2017 W.M. Keck Science Department Publications and Grants

*Indicates student co-author

Chen, Audrey, Chanpreet Singh, Grigrios Oikonomou, and David A. Prober. “Genetic Analysis of Histamine Signaling in Larval Zebrafish Sleep.” eNeuro, vol. 4, issue 1, 2017, pii: ENEURO.0286-16.2017

Abstract: Pharmacological studies in mammals and zebrafish suggest that histamine plays an important role in promoting arousal. However, genetic studies using rodents with disrupted histamine synthesis or signaling have revealed only subtle or no sleep/wake phenotypes. Studies of histamine function in mammalian arousal are complicated by its production in cells of the immune system and its roles in humoral and cellular immunity, which can have profound effects on sleep/wake states. To avoid this potential confound, we used genetics to explore the role of histamine in regulating sleep in zebrafish, a diurnal vertebrate in which histamine production is restricted to neurons in the brain. Similar to rodent genetic studies, we found that zebrafish that lack histamine due to mutation of histidine decarboxylase (hdc) exhibit largely normal sleep/wake behaviors. Zebrafish containing predicted null mutations in several histamine receptors also lack robust sleep/wake phenotypes, although we are unable to verify that these mutants are completely nonfunctional. Consistent with some rodent studies, we found that arousal induced by overexpression of the neuropeptide hypocretin (Hcrt) or by stimulation of hcrt-expressing neurons is not blocked in hdc or hrh1 mutants. We also found that the number of hcrt-expressing or histaminergic neurons is unaffected in animals that lack histamine or Hcrt signaling, respectively. Thus, while acute pharma-cological manipulation of histamine signaling has been shown to have profound effects on zebrafish and mammalian sleep, our results suggest that chronic loss of histamine signaling due to genetic mutations has only subtle effects on sleep in zebrafish, similar to rodents.

Lee, Daniel A., Andrey Andreev, Thai V. Truong , Audrey Chen, Andrew J. Hill, Grigorios Oikonomou, Uyen Pham, Young K. Hong, Steven Tran, Laura Glass, Viveca Sapin, Jae Engle, Scott E. Fraser, and David A. Prober. “Genetic and Neuronal Regulation of Sleep by Neuropeptide VF.” eLife vol. 6, issue 6, 2017, pii: e25727.

Abstract: Sleep is an essential and phylogenetically conserved behavioral state, but it remains unclear to what extent genes identified in invertebrates also regulate vertebrate sleep. RFamide-related neuropeptides have been shown to promote invertebrate sleep, and here we report that the vertebrate hypothalamic RFamide neuropeptide VF (NPVF) regulates sleep in the zebrafish, a diurnal vertebrate. We found that NPVF signaling and npvf-expressing neurons are both necessary and sufficient to promote sleep, that mature peptides derived from the NPVF preproprotein promote sleep in a synergistic manner, and that stimulation of npvf-expressing neurons induces neuronal activity levels consistent with normal sleep. These results identify NPVF signaling and npvf-expressing neurons as a novel vertebrate sleep-promoting system and suggest that RFamide neuropeptides participate in an ancient and central aspect of sleep control.

Abraham, Michael H., William E. Acree, Anthony F. Fucaloro, and Andrew W. Zanella. “Determination of Molar Refractions and Abraham Descriptors for tris(acetylacetanato)chromium(III), tris(acetylacetanato)iron(III) and tris(acetylacetanato)cobalt(III).” New Journal of Chemistry, vol. 41, 2017, pp. 14259-14265.

Abstract: We have determined molar refractions of tris(acetylacetonato)chromium(III), tris(acetylacetonato)iron(III) and tris(acetylacetonato)cobalt(III). Although the d-electron structures of the three metal centres differ significantly, the three molar refractions are actually quite close to each other. We then used these molar refractions to determine the Abraham E-descriptor, we calculated the V-descriptor by McGowan's method, and then used literature data on solubilities and water–solvent partitions to obtain the rest of the set of descriptors for the three tris(acetylacetonato) complexes. If we take E as the average of those for the chromium, iron and cobalt complexes, we can use limited literature data to obtain the full set of Abraham descriptors for the tris(acetylacetonates) of vanadium(III), yttrium(III), samarium(III), lanthanum(III) and neodymium(III). For the eight complexes, the descriptors vary regularly with complex molecular weight. These show that the complexes are quite polarizable, have zero hydrogen-bond acidity and significant hydrogen bond basicity. From the sets of Abraham descriptors, a very large number of physicochemical properties can be predicted for the eight acetonylacetonates.

Gilman, Sarah E. “Predicting Indirect Effects of Predator-Prey Interactions.” Integrative and Comparative Biology, vol. 57, issue 1, 2017, pp. 148-158.

Abstract: Predicting the effects of climate change on species and communities remains a pre-eminent challenge for biologists. Critical among this is understanding the indirect effects of climate change, which arise when the direct, physiological effects of climate on one species change the outcome of its interaction with a second species, altering the success of the second species. A diverse array of approaches to predicting indirect effects exists from mechanistic models, which attempt to build-up from physiological changes to ecological consequences, to ecological models that focus solely on the ecological scale. Here I review studies of the indirect effects of temperature on two predator-prey systems in rocky intertidal habitats. Laboratory and field studies have shown that temperature can indirectly affect interactions through both physiological and behavioral changes in predator and prey, but no model yet captures the full range of these effects. The three main categories of changes are metabolic rate effects, stress effects, and behavioral avoidance. Mechanistic models best capture the first two of these three dynamics, while ecological models have focused mainly on the last two. The challenge remains to correctly identify a species' vulnerability to climate change, which differs from its physiological sensitivity. The best approach may be to use detailed physiological-scale studies of indirect effect in a few systems to ground truth simpler models that can be applied more broadly. Model development and testing is also hampered by the small number of field studies of indirect effects in natural systems, particularly studies that examine natural temporal or spatial variation in climate.

External Grant: External Grant: Gilman, Sarah E. National Science Foundation Research Experience for Teachers supplement, $9,323, 2017-2019.

This proposal will fund an RET supplement for a local elementary school teacher, to participate in full time summer research for six weeks on the NSF-funded project "CAREER: Thermal stress and intertidal zonation: The neglected role of food supply" (IOS-1351445). The research goals of this grant are to test the relative influence of temperature stress and energy limitation on the upper vertical limit of an intertidal barnacle (Balanus glandula). Understanding the mechanisms by which temperature limits an organism's success is critical to generating accurate predictions of the effect of climate change on biological systems. The teacher will contribute to a laboratory study of respiration rates in B. glandula under a range of environmental conditions and develop new science curricula that link the project to California's new Next Generation Science Standards (NGSS, CA Dept. of Education, 2017).

External Grant: NMR Crystallography: Linking Chemical Structure and Mechanism in Tryptophan Synthase Award Number: 1710671; Principal Investigator: Leonard Mueller; Co-Principal Investigator: Li Fan; Organization: University of California-Riverside; NSF Organization: CHE; Start Date: August 1, 2017; Award Amount: $480,000.00. Expert collaborator: Mary Hatcher-Skeers

Prof. Hatcher-Skeers is participating as an expert collaborator and will receive $5000/year plus funding for student researchers. The goal of this proposal is to provide the chemical level details necessary to understand the enzymatic mechanistic pathway in tryptophan synthase. Realizing this goal relies on the synergistic combination of solid-state NMR, X-ray crystallography, and computational chemistry, which together allow a detailed model to be developed for this transformation. The X-ray crystal structure gives outstanding global backbone and side chain information, but poor resolution of catalytic residue and substrate chemical structure. Solid-state NMR can fill in these chemical level details, but would be hard pressed to solve a complete structure this large. Tying them together is computational chemistry, which allows specific models of the chemical structure to be built upon the coarse X-ray framework and then tested by a comparison of predicted and assigned chemical shifts. This comparison is far more stringent than the empirical correlation of chemical shift with structure, which can easily span tens of ppm for 13C and 15N, and in judging agreement we demand 2-5 ppm accuracy. The result is a unique and chemically-rich molecular view into functioning enzyme catalysis. In the case of tryptophan synthase, the application of NMR crystallography is already rewriting the mechanism and offering unique insights into reaction specificity for PLP-dependent enzymes.

Lewis, Eliza L.* and Aaron M. Leconte. “DNA Polymerase Activity Assay Using Near-Infrared Fluorescent Labeled DNA Visualized by Acrylamide Gel Electrophoresis.” Journal of Visualized Experiments, issue 128, 2017, e56228.

Abstract: For any enzyme, robust, quantitative methods are required for characterization of both native and engineered enzymes. For DNA polymerases, DNA synthesis can be characterized using an in vitro DNA synthesis assay followed by polyacrylamide gel electrophoresis. The goal of this assay is to quantify synthesis of both natural DNA and modified DNA (M-DNA). These approaches are particularly useful for resolving oligonucleotides with single nucleotide resolution, enabling observation of individual steps during enzymatic oligonucleotide synthesis. These methods have been applied to the evaluation of an array of biochemical and biophysical properties such as the measurement of steady-state rate constants of individual steps of DNA synthesis, the error rate of DNA synthesis, and DNA binding affinity. By using modified components including, but not limited to, modified nucleoside triphosphates (NTP), M-DNA, and/or mutant DNA polymerases, the relative utility of substrate-DNA polymerase pairs can be effectively evaluated. Here, we detail the assay itself, including the changes that must be made to accommodate nontraditional primer DNA labeling strategies such as near-infrared fluorescently labeled DNA. Additionally, we have detailed crucial technical steps for acrylamide gel pouring and running, which can often be technically challenging.

Rosenblum, Sydney L.*, Aurora G. Weiden*, Eliza L. Lewis*, Alexie L. Ogonowsky*, Hannah E. Chia*, Susanna E. Barrett*, Mira D. Liu*, and Aaron M. Leconte. “Design and Discovery of New Combinations of Mutant DNA Polymerases and Modified DNA Substrates.” ChemBioChem, vol. 18, issue 8, 2017, pp. 816-823.

Abstract: Chemical modifications can enhance the properties of DNA by imparting nuclease resistance and generating more-diverse physical structures. However, native DNA polymerases generally cannot synthesize significant lengths of DNA with modified nucleotide triphosphates. Previous efforts have identified a mutant of DNA polymerase I from Thermus aquaticus DNA (SFM19) as capable of synthesizing a range of short, 2'-modified DNAs; however, it is limited in the length of the products it can synthesize. Here, we rationally designed and characterized ten mutants of SFM19. From this, we identified enzymes with substantially improved activity for the synthesis of 2'F-, 2'OH-, 2'OMe-, and 3'OMe-modified DNA as well as for reverse transcription of 2'OMe DNA. We also evaluated mutant DNA polymerases previously only tested for synthesis for 2'OMe DNA and showed that they are capable of an expanded range of modified DNA synthesis. This work significantly expands the known combinations of modified DNA and Taq DNA polymerase mutants.

External grant: Jean Dreyfus Lectureship for Undergraduate Institutions, “Applying Molecular Evolution to Solve Chemical Problems—Funding to Bring Prof. David R. Liu to the Claremont Colleges,” Jane Liu (Pomona College, lead PI), Aaron Leconte (Keck Science Department, lead PI), $18,500, 2017-2018.

We submitted a joint application from Pomona (Prof. Jane Liu, lead PI) and KSD (Prof. Aaron Leconte, lead PI) to the Dreyfus Foundation to bring Prof. David R. Liu (Harvard University and The Broad Institute) to Claremont for a two-day visit in Spring 2018. The grant was awarded and provides $18,500 to fund Prof. David R. Liu's visit in April 2018 as well as two undergraduate summer research stipends in Summer 2018.

Diedrich, Cajus G. and Donald A. McFarlane. “Homotherium From Middle Pleistocene Archaeological and Carnivore Den Sites of Germany - Taxonomy, Taphonomy and a Revision of the Schöningen, West Runton and Other Saber-Tooth Cat sites.” Quaternary International, vol. 436, 2017, pp. 76-83.

Abstract: Four new saber-tooth cat (Homotherium) sites in Germany with new dental and postcranial bone material are different in their taphonomic context: 1. The Archaeological Middle Palaeolithic (MIS 9eInterglacial) Schoningen Lake site with remains of a cub carcass, 2. The Middle Palaeolithic (MIS 5e-9) Archaeological/cave bear den site of Balve Cave yielding a lower canine tooth of an older individual, 3. The Zoolithen Cave (MIS 3e9) cave bear/hyena den with one distal half humerus of an adult, 4. The Ketsch open air Rhine River terrace site which has provided another distal humerus of an adult sabertooth cat. Whereas only the Schoningen site is precisely dated as Holsteinian Interglacial (approx. 330.000-315.000 BP), all other material seems to come from the same Middle Pleistocene warm period, or few younger Saalian interstadials (MIS 7a, e) deposits, and did not extend over the last MIS 7 glacial into the Late Pleistocene. Homotherium as hyena-like slow moving cat seems to have disappeared within the Saalian due to competition with other scavengers like Ice Age spotted and brown hyenas (Crocuta crocuta praespelaea/ultima and Pachycrocuta brunnea mosbachensis). The juvenile saber-tooth cat cub from Schoningen might be in archaeological context or represent only a carnivore kill. At the Zoolithen Cave, the single bone must have been imported into a hyena prey bone assemblage. The situation is possibly similar at the two other sites Ketsch and Balve Cave. The formerly described Schoningen “sabertooth cat” humerus is revised, such as other opposite as lion humeri described material from different European sites. The presence of the well-developed supracondylar ridge distinguishes Homotherium well from Middle/Late Pleistocene lions Panthera leo (e.g. spelaea, fossilis). The Schoningen lion humerus has been chew-cut first most probably by a stripped hyena whose cutting scissor teeth produced a diagonal bite cut and P4 /M1 impact marks around the trochlea. 1e2 mm small, mostly triangular-oval bite marks on the lion humerus shaft compacta results from a second scavenger and not from “Neanderthal tool use”. Those bite mark sizes are produced mainly of the upper molar teeth of the red wolf Cuon alpinus subsp. (or small fox Vulpes praecorsac), which were present in the region within the Holsteinian/Saalian.

Lundberg, J., W. Carroll, W. Roberts, D.A. McFarlane, M. Buchroithner, and G. van Rentergem. “Analysis of Scallops in Gomantong Caves, by GIS Processing of 3-D Terrestrial Laser Scanner Data.” Proceedings of the 17th International Congress of Speleology, Penrith, Australia, vol. 2, 2017, pp. 285-288.

Lundberg, Joyce, and Donald A. McFarlane. “Speleothems and Spiders: Morphology and Origin of Gypsum Nucleated on Spider Webs, Deer Cave, Sarawak, Borneo.” Cave and Karst Science, vol. 44, no. 3, 2017, pp. 127-131.

Abstract: An unusual form of gypsum is reported from Deer Cave, Gunung Mulu National Park, Sarawak, Malaysia. The gypsum is originally derived from decomposing bat guano, is air-dispersed, dissolved in condensation water entrained in spiders’ webs, and then recrystallized on the spider silk matrix.

Marx, Andrew, Donald McFarlane, and Ahmed Alzahrani. "UAV Data for Multi-Temporal Landsat Analysis of Historic Reforestation: A Case Study in Costa Rica." International Journal of Remote Sensing, vol 38, issue 8-10, 2017, pp. 2331-2348.

Abstract: The use of the Landsat constellation to quantify historic deforestation and reforestation over time is well established. This analysis, however, requires ground-referenced data that is often inaccessible in remote areas or expensive if no existing high-resolution satellite imagery exists. In response, we evaluate the capability of unmanned aerial vehicle (UAV) imagery to serve as ground-reference data for identifying land-cover classes in Landsat imagery. We then apply these classes to quantify 30 years of historical deforestation and reforestation of an ecological reserve in Costa Rica. While spatial and spectral disparities between the sensors limit the generalization of the approach, our results demonstrate the ability of UAV and Landsat data to inexpensively classify a reserve’s historic land cover over time and suggest an 11 year period for land cover to transition from pasture to secondary forest in lowland tropical environments.

McFarlane, D.A., J. Lundberg, and G. van Rentergem. “Preliminary Observations on Tropical Bat Caves as Biogeochemical Nitrogen Sinks.” Proceedings of the 17th International Congress of Speleology, Penrith, Australia, vol. 1, 2017, pp. 157-160.

Schertler, N., M. Buchroithner, D.A McFarlane, G. van Rentergem, J. Lundberg, and S. Gumhold. “Deterministically Defining Chambers in 3-D Scans of Caves.” Proceedings of the 17th International Congress of Speleology, Penrith, Australia, vol. 2, 2017, pp. 140-142.

van Rentergem, G., D.A. McFarlane., J. Lundberg, and M. Buchroithner. “Lessons Learned From a Large-Scale 3-D Mapping Project With FARO Laser Scanners of the Gomantong Caves, Borneo.” Proceedings of the 17th International Congress of Speleology, Penrith, Australia, vol. 2, 2017, pp. 144-146.

Abstract: During a 24-day T-Lidar scanning project of the Gomantong Caves in Sabah, Malaysia (some 4 km of often very physically demanding passage), we collected 271 scans, resulting in a massive data set of 12.6 billion scan points. In hindsight, we can now offer some new protocols that should enhance future fieldwork and subsequent data processing. The main lesson we learned is that using reference spheres is not really necessary: instead, we can use features of the complex natural surfaces of the cave as reference. Tis accelerates the pace of scanning greatly, and eliminates the dangers associated with placements of spheres in hazardous situations. Tis increase in scanning efficiency does come at a price because subsequent scan registration becomes more complex. However, the extended time required for a more complex cloud-to-cloud registration in an office environment is more-than-compensated for by the increased efficiency and reduced risk of the fieldwork. In this paper, we also review some other lessons learned during this project.

van Rentergem, G., D.A. McFarlane, J. Lundberg, and M. Buchroithner. “Mathematical Modelling of the Relationship Between Terrestrial LIDAR Scan Point Density and Volumetric Assessment of Underground Cavities. Proceedings of the 17th International Congress of Speleology, Penrith, Australia, vol. 2, 2017, pp. 147-149.

Insperger, Tamas, and John Milton. “Stick Balancing with Feedback Delay, Sensory Dead Zone and Jerk Limitation.” Procedia IUTAM, vol. 22, 2017, pp. 59-66.

Abstract: A simplified model of stick balancing on the fingertip subjected to predictor feedback is investigated, which accounts for three important modeling issues: (1) feedback delay; (2) the sensory dead zone; and (3) limitation of the control force corresponding to the maximum acceleration and the maximum jerk of human hand movement. Eight different cases (± sensory dead zone, ± acceleration limitation, ± jerk limitation) are compared by estimating the maximum balance time out of five time-domain simulations with different initial conditions. It is shown that the region of linear stability in the plane of control parameters is reduced by the presence of dead zone, not affected by limitations on hand acceleration, but is increased by limitations on the jerk.

Milton, John, Jianhong Wu, Sue Ann Campbell, and Jacques Bélair. “Outgrowing Neurological Diseases: Microcircuits, Conduction Delay and Dynamic Diseases.” Computational Neurology and Psychiatry, edited by Péter Érdi, Basabdatta Sen Bhattacharya, and Amy L. Cochran. Springer, 2017, pp. 11-47.

Nessler, Jeff A., Severne Heredia, Jacques Bélair, and John Milton. “Walking on a Vertically Oscillating Treadmill: Phase Synchronization and Gait Kinematics.” PLOS ONE, vol. 12, issue 1, 2017, e0169924.

Abstract: Sensory motor synchronization can be used to alter gait behavior. This type of therapy may be useful in a rehabilitative setting, though several questions remain regarding the most effective way to promote and sustain synchronization. The purpose of this study was to describe a new technique for using synchronization to influence a person’s gait and to compare walking behavior under this paradigm with that of side by side walking. Thirty one subjects walked on a motorized treadmill that was placed on a platform that oscillated vertically at various frequencies and amplitudes. Synchronization with the platform and stride kinematics were recorded during these walking trials and compared with previously reported data from side by side walking. The results indicated that vertical oscillation of the treadmill surface at frequencies that matched subjects preferred stride or step frequency resulted in greater unintentional synchronization when compared with side by side walking data (up to 78.6±8.3% of the trial vs 59.2±17.4%). While intermittent phase locking was observed in all cases, periods of synchronization occurred more frequently and lasted longer while walking on the oscillating treadmill (mean length of periods of phase locking 11.85 steps vs 5.18 steps). Further, stride length, height and duration were altered by changing the frequency of treadmill oscillation. These results suggest that synchronization to a haptic signal may hold implications for use in a clinical setting.

Stepan, Gabor, John G., and Tamas Insperger. “Quantization Improves Stabilization of Dynamical Systems with Delayed Feedback.” Chaos, vol. 27, issue 11, 2017, 114306.

Abstract: We show that an unstable scalar dynamical system with time-delayed feedback can be stabilized by quantizing the feedback. The discrete time model corresponds to a previously unrecognized case of the microchaotic map in which the fixed point is both locally and globally repelling. In the continuous-time model, stabilization by quantization is possible when the fixed point in the absence of feedback is an unstable node, and in the presence of feedback, it is an unstable focus (spiral). The results are illustrated with numerical simulation of the unstable Hayes equation. The solutions of the quantized Hayes equation take the form of oscillations in which the amplitude is a function of the size of the quantization step. If the quantization step is sufficiently small, the amplitude of the oscillations can be small enough to practically approximate the dynamics around a stable fixed point.

Stanhope, Liz, Laura Ziegler, Tabassum Haque, Laura Le, Marcelo Vinces, Gregory K. Davis, Andrew Zieffler, Peter Brodfuehrer, Marion Preest, Jason M. Belitsky, Charles Umbanhowar, Jr., and Paul J. Overvoorde. “Development of a Biological Science Quantitative Reasoning Exam (BioSQuaRE).” CBE Life Science Education, vol. 16, no. 4, 2017, ar66.

Abstract: Multiple reports highlight the increasingly quantitative nature of biological research and the need to innovate means to ensure that students acquire quantitative skills. We present a tool to support such innovation. The Biological Science Quantitative Reasoning Exam (BioSQuaRE) is an assessment instrument designed to measure the quantitative skills of undergraduate students within a biological context. The instrument was developed by an interdisciplinary team of educators and aligns with skills included in national reports such as BIO2010, Scientific Foundations for Future Physicians, and Vision and Change. Undergraduate biology educators also confirmed the importance of items included in the instrument. The current version of the BioSQuaRE was developed through an iterative process using data from students at 12 postsecondary institutions. A psychometric analysis of these data provides multiple lines of evidence for the validity of inferences made using the instrument. Our results suggest that the BioSQuaRE will prove useful to faculty and departments interested in helping students acquire the quantitative competencies they need to successfully pursue biology, and useful to biology students by communicating the importance of quantitative skills. We invite educators to use the BioSQuaRE at their own institutions.

Fahlman, Brad D., Kathleen L. Purvis-Roberts, John S. Kirk, Anne K. Bentley, Patrick L. Daubenmire, Jamie P. Ellis, and Michael T. Mury. Chemistry in Context: Applying Chemistry to Society, 9th Edition. McGraw-Hill, 2017.

Abstract: Chemistry in Context, 9th Edition, is the newest edition of a successful, issues-based curriculum developed by the American Chemical Society for non-science majors at the college level. The book teaches students chemistry in the context of their own lives and examines world issues through a science lens.

Kiessling, Roxanna*, Samuel J.S. Rubin*, Jacquelyn Zehner*, Collin Barraugh*, Katherine Snell*, Corinna Fukushima*, Matthew Mulligan*, Melissa Keckley*, Anthony Bosshardt*, Walter Cook* and Babak Sanii. “Gravity-Drawn Silicone Filaments: Production, Characterization, and Wormlike Chain Dynamics.” ACS Applied Materials and Interfaces, vol. 9, issue 46, 2017, pp. 39916-39920.

Abstract: We introduce a method to produce continuous polydimethylsiloxane (PDMS) silicone filaments on the order of 0.5 m long and 100 µm in diameter. The approach overcomes traditional limitations in silicone drawing by partially precuring the polymer and drawing through a tube furnace. We characterize the filaments' mechanical properties, and their ability to switch hydrophobicity by UV-ozone and corona discharge patterning. The flexible filaments' dynamic properties were evaluated by way of athermal acoustic excitation at the air-water interface, revealing conformational reconfigurability consistent with a wormlike chain model. We envision applications in rapid prototyping and as a platform for model foldamer studies

External Grant: Tang, Zhaohua, NIH AREA Grant, “Novel Functions of LAMMER-related Kinases in Gene Expression,” $412,415, September 8, 2017-August 31, 2020.

A Small Protein Family, A Large Presence in the Cell --Exploring Novel Functions of LAMMER-related Kinases in Gene Expression The human genome harbors genes encoding a family of more than 500 different proteins known as kinases. These protein kinases are players mediating signal transduction pathways that control virtually every aspect of cell function and survival. LAMMER-related kinases, although a relatively small subgroup among kinase families, play major roles in cell growth, differentiation and death, insulin-regulated metabolism, hepatitis B virus infection, cancer development and cellular sensitivity to anti-cancer drugs. They are subjects of extensive interest because of their potential to serve as therapeutic targets for various human diseases. Despite their importance and disease relevance, considerable gaps of knowledge exist regarding the mechanisms by which the LAMMER-related kinases carry out their functions. The NIH-supported research aims at exploring the novel roles of the protein factors in various steps of gene expression. Achieving the goals of the project will lay the foundation for the long-term investigation to decipher the molecular basis for integrating the multiple steps of complex gene expression in response to diverse cellular signals. Furthermore, this project also aims to provide opportunities for student research experience in the areas relevant to public health, including senior theses, independent studies, and biology course-based investigations. The educational objectives of the project are intertwined with the specific research aims to strengthen investigative components of science education, to stimulate students' interest in science, to enhance their understanding of research logics and themes, and to encourage women and underrepresented groups in science to participate in research.

External Grant: “Organic Syntheses, Inc. Grant for Summer Research at an Undergraduate Institution.” Organic Syntheses, Inc. PI: Anna Wenzel; $8,000; Keck Science Department, Claremont, CA, 2017.

This prestigious mentorship grant supports the ongoing research of Ellen Berkley ’18, a student in Prof. Wenzel’s lab. Berkley’s research concerns the [3,3]-sigmatropic rearrangement of allyl vinyl ethers, the Claisen rearrangement, which is a prominent method for the rapid construction of carbon-carbon bonds. Berkley is working on the first enantioselective allenoate Claisen rearrangement reaction, which was recently discovered in Wenzel’s lab by Berkley, Rachael Hamilton SCR’16 and Iain Laufer ’17.

Elgin, Sarah C. R., Gita Bangera, Vincent P. Buonaccorsi, Douglas L. Chalker, Elizabeth Dinsdale, Erin L. Dolan, Linnea Fletcher, Arthur Hunt, Carolyn J. Lawrence-Dill, Wilson Leung, Laura K. Reed, Anne G. Rosenwald, Sandesh Subramanya, Emily Wiley, and Jason Williams. “A Genomics Education Alliance.” Figshare, 2017.

Abstract: Genomics has emerged as a critical area of research for the life sciences, generating new social and scientific perspectives. Low-cost sequencing and advances in computing have accelerated genomics research at a pace that leaves educators at the undergraduate level struggling to keep up. We present a call to action, advocating for creation of a Genomics Education Alliance (GEA) - a global, sustainable, community-driven organization that can coalesce disparate efforts to deliver on the educational and scientific promise of genomics in the 21st century. Addressing the emerging challenges in human health, agriculture, and climate will depend on training the next generation of biology students to be data-savvy scientists. Genome annotation and analysis, as a stand-alone effort or in conjunction with wet-bench investigation, has proven to be an effective way to a) introduce large numbers of biology students to bioinformatics, and b) provide students with a course-based research experiences (CUREs). GEA can implement and maintain an up-to-date framework, including accessible tools and research problems, to support undergraduate education, promoting CURE-based approaches and addressing barriers (e.g. technological, training, pedagogical) that educators face in bringing genomics to undergraduates at scale. We invite the community of researchers and educators working in genomics and related fields to join us in shaping this alliance with the aim of achieving transformative change in life science education.

Gallagher, Sean R., and Emily A. Wiley, eds. Current Protocols: Essential Laboratory Techniques, Supplement 14. John Wiley and Sons, 2017.

Gallagher, Sean R., and Emily A. Wiley, eds. Current Protocols: Essential Laboratory Techniques, Supplement 15. John Wiley and Sons, 2017.

Chan, P., Halfar, J., Hetzinger, S., Adey, W., Zack, T., Moore, G.W.K., Wortmann, U.G., Williams, B., and Hou, A. “Multicentennial Record of Labrador Sea Primary Productivity and Sea-Ice Variability Archived in Coralline Algal Barium.” Nature Communications, 8, 2017, 15543.

Abstract: Accelerated warming and melting of Arctic sea-ice has been associated with significant increases in phytoplankton productivity in recent years. Here, utilizing a multiproxy approach, we reconstruct an annually resolved record of Labrador Sea productivity related to sea-ice variability in Labrador, Canada that extends well into the Little Ice Age (LIA; 1646 AD). Barium-to-calcium ratios (Ba/Ca) and carbon isotopes (δ13C) measured in long-lived coralline algae demonstrate significant correlations to both observational and proxy records of sea-ice variability, and show persistent patterns of co-variability broadly consistent with the timing and phasing of the Atlantic Multidecadal Oscillation (AMO). Results indicate reduced productivity in the Subarctic Northwest Atlantic associated with AMO cool phases during the LIA, followed by a step-wise increase from 1910 to present levels--unprecedented in the last 363 years. Increasing phytoplankton productivity is expected to fundamentally alter marine ecosystems as warming and freshening is projected to intensify over the coming century.

Dassié, Emilie, Kristine DeLong, Hali Kilbourne, Branwen Williams, et al. “Saving Our Marine Archives.” EOS, 98, 2017.

Abstract: A concerted effort has begun to gather and preserve archives of marine samples and descriptive data, giving scientists ready access to insights on ancient environments.

Prouty, Nancy G., E. Brendan Roark, Allen Andrews, Laura Robinson, Tessa Hill, Owen Sherwood, Branwen Williams, Thomas P. Guilderson, and Stewart Fallon. “Age, Growth Rates, and Paleoclimate Studies of Deep Sea Corals.” The State of Deep‐Sea Coral and Sponge Ecosystems of the United States, print edition, edited by Thomas F. Hourigan, Peter J. Etnoyer, and Stephen D. Cairns, NOAA Technical Memorandum NMFS‐OHC‐4, 2017, pp. 297-319.

Abstract: Deep-water corals are some of the slowest growing, longest-lived skeletal accreting marine organisms. These habitat-forming species support diverse faunal assemblages that include commercially and ecologically important organisms. Therefore, effective management and conservation strategies for deep-sea corals can be informed by precise and accurate age, growth rate, and lifespan characteristics for proper assessment of vulnerability and recovery from perturbations. This is especially true for the small number of commercially valuable, and potentially endangered, species that are part of the black and precious coral fisheries (Tsounis et al. 2010). In addition to evaluating time scales of recovery from disturbance or exploitation, accurate age and growth estimates are essential for understanding the life history and ecology of these habitat-forming corals. Given that longevity is a key factor for population maintenance and fishery sustainability, partly due to limited and complex genetic flow among coral populations separated by great distances, accurate age structure for these deep-sea coral communities is essential for proper, long-term resource management. The importance of accurate age and growth characteristics has another important utility in marine sciences. Many deep-sea corals have been useful as biogeochemical proxies that provide a unique view of marine climate and environmental change over time (e.g., Adkins et al. 1998, Robinson et al. 2005, LaVigne et al. 2011). Similar to trees on land, many corals have concentric growth rings that allow scientists to track growth patterns, which can be used to look back into climate history over the coral’s lifespan using stable and radio-isotope techniques. Here we summarize recent developments in determining age and growth characteristics for structure-forming deepsea corals, many of which are vulnerable to disturbance, with highlights on recent advances in paleoclimate reconstruction efforts using deep-sea corals.

Williams, B., Halfar, J., DeLong, K.L., Smith, E., Steneck, R., Lebednik, P., Jacob, D.E., Fietzke, J., and Moore, G.W.K. “North Pacific Twentieth Century Decadal-Scale Variability is Unique for the Past 342 Years.” Geophysical Research Letters, vol. 44, issue 8, 2017, pp. 3761-3769.

Abstract: Reconstructed sea surface temperatures (SSTs) derived from Mg/Ca measurements in nine encrusting coralline algal skeletons from the Aleutian archipelago in the northernmost Pacific Ocean reveal an overall increase in SST from 1665 to 2007. In the Aleutian SST reconstruction, decadal-scale variability is a transient feature present during the 1700s and early 1800s and then fully emerging post-1950. SSTs vary coherently with available instrument records of cyclone variance and vacillate in and out of coherence with multicentennial Pacific Northwest drought reconstructions as a response to SST-driven alterations of storm tracks reaching North America. These results indicate that an influence of decadal-scale variability on the North Pacific storm tracks only became apparent during the midtwentieth century. Furthermore, what has been assumed as natural variability in the North Pacific, based on twentieth century instrumental data, is not consistent with the long-term natural variability evident in reconstructed SSTs predating the anthropogenic influence.

External Grant: Henry Luce Foundation’s LIASE (Luce Initiative on Asian Studies and the Environment) Program: “Environmental Infrastructure in Asia: Nature, Networks and People in the Anthropocene.” Albert Park (lead-PI), Branwen Williams, and Marc Los-Huertos (co-PIs). $1,400,000, 2017–2021.

EnviroLab Asia is a laboratory for cross-disciplinary research and experiential learning that links knowledge with practice. We aim to engage communities and explore what comes out of the intellectual exchange between the humanities and social sciences, environmental analysis, and various other fields to generate new scholarship about environmental issues in Asia. This is an initiative at the Claremont Colleges funded by the Henry Luce Foundation's LIASE (Luce Initiative on Asian Studies and the Environment) Program and is anchored at Claremont McKenna College. In May 2017, the Henry Luce Foundation awarded EnviroLab Asia a $1.4 million grant to expand its activities at the Claremont Colleges for the next four years.

External grants: National Science Foundation, IUSE-Development and Implementation, Institutional and Community Transformation, "Collaborative Research: Improving Inorganic Chemistry Education Through a Community-Developed Student-Centered Curriculum." September 2017-August 2022, Joanne L Stewart (Hope College, PI), Anne K Bentley (Lewis & Clark, co-PI), Sheila R Smith (UM Dearborn, co-PI), Nancy S Williams (Claremont Colleges Joint Science Department, co-PI): $594,291. Barbara Reisner (James Madison, PI): $223,908. Jeffrey Raker (University of South Florida, PI): $303,577. TOTAL FUNDING: $1,110,260.

National Science Foundation, ROA-Facilitating Research at Primarily Undergraduate Institutions: Research Opportunity Awards "A Strong Pi-Donor Ligand to Enhance Late Metal Back Donation" January 2018-March 2018, Elizabeth R. Jarvo (UC Irvine, PI), Nancy S. B. Williams, Keck Science Department, Visiting Associate Researcher) TOTAL FUNDING: $55,643.

Abraham, Michael H., William E. Acree, Anthony F. Fucaloro, and Andrew W. Zanella. “Determination of Molar Refractions and Abraham Descriptors for tris(acetylacetanato)chromium(III), tris(acetylacetanato)iron(III) and tris(acetylacetanato)cobalt(III).” New Journal of Chemistry, vol. 41, 2017, pp. 14259-14265.

Abstract: We have determined molar refractions of tris(acetylacetonato)chromium(III), tris(acetylacetonato)iron(III) and tris(acetylacetonato)cobalt(III). Although the d-electron structures of the three metal centres differ significantly, the three molar refractions are actually quite close to each other. We then used these molar refractions to determine the Abraham E-descriptor, we calculated the V-descriptor by McGowan's method, and then used literature data on solubilities and water–solvent partitions to obtain the rest of the set of descriptors for the three tris(acetylacetonato) complexes. If we take E as the average of those for the chromium, iron and cobalt complexes, we can use limited literature data to obtain the full set of Abraham descriptors for the tris(acetylacetonates) of vanadium(III), yttrium(III), samarium(III), lanthanum(III) and neodymium(III). For the eight complexes, the descriptors vary regularly with complex molecular weight. These show that the complexes are quite polarizable, have zero hydrogen-bond acidity and significant hydrogen bond basicity. From the sets of Abraham descriptors, a very large number of physicochemical properties can be predicted for the eight acetonylacetonates.


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