Temperature−field phase diagram of extreme magnetoresistance
Fazel Fallah Tafti, Quinn Gibson, Satya Kushwaha, Jason W. Krizan, Neel Haldolaarachchige, and Robert Joseph Cava
Extreme magnetoresistance (XMR) has been recently discovered in a number of seemingly unrelated materials with diverse crystalline and electronic structures. In this work, we use lanthanum monopnictides, LaBi and LaSb, as simple platforms to reveal a common triangular Temperature–field phase diagram for XMR. Further, we show that, in the electronic structure of both materials, lanthanum d orbitals mix with the pnictogen p orbitals. Remarkably, we find that both the triangular phase diagram and the orbital texture exist in all families of semimetals with XMR. These results show that XMR is a ubiquitous phenomenon with a universal phase diagram that goes beyond certain material specifications; it is not a rare commodity of topological materials or noncentrosymmetric structures. (See pp. E3475–E3481.)
Phosphorylation of spore coat proteins by a family of atypical protein kinases
Kim B. Nguyen, Anju Sreelatha, Eric S. Durrant, Javier Lopez-Garrido, Anna Muszewska, Małgorzata Dudkiewicz, Marcin Grynberg, Samantha Yee, Kit Pogliano, Diana R. Tomchick, Krzysztof Pawłowski, Jack E. Dixon, and Vincent S. Tagliabracci
The posttranslational modification of proteins with a molecule of phosphate, termed protein phosphorylation, is a mechanism used by cells to regulate cellular activities. Protein phosphorylation occurs in all life forms and is catalyzed by a superfamily of enzymes known as protein kinases. Using bioinformatics, we have identified a family of spore coat protein (Cot) kinases, which are related to the secreted kinase, family with sequence similarity 20C (Fam20C). The founding member of this family is CotH from the spore-forming bacterium Bacillus subtilis. We show that CotH-dependent phosphorylation of the spore proteins CotB and CotG is necessary for the proper germination of spores. Because several CotH-containing organisms are human pathogens, our work has important clinical implications to combat human diseases, such as anthrax. (See pp. E3482–E3491.)
Transplantation of iPSC-derived TM cells rescues glaucoma phenotypes in vivo
Wei Zhu, Oliver W. Gramlich, Lauren Laboissonniere, Ankur Jain, Val C. Sheffield, Jeffrey M. Trimarchi, Budd A. Tucker, and Markus H. Kuehn
The regulation of intraocular pressure (IOP) is vital for the health of the eye. Failure to maintain IOP frequently leads to vision loss in glaucoma. The IOP is maintained by the trabecular meshwork (TM), which exhibits decreased cellular density with age and disease. Here we demonstrate that induced pluripotent stem cells differentiated into TM cells (designated iPSC-TM) restore TM function for over 9 wk, regulate IOP, and prevent neuronal loss in a glaucoma mouse model. Transplanted iPSC-TM survive in the TM, but the most pronounced effect of transplantation is a robust proliferative response of endogenous TM cells. These findings suggest that lasting restoration of IOP control through iPSC-TM transplantation is possible and may represent a novel treatment approach for glaucoma. (See pp. E3492–E3500.)
A scalable strategy for high-throughput GFP tagging of endogenous human proteins
Manuel D. Leonetti, Sayaka Sekine, Daichi Kamiyama, Jonathan S. Weissman, and Bo Huang
The function of a large fraction of the human proteome still remains poorly characterized. Tagging proteins with a functional sequence is a powerful way to access function, and inserting tags at endogenous genomic loci allows the preservation of a near-native cellular background. To characterize the cellular role of human proteins in a systematic manner and in a native context, we developed a method for tagging endogenous human proteins with GFP that is both rapid and readily applicable at a genome-wide scale. Our approach allows studying both localization and interaction partners of the protein target. Our results pave the way for the large-scale generation of endogenously tagged human cell lines for a systematic functional interrogation of the human proteome. (See pp. E3501–E3508.)
A premeiotic function for boule in the planarian Schmidtea mediterranea
Harini Iyer, Melanie Issigonis, Prashant P. Sharma, Cassandra G. Extavour, and Phillip A. Newmark
The Deleted in Azoospermia (DAZ) family of RNA-binding proteins, consisting of Boule, Daz-like (Dazl), and DAZ, plays important roles in gametogenesis. Here we demonstrate that boule2 in the freshwater planarian Schmidtea mediterranea is necessary for the maintenance of early male germ cells, similar to the function of its vertebrate ortholog, Dazl. Our results are significant in that a premeiotic role for an invertebrate boule homolog has not been described to date. Furthermore, we functionally characterize planarian homologs of human DAZL/DAZ-associated proteins and mRNA targets. Our study alters the current understanding of DAZ family evolution and establishes S. mediterranea as a tractable model organism for the study of premeiotic functions of the DAZ family, and its binding partners and targets. (See pp. E3509–E3518.)
LAP-like process as an immune mechanism downstream of IFN-γ in control of the human malaria Plasmodium vivax liver stage
Rachasak Boonhok, Nattawan Rachaphaew, Apisak Duangmanee, Pornpimol Chobson, Sittiporn Pattaradilokrat, Pongsak Utaisincharoen, Jetsumon Sattabongkot, and Marisa Ponpuak
IFN-γ plays an important role in the elimination of liver-stage Plasmodium parasites, but the mechanism involved in this process is unclear. In this study, we demonstrate that IFN-γ treatment induces a noncanonical autophagy pathway in human hepatocytes dubbed an LC3-associated phagocytosis (LAP)-like process, in which the parasitophorous vacuole membrane of the parasites is decorated with LC3, resulting in the colocalization of parasite compartments with lysosomes. Downstream autophagy-related proteins are involved in this pathway, whereas the upstream autophagy-initiating protein is not. Our work shows that a LAP-like process serves as a previously unidentified downstream effector of IFN-γ in elimination of the liver-stage human malarial parasite Plasmodium vivax. (See pp. E3519–E3528.)
Diversity and divergence of the glioma-infiltrating T-cell receptor repertoire
Jennifer S. Sims, Boris Grinshpun, Yaping Feng, Timothy H. Ung, Justin A. Neira, Jorge L. Samanamud, Peter Canoll, Yufeng Shen, Peter A. Sims, and Jeffrey N. Bruce
High-throughput sequencing of T-cell receptor (TCR) repertoires provides a high-dimensional biomarker for monitoring the immune system. We applied this approach, measuring the extent to which the TCR repertoires of T-cell populations infiltrating malignant brain tumors diverge from their peripheral blood. Our analytical strategy separates the statistical properties of the repertoire derived from VJ cassette combination usage from the VJ-independent contribution that reflects the antigen-binding component of the receptor. We discovered a TCR signature strongly inversely correlated with the VJ-independent divergence between the peripheral and tissue-infiltrating repertoires of these patients. Importantly, this signature is detectable in peripheral blood and could serve as a means of noninvasively monitoring immune response in patients. (See pp. E3529–E3537.)
The Pseudomonas aeruginosa efflux pump MexGHI-OpmD transports a natural phenazine that controls gene expression and biofilm development
Hassan Sakhtah, Leslie Koyama, Yihan Zhang, Diana K. Morales, Blanche L. Fields, Alexa Price-Whelan, Deborah A. Hogan, Kenneth Shepard, and Lars E. P. Dietrich
Efflux-based drug resistance complicates the treatment of infectious diseases and cancers. Cellular exposure to ecological toxins or reactive metabolites may influence the conservation and activity of efflux pumps. Yet, for most such systems, we know very little about their natural substrates and the signals controlling pump expression. Using diverse approaches, including a chip-based method of electrochemical detection, we show that the endogenous and reactive antibiotic 5-methylphenazine-1-carboxylate (5-Me-PCA) is transported by the efflux pump MexGHI-OpmD in Pseudomonas aeruginosa. Furthermore, we demonstrate that 5-Me-PCA activates expression of its cognate transporter and that it is required for normal P. aeruginosa biofilm morphogenesis. Our results provide insight into mechanisms of self-resistance and determinants of multicellular behavior in this major cause of biofilm-based infections. (See pp. E3538–E3547.)
Adaptable history biases in human perceptual decisions
Arman Abrahamyan, Laura Luz Silva, Steven C. Dakin, Matteo Carandini, and Justin L. Gardner
Adapting to the environment requires using feedback about previous decisions to make better future decisions. Sometimes, however, the past is not informative and taking it into consideration leads to worse decisions. In psychophysical experiments, for instance, humans use past feedback when they should ignore it and thus make worse decisions. Those choice history biases persist even in disadvantageous contexts. To test this persistence, we adjusted trial sequence statistics. Subjects adapted strongly when the statistics confirmed their biases, but much less in the opposite direction; existing biases could not be eradicated. Thus, even in our simplest sensory decisions, we exhibit a form of confirmation bias in which existing choice history strategies are easier to reinforce than to relinquish. (See pp. E3548–E3557.)
APE1/Ref-1 facilitates recovery of gray and white matter and neurological function after mild stroke injury
R. Anne Stetler, Yanqin Gao, Rehana K. Leak, Zhongfang Weng, Yejie Shi, Lili Zhang, Hongjian Pu, Feng Zhang, Xiaoming Hu, Sulaiman Hassan, Carolyn Ferguson, Gregg E. Homanics, Guodong Cao, Michael V. L. Bennett, and Jun Chen
AP endonuclease-1 (APE1)/redox effector factor-1 (Ref-1) is an essential DNA repair enzyme that has been difficult to study mechanistically because of embryonic lethality in conventional knockout animals. Thus, we generated a conditional APE1 knockout model to examine the protective role of endogenous APE1 in experimental stroke. Induced APE1 knockout in adulthood greatly exacerbated neuron and oligodendrocyte loss after mild ischemic stroke and prevented the intrinsic, long-term recovery of sensorimotor function and spatial learning and memory. APE1 knockout also aggravated ischemia-induced destruction of myelin and impairment of axon conduction in white matter. We conclude that APE1 dictates fundamental life and death decisions in both gray and white matter and plays an indispensable role in intrinsic recovery after mild ischemic injury. (See pp. E3558–E3567.)
DEG9, a serine protease, modulates cytokinin and light signaling by regulating the level of ARABIDOPSIS RESPONSE REGULATOR 4
Wei Chi, Jing Li, Baoye He, Xin Chai, Xiumei Xu, Xuwu Sun, Jingjing Jiang, Peiqiang Feng, Jianru Zuo, Rongcheng Lin, Jean-David Rochaix, and Lixin Zhang
Selective protein proteolysis is essential for many plant signal transduction pathways and regulates developmental stages of a plant. In addition to the well-characterized ubiquitin-proteasome system, other factors appear to be involved in the degradation of plant signaling components. Here we describe the function of the serine protease degradation of periplasmic protein 9 (DEG9) in plant signaling. We found that DEG9 mediates the degradation of ARABIDOPSIS RESPONSE REGULATOR 4, which is critical for regulating the cross-talk between cytokinin and light-signaling pathways. This study adds to our knowledge about the function of DEG proteases, which are common in the plant kingdom, and emphasizes their importance in plant development. (See pp. E3568–E3576.)
Pseudomonas syringae type III effector HopAF1 suppresses plant immunity by targeting methionine recycling to block ethylene induction
Erica J. Washington, M. Shahid Mukhtar, Omri M. Finkel, Li Wan, Mark J. Banfield, Joseph J. Kieber, and Jeffery L. Dangl
Pseudomonas syringae is a Gram-negative bacterium that uses a type III secretion system to inject type III effector (T3E) proteins into the host to cause disease in plants. Multiple P. syringae T3Es promote virulence by targeting immune system signaling pathways using diverse biochemical mechanisms. We provide evidence for a molecular function of the P. syringae T3E HopAF1. We demonstrate that the C-terminal region of HopAF1 has structural homology to deamidases. We demonstrate that an enzyme important for production of the gaseous signaling hormone ethylene is a target for HopAF1 and show that HopAF1 targets methylthioadenosine nucleosidase proteins MTN1 and MTN2 to dampen ethylene production during bacterial infection. (See pp. E3577–E3586.)