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Ethylene controls translational gatekeeping to overcome flooding stress in plants EMBO J. (IF 14.012) Pub Date : 2022-08-17 Aida Maric, Sjon Hartman
Protein synthesis is an essential but energetically expensive cellular process that is challenged under environmental stress in plants. Recent work demonstrates that the plant hormone ethylene, through GCN2, represses general translation during flooding stress to conserve energy. Moreover, ethylene also promotes the translation of specific stress-responsive mRNAs to survive submergence stress.
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The function of BK channels extracted and purified within SMALPs Biochem. J. (IF 3.766) Pub Date : 2022-08-12 Patel, Jaimin H., Pollock, Naomi L., Maher, Jacqueline, Rothnie, Alice J., Allen, Marcus C.
Human BK channels are large voltage and Ca2+-activated K+ channels, involved in several important functions within the body. The core channel is a tetramer of α subunits, and its function is modulated by the presence of β and γ accessory subunits. BK channels composed of α subunits, as well as BK channels composed of α and β1 subunits, were successfully solubilised from HEK cells with styrene maleic
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Glucose feeds the tricarboxylic acid cycle via excreted ethanol in fermenting yeast Nat. Chem. Biol. (IF 16.174) Pub Date : 2022-08-15 Tianxia Xiao, Artem Khan, Yihui Shen, Li Chen, Joshua D. Rabinowitz
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Chemical genomics with pyrvinium identifies C1orf115 as a regulator of drug efflux Nat. Chem. Biol. (IF 16.174) Pub Date : 2022-08-15 Sanna N. Masud, Megha Chandrashekhar, Michael Aregger, Guihong Tan, Xiaoyu Zhang, Patricia Mero, David A. Pirman, Olga Zaslaver, Gromoslaw A. Smolen, Zhen-Yuan Lin, Cassandra J. Wong, Charles Boone, Anne-Claude Gingras, Rafael J. Montenegro-Burke, Jason Moffat
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m6A is required for resolving progenitor identity during planarian stem cell differentiation EMBO J. (IF 14.012) Pub Date : 2022-08-16 Yael Dagan, Yarden Yesharim, Ashley R Bonneau, Tamar Frankovits, Schraga Schwartz, Peter W Reddien, Omri Wurtzel
Regeneration and tissue homeostasis require accurate production of missing cell lineages. Cell production is driven by changes to gene expression, which is shaped by multiple layers of regulation. Here, we find that the ubiquitous mRNA base-modification, m6A, is required for proper cell fate choice and cellular maturation in planarian stem cells (neoblasts). We mapped m6A-enriched regions in 7,600
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Quorum sensing componentry opens new lines of communication. EMBO J. (IF 14.012) Pub Date : 2022-08-16 Sally Wang,Gregory F Payne,William E Bentley
Autoinducer-2 is a key molecule for bacterial quorum sensing. New exporter structures may now help narrow the gap between biology and engineering.
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Disulfide-crosslink analysis of the ubiquitin ligase Hrd1 complex during endoplasmic reticulum-associated protein degradation J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-13 Rudolf Pisa, Tom A. Rapoport
Misfolded proteins in the lumen of the endoplasmic reticulum (ER) are retro-translocated into the cytosol and degraded by the ubiquitin-proteasome system, a pathway termed luminal ER-associated protein degradation (ERAD-L). Retro-translocation is mediated by a conserved protein complex, consisting of the ubiquitin ligase Hrd1 and four associated proteins (Der1, Usa1, Hrd3, and Yos9). Photo-crosslinking
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Endosome maturation links PI3Kα signaling to lysosome repopulation during basal autophagy EMBO J. (IF 14.012) Pub Date : 2022-08-15 Samuel J Rodgers, Emily I Jones, Senthil Arumugam, Sabryn A Hamila, Jill Danne, Rajendra Gurung, Matthew J Eramo, Randini Nanayakkara, Georg Ramm, Meagan J McGrath, Christina A Mitchell
Autophagy depends on the repopulation of lysosomes to degrade intracellular components and recycle nutrients. How cells co-ordinate lysosome repopulation during basal autophagy, which occurs constitutively under nutrient-rich conditions, is unknown. Here, we identify an endosome-dependent phosphoinositide pathway that links PI3Kα signaling to lysosome repopulation during basal autophagy. We show that
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Vaginal bacterium Prevotella timonensis turns protective Langerhans cells into HIV-1 reservoirs for virus dissemination EMBO J. (IF 14.012) Pub Date : 2022-08-15 Nienke H van Teijlingen, Leanne C Helgers, Ramin Sarrami-Forooshani, Esther M Zijlstra-Willems, John L van Hamme, Celia Segui-Perez, Marleen Y van Smoorenburg, Hanneke Borgdorff, Janneke HHM van de Wijgert, Elisabeth van Leeuwen, Joris AM van der Post, Karin Strijbis, Carla MS Ribeiro, Teunis BH Geijtenbeek
Dysbiosis of vaginal microbiota is associated with increased HIV-1 acquisition, but the underlying cellular mechanisms remain unclear. Vaginal Langerhans cells (LCs) protect against mucosal HIV-1 infection via autophagy-mediated degradation of HIV-1. As LCs are in continuous contact with bacterial members of the vaginal microbiome, we investigated the impact of commensal and dysbiosis-associated vaginal
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Differential roles and regulation of the protein kinases PAK4, PAK5 and PAK6 in melanoma cells. Biochem. J. (IF 3.766) Pub Date : 2022-08-15 Gavuthami Murugesan,Alan R Prescott,Rachel Toth,David G Campbell,Claire M Wells,Carol MacKintosh
The protein kinases PAK4, PAK5 and PAK6 comprise a family of ohnologues. In multiple cancers including melanomas PAK5 most frequently carries non-synonymous mutations; PAK6 and PAK4 have fewer; and PAK4 is often amplified. To help interpret these genomic data, initially we compared the cellular regulation of the sister kinases and their roles in melanoma cells. In common with many ohnologue protein
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Transcriptional regulator Taf14 binds DNA and is required for the function of transcription factor TFIID in the absence of histone H2A.Z J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-13 Kadri Peil, Signe Värv, Ivar Ilves, Kersti Kristjuhan, Henel Jürgens, Arnold Kristjuhan
The transcriptional regulator Taf14 is a component of multiple protein complexes involved in transcription initiation and chromatin remodeling in yeast cells. Although Taf14 is not required for cell viability, it becomes essential in conditions where the formation of the transcription pre-initiation complex (PIC) is hampered. The specific role of Taf14 in mediating transcription initiation and PIC
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An evolutionary divergent thermodynamic brake in ZAP-70 fine-tunes the kinetic proofreading in T cells J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-13 Kaustav Gangopadhyay, Arnab Roy, Athira C. Chandradasan, Swarnendu Roy, Olivia Debnath, Soumee SenGupta, Subhankar Chowdhury, Dipjyoti Das, Rahul Das
T cell signaling starts with assembling several tyrosine kinases and adaptor proteins to the T cell receptor (TCR), following the antigen-binding to the TCR. The stability of the TCR-antigen complex and the delay between the recruitment and activation of each kinase determines the T cell response. Integration of such delays constitutes a kinetic proofreading mechanism to regulate T cell response to
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Swapping N-terminal regions among tick evasins reveals cooperative interactions influencing chemokine binding and selectivity J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-13 Pramod Aryal, Shankar Raj Devkota, Devadharshini Jeevarajah, Ruby Law, Richard J. Payne, Ram Prasad Bhusal, Martin J. Stone
Class A tick evasins are natural chemokine-binding proteins that block the signaling of multiple chemokines from the CC subfamily through their cognate receptors, thus suppressing leukocyte recruitment and inflammation. Development of tick evasins as chemokine-targeted anti-inflammatory therapeutics requires an understanding of the factors controlling their chemokine recognition and selectivity. To
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A novel formamidase is required for riboflavin biosynthesis in invasive bacteria J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-13 Svetlana N. Yurgel, Skylar A. Johnson, Jennifer Rice, Na Sa, Clayton Bailes, John Baumgartner, Josh E. Pitzer, R. Martin Roop, Sanja Roje
Biosynthesis of riboflavin, the precursor of the redox cofactors FMN and FAD, was thought to be well understood in bacteria, with all the pathway enzymes presumed to be known and essential. Our previous research has challenged this view by showing that, in the bacterium Sinorhizobium meliloti, deletion of the ribBA gene encoding the enzyme that catalyzes the initial steps on the riboflavin biosynthesis
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Placental growth factor stabilizes VEGF receptor-2 protein in retinal pigment epithelial cells by downregulating glycogen synthase kinase 3 activity J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-13 Miyuki Murata, Kousuke Noda, Satoru Kase, Keitaro Hase, Di Wu, Ryo Ando, Susumu Ishida
Placental growth factor (PlGF) belongs to the vascular endothelial growth factor (VEGF) family of proteins that participate in angiogenesis and vasculogenesis. Anti-VEGF therapy has become the standard treatment for ocular angiogenic disorders in ophthalmological practice. However, there is emerging evidence that anti-VEGF treatment may increase the risk of atrophy of the retinal pigment epithelium
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Lysine demethylase KDM1A promotes cell growth via FKBP8-BCL2 axis in hepatocellular carcinoma J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-13 Suli Lv, Xuefeng Zhao, Erlei Zhang, Yingying Yan, Xianyun Ma, Neng Li, Qingli Zou, Lidong Sun, Tanjing Song
Advanced hepatocellular carcinoma (HCC) has a dismal prognosis. KDM1A, overexpressed in multiple cancer types, is a lysine demethylase that targets both histone and non-histone proteins. However, it is unclear how KDM1A expression affects HCC etiology. Here, we show KDM1A can interact with and demethylate FKBP8, a cytoplasmic protein which regulates cell survival through the anti-apoptotic protein
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The efficacy of receptor tyrosine kinase EphA2 autophosphorylation increases with EphA2 oligomer size J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-13 Elmer Zapata-Mercado, Gabriel Biener, Daniel M. McKenzie, William C. Wimley, Elena B. Pasquale, Valerica Raicu, Kalina Hristova
The receptor tyrosine kinase (RTK) EphA2 is expressed in epithelial and endothelial cells and controls the assembly of cell-cell junctions. EphA2 has also been implicated in many diseases, including cancer. Unlike most RTKs, which signal predominantly as dimers, EphA2 readily forms higher order oligomers upon ligand binding. Here, we investigated if a correlation exists between EphA2 signaling properties
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Central Residues in Prion Protein PrPC Are Crucial for Its Conversion into the Pathogenic Isoform J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-13 Agriani Dini Pasiana, Hironori Miyata, Junji Chida, Hideyuki Hara, Morikazu Imamura, Ryuichiro Atarashi, Suehiro Sakaguchi
Conformational conversion of the cellular prion protein, PrPC, into the amyloidogenic isoform, PrPSc, is a key pathogenic event in prion diseases. However, the conversion mechanism remains to be elucidated. Here, we generated Tg(PrPΔ91-106)-8545/Prnp0/0 mice, which overexpress mouse PrP lacking residues 91-106. We showed that none of the mice became sick after intracerebral inoculation with RML, 22L
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Proximity labeling of endogenous RICTOR identifies mTOR Complex 2 regulation by ADP ribosylation factor ARF1 J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-13 Amelia K. Luciano, Ekaterina Korobkina, Scott P. Lyons, John A. Haley, Shelagh Fluharty, Su Myung Jung, Arminja N. Kettenbach, David A. Guertin
Mechanistic Target of Rapamycin (mTOR) complex 2 (mTORC2) regulates metabolism, cell proliferation, and cell survival. mTORC2 activity is stimulated by growth factors, and it phosphorylates the hydrophobic motif site of the AGC kinases AKT, SGK, and PKC. However, the proteins that interact with mTORC2 to control its activity and localization remain poorly defined. To identify mTORC2 interacting proteins
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Identification and characterization of a novel hydroxylamine oxidase, DnfA, that catalyzes the oxidation of hydroxylamine to N2 J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-13 Meng-Ru Wu, Li-Li Miao, Ying Liu, Xin-Xin Qian, Ting-Ting Hou, Guo-Min Ai, Lu Yu, Lan Ma, Xi-Yan Gao, Ya-Ling Qin, Hai-Zhen Zhu, Lei Du, Sheng-Ying Li, Chang-Lin Tian, De-Feng Li, Zhi-Pei Liu, Shuang-Jiang Liu
Nitrogen gas in the atmosphere is partially replenished by microbial denitrification of ammonia. Recent study has shown Alcaligenes ammonioxydans oxidizes ammonia to dinitrogen via a process featuring the intermediate hydroxylamine, termed “Dirammox” (direct ammonia oxidation). However, the unique biochemistry of this process remains unknown. Here we report an enzyme involved in Dirammox that catalyzes
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Crystal structures of Schistosoma mansoni histone deacetylase 8 reveal a novel binding site for allosteric inhibitors. J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-13 Fulvio Saccoccia, Luca Pozzetti, Roberto Gimmelli, Stefania Butini, Alessandra Guidi, Giuliana Papoff, Marialaura Giannaccari, Simone Brogi, Viviana Scognamiglio, Sandra Gemma, Giovina Ruberti, Giuseppe Campiani
Parasitic diseases cause significant global morbidity and mortality particularly in the poorest regions of the world. Schistosomiasis, one of the most widespread neglected tropical diseases, affects more than 200 million people worldwide. Histone deacetylase (HDAC) inhibitors are prominent epigenetic drugs that are being investigated in the treatment of several diseases, including cancers and parasitic
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Glycosylation of a key cubilin Asn residue results in reduced binding to albumin J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-13 Shiv Pratap Yadav, Aiying Yu, Jingfu Zhao, Jasdeep Singh, Saloni Kakkar, Srinivas Chakraborty, Yehia Mechref, Bruce Molitoris, Mark C. Wagner
Kidney disease often manifests with an increase in proteinuria, which can result from both glomerular and/or proximal tubule injury. The proximal tubules are the major site of protein and peptide endocytosis of the glomerular filtrate, and cubilin is the proximal tubule brushborder membrane glycoprotein receptor that binds filtered albumin and initiates its processing in proximal tubules. Albumin also
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Engineered Cas13 variants with minimal collateral RNA targeting Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-12
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Human CIDEC transgene improves lipid metabolism and protects against high-fat diet-induced glucose intolerance in mice J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-11 Abhishek Gupta, Bijinu Balakrishnan, Shakun Karki, Mark Slayton, Sukanta Jash, Sayani Banerjee, Tan Hooi Min Grahn, Srikarthika Jambunathan, Sarah Disney, Hebaallaha Hussein, Dong Kong, Bradford B. Lowell, Purushothaman Natarajan, Umesh K. Reddy, Noyan Gokce, Vishva M. Sharma, Vishwajeet Puri
Cell death-inducing DNA fragmentation factor-like effector C (CIDEC) expression in adipose tissue positively correlates with insulin sensitivity in obese humans. Further, E186X, a single-nucleotide CIDEC variant is associated with lipodystrophy, hypertriglyceridemia, and insulin resistance. To establish the unknown mechanistic link between CIDEC and maintenance of systemic glucose homeostasis, we generated
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Extracellular 5’-methylthioadenosine inhibits intracellular symmetric dimethylarginine protein methylation of FUSE-element binding proteins J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-11 Baiqing Tang, Hyung-Ok Lee, Sapna Gupta, Liqun Wang, Alison M. Kurimchak, James S. Duncan, Warren D. Kruger
Methylthioadenosine phosphorylase (MTAP) is a key enzyme in the methionine salvage pathway that converts the polyamine synthesis byproduct 5′-deoxy-5′-methylthioadenosine (MTA) into methionine. Inactivation of MTAP, often by homozygous deletion, is found in both solid and hematologic malignancies and is one of the most frequently observed genetic alterations in human cancer. Previous work established
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Reisomerization of retinal represents a molecular switch mediating Na+ uptake and release by a bacterial sodium-pumping rhodopsin J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-11 Tomotsumi Fujisawa, Kouta Kinoue, Ryouhei Seike, Takashi Kikukawa, Masashi Unno
Sodium-pumping rhodopsins (NaRs) are membrane transporters that utilize light energy to pump Na+ across the cellular membrane. Within the NaRs, the retinal Schiff base chromophore absorbs light, and a photochemically-induced transient state, referred to as the “O intermediate”, performs both the uptake and release of Na+. However, the structure of the O intermediate remains unclear. Here, we used time-resolved
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Human eukaryotic initiation factor 4E (eIF4E) and the nucleotide-bound state of eIF4A regulate eIF4F binding to RNA J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-11 Mario Servulo Izidoro, Masaaki Sokabe, Nancy Villa, William C. Merrick, Christopher S. Fraser
During translation initiation, the underlying mechanism by which the eukaryotic initiation factor (eIF) 4E, eIF4A, and eIF4G components of eIF4F coordinate their binding activities to regulate eIF4F binding to mRNA is poorly defined. Here, we used fluorescence anisotropy to generate thermodynamic and kinetic frameworks for the interaction of uncapped RNA with human eIF4F. We demonstrate the binding
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AMPK-related protein kinase ARK5 regulates subcellular localization of RNA-binding protein hnRNP A1 during hypertonic stress J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-11 Krishna Bhattarai, Travis Richard, Thet Fatica, Brianna Frangione, William G. Willmore, Martin Holcik
The heterogeneous nuclear ribonucleoprotein hnRNP A1 is a nucleocytoplasmic-shuttling RNA-binding protein that plays an important role in nucleic acid metabolism and gene expression regulation. The function of hnRNP A1 is determined in part by its specific location within the cell. Although some work has been done to elucidate the signaling pathways that regulate the cellular localization of hnRNP
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Phase-separation antagonists potently inhibit transcription and broadly increase nucleosome density J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-11 Rajyalakshmi Meduri, Linda S. Rubio, Suman Mohajan, David S. Gross
Biomolecular condensates are self-organized, membraneless bodies involved in many critical cellular activities including ribosome biogenesis, protein synthesis and gene transcription. Aliphatic alcohols are commonly used to study biomolecular condensates, but their effects on transcription are unclear. Here, we explore the impact of the aliphatic di-alcohol, 1,6-hexanediol, on Pol II transcription
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Phosphatidic acid inhibits inositol synthesis by inducing nuclear translocation of kinase IP6K1 and repression of myo-inositol-3-P synthase J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-10 Pablo Lazcano, Michael W. Schmidtke, Chisom Onu, Miriam L. Greenberg
Inositol is an essential metabolite that serves as a precursor for structural and signaling molecules. Although perturbation of inositol homeostasis has been implicated in numerous human disorders, surprisingly little is known about how inositol levels are regulated in mammalian cells. A recent study in mouse embryonic fibroblasts (MEFs) demonstrated that nuclear translocation of inositol hexakisphosphate
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Impaired myocellular Ca2+ cycling in protein phosphatase PP2A-B56α knockout mice is normalized by β-adrenergic stimulation J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-10 Dennis Glaser, Alexander Heinick, Julius R. Herting, Fabian Massing, Frank U. Müller, Paul Pauls, Timofey S. Rozhdestvensky, Jan S. Schulte, Matthias D. Seidl, Boris V. Skryabin, Frank Stümpel, Uwe Kirchhefer
The activity of protein phosphatase 2A (PP2A) is determined by the expression and localization of the regulatory B-subunits. PP2A-B56α is the dominant isoform of the B'-family in the heart. Its role in regulating the cardiac response to β-adrenergic stimulation is not yet fully understood. We therefore generated mice deficient in B56α to test the functional cardiac effects in response to catecholamine
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Functional inactivation of Plasmodium falciparum glycogen synthase kinase GSK3 modulates erythrocyte invasion and blocks gametocyte maturation J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-10 Arne Alder, Louisa Wilcke, Emma Pietsch, Heidrun von Thien, Samuel Pazicky, Christian Löw, Paolo Mesen-Ramirez, Anna Bachmann, Paul-Christian Burda, Conrad Kunick, Holger Sondermann, Danny Wilson, Tim-Wolf Gilberger
Malaria is responsible for hundreds of thousands of deaths every year. The lack of an effective vaccine and the global spread of multi-drug resistant parasites hampers the fight against the disease and underlines the need for new antimalarial drugs. Central to the pathogenesis of malaria is the proliferation of Plasmodium parasites within human erythrocytes. Parasites invade erythrocytes via a coordinated
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Autoinhibition of the GEF activity of cytoskeletal regulatory protein Trio is disrupted in neurodevelopmental disorder-related genetic variants. J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-10 Josie E. Bircher, Ellen E. Corcoran, TuKiet T. Lam, Michael J. Trnka, Anthony J. Koleske
TRIO encodes a cytoskeletal regulatory protein with three catalytic domains – two guanine exchange factor (GEF) domains, GEF1 and GEF2, and a kinase domain – as well as several accessory domains that have not been extensively studied. Function-damaging variants in the TRIO gene are known to be enriched in individuals with neurodevelopmental disorders (NDDs). Disease variants in the GEF1 domain or the
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Development, structure, and mechanism of synthetic antibodies that target claudin and Clostridium perfringens enterotoxin complexes J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-09 Benjamin J. Orlando, Pawel K. Dominik, Sourav Roy, Chinemerem P. Ogbu, Satchal K. Erramilli, Anthony A. Kossiakoff, Alex J. Vecchio
Strains of Clostridium perfringens produce a two-domain enterotoxin (CpE) that afflicts humans and domesticated animals, causing prevalent gastrointestinal illnesses. CpE’s C-terminal domain (cCpE) binds cell surface receptors, followed by a restructuring of its N-terminal domain to form a membrane-penetrating β-barrel pore, which is toxic to epithelial cells of the gut. The claudin family of membrane
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Abalos Therapeutics---arenaviruses take on cancer Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-12
After >20 years of research at the intersection of virology and immunology, two brothers have launched a venture seeking to turn arenaviruses into an anticancer virotherapy.
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Accessible bioengineered corneal tissue to address a blinding disease globally Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-11
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High-fidelity Cas13 variants for targeted RNA degradation with minimal collateral effects Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-11 Huawei Tong, Jia Huang, Qingquan Xiao, Bingbing He, Xue Dong, Yuanhua Liu, Xiali Yang, Dingyi Han, Zikang Wang, Xuchen Wang, Wenqin Ying, Runze Zhang, Yu Wei, Chunlong Xu, Yingsi Zhou, Yanfei Li, Minqing Cai, Qifang Wang, Mingxing Xue, Guoling Li, Kailun Fang, Hainan Zhang, Hui Yang
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Bioengineered corneal tissue for minimally invasive vision restoration in advanced keratoconus in two clinical cohorts Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-11 Mehrdad Rafat, Mahmoud Jabbarvand, Namrata Sharma, Maria Xeroudaki, Shideh Tabe, Raha Omrani, Muthukumar Thangavelu, Anthony Mukwaya, Per Fagerholm, Anton Lennikov, Farshad Askarizadeh, Neil Lagali
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Unbiased matchmaking Nat. Chem. Biol. (IF 16.174) Pub Date : 2022-08-11 Cecilia Ka Wing Chan, Sze Ho Gwyneth Lau, Chung Hang Jonathan Choi
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Bicyclostreptins are radical SAM enzyme-modified peptides with unique cyclization motifs Nat. Chem. Biol. (IF 16.174) Pub Date : 2022-08-11 Leah B. Bushin, Brett C. Covington, Kenzie A. Clark, Alessio Caruso, Mohammad R. Seyedsayamdost
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Identifying cell receptors for the nanoparticle protein corona using genome screens Nat. Chem. Biol. (IF 16.174) Pub Date : 2022-08-11 Wayne Ngo, Jamie L. Y. Wu, Zachary P. Lin, Yuwei Zhang, Bram Bussin, Adrian Granda Farias, Abdullah M. Syed, Katherine Chan, Andrea Habsid, Jason Moffat, Warren C. W. Chan
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Artificial intelligence uncovers carcinogenic human metabolites Nat. Chem. Biol. (IF 16.174) Pub Date : 2022-08-11 Aayushi Mittal, Sanjay Kumar Mohanty, Vishakha Gautam, Sakshi Arora, Sheetanshu Saproo, Ria Gupta, Roshan Sivakumar, Prakriti Garg, Anmol Aggarwal, Padmasini Raghavachary, Nilesh Kumar Dixit, Vijay Pal Singh, Anurag Mehta, Juhi Tayal, Srivatsava Naidu, Debarka Sengupta, Gaurav Ahuja
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Damage-induced regeneration of the intestinal stem cell pool through enteroblast mitosis in the Drosophila midgut EMBO J. (IF 14.012) Pub Date : 2022-08-11 Aiguo Tian, Virginia Morejon, Sarah Kohoutek, Yi-Chun Huang, Wu-Min Deng, Jin Jiang
Many adult tissues and organs including the intestine rely on resident stem cells to maintain homeostasis and regeneration. In mammals, the progenies of intestinal stem cells (ISCs) can dedifferentiate to generate ISCs upon ablation of resident stem cells. However, whether and how mature tissue cells generate ISCs under physiological conditions remains unknown. Here, we show that infection of the Drosophila
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Salicylic acid-activated BIN2 phosphorylation of TGA3 promotes Arabidopsis PR gene expression and disease resistance EMBO J. (IF 14.012) Pub Date : 2022-08-11 Qing Han, Wenrong Tan, Yuqing Zhao, Feng Yang, Xiuhong Yao, Honghui Lin, Dawei Zhang
The plant defense hormone, salicylic acid (SA), plays essential roles in immunity and systemic acquired resistance. Salicylic acid induced by the pathogen is perceived by the receptor nonexpressor of pathogenesis-related genes 1 (NPR1), which is recruited by TGA transcription factors to induce the expression of pathogenesis-related (PR) genes. However, the mechanism by which post-translational modifications
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Binary organization of epidermal basal domains highlights robustness to environmental exposure EMBO J. (IF 14.012) Pub Date : 2022-08-10 Sangeeta Ghuwalewala, Seon A Lee, Kevin Jiang, Joydeep Baidya, Gopal Chovatiya, Pritinder Kaur, David Shalloway, Tudorita Tumbar
Adulte interfollicular epidermis (IFE) renewal is likely orchestrated by physiological demands of its complex tissue architecture comprising spatial and cellular heterogeneity. Mouse tail and back skin display two kinds of basal IFE spatial domains that regenerate at different rates. Here, we elucidate the molecular and cellular states of basal IFE domains by marker expression and single-cell transcriptomics
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Discovery of compounds that reactivate p53 mutants in vitro and in vivo Cell Chem. Bio. (IF 9.039) Pub Date : 2022-08-10 Geetha Durairaj, Özlem Demir, Bryant Lim, Roberta Baronio, Delia Tifrea, Linda V. Hall, Jacob C. DeForest, Linda Lauinger, Maryam M. Jebril Fallatah, Clinton Yu, Hosung Bae, Da-Wei Lin, Jin Kwang Kim, Faezeh Salehi, Cholsoon Jang, Feng Qiao, Richard H. Lathrop, Lan Huang, Peter Kaiser
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Epigenomics Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-09
Recent patents relating to epigenomic analyses, modification and engineering.
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Second-quarter biotech job picture Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-09 Michael Francisco
A quarterly snapshot of job expansions, reductions and availability in the biotech and pharma sectors.
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Patents benefit patients and patent reform would spur diagnostic and therapeutic development Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-09 Laura A. Coruzzi
Patients need the patent system to spur the investment necessary for the continued development of life-saving diagnostics and therapies.
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Can hackathons unlock a new talent pool from the developing world? Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-09 Timothy P. Jenkins, Nicolas Lopez Carranza, Amy Bray, Karim Beguir, Andreas H. Laustsen
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People Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-09
Recent moves of note in and around the biotech and pharma industries.
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HER3-addicted tumors: how biotechs are closing in Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-09
The elusive HER3, known to drive aggressive cancers, may finally be toppled by once-abandoned antibody drugs.
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mRNA printers kick-start personalized medicines for all Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-09
mRNA printers will bring low-cost vaccines and made-to-order treatments for a range of different diseases.
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A newly identified flavoprotein disulfide reductase Har protects Streptococcus pneumoniae against hypothiocyanous acid J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-09 Heather L. Shearer, Paul E. Pace, James C. Paton, Mark B. Hampton, Nina Dickerhof
Hypothiocyanous acid (HOSCN) is an antimicrobial oxidant produced by heme peroxidases from hydrogen peroxide and thiocyanate anions in secretory fluids such as in the human respiratory tract. While some respiratory tract pathogens display tolerance to HOSCN, there might be therapeutic value in targeting bacterial antioxidant systems that protect against HOSCN; however, surprisingly little is known
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RAD54B mutations enhance the sensitivity of ovarian cancer cells to poly(ADP-ribose) polymerase (PARP) inhibitors J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-09 Peng Liu, Chunxiu Lin, Lanlan Liu, Ziwen Lu, Zhigang Tu, Hanqing Liu
Synthetic lethal targeting of homologous recombination (HR)-deficient ovarian cancers with poly(ADP-ribose) polymerase inhibitors (PARPis) has attracted considerable attention. Olaparib was the first PARPi approved by the FDA, offering significant clinical benefits in BRCA1/2-deficient ovarian cancers. However, only approximately 20% of ovarian cancer patients harbor BRCA1/2 mutations. Given the shared
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The nepenthesin insert in the Plasmodium falciparum aspartic protease plasmepsin V is necessary for enzyme function J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-09 Alexander J. Polino, Justin J. Miller, Soumendranath Bhakat, Sumit Mukherjee, Suhas Bobba, Gregory R. Bowman, Daniel E. Goldberg
Plasmepsin V (PM V) is a pepsin-like aspartic protease essential for growth of the malaria parasite Plasmodium falciparum. Previous work has shown PM V to be an ER-resident protease that processes parasite proteins destined for export into the host cell. Depletion or inhibition of the enzyme is lethal during asexual replication within red blood cells, as well as during the formation of sexual stage
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Interplay of carbon dioxide and peroxide metabolism in mammalian cells J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-09 Rafael Radi
The carbon dioxide/bicarbonate (CO2/HCO3-) molecular pair is ubiquitous in mammalian cells and tissues, mainly as a result of oxidative decarboxylation reactions that occur during intermediary metabolism. CO2 is in rapid equilibrium with HCO3- via the hydration reaction catalyzed by carbonic anhydrases. Far from being an inert compound in redox biology, CO2 enhances or redirects the reactivity of peroxides
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The nematode serotonin-gated chloride channel MOD-1: A novel target for anthelmintic therapy J. Biol. Chem. (IF 5.486) Pub Date : 2022-08-09 Noelia Rodriguez Araujo, Guillermina Hernando, Jeremías Corradi, Cecilia Bouzat
Anthelmintics are used to treat human and veterinary parasitic diseases, as well as to reduce crop and livestock production loss associated with parasitosis. The free-living nematode Caenorhabditis elegans, a model system for anthelmintic drug discovery, has a serotonin (5-HT)-gated chloride channel, MOD-1, which belongs to the Cys-loop receptor family and modulates locomotory and behavioral functions
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Programmable DARPin-based receptors for the detection of thrombotic markers Nat. Chem. Biol. (IF 16.174) Pub Date : 2022-08-08 Tobias Strittmatter, Yidan Wang, Adrian Bertschi, Leo Scheller, Patrick C. Freitag, Preetam Guha Ray, Pascal Stuecheli, Jonas V. Schaefer, Thomas Reinberg, Dimitrios Tsakiris, Andreas Plückthun, Haifeng Ye, Martin Fussenegger
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ARF2-PIF5 interaction controls transcriptional reprogramming in the ABS3-mediated plant senescence pathway EMBO J. (IF 14.012) Pub Date : 2022-08-09 Hui Xue, Jingjing Meng, Pei Lei, Yongxin Cao, Xue An, Min Jia, Yan Li, Haofeng Liu, Jen Sheen, Xiayan Liu, Fei Yu
One of the hallmarks of plant senescence is the global transcriptional reprogramming coordinated by a plethora of transcription factors (TFs). However, mechanisms underlying the interactions between different TFs in modulating senescence remain obscure. Previously, we discovered that plant ABS3 subfamily MATE transporter genes regulate senescence and senescence-associated transcriptional changes. In