2023 W.M. Keck Science Publications and Grants

* Indicates student co-author.

Budischak, Sarah A., Sarah Halvorsen, and Findley Finseth. “Genetic Heterozygosity Is Associated With Parasite Abundance, but the Effects Are Not Mediated by Host Condition.” Evolutionary Ecology, vol. 37, 2023, pp. 75-96.

Abstract: Whether, when, and how genetic diversity buffers individuals and populations against infectious disease risk is a critical and open question for understanding wildlife disease and zoonotic disease risk. Several, but not all, studies have found negative relationships between infection and heterozygosity in wildlife. Since they can host multiple zoonotic infections, we sampled a population of wild deer mice (Peromyscus maniculatus), sequenced their genomes, and examined their fecal samples for coccidia and nematode eggs. We analyzed coccidia infection status, abundance, and coinfection status in relation to per-locus and per-individual measures of heterozygosity, as well as identified SNPs associated with infection status. Since heterozygosity might affect host condition, and condition is known to affect immunity, it was included as a co-variate in the per-individual analyses and as response variable in relation to heterozygosity. Not only did coccidia-infected individuals have lower levels of genome-wide per-locus diversity across all metrics, but we found an inverse relationship between genomic diversity and severity of coccidia infection. We also found weaker evidence that coinfected individuals had lower levels of private allelic variation than all other groups. In the per-individual analyses, relationships between heterozygosity and infection were marginal but followed the same negative trends. Condition was negatively correlated with infection, but was not associated with heterozygosity, suggesting that effects of heterozygosity on infection were not mediated by host condition in this system. Association tests identified multiple loci involved in the inflammatory response, with a particular role for NF-κB signaling, supporting previous work on the genetic basis of coccidia resistance. Taken together, we find that increased genome-wide neutral diversity, the presence of specific genetic variants, and improved condition positively impact infection status. Our results underscore the importance of considering host genomic variation as a buffer against infection, especially in systems that can harbor zoonotic diseases.


Seguel, Mauricio, Sarah A. Budischak, Anna E. Jolles, and Vanessa O. Ezenwa. “Helminth-Associated Changes in Host Immune Phenotype Connect Top-Down and Bottom-Up Interactions During Co-Infection.” Functional Ecology, vol. 37, issue 4, 2023, pp. 860-872.

Abstract:

  1. Within-host parasite interactions can be mediated by the host and changes in host phenotypes often serve as indicators of the presence or intensity of parasite interactions.
  2. Parasites like helminths induce a range of physiological, morphological and immunological changes in hosts that can drive bottom-up (resource-mediated) or top-down (immune-mediated) interactions with co-infecting parasites. Although top-down and bottom-up interactions are typically studied in isolation, the diverse phenotypic changes induced by parasite infection may serve as a useful tool for understanding if, and when, these processes act in concert.
  3. Using an anthelmintic treatment study of African buffalo, Syncerus caffer, we tracked changes in host immunological and morphological phenotypes during helminth-coccidia co-infection to investigate their role in driving independent and combinatorial bottom-up and top-down parasite interactions. We also examined repercussions for host fitness.
  4. Clearance of a blood-sucking helminth, Haemonchus, from the host gastrointestinal tract induced a systemic Th2 immune phenotype, while clearance of a tissue-feeding helminth, Cooperia, induced a systemic Th1 phenotype. Furthermore, the Haemonchus-associated systemic Th2 immune phenotype drove simultaneous top-down and bottom-up effects that increased coccidia shedding by changing the immunological and morphological landscapes of the intestine.
  5. Higher coccidia shedding was associated with lower host body condition, a lower chance of pregnancy and older age at first pregnancy, suggesting that coccidia infection imposed significant condition and reproductive costs on the host.
  6. Our findings suggest that top-down and bottom-up interactions may commonly co-occur and that tracking key host phenotypes that change in response to infection can help uncover complex pathways by which parasites interact.

Warburton, Elizabeth M., Sarah A. Budischak, Anna E. Jolles, and Vanessa O. Ezenwa. “Within-Host and External Environments Differentially Shape β-Diversity Across Parasite Life Stages.” Journal of Animal Ecology, vol. 92, issue 3, 2023, pp. 665-676.

Abstract:

  1. Uncovering drivers of community assembly is a key aspect of learning how biological communities function. Drivers of community similarity can be especially useful in this task as they affect assemblage-level changes that lead to differences in species diversity between habitats. Concepts of β-diversity originally developed for use in free-living communities have been widely applied to parasite communities to gain insight into how infection risk changes with local conditions by comparing parasite communities across abiotic and biotic gradients.
  2. Factors shaping β-diversity in communities of immature parasites, such as larvae, are largely unknown. This is a key knowledge gap as larvae are frequently the infective life-stage and understanding variation in these larval communities is thus key for disease prevention. Our goal was to uncover links between β-diversity of parasite communities at different life stages; therefore, we used gastrointestinal nematodes infecting African buffalo in Kruger National Park, South Africa, to investigate within-host and extra-host drivers of adult and larval parasite community similarity.
  3. We employed a cross-sectional approach using PERMANOVA that examined each worm community at a single time point to assess independent drivers of β-diversity in larvae and adults as well as a longitudinal approach with path analysis where adult and larval communities from the same host were compared to better link drivers of β-diversity between these two life stages.
  4. Using the cross-sectional approach, we generally found that intrinsic, within-host traits had significant effects on β-diversity of adult nematode communities, while extrinsic, extra-host variables had significant effects on β-diversity of larval nematode communities. However, the longitudinal approach provided evidence that intrinsic, within-host factors affected the larval community indirectly via the adult community.
  5. Our results provide key data for the comparison of community-level processes where adult and immature stages inhabit vastly different habitats (i.e. within-host vs. abiotic environment). In the context of parasitism, this helps elucidate host infection risk via larval stages and the drivers that shape persistence of adult parasite assemblages, both of which are useful for predicting and preventing infectious disease.

Mills, Jessie Lee and Pete Chandrangsu. “Building Radical Listening and Empathy through an Implementation Lab in an Undergraduate Microbiology Course.” Journal of Microbiology and Biology Education, vol. 24, no. 1, 2023, e00158-22.

Abstract: With rapid advances in science and technology, individuals are faced with the challenging process of making decisions based on sound and accurate information. As a result, to promote scientific literacy, scientists must be able to engage with a wide range of audiences in an inclusive and engaging manner. In addition to a solid knowledge of facts and data, effective scientific communication requires an empathetic approach that comes from a place of understanding and values the knowledge and experience of the intended audience. Here, we present two modules designed to introduce undergraduate students to fundamental concepts in empathetic science communication and provide an opportunity for students to develop a personalized methodology. Over the course of two 75-min classes, students engaged in the process of character development and role play in support of discussions around vaccine hesitancy or community-based service learning. Based on student feedback, the module was well received and supported student growth as engaged scientists and citizens.

Ferree, Patrick. “Cell Biology: Selfish B Chromosomes Unleashed by a Dysfunctional Chromosome Segregation System.” Dispatch, vol. 33, issue 11, 2023, pp. 431-434.

Abstract: A study in the fruit fly Drosophila melanogaster shows that a defective chromosome segregation system allows non-essential B chromosomes to transmit at higher-than-Mendelian frequencies.


Lee, Haena, Pooreum Seo, Salina Teklay, Emily Yuguchi, Elena Dalla Benetta, John H. Werren, and Patrick Ferree. “Ability of a Selfish B Chromosome to Evade Genome Elimination in the Jewel Wasp, Nasonia Vitripennis.” Heredity, vol. 131, 2023, pp. 230-237.

Abstract: B chromosomes are non-essential, extra chromosomes that can exhibit transmission-enhancing behaviors, including meiotic drive, mitotic drive, and induction of genome elimination, in plants and animals. A fundamental but poorly understood question is what characteristics allow B chromosomes to exhibit these extraordinary behaviors. The jewel wasp, Nasonia vitripennis, harbors a heterochromatic, paternally transmitted B chromosome known as paternal sex ratio (PSR), which causes complete elimination of the sperm-contributed half of the genome during the first mitotic division of fertilized embryos. This genome elimination event may result from specific, previously observed alterations of the paternal chromatin. Due to the haplo-diploid reproduction of the wasp, genome elimination by PSR causes female-destined embryos to develop as haploid males that transmit PSR. PSR does not undergo self-elimination despite its presence with the paternal chromatin until the elimination event. Here we performed fluorescence microscopic analyses aimed at understanding this unexplained property. Our results show that PSR, like the rest of the genome, participates in the histone-to-protamine transition, arguing that PSR does not avoid this transition to escape self-elimination. In addition, PSR partially escapes the chromatin-altering activity of the intracellular bacterium, Wolbachia, demonstrating that this ability to evade chromatin alteration is not limited to PSR’s own activity. Finally, we observed that the rDNA locus and other unidentified heterochromatic regions of the wasp’s genome also seem to evade chromatin disruption by PSR, suggesting that PSR’s genome-eliminating activity does not affect heterochromatin. Thus, PSR may target an aspect of euchromatin to cause genome elimination.

Budischak, Sarah A., Sarah Halvorsen, and Findley Finseth. “Genetic Heterozygosity is Associated with Parasite Abundance, but the Effects are Not Mediated by Host Condition.” Evolutionary Ecology, vol. 37, 2023, pp. 75-96.

Abstract: Whether, when, and how genetic diversity buffers individuals and populations against infectious disease risk is a critical and open question for understanding wildlife disease and zoonotic disease risk. Several, but not all, studies have found negative relationships between infection and heterozygosity in wildlife. Since they can host multiple zoonotic infections, we sampled a population of wild deer mice (Peromyscus maniculatus), sequenced their genomes, and examined their fecal samples for coccidia and nematode eggs. We analyzed coccidia infection status, abundance, and coinfection status in relation to per-locus and per-individual measures of heterozygosity, as well as identified SNPs associated with infection status. Since heterozygosity might affect host condition, and condition is known to affect immunity, it was included as a co-variate in the per-individual analyses and as response variable in relation to heterozygosity. Not only did coccidia-infected individuals have lower levels of genome-wide per-locus diversity across all metrics, but we found an inverse relationship between genomic diversity and severity of coccidia infection. We also found weaker evidence that coinfected individuals had lower levels of private allelic variation than all other groups. In the per-individual analyses, relationships between heterozygosity and infection were marginal but followed the same negative trends. Condition was negatively correlated with infection, but was not associated with heterozygosity, suggesting that effects of heterozygosity on infection were not mediated by host condition in this system. Association tests identified multiple loci involved in the inflammatory response, with a particular role for NF-κB signaling, supporting previous work on the genetic basis of coccidia resistance. Taken together, we find that increased genome-wide neutral diversity, the presence of specific genetic variants, and improved condition positively impact infection status. Our results underscore the importance of considering host genomic variation as a buffer against infection, especially in systems that can harbor zoonotic diseases.


Finseth, Findley. “Female Meiotic Drive in Plants: Mechanisms and Dynamics.” Current Opinion in Genetics & Development, vol. 82, 2023, 102101.

Abstract: Female meiosis is fundamentally asymmetric, creating an arena for genetic elements to compete for inclusion in the egg to maximize their transmission. Centromeres, as mediators of chromosomal segregation, are prime candidates to evolve via ‘female meiotic drive’. According to the centromere-drive model, the asymmetry of female meiosis ignites a coevolutionary arms race between selfish centromeres and kinetochore proteins, the by-product of which is accelerated sequence divergence. Here, I describe and compare plant models that have been instrumental in uncovering the mechanistic basis of female meiotic drive (maize) and the dynamics of active selfish centromeres in nature (monkeyflowers). Then, I speculate on the mechanistic basis of drive in monkeyflowers, discuss how centromere strength influences chromosomal segregation in plants, and describe new insights into the evolution of plant centromeres.

Fucaloro, Anthony F. and Andrew Zanella. “A Comparison of the Volumetric Properties of Proteated and Deuterated Water and Their Relation to Other Thermodynamic Properties.” Journal of Solution Chemistry, vol 52, 2023, pp 671-684.

Abstract: The unusual volumetric properties of both proteated and deuterated water are explored by carefully comparing their volumetric properties and developing a heuristic molecular model to describe the behavior. The behavior is further explored by relating these properties to other well-known thermodynamic properties.

Williams, Sierra J., Jordan A. Gewing-Mullins, Whitney K. Lieberman, Bethany Kolbaba Kartchner, Reema Iqbal, Hana M. Burgess, Claire M. Colee, Marya Y. Ornelas, Edison S. Reid-McLaughlin, Jeremy H. Mills, Jennifer A. Prescher, and Aaron M. Leconte. “Biochemical Analysis Leads to Improved Orthogonal Bioluminescent Tools.” ChemBioChem, vol. 24, issue 6, 2023, e202200726.

Abstract: Engineered luciferase-luciferin pairs have expanded the number of cellular targets that can be visualized in tandem. While light production relies on selective processing of synthetic luciferins by mutant luciferases, little is known about the origin of selectivity. The development of new and improved pairs requires a better understanding of the structure−function relationship of bioluminescent probes. In this work, we report a biochemical approach to assessing and optimizing two popular bioluminescent pairs: Cashew/d-luc and Pecan/4′-BrLuc. Single mutants derived from Cashew and Pecan revealed key residues for selectivity and thermal stability. Stability was further improved through a rational addition of beneficial residues. In addition to providing increased stability, the known stabilizing mutations surprisingly also improved selectivity. The resultant improved pair of luciferases are >100-fold selective for their respective substrates and highly thermally stable. Collectively, this work highlights the importance of mechanistic insight for improving bioluminescent pairs and provides significantly improved Cashew and Pecan enzymes which should be immediately suitable for multicomponent imaging applications.


External Grant: Leconte, Aaron M, Principal Investigator. “Marcell Simon: Exploring the C-terminal Domain of Firefly Luciferase.” Cottrell Postbaccalaureate Research Award, Research Corporation for Science Advancement, 2023 - 2024, $50,000.

Abstract: This award provides funding for a full-time post-baccalaureate research assistant (Marcell Simon) for June 2023-June 2024. With this funding, the research assistant will complete ongoing projects and generate preliminary data for an upcoming NIH R15 renewal award by exploring the role of the C-terminal domain in the function of the protein luciferase. This award effectively seeks to to help mitigate the disruptions to my lab and our NIH-funded work that were caused by Covid. It provides a bridge between my recently completed NIH R15 award and the impending application for renewal of the NIH R15 award.

Duran-Urriago, Alejandra and Sarah Marzen. “Not So Optimal: The Evolution of Mutual Information in Potassium Voltage-Gated Channels.” PLOS One, vol. 18, issue 2, 2023, e0264424.

Abstract: Potassium voltage-gated (Kv) channels need to detect and respond to rapidly changing ionic concentrations in their environment. With an essential role in regulating electric signaling, they would be expected to be optimal sensors that evolved to predict the ionic concentrations. To explore these assumptions, we use statistical mechanics in conjunction with information theory to model how animal Kv channels respond to changes in potassium concentrations in their environment. By measuring mutual information in representative Kv channel types across a variety of environments, we find two things. First, under weak conditions, there is a gating charge that maximizes mutual information with the environment. Second, as Kv channels evolved, they have moved towards decreasing mutual information with the environment. This either suggests that Kv channels do not need to act as sensors of their environment or that Kv channels have other functionalities that interfere with their role as sensors of their environment.


Hsu, Alexander and Sarah E. Marzen. “Strange Properties of Linear Reservoirs in the Infinitely Large Limit for Prediction of Continuous-Time Signals.” Journal of Statistical Physics, vol. 190, 2023, article no. 32.

Abstract: Large linear reservoirs, while not necessarily of practical utility, might provide insight to large nonlinear reservoirs. Our study of large linear reservoirs in the context of improving predictive capabilities suggests that: one desires to be near the edge of instability; and random matrix theory guarantees that the performance of large linear random matrices is only dependent on how weights in the weight matrix are chosen and not the individual weights. It also seems as though dynamic and static weights are quite different in performance. We comment on how these lessons may or may not apply to the large nonlinear reservoirs that are typically used for prediction applications.


Lamberti, Martina, Shiven Tripathi, Michel J A M van Putten, Sarah Marzen, and Joost le Feber. “Prediction in Cultured Cortical Neural Networks.” PNAS Nexus, vol. 2, issue 6, 2023, pp. 188.

Abstract: Theory suggest that networks of neurons may predict their input. Prediction may underlie most aspects of information processing and is believed to be involved in motor and cognitive control and decision-making. Retinal cells have been shown to be capable of predicting visual stimuli, and there is some evidence for prediction of input in the visual cortex and hippocampus. However, there is no proof that the ability to predict is a generic feature of neural networks. We investigated whether random in vitro neuronal networks can predict stimulation, and how prediction is related to short- and long-term memory. To answer these questions, we applied two different stimulation modalities. Focal electrical stimulation has been shown to induce long-term memory traces, whereas global optogenetic stimulation did not. We used mutual information to quantify how much activity recorded from these networks reduces the uncertainty of upcoming stimuli (prediction) or recent past stimuli (short-term memory). Cortical neural networks did predict future stimuli, with the majority of all predictive information provided by the immediate network response to the stimulus. Interestingly, prediction strongly depended on short-term memory of recent sensory inputs during focal as well as global stimulation. However, prediction required less short-term memory during focal stimulation. Furthermore, the dependency on short-term memory decreased during 20 h of focal stimulation, when long-term connectivity changes were induced. These changes are fundamental for long-term memory formation, suggesting that besides short-term memory the formation of long-term memory traces may play a role in efficient prediction.


Levenstein, Daniel, Veronica A. Alvarez, Asohan Amarasingham, Habiba Azab, Zhe S. Chen, Richard C. Gerkin, Andrea Hasenstaub, Ramakrishnan Iyer, Renaud B. Jolivet, Sarah Marzen, Joseph D. Monaco, Astrid A. Prinz, Salma Quraishi, Fidel Santamaria, Sabyasachi Shivkumar, Matthew F. Singh, Roger Traub, Farzan Nadim, Horacio G. Rotstein, and A. David Redish. “On the Role of Theory and Modeling in Neuroscience.” Journal of Neuroscience, vol. 43, no. 7, 2023, pp. 1074-1088.

Abstract: In recent years, the field of neuroscience has gone through rapid experimental advances and a significant increase in the use of quantitative and computational methods. This growth has created a need for clearer analyses of the theory and modeling approaches used in the field. This issue is particularly complex in neuroscience because the field studies phenomena that cross a wide range of scales and often require consideration at varying degrees of abstraction, from precise biophysical interactions to the computations they implement. We argue that a pragmatic perspective of science, in which descriptive, mechanistic, and normative models and theories each play a distinct role in defining and bridging levels of abstraction, will facilitate neuroscientific practice. This analysis leads to methodological suggestions, including selecting a level of abstraction that is appropriate for a given problem, identifying transfer functions to connect models and data, and the use of models themselves as a form of experiment. 


Sawaya, Yorgo, George Issa, and Sarah Marzen. “Framework for Solving Time-Delayed Markov Decision Processes.” Physics Review Research, vol. 5, issue 3, 2023, pp. 033034.

Abstract: Reinforcement learning has revolutionized our understanding of evolved systems and our ability to engineer systems based on a theoretical framework for understanding how to maximize expected reward. However, time delays between the observation and action are estimated to be roughly ∼ 150 ms for humans, and this should affect reinforcement learning algorithms. We reformulate the Markov Decision Process framework to include time delays in action, first deriving a new Bellman equation in a way that unifies previous attempts and then implementing the corresponding SARSA-like algorithm. The main ramification—potentially useful for both evolved and engineered systems—is that, when the size of the state space is lower than that of the action space, the modified reinforcement learning algorithms will prefer to operate on sequences of states rather than just the present state with the length of the sequence equal to 1 plus the time delay.


Soriano, Jonathan and Sarah Marzen. “How Well Can We Infer Selection Benefits and Mutation Rates from Allele Frequencies?Entropy, vol. 25, issue 4, 2023, pp. 615.

Abstract: Experimentalists observe allele frequency distributions and try to infer mutation rates and selection coefficients. How easy is this? We calculate limits to their ability in the context of the Wright-Fisher model by first finding the maximal amount of information that can be acquired using allele frequencies about the mutation rate and selection coefficient– at least 2 bits per allele– and then by finding how the organisms would have shaped their mutation rates and selection coefficients so as to maximize the information transfer.


External Grant: Marzen, Sarah. “Hyperspectral-Hyperdimensional Engines via Ultralow-Power Resonant In-Memory-Compute Systems and Tunable Phononic Combs (HEURISTIC).” Defense Advanced Research Projects Agency, 2023.

Abstract: We propose a two‐phase (48‐month) project to develop new computational processors based upon arrays of nanoelectromechanical systems (NEMS). Our effort, which we call HEURISTiC (Hyperspectral‐Hyperdimensional Engines via Ultralow‐Power Resonant In‐Memory‐Compute Systems and Tunable Phononic Combs), will meet all NaPSAC program goals. In HEURISTiC we will explore three complementary tracks to build and explore computational architectures based upon voltage‐tunable and ‐programmable NEMS resonators. The individual devices (nodes) are fabricated from piezoelectric‐ferroelectric AlN and Al1‐xScxN (hereafter Al(Sc)N) thin films; each node provides high electromechanical coupling efficiency, excellent CMOS compatibility and scalability, and local nonvolatile memory. Together, these attributes permit in‐memory processing with optimal processing speed and efficiency.


External Grant: Marzen, Sarah. Santa Fe Institute, 2023, $20,000.

Nagy, Dalma J., John G. Milton, and Tamas Insperger. “Controlling Stick Balancing on a Linear Track: Delayed State Feedback or Delay-Compensating Predictor Feedback?Biological Cybernetics, vol. 117, 2023, pp. 113-127.

Abstract: A planar stick balancing task was investigated using stabilometry parameters (SP); a concept initially developed to assess the stability of human postural sway. Two subject groups were investigated: 6 subjects (MD) with many days of balancing a 90 cm stick on a linear track and 25 subjects (OD) with only one day of balancing experience. The underlying mechanical model is a pendulum-cart system. Two control force models were investigated by means of numerical simulations: (1) delayed state feedback (DSF); and (2) delay-compensating predictor feedback (PF). Both models require an internal model and are subject to certainty thresholds with delayed switching. Measured and simulated time histories were compared quantitatively using a cost function in terms of some essential SPs for all subjects. Minimization of the cost function showed that the control strategy of both OD and MD subjects can better be described by DSF. The control mechanism for the MD subjects was superior in two aspects: (1) they devoted less energy to controlling the cart’s position; and (2) their perception threshold for the stick’s angular velocity was found to be smaller. Findings support the concept that when sufficient sensory information is readily available, a delay-compensating PF strategy is not necessary.

Valencia, Miles, Apolo Ibáñez Rincon, Jenna A. Monroy, Theodore Garland, and Angela Horner. “Wheel Running Intensity Effects on Mice Tendon Mechanics.” Physiology, vol. 38, issue 1, 2023, 5735190. 

Abstract: Exercise has numerous effects on the musculoskeletal system, including muscle hypertrophy and tendon remodeling. Although exercise is well documented to affect tendon materials properties, the impacts of exercise intensity are less understood. To study the effects of exercise intensity on adult tendon, we used a line of mice artificially selected for high voluntary wheel running for over 90 generations (High Runner, HR). HR and control line mice were separated into wheel running and sedentary training groups at 9-weeks of age. Wheel activity was quantified using tachometers and collected weekly. After 9 weeks of exercise, mice were sacrificed and stored at -20 °C until the plantarflexor tendons were isolated for processing. Tendon cross-sectional area and length were measured in ImageJ. Tendons were marked with indelible ink for direct strain measurements and then were attached to an ergometer for sinusoidal and ramp-to-failure excursions. Force and lever displacement were recorded directly from the ergometer while actual tissue strain was obtained via high-speed videography. When analyzing our data with body mass as a covariate, our results suggest that exercise or linetype have no significant effect on tendon morphology; however, tendon length is significantly affected by the interaction of linetype and exercise. The interaction of exercise and linetype significantly affected yield and failure strain where wheel training increased strain in control mice and decreased strain in HR mice. Interestingly, wheel exercise and training intensity do not synergistically affect tendon material properties but result in varying changes. Total kilometers ran per day had an inverse relationship with yield and failure strain for control mice whereas HR mice showed no correlation for either; ultimately, no relationships with total kilometers ran per day were significant. Future studies should incorporate histological approaches to understand the tendon compositional changes leading to these variable responses.

Silva, Philip J., Tanner Cress, Ryan Drover, Cara Michael, Gregory Docekal, Pierce Larkin, Antonio Godoy, Devin A. Cavero, Crystal Sin, Janise Waites, Rezaul Mahmood, Martin Cohron, and Kathleen Purvis-Roberts. “Characterization of Particle Size Distributions and Water-Soluble Ions in Particulate Matter Measured at a Broiler Farm.” Agriculture, vol. 13, no. 7, 2023, 1284.

Abstract: The chemical composition and size distribution of particulate matter produced at broiler poultry houses is not well understood, so this is a novel study to understand the particulate size distributions at a poultry house as well as the ionic composition of the particulate matter using real-time methods. Two optical particle counters provided particle size distributions inside and outside the house. An ambient ion monitor and a particle-in-liquid sampler analyzed the ionic chemical composition of the particulate matter in the house while a scanning mobility particle sizer provided size information in the nanoparticle range. Ammonia concentrations in the house were measured using a chemical sensor. Ammonia concentrations in the house were consistently in the lower part of the per million range 2–20 ppm. The optical particle counter and ion chromatography measurements both showed a strong diurnal variation of particulate matter concentration in the house throughout the study, associated with the lights being on and animal activity. Particulate mass concentration inside the house was dominated by coarse mode particles as opposed to the outdoor sampler which showed much smaller sizes. A few new particle formation and growth events were observed in the house. Ionic constituents detected by chromatography made up a small fraction of the overall mass concentration. The composition of the ionic constituents was similar for most of the study with typical ions being ammonium, sodium, potassium, chloride, sulfate, nitrate, nitrite, phosphate, and several carboxylates (formate, acetate, propionate, and butyrate.) At the end of the study, bromide was also detected during the last several days. Overall, we determined that the ionic components of the particulate matter formed through secondary particle formation was small, but also that some ionic constituents can be associated with management practices.

Achiriloaie, Daisy H., Mehrzad Sasanpour, Karthik R. Peddireddy, Janet Y. Sheung, Ryan J. McGorty, and Rae Robertson-Anderson. “Mechanics and Stress Propagation in Non-Equilibrium Cytoskeleton Composites.” Biophysical Journal, vol. 122, issue 3, 2023, 536a.

Abstract: The cytoskeleton is able to access a wide range of material properties to facilitate cellular processes in a controlled and precise manner via active restructuring and reconfiguration of its constituents by ATP-consuming motor proteins. In vitro cytoskeleton composites have been shown to exhibit tunable mechanical properties, and the addition of force-generating motors to these composites induces non-equilibrium dynamics and restructuring. We characterize the effects of non-equilibrium activity on the mechanical properties of actin-microtubule composites driven by variable concentrations of kinesin motor clusters by performing optical tweezers microrheology experiments. We measure the nonlinear force response of the composites subject to cyclical strain at varied strain rates. Additionally, we measure stress propagation through the composites due to locally imposed strain using differential dynamic microscopy (DDM). We uncover a transition from dissipative to stiffening force response of the composites at mesoscopic lengthscales, with a non-monotonic dependence on kinesin concentration. Our work sheds light on how active restructuring by motor proteins tunes the material response of the cytoskeleton to local stresses, enabling diverse processes such as shape change, motility, and repair.

Kim, Joyce H., Georgia Scherer, Dellencia S. Lumpkin, Krithika Rao, Carmen D. Puentes Flores, and Ethan B. Van Arnam. “Amycolatopsis From Desert Specialist Fungus-Growing Ants Suppresses Contaminant Fungi Using the Antibiotic ECO-0501.” Applied and Environmental Microbiology, vol. 89, issue 2, 2023, e01838-22.

Abstract: Symbiotic Actinobacteria help fungus-growing ants suppress fungal pathogens through the production of antifungal compounds. Trachymyrmex ants of the southwest desert of the United States inhabit a unique niche far from the tropical rainforests in which most fungus-growing ant species are found. These ants may not encounter the specialist fungal pathogen Escovopsis known to threaten colonies of other fungus-growing ants. It is unknown whether Actinobacteria associated with these ants antagonize contaminant fungi and, if so, what the chemical basis of such antagonism is. We find that Pseudonocardia and Amycolatopsis strains isolated from three desert specialist Trachymyrmex species do antagonize diverse contaminant fungi isolated from field-collected ant colonies. We did not isolate the specialist fungal pathogen Escovopsis in our sampling. We trace strong antifungal activity from Amycolatopsis isolates to the molecule ECO-0501, an antibiotic that was previously under preclinical development as an antibacterial agent. In addition to suppression of contaminant fungi, we find that this molecule has strong activity against ant-associated Actinobacteria and may also play a role in bacterial competition in this niche. By studying interspecies interactions in a previously unexplored niche, we have uncovered novel bioactivity for a structurally unique antibiotic.

Williams, Nancy. “Queer in Chem: Q&A with Professor Nancy Williams.” Interviewed by the Editors of Communications Chemistry. Nature: Communications Chemistry, vol. 6, 2023, article no. 209.

Williams, Sierra J., Jordan A. Gewing-Mullins, Whitney K. Lieberman, Bethany Kolbaba Kartchner, Reema Iqbal, Hana M. Burgess, Claire M. Colee, Marya Y. Ornelas, Edison S. Reid-McLaughlin, Jeremy H. Mills, Jennifer A. Prescher, and Aaron Leconte. “Biochemical Analysis Leads to Improved Orthogonal Bioluminescent Tools.” ChemBioChem, vol. 24, issue 6, 2023, e202200726.

Abstract: Engineered luciferase-luciferin pairs have expanded the number of cellular targets that can be visualized in tandem. While light production relies on selective processing of synthetic luciferins by mutant luciferases, little is known about the origin of selectivity. The development of new and improved pairs requires a better understanding of the structure−function relationship of bioluminescent probes. In this work, we report a biochemical approach to assessing and optimizing two popular bioluminescent pairs: Cashew/d-luc and Pecan/4′-BrLuc. Single mutants derived from Cashew and Pecan revealed key residues for selectivity and thermal stability. Stability was further improved through a rational addition of beneficial residues. In addition to providing increased stability, the known stabilizing mutations surprisingly also improved selectivity. The resultant improved pair of luciferases are >100-fold selective for their respective substrates and highly thermally stable. Collectively, this work highlights the importance of mechanistic insight for improving bioluminescent pairs and provides significantly improved Cashew and Pecan enzymes which should be immediately suitable for multicomponent imaging applications.

Fucaloro, Anthony F. and Andrew Zanella. “A Comparison of the Volumetric Properties of Proteated and Deuterated Water and Their Relation to Other Thermodynamic Properties.” Journal of Solution Chemistry, vol 52, 2023, pp 671-684.

Abstract: The unusual volumetric properties of both proteated and deuterated water are explored by carefully comparing their volumetric properties and developing a heuristic molecular model to describe the behavior. The behavior is further explored by relating these properties to other well-known thermodynamic properties.