Publications

Submitted
Pourfathollah AA. Submitted. “JA888”.
Kristjansson A. Submitted. “JA999”.
T Francis, EM Wolkovich, MD Scheuerell, S Katz, E Holmes, and SE Hampton. Submitted. “Shifting drivers and changing interactions: Detecting regime, driver and interaction changes using moving-window autoregressive models.” Canadian Journal of Fisheries and Aquatic Sciences.
Sourav Chowdhury, Daniel C. Zielinski, Christopher Dalldorf, Joao V Rodrigues, Bernhard O. Palsson, and EugeneI. Shakhnovich. Submitted. “A systems-guided approach to discover the intracellular target of a novel evolution-drug lead.” bioRxiv. Publisher's VersionAbstract
Understanding intracellular antibiotic targeting and the associated mechanisms leading to bacterial growth inhibition has been a difficult problem. Here, we discovered the additional intracellular targets of the novel “evolution-drug” lead CD15-3 designed to delay the emergence of antibiotic resistance by inhibiting bacterial DHFR and its Trimethoprim resistant variants. Overexpression of DHFR only partially rescued inhibition of E. coli growth by CD15.3 suggesting that CD15.3 also inhibits a non-DHFR target in the cell. We utilized untargeted global metabolomics and the metabolic network analysis along with structural similarity search of the putative targets to identify the additional target of CD15-3. We validated in vivo and in vitro that besides DHFR CD15-3 inhibits HPPK (folK), an essential protein upstream of DHFR in bacterial folate metabolism. This bivalent cellular targeting makes CD15-3 a promising lead to develop a “monotherapy analogue” of combination drugs.Competing Interest StatementThe authors have declared no competing interest.
A.M. Conard, N. Goodman, Hu, Y, N. Perrimon, R. Singh, C. Lawrence, and E. Larschan. Submitted. “TIMEOR: a web-based tool to uncover temporal regulatory mechanisms from multi-omics data.” BioRxiv. Publisher's VersionAbstract
Uncovering how transcription factors (TFs) regulate their targets at the DNA, RNA and protein levels over time is critical to define gene regulatory networks (GRNs) in normal and diseased states. RNA-seq has become a standard method to measure gene regulation using an established set of analysis steps. However, none of the currently available pipeline methods for interpreting ordered genomic data (in time or space) use time series models to assign cause and effect relationships within GRNs, are adaptive to diverse experimental designs, or enable user interpretation through a web-based platform. Furthermore, methods which integrate ordered RNA-seq data with transcription factor binding data are urgently needed. Here, we present TIMEOR (Trajectory Inference and Mechanism Exploration with Omics data in R), the first web-based and adaptive time series multi-omics pipeline method which infers the relationship between gene regulatory events across time. TIMEOR addresses the critical need for methods to predict causal regulatory mechanism networks between TFs from time series multi-omics data. We used TIMEOR to identify a new link between insulin stimulation and the circadian rhythm cycle. TIMEOR is available at https://github.com/ashleymaeconard/TIMEOR.git.
2020.09.14.296418v1.full_.pdf
Forthcoming
Josiah Blackmore. Forthcoming. “Lisbon.” In Europe: A Literary History, edited by David Wallace, Pp. 1348-1481. Oxford Univ. Press.
Josiah Blackmore. Forthcoming. “Singing the Scene of History in Fernão Lopes.” In and Out of the Mediterranean: Medieval and Early Modern Iberian Studies, Hispanic Issues.
Tey Meadow. Forthcoming. “Unnatural Boundaries: the Challenge of Transgender.” In Edges, edited by Craig J Calhoun and Richard Sennett. New York, NY: NYU Press.Abstract

For many people, the “M” or “F” stamped on government-issued identity documentation represents little more than a common formality, a universally applicable biometric, an unquestioned indicator of group membership. This is not true for everyone. Over the last few decades, an international transgender community, given shape, in some part, by victories of feminist and gay liberation movements and larger transformations in scientific thinking about sex and sexuality, has called upon law and the broader culture to remake understandings of male/female difference. Thus begins a series of public contests over the border between “M” and “F.” Will biomedicine and law recognize a more diverse constellation of indicia of gender, including personal identity? What are the conditions under which the state will allow individuals to elect to alter their legal identities? What counts as gender, and who can be the target of “gender discrimination?” At base, in the words of Judith Butler (2004): “whose world is legitimated as real?” These questions are answered in small ways in a variety of local settings, and the answers often conflict. In this chapter, I explore the paradoxical role played by legal gender classifications in ongoing cultural disagreements about gender difference. On one hand, they reinforce the notion that there are predictable, stable ways to identify, mark and secure the individual. On the other, law has become an expressive tool in the lives of individuals, who both depend on its recognition for access to the most basic forms of social participation, yet whose own transgressive identity practices can push against, resist and transform the very ways the law codifies its categories. Much like the edge effects identified by urban sociologists, ecologists and literary and queer theorists in other contexts, gender diversity flourishes at the edges of legal recognition. State identity schemes vary widely, and their inconsistencies open up a space to think in nuanced ways about how gender is lived and recognized. While the law constructs gender classifications as boundaries, in fact, they function more like borderlines. Though a repressive and regulatory state apparatus keenly guards the edges of gender, they remain surprisingly permeable. In their most ideal forms, they respond to the demands, needs and resistances of individuals. Indeed, if legal gender classifications wish to do their work, they must become more fully the open systems they suggest—that is, always in evolution, responsive to the multiplying ways in which individuals embody, express and assert their identities. They must allow for the expressive movement through, and use by individuals of, the categories themselves.

Catherine O'Neill. Forthcoming. “this is the title of Ðjournal article.” Edited by Mary Fowkes. this is the title, 2, 661, Pp. 42-55. Publisher's VersionAbstract

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Tey Meadow and Kristen Schlit. Forthcoming. Re: Doing Gender: A Queer Response to Feminist Social Theory. University of California Press.
Lorgia García Peña. Forthcoming. Almost Citizens: Racial Translations, National Belonging and the Global “Immigration Crisis”. Humanities Series - Duke University Press.
John Aldrich and Samuel Abrams ABCDEFG. Forthcoming. “artwork1.” SecondaryTitle VolumnNumber, Pp. Description. Salt Lake City: DDD Museum. Publisher's Version
Nathaniel Wolfson. Forthcoming. “Brazil After History, or Two German Accounts of Post-War Brazilian Literature.” The Germanic Review: Literature, Culture Theory.
Tianzhu Xiong and James Mallet. Forthcoming. “The collapse of genetic incompatibilities in a hybridizing population.” BioRxiv, Pp. 2021.01.08.425971v1. Publisher's VersionAbstract
Genetic incompatibility has long been considered to be a hallmark of speciation due to its role in reproductive isolation. Previous analyses of the stability of epistatic incompatibility show that it is subject to collapse upon hybridization. In the present work, we derive explicitly the distribution of the lifespan of two-locus incompatibilities, and show that genetic drift, along with recombination, is critical in determining the time scale of collapse. The first class of incompatibilities, where derived alleles separated in parental populations act antagonistically in hybrids, survive longer in smaller populations when incompatible alleles are (co)dominant and tightly linked, but collapse more quickly when they are recessive. The second class of incompatibilities, where fitness is reduced by disrupting co-evolved elements in gene regulation systems, collapse on a time scale proportional to the exponential of effective recombination rate. Overall, our result suggests that the effects of genetic drift and recombination on incompatibility’s lifespan depend strongly on the underlying mechanisms of incompatibilities. As the time scale of collapse is usually shorter than the time scale of establishing a new incompatibility, the observed level of genetic incompatibilities in a particular hybridizing population may be shaped more by the collapse than by their initial accumulation. Therefore, a joint theory of accumulation-erosion of incompatibilities is in need to fully understand the genetic process under speciation with hybridization
Sylvaine Guyot and Clotilde Thouret. Forthcoming. “Communities of Production and Consumption.” In Rebecca Bushnell / Mitchell Greenberg (eds). A Cultural History of Tragedy. Vol. 4, The Age of Enlightenment (1650-1800). London-Oxford-New York: Bloomsbury Publishing.
Neil Rosser, Nathaniel B. Edelman, Lucie M. Queste, Michaela Nelson, Fernando Seixas, Kanchon K. Dasmahapatra, and James Mallet. Forthcoming. “Complex basis of hybrid female sterility and Haldane’s rule in Heliconius butterflies: Z-linkage and epistasis.” BioRxiv, Pp. 2021.06.28.450252. Publisher's VersionAbstract
Hybrids between diverging populations are often sterile or inviable. Hybrid unfitness usually evolves first in the heterogametic sex – a pattern known as Haldane’s rule. The genetics of Haldane’s Rule have been extensively studied in species where the male is the heterogametic (XX/XY) sex, but its basis in taxa where the female is heterogametic (ZW/ZZ), such as Lepidoptera and birds, is largely unknown. Here, we analyse a new case of female hybrid sterility between geographic subspecies of Heliconius pardalinus. The two subspecies mate freely in captivity, but female F1 hybrids in both directions of cross are sterile. Sterility is due to arrested development of oocytes after they become differentiated from nurse cells, but before yolk deposition. We backcrossed fertile male F1 hybrids to parental females, and mapped quantitative trait loci (QTLs) for female sterility. We also identified genes differentially expressed in the ovary, and as a function of oocyte development. The Z chromosome has a major effect, similar to the “large X effect” in Drosophila, with strong epistatic interactions between loci at either end of the Z chromosome, and between the Z chromosome and autosomal loci on chromosomes 8 and 20. Among loci differentially expressed between females with arrested vs. non-arrested ovary development, we identified six candidate genes known also from Drosophila melanogaster and Parage aegeria oogenesis. This study is the first to characterize hybrid sterility using genome mapping in the Lepidoptera. We demonstrate that sterility is produced by multiple complex epistastic interactions often involving the sex chromosome, as predicted by the dominance theory of Haldane’s Rule.
Charline Pluvinet. Forthcoming. “Courage, pouvoir et performance dans deux poèmes médiévaux: Les vers de la mort d'Hélinand de Froidmont et Les congés de Jean Bodel.” Edited by Emmanuel Bouju and Yolaine Parisot. Rennes: Université de Rennes.
C. Zhang, Y. Liu, J. Ortega-Hernández, J. M. Wolfe, C. Jin, H. Mai, X. G. Hou, J. Guo, and D. Zhai. Forthcoming. “Differentiated appendages in Isoxys illuminate origin of arthropodization.” Research Square. Publisher's VersionAbstract

The Cambrian fossil record has produced remarkable insights into the origin of euarthropods, particularly the evolution of their versatile body plan of segments bearing specialized, jointed appendages for different functions including feeding and locomotion. Early euarthropod evolution involved a major transition from lobopodian-like taxa to organisms featuring a fully sclerotized trunk (arthrodization) and limbs (arthropodization). However, the precise origin of arthropodization remains controversial because some of the earliest branching euarthropods possess a broad dorsal carapace that obscures critical details of the trunk and appendage organization. Here, we demonstrate the presence of fully arthropodized ventral appendages in the upper stem-group euarthropod Isoxys curvirostratus from the early Cambrian Chengjiang biota in South China. Micro-computed tomography reveals the detailed three-dimensional structure of the biramous appendages in I. curvirostratus for the first time. In addition to the raptorial frontal appendages I. curvirostratus also possesses two batches of morphologically distinct biramous limbs, with the first batch consisting of four pairs of short cephalic appendages bearing prominent endites with a feeding function, followed by a second batch of elongate trunk appendages for locomotion. Each biramous limb bears an endopod with more than 12 well-defined podomeres, and an exopod consisting of a slender shaft carrying approximately a dozen paddle-shaped lamellae. Our findings clarify the enigmatic appendicular organization of Isoxys, one of the most ubiquitous euarthropods in Cambrian Burgess Shale-type deposits worldwide. Critically, our new material shows that the trunk of I. curvirostratus was not arthrodized. The phylogenetic position of isoxyiids as possibly the earliest branching members of Deuteropoda, suggests that arthropodized biramous appendages evolved before the pattern of full trunk arthrodization that characterizes most extant and extinct members of this successful animal phylum.

Ryan J. Owens and Ryan C. Black. Forthcoming. “Agenda-Setting in the Supreme Court: The Collision of Policy and Jurisprudence.” Journal of Politics.
Sylvaine Guyot and Jeff (eds) Ravel. Forthcoming. Early Modern Theater History and the Digital Archive. Cambridge (Mass): MIT Press.

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