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2019 W.M. Keck Science Department Publications and Grants

*Indicates student co-author

Dallas, Tad, Alyssa-Lois M. Gehman, A. Alonso Aguirre, Sarah A. Budischak, John M. Drake, Maxwell J. Farrell, Ria Ghai, Shan Huang, and Ignacio Morales-Castilla. “Contrasting Latitudinal Gradients of Body Size in Helminth Parasites and Their Hosts.” Global Ecology and Biogeography, vol. 28, issue 6, 2019, pp. 804-813.

Aim: We examined body size scaling relationships for two developmental life stages of parasitic helminths (egg and adult) separately in relationship to latitude (i.e. Bergmann's rule), temperature and temperature seasonality. Given that helminth eggs experience environmental conditions more directly, whereas adults live inside infected host individuals, we predict stronger environmentally driven gradients of body size for eggs than for adults. Location: Global. Time period: Present day. Major taxa studied: Parasitic helminths. Methods: We compiled egg size and adult body size data (both minimum and maximum) for 265 parasitic helminth species from the literature, along with species latitudinal distribution information using an extensive global helminth occurrence database. We then examined how the average helminth egg and adult body size of all helminth species present (minimum and maximum separately) scaled with latitude, temperature and temperature variability, using generalized linear models. Results: Both the egg size and the adult body size of helminths tended to decrease towards higher latitudes, although we found the opposite body size scaling pattern for their host species. Helminth sizes were also positively correlated with temperature and negatively, but more weakly, with temperature seasonality. Main conclusions: Instead of following the body size patterns of their hosts, helminth parasites are more similar to other ectotherms in that they follow the converse Bergmann's rule. This pattern did not differ between helminth developmental stages, suggesting that mean annual temperature and seasonality are unlikely to be related mechanistically to body size variation in this case.


Ezenwa, Vanessa O., Anna E. Jolles, Brianna R. Beechler, Sarah A. Budischak, and Erin E. Gorsich. “The Causes and Consequences of Parasite Interactions: African Buffalo as a Case.” Wildlife Disease Ecology: Linking Theory to Data and Application, edited by Kenneth Wilson, Andy Fenton, and Dan Tompkins. Cambridge University Press, 2019, pp. 129-160


Gehman, Alyssa-Lois M., Dara A. Satterfield, Carolyn L. Keogh, Alexa Fritzsche McKay, and Sarah A. Budischak. “To Improve Ecological Understanding, Collect Infection Data.” Ecosphere, vol. 10, issue 6, e02770.

Abstract: Ecologists seek to understand and predict how organisms respond to multiple interacting biotic and abiotic influences, an increasingly difficult task under anthropogenic change. Parasites are one of these biotic influences that are pervasive in natural systems and frequently interact with other stressors. Because they often have cryptic effects on their host organisms, their role in the distribution, abundance, composition, and dynamics of populations, communities, and ecosystems is easy to overlook. However, studies that neglect the role of parasitism may miss or misinterpret organismal responses to environmental change, hampering ecological predictions. We discuss case studies wherein the inclusion of parasite infection status altered the interpretation of ecological outcomes, and offer paths forward to make parasite data acquisition, analysis, and interpretation more accessible to ecologists. Given that parasites are responsive to environmental changes, timely attention to their influence on host responses is critical for accurately predicting future ecological states.


van Leeuwen, Anieke, Sarah A. Budischak, Andrea L. Graham, and Clayton E. Cressler. “Parasite Resource Manipulation Drives Bimodal Variation in Infection Duration.” Proceedings of the Royal Society B, vol. 286, issue 1902, 2019, 20190456.

Abstract: Over a billion people on earth are infected with helminth parasites and show remarkable variation in parasite burden and chronicity. These parasite distributions are captured well by classic statistics, such as the negative binomial distribution. But the within-host processes underlying this variation are not well understood. In this study, we explain variation in macroparasitic infection outcomes on the basis of resource flows within hosts. Resource flows realize the interactions between parasites and host immunity and metabolism. When host metabolism is modulated by parasites, we find a positive feedback of parasites on their own resources. While this positive feedback results in parasites improving their resource availability at high burdens, giving rise to chronic infections, it also results in a threshold biomass required for parasites to establish in the host, giving rise to acute infections when biomass fails to clear the threshold. Our finding of chronic and acute outcomes in bistability contrasts with class theory, yet is congruent with the variation in helminth burdens observed in human and wildlife populations.


External Grant: National Science Foundation, Division of Environmental Biology- Ecology of Infectious Diseases. “Habitat and Coinfection as Drivers of Heterogeneity in Cross-Scale Wildlife Infectious Disease Processes.” Principal Investigator: Kristian Forbes. Co-Principal Investigators: Clayton Cressler, Richard Hall, and Sarah Budischak. Award #1911925, June 15, 2019-June 30, 2024.

Abstract: In order to predict and control the spread of infectious diseases, it is important to understand the role of "superspreaders". These are hosts who transmit disease more often than most other infected individuals. To understand superspreaders this project will investigate how immunity to infections, host diet, and whether or not the host is infected with other parasites creates variation among individuals in susceptibility to pathogens and the ability to transmit infections. To do so, this project will develop mathematical frameworks of virus spread, to predict how food resources and infection with a parasite will first shape the risk that an individual will become infected, and then, will shape the spread of disease across populations and landscapes. These predictions will be tested using laboratory and field experiments with bank voles infected with Puumala hantavirus. The results of this project will shed new light on why some individuals become superspreaders and others do not. This has relevance to improving surveillance and management of this hantavirus, which regularly spills over from its vole reservoir host to infect humans, as well to other pathogens of concern to human and agricultural health. The project will also support the training of high school science teachers from across the United States, providing them with a hands-on research experience in Finland. This will equip them with activities and materials to use to teach high school students about the importance of emerging infectious diseases. This research will examine the individual and synergistic effects of habitat quality and helminth coinfection on wild bank voles infected with the zoonotic pathogen, Puumala hantavirus. The project will develop novel mathematical theory to mechanistically link diet and coinfection with pathogen transmission to predict how bottom-up (diet-driven) and top-down (coinfection-driven) processes interact to drive the emergence of superspreaders, and how this individual-level variation scales up to influence pathogen transmission at the population- and landscape-level. These predictions will be tested using both laboratory vole infection experiments and powerful manipulative experiments involving supplemental feeding and de-worming treatments of wild vole populations in forests. By concurrently developing mathematical models and integrating them with empirical data, this project will quantify how habitat and coinfection influence (1) individual host competence for microparasite infection, (2) demographic and contact processes governing local transmission and (3) dispersal rates and landscape attributes that determine spatial spread of disease.

Chandrangsu, Pete, Xiaojuan Huang, Ahmed Gaballa, and John D. Helmann. “Bacillus Subtilis FolE is Sustained by the ZagA Zinc Metallochaperone and the Alarmone ZTP Under Conditions of Zinc Deficiency.” Molecular Microbiology, vol. 112, issue 3, 2019, pp. 751-765.

Abstract: Bacteria tightly regulate intracellular zinc levels to ensure sufficient zinc to support essential functions, while preventing toxicity. The bacterial response to zinc limitation includes the expression of putative zinc metallochaperones belonging to subfamily 1 of the COG0523 family of G3E GTPases. However, the client proteins and the metabolic processes served by these chaperones are unclear. Here, we demonstrate that the Bacillus subtilis YciC zinc metallochaperone (here renamed ZagA for ZTP activated GTPase A) supports de novo folate biosynthesis under conditions of zinc limitation, and interacts directly with the zinc-dependent GTP cyclohydrolase IA, FolE (GCYH-IA). Furthermore, we identify a role for the alarmone ZTP, a modified purine biosynthesis intermediate, in the response to zinc limitation. ZTP, a signal of 10-formyl-tetrahydrofolate (10f-THF) deficiency in bacteria, transiently accumulates as FolE begins to fail, stimulates the interaction between ZagA and FolE, and thereby helps to sustain folate synthesis despite declining zinc availability.


Do, Hackwon, Nishanth Makthal, Pete Chandrangsu, Randall J. Olsen, John D. Helmann, James M. Musser, and Muthiah Kumaraswami. “Metal Sensing and Regulation of Adaptive Responses to Manganese Limitation by MtsR is Critical for Group A Streptococcus Virulence.” Nucleic Acids Research, 2019, vol. 47, issue 15, 2019, pp. 8333-8334.

Abstract: Pathogenic bacteria encounter host-imposed manganese (Mn) limitation during infection. Herein we report that in the human pathogen Streptococcus pyogenes, the adaptive response to Mn limitation is controlled by a DtxR family metalloregulator, MtsR. Genes upregulated by MtsR during Mn limitation include Mn (mtsABC) and Fe acquisition systems (sia operon), and a metal-independent DNA synthesis enzyme (nrdFEI.2). To elucidate the mechanism of metal sensing and gene regulation by MtsR, we determined the crystal structure of MtsR. MtsR employs two Mn sensing sites to monitor metal availability, and metal occupancy at each site influences MtsR regulatory activity. The site 1 acts as the primary Mn sensing site, and loss of metal at site 1 causes robust upregulation of mtsABC. The vacant site 2 causes partial induction of mtsABC, indicating that site 2 functions as secondary Mn sensing site. Furthermore, we show that the C-terminal FeoA domains of adjacent dimers participate in the oligomerization of MtsR on DNA, and multimerization is critical for MtsR regulatory activity. Finally, the mtsR mutant strains defective in metal sensing and oligomerization are attenuated for virulence in a mouse model of invasive infection, indicating that Mn sensing and gene regulation by MtsR are critical processes during S. pyogenes infection.

Coleman, Melissa J., David Saxon*, Anastasia Robbins*, Natalie Lillie*, and Nancy F. Day. “Operant Conditioning Task to Measure Song Preference in Zebra Finches.” Journal of Visualized Experiments, issue 154, e60590.

Abstract: An operant conditioning paradigm is used to test the song preference of female zebra finches. Finches are placed in a two-chambered cage with a connecting opening and indicate their preference for a song by landing on a perch within each chamber. By interrupting the infrared beam from a photoelectric sensor above each perch, the bird activates the playback of a song through a speaker located on each side of the cage. Freely available software is used to trigger the song playback from each perch. To determine the song preference of each animal, her chamber preference is first identified by triggering no song playback when she lands on each perch. This chamber preference is then compared to her song preference. A minimum activity threshold is set to ensure the preference is real. Using this method, we show that paired females prefer the song of their partner. This method was used to understand the contribution of dopamine to the formation and maintenance of song preference.


Day, Nancy F., David Saxon*, Anastasia Robbins*, Lily Harris*, Emily Nee*, Naomi Shroff-Mehta*, Kaeley Stout*, Julia Sun*, Natalie Lillie*, Mara Burns*, and Melissa J. Coleman. “D2 Dopamine Receptor Activation Induces Female Preference for Male Song in the Monogamous Zebra Finch.” Journal of Experimental Biology, vol. 222, issue 5, 2019, jeb191510.

Abstract: The evolutionary conservation of neural mechanisms for forming and maintaining pair bonds is unclear. Oxytocin, vasopressin and dopamine (DA) transmitter systems have been shown to be important in pair-bond formation and maintenance in several vertebrate species. We examined the role of dopamine in formation of song preference in zebra finches, a monogamous bird. Male courtship song is an honest signal of sexual fitness; thus, we measured female song preference to evaluate the role of DA in mate selection and pairbond formation, using an operant conditioning paradigm. We found that DA acting through the D2 receptor, but not the D1 receptor, can induce a song preference in unpaired female finches and that blocking the D2 receptor abolished song preference in paired females. These results suggest that similar neural mechanisms for pair-bond formation are evolutionarily conserved in rodents and birds. This article was short-listed for the JEB Outstanding Paper Prize.


Elie, J.E., S. Hoffmann, J.L, Dunning, Melissa J. Coleman, E.S. Fortune, and J.F. Prather. “From Perception to Action: The Role of Auditory Input in Shaping Vocal Communication and Social Behaviors in Birds.” Brain, Behavior and Evolution, vol. 94, 2019, pp. 51-60.

Abstract: Acoustic communication signals are typically generated to influence the behavior of conspecific receivers. In songbirds, for instance, such cues are routinely used by males to influence the behavior of females and rival males. There is remarkable diversity in vocalizations across songbird species, and the mechanisms of vocal production have been studied extensively, yet there has been comparatively little emphasis on how the receiver perceives those signals and uses that information to direct subsequent actions. Here, we emphasize the receiver as an active participant in the communication process. The roles of sender and receiver can alternate between individuals, resulting in an emergent feedback loop that governs the behavior of both. We describe three lines of research that are beginning to reveal the neural mechanisms that underlie the reciprocal exchange of information in communication. These lines of research focus on the perception of the repertoire of songbird vocalizations, evaluation of vocalizations in mate choice, and the coordination of duet singing.

Alhoch, Bashar*, Alan Chen*, Elaine Chan*, Asmaa Elkabti*, Sasha Fariña*, Catherine Gilbert*, Jean Kang*, Bradley King*, Karen Leung*, Julia Levy*, Elizabeth Martin*, Benjamin Mazer*, Sara McKinney*, Alexandra Moyzis*, Margaret Nurimba*, Michelle Ozaki*, Kathleen Purvis-Roberts, Joshua Marc Rothman*, Shravya Raju*, Cynthia Selassie, Oliver Smith*, Julia Ticus*, Gretchen Edwalds-Gilbert, M. Cristina Negritto, Ruye Wang, and Zhaohua Tang. “Comparative Genomic Screen in Two Yeast Reveals Conserved Pathways in the Response Network to Phenol Stress.” G3: Genes, Genomes, Genetics, vol. 9, no. 3, 2019, pp. 639-650.

Abstract: Living organisms encounter various perturbations, and response mechanisms to such perturbations are vital for species survival. Defective stress responses are implicated in many human diseases including cancer and neurodegenerative disorders. Phenol derivatives, naturally occurring and synthetic, display beneficial as well as detrimental effects. The phenol derivatives in this study, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and bisphenol A (BPA), are widely used as food preservatives and industrial chemicals. Conflicting results have been reported regarding their biological activity and correlation with disease development; understanding the molecular basis of phenol action is a key step for addressing issues relevant to human health. This work presents the first comparative genomic analysis of the genetic networks for phenol stress response in an evolutionary context of two divergent yeasts, Schizosaccharomyces pombe and Saccharomyces cerevisiae. Genomic screening of deletion strain libraries of the two yeasts identified genes required for cellular response to phenol stress, which are enriched in human orthologs. Functional analysis of these genes uncovered the major signaling pathways involved. The results provide a global view of the biological events constituting the defense process, including cell cycle arrest, DNA repair, phenol detoxification by V-ATPases, reactive oxygen species alleviation, and endoplasmic reticulum stress relief through ergosterol and the unfolded protein response, revealing novel roles for these cellular pathways.


Edwalds-Gilbert, Gretchen. “Building Bridges between Basic Science and Clinical Medicine: A Liberal Arts Perspective.” Medical Science Pulse, vol. 13, issue 1, 2019, pp. 55-59.

Abstract: A critical issue for improving global health care is to better integrate basic science and clinical practice, as such integration will lead to innovative solutions. In this article, I will present models for how to prepare students to participate effectively on multidisciplinary teams that foster cooperation between scientists, medical centers, biotechnology businesses, and governmental bodies. I will provide examples of training programs in the United States (USA) designed to increase the number of and diversity of scientists and clinicians engaged in bridging basic science and clinical medicine, also called translational research. The training programs target different stages in career development, from pre-medical students through early career faculty, and have varied organisational structures. Many of the programs have existed long enough for institutions to be able to evaluate their effectiveness, and despite the different program contexts, there are key characteristics common to all of the programs that correlate with successful outcomes. Many of these characteristics can be adapted to other career stages and settings. I will summarize these and describe an example of an interdisciplinary, integrated science course for undergraduates that introduces students at the earliest stage of their careers to addressing complex problems through teamwork. Finally, I will provide suggestions for how other institutions can implement training programs that will build bridges between basic science and clinical medicine.


External Grant: Fulbright Scholar Award extension, Regulation of gene expression by mRNA translation in response to stress. University of Warsaw Institute for Genetics and Biotechnology, extension granted July-September 2019.

Abstract: Cells encounter stress through their interactions with the environment and either respond successfully, maintaining homeostasis, or do not, leading to cell death. Changes in gene expression critical to resolving the stress response are regulated at many stages, including gene transcription, pre-mRNA alternative processing, mRNA modification, transport, and translation. While scientists have been aware of these steps for many years, the recognition of translation as a key regulated step depended on the development of high-resolution techniques that permit detailed analysis of the translation machinery, the ribosome, as it is translating. Through these techniques, called ribosome profiling, scientists identified many new longer or shorter proteins or peptides that influence the expression of the major translation product of the same mRNA (Cabrero-Quio et al. 2016; Gerashchenko et al. 2012; Olexiouk et al. 2015). Scientists recognize that specific types of stress can induce different changes in gene expression through translation regulation that is key to maintaining homeostasis. Regulation of translation after stress exposure is associated with many diseases, including cancer (reviewed in Leprivier et al. 2015; Sendoel et al. 2017) and is also relevant to environmental stresses organisms face with climate changes. This research will investigate how cells regulate translation, specifically of upstream non-AUG open reading frames (u-ORFs), after exposure to different types of stress.

Ferree, Elise D. “An Experimental Test of the Effect of Male Attractiveness on Maternal Investment in Dark-Eyed Juncos.” The Auk: Ornithological Advances, vol. 136, 2019, pp. 1-12.

Abstract: While social mate choice is an obvious point where sexual selection acts on males, cryptic selection can occur based on how much females invest in a male’s offspring. I tested 4 hypotheses about the relationship between female investment and social mate attractiveness by manipulating a sexually selected trait, white tail feathers (“tail white”), in male Dark-eyed Juncos (Junco hyemalis thurberi): (1) the differential allocation hypothesis predicts that females optimize lifetime reproductive success by maximizing parental investment in the offspring of ornamented mates and minimizing investment when mated to less attractive males; (2) instead of positive differential allocation, females could show negative differential allocation by investing more in less attractive males to compensate for their lower quality; (3) female care could also be influenced directly by paternal investment, in particular what appears to be positive differential allocation could be compensation for reduced care by attractive males; or (4) females could reduce care when paired with socially attractive males that are “good parents”. To evaluate these hypotheses, I examined the impact of tail white manipulation on clutch size, female incubation and brooding, and female and male provisioning. Females did not differentially allocate in relation to social mate attractiveness, nor were females responsive to patterns of male investment, even although artificially attractive males provisioned offspring significantly more than did controls. Naturally bright males, who were also the largest males, did not provision at higher rates, highlighting the need to experimentally separate the role of specific traits from other correlated factors. Tail whitemanipulated males were involved in rare cases of polygyny and at times were actively guarded by their mates. Together, these results suggest that tail white influences reproductive behaviors in this junco population, but because of the potential for extrapair paternity, additional data are needed to accurately investigate the trait’s role in female investment.

Muenzen, Kathleen*, Jenna Monroy, and Findley R. Finseth. “Evolution of the Highly Repetitive PEVK Region of Titin Across Mammals.” G3: Genes, Genomes, Genetics, vol. 9, issue 4, 2019, pp. 1103-1115.

Abstract: The protein titin plays a key role in vertebrate muscle where it acts like a giant molecular spring. Despite its importance and conservation over vertebrate evolution, a lack of high quality annotations in non-model species makes comparative evolutionary studies of titin challenging. The PEVK region of titin—named for its high proportion of Pro-Glu-Val-Lys amino acids—is particularly difficult to annotate due to its abundance of alternatively spliced isoforms and short, highly repetitive exons. To understand PEVK evolution across mammals, we developed a bioinformatics tool, PEVK_Finder, to annotate PEVK exons from genomic sequences of titin and applied it to a diverse set of mammals. PEVK_Finder consistently outperforms standard annotation tools across a broad range of conditions and improves annotations of the PEVK region in non-model mammalian species. We find that the PEVK region can be divided into two subregions (PEVK-N, PEVK-C) with distinct patterns of evolutionary constraint and divergence. The bipartite nature of the PEVK region has implications for titin diversification. In the PEVK-N region, certain exons are conserved and may be essential, but natural selection also acts on particular codons. In the PEVK-C, exons are more homogenous and length variation of the PEVK region may provide the raw material for evolutionary adaptation in titin function. The PEVK-C region can be further divided into a highly repetitive region (PEVK-CA) and one that is more variable (PEVK-CB). Taken together, we find that the very complexity that makes titin a challenge for annotation tools may also promote evolutionary adaptation.


Nelson, Thomas C., Patrick J. Monnahan, Mariah K. McIntosh, Kayli Anderson, Evan MacArthur-Waltz, Findley R. Finseth, John K. Kelly, and Lila Fishman. “Extreme Copy Number Variation at a tRNA Ligase Gene Affecting Phenology and Fitness in Yellow Monkeyflowers.” Molecular Ecology, vol. 28, issue 6, 2019, pp. 1460-1475.

Abstract: Copy number variation (CNV) is a major part of the genetic diversity segregating within populations, but remains poorly understood relative to single nucleotide variation. Here, we report on a tRNA ligase gene (Migut.N02091; RLG1a) exhibiting unprecedented, and fitness‐relevant, CNV within an annual population of the yellow monkeyflower Mimulus guttatus. RLG1a variation was associated with multiple traits in pooled population sequencing (PoolSeq) scans of phenotypic and phenological cohorts. Resequencing of inbred lines revealed intermediate frequency three‐copy variants of RLG1a (trip+; 5/35 = 14%), and trip+ lines exhibited elevated RLG1a expression under multiple conditions. trip+ carriers, in addition to being over‐represented in late‐flowering and large‐flowered PoolSeq populations, flowered later under stressful conditions in a greenhouse experiment (P < 0.05). In wild population samples, we discovered an additional rare RLG1a variant (high+) that carries 250‐300 copies of RLG1a totaling ~5.7Mb (20‐40% of a chromosome). In the progeny of a high+ carrier, Mendelian segregation of diagnostic alleles and qPCR‐based copy counts indicate that high+ is a single tandem array unlinked from the single copy RLG1a locus. In the wild, high+ carriers had highest fitness in two particularly dry and/or hot years (2015 and 2017; both p < 0.01), while single copy individuals were twice as fecund as either CNV type in a lush year (2016: p < 0.005). Our results demonstrate fluctuating selection on CNVs affecting phenological traits in a wild population, suggest that plant tRNA ligases mediate stress‐responsive life‐history traits, and introduce a novel system for investigating the molecular mechanisms of gene amplification.

Ober, Gordon T., Rhiannon L. Rognstad, and Sarah E. Gilman. “The Cost of Emersion for the Barnacle Balanus Glandula.” Marine Ecology Progress Series, vol. 627, 2019, pp. 95-107.

Abstract: Temperate intertidal species frequently experience broad temperature fluctuations during emersion. However, the metabolic cost of exposure to a particular emersion temperature is not known for most species. We quantified oxygen (O2) consumption by the intertidal barnacle Balanus glandula over a combined 5 h emersion and a 6 h immersion period. Barnacles were ex - posed to air temperatures of 10, 15, 20, 25, 30, 35, or 38°C followed by a 10°C immersion. Respiration was monitored using a fluorometric O2 system. Total O2 consumption over the 11 h period by B. glandula increased with increasing emersion temperatures, reaching a maximum between 20 and 30°C, where consumption was significantly greater than that at 10°C. Aerial and aquatic phases showed similar patterns with temperature, but significant differences among temperatures were only detected in the aerial phase. We also found that respiration rates peaked during the first hour at temperature during emersion and the second hour of immersion. A separate analysis of barnacle behavior over a longer immersion period suggested that stressful emersion temperatures require recovery periods longer than 6 h; thus, our results may underestimate the full cost of thermal stress. When compared to previously published measurements of barnacle body temperatures in the field, our results suggest a large vertical gradient in thermal exposure costs, nearly doubling with a 1 m increase in shore height. We highlight both the difficulty and importance of generating accurate estimates of emersion costs. Such costs are likely to be critical in determining organismal and population responses to changing climate.


External Grant: 2019 National Science Foundation Research Experience for Teachers supplement, 2019,  $9,322.

Abstract: The teacher will participate for 6-weeks this summer in an ongoing study of the thermal physiology of the barnacle Balanus glandula. As an RET fellow, she will be a full participant in all laboratory activities and learn techniques in experimental design, whole-animal respirometry, and data presentation and analysis. During the summer she will also meet with the PI regularly to plan new curricula for her 5th grade class at Oakmont Elementary School. These activities will meet California's new Next Generation Science Standards and will focus on the full process of science, from experimental design through to making evidence-based arguments. Ms. Emilia Marquez, a 4th/5th grade teacher at Oakmont Elementary School in Claremont, California, has been selected as the RET teacher for this proposal. Oakmont is a Title 1 school, with 54.5% of students considered low-income and 62.4% from communities under-represented in science. The ability of these students to access realistic science experiences early in their education is a critical first step for them to envision a future STEM career.

Friedman, Eric, Scott M. Garrabrant*, Ilona Phipps-Morgan*, Adam S. Landsberg, and Urban Larsson. “Geometric Analysis of a Generalized Wythoff Game.” Games of No Chance 5, MSRI series 70, edited by Urban Larsson. Cambridge University Press, 2019, pp. 343-373.

Abstract: Combinatorial 2-player games can be studied from different perspectives. Traditionally the goal has been to acquire a perfect strategy, and to this purpose an efficient procedure (polynomial in succinct input size) is required. However, most combinatorial games are intrinsically hard to analyze; success is limited to a small number of games with predominant 'mathematical structure'. The classical games of Nim (Bouton 1901) and Wythoff Nim (Wythoff 1907) are easy to analyze rigorously, but already seemingly modest variants, like (p, q)-GDWN (Larsson 2012, 2014), appear to withstand log-polynomial descriptions. Therefore, development of new methods is highly desirable. Here, we use methods from physics, e.g. renormalization, in an attempt to understand the larger geometry of a game's P-positions (safe positions for the Previous player), rather than their exact configurations (Friedman et al. 2007, 2009). By studying evolution diagrams of a general class of linear extensions of Nim, Wythoff Nim and GDWN, we observe that P-positions often distribute uniformly along lines (a.k.a. P-beams), visually separated from the move lines. Given a fundamental hypothesis, a filling property which generalizes directly from Wythoff Nim, we formulate natural equations on the slopes and densities of P-positions along these lines; here, a key innovation, a reorganization model, guides us in selecting the relevant rules (move lines). The exceptional case of the symmetric (p, q)-GDWN is interesting, because of observed quasi-log repetitive fluctuations, and these games have defied all previous analysis.

External Grant: R15 Award (National Institutes of Health), "High-throughput engineering and characterization of brighter luciferases." Principal Investigator: Aaron Leconte, 2019-2022, $362,752.

Abstract: Luciferase Bioluminescence Imaging (BLI) is a non-invasive method for monitoring diverse processes in living systems. BLI couples in vitro and in vivo biological events to the bioluminescent output of the enzyme luciferase. The potential detection limit, versatility, and temporal and spatial resolution of BLI assays can even exceed fluorescence-based methods when in the context of deep tissue or whole animal imaging applications. For these reasons, BLI has been a foundational imaging tool in whole animal imaging applied to both the study of diseases as well as in the evaluation of potential therapies. The most frequently used enzyme for BLI is Firefly luciferase (F-Luc), the luciferase enzyme from the North American firefly (Photinus pyralis); engineering of F-Luc is needed to expand and improve its applications. Here, we propose methodological advances to F-Luc engineering, which should yield important biochemical data, generate potentially useful enzymes, and provide important precedent for further studies in the field. One of the current challenges of F-Luc engineering is the dearth of biochemical data that can be used to guide evolution efforts in the laboratory. In Aim 1, we propose to use high-throughput biochemical approaches, which combine high-throughput screening, next generation sequencing, and computational analysis to measure four important biochemical parameters (brightness, emission color, thermostability, and substrate selectivity) for 500 amino acid mutations en masse. This work will provide insight into the relationship between sequence and protein function for a substantial portion of the luciferase protein, which will inform future engineering efforts by our lab and others, as well as lead to a broader understanding of luciferase function. A second major challenge in F-Luc engineering is that improvement of one property (e.g. emission color) is often coupled to loss of the enzyme's brightness, diminishing the value of engineered F-Luc mutants. In Aim 2, we propose to apply a method that we have recently developed to identify brighter luciferase enzymes; we will apply the method to two recently discovered F-Luc mutants, which have applications in multi-component imaging applications. In addition to improved enzymes with immediate imaging applications, this work will constitute the first direct screen for luciferase brightness to date, providing a methodological advancement for the field of luciferase engineering.

Marzen, Sarah. “Novelty Detection Improves Performance of Reinforcement Learners in Fluctuating, Partially Observable Environments.” Journal of Theoretical Biology, vol. 477, 2019, pp. 44-50.

Abstract: Evolved and engineered organisms must adapt to fluctuating environments that are often only partially observed. We show that adaptation to a second environment can be significantly harder after adapting to a first, completely unrelated environment, even when using second-order learning algorithms and a constant learning rate. In effect, there is a lack of fading memory in the organism’s performance. However, organisms can adapt well to the second environment by incorporating a simple novelty detection algorithm that signals when the environment has changed and reinitializing the parameters that define their behavior if so. We propose that it may be fruitful to look for signs of this novelty detection in biological organisms, and to engineer novelty detection algorithms into artificial organisms.


External Grant: Marzen, Sarah. “Minimal Models of Sensory Prediction.” Air Force Office of Scientific Research (AFOSR), 2019.

Abstract: Although many neuroscientists seem to believe that the brain predicts sensory input, such assertions still lack conclusive evidence and associated understanding of the neural code and neural mechanisms. Using a recent technical advance in the benchmarking of predictive performance, we aim to: test the ability of humans and networks of cultured neurons to predict sensory input; unravel the neural code of prediction in the network of neurons; and explore the effects of synaptic dysfunction on prediction capability of the neurons. The results of this research will rigorously demonstrate when and how humans and neurons are good at predicting input, and may lead to new learning rules for recurrent neural networks trying to predict.

Muenzen, Kathleen*, Jenna Monroy, and Findley R. Finseth. “Evolution of the Highly Repetitive PEVK Region of Titin Across Mammals.” G3: Genes, Genomes, Genetics, vol. 9, issue 4, 2019, pp. 1103-1115.

Abstract: The protein titin plays a key role in vertebrate muscle where it acts like a giant molecular spring. Despite its importance and conservation over vertebrate evolution, a lack of high quality annotations in non-model species makes comparative evolutionary studies of titin challenging. The PEVK region of titin—named for its high proportion of Pro-Glu-Val-Lys amino acids—is particularly difficult to annotate due to its abundance of alternatively spliced isoforms and short, highly repetitive exons. To understand PEVK evolution across mammals, we developed a bioinformatics tool, PEVK_Finder, to annotate PEVK exons from genomic sequences of titin and applied it to a diverse set of mammals. PEVK_Finder consistently outperforms standard annotation tools across a broad range of conditions and improves annotations of the PEVK region in non-model mammalian species. We find that the PEVK region can be divided into two subregions (PEVK-N, PEVK-C) with distinct patterns of evolutionary constraint and divergence. The bipartite nature of the PEVK region has implications for titin diversification. In the PEVK-N region, certain exons are conserved and may be essential, but natural selection also acts on particular codons. In the PEVK-C, exons are more homogenous and length variation of the PEVK region may provide the raw material for evolutionary adaptation in titin function. The PEVK-C region can be further divided into a highly repetitive region (PEVK-CA) and one that is more variable (PEVK-CB). Taken together, we find that the very complexity that makes titin a challenge for annotation tools may also promote evolutionary adaptation.

Golden-Marx, Emmet, Elizabeth L. Blanton, Rachel Paterno-Mahler, Mark Brodwin, Matthew L.N. Ashby, Brian C. Lemaux, Lori M. Lubin, Roy R. Gal, and Adam R. Tomczak. “The High-Redshift Clusters Occupied by Bent Radio AGN (COBRA) Survey: Follow-Up Optical Imaging.” The Astrophysical Journal, vol. 887, no. 1, article 50.

Abstract: Here we present new red sequence overdensity measurements for 77 fields in the high-z Clusters Occupied by Bent Radio AGN (COBRA) survey, based on r- and i-band imaging taken with the Lowell Observatory's Discovery Channel Telescope. We observe 38 COBRA fields in the r-band and 90 COBRA fields in the i-band. By combining the r- and i-band photometry with our 3.6 and 4.5 μSpitzer IRAC observations, we identify 39 red sequence cluster candidates that host a strong overdensity of galaxies when measuring the excess of red sequence galaxies relative to a background field. We initially treat the radio host as the cluster center and then determine a new cluster center based on the surface density of red sequence sources. Using our color selection, we identify which COBRA cluster candidates have strong red sequence populations. By removing foreground and background contaminants, we more securely determine which fields include cluster candidates with a higher significance than our single-band observations. Additionally, of the 77 fields we analyze with a redshift estimate, 26 include newly estimated photometric redshifts.

Alhoch, Bashar*, Alan Chen*, Elaine Chan*, Asmaa Elkabti*, Sasha Fariña*, Catherine Gilbert*, Jean Kang*, Bradley King*, Karen Leung*, Julia Levy*, Elizabeth Martin*, Benjamin Mazer*, Sara McKinney*, Alexandra Moyzis*, Margaret Nurimba*, Michelle Ozaki*, Kathleen Purvis-Roberts, Joshua Marc Rothman*, Shravya Raju*, Cynthia Selassie, Oliver Smith*, Julia Ticus*, Gretchen Edwalds-Gilbert, M. Cristina Negritto, Ruye Wang, and Zhaohua Tang. “Comparative Genomic Screen in Two Yeast Reveals Conserved Pathways in the Response Network to Phenol Stress.” G3: Genes, Genomes, Genetics, vol. 9, no. 3, 2019, pp. 639-650.

Abstract: Living organisms encounter various perturbations, and response mechanisms to such perturbations are vital for species survival. Defective stress responses are implicated in many human diseases including cancer and neurodegenerative disorders. Phenol derivatives, naturally occurring and synthetic, display beneficial as well as detrimental effects. The phenol derivatives in this study, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and bisphenol A (BPA), are widely used as food preservatives and industrial chemicals. Conflicting results have been reported regarding their biological activity and correlation with disease development; understanding the molecular basis of phenol action is a key step for addressing issues relevant to human health. This work presents the first comparative genomic analysis of the genetic networks for phenol stress response in an evolutionary context of two divergent yeasts, Schizosaccharomyces pombe and Saccharomyces cerevisiae. Genomic screening of deletion strain libraries of the two yeasts identified genes required for cellular response to phenol stress, which are enriched in human orthologs. Functional analysis of these genes uncovered the major signaling pathways involved. The results provide a global view of the biological events constituting the defense process, including cell cycle arrest, DNA repair, phenol detoxification by V-ATPases, reactive oxygen species alleviation, and endoplasmic reticulum stress relief through ergosterol and the unfolded protein response, revealing novel roles for these cellular pathways.


Purvis-Roberts, Kathleen. “Collaborative Environmental Chemistry Projects: Universiti Kebangsaan Malaysia and the Claremont Colleges.” EnviroLab Asia, vol. 2, issue 4, 2019, Article 1.

Abstract: I received a course redevelopment grant from the Claremont Colleges EnviroLab Asia for my Environmental Chemistry (CHEM139) course. This allowed me to add a focus on environmental issues in Asia to the course and, more important, co-teach the class with a colleague at the Universiti Kebangsaan Malaysia (UKM).The many results of that cross-Pacific teaching project are the key subject of this reflective essay.


Purvis Roberts, Kathleen and Thomas Poon. “Equity through Access to Computer Science Learning at a Small Liberal Arts College.” Culturally Responsive Strategies for Reforming STEM Higher Education: Turning the TIDES on Inequity, edited by Kelly M. Mack, Kate Winter, and Melissa Soto. Emerald Publishing Limited, 2019, pp.173 – 186.

Abstract: By the end of this decade, the U.S. economy will annually create hundreds of thousands of new jobs requiring a bachelor's degree in STEM fields, particularly computer science. This increasing need for computer scientists, coupled with an inconsistent agenda for managing dramatic shifts in the demographic landscape of higher education, compromises our competitiveness in scientific discovery and innovation. As higher education seeks to address this issue, the need for more culturally responsive approaches to undergraduate STEM teaching also increases. This book uses the power of reflection, storytelling, and data to holistically demonstrate the effectiveness of a novel professional development intervention for STEM faculty - Teaching to Increase Diversity and Equity in STEM, or TIDES - that significantly increased faculty self-efficacy in implementing culturally responsive pedagogies. In it, the editors combine the authentic voices of authors from multiple institutional contexts and individual worldviews to assimilate and synthesize broad theoretical concepts into practice in usable ways, while also offering concrete applicable examples of strategies and solutions that serve as an important comprehensive reference for all undergraduate educators and administrators. This practical guide provides a durable platform for building capacity in understanding of the cultural complexities and institutional realities of recruiting and retaining diverse students in STEM, particularly the computer sciences.


External Grant: Asia-Pacific Economic Cooperation (APEC) Grant  APEC Workshop on University Collaboration to Support Data Gathering and Analysis in Energy Efficiency and Renewable Energy in collaboration with the APEC Energy Working Group/Expert Group on New and Renewable Energy Technologies/Expert Group on Clean Fossil Energy. Principal Investigator: Kathleen Purvis-Roberts, $100,000, August 2019-January 2021.

Abstract: The Energy Working Group (EWG) and its expert groups and task forces are working on projects with ambitious goals and targets that require extensive data collection and analysis. Each Asia-Pacific Economic Cooperation (APEC) economy has excellent Universities that could help fill this data collection and analysis need by enabling faculty to teach project-based courses with students doing research to support the work of the EWG and its subfora. The three-day workshop will bring together APEC members, faculty from APEC Universities, and members of Asia-Pacific Energy Research Center (APERC) to talk about potential EWG/University collaboration. The workshop will identify how to distinguish the most appropriate projects, best practices for communication, potential collaborations between different APEC Universities, and methods for sharing results from course research projects. The workshop will provide an excellent networking opportunity to begin the development of a consortium of Universities in APEC economies to work in collaboration with the EWG and APERC on EWG goals.

Caspi, Tal*, Lauren A. Hartz*, Alondra E. Soto Villa*, Jenna A. Loesberg*, Colin Robins, and Wallace M. Meyer III. “Impacts of Invasive Annuals on Soil Carbon and Nitrogen Storage in Southern California on the Identity of the Invader.” Ecology and Evolution, vol. 9, issue 8, 2019, pp. 4980-4993.

Abstract: Non‐native plant invasions can alter nutrient cycling processes and contribute to global climate change. In southern California, California sage scrub (hereafter sage scrub), a native shrub‐dominated habitat type in lowland areas, has decreased to <10% of its original distribution. Postdisturbance type‐conversion to non‐native annual grassland, and increasingly to mustard‐dominated invasive forbland, is a key contributor to sage scrub loss. To better understand how type‐conversion by common invasive annuals impacts carbon (C) and nitrogen (N) storage in surface soils, we examined how the identity of the invader (non‐native grasses, Bromus spp.; and non‐native forbs, Brassica nigra), microbial concentrations, and soil properties interact to influence soil nutrient storage in adjacent native and invasive habitat types at nine sites along a coast to inland gradient. We found that the impact of type‐conversion on nutrient storage was contingent upon the invasive plant type. Sage scrub soils stored more C and N than non‐native grasslands, whereas non‐native forblands had nutrient storage similar to or higher than sage scrub. We calculate that >940 t C km−2 and >60 t N km−2 are lost when sage scrub converts to grass‐dominated habitat, demonstrating that grass invasions are significant regional contributors to greenhouse gas emissions. We found that sites with greater total C and N storage were associated with high cation exchange capacities and bacterial concentrations. Non‐native grassland habitat type was a predictor of lower total C, and soil pH, which was greatest in invasive habitats, was a predictor of lower total N. We demonstrate that modeling regional nutrient storage requires accurate classification of habitat type and fine‐scale quantification of cation exchange capacity, pH, and bacterial abundance. Our results provide evidence that efforts to restore and conserve sage scrub enhance nutrient storage, a key ecosystem service reducing atmospheric CO2 concentrations.

Snell, Katherine*, Isabelle Lopez*, Brandon Louie*, Roxanna Kiessling*, and Babak Sanii. “Drawing and Hydrophobicity-Patterning Long Polydimethylsiloxane Silicone Filaments.” Journal of Visualized Experiments, vol. 143, 2019, e58826.

Abstract: Polydimethylsiloxane (PDMS) silicone is a versatile polymer that cannot readily be formed into long filaments. Traditional spinning methods fail because PDMS does not exhibit long-range fluidity at melting. We introduce an improved method to produce filaments of PDMS by a stepped temperature profile of the polymer as it cross-links from a fluid to an elastomer. By monitoring its warm-temperature viscosity, we estimate a window of time when its material properties are amendable to drawing into long filaments. The filaments pass through a high-temperature tube oven, curing them sufficiently to be harvested. These filaments are on the order of hundreds of micrometers in diameter and tens of centimeters in length, and even longer and thinner filaments are possible. These filaments retain many of the material properties of bulk PDMS, including switchable hydrophobicity. We demonstrate this capability with an automated corona-discharge patterning method. These patternable PDMS silicone filaments have applications in silicone weavings, gas-permeable sensor components, and model microscale foldamers.

Higham, Timothy E. and Lars Schmitz. “A Hierarchical View of Gecko Locomotion: Photic Environment, Physiological Optics, and Locomotor Performance.” Integrative and Comparative Biology, vol. 59, no. 2, 2019, pp. 443-455.

Abstract: Terrestrial animals move in complex habitats that vary over space and time. The characteristics of these habitats are not only defined by the physical environment, but also by the photic environment, even though the latter has largely been overlooked. For example, numerous studies of have examined the role of habitat structure, such as incline, perch diameter, and compliance, on running performance. However, running performance likely depends heavily on light level. Geckos are an exceptional group for analyzing the role of the photic environment on locomotion as they exhibit several independent shifts to diurnality from a nocturnal ancestor, they are visually-guided predators, and they are extremely diverse. Our initial goal is to discuss the range of photic environments that can be encountered in terrestrial habitats, such as day versus night, canopy cover in a forest, fog, and clouds. We then review the physiological optics of gecko vision with some new information about retina structures, the role of vision in motor-driven behaviors, and what is known about gecko locomotion under different light conditions, before demonstrating the effect of light levels on gecko locomotor performance. Overall, we highlight the importance of integrating sensory and motor information and establish a conceptual framework as guide for future research. Several future directions, such as understanding the role of pupil dynamics, are dependent on an integrative framework. This general framework can be extended to any motor system that relies on sensory information, and can be used to explore the impact of performance features on diversification and evolution.


Wintrich, Tanja, René Jonas, Hans-Joachim Wilke, Lars Schmitz, and P. Martin Sander. “Neck Mobility in the Jurassic Plesiosaur Cryptoclidus eurymerus: Finite Element Analysis as a New Approach to Understanding the Cervical Skeleton in Fossil Vertebrates.” Peer Journal of Paleontology and Evolutionary Science, vol. 7, 2019, e7658.

Abstract: The sauropterygian clade Plesiosauria arose in the Late Triassic and survived to the very end of the Cretaceous. Plesiosauria evolved the greatest species diversity of any marine reptile clade, attaining a global distribution. Plesiosauria consist of two clades, Rhomaleosauridae and Neoplesiosauria. Basal Neoplesiosauria have long necks with at least 30 cervicals, but show qualitative osteological evidence for a stiff neck. Here we quantify neck mobility in lateral, ventral, and dorsal directions based on finite element modeling of neck vertebrae from the Middle Jurassic plesiosaur Cryptoclidus eurymerus. We model the mobility in a single motion segment, consisting of two adjacent cervical vertebrae and the joints connecting them. Based on the model with a maximum intervertebral spacing of 3 mm, we find that in Cryptoclidus, the maximum angle of lateral deflection in the motion segment was 2°. The maximum angle of ventral deflection was 5° and of dorsal deflection was 5°. When these values are multiplied by the number of cervical vertebrae, it becomes apparent that neck mobility was limited in all directions. The maximum angle of total lateral deflection in the neck was 67°. The maximum angle of total ventral deflection was 148° and of total dorsal deflection was 157°. This raises the question of the function of such a long, multi-segment but immobile neck. We posit that the long neck served in hydrodynamic and visual camouflage, hiding the bulk of the body from the small but abundant prey, such as schooling fish and squid. Neck immobility may have been advantageous in withstanding strong hydrodynamic forces acting on the neck during predatory strikes.

Holt, Megan, Daniel Gillen, Sacha D. Nandlall, Kevin Setter, Paul Thorman, Suzanne Amador Kane, Christa Hixson Miller, Chelsea Cook, and Cary Supalo. “Making Physics Courses Accessible for Blind Students: Strategies for Course Administration, Class Meetings, and Course Materials.” The Physics Teacher, vol. 57, 2019, pp. 94-98.

Abstract: The Americans with Disabilities Act (ADA) mandates that U.S. institutions of higher education provide “reasonable accommodations” to students with disabilities to ensure equal educational opportunities. However, despite the key role of physics as a gateway to science, technology, engineering and mathematics (STEM) studies, only limited resources exist for teaching physics to students who are blind or visually impaired. Here we share lessons from our experience creating an accessible physics curriculum for a blind physics major. The authors include the student himself, a blind physics BS who graduated from a different institution, a PhD chemist and consultant on STEM accessibility who is himself blind, and several sighted educators and course assistants who worked regularly with the students. This article focuses on issues for which instructors are responsible: how to make class meetings, curricular materials, tutorials, and demonstrations accessible (as opposed to accommodations determined at an administrative level, such as additional time on tests). An online appendix provides additional resources and specifics to guide actual implementation of these ideas, including a guide to further reading. Once an institution learns that a blind student will enroll in a physics course, the course instructor and the institutional disabilities coordinator should meet to discuss course logistics well before the semester begins (ideally, over a month or two in advance to allow sufficient lead time). They should begin the process of creating an effective instructional and support team, ensuring key assistive technologies are in place, making all class meetings accessible, and preparing accessible course materials. The most fundamental decision is whether to use individualized instruction, in which the student and instructor meet in separate one-on-one tutorials, or mainstreaming, in which the student attends regular class meetings with other students. We primarily used mainstreaming, supplemented with one-on-one instruction. Instructors should work with the student in question to determine which approach is most suitable given their students’ individual needs and the available institutional resources.

Wan, Kirsty Y., Sylvia K. Hürlimann, Aidan M. Fenix, Rebecca M. McGillivary, Tatyana Makushok, Evan Burns, Janet Y. Sheung, and Wallace F. Marshall. “Reorganization of Complex Ciliary Flows around Regenerating Stentor coeruleus.” Philosophical Transactions of the Royal Society B, vol. 375, issue 1792, 2019, 20190167.

Abstract: The phenomenon of ciliary coordination has garnered increasing attention in recent decades and multiple theories have been proposed to explain its occurrence in different biological systems. While hydrodynamic interactions are thought to dictate the large-scale coordinated activity of epithelial cilia for fluid transport, it is rather basal coupling that accounts for synchronous swimming gaits in model microeukaryotes such as Chlamydomonas. Unicellular ciliates present a fascinating yet understudied context in which coordination is found to persist in ciliary arrays positioned across millimetre scales on the same cell. Here, we focus on the ciliate Stentor coeruleus, chosen for its large size, complex ciliary organization, and capacity for cellular regeneration. These large protists exhibit ciliary differentiation between cortical rows of short body cilia used for swimming, and an anterior ring of longer, fused cilia called the membranellar band (MB). The oral cilia in the MB beat metachronously to produce strong feeding currents. Remarkably, upon injury, the MB can be shed and regenerated de novo. Here, we follow and track this developmental sequence in its entirety to elucidate the emergence of coordinated ciliary beating: from band formation, elongation, curling and final migration towards the cell anterior. We reveal a complex interplay between hydrodynamics and ciliary restructuring in Stentor, and highlight for the first time the importance of a ring-like topology for achieving long-range metachronism in ciliated structures.

Solomon-Lane, Tessa K, and Hans A. Hofmann. “Early-Life Social Environment Alters Juvenile Behavior and Neuroendocrine Function in a Highly Social Cichlid Fish.” Hormones and Behavior, vol. 115, 2019, 104552.

Abstract: Early-life experiences can shape adult behavior, with consequences for fitness and health, yet fundamental questions remain unanswered about how early-life social experiences are translated into variation in brain and behavior. The African cichlid fish Astatotilapia burtoni, a model system in social neuroscience, is well known for its highly plastic social phenotypes in adulthood. Here, we rear juveniles in either social groups or pairs to investigate the effects of early-life social environments on behavior and neuroendocrine gene expression. We find that both juvenile behavior and neuroendocrine function are sensitive to early-life effects. Behavior robustly co-varies across multiple contexts (open field, social cue investigation, and dominance behavior assays) to form a behavioral syndrome, with pair-reared juveniles towards the end of syndrome that is less active and socially interactive. Pair-reared juveniles also submit more readily as subordinates. In a separate cohort, we measured whole brain expression of stress and sex hormone genes. Expression of glucocorticoid receptor 1a was elevated in group-reared juveniles, supporting a highly-conserved role for the stress axis mediating early-life effects. The effect of rearing environment on androgen receptor α and estrogen receptor α expression was mediated by treatment duration (1 vs. 5 weeks). Finally, expression of corticotropin-releasing factor and glucocorticoid receptor 2 decreased significantly over time. Rearing environment also caused striking differences in gene co- expression, such that expression was tightly integrated in pair-reared juveniles but not group-reared or isolates. Together, this research demonstrates the important developmental origins of behavioral phenotypes and identifies potential behavioral and neuroendocrine mechanisms.

Alhoch, Bashar*, Alan Chen*, Elaine Chan*, Asmaa Elkabti*, Sasha Fariña*, Catherine Gilbert*, Jean Kang*, Bradley King*, Karen Leung*, Julia Levy*, Elizabeth Martin*, Benjamin Mazer*, Sara McKinney*, Alexandra Moyzis*, Margaret Nurimba*, Michelle Ozaki*, Kathleen Purvis-Roberts, Joshua Marc Rothman*, Shravya Raju*, Cynthia Selassie, Oliver Smith*, Julia Ticus*, Gretchen Edwalds-Gilbert, M. Cristina Negritto, Ruye Wang, and Zhaohua Tang. “Comparative Genomic Screen in Two Yeast Reveals Conserved Pathways in the Response Network to Phenol Stress.” G3: Genes, Genomes, Genetics, vol. 9, no. 3, 2019, pp. 639-650.

Abstract: Living organisms encounter various perturbations, and response mechanisms to such perturbations are vital for species survival. Defective stress responses are implicated in many human diseases including cancer and neurodegenerative disorders. Phenol derivatives, naturally occurring and synthetic, display beneficial as well as detrimental effects. The phenol derivatives in this study, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and bisphenol A (BPA), are widely used as food preservatives and industrial chemicals. Conflicting results have been reported regarding their biological activity and correlation with disease development; understanding the molecular basis of phenol action is a key step for addressing issues relevant to human health. This work presents the first comparative genomic analysis of the genetic networks for phenol stress response in an evolutionary context of two divergent yeasts, Schizosaccharomyces pombe and Saccharomyces cerevisiae. Genomic screening of deletion strain libraries of the two yeasts identified genes required for cellular response to phenol stress, which are enriched in human orthologs. Functional analysis of these genes uncovered the major signaling pathways involved. The results provide a global view of the biological events constituting the defense process, including cell cycle arrest, DNA repair, phenol detoxification by V-ATPases, reactive oxygen species alleviation, and endoplasmic reticulum stress relief through ergosterol and the unfolded protein response, revealing novel roles for these cellular pathways.

Thomson, Diane M. “Effects of Long-Term Variation in Pollinator Abundance and Diversity on Reproduction of a Generalist Plant.” Journal of Ecology, vol. 107, issue 1, 2019, pp. 491-502.

Abstract: Quantifying the benefits of pollinator abundance and diversity for plant reproduction is a critical challenge, especially given recent pollinator declines. Many studies test for pollen limitation (PL), but huge gaps remain in our understanding of how often and why plants experience PL. Most studies are limited to a few sites or years. Little existing research mechanistically links pollinator visitation with plant reproduction. Also, buffering against variability in visitation is a key but largely untested potential benefit of pollinator diversity. Long‐term studies pairing visitation data with PL experiments are essential to addressing these gaps, but extremely rare. I measured pollinator visitation, responses to pollen supplementation, and fruit weights in the generalist plant Scrophularia californica across multiple sites for 8 years. I determined how often S. californica experienced significant PL and tested mechanistic models predicting PL and fruit (capsule) weight from visitation. I then used those models to simulate pollinator loss and evaluate the relative effects of changes in visit quantity and quality. I explored the stabilizing benefits of visitor diversity by quantifying both covariation among pollinators and effects of simulated species loss on variation in PL and capsule weights. Scrophularia showed significant PL in only 26.9% of patch/year combinations tested. Visitation by the most abundant (Apis mellifera) and effective (Vespulapensylvanica) pollinators strongly predicted PL and capsule weights. Both response curves were highly nonlinear, but PL saturated more with increased visitation. Pollinator loss simulations predicted substantially increased PL and reduced capsule weights, mostly because of lower visit numbers rather than changes in visit quality. Visitation rates of individual pollinators varied substantially and without correlation. Simulated pollinator loss increased the spatial and temporal skew in visitation, resulting in higher predicted coefficients of variation for PL and capsule weights. Synthesis. Previous work predicts a nonlinear relationship between pollinator visitation and plant reproduction, but this is the first long‐term study I am aware of that quantifies such a pattern. The analysis of covariance in pollinator visitation combined with my simulation results provide novel empirical support for another important hypothesis, that multiple pollinators can provide stabilizing benefits for plant reproduction.

Oakley, James V., Tyler J. Stanley, Kate A. Jesse*, Amanda K. Melanese, Araceli A. Alvarez, Aloha L. Prince, Stephanie E. Cain, Anna G. Wenzel, and Robert G. Iafe. “Gold-Catalyzed Friedel-Crafts-Like Reaction of Benzylic Alcohols to Afford 1,1-Diarylalkanes.” European Journal of Organic Chemistry, issue 42, 2019, pp. 7063-7066.

Abstract: A gold‐catalyzed, Friedel–Crafts‐like benzylation of unactivated benzylic alcohols to form 1,1‐diarylalkanes has been developed. The operationally convenient method uses only 1.3 equivalents of the electron‐rich arene, employs readily available starting materials, is highly reproducible, and is tolerant of moisture. Moderate‐to‐high product yields (34–99 %) with excellent regioselectivity were obtained. In particular, the intramolecular arylation of benzylic alcohols to afford substituted fluorenes represents a new avenue for gold research.

Gallagher, Sean R., and Emily A. Wiley, eds. Current Protocols: Essential Laboratory Techniques, vols. 18 & 19. John Wiley and Sons, 2019.

Anagnostou, Eleni, Branwen Williams, Isaac Westfield, Gavin L. Foster, and Justin Baker Ries. “Calibration of the pH-δ11B and Temperature-Mg/Li Proxies in the Long-Lived High-Latitude Crustose Coralline Red Alga Clathromorphum compactum via Controlled Laboratory Experiments.” Geochemica et Cosmochimica Acta, vol. 254, 2019, pp. 142-155.

Abstract: A solid understanding of global oceanic change throughout Holocene time is needed to contextualize and interpret recent observations of rapid warming (Moore, 2016), ocean acidification (Popova et al., 2014; Qi et al., 2017), increasing meltwater input (Halfar et al., 2013; Notz and Stroeve, 2016) and circulation changes (Liu et al., 2017; Rahmstorf et al., 2015; Yang et al., 2016) in the Arctic and subarctic Oceans. Precisely reconstructing acidification and temperature variations throughout the Holocene will provide a vital context for interpreting current environmental changes and future climate projections in the region. However, existing paleoenvironmental reconstructions are sparse and uncertain, largely owing to limited availability of high fidelity paleoceanographic archives, such as marine carbonates, in high latitude waters. Coralline algae of the genus Clathromorphum have emerged as key candidates for reconstructing high-latitude environmental variability at annual to sub-annual resolution. Here, we present the first empirical calibrations of boron isotope-pH and Mg/Li-temperature relationships within the long-lived, crustose coralline red alga Clathromorphum compactum. Calibration experiments were performed in triplicate, growing wild-collected specimens for four months at three controlled temperatures (6.4–12.4 °C) and four pCO2 conditions (352–3230 ppm), to test the effects of these environmental parameters on the isotopic and elemental composition of the algal skeleton. We find that boron isotopes within the skeleton of C. compactum (δ11Bcc) are well correlated with δ11B of seawater borate (δ11Βborate), defining the following equation: δ11Βcc (2σ) = 1.46 (0.06) δ11Βborate + 6.91 (0.72). This equation can be used to reconstruct δ11Βborate of the coralline alga’s ambient seawater, from which past seawater pH can be calculated. We also identified a strong correlation between skeletal Mg/Li ratio and seawater temperature, defined by the equation: Mg/Li (2σ) = 0.17 (0.02) temperature (oC) + 1.02 (0.16). Therefore, despite the strong biological control that this species appears to exert on calcification site pH (elevated 1.0–1.6 pH units above seawater pH, inferred from δ11Bcc > δ11Βborate), and the apparent relationship between skeletal extension rate and skeletal Li/Ca and Mg/Ca, the δ11Bcc and Mg/Li ratios of the coralline alga’s skeleton strongly and significantly respond to ambient seawater pH and temperature, respectively. These results support the use of δ11B and Mg/Li within C. compactum for pH and temperature reconstructions of northern high-latitude oceans.


Hou, Alicia, Jochen Halfar, Walter H. Adey, Ulrich Georg Wortmann, Zoltan Zajacz, Alexandra Tsay, Branwen Williams, and Phoebe Chan. “Long-Lived Coralline Alga Records Multidecadal Variability in Labrador Sea Carbon Isotopes.” Chemical Geology, vol. 526, 2019, pp. 93-100.

Abstract: While the recent decline in the δ13C composition of oceanic dissolved inorganic carbon (DIC) can be attributed to increasing anthropogenic CO2 emissions (13C Suess effect), the causes of natural variability in the δ13C of oceanic DIC (δ13CDIC) are far less understood. Unfortunately, instrumental oceanic DIC measurements are not available prior to the 1970s, prohibiting the observation and study of long-term variability in oceanic carbon isotope dynamics. Thus, in order to identify the main driving forces of changes in oceanic δ13CDIC, multicentury carbon isotope time series that extend from the present into the preindustrial period are required. Such time series may be extracted from the carbonate skeletons of long-lived marine organisms, which have been shown to be robust recorders of fluctuations and trends in oceanic δ13CDIC. In this study, we use an annually-banded coralline alga live-collected from the Labrador shelf to generate a 266-year time series of δ13CDIC changes in the Labrador Sea. Our results indicate that from the 1960s onwards, the rate of δ13CDIC decline in the Labrador Sea slightly exceeds the rate of δ13C decline in the atmosphere, providing support for the enhanced CO2 uptake ability of the Labrador Sea. In addition, the detrended algal δ13C time series displays multidecadal variability with typical Atlantic Multidecadal Oscillation (AMO) frequencies. We show that prior to the late 1980s, algal δ13C compositions significantly correlate with regional sea ice cover (SIC) variability, post-1850 instrumental, reconstructed AMO indices, and solar variability. We speculate that these low-frequency oscillations in δ13C reflect changes in marine primary productivity modulated by a mechanism involving solar changes, the AMO and SIC variability. Our algal carbon isotope time series suggests that while the anthropogenic Suess effect has influenced Labrador Sea δ13CDIC since the 1960s, its influence may have been obscured by the effects of natural climatic variability up until the late 1980s.


Williams, Branwen, Kelton McMahon, Sarah Barnes*, Devyn Parks*, Ella Kim*, Tanja Srebotnjak, and Peter Etnoyer. “Impact of Skeletal Heterogeneity and Treatment Method on Interpretation of Environmental Variability from the Skeletons of Deep-Sea Gorgonian Corals.” Chemical Geology, vol. 526, 2019, pp. 101-109.

Abstract: The stable isotope geochemistry of gorgonian octocoral skeletons facilitates detailed time series reconstructions of nutrient biogeochemistry. However, comparisons among reconstructions from different locations require realistic estimates of the uncertainty surrounding each measured geochemical value. Here, we determine quantitative uncertainties related to 1) standard skeletal pretreatment in preparation for stable isotopic analysis and 2) biological variability associated with a heterogeneous isotopic composition of the gorgonin skeleton. We found that the 5% HCl pretreatment required for the δ13C measurements does not significantly impact the δ15N values of the skeleton nor the reproducibility of the δ15N measurements. In contrast, while 5% HCl pretreatment significantly altered bulk δ13C values via removal of CaCO3, it did not change amino acid δ13C values in the organic skeleton. We found that the variance of repeat measurements of skeleton samples formed contemporaneously and homogenized skeleton for both δ13C and δ15N exceeded that of instrumental uncertainty of an acetanilide standard. This indicates that instrumental uncertainty underestimates the true precision of an isotopic measurement of the organic skeleton. Furthermore, measurements of contemporaneous skeleton around the circumference of an octocoral colony yielded variability exceeding that of homogenized skeleton. Based on these results, we find that 1) both δ13C and δ15N values can be measured simultaneously in pretreated skeleton, 2) growth bands should be homogenized prior to analysis, and 3) reported error should include uncertainty due to biological effects determined from repeat analysis of homogenized skeleton and not just instrument error to reduce false significant differences. Our results present an important protocol for processing proteinaceous octocoral skeletons and propagating uncertainty to more accurately reconstruct nutrient dynamics from proteinaceous deep-sea octocoral skeletons.

Williams, Nancy. “LGBT STEM Day: Nancy Williams.” Interview by Jesse Stanchak. ACS Axial. July 15, 2019,

axial.acs.org/2019/07/05/pride-in-stem-nancy-williams/