Publications

2018
Mathis A, Mamidanna P, Cury KM, Abe T, Murthy VN, Weygandt M, Bethge M. DeepLabCut: markerless pose estimation of user-defined body parts with deep learning [Internet]. Nature Neuroscience 2018;21:1281-1289. Publisher's VersionAbstract
Quantifying behavior is crucial for many applications in neuroscience. Videography provides easy methods for the observation and recording of animal behavior in diverse settings, yet extracting particular aspects of a behavior for further analysis can be highly time consuming. In motor control studies, humans or other animals are often marked with reflective markers to assist with computer-based tracking, but markers are intrusive, and the number and location of the markers must be determined a priori. Here we present an efficient method for markerless pose estimation based on transfer learning with deep neural networks that achieves excellent results with minimal training data. We demonstrate the versatility of this framework by tracking various body parts in multiple species across a broad collection of behaviors. Remarkably, even when only a small number of frames are labeled (~200), the algorithm achieves excellent tracking performance on test frames that is comparable to human accuracy.
Hou S, Gangishetty MK, Quan Q, Congreve DN. Efficient Blue and White Perovskite Light-Emitting Diodes via Manganese Doping [Internet]. Joule 2018; Publisher's VersionAbstract
Despite heavy research, blue perovskite nanocrystal LEDs have struggled to match the high efficiencies of their red and green cousins, particularly at wavelengths blue enough to meet the NTSC blue standard. One of the most critical problems is the low photoluminescence yield of the nanocrystals in thin films. Recently, manganese doping has been shown to increase the photoluminescence yield of the perovskite even as a decay pathway to a long-lived emissive state on the manganese ion is introduced. Here, we employ a two-step synthetic approach to carefully tune the manganese doping to increase the blue photoluminescence while preventing significant manganese emission, allowing for blue perovskite LEDs with quantum efficiencies over 2% that meet the NTSC standard. Manganese doping increases the photoluminescence yield and lifetime, reduces trap states, and makes the dots more monodisperse, reducing the emission bandwidth. Finally, we utilize perovskite nanocrystal downconverters to build an all-perovskite white LED.
Gangishetty MK, Hou S, Quan Q, Congreve DN. Reducing Architecture Limitations for Efficient Blue Perovskite Light-Emitting Diodes [Internet]. Advanced Materials 2018; Publisher's VersionAbstract
Light‐emitting diodes utilizing perovskite nanocrystals have generated strong interest in the past several years, with green and red devices showing high efficiencies. Blue devices, however, have lagged significantly behind. Here, it is shown that the device architecture plays a key role in this lag and that NiOx, a transport layer in one of the highest efficiency devices to date, causes a significant reduction in perovskite luminescence lifetime. An alternate transport layer structure which maintains robust nanocrystal emission is proposed. Devices with this architecture show external quantum efficiencies of 0.50% at 469 nm, seven times higher than state‐of‐the‐art devices at that wavelength. Finally, it is demonstrated that this architecture enables efficient devices across the entire blue‐green portion of the spectrum. The improvements demonstrated here open the door to efficient blue perovskite light‐emitting diodes.          
adma.201706226.pdf
Jiang K, Siahrostami S, Zheng T, Hu Y, Hwang S, Stavitski E, Peng Y, Dynes J, Gangishetty M, Su D, Attenkofer K, Wang H. Isolated Ni single atoms in graphene nanosheets for high-performance CO2 reduction [Internet]. Energy & Environmental Science 2018;(2):225-458. Publisher's VersionAbstract
Single-atom catalysts have emerged as an exciting paradigm with intriguing properties different from their nanocrystal counterparts. Here we report Ni single atoms dispersed into graphene nanosheets, without Ni nanoparticles involved, as active sites for the electrocatalytic CO2 reduction reaction (CO2RR) to CO. While Ni metal catalyzes the hydrogen evolution reaction (HER) exclusively under CO2RR conditions, Ni single atomic sites present a high CO selectivity of 95% under an overpotential of 550 mV in water, and an excellent stability over 20 hours’ continuous electrolysis. The current density can be scaled up to more than 50 mA cm−2 with a CO evolution turnover frequency of 2.1 × 105 h−1 while maintaining 97% CO selectivity using an anion membrane electrode assembly. Different Ni sites in graphene vacancies, with or without neighboring N coordination, were identified by in situ X-ray absorption spectroscopy and density functional theory calculations. Theoretical analysis of Ni and Co sites suggests completely different reaction pathways towards the CO2RR or HER, in agreement with experimental observations.
c7ee03245e_01.pdf
Jiang K, Sandberg RB, Akey AJ, Liu X, Bell DC, Nøskov JK, Chan K, Wang H. Metal ion cycling of Cu foil for selective C-C coupling in electrochemical CO2 reduction [Internet]. Nature Catalysis 2018; Publisher's VersionAbstract
Electrocatalytic CO2 reduction to higher-value hydrocarbons beyond C1products is desirable for applications in energy storage, transportation and the chemical industry. Cu catalysts have shown the potential to catalyse C–C coupling for C2+ products, but still suffer from low selectivity in water. Here, we use density functional theory to determine the energetics of the initial C–C coupling steps on different Cu facets in CO2 reduction, and suggest that the Cu(100) and stepped (211) facets favour C2+ product formation over Cu(111). To demonstrate this, we report the tuning of facet exposure on Cu foil through the metal ion battery cycling method. Compared with the polished Cu foil, our 100-cycled Cu nanocube catalyst with exposed (100) facets presents a sixfold improvement in C2+ to C1 product ratio, with a highest C2+Faradaic efficiency of over 60% and H2 below 20%, and a corresponding C2+ current of more than 40 mA cm–2.
2017
Jiang K, Siahrostami S, Akey AJ, Li Y, Lu Z, Lattimer J, Hu Y, Stokes C, Gangishetty M, Chen G, Zhou Y, Hill W, Cai W-B, Bell D, Chan K, Nørskov JK, Cui Y, Wang H. Transition-Metal Single Atoms in a Graphene Shell as Active Centers for Highly Efficient Artificial Photosynthesis. Chem 2017;3(1-11) 10.1016j.chempr.2017.09.014.pdf
Siahrostami S, Jiang K, Karamad M, Chan K, Wang H, Nørskov J. Theoretical Investigations into Defected Graphene for Electrochemical Reduction of CO2 [Internet]. ACS Sustainable Chemistry & Engineering 2017; Publisher's Version
Jiang K, Kharel P, Peng Y, Gangishetty MK, Lin H-YG, Stavitski E, Attenkofer K, Wang H. Silver Nanoparticles with Surface-Bonded Oxygen for Highly Selective CO2 Reduction [Internet]. ACS Sustainable Chemistry & Engineering 2017; Publisher's VersionAbstract
The surface electronic structures of catalysts need to be carefully engineered in CO2 reduction reaction (CO2RR), where the hydrogen evolution side reaction usually takes over under a significant overpotential, and thus dramatically lowers the reaction selectivity. Surface oxides can play a critical role in tuning the surface oxidation state of metal catalysts for a proper binding with CO2RR reaction intermediates, which may significantly improve the catalytic activity and selectivity. Here, we demonstrate the importance of surface-bonded oxygen on silver nanoparticles in altering the reaction pathways and improving the CO2RR performances. A comparative investigation on air-annealed Ag (Air-Ag) catalyst with or without the post-treatment of H2 thermal annealing (H2-Ag) was performed. In Air-Ag, the subsurface chemically bonded O species (O–Agδ+) was identified by angle resolved X-ray photoelectron spectroscopy and X-ray absorption spectroscopy techniques, and contributed to the improved CO selectivity rather than H2in CO2RR electrolysis. As a result, though the maximal CO Faradaic efficiency of H2-Ag is at ∼30%, the Air-Ag catalyst presented a high CO selectivity of more than 90% under a current density of ∼21 mA/cm2.
Kim DH, Kim J, Marques JC, Grama A, Hildebrand DGC, Gu W, Li JM, Robson DN. Pan-neuronal calcium imaging with cellular resolution in freely swimming zebrafish [Internet]. Nature Methods 2017; Publisher's Version
Jiang K, Wang H, Cai W-B, Wang H. Li Electrochemical Tuning of Metal Oxide for Highly Selective CO2 Reduction [Internet]. ACS Nano 2017;(DOI: 10.1021) Publisher's Version acsnano2e7b03029.pdf
Liang F, Guo Y, Hou S, Quan Q. Photonic-plasmonic hybrid single-molecule nano sensor measures the effect of fluorescent labels on DNA-protein dynamics [Internet]. Sciences Advances 2017;3(5) Publisher's Version
Hou S, Guo Y, Tang Y, Quan Q. Synthesis and Stabilization of Colloidal Perovskite Nanocrystals by Multidentate Polymer Micelles [Internet]. ACS Applied Materials & Interfaces 2017; Publisher's Version
Novakova E, Woodhams DC, Rodriguez-Ruano SM, Brucker RM, Leff JW, Maharaj A, Knight R, Scott J. Mosquito Microbiome Dynamics, a Background for Prevalence and Seasonality of West Nile Virus. [Internet]. Frontiers in Microbiology 2017;(1664-302X) Publisher's Version 227863_woodhams_provisionalpdf.pdf
Saulsberry A, Pinchas M, Noll A, Lynch JA, Bordenstein SR, Brucker RM. Establishment of F1 hybrid mortality in real time. BMC Evolutionary Biology 2017;17.1
Brooks AW, Kohl KD, Brucker RM, van Opstal EJ, Bordenstein SR. Phylosymbiosis: Relationships and Functional Effects of Microbial Communities across Host Evolutionary History. PLOS Biology 2017;15.1(e1002587):1-29. journal.pbio_.2000225.pdf
Ouyang M, Hill W, Lee JH, Hur SC. Microscale Symmetrical Electroporator Array as a Versatile Molecular Delivery System [Internet]. Scientific Reports 2017;7:11. Publisher's VersionAbstract

Successful developments of new therapeutic strategies often rely on the ability to deliver exogenous molecules into cytosol. We have developed a versatile on-chip vortex-assisted electroporation system, engineered to conduct sequential intracellular delivery of multiple molecules into various cell types at low voltage in a dosage-controlled manner. Micro-patterned planar electrodes permit substantial reduction in operational voltages and seamless integration with an existing microfluidic technology. Equipped with real-time process visualization functionality, the system enables on-chip optimization of electroporation parameters for cells with varying properties. Moreover, the system’s dosage control and multi-molecular delivery capabilities facilitate intracellular delivery of various molecules as a single agent or in combination and its utility in biological research has been demonstrated by conducting RNA interference assays. We envision the system to be a powerful tool, aiding a wide range of applications, requiring single-cell level co-administrations of multiple molecules with controlled dosages.

ouyang_et_al-2017-scientific_reports.pdf
2016
Lin Z, Guo H, Cao Y, Zohrabian S, Zhou P, Ma Q, VanDusen N, Guo Y, Zhang J, Stevens SM, Liang F, Quan Q, van Gorp P R, Li A, dos Remedios C, He A, Bezzerides V J, Pu W T. Acetylation of \VGLL4\ Regulates Hippo-YAP Signaling and Postnatal Cardiac Growth [Internet]. Developmental Cell 2016;39(4):466 - 479. Publisher's VersionAbstract
Summary Binding of the transcriptional co-activator \YAP\ with the transcription factor \TEAD\ stimulates growth of the heart and other organs. \YAP\ overexpression potently stimulates fetal cardiomyocyte (CM) proliferation, but YAP's mitogenic potency declines postnatally. While investigating factors that limit YAP's postnatal mitogenic activity, we found that the CM-enriched \TEAD1\ binding protein \VGLL4\ inhibits \CM\ proliferation by inhibiting TEAD1-YAP interaction and by targeting \TEAD1\ for degradation. Importantly, \VGLL4\ acetylation at lysine 225 negatively regulated its binding to TEAD1. This developmentally regulated acetylation event critically governs postnatal heart growth, since overexpression of an acetylation-refractory VGLL4 mutant enhanced \TEAD1\ degradation, limited neonatal \CM\ proliferation, and caused \CM\ necrosis. Our study defines an acetylation-mediated, VGLL4-dependent switch that regulates \TEAD\ stability and YAP-TEAD activity. These insights may improve targeted modulation of TEAD-YAP activity in applications from cardiac regeneration to cancer.
Richmond BW, Brucker RM, Han W, Du R-H, Zhang Y, Cheng D-S, Gleaves L, Abdolrasulinia R, Polosukhina D, Clark PE, Bordenstein SR, Blackwell TS, Polosukhin VV. Airway bacteria drive a progressive COPD-like phenotype in mice with polymeric immunoglobulin receptor deficiency [Internet]. Nature Communications 2016;7:11240. Publisher's VersionAbstract

Mechanisms driving persistent airway inflammation in chronic obstructive pulmonary disease (COPD) are incompletely understood. As secretory immunoglobulin A (SIgA) deficiency in small airways has been reported in COPD patients, we hypothesized that immunobarrier dysfunction resulting from reduced SIgA contributes to chronic airway inflammation and disease progression. Here we show that polymeric immunoglobulin receptor-deficient (pIgR−/−) mice, which lack SIgA, spontaneously develop COPD-like pathology as they age. Progressive airway wall remodelling and emphysema in pIgR−/− mice are associated with an altered lung microbiome, bacterial invasion of the airway epithelium, NF-κB activation, leukocyte infiltration and increased expression of matrix metalloproteinase-12 and neutrophil elastase. Re-derivation of pIgR−/− mice in germ-free conditions or treatment with the anti-inflammatory phosphodiesterase-4 inhibitor roflumilast prevents COPD-like lung inflammation and remodelling. These findings show that pIgR/SIgA deficiency in the airways leads to persistent activation of innate immune responses to resident lung microbiota, driving progressive small airway remodelling and emphysema.

ncomms11240.pdf
Theis KR, Dheilly NM, Klassen JL, Brucker RM, Baines JF, Bosch TCG, Cryan JF, Gilbert SF, Goodnight CJ, Lloyd EA, Sapp J, Vandenkoornhuyse P, Zilber-Rosenberg I, Rosenberg E, Bordenstein SR. Getting the Hologenome Concept Right: an Eco-Evolutionary Framework for Hosts and Their Microbiomes [Internet]. mSystems 2016;1(2) Publisher's VersionAbstract

Given the complexity of host-microbiota symbioses, scientists and philosophers are asking questions at new biological levels of hierarchical organization—what is a holobiont and hologenome? When should this vocabulary be applied? Are these concepts a null hypothesis for host-microbe systems or limited to a certain spectrum of symbiotic interactions such as host-microbial coevolution? Critical discourse is necessary in this nascent area, but productive discourse requires that skeptics and proponents use the same lexicon. For instance, critiquing the hologenome concept is not synonymous with critiquing coevolution, and arguing that an entity is not a primary unit of selection dismisses the fact that the hologenome concept has always embraced multilevel selection. Holobionts and hologenomes are incontrovertible, multipartite entities that result from ecological, evolutionary, and genetic processes at various levels. They are not restricted to one special process but constitute a wider vocabulary and framework for host biology in light of the microbiome.

2016_theis_perspective_host-microbe_biology.pdf
Rebollar EA, Antwis RE, Becker MH, Belden LK, Bletz MC, Brucker RM, Harrison XA, Hughey MC, Kueneman JG, Loudon AH, McKenzie V, Medina D, Minbiole KPC, Rollins-Smith LA, Walke JB, Weiss S, Woodhams DC, Harris RN. Using “omics” and integrated multi-omics approaches to guide probiotic selection to mitigate chytridiomycosis and other emerging infectious diseases [Internet]. Frontiers in Microbiology 2016;7(68) Publisher's VersionAbstract

Emerging infectious diseases in wildlife are responsible for massive population declines. In amphibians, chytridiomycosis caused by Batrachochytrium dendrobatidis, Bd, has severely affected many amphibian populations and species around the world. One promising management strategy is probiotic bioaugmentation of antifungal bacteria on amphibian skin. In vivo experimental trials using bioaugmentation strategies have had mixed results, and therefore a more informed strategy is needed to select successful probiotic candidates. Metagenomic, transcriptomic, and metabolomic methods, colloquially called “omics,” are approaches that can better inform probiotic selection and optimize selection protocols. The integration of multiple omic data using bioinformatic and statistical tools and in silico models that link bacterial community structure with bacterial defensive function can allow the identification of species involved in pathogen inhibition. We recommend using 16S rRNA gene amplicon sequencing and methods such as indicator species analysis, the Kolmogorov–Smirnov Measure, and co-occurrence networks to identify bacteria that are associated with pathogen resistance in field surveys and experimental trials. In addition to 16S amplicon sequencing, we recommend approaches that give insight into symbiont function such as shotgun metagenomics, metatranscriptomics, or metabolomics to maximize the probability of finding effective probiotic candidates, which can then be isolated in culture and tested in persistence and clinical trials. An effective mitigation strategy to ameliorate chytridiomycosis and other emerging infectious diseases is necessary; the advancement of omic methods and the integration of multiple omic data provide a promising avenue toward conservation of imperiled species.

2016_rebollar_using_multi-omics_for_probiotic_selection.pdf

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