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Article
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Metabolic cross-feeding in imbalanced diets allows gut microbes to improve reproduction and alter host behaviour
In the fly Drosophila melanogaster commensal bacteria and dietary essential amino acids control food choice behavior. Here, by using chemically defined diets and metabolomics, the authors show that Acetobacter pomorum (Ap) and Lactobacilli plantarum (Lp) engage in a mutualistic metabolic relationship to overcome detrimental diets, and identify Ap as the bacterium altering the host’s feeding decisions.
- Sílvia F. Henriques
- , Darshan B. Dhakan
- & Carlos Ribeiro
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| Open Access
Transcriptional activity and strain-specific history of mouse pseudogenes
Pseudogenes are key markers of genome remodelling processes. Here the authors present genome-wide annotation of the pseudogenes in the mouse reference genome and 18 inbred mouse strains, update human pseudogene annotations, and characterise the transcription and evolution of mouse pseudogenes.
- Cristina Sisu
- , Paul Muir
- & Mark Gerstein
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| Open Access
Sub-nanowatt resolution direct calorimetry for probing real-time metabolic activity of individual C. elegans worms
Calorimetry is widely used for metabolic studies, but measurements of single cells and small organisms are limited by the sensitivity of current techniques. Here the authors develop a sensitive platform for performing time-resolved metabolic measurements of single C. elegans worms from larval to adult stages.
- Sunghoon Hur
- , Rohith Mittapally
- & Edgar Meyhofer
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| Open Access
A HaloTag-TEV genetic cassette for mechanical phenotyping of proteins from tissues
Testing mechanical forces on native molecules in natural environments remains a challenge. Here the authors engineer titin to carry a HaloTag-TEV insertion to allow analysis of dynamics under force in muscle fibers.
- Jaime Andrés Rivas-Pardo
- , Yong Li
- & Jorge Alegre-Cebollada
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A fully orthogonal system for protein synthesis in bacterial cells
Ribosome engineering is an emerging powerful approach for synthetic protein synthesis. Here the authors invert the Ribo-T system, using the engineered ribosome to translate the proteome while the native ribosome translates specific mRNA.
- Nikolay A. Aleksashin
- , Teresa Szal
- & Alexander S. Mankin
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Cep55 promotes cytokinesis of neural progenitors but is dispensable for most mammalian cell divisions
In mammalian cell lines, Cep55 protein recruits the endosomal sorting complex required for transport (ESCRT) and promotes the completion of cell division. Here, the authors show that Cep55-knockout mice are viable and primary fibroblasts cultured in vitro divide in a Cep55 and ESCRT-independent way.
- Antonio Tedeschi
- , Jorge Almagro
- & Mark Petronczki
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Generating high quality libraries for DIA MS with empirically corrected peptide predictions
Data-independent acquisition-mass spectrometry (MS) typically requires many preparatory MS runs to produce experiment-specific spectral libraries. Here, the authors show that empirical correction of in silico predicted spectral libraries enables efficient generation of high-quality experiment-specific libraries.
- Brian C. Searle
- , Kristian E. Swearingen
- & Mathias Wilhelm
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Single-molecule live-cell imaging visualizes parallel pathways of prokaryotic nucleotide excision repair
In Escherichia coli, the UvrAB damage sensor recognizes helix-distorting lesions by itself or via Mfd bound to stalled RNA polymerase. Here authors use single-molecule fluorescence imaging to quantify the kinetic signatures of interactions of UvrA with Mfd and UvrB in live cells.
- Harshad Ghodke
- , Han Ngoc Ho
- & Antoine M. van Oijen
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Adverse caregiving in infancy blunts neural processing of the mother
The roots of psychopathology take shape during adverse parent-infant interactions, shown through infant attachment quality. Using rodents, the authors show that blunted infant cortical processing of the mother determines attachment quality through a stress hormone-dependent mechanism.
- Maya Opendak
- , Emma Theisen
- & Regina M. Sullivan
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Mechanical properties measured by atomic force microscopy define health biomarkers in ageing C. elegans
The development of reliable measures of health in ageing organisms is a need in ageing research. Using atomic force microscopy, here, the authors assess whole body stiffness of worms and show that it reflects organismal fitness.
- Clara L. Essmann
- , Daniel Martinez-Martinez
- & Filipe Cabreiro
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| Open Access
Tissue mechanics drives regeneration of a mucociliated epidermis on the surface of Xenopus embryonic aggregates
The role of tissue mechanics in the regeneration of mucociliated epithelium in Xenopus is unclear. Here, the authors show that Xenopus ectoderm aggregates undergo epithelial-like phenotypic transition prior to differentiation of mucus-secreting goblet cells to enable regeneration.
- Hye Young Kim
- , Timothy R. Jackson
- & Lance A. Davidson
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Article
| Open Access
Molecular signatures of aneuploidy-driven adaptive evolution
Aneuploidy (abnormal chromosome number) can enable rapid adaptation to stress conditions, but it also entails fitness costs from gene imbalance. Here, the authors experimentally evolve yeast while forcing maintenance of aneuploidy to identify the mechanisms that promote tolerance of aneuploidy.
- Alaattin Kaya
- , Marco Mariotti
- & Vadim N. Gladyshev
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Image quality guided smart rotation improves coverage in microscopy
Multi-view SPIM imaging can improve coverage of large samples such as whole embryos, but the procedure increases phototoxicity and involves manual steps that can introduce inconsistencies. Here the authors develop a smart rotation workflow that performs on-the-fly image analysis and identifies optimal set of views to maximize sample coverage.
- Jiaye He
- & Jan Huisken
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Symmetry group factorization reveals the structure-function relation in the neural connectome of Caenorhabditis elegans
The 302-neuron connectome of the nematode C. elegans has been completely mapped, yet the design principles that explain how the connectome structure determines its function are unknown. Here, the authors show that physical principles of symmetry and mathematical tools of symmetry groups can be used to understand C. elegans neural locomotion circuits.
- Flaviano Morone
- & Hernán A. Makse
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| Open Access
Zika virus enhances monocyte adhesion and transmigration favoring viral dissemination to neural cells
Zika virus (ZIKV) can infect the central nervous system, but it is not clear how it reaches the brain. Here, Ayala-Nunez et al. show in ex vivo and in vivo models that ZIKV can hitch a ride in monocytes in a Trojan Horse manner to cross the endothelium and disseminate the virus.
- Nilda Vanesa Ayala-Nunez
- , Gautier Follain
- & Raphael Gaudin
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Identification of proteins and miRNAs that specifically bind an mRNA in vivo
The entire mRNA interactome capture has been established but identification of specific mRNA-binding proteins has been challenging. Here, the authors developed an in vivo RNA–protein crosslinking and RNA pulldown approach and characterized novel interactors of the C. elegans gld-1 mRNA, including DAZ-1 and miR-84.
- Kathrin Theil
- , Koshi Imami
- & Nikolaus Rajewsky
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Ubiquitination of RIPK1 suppresses programmed cell death by regulating RIPK1 kinase activation during embryogenesis
RIPK1 integrates signals that drive both NF-κB activation and cell death pathways. Here Zhang et al. generate RIPK1 knock-in mice lacking a major ubiquitination site and demonstrate that this modification is important to suppress cell death during embryogenesis and inflammation postnatally.
- Xixi Zhang
- , Haiwei Zhang
- & Haibing Zhang
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| Open Access
Rapid metabolic shifts occur during the transition between hunger and satiety in Drosophila melanogaster
The relationship between metabolomic and behavioral changes is not well understood. Here, the authors analyze metabolome changes in D. melanogaster heads and bodies during hunger and satiety, and develop the Flyscape tool to visualize the resulting metabolic networks and integrate them with other omics data.
- Daniel Wilinski
- , Jasmine Winzeler
- & Monica Dus
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| Open Access
The marginal cells of the Caenorhabditis elegans pharynx scavenge cholesterol and other hydrophobic small molecules
The C. elegans nematode worm is a filter-feeder and requires dietary sources of cholesterol. Here, the authors show that the C. elegans pharynx works as a filter to scavenge hydrophobic small molecules from its surrounding liquid environment.
- Muntasir Kamal
- , Houtan Moshiri
- & Peter J. Roy
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| Open Access
Inhibition of amyloid beta toxicity in zebrafish with a chaperone-gold nanoparticle dual strategy
Treating Alzheimer’s disease, one of the most common neurodegenerative diseases, is of wide interest. Here, the authors report on the development of casein coated gold nanoparticles which were able to cross the blood brain barrier and protect against amyloid beta toxicity in a zebrafish model.
- Ibrahim Javed
- , Guotao Peng
- & Sijie Lin
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| Open Access
Repeated semen exposure decreases cervicovaginal SIVmac251 infection in rhesus macaques
High frequency semen exposure has been associated with activation of anti-HIV mechanisms in HIV negative sex workers. Here, Abdulhaqq et al. show that repeated vaginal exposure to semen reduces vaginal infection by SIV in non-human primates, and is associated with lower CCR5 expression in CD4 T-cells and a local type-I interferon response.
- Shaheed A. Abdulhaqq
- , Melween Martinez
- & Luis J. Montaner
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| Open Access
Robust continuous in vitro culture of the Plasmodium cynomolgi erythrocytic stages
Present understanding of Plasmodium vivax biology is hampered by its inability to grow in vitro. Here, the authors developed an in vitro culture of its simian counterpart, P. cynomolgi, which shares morphological and phenotypic similarities with P. vivax, initiating a new phase in vivax research.
- Adeline C. Y. Chua
- , Jessica Jie Ying Ong
- & Pablo Bifani
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| Open Access
The autism- and schizophrenia-associated protein CYFIP1 regulates bilateral brain connectivity and behaviour
In humans, copy-number variants of the CYFIP1 gene have been associated with autism spectrum disorders and schizophrenia. Here, the authors characterize Cyfip1-heterozygous mice, revealing that they display deficits in brain white matter structure and functional connectivity along with abnormal behaviours.
- Nuria Domínguez-Iturza
- , Adrian C. Lo
- & Claudia Bagni
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Cyfip1 haploinsufficient rats show white matter changes, myelin thinning, abnormal oligodendrocytes and behavioural inflexibility
People with a genetic deletion of the 15q11.2 locus are at increased risk for psychiatric disorders and white matter disturbances, but the gene(s) responsible are unclear. Here, the authors show that low dosage of CYFIP1, present in the human 15q11.2 region, alters white matter structure and cognition in rats.
- Ana I. Silva
- , Josephine E. Haddon
- & Lawrence S. Wilkinson
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Article
| Open Access
KLF-1 orchestrates a xenobiotic detoxification program essential for longevity of mitochondrial mutants
Cytochrome P450 oxidases (CYPs) are enzymes that participate in the xenobiotic detoxification and their expression is enhanced in long-lived model organisms. Here the authors show that KLF-1 promotes cyp expression and ensures lifespan extension in C. elegans mitomutants by activating mitohormesis.
- Marija Herholz
- , Estela Cepeda
- & Aleksandra Trifunovic
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| Open Access
The longevity-promoting factor, TCER-1, widely represses stress resistance and innate immunity
Resistance to stress is often associated with increased longevity. Using the model organism C. elegans the authors here show that TCER-1 enhances lifespan while at the same time increasing sensitivity to a number of biotic and abiotic stressors.
- Francis R. G. Amrit
- , Nikki Naim
- & Arjumand Ghazi
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| Open Access
Dietary fatty acids promote lipid droplet diversity through seipin enrichment in an ER subdomain
Lipid droplets (LDs) are fat storage organelles that are initiated and expanded by seipins at ER contact sites. Here the authors show that the C. elegans seipin ortholog SEIP-1 is recruited to these sites by certain dietary fatty acids to support the expansion of a subset of LDs.
- Zhe Cao
- , Yan Hao
- & Ho Yi Mak
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Sensory perception of dead conspecifics induces aversive cues and modulates lifespan through serotonin in Drosophila
Different sensory experiences can affect longevity in Drosophila. Here the authors find that exposure of Drosophila directly to dead conspecifics affects longevity via a serotonergic mechanism, and that Drosophila exposed to dead conspecifics also become an aversive stimulus to naïve choosers.
- Tuhin S. Chakraborty
- , Christi M. Gendron
- & Scott D. Pletcher
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Tissue-specific (ts)CRISPR as an efficient strategy for in vivo screening in Drosophila
Applicability of CRISPR-Cas9 for in vivo screening has so far been limited. Here the authors characterize tissue specific CRISPR in the Drosophila mushroom body, generating a library of gRNA-harboring plasmids and fly lines for in vivo screening.
- Hagar Meltzer
- , Efrat Marom
- & Oren Schuldiner
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A fat-tissue sensor couples growth to oxygen availability by remotely controlling insulin secretion
The mechanisms by which organisms adapt their growth according to the availability of oxygen are incompletely understood. Here the authors identify the Drosophila fat body as a tissue regulating growth in response to oxygen sensing via a mechanism involving Hph inhibition, HIF1-a activation and insulin secretion.
- Michael J. Texada
- , Anne F. Jørgensen
- & Kim F. Rewitz
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| Open Access
The development of synaptic transmission is time-locked to early social behaviors in rats
The development of functional synapses is a key milestone in neurodevelopment. Here, the authors show how serotonin signalling coordinates development of glutamatergic and GABAergic currents and triggers the emergence of integrative behavior (huddling) in rat pups.
- Shovan Naskar
- , Roberto Narducci
- & Laura Cancedda
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Etv6 activates vegfa expression through positive and negative transcriptional regulatory networks in Xenopus embryos
How vegfa expression is transcriptionally regulated in vivo is unclear. Here, the authors demonstrate that the ETS transcription factor Etv6 acts as a repressor and an activator of two direct regulators of vegfa expression (foxo3 and klf4, respectively) to control blood formation in Xenopus.
- Lei Li
- , Rossella Rispoli
- & Catherine Porcher
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Znhit1 controls intestinal stem cell maintenance by regulating H2A.Z incorporation
Lgr5+ stem cells in intestinal crypts are critical for gut epithelium homeostasis. Here, the authors show that Znht1 critically regulates intestinal homeostasis by promoting interaction between histone variant H2A.Z and its chaperone YL1 to incorporate H2A.Z into genes involved in intestinal stem cell fate.
- Bing Zhao
- , Ying Chen
- & Xinhua Lin
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| Open Access
Stem cell proliferation is induced by apoptotic bodies from dying cells during epithelial tissue maintenance
Damaged epithelial tissues are known to compensate for cell death through compensatory cell divisions to maintain epithelial integrity. Here, the authors show in living epithelia that dying cells stimulate adjacent stem cells to divide through caspase-dependent production of Wnt8a-containing apoptotic bodies.
- Courtney K. Brock
- , Stephen T. Wallin
- & George T. Eisenhoffer
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Systematic analysis reveals the prevalence and principles of bypassable gene essentiality
An essential gene may become non-essential when another gene is mutated. Here, the authors investigate this type of digenic interaction, termed ‘bypass of essentiality’, in the fission yeast Schizosaccharomyces pombe, and show that bypassable essential genes are common and share certain features.
- Jun Li
- , Hai-Tao Wang
- & Li-Lin Du
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| Open Access
Mutation of a single residue promotes gating of vertebrate and invertebrate two-pore domain potassium channels
Mutations that modulate the activity of ion channels are essential tools to understand the biophysical determinants that control their gating. Here authors reveal the role played by a single residue in the second transmembrane domain of vertebrate and invertebrate two-pore domain potassium channels.
- Ismail Ben Soussia
- , Sonia El Mouridi
- & Thomas Boulin
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| Open Access
Single gametophyte sequencing reveals that crossover events differ between sexes in maize
Meiotic crossover (CO) landscape differs inter- and intra-species, as well as between sexes. Here, the authors show that male meiosis produces more COs than female in maize and detect CO maturation inefficiency in some genetic backgrounds, which may help to improve breeding efficiency.
- Cheng Luo
- , Xiang Li
- & Jianbing Yan
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ASPP proteins discriminate between PP1 catalytic subunits through their SH3 domain and the PP1 C-tail
Serine/threonine phosphatases such as PP1 associate with a large array of subunit proteins, such as ASPP (apoptosis-stimulating protein of p53) to achieve selective targeting. Here authors solved the crystal structure of the human ASPP2/PP1 complex and explain how ASPP2 can distinguish between PP1 isoforms.
- M. Teresa Bertran
- , Stéphane Mouilleron
- & Nicolas Tapon
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| Open Access
tmem33 is essential for VEGF-mediated endothelial calcium oscillations and angiogenesis
Calcium signalling downstream of VEGF is essential for VEGF-induced angiogenesis. Here Savage et al. show that Transmembrane Protein 33 (TMEM33) is required for angiogenesis and the endothelial calcium response to VEGF, revealing a function for TMEM33 in multicellular organisms.
- Aaron M. Savage
- , Sathishkumar Kurusamy
- & Robert N. Wilkinson
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| Open Access
BMP-dependent synaptic development requires Abi-Abl-Rac signaling of BMP receptor macropinocytosis
BMP ligands act as retrograde signalling molecules to regulate presynaptic development, and regulation of BMP receptors by endocytosis may be an important component of this signalling pathway. Here, the authors show that Abi-mediated macropinocytosis of BMP receptors in Drosophila larva and contributes to neuromuscular development.
- Najin Kim
- , Sungdae Kim
- & Seungbok Lee
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Article
| Open Access
Differentiation of primate primordial germ cell-like cells following transplantation into the adult gonadal niche
Human embryonic stem cells can be differentiated in vitro into primordial germ cell-like cells (PGCLCs) that resemble early primordial germ cells (PGCs). Here the authors transplant PGCLCs generated from rhesus macaque iPSCs into mouse and rhesus macaque seminiferous tubules, which matures these into late PGCs and spermatogonia-like cells.
- Enrique Sosa
- , Di Chen
- & Amander T. Clark
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| Open Access
Quantifying post-transcriptional regulation in the development of Drosophila melanogaster
Proteome and transcriptome often show poor correlation, hindering the system-wide analysis of post-transcriptional regulation. Here, the authors study proteome and transcriptome dynamics during Drosophila embryogenesis and present basic mathematical models describing the temporal regulation of most protein-RNA pairs.
- Kolja Becker
- , Alina Bluhm
- & Stefan Legewie
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| Open Access
Heart enhancers with deeply conserved regulatory activity are established early in zebrafish development
During early embryogenesis, critical cardiac specification events occur. Here the authors isolate cardiac progenitor cells from early zebrafish embryos and characterize accessible chromatin regions specific to this cell population, finding that many of these regions overlap with conserved non-coding elements that are ortholgous to accessible chromatin regions in human.
- Xuefei Yuan
- , Mengyi Song
- & Michael D. Wilson
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| Open Access
Wnt/β-catenin signaling regulates VE-cadherin-mediated anastomosis of brain capillaries by counteracting S1pr1 signaling
Wnt signaling is known to regulate the formation of the blood-brain barrier. Here Hübner et al. dissect the underlying mechanisms using high resolution live imaging in zebrafish, and find that Wnt regulates anastomosis of angiogenic sprouts in the brain by counteracting sphingosine-1-phosphate receptor signaling.
- Kathleen Hübner
- , Pauline Cabochette
- & Wiebke Herzog
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| Open Access
Engulfing cells promote neuronal regeneration and remove neuronal debris through distinct biochemical functions of CED-1
It is unclear how removal of axon debris and initiation of axon regeneration following nerve injury is co-regulated. In this study, the authors show that the extracellular domain (ECD) of the engulfment receptor, CED-1, functions as an adhesion molecule to promote axonal regeneration after injury, independent of its function in phagocytosis
- Hui Chiu
- , Yan Zou
- & Chieh Chang
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| Open Access
Systems glycomics of adult zebrafish identifies organ-specific sialylation and glycosylation patterns
Zebrafish is a popular system for studying the molecular basis of glycan-related human diseases. Here, the authors present glycomic profiles of eight zebrafish organs and establish the organ-specific expression patterns of related biosynthetic enzymes.
- Nao Yamakawa
- , Jorick Vanbeselaere
- & Yann Guerardel
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| Open Access
Differential lateral and basal tension drive folding of Drosophila wing discs through two distinct mechanisms
Epithelial folding has mainly been linked to forces acting in the apical actomyosin network of cells. Here, the authors show using live imaging that two distinct mechanisms, changes in basal surface tension and changes in lateral surface tension, drive the formation of two folds in the Drosophila wing disc.
- Liyuan Sui
- , Silvanus Alt
- & Christian Dahmann
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| Open Access
Engineered bidirectional promoters enable rapid multi-gene co-expression optimization
Classic monodirectional promoters are of limited use for multiple gene co-expression. Here the authors generate a library of 168 bidirectional promoters for the yeast K. phaffii (syn. P. pastoris) with diverse expression profiles to optimize metabolic pathway design.
- Thomas Vogl
- , Thomas Kickenweiz
- & Anton Glieder
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| Open Access
Iridophores as a source of robustness in zebrafish stripes and variability in Danio patterns
Iridophores interact with other cells to give zebrafish their stripes, but what drives their form shifts is unknown. Here, modelling allows the authors to identify robust cues that may specify iridophore form and to find changes to these cues that likely account for altered patterns on related fish.
- Alexandria Volkening
- & Björn Sandstede
Eukaryotic cell biology is temporally coordinated to support the energetic demands of protein homeostasis