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| Open AccessThinking multi-scale to advance mechanobiology
We are inviting submissions of articles on the role of mechanobiology in health and disease with the aim of publishing high quality research devoted to advance our understanding of mechanics shaping biological function. We are also happy to present a
Collection - Marco Fritzsche
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Article
| Open AccessIterative evolution of large-bodied hypercarnivory in canids benefits species but not clades
Balisi and Van Valkenburgh analyse the effect of body size and dietary specialization on extinction regimes in North American Canidae. They find that hypercarnivory, which evolved independently multiple times, does not increase species-level extinction but is associated with extinctions of clades.
- Mairin A. Balisi
- & Blaire Van Valkenburgh
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Article
| Open AccessGlycovariant-based lateral flow immunoassay to detect ovarian cancer–associated serum CA125
Sherif Bayoumy et al. report a lateral flow immunoassay (LFIA) to quantify aberrantly glycosylated CA125 to diagnose epithelial ovarian cancer. Their method has a 30-minute read-out time, high sensitivity and specificity, and can distinguish ovarian cancer from benign endometriosis and other cancers.
- Sherif Bayoumy
- , Heidi Hyytiä
- , Janne Leivo
- , Sheikh M. Talha
- , Kaisa Huhtinen
- , Matti Poutanen
- , Johanna Hynninen
- , Antti Perheentupa
- , Urpo Lamminmäki
- , Kamlesh Gidwani
- & Kim Pettersson
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Article
| Open AccessGenetic control of CCL24, POR, and IL23R contributes to the pathogenesis of sarcoidosis
Akira Meguro et al. report a genome-wide association study for sarcoidosis—a systemic inflammatory disease—in the Japanese population. They identify 3 non-HLA loci with genome-wide significance, 2 of which have not been previously associated with sarcoidosis in any population.
- Akira Meguro
- , Mami Ishihara
- , Martin Petrek
- , Ken Yamamoto
- , Masaki Takeuchi
- , Frantisek Mrazek
- , Vitezslav Kolek
- , Alzbeta Benicka
- , Takahiro Yamane
- , Etsuko Shibuya
- , Atsushi Yoshino
- , Akiko Isomoto
- , Masao Ota
- , Keisuke Yatsu
- , Noriharu Shijubo
- , Sonoko Nagai
- , Etsuro Yamaguchi
- , Tetsuo Yamaguchi
- , Kenichi Namba
- , Toshikatsu Kaburaki
- , Hiroshi Takase
- , Shin-ichiro Morimoto
- , Junko Hori
- , Keiko Kono
- , Hiroshi Goto
- , Takafumi Suda
- , Soichiro Ikushima
- , Yasutaka Ando
- , Shinobu Takenaka
- , Masaru Takeuchi
- , Takenosuke Yuasa
- , Katsunori Sugisaki
- , Nobuyuki Ohguro
- , Miki Hiraoka
- , Nobuyoshi Kitaichi
- , Yukihiko Sugiyama
- , Nobuyuki Horita
- , Yuri Asukata
- , Tatsukata Kawagoe
- , Ikuko Kimura
- , Mizuho Ishido
- , Hidetoshi Inoko
- , Manabu Mochizuki
- , Shigeaki Ohno
- , Seiamak Bahram
- , Elaine F. Remmers
- , Daniel L. Kastner
- & Nobuhisa Mizuki
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Article
| Open AccessThe oligomeric assembly of galectin-11 is critical for anti-parasitic activity in sheep (Ovis aries)
Sakthivel et al. report two natural genetic variants of galectin-11 in sheep and demonstrate that their ability to dimerise correlates with the differences in their anti-parasitic activity that triggers larval arrest. This study provides a basis for genetic studies toward selective breeding of animals to improve their resistance to parasites.
- Dhanasekaran Sakthivel
- , Sarah Preston
- , Robin B. Gasser
- , Tatiana P. Soares da Costa
- , Julia N. Hernandez
- , Adam Shahine
- , M. D. Shakif-Azam
- , Peter Lock
- , Jamie Rossjohn
- , Matthew A. Perugini
- , Jorge Francisco González
- , Els Meeusen
- , David Piedrafita
- & Travis Beddoe
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Article
| Open AccessProteosomal degradation of NSD2 by BRCA1 promotes leukemia cell differentiation
Park et al. identify Multiple Myeloma SET domain (MMSET/NSD2) in a large-scale CRISPR screen of genes whose depletion regulates hematopoietic differentiation and found it to interact with BRCA1. Thus regulation of MMSET/NSD2 stability BRCA1-mediated ubiquitination could be explored for potential therapeutic interventions in multiple myeloma.
- Jin Woo Park
- , Joo-Young Kang
- , Ja Young Hahm
- , Hyun Jeong Kim
- & Sang-Beom Seo
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Article
| Open AccessThickness of the cerebral cortex shows positive association with blood levels of triacylglycerols carrying 18-carbon fatty acids
Eeva Sliz et al. show an association between triacylglycerols species carrying 18-carbon unsaturated fatty acids and cortical thickness by combining serum lipidomics and brain imaging data. This association is more pronounced in cortical regions with higher expression of genes regulating fatty acid metabolism and cellular membranes.
- Eeva Sliz
- , Jean Shin
- , Catriona Syme
- , Sandra Black
- , Sudha Seshadri
- , Tomas Paus
- & Zdenka Pausova
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Article
| Open AccessA droplet reactor on a super-hydrophobic surface allows control and characterization of amyloid fibril growth
Zhang et al present an integrated real-time imaging and flow field control platform based on water droplet evaporation on super-hydrophobic substrate (SHS) to enable amyloid fibril aggregation. They apply this methodology to observe structural polymorphism in PHF6 peptide and full length Tau441.
- Peng Zhang
- , Manola Moretti
- , Marco Allione
- , Yuansi Tian
- , Javier Ordonez-Loza
- , Davide Altamura
- , Cinzia Giannini
- , Bruno Torre
- , Gobind Das
- , Erqiang Li
- , Sigurdur T. Thoroddsen
- , S. Mani Sarathy
- , Ida Autiero
- , Andrea Giugni
- , Francesco Gentile
- , Natalia Malara
- , Monica Marini
- & Enzo Di Fabrizio
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Article
| Open AccessLIVE-PAINT allows super-resolution microscopy inside living cells using reversible peptide-protein interactions
Oi et al. describe LIVE-PAINT, a new method to achieve superresolution fluorescent imaging within live cells. They demonstrate its efficacy by imaging a number of different proteins inside live S. cerevisiae cells. Their method is widely applicable, easily implemented with extended data acquisition times.
- Curran Oi
- , Zoe Gidden
- , Louise Holyoake
- , Owen Kantelberg
- , Simon Mochrie
- , Mathew H. Horrocks
- & Lynne Regan
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Article
| Open AccessStructural studies reveal flexible roof of active site responsible for ω-transaminase CrmG overcoming by-product inhibition
Xu, Tang et al. show that ω-transaminase CrmG is insensitive to the inhibition from by-products α-ketoglutarate or pyruvate. They find that these by-products cannot interact strongly with the flexible roof of the active site in CrmG. This study provides insights into the rational design of transaminase to eliminate by-product inhibition.
- Jinxin Xu
- , Xiaowen Tang
- , Yiguang Zhu
- , Zhijun Yu
- , Kai Su
- , Yulong Zhang
- , Yan Dong
- , Weiming Zhu
- , Changsheng Zhang
- , Ruibo Wu
- & Jinsong Liu
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Article
| Open AccessA fraction of barrier-to-autointegration factor (BAF) associates with centromeres and controls mitosis progression
Torras-Llort et al. find that the chromatin binding protein Barrier-to-Autointegration Factor (BAF) associates with centromeres and is required for proper centromere assembly and function in Drosophila. They show that disruption of centromeric BAF localization prevents PP2A inactivation in mitosis compromising global BAF phosphorylation and leading to delayed anaphase onset and nuclear envelope defects.
- Mònica Torras-Llort
- , Sònia Medina-Giró
- , Paula Escudero-Ferruz
- , Zoltan Lipinszki
- , Olga Moreno-Moreno
- , Zoltan Karman
- , Marcin R. Przewloka
- & Fernando Azorín
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Article
| Open AccessBedaquiline inhibits the yeast and human mitochondrial ATP synthases
Luo, Zhou et al. show that Bedaquiline (BDQ, Sirturo), approved to treat multi-drug-resistant tuberculosis, inhibits the yeast and human mitochondrial ATP synthases in addition to its intended target, the Mycobacterium tuberculosis ATP synthase. The structure of the mitochondrial ATP synthase bound to BDQ suggests a means to modify this inhibitor to increase its specificity for the M. tuberculosis enzyme, thereby reducing its side effects for patients.
- Min Luo
- , Wenchang Zhou
- , Hiral Patel
- , Anurag P. Srivastava
- , Jindrich Symersky
- , Michał M. Bonar
- , José D. Faraldo-Gómez
- , Maofu Liao
- & David M. Mueller
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Article
| Open AccessTranscriptomic and proteomic signatures of stemness and differentiation in the colon crypt
Habowski et al. develop a sorting protocol for purification and comparative analysis of mouse colon stem cells and their progeny. By proteomic and transcriptomic analysis, they determine that lineage commitment is accompanied by a greater change in mRNA splicing and polyadenylation than in gene expression and they characterise signalling pathways involved in differentiation.
- Amber N. Habowski
- , Jessica L. Flesher
- , Jennifer M. Bates
- , Chia-Feng Tsai
- , Kendall Martin
- , Rui Zhao
- , Anand K. Ganesan
- , Robert A. Edwards
- , Tujin Shi
- , H. Steven Wiley
- , Yongsheng Shi
- , Klemens J. Hertel
- & Marian L. Waterman
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Author Correction
| Open AccessAuthor Correction: Detecting protein and post-translational modifications in single cells with iDentification and qUantification sEparaTion (DUET)
- Yandong Zhang
- , Changho Sohn
- , Seoyeon Lee
- , Heejeong Ahn
- , Jinyoung Seo
- , Junyue Cao
- & Long Cai
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Article
| Open AccessThermodynamic efficiency, reversibility, and degree of coupling in energy conservation by the mitochondrial respiratory chain
Wikström and Springett analyze the thermodynamic efficiency of redox reactions and proton translocation by the complexes of mitochondrial respiratory chain. They report that the thermodynamic efficiency is about 80–90% and that the degree of coupling between the redox and proton translocation reactions is very high during active ATP synthesis, but decreases when ATP synthesis stops.
- Mårten Wikström
- & Roger Springett
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Article
| Open AccessNetwork pharmacology suggests biochemical rationale for treating COVID-19 symptoms with a Traditional Chinese Medicine
Deng-hai Zhang et al. report a network pharmacology analysis of the Traditional Chinese Medicine (TCM) lung-cleaning and toxicity-excluding (LCTE) soup. By exploring the chemical compounds that make up LCTE and the likely pathways and proteins that they target, the authors show that LCTE may have the potential to directly inhibit the SARS-CoV-2 virus and relieve inflammatory symptoms.
- Deng-hai Zhang
- , Xue Zhang
- , Bin Peng
- , Sheng-qiong Deng
- , Yu-fang Wang
- , Lin Yang
- , Kai-zheng Zhang
- , Chang-quan Ling
- & Kun-lun Wu
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Article
| Open Access2-Nitroimidazoles induce mitochondrial stress and ferroptosis in glioma stem cells residing in a hypoxic niche
Koike et al. show that the 2-nitroimidazole doranidazole increases radiation-induced DNA damage in hypoxic glioma stem cells (GSCs). They further demonstrate that additional radiation-independent cytotoxicity of 2-nitroimidazoles is due to ferroptosis that occurs through blockade of mitochondrial complexes I and II leading to metabolic changes in the oxidative stress response.
- Naoyoshi Koike
- , Ryuichi Kota
- , Yoshiko Naito
- , Noriyo Hayakawa
- , Tomomi Matsuura
- , Takako Hishiki
- , Nobuyuki Onishi
- , Junichi Fukada
- , Makoto Suematsu
- , Naoyuki Shigematsu
- , Hideyuki Saya
- & Oltea Sampetrean
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Article
| Open AccessFAM46C/TENT5C functions as a tumor suppressor through inhibition of Plk4 activity
Kazazian and colleagues identify FAM46C/TENT5C as an interactor and negative regulator of PLK4 activity in centriole duplication. The authors also find that FAM46C expression strongly reduces cancer cell invasion, uncovering a role for FAM46C as tumor suppressor.
- Karineh Kazazian
- , Yosr Haffani
- , Deanna Ng
- , Chae Min Michelle Lee
- , Wendy Johnston
- , Minji Kim
- , Roland Xu
- , Karina Pacholzyk
- , Francis Si-Wah Zih
- , Julie Tan
- , Alannah Smrke
- , Aaron Pollett
- , Hannah Sun-Tsi Wu
- & Carol Jane Swallow
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Article
| Open AccessPheromone components affect motivation and induce persistent modulation of associative learning and memory in honey bees
David Baracchi et al. show that honey bees exposed to geraniol, a component of an attractant pheromone, exhibit improved olfactory learning and memory while the opposite effect was seen in honey bees exposed to the aversive pheromone, 2- heptanone. These changes occurred through a modulation of appetitive motivation without affecting odor processing, suggesting an important role for pheromones as modulators of motivational and learning processes.
- David Baracchi
- , Amélie Cabirol
- , Jean-Marc Devaud
- , Albrecht Haase
- , Patrizia d’Ettorre
- & Martin Giurfa
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Article
| Open AccessMaximizing transcription of nucleic acids with efficient T7 promoters
Thomas Conrad et al. identify sequences downstream of transcription start sites that affect T7 promoter activity and use this to generate promoter variants with enhanced transcriptional output. They use the optimized promoters to prepare cDNA libraries for single-cell RNA sequencing with increased complexity compared to those prepared with standard T7 promoters.
- Thomas Conrad
- , Izabela Plumbom
- , Maria Alcobendas
- , Ramon Vidal
- & Sascha Sauer
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Article
| Open AccessHuman adiponectin receptor AdipoR1 assumes closed and open structures
Tanabe, Fujii, Okada-Iwabu, Iwabu et al. report the crystal structures of the D208A variant of human adiponectin receptor AdipoR1 as well as the revised structures of the wild-type AdipoR1. These structures clarify the interconversion between the open and closed states of this protein, which may be relevant to its function.
- Hiroaki Tanabe
- , Yoshifumi Fujii
- , Miki Okada-Iwabu
- , Masato Iwabu
- , Kuniyuki Kano
- , Hiroki Kawana
- , Masakatsu Hato
- , Yoshihiro Nakamura
- , Takaho Terada
- , Tomomi Kimura-Someya
- , Mikako Shirouzu
- , Yoshiaki Kawano
- , Masaki Yamamoto
- , Junken Aoki
- , Toshimasa Yamauchi
- , Takashi Kadowaki
- & Shigeyuki Yokoyama
-
Article |
An essential role of acetyl coenzyme A in the catalytic cycle of insect arylalkylamine N-acetyltransferase
Wu et al. provide insight to the role of acetyl coenzyme A in regulating N-acetylation in insect AANAT using ITC and NMR methods. These results provide useful data on the structural function of insect AANATs.
- Chu-Ya Wu
- , I-Chen Hu
- , Yi-Chen Yang
- , Wei-Cheng Ding
- , Chih-Hsuan Lai
- , Yi-Zong Lee
- , Yi-Chung Liu
- , Hui-Chun Cheng
- & Ping-Chiang Lyu
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Article
| Open AccessCritical enzymes for biosynthesis of cucurbitacin derivatives in watermelon and their biological significance
Kim et al. use RNAseq of two watermelons to select candidate genes coding for enzymes that catalyze modifications of cucurbitacins. They characterise four of the 16 candidate enzymes (3 different acetyltransferases and one UDP-glucosyltransferase) by HPLC, LC-MS, NMR, and in vitro enzymatic assay. They further show with in vivo assay in Drosophila, that acetylation of cucurbitacin increases neuronal activity in insects.
- Young-Cheon Kim
- , Daeun Choi
- , Ahra Cha
- , Yeong-Geun Lee
- , Nam-In Baek
- , Suman Rimal
- , Jiun Sang
- , Youngseok Lee
- & Sanghyeob Lee
-
Article
| Open AccessGenetic alterations in the 3q26.31-32 locus confer an aggressive prostate cancer phenotype
Benjamin Simpson et al. use publicly available cancer genomic data to investigate copy number changes at the 3q26.31–32 locus, which has been associated with aggressive prostate cancer based on single-nucleotide polymorphisms. They find that gains of NAALADL2 and TBL1XR1 in this locus are associated with more aggressive subtypes of prostate cancer and the transcription of pro-proliferative signalling processes.
- Benjamin S. Simpson
- , Niedzica Camacho
- , Hayley J. Luxton
- , Hayley Pye
- , Ron Finn
- , Susan Heavey
- , Jason Pitt
- , Caroline M. Moore
- & Hayley C. Whitaker
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Article
| Open AccessBiohydrogen production beyond the Thauer limit by precision design of artificial microbial consortia
Ergal et al. report that biohydrogen production from glucose by an engineered microbial consortium of Clostridium acetobutylicum and Enterobacter aerogenes can be 40% higher than the “Thauer limit”. They further show that the volumetric H2 production rates of their system are superior compared to any mono-, co- or multi-culture system reported to date.
- İpek Ergal
- , Oliver Gräf
- , Benedikt Hasibar
- , Michael Steiner
- , Sonja Vukotić
- , Günther Bochmann
- , Werner Fuchs
- & Simon K.-M. R. Rittmann
-
Article
| Open AccessSpatial patterns of microbial communities across surface waters of the Great Barrier Reef
Pedro R. Frade et al. analyze published bacterial data and environmental data from the eReefs platform to study bacterioplankton community dynamics across the Great Barrier Reef. They identify communities within inshore and outershelf reefs that are susceptible to nutrient and temperature changes, highlighting the importance of understanding microbial ecosystems dynamics informing reef health.
- Pedro R. Frade
- , Bettina Glasl
- , Samuel A. Matthews
- , Camille Mellin
- , Ester A. Serrão
- , Kennedy Wolfe
- , Peter J. Mumby
- , Nicole S. Webster
- & David G. Bourne
-
Article
| Open AccessStructure of phospholipase Cε reveals an integrated RA1 domain and previously unidentified regulatory elements
Rugema, Garland-Kuntz et al. report the 2.7 Å crystal structure of a fragment of a catalytically active PLCε in which the RA1 domain is integrated into the core. They find that a conserved amphipathic helix in the autoregulatory X–Y linker of PLCε modulates its catalytic activity in cells. This study provides structural insights into the regulation of this essential cardiovascular enzyme.
- Ngango Y. Rugema
- , Elisabeth E. Garland-Kuntz
- , Monita Sieng
- , Kaushik Muralidharan
- , Michelle M. Van Camp
- , Hannah O’Neill
- , William Mbongo
- , Arielle F. Selvia
- , Andrea T. Marti
- , Amanda Everly
- , Emmanda McKenzie
- & Angeline M. Lyon
-
Article
| Open AccessChemically induced mutations in a MutaMouse reporter gene inform mechanisms underlying human cancer mutational signatures
Marc A. Beal, Matt J. Meier et al. use a transgenic rodent model with NGS to inform mutational signature analyses. They analyze lacZ mutations from the bone marrow of MutaMouse animals exposed to chemical mutagens. They report that lacZ sequencing generates chemical-specific mutation signatures observed in human cancers with established environmental causes.
- Marc A. Beal
- , Matthew J. Meier
- , Danielle P. LeBlanc
- , Clotilde Maurice
- , Jason M. O’Brien
- , Carole L. Yauk
- & Francesco Marchetti
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Article
| Open AccessOxytocin facilitates valence-dependent valuation of social evaluation of the self
Danyang Wang and Yina Ma measure the amount of money participants are willing to forgo for the opportunity to access social or non-social evaluations of the self. They show that subjective values on knowing social evaluation is valence-dependent whereas that on non-social evaluation is valence-insensitive. Moreover, oxytocin contributes to valence-dependent valuation on social evaluation.
- Danyang Wang
- & Yina Ma
-
Article
| Open AccessLionheart LincRNA alleviates cardiac systolic dysfunction under pressure overload
Kuwabara et al. identify a novel long intergenic noncoding RNA (lincRNA), termed Lionheart, upregulated in pressure overloaded hearts in mice. Deleting this gene results in decreased systolic function and reduction in MYH6 protein levels following pressure overload. They demonstrate that Lionheart interacts with PURA, preventing its binding to the promoter region of Myh6 locus, leading to reduced MYH6 protein expression.
- Yasuhide Kuwabara
- , Shuhei Tsuji
- , Masataka Nishiga
- , Masayasu Izuhara
- , Shinji Ito
- , Kazuya Nagao
- , Takahiro Horie
- , Shin Watanabe
- , Satoshi Koyama
- , Hisanori Kiryu
- , Yasuhiro Nakashima
- , Osamu Baba
- , Tetsushi Nakao
- , Tomohiro Nishino
- , Naoya Sowa
- , Yui Miyasaka
- , Takeshi Hatani
- , Yuya Ide
- , Fumiko Nakazeki
- , Masahiro Kimura
- , Yoshinori Yoshida
- , Tsukasa Inada
- , Takeshi Kimura
- & Koh Ono
-
Article
| Open AccessEngineering combinatorial and dynamic decoders using synthetic immediate-early genes
Ravindran et al. report the construction of synthetic immediate-early genes (SynIEGs), target genes of the Erk signaling pathway. SynIEGs implement user-defined regulation while tracking transcription and translation. This study underscores post-transcriptional regulation in signal decoding that may be masked by analyses of RNA abundance alone.
- Pavithran T. Ravindran
- , Maxwell Z. Wilson
- , Siddhartha G. Jena
- & Jared E. Toettcher
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Article
| Open AccessTrodusquemine displaces protein misfolded oligomers from cell membranes and abrogates their cytotoxicity through a generic mechanism
Limbocker et al. show that trodusquemine, an aminosterol, reduces the cytotoxicity of protein misfolded oligomers by displacing them from cell membranes in the absence of any overt structural/ morphological changes in them. This mechanism appears to be general, as they test it for oligomers of αS, Aβ and the model protein HypF-N to human neuroblastoma cells.
- Ryan Limbocker
- , Benedetta Mannini
- , Francesco S. Ruggeri
- , Roberta Cascella
- , Catherine K. Xu
- , Michele Perni
- , Sean Chia
- , Serene W. Chen
- , Johnny Habchi
- , Alessandra Bigi
- , Ryan P. Kreiser
- , Aidan K. Wright
- , J. Alex Albright
- , Tadas Kartanas
- , Janet R. Kumita
- , Nunilo Cremades
- , Michael Zasloff
- , Cristina Cecchi
- , Tuomas P. J. Knowles
- , Fabrizio Chiti
- , Michele Vendruscolo
- & Christopher M. Dobson
-
Article
| Open AccessComparative genomics of muskmelon reveals a potential role for retrotransposons in the modification of gene expression
Ryoichi Yano et al. report a Nanopore-based reference genome assembly of muskmelon—a fruit known for its many cultivated varieties, including cantaloupe and honeydew—using the Japanese Harukei-3 cultivar. They identify structural genetic variation by comparing the reference to several melon genome assemblies and investigate tissue-wide gene expression patterns by RNA sequencing.
- Ryoichi Yano
- , Tohru Ariizumi
- , Satoko Nonaka
- , Yoichi Kawazu
- , Silin Zhong
- , Lukas Mueller
- , James J. Giovannoni
- , Jocelyn K. C. Rose
- & Hiroshi Ezura
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Author Correction
| Open AccessAuthor Correction: Diethylcarbamazine activates TRP channels including TRP-2 in filaria, Brugia malayi
- Saurabh Verma
- , Sudhanva S. Kashyap
- , Alan P. Robertson
- & Richard J. Martin
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Article
| Open AccessThe Rnf complex is a Na+ coupled respiratory enzyme in a fermenting bacterium, Thermotoga maritima
From a fermenting bacterium, Thermotoga maritima, Kuhns, Trifunovi ć et al. purify a complex that includes a respiratory enzyme, Rnf. They find that the Rnf complex requires Na+ for activity and that it catalyzes Na+ transport in liposomes. This study shows that the Rnf complex is indeed an ion translocating, respiratory enzyme.
- Martin Kuhns
- , Dragan Trifunović
- , Harald Huber
- & Volker Müller
-
Article
| Open AccessArtificial eyespots on cattle reduce predation by large carnivores
Radford et al. monitored cattle marked with artificial eyespots in non-commercial cattle farms in northern Botswana, and demonstrate that cattle with these eyespot markings were more likely to avoid predation by large carnivores. Their findings have applications as a cost-effective tool to reduce livestock predation by ambush predators.
- Cameron Radford
- , John Weldon McNutt
- , Tracey Rogers
- , Ben Maslen
- & Neil Jordan
-
Article
| Open AccessSingle-cell analysis of EphA clustering phenotypes to probe cancer cell heterogeneity
Ravasio et al. develop an assay to quantify the clustering of Eph receptor EphA2 upon ligand binding, based on the scoring of single cells. They discover that clustering phenotype predicts cell and population migration potential in cancer cells and reflects Eph associated gene expression profiles in cancer cell lines.
- Andrea Ravasio
- , Myint Z. Myaing
- , Shumei Chia
- , Aditya Arora
- , Aneesh Sathe
- , Elaine Yiqun Cao
- , Cristina Bertocchi
- , Ankur Sharma
- , Bakya Arasi
- , Vin Yee Chung
- , Adrianne C. Green
- , Tuan Zea Tan
- , Zhongwen Chen
- , Hui Ting Ong
- , N. Gopalakrishna Iyer
- , Ruby YunJu Huang
- , Ramanuj DasGupta
- , Jay T. Groves
- & Virgile Viasnoff
-
Article
| Open AccessImprovement of CRISPR/Cas9 system by transfecting Cas9-expressing Plasmodium berghei with linear donor template
Shinzawa et al. develop a method that improves the transfection efficiency for Plasmodium parasites that cause malaria by transfecting Cas9-expressing parasites with linear donor templates. This method allows efficient integration of the donor template while preventing unexpected recombination.
- Naoaki Shinzawa
- , Tsubasa Nishi
- , Fumiya Hiyoshi
- , Daisuke Motooka
- , Masao Yuda
- & Shiroh Iwanaga
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Article
| Open AccessThe rare sugar d-tagatose protects plants from downy mildews and is a safe fungicidal agrochemical
Mochizuki, Fukumoto, Ohara, et al. study the protective role of the rare sugar d-tagatose against plant disease. They focus on its effects against the downy mildews and delineate the metabolic pathway that blocks the initial infection. Their work paves the way for the development of safe fungicidal agrochemicals using natural products.
- Susumu Mochizuki
- , Takeshi Fukumoto
- , Toshiaki Ohara
- , Kouhei Ohtani
- , Akihide Yoshihara
- , Yoshio Shigematsu
- , Keiji Tanaka
- , Koichi Ebihara
- , Shigeyuki Tajima
- , Kenji Gomi
- , Kazuya Ichimura
- , Ken Izumori
- & Kazuya Akimitsu
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Article
| Open AccessPRMT5 promotes DNA repair through methylation of 53BP1 and is regulated by Src-mediated phosphorylation
Hwang et al. show that the activity of PRMT5 methyltransferase is regulated by Src kinase-mediated phosphorylation at Y324 in response to DNA damage. They also show that PRMT5 participates in NHEJ repair by regulating 53BP1 protein levels and is critical for cellular survival after DNA damage.
- Jee Won Hwang
- , Su-Nam Kim
- , Nayeon Myung
- , Doona Song
- , Gyoonhee Han
- , Gyu-Un Bae
- , Mark T. Bedford
- & Yong Kee Kim
-
Article
| Open AccessGenetically detoxified pertussis toxin displays near identical structure to its wild-type and exhibits robust immunogenicity
Ausar et al. show that the crystal structure of gdPT, a mutant pertussis toxin (PTx), is nearly identical to that of PTx. They also find that gdPT exhibits broader immunogenicity than the pertussis toxoid antigen. This study suggests a promising potential of gdPT as an improved acellular pertussis vaccine candidate due to its reduced toxicity and greater immunogenicity.
- Salvador F. Ausar
- , Shaolong Zhu
- , Jessica Duprez
- , Michael Cohen
- , Thomas Bertrand
- , Valérie Steier
- , Derek J. Wilson
- , Stephen Li
- , Anthony Sheung
- , Roger H. Brookes
- , Artur Pedyczak
- , Alexey Rak
- & D. Andrew James
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Article
| Open AccessGenomic analyses of a livestock pest, the New World screwworm, find potential targets for genetic control programs
Maxwell Scott et al. report the genome of the New World screwworm, a devastating livestock pest in South America and the Caribbean. Using transcriptomic analysis of the insect’s developmental stages combined with genomic analyses, the authors identify genes that may be important for its parasitic lifestyle.
- Maxwell J. Scott
- , Joshua B. Benoit
- , Rebecca J. Davis
- , Samuel T. Bailey
- , Virag Varga
- , Ellen O. Martinson
- , Paul V. Hickner
- , Zainulabeuddin Syed
- , Gisele A. Cardoso
- , Tatiana T. Torres
- , Matthew T. Weirauch
- , Elizabeth H. Scholl
- , Adam M. Phillippy
- , Agustin Sagel
- , Mario Vasquez
- , Gladys Quintero
- & Steven R. Skoda
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Article
| Open AccessQuantitative analysis of heparan sulfate using isotopically labeled calibrants
Wang et al. describe a strategy for quantitatively performing composition analysis of heparan sulfate using 13C-labeled disaccharides and polysaccharides that mimic the glycosaminoglycan chemical structure. They further show that these isotopically labelled small molecules can be used as internal standards for mass spectrometry analysis of heparan sulfate derived from mouse tissue and plasma.
- Zhangjie Wang
- , Katelyn Arnold
- , Yongmei Xu
- , Vijayakanth Pagadala
- , Guowei Su
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| Open AccessDetecting protein and post-translational modifications in single cells with iDentification and qUantification sEparaTion (DUET)
Yandong Zhang, et al. develop iDentification and qUantification sEparaTion (DUET) to quantify target protein and its post-translational modification isoforms in single cells. Using their method, they report heterogeneities in the ubiquitination levels of histone H2B in single yeast cells and reveal the cell-cycle dynamics of H2B monoubiquitination.
- Yandong Zhang
- , Changho Sohn
- , Seoyeon Lee
- , Heejeong Ahn
- , Jinyoung Seo
- , Junyue Cao
- & Long Cai
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Article
| Open AccessLigand-bound glutamine binding protein assumes multiple metastable binding sites with different binding affinities
Zhang, Wu, Feng et al. show that ligand-bound glutamine binding protein assumes multiple metastable binding sites, presenting a more dynamic energy landscape than its ligand-free form. This study provides insights into the ligand-binding mechanisms coupled with protein dynamics that underly the apparent binding affinity.
- Lu Zhang
- , Shaowen Wu
- , Yitao Feng
- , Dan Wang
- , Xilin Jia
- , Zhijun Liu
- , Jianwei Liu
- & Wenning Wang
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Article
| Open AccessMolecular basis of the lipid-induced MucA-MucB dissociation in Pseudomonas aeruginosa
Tao Li et al. report crystal structure of MucA-MucB complex and identify a cavity region of MucB that binds PEG molecule. They further show that this hydrophobic cavity of MucB is a primary site for sensing lipid molecules and that lipid A stimulates MucB to release MucA for AlgW cleavage, helping to understand the regulation mechanism of alginate biosynthesis.
- Tao Li
- , Lihui He
- , Changcheng Li
- , Mei Kang
- , Yingjie Song
- , Yibo Zhu
- , Yalin Shen
- , Ninglin Zhao
- , Chang Zhao
- , Jing Yang
- , Qin Huang
- , Xingyu Mou
- , Aiping Tong
- , Jinliang Yang
- , Zhenling Wang
- , Chengjie Ji
- , Hong Li
- , Hong Tang
- & Rui Bao
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Article
| Open AccessMutational signature SBS8 predominantly arises due to late replication errors in cancer
Vinod Kumar Singh, Arnav Rastogi, et al. study etiology of mutational signature 8 (SBS8) in human cancers. They develop genome-wide composite epigenomic context maps related to mutagenesis and DNA repair. They report that SBS8 preferentially occurs in heterochromatin and likely arises from late replication errors during cancer progression.
- Vinod Kumar Singh
- , Arnav Rastogi
- , Xiaoju Hu
- , Yaqun Wang
- & Subhajyoti De
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Article
| Open AccessMethylResolver—a method for deconvoluting bulk DNA methylation profiles into known and unknown cell contents
Douglas Arneson et al. develop MethylResolver that enables the deconvolution of cellular fractions from bulk DNA methylation data. Using this method, the authors resolve tumor purity-scaled immune cell-type fractions without requiring cancer-specific signatures and identify cellular fractions as prognostic factors of multiple human cancers.
- Douglas Arneson
- , Xia Yang
- & Kai Wang
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Article
| Open AccessA mixed culture of bacterial cells enables an economic DNA storage on a large scale
Hao, Qiao, Gao et al. show that over ten thousand oligonucleotides encoding 445 KB of digital data can be stored in cultured bacterial cells. Data storage in living cells increases the information storage capacity while enabling its economical propagation.
- Min Hao
- , Hongyan Qiao
- , Yanmin Gao
- , Zhaoguan Wang
- , Xin Qiao
- , Xin Chen
- & Hao Qi