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Article
| Open AccessOrganochlorinated pesticides expedite the enzymatic degradation of DNA
Chao Qin, Bing Yang et al. show that organochlorinated pesticides as environmentally persistent organic contaminants enhance the degradation of extracellular DNA by making it more accessible to DNase I. This study provides insight into the persistence of DNA in contaminated environments.
- Chao Qin
- , Bing Yang
- , Wei Zhang
- , Wanting Ling
- , Cun Liu
- , Juan Liu
- , Xu Li
- & Yanzheng Gao
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Article
| Open Access90Y-NM600 targeted radionuclide therapy induces immunologic memory in syngeneic models of T-cell Non-Hodgkin’s Lymphoma
Hernandez et al. show the effectiveness of 90Y for targeted radionucleotide therapy of T-cell Non-Hodgkin’s Lymphoma (NHL). This study suggests that delivering radiation to all NHL disease sites elicits minimal toxicity and induces a memory T-cell response, inviting combination therapies with immune activating agents.
- Reinier Hernandez
- , Kirsti L. Walker
- , Joseph J. Grudzinski
- , Eduardo Aluicio-Sarduy
- , Ravi Patel
- , Christopher D. Zahm
- , Anatoly N. Pinchuk
- , Christopher F. Massey
- , Ariana N. Bitton
- , Ryan J. Brown
- , Paul M. Sondel
- , Zachary S. Morris
- , Jonathan W. Engle
- , Christian M. Capitini
- & Jamey P. Weichert
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Article
| Open AccessVascular RAGE transports oxytocin into the brain to elicit its maternal bonding behaviour in mice
Yasuhiko Yamamoto et al. show that oxytocin is transported into the brain by the receptor for advanced glycation end-products (RAGE) on the blood-brain barrier. This study explains how circulating oxytocin crosses the blood-brain barrier, which is important to manifest oxytocin’s maternal bonding effects.
- Yasuhiko Yamamoto
- , Mingkun Liang
- , Seiichi Munesue
- , Kisaburo Deguchi
- , Ai Harashima
- , Kazumi Furuhara
- , Teruko Yuhi
- , Jing Zhong
- , Shirin Akther
- , Hisanori Goto
- , Yuya Eguchi
- , Yasuko Kitao
- , Osamu Hori
- , Yoshitake Shiraishi
- , Noriyuki Ozaki
- , Yu Shimizu
- , Tomoya Kamide
- , Akifumi Yoshikawa
- , Yasuhiko Hayashi
- , Mitsutoshi Nakada
- , Olga Lopatina
- , Maria Gerasimenko
- , Yulia Komleva
- , Natalia Malinovskaya
- , Alla B. Salmina
- , Masahide Asano
- , Katsuhiko Nishimori
- , Steven E. Shoelson
- , Hiroshi Yamamoto
- & Haruhiro Higashida
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Article
| Open AccessRisk prediction models for dementia constructed by supervised principal component analysis using miRNA expression data
Daichi Shigemizu et al. developed a risk prediction model using potential miRNA biomarkers of different dementias identified by a supervised principal component analysis logistic regression method. Their models achieved high accuracy when tested on a validation cohort and demonstrate the potential application of miRNA-based risk prediction models.
- Daichi Shigemizu
- , Shintaro Akiyama
- , Yuya Asanomi
- , Keith A. Boroevich
- , Alok Sharma
- , Tatsuhiko Tsunoda
- , Kana Matsukuma
- , Makiko Ichikawa
- , Hiroko Sudo
- , Satoko Takizawa
- , Takashi Sakurai
- , Kouichi Ozaki
- , Takahiro Ochiya
- & Shumpei Niida
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Article
| Open AccessA simple high-throughput approach identifies actionable drug sensitivities in patient-derived tumor organoids
Nhan Phan et al. present a high-throughput approach to screen tumor organoids by seeding cells in mini-rings. They apply their method to cell lines and patient-derived tumor organoids representing four different cancers, and identified personalized responses for each organoid within a clinically relevant timeline.
- Nhan Phan
- , Jenny J. Hong
- , Bobby Tofig
- , Matthew Mapua
- , David Elashoff
- , Neda A. Moatamed
- , Jin Huang
- , Sanaz Memarzadeh
- , Robert Damoiseaux
- & Alice Soragni
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Article
| Open AccessCoupling of a viral K+-channel with a glutamate-binding-domain highlights the modular design of ionotropic glutamate-receptors
Michael Schönrock et al. created a functional chimeric channel composed of the pore domain of the potassium channel, KcvATCV-1, and the glutamate binding domain of the mammalian ionotropic glutamate receptor, GluA1. This chimera recognized glutamate as a ligand while displaying the potassium selectivity of KcvATCV-1; highlighting the modular design of ionotropic glutamate receptors.
- Michael Schönrock
- , Gerhard Thiel
- & Bodo Laube
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Article
| Open AccessSolid immersion microscopy images cells under cryogenic conditions with 12 nm resolution
Lin Wang et al. present a new super-resolution modality using a super-hemispherical immersion lens. They achieve a 12 nm spatial resolution in cells under cryogenic conditions, which offers the technical means to study bacterial and mammalian cell samples at molecule localisation length-scales.
- Lin Wang
- , Benji Bateman
- , Laura C. Zanetti-Domingues
- , Amy N. Moores
- , Sam Astbury
- , Christopher Spindloe
- , Michele C. Darrow
- , Maria Romano
- , Sarah R. Needham
- , Konstantinos Beis
- , Daniel J. Rolfe
- , David T. Clarke
- & Marisa L. Martin-Fernandez
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Article
| Open AccessDiminutive fleet-footed tyrannosauroid narrows the 70-million-year gap in the North American fossil record
Lindsay Zanno et al. report the discovery of a new tyrannosaur that helps to fill in a 70 million year gap in the fossil record. This new species reveals that the earliest North American tyrannosaurs relied on speed and small body size to survive and that apex predator status and large body sizes were not reached until much later in their evolutionary history.
- Lindsay E. Zanno
- , Ryan T. Tucker
- , Aurore Canoville
- , Haviv M. Avrahami
- , Terry A. Gates
- & Peter J. Makovicky
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Article
| Open AccessMG53 promotes corneal wound healing and mitigates fibrotic remodeling in rodents
Heather Chandler, Tao Tan, Chunlin Yang et al. find that the cell membrane repair protein MG53 plays a key role in repairing cornea injury. Using mouse and rat models, they show that recombinant human MG53 protects the cornea against injury and enhances healing.
- Heather L. Chandler
- , Tao Tan
- , Chunlin Yang
- , Anne J. Gemensky-Metzler
- , Rita F. Wehrman
- , Qiwei Jiang
- , Cornelia M. W. Peterson
- , Bingchuan Geng
- , Xinyu Zhou
- , Qiang Wang
- , Denis Kaili
- , T. M. Ayodele Adesanya
- , Frank Yi
- , Hua Zhu
- & Jianjie Ma
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Article
| Open AccessThe atomic structures of shrimp nodaviruses reveal new dimeric spike structures and particle polymorphism
Nai-Chi Chen et al. solved the structures of two shrimp nodaviruses, focusing on the major domains to improve understanding of capsid organization. By combining cryo-EM and x-ray crystallography, the authors were able to observe the structures at a high resolution.
- Nai-Chi Chen
- , Masato Yoshimura
- , Naoyuki Miyazaki
- , Hong-Hsiang Guan
- , Phimonphan Chuankhayan
- , Chien-Chih Lin
- , Shao-Kang Chen
- , Pei-Ju Lin
- , Yen-Chieh Huang
- , Kenji Iwasaki
- , Atsushi Nakagawa
- , Sunney I. Chan
- & Chun-Jung Chen
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Article
| Open AccessYoung bone marrow transplantation preserves learning and memory in old mice
Melanie Das et al. demonstrate that transplantation of young bone marrow preserves the cognitive function of old recipient mice. This study suggests that microglial rejuvenation via peripheral manipulation of the hematopoietic system may be sufficient to delay a cognitive decline during aging.
- Melanie M. Das
- , Marlesa Godoy
- , Shuang Chen
- , V. Alexandra Moser
- , Pablo Avalos
- , Kristina M. Roxas
- , Ivy Dang
- , Alberto Yáñez
- , Wenxuan Zhang
- , Catherine Bresee
- , Moshe Arditi
- , George Y. Liu
- , Clive N. Svendsen
- & Helen S. Goodridge
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Article
| Open AccessA large CRISPR-induced bystander mutation causes immune dysregulation
Dimitre Simeonov, Alexander Brandt et al. report a pathogenic bystander mutation caused by unintended repair of a CRISPR-Cas9-mediated deletion in mice. They generate mice lacking an IL2RA intronic enhancer previously associated with human disease risk and find that one line of edited mice show unexpected disease features due to a bystander mutation.
- Dimitre R. Simeonov
- , Alexander J. Brandt
- , Alice Y. Chan
- , Jessica T. Cortez
- , Zhongmei Li
- , Jonathan M. Woo
- , Youjin Lee
- , Claudia M. B. Carvalho
- , Alyssa C. Indart
- , Theodore L. Roth
- , James Zou
- , Andrew P. May
- , James R. Lupski
- , Mark S. Anderson
- , F. William Buaas
- , Daniel S. Rokhsar
- & Alexander Marson
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Article
| Open AccessMimicry in viceroy butterflies is dependent on abundance of the model queen butterfly
Kathleen Prudic et al. examine the persistence of mimicry in viceroy butterflies in locations with low model abundance. They show that when queen butterflies are less abundant, viceroy butterflies become more abundant, but also increase their chemical defenses to gain protection from predation.
- Kathleen L. Prudic
- , Barbara N. Timmermann
- , Daniel R. Papaj
- , David B. Ritland
- & Jeffrey C. Oliver
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Article
| Open AccessQuantitative intrinsic auto-cathodoluminescence can resolve spectral signatures of tissue-isolated collagen extracellular matrix
Zielinski et al. show that quantitative label-free cathodoluminescence-scanning electron microscopy differentiates spectral signatures of two extracellular matrices. This method can monitor the progress of a smooth muscle cell-mediated remodeling process without using antibodies to enhance the optical signal.
- Marcin S. Zielinski
- , Elif Vardar
- , Ganesh Vythilingam
- , Eva-Maria Engelhardt
- , Jeffrey A. Hubbell
- , Peter Frey
- & Hans M. Larsson
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Article
| Open AccessMembrane charge and lipid packing determine polymyxin-induced membrane damage
Adree Khondker et al. identify new mechanisms by which the membrane surface and lipid packing in the bacterial membrane control the penetration of antibiotics such as of polymyxin B. These findings indicate that biophysical factors might influence the resistance strength of bacteria to antibiotics.
- Adree Khondker
- , Alexander K. Dhaliwal
- , Sokunthearath Saem
- , Ahmad Mahmood
- , Cécile Fradin
- , Jose Moran-Mirabal
- & Maikel C. Rheinstädter
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Article
| Open AccessOxylipins mediate cell-to-cell communication in Pseudomonas aeruginosa
Eriel Martínez et al. report that the bacterial pathogen Pseudomonas aeruginosa can convert oleic acids into oxylipins for use in cell-cell communication. This quorum sensing system is regulated by the bacterial protein called oxylipin-dependent diol synthase regulator OdsR.
- Eriel Martínez
- , Rachael K. Cosnahan
- , Mousheng Wu
- , Shiva. K. Gadila
- , Eric B. Quick
- , James A. Mobley
- & Javier Campos-Gómez
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Article
| Open AccessNematodes in a polar desert reveal the relative role of biotic interactions in the coexistence of soil animals
Tancredi Caruso et al. analyze biodiversity survey data from the McMurdo Dry Valleys, an extreme desert ecosystem in Antarctica in which abiotic factors are thought to determine species distributions. Focusing on three nematode species, they find that abiotic factors alone cannot explain the data and interaction between species have been historically underestimated.
- Tancredi Caruso
- , Ian D. Hogg
- , Uffe N. Nielsen
- , Eric M. Bottos
- , Charles K. Lee
- , David W. Hopkins
- , S. Craig Cary
- , John E. Barrett
- , T. G. Allan Green
- , Bryan C. Storey
- , Diana H. Wall
- & Byron J. Adams
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Article
| Open AccessScreening and identification of a non-peptide antagonist for the peptide hormone receptor in Arabidopsis
Hidefumi Shinohara and colleagues used the CLE9-BAM1 ligand-receptor pair as a model system for screening peptide hormone receptor-binding small molecules in plants. They identified the small molecule NPD12704 as an antagonist for BAM1 and demonstrated the specific regulatory activity of NPD12704 in shoot apical meristem.
- Hidefumi Shinohara
- , Naoko Yasue
- , Tetsuo Onuki
- , Yasumitsu Kondoh
- , Minoru Yoshida
- & Yoshikatsu Matsubayashi
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Article
| Open AccessNapM enhances the survival of Mycobacterium tuberculosis under stress and in macrophages
Yu Liu, Zhiwei Xie et al. show that nucleoid-associated protein NapM enhances the survival of M. tuberculosis in macrophages under stress by inhibiting DNA synthesis as a DnaA antagonist. This study suggests NapM as a potential drug target for tuberculosis control.
- Yu Liu
- , Zhiwei Xie
- , Xiling Zhou
- , Weihui Li
- , Hua Zhang
- & Zheng-Guo He
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Article
| Open AccessBiotic interactions are an unexpected yet critical control on the complexity of an abiotically driven polar ecosystem
Charles Lee, Daniel Laughlin et al. use structural equation modeling to analyze ecological data from more than 500 sites in the Antarctic Dry Valleys. They find that although abiotic factors are the primary drivers of biodiversity variation, biotic interactions are needed to explain the data fully and may play previously underestimated roles.
- Charles K. Lee
- , Daniel C. Laughlin
- , Eric M. Bottos
- , Tancredi Caruso
- , Kurt Joy
- , John E. Barrett
- , Lars Brabyn
- , Uffe N. Nielsen
- , Byron J. Adams
- , Diana H. Wall
- , David W. Hopkins
- , Stephen B. Pointing
- , Ian R. McDonald
- , Don A. Cowan
- , Jonathan C. Banks
- , Glen A. Stichbury
- , Irfon Jones
- , Peyman Zawar-Reza
- , Marwan Katurji
- , Ian D. Hogg
- , Ashley D. Sparrow
- , Bryan C. Storey
- , T. G. Allan Green
- & S. Craig Cary
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Article
| Open AccessCaMello-XR enables visualization and optogenetic control of Gq/11 signals and receptor trafficking in GPCR-specific domains
Dennis Eickelbeck et al. engineered light-activated constructs, CaMello and CaMello-5HT2A, which are targeted to the 5HT2A-R domains and enable visualization of calcium signals and receptor trafficking in response to activation. The reported CaMello tool could be applied to other GPCRs coupled to the Gq/11 signaling pathways which may shed light on mechanisms of GPCR localization and plasticity.
- Dennis Eickelbeck
- , Raziye Karapinar
- , Alexander Jack
- , Sandra T. Suess
- , Ruxandra Barzan
- , Zohre Azimi
- , Tatjana Surdin
- , Michelle Grömmke
- , Melanie D. Mark
- , Klaus Gerwert
- , Dirk Jancke
- , Petra Wahle
- , Katharina Spoida
- & Stefan Herlitze
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Article
| Open AccessEndogenous pore-forming protein complex targets acidic glycosphingolipids in lipid rafts to initiate endolysosome regulation
Guo et al. identify the role of acidic glycosphingolipids as the mechanism of action of the pore-forming protein complex βγ-CAT from the frog. This study suggests that βγ-CAT binds to both gangliosides and sulfatides, initiating its endocytosis and ultimately exerting its antimicrobial effects.
- Xiao-Long Guo
- , Ling-Zhen Liu
- , Qi-Quan Wang
- , Jin-Yang Liang
- , Wen-Hui Lee
- , Yang Xiang
- , Sheng-An Li
- & Yun Zhang
-
Article
| Open AccessPeptidyl prolyl cis/trans isomerase activity on the cell surface correlates with extracellular matrix development
Weilin Lin et al. report a new assay for measuring the activity of peptidyl prolyl cis/trans isomerase (PPIase) at the cell surface using ultra performance liquid chromatography. They find that PPIase activity correlates with development and functional properties of the extracellular matrix in primary healthy and leukemic cells.
- Weilin Lin
- , Malte Bonin
- , Annett Boden
- , Robert Wieduwild
- , Priyanka Murawala
- , Martin Wermke
- , Helena Andrade
- , Martin Bornhäuser
- & Yixin Zhang
-
Article
| Open AccessExosome-mediated horizontal gene transfer occurs in double-strand break repair during genome editing
Ryuichi Ono et al. show that a large number of unintentional trans-species gene transfers can occur when double-strand breaks are introduced by CRISPR-Cas9 in mouse eggs and cell lines. They propose a mechanism of trans-species horizontal gene transfer via double-strand break repair.
- Ryuichi Ono
- , Yukuto Yasuhiko
- , Ken-ichi Aisaki
- , Satoshi Kitajima
- , Jun Kanno
- & Yoko Hirabayashi
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Article
| Open AccessMechanistic insights into the evolution of DUF26-containing proteins in land plants
Aleksia Vaattovaara et al. investigate the evolutionary history of a representative protein family, the DUF26-containing proteins, which is specific to land plants. They suggest that domain duplications and rearrangement led to the protein family’s two main subclasses.
- Aleksia Vaattovaara
- , Benjamin Brandt
- , Sitaram Rajaraman
- , Omid Safronov
- , Andres Veidenberg
- , Markéta Luklová
- , Jaakko Kangasjärvi
- , Ari Löytynoja
- , Michael Hothorn
- , Jarkko Salojärvi
- & Michael Wrzaczek
-
Article
| Open AccessNeighborhood size-effects shape growing population dynamics in evolutionary public goods games
Gregory Kimmel et al. model the population dynamics of public goods games in which interactions occur within local neighborhoods but density dependence is global. They find that neighborhood size drives changes between different evolutionary dynamics and apply their model to dynamics observed in cell populations.
- Gregory J. Kimmel
- , Philip Gerlee
- , Joel S. Brown
- & Philipp M. Altrock
-
Article
| Open AccessCrystal structures of human lysosomal EPDR1 reveal homology with the superfamily of bacterial lipoprotein transporters
Yong Wei et al. present the crystal structure of the human lysosomal protein EPDR1 and reveal a role in lipid-binding. They show that the larger family of ependymin-related proteins adopt a β-sheet fold previously seen only in bacterial proteins, and that this fold is found throughout the archaea and eukaryotes.
- Yong Wei
- , Zi Jian Xiong
- , Jun Li
- , Chunxia Zou
- , Christopher W. Cairo
- , John S. Klassen
- & Gilbert G. Privé
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Article
| Open AccessRegional protein expression in human Alzheimer’s brain correlates with disease severity
Jingshu Xu et al. did a comprehensive post-mortem proteomics analysis across six brain regions obtained from Alzheimer’s disease patients and controls. With this spatial proteomics approach, they identified new disease-related pathways and a gradient of protein expression changes that correlates with the pathology of the affected regions.
- Jingshu Xu
- , Stefano Patassini
- , Nitin Rustogi
- , Isabel Riba-Garcia
- , Benjamin D. Hale
- , Alexander M Phillips
- , Henry Waldvogel
- , Robert Haines
- , Phil Bradbury
- , Adam Stevens
- , Richard L. M. Faull
- , Andrew W. Dowsey
- , Garth J. S. Cooper
- & Richard D. Unwin
-
Article
| Open AccessOn-demand serum-free media formulations for human hematopoietic cell expansion using a high dimensional search algorithm
Kim and Audet present a model-free, iterative search algorithm that optimizes serum-free formulations used to expand human hematopoietic cells. This method automatically identifies serum-free formulations that support cell expansions as effectively as the serum-containing conditions, demonstrating its utility.
- Michelle M. Kim
- & Julie Audet
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Article
| Open AccessSomatic mutation detection and classification through probabilistic integration of clonal population information
Fatemeh Dorri et al. present MuClone, a method for simultaneous detection and classification of mutations across multiple tumor samples derived from one patient. They show that clonal information improves sensitivity in detecting somatic mutations.
- Fatemeh Dorri
- , Sean Jewell
- , Alexandre Bouchard-Côté
- & Sohrab P. Shah
-
Article
| Open AccessCRISPR/Cas9 editing of endogenous banana streak virus in the B genome of Musa spp. overcomes a major challenge in banana breeding
Jaindra Tirpathi et al. report a strategy for inactivating endogenous banana streak virus sequences in the plantain B genome using CRISPR/Cas9. They show that three-quarters of edited plants had no viral symptoms under stress conditions, providing an improved B genome germplasm for plantain and banana breeding.
- Jaindra N. Tripathi
- , Valentine O. Ntui
- , Mily Ron
- , Samwel K. Muiruri
- , Anne Britt
- & Leena Tripathi
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Article
| Open AccessClostridium perfringens α-toxin impairs granulocyte colony-stimulating factor receptor-mediated granulocyte production while triggering septic shock
Takehara et al. show that Clostridium perfringens alpha-toxin impairs granulocyte colony-stimulating factor receptor-mediated granulocyte production while enhancing host inflammation. This study identifies dual mechanisms, whereby bacterial toxin simultaneously cripples and overstimulates host immunity to its demise.
- Masaya Takehara
- , Soshi Seike
- , Yuuta Sonobe
- , Hiroto Bandou
- , Saki Yokoyama
- , Teruhisa Takagishi
- , Kazuaki Miyamoto
- , Keiko Kobayashi
- & Masahiro Nagahama
-
Article
| Open AccessIdentification of 12 genetic loci associated with human healthspan
Aleksandr Zenin et al. present a genome-wide association study and genetic risk model for human healthspan, the length of morbidity-free life. They identify 12 loci associated with healthspan and osbserve genetic correlations between healthspan and life-history and lifestyle traits, such as obesity and smoking.
- Aleksandr Zenin
- , Yakov Tsepilov
- , Sodbo Sharapov
- , Evgeny Getmantsev
- , L. I. Menshikov
- , Peter O. Fedichev
- & Yurii Aulchenko
-
Article
| Open AccessA high-throughput integrated microfluidics method enables tyrosine autophosphorylation discovery
Hadas Nevenzal, Meirav Noach-Hirsh et al. present a method for direct detection and analysis of tyrosine autophosphorylation using integrated microfluidics and arrays. They show that their method can be applied to soluble and transmembrane tyrosine kinases as well as to membranes in vitro.
- Hadas Nevenzal
- , Meirav Noach-Hirsh
- , Or Skornik-Bustan
- , Lev Brio
- , Efrat Barbiro-Michaely
- , Yair Glick
- , Dorit Avrahami
- , Roxane Lahmi
- , Amit Tzur
- & Doron Gerber
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Article
| Open AccessPharmacological cholesterol depletion disturbs ciliogenesis and ciliary function in developing zebrafish
Lars Maerz et al. show that pharmacological inhibition of cholesterol synthesis in zebrafish embryos leads to organ malformations and dysfunctions in cilium formation and signaling. These findings together with alterations to the cilia transition zone suggest an important role of cholesterol in cilia biogenesis and function.
- Lars D. Maerz
- , Martin D. Burkhalter
- , Carolin Schilpp
- , Oliver H. Wittekindt
- , Manfred Frick
- & Melanie Philipp
-
Article
| Open AccessHistorical contingency and productivity effects on food-chain length
Hideyuki Doi and Helmut Hillebrand investigate how the sequence of species immigration affects food-chain length and whether the effect depends on productivity. Using a microcosm experiment including a copepod predator, ciliate species, and bacteria, they find that food chains are longest when the top predator is added last and that high productivity reduces food-chain length.
- Hideyuki Doi
- & Helmut Hillebrand
-
Article
| Open AccessA visual illusion that influences perception and action through the dorsal pathway
Cristina de la Malla et al. show that an individual with extensive lesions to the ventral visual pathway can accurately judge the velocity at which an object moves despite not being able to correctly identify the object in question. This findings support a role of the dorsal visual pathway in judging velocity irrespective of perceptual processing.
- Cristina de la Malla
- , Eli Brenner
- , Edward H. F. de Haan
- & Jeroen B. J. Smeets
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Article
| Open AccessChanges in long-range rDNA-genomic interactions associate with altered RNA polymerase II gene programs during malignant transformation
Jeannine Diesch et al. report the changes in rDNA chromatin state associated with cell transition into malignancy. They show that a specific transcription factor regulates this transition by altering rDNA chromatin, resulting in the reorganization of contacts between rDNA and the genome.
- Jeannine Diesch
- , Megan J. Bywater
- , Elaine Sanij
- , Donald P. Cameron
- , William Schierding
- , Natalie Brajanovski
- , Jinbae Son
- , Jirawas Sornkom
- , Nadine Hein
- , Maurits Evers
- , Richard B. Pearson
- , Grant A. McArthur
- , Austen R. D. Ganley
- , Justin M. O’Sullivan
- , Ross D. Hannan
- & Gretchen Poortinga
-
Article
| Open AccessAction and mechanism of the colistin resistance enzyme MCR-4
Zhang, Hou, Xu, Srinivas et al. report the mechanism of colistin resistance imparted by MCR-4, which has a distinct catalytic domain but employs a similar ping-pong catalysis mechanism to that used by the well-studied MCR-1. This study provides further insights into the bacterial resistance to colistin, the last-resort antibiotic.
- Huimin Zhang
- , Mengyun Hou
- , Yongchang Xu
- , Swaminath Srinivas
- , Man Huang
- , Lizhang Liu
- & Youjun Feng
-
Article
| Open AccessBeclin 1 regulates recycling endosome and is required for skin development in mice
Saori Noguchi et al. demonstrate the role of Beclin 1 for recycling endosome during skin development, using keratinocyte-specific Beclin 1-knockout mice. This study suggests that a key autophagy player Beclin 1 is also important for skin formation by ensuring a proper localization of integrins.
- Saori Noguchi
- , Shinya Honda
- , Tatsuya Saitoh
- , Hiroyuki Matsumura
- , Emi Nishimura
- , Shizuo Akira
- & Shigeomi Shimizu
-
Article
| Open AccessAcute tobacco smoke exposure exacerbates the inflammatory response to corneal wounds in mice via the sympathetic nervous system
Chengju Xiao et al. find that acute tobacco smoke exaggerates inflammation in recently wounded mouse corneas, thereby impairing wound repair. They show that the effect of tobacco smoke is mediated by activation of the sympathetic nervous system.
- Chengju Xiao
- , Mingjuan Wu
- , Jun Liu
- , Jianqin Gu
- , Xinwei Jiao
- , Dingli Lu
- , Jingxin He
- , Cuipei Lin
- , Yunxia Xue
- , Ting Fu
- , Hanqing Wang
- , Guang Wang
- , Xuesong Yang
- & Zhijie Li
-
Article
| Open AccessCollective cell migration of Dictyostelium without cAMP oscillations at multicellular stages
Hidenori Hashimura et al. show that cAMP-mediated signaling changes from propagating waves to a steady state at a multicellular stage of amoeba Dictyostelium discoideum. This study suggests that cAMP oscillation is not required for collective cell migration despite its importance at a unicellular stage.
- Hidenori Hashimura
- , Yusuke V. Morimoto
- , Masato Yasui
- & Masahiro Ueda
-
Article
| Open AccessA high-throughput microscopy method for single-cell analysis of event-time correlations in nanoparticle-induced cell death
Alexandra Murschhauser et al. present a high-throughput microscopy method for the analysis of single-cell longitudinal data using fluorescent markers. They apply the method to cancer cell lines exposed to cytotoxic nanoparticles and find that 58 nm PS-NH2 nanoparticles induce a lysosomal pathway and, at high doses, lead to cell death via a mitochondrial pathway.
- Alexandra Murschhauser
- , Peter J. F. Röttgermann
- , Daniel Woschée
- , Martina F. Ober
- , Yan Yan
- , Kenneth A. Dawson
- & Joachim O. Rädler
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Article
| Open AccessTranscriptomic immaturity inducible by neural hyperexcitation is shared by multiple neuropsychiatric disorders
Tomoyuki Murano et al. showed that neural hyperexcitation increases the expression of immaturity related genes. These changes in gene expression are shared among different neuropsychiatric and neurological conditions, hinting at their potential role as biomarkers.
- Tomoyuki Murano
- , Hideo Hagihara
- , Katsunori Tajinda
- , Mitsuyuki Matsumoto
- & Tsuyoshi Miyakawa
-
Article
| Open AccessThe Cdc48 unfoldase prepares well-folded protein substrates for degradation by the 26S proteasome
Michal Olszewski et al. demonstrate the collaboration of Cdc48 and the 26S proteasome in degrading ubiquitinated, well-folded proteins that lack unstructured segments. This study suggests that Cdc48 creates flexible initiation regions in compact substrates for their proteasome-mediated degradation.
- Michal M. Olszewski
- , Cameron Williams
- , Ken C. Dong
- & Andreas Martin
-
Article
| Open AccessSnRK2 protein kinases represent an ancient system in plants for adaptation to a terrestrial environment
Akihisa Shinozawa, Ryoko Otake et al. report on an ancient subclass of the SNF1-related protein kinase 2 family involved in ABA signaling, which protect moss from drought stress. They propose that this signaling module evolved in early land plants to regulate dehydration-response.
- Akihisa Shinozawa
- , Ryoko Otake
- , Daisuke Takezawa
- , Taishi Umezawa
- , Kenji Komatsu
- , Keisuke Tanaka
- , Anna Amagai
- , Shinnosuke Ishikawa
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Billing et al. clarify mechanisms ensuring reliable cytokine signaling despite variable expression and activation of signaling proteins in cells. Limited activation of signaling proteins either by feedback inhibition or low cytokine doses, and STAT3 serine phosphorylation timely orchestrate robustness and capacity of IL-6-induced signaling.
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Ming-Tsung Chung et al. report a method for estimating field metabolic rate (FMR) in teleost fishes using the isotopic composition of carbon found in inner ear structures called otoliths. They show that their method can provide accurate estimates of FMR for free-ranging wild fishes and allows for tracking FMR of individual fish over time.
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Fujisawa, Ichinose, and Dobata used simulated robot swarms to study the evolution of pheromone-guided foraging and traffic rules. Interestingly, they showed that in most cases traffic rules evolved before the foraging traits suggesting an important role for regulatory mechanisms in guiding core evolutionary adaptations.
- Ryusuke Fujisawa
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