"Microbiome: Focus on Causation and Mechanism.", M. A. Fischbach. Cell., 174, 785–790 (2018). DOI: 10.1016/j.cell.2018.07.0
There is tremendous enthusiasm for the microbiome in academia and industry. This Perspective argues that in order to realize its potential, the field needs to focus on establishing causation and molecular mechanism with an emphasis on phenotypes that are large in magnitude, easy to measure, and unambiguously driven by the microbiota.
"Chlorine Production by HCl Oxidation in a Molten Chloride Salt Catalyst", Shizhao Su, Davide Mannini, Horia Metiu, Michael J Gordon, and Eric W McFarland. Industrial & Engineering Chemistry Research, 57, 7795–7801 (2018). DOI: 10.1021/acs.iecr.8b01141
"Synthesis of Silver Nanowires with Reduced Diameters Using Benzoin-Derived Radicals to Make Transparent Conductors with High Transparency and Low Haze", Zhiqiang Niu, Fan Cui, Elisabeth Kuttner, Chenlu Xie, Hong Chen, Yuchun Sun, Ahmad Dehestani, Kerstin Schierle-Arndt, and Peidong Yang. Nano Lett., in press (2018).
"A molecular cross-linking approach for hybrid metal oxides.", Dahee Jung, Liban M A Saleh, Zachariah J Berkson, Maher F El-Kady, Jee Youn Hwang, Nahla Mohamed, Alex I Wixtrom, Ekaterina Titarenko, Yanwu Shao, Kassandra McCarthy, Jian Guo, Ignacio B Martini, Stephan Kraemer, Evan C Wegener, Philippe Saint-Cricq, Bastian Ruehle, Ryan R Langeslay, Massimiliano Delferro, Jonathan L Brosmer, Christopher H Hendon, Marcus Gallagher-Jones, Jose Rodriguez, Karena W Chapman, Jeffrey T Miller, Xiangfeng Duan, Richard B Kaner, Jeffrey I Zink, Bradley F Chmelka, and Alexander M Spokoyny. Nat Mater. 17, 341–348 (2018). DOI: 10.1038/s41563-018-0021-9
"Quantitative characterization of all single amino acid variants of a viral capsid-based drug delivery vehicle.", Emily C Hartman, Christopher M Jakobson, Andrew H Favor, Marco J Lobba, Ester Álvarez-Benedicto, Matthew B Francis, and Danielle Tullman-Ercek. Nature Communications 1–11 (2018). DOI: 10.1038/s41467-018-03783-y/a>
"Rapid Microwave Preparation and Composition Tuning of the High-Performance Magnetocalorics (Mn,Fe) 2(P,Si)",
Jason H Grebenkemper, Joshua D Bocarsly, Emily E Levin, Gareth Seward, Colin Heikes, Craig Brown, Sumohan Misra, Fabian Seeler, Kerstin Schierle-Arndt, Stephen D Wilson, and Ram Seshadri. ACS applied materials & interfaces. 10, 7208–7213 (2018). DOI: 10.1021/acsami.7b16988
"Assessing Local Structure Motifs Using Order Parameters for Motif Recognition, Interstitial Identification, and Diffusion Path Characterization.", Nils E R Zimmermann, Matthew K Horton, Anubhav Jain, and Maciej Haranczyk. Front. Mater. 4, 054104–13 (2017). DOI: 10.1016/j.chembiol.2015.09.008
"Hydrogen Gas-Mediated Deoxydehydration/Hydrogenation of Sugar Acids: Catalytic Conversion of Glucarates to Adipates", Reed T Larson, Andrew Samant, Jianbin Chen, Woojin Lee, Martin A Bohn, Dominik M Ohlmann, Stephan J Zuend, and F Dean Toste. J. Am. Chem. Soc. 139, 14001–14004 (2017). DOI: 10.1021/jacs.7b07801
"Solution-Processed Complementary Resistive Switching Arrays for Associative Memory", Jeremy Smith, Seungjun Chung, Jaewon Jang, Carlos Biaou, and Vivek Subramanian. IEEE Trans. Electron Devices. 64, 4310–4316 (2017). DOI: 10.1109/TED.2017.2732920
Complementary resistive switches (CRS) based on back-to-back nanofilamentary resistive RAM devices have been fabricated by an all-solution-processed method, employing inkjet-printed Ag and Au contacts and a spin-coated sol–gel zirconium oxide dielectric layer. The devices demonstrate electrical switching behavior below 3 V, stable on-state windows, reasonable cycle lifetimes, and can be implemented in 2×2 memory arrays with no crosstalk during addressing. For reliable operation and high yields of the CRS devices, printing and annealing processes were carefully optimized to eliminate the coffee- ring effect on the bottom electrode, and produce a pin-hole free dielectric. The arrays are fully pulse programmable and are able to retain their state for >104 s. Additionally, the arrays can be operated as associative or content addressable, memory for pattern matching applications, which is demonstrated through a basic hamming distance mapping measurement for different stored data states.
"Electrostatic Tuning of Spray-Deposited ZnO for Controlled Mobility Enhancement", Andre Zeumault, William Scheideler, and Vivek Subramanian. Adv. Funct. Mater. 40, 1701021–10 (2017). DOI: 10.1002/adfm.201701021
Spray-deposited nanocrystalline ZnO films are produced in order to establish empirical relationships between synthetic conditions and the density of states as a means of achieving electrostatic control. By varying the spray-pyrolysis deposition conditions, i.e., substrate temperature, precursor concentration, and flow rate, a wide range of exponentially distributed density of localized states profiles and field-effect mobility values ranging over three orders of magnitude (0.02–30 cm2 V−1 s−1) are obtained for analysis. It is found that mobility can be controlled by appropriately tuning the shape of the density of states profile, increasing the band tail slope and reducing the band edge concentration of shallow states. Most significantly, it is shown that the shape of the density of states can be modified by adjusting the spray-pyrolysis deposition conditions for electrostatic control. It is found that higher Zn precursor concentration in solution increases the slope of the band tails, leading to higher mobility. Additionally, the band edge concentration is reduced with increased substrate temperature also leading to higher mobility. These results quantify the relationship between defect electrostatics and electron transport while demonstrating electrostatic control via synthetic modification of localized states.
"Benzoin Radicals as Reducing Agent for Synthesizing Ultrathin Copper Nanowires", Fan Cui, Letian Dou, Qin Yang, Yi Yu, Zhiqiang Niu, Yuchun Sun, Hao Liu, Ahmad Dehestani, Kerstin Schierle-Arndt, and Peidong Yang. J. Am. Chem. Soc., 139, 3027–3032 (2017). DOI: 10.1021/jacs.6b11900
In this work, we report a new, general synthetic approach that uses heat driven benzoin radicals to grow ultrathin copper nanowires with tunable diameters. This is the first time carbon organic radicals have been used as a reducing agent in metal nanowire synthesis. In-situ temperature dependent electron paramagnetic resonance (EPR) spectro- scopic studies show that the active reducing agent is the free radicals produced by benzoins under elevated temperature. Furthermore, the reducing power of benzoin can be readily tuned by symmetrically decorating functional groups on the two benzene rings. When the aromatic rings are modified with electron donating (withdrawing) groups, the reducing power is promoted (suppressed). The controllable reactivity gives the carbon organic radical great potential as a versatile reducing agent that can be generalized in other metallic nanowire syntheses.
"Ultrathin Epitaxial Cu@Au Core–Shell Nanowires for Stable Transparent Conductors. ", Zhiqiang Niu*, Fan Cui*, Yi Yu, Nigel Becknell, Yuchun Sun, Garo Khanarian, Dohyung Kim, Letian Dou, Ahmad Dehestani, Kerstin Schierle-Arndt, and Peidong Yang. J. Am. Chem. Soc.,139, 7348−7354 (2017). DOI: 10.1021/jacs.7b02884
"Discovery of Reactive Microbiota-Derived Metabolites that Inhibit Host Proteases", Chun-Jun Guo, Fang-Yuan Chang, Thomas P Wyche, Keriann M Backus, Timothy M Acker, Masanori Funabashi, Mao Taketani, Mohamed S Donia, Stephen Nayfach, Katherine S Pollard, Charles S Craik, Benjamin F Cravatt, Jon Clardy, Christopher A Voigt, and Michael A Fischbach. Cell. 168, 517–526.e18 (2017). DOI: 10.1016/j.cell.2016.12.021
The gut microbiota modulate host biology in numerous ways, but little is known about the molecular mediators of these interactions. Previously, we found a widely distributed family of nonribosomal peptide synthetase gene clusters in gut bacteria. Here, by expressing a subset of these clusters in Escherichia coli or Bacillus subtilis, we show that they encode pyrazinones and dihydropyrazinones. At least one of the 47 clusters is present in 88% of the National Institutes of Health Human Microbiome Project (NIH HMP) stool samples, and they are transcribed under conditions of host colonization. We present evidence that the active form of these molecules is the initially released peptide aldehyde, which bears potent protease inhibitory activity and selectively targets a subset of cathepsins in human cell proteomes. Our findings show that an approach combining bioinformatics, synthetic biology, and heterologous gene cluster expression can rapidly expand our knowledge of the metabolic potential of the microbiota while avoiding the challenges of cultivating fastidious commensals.
"Synthesis of Pt3Y and Other Early−Late Intermetallic Nanoparticles by Way of a Molten Reducing Agent", Jacob S Kanady, Peter Leidinger, Andreas Haas, Sven Titlbach, Stephan Schunk, Kerstin Schierle-Arndt, Ethan J Crumlin, Cheng Hao Wu, and A Paul Alivisatos. J. Am. Chem. Soc. 139, 5672–5675 (2017). DOI: 10.1021/jacs.7b01366
Early−late intermetallic phases have gar- nered increased attention recently for their catalytic properties. To achieve the high surface areas needed for industrially relevant applications, these phases must be synthesized as nanoparticles in a scalable fashion. Herein, Pt3Y targeted as a prototypical example of an early−late intermetallic has been synthesized as nanoparticles approximately 5−20 nm in diameter via a solution process and characterized by XRD, TEM, EDS, and XPS. The key development is the use of a molten borohydride (MEt3BH, M = Na, K) as both the reducing agent and reaction medium. Readily available halide precursors of the two metals are used. Accordingly, no organic ligands are necessary, as the resulting halide salt byproduct prevents sintering, which further permits dispersion of the nano- scale intermetallic onto a support. The versatility of this approach was validated by the synthesis of other intermetallic phases such as Pt3Sc, Pt3Lu, Pt2Na, and Au2Y.
"A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites", Dylan Dodd, Matthew H Spitzer, William Van Treuren, Bryan D Merrill, Andrew J Hryckowian, Steven K Higginbottom, Le Anthony, Tina M Cowan, Garry P Nolan, Michael A Fischbach, and Justin L Sonnenburg. Nature. 336, 1262 (2017). DOI: 10.1038/nature24661
The human gut microbiota produces dozens of metabolites that accumulate in the bloodstream, where they can have systemic effects on the host. Although these small molecules commonly reach concentrations similar to those achieved by pharmaceutical agents, remarkably little is known about the microbial metabolic pathways that produce them. Here we use a combination of genetics and metabolic profiling to characterize a pathway from the gut symbiont Clostridium sporogenes that generates aromatic amino acid metabolites. Our results reveal that this pathway produces twelve compounds, nine of which are known to accumulate in host serum. All three aromatic amino acids (tryptophan, phenylalanine and tyrosine) serve as substrates for the pathway, and it involves branching and alternative reductases for specific intermediates. By genetically manipulating C. sporogenes, we modulate serum levels of these metabolites in gnotobiotic mice, and show that in turn this affects intestinal permeability and systemic immunity. This work has the potential to provide the basis of a systematic effort to engineer the molecular output of the gut bacterial community.
"Mobility Enhancement in Solution‐Processed Transparent Conductive Oxide TFTs due to Electron Donation from Traps in High‐k Gate Dielectrics", Andre Zeumault and Vivek Subramanian. Adv. Funct. Mater., 26: 955–963. doi:10.1002/adfm.201503940
"Protein Sialylation Regulates a Gene Expression Signature that Promotes Breast Cancer Cell Pathogenicity", Rebecca A Kohnz, Lindsay S Roberts, David DeTomaso, Lara Bideyan, Peter Yan, Sourav Bandyopadhyay, Andrei Goga, Nir Yosef, and Daniel K Nomura. ACS Chem. Biol. 11, 2131–2139 (2016). DOI: 10.1021/acschembio.6b00433
Many mechanisms have been proposed for how heightened aerobic glycolytic metabolism fuels cancer pathogenicity, but there are still many unexplored pathways. Here, we have performed metabolomic profiling to map glucose incorporation into metabolic pathways upon transformation of mammary epithelial cells by 11 commonly mutated human oncogenes. We show that transformation of mammary epithelial cells by oncogenic stimuli commonly shunts glucose-derived carbons into synthesis of sialic acid, a hexosamine pathway metabolite that is converted to CMP-sialic acid by cytidine monophosphate N-acetylneuraminic acid synthase (CMAS) as a precursor to glycoprotein and glycolipid sialylation. We show that CMAS knockdown leads to elevations in intracellular sialic acid levels, a depletion of cellular sialylation, and alterations in the expression of many cancer-relevant genes to impair breast cancer pathogenicity. Our study reveals the heretofore unrecognized role of sialic acid metabolism and protein sialylation in regulating the expression of genes that maintain breast cancer pathogenicity.
1. R. A. Kohnz et al., Protein Sialylation Regulates a Gene Expression Signature that Promotes Breast Cancer Cell Pathogenicity. ACS Chem. Biol.11, 2131–2139 (2016).
Protein Sialylation Regulates a Gene Expression Signature that Promotes Breast Cancer Cell Pathogenicity.
Rebecca A Kohnz, Lindsay S Roberts, David DeTomaso, Lara Bideyan, Peter Yan, Sourav Bandyopadhyay, Andrei Goga, Nir Yosef, and Daniel K Nomura.
ACS Chemical Biology, 2016 vol. 11 (8) pp. 2131-2139.
"High-Performance Lithium Metal Negative Electrode with a Soft and Flowable Polymer Coating", Guangyuan Zheng, Chao Wang, Allen Pei, Jeffrey Lopez, Feifei Shi, Zheng Chen, Austin D Sendek, Hyun-Wook Lee, Zhenda Lu, Holger Schneider, Marina M Safont-Sempere, Steven Chu, Zhenan Bao, and Yi Cui. ACS Energy Lett. 1, 1247–1255 (2016). DOI: 10.1021/acsenergylett.6b00456
The future development of low-cost, high-performance electric vehicles depends on the success of next-generation lithium-ion batteries with higher energy density. The lithium metal negative electrode is key to applying these new battery technologies. However, the problems of lithium dendrite growth and low Coulombic efficiency have proven to be difficult challenges to overcome. Fundamentally, these two issues stem from the instability of the solid electrolyte interphase (SEI) layer, which is easily damaged by the large volumetric changes during battery cycling. In this work, we show that when a highly viscoelastic polymer was applied to the lithium metal electrode, the morphology of the lithium deposition became significantly more uniform. At a high current density of 5 mA/cm2 we obtained a flat and dense lithium metal layer, and we observed stable cycling Coulombic efficiency of ∼97% maintained for more than 180 cycles at a current density of 1 mA/cm2.