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| Open AccessBat teeth illuminate the diversification of mammalian tooth classes
Despite their key role in the evolution of mammals, the origin and diversification of tooth classes (incisors, canines, premolars and molars) remain relatively obscure. Here the authors use integrative approaches to explain the independent evolution and rapid diversification of two tooth classes, premolar and molars, in noctilionoid bats.
- Alexa Sadier
- , Neal Anthwal
- & Karen E. Sears
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Article
| Open AccessEarly-adulthood spike in protein translation drives aging via juvenile hormone/germline signaling
The transient elevation in protein translation during early-adulthood in Drosophila imposes long-lasting negative impacts on future aging trajectories by triggering proteostatic dysfunction at old ages.
- Harper S. Kim
- , Danitra J. Parker
- & Andrew M. Pickering
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Article
| Open AccessA mosaic adeno-associated virus vector as a versatile tool that exhibits high levels of transgene expression and neuron specificity in primate brain
Viral vectors with intense and long-lasting transgene expression are essential for manipulating and imaging of neuronal activity in the primate brain. Here, the authors created a mosaic vector composed of capsid proteins derived from AAV1 and AAV2 that exhibits improved transgene expression and neuronal specificity.
- Kei Kimura
- , Yuji Nagai
- & Masahiko Takada
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Article
| Open AccessComparing molnupiravir and nirmatrelvir/ritonavir efficacy and the effects on SARS-CoV-2 transmission in animal models
There is limited data on how SARS-CoV-2 antivirals compare regarding efficacy and blocking transmission. Here, treating dwarf hamsters and ferrets with either molnupiravir or paxlovid the authors find comparable efficacy against severe COVID-19-like disease and complete block of transmission by molnupiravir.
- Robert M. Cox
- , Carolin M. Lieber
- & Richard K. Plemper
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Article
| Open AccessMAVS signaling is required for preventing persistent chikungunya heart infection and chronic vascular tissue inflammation
Mosquito-borne viruses are serious global public health threats associated with severe atypical cardiovascular manifestations. Here, the authors dissect how chikungunya virus directly infects cardiac tissue leading to heart disease and define key host pathways involved in viral cardiac persistence and tissue damage.
- Maria G. Noval
- , Sophie N. Spector
- & Kenneth A. Stapleford
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Article
| Open AccessTwo point mutations in protocadherin-1 disrupt hantavirus recognition and afford protection against lethal infection
Protocadherin-1 (PCDH1) is a critical host factor for hantaviruses that can cause severe cardiopulmonary syndrome. Here, the authors map the binding site of the viral glycoprotein complex within PCDH1 and show that mutations engineered at this site can protect Syrian hamsters from viral challenge.
- Megan M. Slough
- , Rong Li
- & Kartik Chandran
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Article
| Open AccessImmunogenicity and efficacy of vaccine boosters against SARS-CoV-2 Omicron subvariant BA.5 in male Syrian hamsters
Long-term BA.5-specific efficiency of booster vaccination is incompletely understood. Here, analyzing immunity to and efficacy of various COVID-19 vaccination regimens in Syrian hamster, the authors found that heterologous boosting provides more durable immunity and that NVX-CoV2373 provides the strongest boosting effect.
- Rafael R. G. Machado
- , Jordyn L. Walker
- & Scott C. Weaver
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Article
| Open AccessIn vitro and in vivo characterization of SARS-CoV-2 strains resistant to nirmatrelvir
Resistance to nirmatrelvir, an oral antiviral agent that targets SARS-CoV-2 and is clinically useful against infection with Omicron variants, is currently not well understood. In this study, the authors characterize mutant viruses with reduced sensitivity to nirmatrelvir in vitro and in vivo.
- Maki Kiso
- , Yuri Furusawa
- & Yoshihiro Kawaoka
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Article
| Open AccessSingle-cell profiling of lncRNA expression during Ebola virus infection in rhesus macaques
Long non-coding RNAs (lncRNAs) play key roles in the immune response but their properties at the single-cell level are less well understood. Here, the authors characterize differential features of lncRNAs and protein-coding genes upon Ebola infection in macaques at single-cell resolution.
- Luisa Santus
- , Maria Sopena-Rios
- & Marta Melé
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Article
| Open AccessCisplatin toxicity is counteracted by the activation of the p38/ATF-7 signaling pathway in post-mitotic C. elegans
In contrast to mammalian cells, C. elegans models can be useful because of cells being post-mitotic in adults. Here the authors show activation of the p38 pathway in cisplatin resistant adult animals and characterise the proteins upstream and downstream of the p38 MAPK signalling pathway that are involved in the cisplatin response.
- Dorota Raj
- , Bashar Kraish
- & Peter Naredi
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Article
| Open AccessArtificial Hsp104-mediated systems for re-localizing protein aggregates
Protein aggregates are a hallmark of neurodegenerative disease and aging. Here, Fischbach et al. report engineered, artificial systems to re-localise or export protein aggregates from cells, with preliminary data showing that mHtt inclusions in S. cerevisiae may be cytotoxic.
- Arthur Fischbach
- , Angela Johns
- & Thomas Nyström
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Article
| Open AccessNirmatrelvir-resistant SARS-CoV-2 is efficiently transmitted in female Syrian hamsters and retains partial susceptibility to treatment
Characteristics of drug-resistant SARS-CoV-2 viruses are unclear. Here, the authors report that an in vitro selected nirmatrelvir-resistant virus replicates efficiently and can be transmitted in Syrian hamsters but that nirmatrelvir retains some antiviral activity against that virus in infected hamsters.
- Rana Abdelnabi
- , Dirk Jochmans
- & Johan Neyts
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Article
| Open AccessThe dynamic nature of netrin-1 and the structural basis for glycosaminoglycan fragment-induced filament formation
In this work, the authors report that heparin oligosaccharides have a significant impact on the highly dynamic behaviour of netrin-1 by inducing hierarchical and distinct super assemblies leading to unique, yet unknown netrin-1 filament formation.
- Markus Meier
- , Monika Gupta
- & Jörg Stetefeld
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Article
| Open AccessHedgehog is relayed through dynamic heparan sulfate interactions to shape its gradient
The Hedgehog morphogen creates gradients during development, but diffusion alone cannot explain its spatiotemporal dynamics. Hedgehog transport requires binding heparan sulfate sugar chains, and the authors now show that Hedgehogs can spread by interacting with sequential heparan molecules.
- Fabian Gude
- , Jurij Froese
- & Kay Grobe
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Article
| Open AccessUltra-long-acting in-situ forming implants with cabotegravir protect female macaques against rectal SHIV infection
In this study, the authors developed an ultra-long-acting injectable, biodegradable, and removable in-situ forming implant delivering cabotegravir (CAB ISFI). CAB ISFI was well tolerated and protected against multiple rectal SHIV challenges in female macaques.
- Isabella C. Young
- , Ivana Massud
- & S. Rahima Benhabbour
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Article
| Open AccessMacroevolutionary diversity of traits and genomes in the model yeast genus Saccharomyces
Here, the authors describe the geographies, hosts, substrates, and phylogenetic relationships for 1,794 Saccharomyces strains. They provide insight into the genetic and phenotypic diversity in the genus, not seen through prior work focused on the model species Saccharomyces cerevisiae.
- David Peris
- , Emily J. Ubbelohde
- & Chris Todd Hittinger
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Article
| Open AccessSex-specificity of the C. elegans metabolome
Biological sex affects all aspects of animal physiology. Using the model C. elegans, the authors show that metabolomes are highly sex-specific and include a vast space of yet unidentified metabolites that may control development and lifespan.
- Russell N. Burkhardt
- , Alexander B. Artyukhin
- & Frank C. Schroeder
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Article
| Open AccessEvolutionary rescue of resistant mutants is governed by a balance between radial expansion and selection in compact populations
Antibiotic and anti-cancer therapy are challenged by mutation-mediated treatment resistance despite many mutations being maladaptive. Here, the authors introduce a system that shows how the probability of the long-term persistence of drug-resistant mutant lineages can be increased in dense microbial populations by acquiring multiple mutations.
- Serhii Aif
- , Nico Appold
- & Jona Kayser
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Article
| Open AccessTagging active neurons by soma-targeted Cal-Light
Techniques for tagging active neurons with high spatiotemporal precision are limited. Here the authors report soma-targeted CalLight (ST-Cal-Light) which selectively converts somatic calcium rise triggered by action potentials into gene expression, and generate a conditional ST-Cal-Light knock-in mouse.
- Jung Ho Hyun
- , Kenichiro Nagahama
- & Hyung-Bae Kwon
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Article
| Open AccessSex differences in allometry for phenotypic traits in mice indicate that females are not scaled males
Research aimed at improving healthcare has largely focused on male animals and cells. Here, the authors use data from the International Mouse Phenotyping Consortium to show that body weight does not account for all phenotypic differences between male and female mice, supporting more female-focused research.
- Laura A. B. Wilson
- , Susanne R. K. Zajitschek
- & Shinichi Nakagawa
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Article
| Open AccessHypothermia evoked by stimulation of medial preoptic nucleus protects the brain in a mouse model of ischaemia
Developing brain-protective hypothermia is a medical challenge. Here, the authors show that deep brain stimulation of a particular brain area is a new way to trigger the body into a hibernation-like state with reduced body temperature and brain protection in a mouse model of stroke.
- Shuai Zhang
- , Xinpei Zhang
- & Sheng-Tao Hou
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Article
| Open AccessA doxycycline- and light-inducible Cre recombinase mouse model for optogenetic genome editing
Achieving spatial control of gene expression is important. Here the authors report an optimised photoactivatable Cre recombinase system, doxycycline- and light-inducible Cre recombinase (DiLiCre), and generate a DiLiCre mouse line which they use for mutagenesis in vivo and positional cell-tracing.
- Miguel Vizoso
- , Colin E. J. Pritchard
- & Jacco van Rheenen
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Article
| Open AccessSublinear scaling of the cellular proteome with ploidy
Increasing the number of chromosome sets alters the physiology of cells. Here, the authors show that although the number of chromosome sets increases, the proteome does not scale linearly with the increasing ploidy.
- G. Yahya
- , P. Menges
- & Z. Storchova
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Article
| Open AccessThermosensation in Caenorhabditis elegans is linked to ubiquitin-dependent protein turnover via insulin and calcineurin signalling
Sensation of environmental changes is vital for organismal homeostasis. Here, the authors report that protein degradation in the gut of Caenorhabditis elegans is regulated through insulin and calcineurin signalling upon neuronal sensation of temperature changes.
- Alexandra Segref
- , Kavya L. Vakkayil
- & Thorsten Hoppe
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Article
| Open AccessA Dilp8-dependent time window ensures tissue size adjustment in Drosophila
Mechanisms ensuring developmental precision are poorly understood. Here Blanco-Obregon et al. report reciprocal feedback between Dilp8 and Ecdysone, two hormones required during a precise time window of Drosophila development for organ size adjustment.
- D. Blanco-Obregon
- , K. El Marzkioui
- & L. Boulan
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Article
| Open AccessScreening microbially produced Δ9-tetrahydrocannabinol using a yeast biosensor workflow
Microbial production of cannabinoids promises a cheaper and more sustainable route to these important therapeutic molecules, but strain improvement and screening is challenging. Here, the authors develop a yeast-based Δ9-tetrahydrocannabinol (THC) biosensor for screening microbial mutant libraries.
- William M. Shaw
- , Yunfeng Zhang
- & Tom Ellis
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Article
| Open AccessA single WNT enhancer drives specification and regeneration of the Drosophila wing
The wing is a remarkable evolutionary novelty in insects. Here the authors demonstrate that the specification and regenerative capacity of the wing relies on a single wing-specific enhancer of the wingless gene in Drosophila.
- Elena Gracia-Latorre
- , Lidia Pérez
- & Marco Milán
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Article
| Open AccessGLI3 regulates muscle stem cell entry into GAlert and self-renewal
Primary cilia regulate the processing of the GLI transcription factors and Hedgehog signaling. Here, the authors show that cilia-related GLI3 controls both the quiescence-to-activation transition and self-renewal in muscle stem cells.
- Caroline E. Brun
- , Marie-Claude Sincennes
- & Michael A. Rudnicki
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Article
| Open AccessTranscription factor paralogs orchestrate alternative gene regulatory networks by context-dependent cooperation with multiple cofactors
Feng et al. compare the genome-wide binding and activity of two Drosophila Hox transcription factors that determine the identities of different fly legs. For binding events that are Hox specific, two cofactors, Exd and Dll, are used to achieve specificity in non-overlapping leg domains.
- Siqian Feng
- , Chaitanya Rastogi
- & Richard S. Mann
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Article
| Open AccessThe architecture and operating mechanism of a cnidarian stinging organelle
The venomous stinging cells of jellyfish, anemones, and corals contain an organelle, the nematocyst, which explosively discharges a venom-laden thread. Here, the authors describe the nematocyst thread and its sub-structures in the sea anemone N. vectensis, revealing a complexity and sophistication underpinning this cellular weapon.
- Ahmet Karabulut
- , Melainia McClain
- & Matthew C. Gibson
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Perspective
| Open AccessMicrofluidics for understanding model organisms
Building small-scale tools for biology research eliminates the need for time-consuming methods and enables novel experimental paradigms. Here, the authors discuss microfluidics' potential for manipulating or stimulating model organisms and identify barriers to making these tools accessible.
- Nolan Frey
- , Utku M. Sönmez
- & Philip LeDuc
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Article
| Open AccessProteome allocations change linearly with the specific growth rate of Saccharomyces cerevisiae under glucose limitation
Understanding how yeast organizes its functional proteome is a fundamental task in systems biology. Here, the authors conduct a multiomics analysis on yeast cells cultured with different growth rates, identifying a linear dependence of the functional proteome on the growth rate.
- Jianye Xia
- , Benjamin J. Sánchez
- & Jens Nielsen
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Article
| Open AccessOptogenetic manipulation and photoacoustic imaging using a near-infrared transgenic mouse model
Optogenetic tools can be used as in vivo imaging probes. Here the authors generate a loxP-BphP1 transgenic mouse to enable Cre-dependent temporal and spatial targeting of BphP1 expression in vivo; they show photoacoustic tomography of BphP1 expression in developing embryos and regenerating livers.
- Ludmila A. Kasatkina
- , Chenshuo Ma
- & Vladislav V. Verkhusha
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Article
| Open AccessHand2 delineates mesothelium progenitors and is reactivated in mesothelioma
The mesothelium supports homeostasis and regeneration, yet its development origins remain unclear. Here, the authors uncovered the earliest mesothelium progenitor cells in zebrafish, linking Hand2 gene function to mesothelium formation and its re-activation to mesothelioma tumors.
- Karin D. Prummel
- , Helena L. Crowell
- & Christian Mosimann
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Article
| Open AccessSmad4 controls signaling robustness and morphogenesis by differentially contributing to the Nodal and BMP pathways
The role of the transcriptional effector SMAD4 in vertebrate embryo development remains unresolved. Here the authors show that in the absence of Smad4, dorsal/ventral embryo patterning is disrupted due to the loss of BMP signaling, while Nodal signaling is maintained, but insufficient for optimal endoderm specification.
- Luca Guglielmi
- , Claire Heliot
- & Caroline S. Hill
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Article
| Open AccessIn situ and transcriptomic identification of microglia in synapse-rich regions of the developing zebrafish brain
Microglia remodel synapses and engulf apoptotic cells. The molecular program underlying these distinct functions are unclear. Here, the authors identify distinct microglial subsets associated with synaptic vs. neurogenic regions of the developing zebrafish brain.
- Nicholas J. Silva
- , Leah C. Dorman
- & Anna V. Molofsky
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Article
| Open AccessProfilin and Mical combine to impair F-actin assembly and promote disassembly and remodeling
Actin-based structures in cells and tissues are built and maintained through a poorly understood balance between assembly and disassembly. Here, our findings provide insights into how factors known to promote these opposing effects dynamically integrate to shape cells and tissue systems.
- Elena E. Grintsevich
- , Giasuddin Ahmed
- & Jonathan R. Terman
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Article
| Open AccessDevelopmental genetics of color pattern establishment in cats
Intricate color patterns are a defining aspect of morphological diversity in the Felidae. Here the authors apply morphological and single-cell gene expression analysis to fetal skin of domestic cats to identify when, where, and how, during fetal development, felid color patterns are established.
- Christopher B. Kaelin
- , Kelly A. McGowan
- & Gregory S. Barsh
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Article
| Open AccessDynamic tracking and identification of tissue-specific secretory proteins in the circulation of live mice
The in vivo identification of proteins secreted from a specific cell type or tissue remains challenging. Here, the authors develop a proximity labeling-based method to selectively label secreted proteins and combine it with proteomics to identify liver secretory proteins in mouse plasma.
- Kwang-eun Kim
- , Isaac Park
- & Jae Myoung Suh
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Article
| Open AccessMapping the biosynthetic pathway of a hybrid polyketide-nonribosomal peptide in a metazoan
The only known animal polyketide-nonribosomal peptides, the nemamides, are biosynthesized by two megasynthetases in the canal-associated neurons (CANs) of C. elegans. Here, the authors map the biosynthetic roles of individual megasynthetase domains and identify additional enzymes in the CANs required for nemamide biosynthesis.
- Likui Feng
- , Matthew T. Gordon
- & Rebecca A. Butcher
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Article
| Open AccessCoordination of endothelial cell positioning and fate specification by the epicardium
It remains unclear how spatial information controls endothelial cell identity and behavior in the developing heart. Here the authors perform single cell RNA sequencing at key developmental timepoints in mice to interrogate cellular contributions to coronary vessel patterning and maturation in the epicardium.
- Pearl Quijada
- , Michael A. Trembley
- & Eric M. Small
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Article
| Open AccessAnalysis of gene network bifurcation during optic cup morphogenesis in zebrafish
The gene regulatory network controlling the bifurcation of common progenitors into the neural retina and retinal-pigmented epithelium programs remains poorly understood. Here the authors study transcriptome dynamics and chromatin accessibility during this process in zebrafish, revealing network redundancy, as well as context-dependent and sequential transcription factor activity.
- Lorena Buono
- , Jorge Corbacho
- & Juan-Ramón Martínez-Morales
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Article
| Open AccessHakai is required for stabilization of core components of the m6A mRNA methylation machinery
The E3 ligase Hakai can interact with the m6A methylation machinery but its function is still unclear. Here, the authors show that Hakai is a conserved component of the m6A methyltransferase complex and provide functional and molecular insights into its role in regulating m6A levels in Drosophila.
- Praveen Bawankar
- , Tina Lence
- & Jean-Yves Roignant
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Article
| Open AccessSpatio-temporal mRNA tracking in the early zebrafish embryo
Early stages of embryogenesis are known to depend on subcellular localization and transport of maternal mRNA, but systematic analyses have been hindered by a lack of methods for tracking of RNA. Here the authors combine spatially-resolved transcriptomics and single-cell RNA labeling to perform a spatio-temporal analysis of the transcriptome during early zebrafish development, revealing insights into this process.
- Karoline Holler
- , Anika Neuschulz
- & Jan Philipp Junker
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Article
| Open AccessThe steroid-hormone ecdysone coordinates parallel pupariation neuromotor and morphogenetic subprograms via epidermis-to-neuron Dilp8-Lgr3 signal induction
Pupariation in Drosophila is triggered by the steroid-hormone ecdysone and requires coordination between associated behavioral and body-reshaping motor subprograms. The authors show that coordination requires ecdysone-dependent Dilp8-Lgr3 signaling between the cuticle epidermis and interneurons.
- Fabiana Heredia
- , Yanel Volonté
- & Alisson M. Gontijo
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Article
| Open AccessSubcellular three-dimensional imaging deep through multicellular thick samples by structured illumination microscopy and adaptive optics
Optical aberrations in Structured Illumination Microscopy (SIM) can lead to loss of resolution and artifacts making it unsuitable for thick samples. Here the authors combine Adaptive Optics and SIM (AO-3DSIM) to improve the 3D resolution and reduce artifacts, performing 3D-SIM in C.elegans.
- Ruizhe Lin
- , Edward T. Kipreos
- & Peter Kner
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Article
| Open AccessCryopreservation method for Drosophila melanogaster embryos
The development of a widely adopted cryopreservation method remains a major challenge in Drosophila melanogaster research. Here the authors report a robust cryopreservation protocol of Drosophila embryos and showcase its implementation in 25 distinct strains from different sources.
- Li Zhan
- , Min-gang Li
- & John Bischof
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Article
| Open AccessCell-type-specific profiling of loaded miRNAs from Caenorhabditis elegans reveals spatial and temporal flexibility in Argonaute loading
C. elegans miRNAs associate with AGO proteins ALG-1 and ALG-2. Here the authors provide a map of miRNAs loaded into ALG-1 and ALG-2 from intestine, body wall muscles and nervous system in C. elegans providing insights into spatial and temporal AGO loading flexibility.
- Christopher A. Brosnan
- , Alexander J. Palmer
- & Steven Zuryn
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Article
| Open AccessThe Burkholderia pseudomallei intracellular ‘TRANSITome’
Prokaryotic cell transcriptomics has been limited to mixed or sub-population dynamics and individual cells within heterogeneous populations. Here the authors develop a ‘TRANSITomic’ approach to profile transcriptomes of single Burkholderia pseudomallei cells as they transit through host cell infection.
- Yun Heacock-Kang
- , Ian A. McMillan
- & Tung T. Hoang