Chemistry and Biochemistry Faculty Works

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Open Access
Aging and sperm signals alter DNA break formation and repair in the C. elegans germline
(PLOS, 2022-11-07) Toraason, Erik; Adler, Victoria L.; Libuda, Diana E.
Female reproductive aging is associated with decreased oocyte quality and fertility. The nematode Caenorhabditis elegans is a powerful system for understanding the biology of aging and exhibits age-related reproductive defects that are analogous to those observed in many mammals, including dysregulation of DNA repair. C. elegans germline function is influenced simultaneously by both reproductive aging and signals triggered by limited supplies of sperm, which are depleted over chronological time. To delineate the causes of DNA repair defects in aged C. elegans germlines, we assessed both DNA double strand break (DSB) induction and repair during meiotic prophase I progression in aged germlines which were depleted of self-sperm, mated, or never exposed to sperm. We find that germline DSB induction is dramatically reduced only in hermaphrodites which have exhausted their endogenous sperm, suggesting that a signal due specifically to sperm depletion downregulates DSB formation. We also find that DSB repair is delayed in aged germlines regardless of whether hermaphrodites had either a reduction in sperm supply or an inability to endogenously produce sperm. These results demonstrate that in contrast to DSB induction, DSB repair defects are a feature of C. elegans reproductive aging independent of sperm presence. Finally, we demonstrate that the E2 ubiquitin-conjugating enzyme variant UEV-2 is required for efficient DSB repair specifically in young germlines, implicating UEV-2 in the regulation of DNA repair during reproductive aging. In summary, our study demonstrates that DNA repair defects are a feature of C. elegans reproductive aging and uncovers parallel mechanisms regulating efficient DSB formation in the germline.
Open Access
Ancient hybridization leads to the repeated evolution of red flowers across a monkeyflower radiation
(Oxford Academic, 2023-06-05) Short, Aidan W.; Streisfeld, Matthew A.
The reuse of old genetic variation can promote rapid diversification in evolutionary radiations, but in most cases, the historical events underlying this divergence are not known. For example, ancient hybridization can generate new combinations of alleles that sort into descendant lineages, potentially providing the raw material to initiate divergence. In the Mimulus aurantiacus species complex, there is evidence for widespread gene flow among members of this radiation. In addition, allelic variation in the MaMyb2 gene is responsible for differences in flower color between the closely related ecotypes of subspecies puniceus, contributing to reproductive isolation by pollinators. Previous work suggested that MaMyb2 was introgressed into the red-flowered ecotype of puniceus. However, additional taxa within the radiation have independently evolved red flowers from their yellow-flowered ancestors, raising the possibility that this introgression had a more ancient origin. In this study, we used repeated tests of admixture from whole-genome sequence data across this diverse radiation to demonstrate that there has been both ancient and recurrent hybridization in this group. However, most of the signal of this ancient introgression has been removed due to selection, suggesting that widespread barriers to gene flow are in place between taxa. Yet, a roughly 30 kb region that contains the MaMyb2 gene is currently shared only among the red-flowered taxa. Patterns of admixture, sequence divergence, and extended haplotype homozygosity across this region confirm a history of ancient hybridization, where functional variants have been preserved due to positive selection in red-flowered taxa but lost in their yellow-flowered counterparts. The results of this study reveal that selection against gene flow can reduce genomic signatures of ancient hybridization, but that historical introgression can provide essential genetic variation that facilitates the repeated evolution of phenotypic traits between lineages.
Open Access
Anomalous Dynamics in Macromolecular Liquids
(MDPI, 2022-02-22) Guenza, Marina G.
Macromolecular liquids display short-time anomalous behaviors in disagreement with conventional single-molecule mean-field theories. In this study, we analyze the behavior of the simplest but most realistic macromolecular system that displays anomalous dynamics, i.e., a melt of short homopolymer chains, starting from molecular dynamics simulation trajectories. Our study sheds some light on the microscopic molecular mechanisms responsible for the observed anomalous behavior. The relevance of the correlation hole, a unique property of polymer liquids, in relation to the observed subdiffusive dynamics, naturally emerges from the analysis of the van Hove distribution functions and other properties.
Open Access
Beyond Information: Exploring Patients’ Preferences
(American Medical Association, 2009) Epstein, Ronald; Peters, Ellen
The Institute of Medicine considers patient-centered care (“care that is respectful of and responsive to individual patient preferences, needs and values” 1(p6)) to be a foundation of high-quality health care, along with effectiveness, safety, efficiency, timeliness, and equity. Patient-centered care is empirically based and promotes respect and patient autonomy; it is considered an end in itself, not merely a means to achieve other health outcomes.2 Two parallel efforts have furthered patient-centered care. Shared decision making promotes defining problems, presenting options, and providing high-quality information so patients can participate more actively in care.3 Patient-centered communication promotes healing relationships that elicit and consider patients’ perspectives and understand patients as persons. 2 Both approaches assume that patients can articulate preferences based on stable guiding principles or values. While this may be true in straightforward situations, in novel, unanticipated, and emotionally charged situations, preferences may not be elicited as much as they are constructed—shaped by how information is presented and by the opinions of family, friends, and the media. This Commentary explores how physicians might reconcile the imperative to provide patient-centered care with the complex ways in which clinicians and patients construct preferences.
Open Access
Biological Photocathodes
(Proceedings of the National Academy of Sciences, 1989-03) Griffith, O. H.; Habliston, D. L.; Birrell, G. B.; Skoczylas, W. P.; Hedberg, K. K.
Biological surfaces emit electrons when subjected to UV light. This emission is increased greatly after exposure to cesium vapor. Increases from 2 to 3 orders of magnitude are observed, depending on the biochemicals present. Heme and chlorophyll exhibit unusually high photoemission currents, which are increased further after cesiation. Photoemission from proteins and lipids is much less but also is increased by exposure to cesium. The formation of photocathodes with cesium greatly increases the practical magnifications attainable in photoelectron microscopy of organic and biological specimens. Photoelectron micrographs taken at magnifications ;;;: x 100,000 of chlorophyll-rich thylakoid membranes and of colloidal gold-labeled cytoskeleton preparations of cultured epithelial cells demonstrate the improvement in magnification. The selectivity and stability of the photocathodes suggest the possibility of detecting chromophore binding proteins in membranes and the design of photoelectron labels for tagging specific sites on biological surfaces.
Open Access
The Calculated Properties of Helium II
(University of Oregon, 1973-12) Brooks, James S.; Donnelly, Russell J.
There is a continual need for a consistent set of experimental data on helium II. Compilations have been given in the Appendix of Wilks's "The Properties of Liquid and Solid Helium" and Donnelly's "Experimental Superfluidity." Since then, it has become increasingly evident that all quantities must be known as a function of pressure as well as temperature, and an inspection of experimental data shows that there are many gaps in the (T , P)-plane and not a few inconsistencies. We have decided to try to provide an interim solution to this problem by producing empirical formulae which represent the data over the complete range, excluding the transition region near the A-line. The results of these calculations are tabulated in increments of 0.05 Kin temperature from 0.1 K to 2.10 K, and in increments of 2.5 atmospheres from Oto 25 atmospheres. The tables are presented in Part I and are printed on colored sheets to facilitate reference to different properties. The reliability of each table varies, and in some cases the experimental data are inconsistent. Although most tables are believed to agree with experiment to within± 10% below 1.6 K, the discussions of Part II, and where necessary the original data, should be consulted when accuracy is necessary. The authors are acutely aware of the limitations of these tables and would appreciate receiving suggestions to improve them as well as copies of new experimental data as it becomes available. The success of these tables will be measured, in part, by the speed with which they are superseded.
Open Access
Comparison of fractal and grid electrodes for studying the effects of spatial confinement on dissociated retinal neuronal and glial behavior
(Nature, 2022-10-20) Moslehi, Saba; Rowland, Conor; Smith, Julian H.; Griffiths, Willem; Watterson, William J.; Niell, Cristopher M.; Alemán, Benjamín J.; Perez, Maria-Thereza; Taylor, Richard P.
Understanding the impact of the geometry and material composition of electrodes on the survival and behavior of retinal cells is of importance for both fundamental cell studies and neuromodulation applications. We investigate how dissociated retinal cells from C57BL/6J mice interact with electrodes made of vertically-aligned carbon nanotubes grown on silicon dioxide substrates. We compare electrodes with different degrees of spatial confinement, specifically fractal and grid electrodes featuring connected and disconnected gaps between the electrodes, respectively. For both electrodes, we find that neuron processes predominantly accumulate on the electrode rather than the gap surfaces and that this behavior is strongest for the grid electrodes. However, the ‘closed’ character of the grid electrode gaps inhibits glia from covering the gap surfaces. This lack of glial coverage for the grids is expected to have long-term detrimental effects on neuronal survival and electrical activity. In contrast, the interconnected gaps within the fractal electrodes promote glial coverage. We describe the differing cell responses to the two electrodes and hypothesize that there is an optimal geometry that maximizes the positive response of both neurons and glia when interacting with electrodes.
Open Access
Dinucleotides as simple models of the base stacking-unstacking component of DNA 'breathing' mechanisms
(Oxford Academic, 2021-01) Beyerle, Eric R.; Dinpajooh, Mohammadhasan; Ji, Huiying; von Hippel, Peter H.; Marcus, Andrew H.; Guenza, Marina G.
Regulatory protein access to the DNA duplex 'interior' depends on local DNA 'breathing' fluctuations, and the most fundamental of these are thermally-driven base stacking-unstacking interactions. The smallest DNA unit that can undergo such transitions is the dinucleotide, whose structural and dynamic properties are dominated by stacking, while the ion condensation, cooperative stacking and inter-base hydrogen-bonding present in duplex DNA are not involved. We use dApdA to study stacking-unstacking at the dinucleotide level because the fluctuations observed are likely to resemble those of larger DNA molecules, but in the absence of constraints introduced by cooperativity are likely to be more pronounced, and thus more accessible to measurement. We study these fluctuations with a combination of Molecular Dynamics simulations on the microsecond timescale and Markov State Model analyses, and validate our results by calculations of circular dichroism (CD) spectra, with results that agree well with the experimental spectra. Our analyses show that the CD spectrum of dApdA is defined by two distinct chiral conformations that correspond, respectively, to a Watson-Crick form and a hybrid form with one base in a Hoogsteen configuration. We find also that ionic structure and water orientation around dApdA play important roles in controlling its breathing fluctuations.
Open Access
Electron optical benches for in-line and branched systems. A new bench designed for mirror-based aberration correction and low energy electron microscopy
(Review of Scientific Instruments, 1994-10) Skoczylas, W. P.; Rempfer, G. F.; Griffith, O. H.
A review of electron optical bench literature is presented, and the designs of two optical benches used by the authors are described. One bench was designed for testing individual electrostatic electron lenses and in-line optical systems, for example, emission electron microscopes and transmission electron microscopes. It has been in operation for many years. The second electron optical bench is new. It is a branched system designed for several purposes: to study correction of spherical and chromatic aberration with an electron mirror, and to gain experience with low energy electron microscopy (LEEM) optics. The alignment of the electron optical support structure is independent of the vacuum housing, and the bench is designed to be operated either horizontally or vertically. As a demonstration of the performance of the new bench in the horizontal mode, a test pattern on a silicon surface was imaged with LEEM optics.
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Electron spin resonance and electronic structure of the RCHOR' ether radical
(Journal of Chemical Physics, 1965-04-15) Griffith, O. H.
Single crystals of inclusion compounds formed between urea and aseries of aliphatic ethers were xirradi ated and studied by electron spin resonance. The stable, x-ray-produced free radicals were all of the general type RCHOR'. The approximate value for the spin density on the carbon atom is 0.70±0.10. The unpaired spm distnbution is discussed in terms of the Hiickel and approximate configuration interaction ^--electron molecular orbital models and the valence bond method. The theoretical spin distributions are found tobe in qualitative agreement with the experimental spin distribution.
Open Access
Electron spin resonance and molecular motion of the RCH2CHCOOR' radicals in X‑irradiated ester‑urea inclusion compounds
(Journal of Chemical Physics, 1964-08-15) Griffith, O. H.
Single crystals of the inclusion compounds formed between long-chain alkyl esters and urea were x irradi ated at room temperature, and the free radicals produced were investigated by electron spin resonance. The 11 esters studied were diethyl adipate and the methyl, ethyl, hexyl, and octyl esters of monocarboxylic acids. The long-lived free radicals observed in all of these compounds are of the type RCHaCHCOOR'. These are ir-electron radicals with the unpaired electron largely localized on one carbon 2p orbital. The coupling constants of the alcohol protons (R') were resolved in the spectra of several radicals and the values ranged from 3 to 6 Mc/sec. The ester radicals undergo motion in the tubular cavities formed by the urea molecules of the crystal, and this affects the magnitudes of the proton coupling constants. The de pendence of the a-and /3-proton coupling constants on this motion is briefly considered. From the ethyl heptanoate radical ESR data, recorded over the range of 352° to 7°±3°K, and from the room-temperature ESR data of all eleven ester radicals, information is obtained regarding the motions and orientations of the ester radicals. In addition, two carboxylic-acid-urea inclusion compounds were investigated, and the orientations and motions of the well-known radicals produced in these systems (RCH2CHCOOH) are compared to those of the ester radicals. Approximate equations are given which relate the observed a-proton coupling constants and spectroscopic splitting factors to the diagonal elements of the a-proton tensors and g tensors of all radicals investigated.
Open Access
Electron spin resonance of biological membranes ‑ Spin‑labeled lipids and proteins
(Magnetic Resonance Review, 1988) Volwerk, J. J.; Griffith, O. H.
Open Access
Electron spin resonance of free radicals in perhydrotriphenylene inclusion compounds
(Proceedings of the National Academy of Sciences, 1965-11) Griffith, O. H.
Open Access
Electron spin resonance of oriented RCHSR' sulfide radicals
(Journal of Chemical Physics, 1967-07-15) Griffith, O. H.; Mallon, M. H.
Single crystals of the di-n-hexyl sulfide-urea and diethyl s~lfide--~rea inclusion comi;>ounds were x irradiated at 77°K and the long-lived free radicals produced were mvest1gated by electron spm resonance. The free radicals observed in both crystals were of the type RCHSR'. The value for the spin density on the carbon atom is 0.74±0.07 . The unpaired spin distribution is discussed in terms of simple molecularorbital models.
Open Access
Electron spin resonance of RCHCOR'radicals in X‑irradiated ketone‑urea inclusion compounds
(Journal of Chemical Physics, 1965-04-15) Griffith, O. H.
Single crystals of six inclusion compounds formed between aliphatic ketones and urea were x irradiated at room temperature, and the free radicals produced were investigated by electron spin resonance. The six ketones investigated were 2-nonanone, 6-undecanone, 3-tetradecanone, 2-undecanone, 2-dodecanone, and 3-undecanone. The long-lived free radicals observed in all of these compounds (RCHsCHCOR') are formed by the removal of one a proton from the parent ketone. The unpaired spin density in the 2p orbital adjacent to the carbonyl group is 0.81±0.08. A contour plot of the spin density as a function of the molecular orbital parameters is given. In qualitative agreement with the ESR results, the molecular orbital methods predict the position of maximum spin density to be adjacent to the carbonyl group.
Open Access
Electron spin resonance of X‑irradiated organic inclusion compounds
(Proceedings of the National Academy of Sciences, 1962-11) Griffith, O. H.; McConnell, H. M.
Open Access
Electron spin resonance study of X‑irradiated single crystals of di‑n‑ butyl oxalate‑urea and di‑n‑butyl malonate‑urea inclusion compounds
(Journal of Chemical Physics, 1970-12-01) Lai, A. A.; Birrell, G. B.; Griffith, O. H.
Open Access
ESR of an alkylalkoxyamino radical trapped in X‑irradiated decanal oxime O‑methyl ether‑urea inclusion crystals
(Journal of Chemical Physics, 1972-01-15) Ciecierska‑Tworek, Z; Birrell, G. B.; Griffith, O. H.
Open Access
Evidence for boundary lipid in membranes
(Proceedings of the National Academy of Sciences, 1973-02) Jost, P. C.; Griffith, O. H.; Capaldi, R. A.; Vanderkooi, G.
ABSTH\OT (Mochromc oxidase (EC 1.9.3.1) isolated from hccf-hcarl mitochondria with an appropriate phospholipid content forms vesicular structures. Lipid-protein interactions in this model membrane system were studied with the,lipid spin label, 16-doxylstearic acid. As the phospholipid/ prolein ratio is varied, two spectral components are ohserved. Al low phospholipid/prolcin ratios (<0.19 mg of phospholipid per mg of protein) the lipid spin label is liifCll!) immobilized. At higher phospholipid content an additional component characteristic of fluid lipid hilayers is evideiil. By summation of digilalized spectra and subsequent integration it was shown that all composite spec tra could he approximated by assuming only two com ponents arc present, and that the amount of phospholipid hound In Ihr protein is independent of the extent of the fluid hilaw-r region. The experimentally determined amount of phospholipid for maximum occupancy of pro- Iciii-hound niies is ahouI 0.2 mg of phospholipid per 1.0 nig itl protein. Iialiulalions show that this ralio is con sistent with a single layerof phospholipid surrounding the protein complex. The data are interpreted as evidence for a boundary of immobilized lipid between the hydrophobic protein and adjacent fluid hilayer regions in this membrane model system.
Open Access
Evolving Stark Effect During Growth of Perovskite Nanocrystals Measured Using Transient Absorption
(Frontiers, 2020-10) Sadighian, James C.; Wilson, Kelly S.; Crawford, Michael L.; Wong, Cathy Y.
Methylammonium lead triiodide (MAPbI3) nanocrystals (NCs) are emerging materials for a range of optoelectronic applications. Photophysical characterization is typically limited to structurally stable NCs owing to the long timescales required for many spectroscopies, preventing the accurate measurement of NCs during growth. This is a particular challenge for non-linear spectroscopies such as transient absorption. Here we report on the use of a novel single-shot transient absorption (SSTA) spectrometer to study MAPbI3 NCs as they grow. Comparing the transient spectra to derivatives of the linear absorbance reveals that photogenerated charge carriers become localized at surface trap states during NC growth, inducing a TA lineshape characteristic of the Stark effect. Observation of this Stark signal shows that the contribution of trapped carriers to the TA signal declines as growth continues, supporting a growth mechanism with increased surface ligation toward the end of NC growth. This work opens the door to the application of time-resolved spectroscopies to NCs in situ, during their synthesis, to provide greater insight into their growth mechanisms and the evolution of their photophysical properties.

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