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In vitro production of fertile sperm from murine spermatogonial stem cell lines
Recent technological advances have allowed the expansion of spermatogonial stem cellsin vitro; however, in vivo conditions are required for the full differentiation of the cells. In this study, an in vitroorgan culture system is developed that allows the differentiation of the germ cells in the laboratory.
- Takuya Sato
- , Kumiko Katagiri
- & Takehiko Ogawa
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Plasmonic substrates for multiplexed protein microarrays with femtomolar sensitivity and broad dynamic range
Protein microarrays are useful both in basic research and also in disease monitoring and diagnosis, but their dynamic range is limited. By using plasmonic gold substrates with near-infrared fluorescent enhancement, Tabakman et al. demonstrate a multiplexed protein array with improved detection limits and dynamic range.
- Scott M. Tabakman
- , Lana Lau
- & Hongjie Dai
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Smad6-specific recruitment of Smurf E3 ligases mediates TGF-β1-induced degradation of MyD88 in TLR4 signalling
Transforming growth factor-β blocks the activation of pro-inflammatory cytokines, in part by the degradation of Myd88. This study shows that smad ubiquitin regulator proteins are shown to mediate the destruction of Myd8 and are therefore required for the anti-inflammatory effects of transforming growth factor-β.
- Youn Sook Lee
- , Jin Seok Park
- & Seok Hee Park
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In-vitro derived germinal centre B cells differentially generate memory B or plasma cells in vivo
In response to antigens, B cells proliferate and form germinal centres before differentiating into memory B cells or long-lived plasma cells. Here, a culture method is used to expand B cells in vitro, with the ability to shift the fate of the cells between memory B cells and long-lived plasma cells.
- Takuya Nojima
- , Kei Haniuda
- & Daisuke Kitamura
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| Open AccessBacterial Pili exploit integrin machinery to promote immune activation and efficient blood-brain barrier penetration
Group BStreptococcuscauses meningitis in newborn infants but how the bacterium crosses the blood-brain barrier is unknown. Here, the bacterial pili adhesion molecule, PilA, is shown to bind to collagen and promote binding of the bacteria to integrins expressed on the blood-brain endothelium.
- Anirban Banerjee
- , Brandon J. Kim
- & Kelly S. Doran
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| Open AccessA segmental genomic duplication generates a functional intron
The appearance of a new intron that splits an exon without disrupting the corresponding peptide sequence is a rare event in vertebrate genomes. Hellstenet al.demonstrate that, under certain circumstances, a functional intron can be produced in a single step by segmental genomic duplication.
- Uffe Hellsten
- , Julie L. Aspden
- & Daniel S. Rokhsar
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| Open AccessBackbone rigidity and static presentation of guanidinium groups increases cellular uptake of arginine-rich cell-penetrating peptides
Cell-penetrating peptides can deliver molecular cargoes into living cells, and cross biological membranes by transduction—a non-endocytic mechanism. Here, the transduction efficiency of cyclic arginine-rich peptides is shown to be higher than that of more flexible linear peptides.
- Gisela Lättig-Tünnemann
- , Manuel Prinz
- & M. Cristina Cardoso
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| Open AccessMolecular mechanism for 3:1 subunit stoichiometry of rod cyclic nucleotide-gated ion channels
The assembly mechanisms of heteromeric ion channels are poorly understood. Using a range of techniques, Shuartet al.determine the mechanism by which rod photoreceptor cyclic nucleotide-gated channels assume a 3:1 stoichiometry of CNGA1 and CNGB1 subunits.
- Noah G. Shuart
- , Yoni Haitin
- & William N. Zagotta
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| Open AccessBlimp1 regulates the transition of neonatal to adult intestinal epithelium
Many mammals are born with an immature intestinal epithelium, which adapts to a changing diet during the weaning period. Muncanet al. show that the transcriptional repressor Blimp1is expressed in the intestine of mice at birth, and that expression is lost at the transition to the weaning stage.
- Vanesa Muncan
- , Jarom Heijmans
- & Gijs R. van den Brink
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Direct visualization of microtubules using a genetic tool to analyse radial progenitor-astrocyte continuum in brain
The development of radial progenitor cells and astroglia in the cerebral cortex depends on the microtubule cytoskeleton. Eomet al. have developed a new mouse model where the microtubules of astrocytes and radial glia cells are fluorescently tagged, facilitating the detailed study of microtubule dynamics and development in these cells.
- Tae-Yeon Eom
- , Amelia Stanco
- & E.S. Anton
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Anatomically modern Carboniferous harvestmen demonstrate early cladogenesis and stasis in Opiliones
Harvestmen — Opiliones — are an ancient and diverse arachnid group with a limited fossil record. Here, X-ray micro-tomography of fossils reveals two new Carboniferous harvestmen species, allowing a phylogenetic analysis of these Palaeozoic Opiliones, demonstrating similarities between the fossils and extant groups.
- Russell J. Garwood
- , Jason A. Dunlop
- & Mark D. Sutton
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| Open AccessA stem-group cnidarian described from the mid-Cambrian of China and its significance for cnidarian evolution
The origin of Cnidaria—coral and jellyfish—is still unsolved in the basal metazoan phylogeny. Here, a Cambrian fossil of a stem-group cnidarian,Cambroctoconus orientalisgen. et sp. nov., is found to bear octoradial symmetry, but no jelly-like mesenchyme, suggesting this evolved after octoradial symmetry.
- Tae-yoon Park
- , Jusun Woo
- & Duck K. Choi
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Article
| Open AccessActive sampling and decision making in Drosophila chemotaxis
Drosophila melanogaster larvae demonstrate chemotaxis towards odours but their navigation mechanism is poorly understood. Using computer-vision tracking, Gomez-Marinet al.show that larvae ascend odour gradients using an active sampling strategy that is analogous to sniffing in vertebrates.
- Alex Gomez-Marin
- , Greg J. Stephens
- & Matthieu Louis
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| Open AccessFreely orbiting magnetic tweezers to directly monitor changes in the twist of nucleic acids
Rotational motion and torsional strain affects DNA replication, transcription and repair. Lipfertet al. have developed a new technique that uses freely orbiting magnetic tweezers to measure equilibrium fluctuations and determine the twist of tethered nucleic acid molecules.
- Jan Lipfert
- , Matthew Wiggin
- & Nynke H. Dekker
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Discovery of lost diversity of paternal horse lineages using ancient DNA
Modern female horses are genetically diverse but male horses are relatively homogenous. Lippoldet al. sequence the Y chromosome of nine ancient horses and detect diversity in the ancestral paternal lineage, demonstrating ancient Y-chromosomal DNA sequencing can provide insights into evolution.
- Sebastian Lippold
- , Michael Knapp
- & Michael Hofreiter
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| Open AccessMesozoic retroposons reveal parrots as the closest living relatives of passerine birds
Zebra finches are passerine birds, but their phylogenetic relationship with non-passerine birds remains controversial. By examining retroposon insertion loci in avian genomes, the authors reveal that parrots are the closest relatives of passerines, which may have implications for understanding the evolution of birdsong.
- Alexander Suh
- , Martin Paus
- & Jürgen Schmitz
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| Open AccessParkinson's disease induced pluripotent stem cells with triplication of the α-synuclein locus
Pluripotent stem cells can be generated from the somatic cells of humans and are a useful model to study disease. Here, pluripotent stem cells are made from a patient with familial Parkinson's disease, and the resulting neurons exhibit elevated levels of α-synuclein, recapitulating the molecular features of the patient's disease.
- Michael J. Devine
- , Mina Ryten
- & Tilo Kunath
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SIRT6 is required for maintenance of telomere position effect in human cells
Chromatin is rendered silent by epigenetic marks when in proximity to telomeres, and, in yeast, this effect requires the histone-modifying enzyme Sir2. In this study, the human Sir2 family member SIRT6 is shown to modulate the telomere position effect in human cells.
- Ruth I. Tennen
- , Dennis J. Bua
- & Katrin F. Chua
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Critical roles for EphB and ephrin-B bidirectional signalling in retinocollicular mapping
How retinoganglion cell axons project correctly to the superior colliculus is poorly understood. Here, projections are shown to require EphB1, EphB2 and ephrin-B1 to terminate in the medial superior colliculus, while ephrin-B2 is essential for the mapping of both dorsal and ventral axons.
- Sonal Thakar
- , George Chenaux
- & Mark Henkemeyer
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| Open AccessA CLASP-modulated cell edge barrier mechanism drives cell-wide cortical microtubule organization in Arabidopsis
How microtubules are organized correctly in plant cells is not well understood. Ambroseet al. use 4D imaging and computer modelling to show that sharp cell edges induce microtubule depolymerization and that the microtubule-associated protein CLASP mitigates this process to modulate array organization.
- Chris Ambrose
- , Jun F. Allard
- & Geoffrey O. Wasteneys
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| Open AccessEditing of human KV1.1 channel mRNAs disrupts binding of the N-terminus tip at the intracellular cavity
RNA editing is important in regulating neuronal excitability, and a specific editing event has been shown to alter the permeation pathway of voltage-gate potassium channels. Gonzalezet al.find that the tip of the channel's inactivation gate makes a direct hydrophobic interaction with the edited position.
- Carlos Gonzalez
- , Angelica Lopez-Rodriguez
- & Miguel Holmgren
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Heterothermy in growing king penguins
Small endothermic animals often drop their body temperature—a process known as heterothermy—to conserve energy. This study demonstrates heterothermy in king penguin chicks (Aptenodytes patagonicus), a finding unexpected for such large birds, but which may account for the chicks’ fasting capacity of five months.
- Götz Eichhorn
- , René Groscolas
- & Yves Handrich
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The evolution of antisocial punishment in optional public goods games
Antisocial punishment, where non-cooperators punish cooperators, is a puzzling empirical phenomenon missing from most theoretical models. Here, antisocial punishment is added to an optional public goods game, revealing that evolution favours antisocial punishment and punishment does not promote cooperation.
- David G. Rand
- & Martin A. Nowak
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Insights into bird wing evolution and digit specification from polarizing region fate maps
Bird wings resemble the digits on the hands of dinosaurs, but which digit positions gave rise to those seen in modern birds is still unclear. In this work, long-term fate maps of the chick wing polarizing region are presented, supporting fossil data that birds descended from theropods that had digits 1, 2 and 3.
- Matthew Towers
- , Jason Signolet
- & Cheryll Tickle
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| Open AccessCytosine methylation regulates oviposition in the pathogenic blood fluke Schistosoma mansoni
The chronic disease schistosomiasis is caused by the blood flukeSchistosoma mansoni. By studying DNA modifications throughout the lifecycle of the pathogen, the authors identify DNA methylation as a factor in egg development and suggest that the epigenetic machinery responsible may be a therapeutic target.
- Kathrin K. Geyer
- , Carlos M. Rodríguez López
- & Karl F. Hoffmann
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| Open AccessRhythmic actomyosin-driven contractions induced by sperm entry predict mammalian embryo viability
Cytoplasmic flows—the movement of cytoplasmic material—can be detected following the fertilization of an egg by a sperm in many species. In this study, rhythmic cytoplasmic flows are shown to be induced in mice by calcium-induced cytoskeleton contractions which could be used to predict the successful outcome of fertilization.
- Anna Ajduk
- , Tagbo Ilozue
- & Magdalena Zernicka-Goetz
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Location-specific patterns of exposure to recent pre-pandemic strains of influenza A in southern China
Population demographics affect influenza transmission at large spatial scales. Here, influenza immunity is shown to vary spatially in a way unexplained by differences in demographics, suggesting that there are aspects of locations that drive influenza transmission other than individual and household risk factors.
- Justin Lessler
- , Derek A.T. Cummings
- & Steven Riley
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Delay-induced anomalous fluctuations in intracellular regulation
Direct negative feedback decreases fluctuations in homoeostatic control, but intracellular regulatory systems are indirect. Here, an analytical expression is derived to show that indirect feedback in transcription and translation leads to more fluctuations for intermediate delays but not for long delays.
- Andreas Grönlund
- , Per Lötstedt
- & Johan Elf
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Local BMP receptor activation at adherens junctions in the Drosophila germline stem cell niche
Studying the physical interaction of stem cells with their niche has previously been difficult. Using a fluorescence-based reporter, Michelet al. are able to show that bone morphogenetic protein signalling occurs between Drosophilatestes germline stem cells and their niche and is via adherens junctions.
- Marcus Michel
- , Isabel Raabe
- & Christian Bökel
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Silver hake tracks changes in Northwest Atlantic circulation
Many organisms are responding to a warming climate by shifts in spatial distribution. The poleward movement of silver hake,Merluccius bilinearis, over the last forty years is related to the position of the Gulf Stream and Atlantic meridional overturning circulation through changes in local bottom water temperature.
- Janet A. Nye
- , Terrence M. Joyce
- & Jason S. Link
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Relative comparisons of call parameters enable auditory grouping in frogs
Male túngara frogs produce overlapping mating calls, which poses a challenge for the female frog to group and assign multiple auditory signals to the correct source. Farris and Ryan shows that, like humans, the female frogs compare and group signals using the smallest relative difference in call parameters.
- Hamilton E. Farris
- & Michael J. Ryan
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Structural mechanisms of DIAP1 auto-inhibition and DIAP1-mediated inhibition of drICE
The inhibitor of apoptosis protein DIAP1 exists in an auto-inhibited conformation, but the details of its molecular interactions are poorly understood. Here, crystal structures reveal the auto-inhibition mechanism of DIAP1 and show how the active form of the protein binds to the effector caspase drICE.
- Xiaochun Li
- , Jiawei Wang
- & Yigong Shi
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Regulation of MITF stability by the USP13 deubiquitinase
MITF is a transcription factor required for melanocyte development, which is activated in some melanomas. Zhao and colleagues show that USP13 removes ubiquitin from MITF, stabilizes MITF protein levels and enhances colony formation, suggesting that USP13 may be a therapeutic target in melanoma.
- Xiansi Zhao
- , Brian Fiske
- & David E Fisher
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| Open AccessDust inputs and bacteria influence dissolved organic matter in clear alpine lakes
Dissolved organic matter, the main form of aquatic organic carbon, supports the aquatic food web and regulates light penetration in lakes. This study probes the main influences on the optical properties of dissolved organic matter in a global dataset of alpine and remote lakes revealing latitudinal trends.
- N. Mladenov
- , R. Sommaruga
- & I. Reche
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Detection of focal adhesion kinase activation at membrane microdomains by fluorescence resonance energy transfer
The focal adhesion kinase has a role in cell adhesion and migration. In this study, a fluorescent resonance energy transfer biosensor is designed to monitor focal adhesion kinase activity at membrane microdomains, revealing that the mechanisms that activate focal adhesion kinase are stimulus dependent.
- Jihye Seong
- , Mingxing Ouyang
- & Yingxiao Wang
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Outlines of the pore in open and closed conformations describe the gating mechanism of ASIC1
The pore gating mechanism of the proton-activated sodium channel ASIC1 is poorly understood. Canessaet al.study the shape of the ion pathway in the ASIC1 channel in its open and closed states, and reveal the opening, closing and desensitization mechanisms of the channel.
- Tianbo Li
- , Youshan Yang
- & Cecilia M. Canessa
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Monogamy and haplodiploidy act in synergy to promote the evolution of eusociality
Why some species have evolved to produce sterile individuals working for the benefit of others has yet to be fully explained. Now, a mathematical model of the dynamics of insect colony foundation, growth and death shows that monogamy and haplodiploidy facilitate the evolution of this societal structure.
- Lutz Fromhage
- & Hanna Kokko
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| Open AccessArabidopsis nitrate reductase activity is stimulated by the E3 SUMO ligase AtSIZ1
Posttranslational modification of proteins by small ubiquitin-related modifier is a response to stress signalling in plants. Here, theArabdiposisprotein SIZ1 is shown to cause SUMOylation of nitrate reductases 1 and 2 and to increase their activity, suggesting that SIZ1 controls nitrate uptake via SUMOylation.
- Bong Soo Park
- , Jong Tae Song
- & Hak Soo Seo
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Article
| Open AccessToxicity modelling of Plk1-targeted therapies in genetically engineered mice and cultured primary mammalian cells
Polo-like kinase 1 is a key regulator of mitosis and is a candidate for drug development to treat cancer. Here, reduced expression of polo-like kinase 1 in adult mice has a minor impact on animal physiology, suggesting that polo-like kinase 1 inhibitors may be useful in the killing of tumour cells while sparing normal cells.
- Monika Raab
- , Sven Kappel
- & Klaus Strebhardt
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Ranking stability and super-stable nodes in complex networks
Pagerank is widely used to rank web content; however, it is unknown how network topology affects its performance. The authors demonstrate that, in random networks, pagerank is sensitive to perturbations in topology, whereas scale-free networks contain a few super-stable nodes whose ranking is exceptionally stable.
- Gourab Ghoshal
- & Albert-László Barabási
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Article
| Open AccessFunctional and molecular interactions between ERK and CHK2 in diffuse large B-cell lymphoma
Chk2 is a kinase that is a potential chemotherapeutic target. Here, Chk2 and the kinase ERK are shown to functionally interact, and are elevated in expression in human diffuse B-cell lymphomas. Combinatorial inhibition of the kinases was also shown to block tumour growth in anin vivomouse model.
- Bojie Dai
- , X. Frank Zhao
- & Ronald B. Gartenhaus
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Article
| Open AccessMechanism of 150-cavity formation in influenza neuraminidase
Group-1 influenza A neuramidase proteins have a 150-cavity that can be targeted by drugs, but the 2009 H1N1 virus neuramidase is not thought to have a 150-cavity. Here, biophysical simulations show that the 2009 H1N1 neuramidase exists in solution with an open 150-cavity, which is stabilized by a salt bridge.
- Rommie E. Amaro
- , Robert V. Swift
- & Robin M. Bush
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| Open AccessCalcium modulates force sensing by the von Willebrand factor A2 domain
von Willebrand factor (VWF) multimers mediate primary adhesion and aggregation of platelets. Jakobiet al. reveal a calcium-binding site in the VWF-A2 domain, and show that calcium binding encourages folding of the protein and has a role in mechanosensing.
- Arjen J. Jakobi
- , Alireza Mashaghi
- & Eric G. Huizinga
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Chemotactic antiviral cytokines promote infectious apical entry of human adenovirus into polarized epithelial cells
Studying how pathogens enter polarized epithelial cells is important for understanding infection. Here, activation of chemokine receptors on the apical membrane of epithelial cells, is shown to engage Src family tyrosine signalling, resulting in relocation of the viral co-receptor αvβ3 to the apical membrane and adenovirus entry.
- Verena Lütschg
- , Karin Boucke
- & Urs F. Greber
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A photoconvertible fluorescent reporter to track chaperone-mediated autophagy
Soluble cytosolic proteins can be degraded in lysosomes by chaperone-mediated autophagy, however, the current method to measure this process requires isolation of lysosomes. Now, a fluorescent reporter is described that can measure this type of autophagy in intact cells.
- Hiroshi Koga
- , Marta Martinez-Vicente
- & Ana Maria Cuervo
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| Open AccessRegenerative capacity in newts is not altered by repeated regeneration and ageing
Tissue regeneration is of great interest; however the number of times a given tissue can regenerate is unknown. Now, Eguchiet al. demonstrate that the lens of the Japanese newt—Cynops pyrrhogaster—can regenerate 18 times over a 16-year period, and that the new lenses are similar to those of control adult animals.
- Goro Eguchi
- , Yukiko Eguchi
- & Panagiotis A. Tsonis
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The Wnt3a/β-catenin target gene Mesogenin1 controls the segmentation clock by activating a Notch signalling program
During development, Wnt-mediated Notch signalling controls the generation of somites from the presomitic mesoderm, but the precise signalling mechanism is unknown. Here, the transcription factor Mesogenin 1 is shown to be a direct target of Wnt3a and regulates the transcription of a Notch signalling program.
- Ravindra B. Chalamalasetty
- , William C. Dunty Jr
- & Terry P. Yamaguchi
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TorsinA participates in endoplasmic reticulum-associated degradation
The torsinA protein localizes to the endoplasmic reticulum and, when mutated, causes early onset torsion dystonia. The authors reveal a new role for torsinA in proteosome-mediated degradation of misfolded proteins, and relate this to endoplasmic reticulum stress, in aCaenorhabditis elegansmodel and patient fibroblasts.
- Flávia C. Nery
- , Ioanna A. Armata
- & Xandra O. Breakefield
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Crystal structure of the human thioredoxin reductase–thioredoxin complex
Thioredoxin reductase 1 is a flavoprotein that is involved in the regulation of redox homeostasis. Fritz-Wolfet al. report the first crystal structures of thioredoxin reductase 1 in complex with its substrate, thioredoxin, and confirm that the enzyme uses a flexible carboxy-terminal arm for electron transport to its substrates.
- Karin Fritz-Wolf
- , Sebastian Kehr
- & Katja Becker
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