trend for each AMM species and recognized subpopulation.

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The impact of pulsed versus continuous wave (cw) laser excitation on the photophysical properties of single quantum dots (QDs) has been investigated in an experiment in which all macroscopic variables are identical except the nature of laser excitation. Pulsed excitation exaggerates the effects of photobleaching, results in a lower probability of long ON fluorescence blinking events, and leads to shorter fluorescence lifetimes with respect to cw excitation at the same wavelength and average intensity. Spectral wandering, biexciton quantum yields, and power law exponents that describe fluorescence blinking are largely insensitive to the nature of laser excitation.

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Background: RNA performs many diverse functions in the cell in addition to its role as a messenger of genetic information. These functions depend on its ability to fold to a unique three-dimensional structure determined by the sequence. The conformation of RNA is in part determined by its secondary structure, or the particular set of contacts between pairs of complementary bases.

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Conformational dynamics of proteins are important for function. However, obtaining information about specific conformations is difficult for samples displaying heterogeneity. Here, time-resolved fluorescence resonance energy transfer is used to characterize the folding of single cytochrome molecules.

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Alkynones were treated with boron trifluoride diethyl etherate to generate β-iodoallenolates, which underwent intramolecular aldol reactions to produce cycloalkenyl alcohols. Diastereoselective oxa-Michael ring closure could then be induced by treatment with a catalytic amount of gold(III) chloride, affording highly functionalized tetrahydropyran-containing ring systems.

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The North Water polynya (~76°N to 79°N and 70°W to 80°W) is known to be an important habitat for several species of marine mammals and sea birds. For millennia, it has provided the basis for subsistence hunting and human presence in the northernmost part of Baffin Bay. The abundance of air-breathing top predators also represents a potential source of nutrient cycling that maintains primary production.

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Intraspecific differences in movement behaviour reflect different tactics used by individuals or sexes to favour strategies that maximize fitness. We report movement data collected from n = 23 adult male polar bears with novel ear-attached transmitters in two separate pack ice subpopulations over five breeding seasons. We compared movements with n = 26 concurrently tagged adult females, and analysed velocities, movement tortuosity, range sizes and habitat selection with respect to sex, reproductive status and body mass.

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The selective oxyfunctionalization of isolated sp(3) C-H bonds in complex molecules represents a formidable challenge in organic chemistry. Here, we describe a rational, systematic strategy to expedite the development of P450 oxidation catalysts with refined regio- and stereoselectivity for the hydroxylation of remote, unactivated C-H sites in a complex scaffold. Using artemisinin as model substrate, we demonstrate how a three-tier strategy involving first-sphere active site mutagenesis, high-throughput P450 fingerprinting, and fingerprint-driven P450 reactivity predictions enabled the rapid evolution of three efficient biocatalysts for the selective hydroxylation of a primary and a secondary C-H site (with both S and R stereoselectivity) in a relevant yet previously inaccessible region of this complex natural product.

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The effects of climate change on marine ecosystems and in particular on marine top predators are difficult to assess due to, among other things, spatial variability, and lack of clear delineation of marine habitats. The banks of West Greenland are located in a climate sensitive area and are likely to elicit pronounced responses to oceanographic changes in the North Atlantic. The recent increase in sea temperatures on the banks of West Greenland has had cascading effects on sea ice coverage, residency of top predators, and abundance of important prey species like Atlantic cod (Gadus morhua).

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All-atom force fields are important for predicting thermodynamic, structural, and dynamic properties of RNA. In this paper, results are reported for thermodynamic integration calculations of free energy differences of duplex formation when CG pairs in the RNA duplexes r(CCGG)(2), r(GGCC)(2), r(GCGC)(2), and r(CGCG)(2) are replaced by isocytidine-isoguanosine (iCiG) pairs. Agreement with experiment was improved when ε/ζ, α/γ, β, and χ torsional parameters in the AMBER99 force field were revised on the basis of quantum mechanical calculations.

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Accurately modeling unpaired regions of RNA is important for predicting structure, dynamics, and thermodynamics of folded RNA. Comparisons between NMR data and molecular dynamics simulations provide a test of force fields used for modeling. Here, NMR spectroscopy, including NOESY, (1)H-(31)P HETCOR, DQF-COSY, and TOCSY, was used to determine conformational preferences for single-stranded GACC RNA.

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