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Article
| Open AccessCross-species spill-over potential of the H9N2 bat influenza A virus
In this study, the authors report that a bat influenza A (H9N2) virus shows receptor binding features similar to avian influenza viruses, efficiently infects ex-vivo human respiratory cells and replicates in the lungs of mice and upper respiratory tract of ferrets following airborne transmission.
- Rabeh El-Shesheny
- , John Franks
- & Richard J. Webby
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Article
| Open AccessCortex-wide transcranial localization microscopy with fluorescently labeled red blood cells
Existing neuroimaging tools are still hampered by restricted field-of-view, slow imaging speed or suboptimal spatial resolution. Here, the authors present a fluorescence localization imaging approach aided by sparsely-labeled red blood cells for cortex-wide morphological and functional cerebral angiography with high spatiotemporal resolution.
- Quanyu Zhou
- , Chaim Glück
- & Zhenyue Chen
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Article
| Open AccessDenaturing mass photometry for rapid optimization of chemical protein-protein cross-linking reactions
Choosing best chemical cross-linking (XL) reagents and conditions for studying protein-protein interactions in structural biology is laborious and lacks in accuracy. The authors develop here an accurate, fast, robust and quantiative denaturing mass photometry approach for screening of XL conditions.
- Hugo Gizardin-Fredon
- , Paulo E. Santo
- & Sarah Cianférani
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Article
| Open AccessPersistent TFIIH binding to non-excised DNA damage causes cell and developmental failure
Hereditary nucleotide excision repair deficiencies cause different cancerous and progeroid disorders of which the exact etiology is not understood. This study finds that prolonged binding of DNA repair factor TFIIH to DNA damage contributes to a more severe phenotype caused by DNA repair deficiency.
- Alba Muniesa-Vargas
- , Carlota Davó-Martínez
- & Hannes Lans
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Article
| Open AccessHigh clonal diversity and spatial genetic admixture in early prostate cancer and surrounding normal tissue
It remains challenging to characterise somatic copy number alterations (SCNAs) in tumors and the surrounding tissues with spatial and single-cell resolution. Here, the authors develop the scCUTseq approach to characterise SCNAs from single cells in multi-region prostate cancer samples and identify pseudo-diploid cells and subclones.
- Ning Zhang
- , Luuk Harbers
- & Nicola Crosetto
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Article
| Open AccessMYADM binds human parechovirus 1 and is essential for viral entry
Host factors required for parechovirus entry are not well understood. Here, the authors identify MYADM as an essential host entry factor that directly binds human parechovirus 1 and that is required for PeV-A infection in cell lines and human gastrointestinal epithelial organoids.
- Wenjie Qiao
- , Christopher M. Richards
- & Jan E. Carette
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Article
| Open AccessTyrosine phosphorylation of CARM1 promotes its enzymatic activity and alters its target specificity
Coactivator-associated arginine methyltransferase 1 (CARM1) is an important target in hematologic malignancies. In this work, the authors show that the hyperactivation of Janus kinase 2 (JAK2) by the V617F mutation phosphorylates CARM1 which regulates its methyltransferase activity and alters its target specificity.
- Hidehiro Itonaga
- , Adnan K. Mookhtiar
- & Stephen D. Nimer
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Article
| Open AccessSelective lipid recruitment by an archaeal DPANN symbiont from its host
The symbiont Ca. Nanohaloarchaeum antarcticus is dependent on its host Halorubrum lacusprofundi for lipids due to a lack of certain biosynthetic genes. Here, the authors characterize the lipidome dynamics of this symbiotic relationship.
- Su Ding
- , Joshua N. Hamm
- & Anja Spang
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Article
| Open AccessMulti-omics analysis reveals COVID-19 vaccine induced attenuation of inflammatory responses during breakthrough disease
Here, Drury et al study gene, microRNA and protein expression during COVID-19, in a randomised controlled trial of ChAdOx1 nCoV19 vaccine and find that ChAdOx1 nCoV-19 attenuates the inflammatory response, thought to be the basis for severe COVID-19.
- Ruth E. Drury
- , Susana Camara
- & Daniel O’Connor
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Article
| Open AccessLSD1 drives intestinal epithelial maturation and controls small intestinal immune cell composition independent of microbiota in a murine model
Post birth the gastrointestinal tract undergoes development including the establishment of the microbiome, establishment of tolerance and maturation of the epithelium. Here the authors show a histone demethylase LSD1 is required for postnatal intestinal epithelium maturation and how this impacts local immune cell composition and gut homeostasis.
- Alberto Díez-Sánchez
- , Håvard T. Lindholm
- & Menno J. Oudhoff
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Article
| Open AccessIlluminating the complete ß-cell mass of the human pancreas- signifying a new view on the islets of Langerhans
The pancreatic islets of Langerhans play a pivotal role in regulating blood glucose homeostasis through the regulated secretion of the hormones insulin and glucagon. Here, the authors use deep tissue 3D imaging to re-construct the entire human pancreas at microscopic resolution and display previously unrecognized heterogeneities in the islet’s cellularity with pre-clinical and clinical implications.
- Joakim Lehrstrand
- , Wayne I. L. Davies
- & Ulf Ahlgren
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Article
| Open AccessRapid evolutionary change in trait correlations of single proteins
Trait correlations impact evolvability as selection on one trait can influence others. Here, the authors examine trait correlation in two proteins, a fluorescent protein & an antibiotic resistance enzyme, observing rapid evolution of trait correlations through changes in the biophysical properties of these proteins.
- Pouria Dasmeh
- , Jia Zheng
- & Andreas Wagner
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Article
| Open AccessCross-link assisted spatial proteomics to map sub-organelle proteomes and membrane protein topologies
The spatial mapping of proteins can give important functional insights. Here, Zhu et al. develop a cross-linking mass spectrometry-based spatial proteomics method that does not require protein engineering, affords sub-organelle resolution, and elucidates both protein locations and membrane topologies.
- Ying Zhu
- , Kerem Can Akkaya
- & Fan Liu
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Article
| Open AccessPhylogenomic profiles of whole-genome duplications in Poaceae and landscape of differential duplicate retention and losses among major Poaceae lineages
Grasses share a whole-genome duplication called rho, but the adaptive implications are unclear. Here, the authors conduct phylogenomic and phylotranscriptomic analyses of 363 grasses, identifying additional whole-genome duplications and finding that duplicates are implicated in environmental adaptations or morphogenesis.
- Taikui Zhang
- , Weichen Huang
- & Hong Ma
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Article
| Open AccessSynergistic effect of two human-like monoclonal antibodies confers protection against orthopoxvirus infection
In this study, the authors show that a single dose of a combination of two human-like monoclonal antibodies protect mice in therapeutic treatment against challenges with ectromelia virus and monkeypox virus. Combination treatment provided more effective viral clearance than single antibody treatment.
- Hadas Tamir
- , Tal Noy-Porat
- & Tomer Israely
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Article
| Open AccessExposing the molecular heterogeneity of glycosylated biotherapeutics
The molecular heterogeneity of glycosylated biotherapeutics often complicates analysis by intact mass spectrometry. Here, the authors propose a simplified procedure for characterization that employs proton transfer charge reduction. Integration with glycomic and glycopeptide datasets can further provide glycoform-level information.
- Luis F. Schachner
- , Christopher Mullen
- & Wendy Sandoval
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Article
| Open AccessUltrasensitive single-step CRISPR detection of monkeypox virus in minutes with a vest-pocket diagnostic device
The recent monkeypox outbreak highlighted the need for rapid and accurate diagnosis of this disease. Here, authors develop an ultrasensitive and streamlined CRISPR assay using miniaturized device, which can detect monkeypox virus in rash fluid swab, oral swab, saliva, and urine within 15 minutes.
- Yunxiang Wang
- , Hong Chen
- & Shengqi Wang
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Article
| Open AccessOptogenetic control of mRNA condensation reveals an intimate link between condensate material properties and functions
Biomolecular condensates play important roles in diverse cellular activities. Here the authors employ optogenetic tool and single-molecule mRNA imaging, showing that sequestering target mRNAs into condensates lead to translation inhibition.
- Min Lee
- , Hyungseok C. Moon
- & Yongdae Shin
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Article
| Open AccessMicroenvironmental reorganization in brain tumors following radiotherapy and recurrence revealed by hyperplexed immunofluorescence imaging
Improved imaging techniques are required to help advance our understanding of the complex role of the tumour microenvironment (TME). Here, the authors develop a high-throughput, highly multiplexed tissue visualisation workflow and demonstrate its utility by characterising the response of the TME to radiotherapy in preclinical models of glioblastoma.
- Spencer S. Watson
- , Benoit Duc
- & Johanna A. Joyce
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Article
| Open AccessFunctional protein dynamics in a crystal
Work by Klyshko and Kim et al. lays the foundation for simulating pump-probe experiments and demonstrates how the dynamic behaviour of proteins extends to the crystal environment, emphasizing the need for an ensemble view in understanding functional motions.
- Eugene Klyshko
- , Justin Sung-Ho Kim
- & Sarah Rauscher
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Article
| Open AccessAlkyne-tagged SERS nanoprobe for understanding Cu+ and Cu2+ conversion in cuproptosis processes
Simultaneously quantifying mitochondrial Cu+ and Cu2+ levels is vital for understanding the molecular mechanism of mitochondria-related biological events. Here the authors report an alkynyl-labeled SERS probe to simultaneously monitor free Cu+ and Cu2+ in mitochondria, and unveil their roles during ischemia and cuproptosis processes.
- Sihan Zhang
- , Yuxiao Mei
- & Yang Tian
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Article
| Open AccessIntegrated proteogenomic and metabolomic characterization of papillary thyroid cancer with different recurrence risks
Papillary thyroid cancers (PTC) generally have good prognosis, but their recurrence rate remains high. Here, the authors use proteogenomics and metabolomics to identify molecular features in PTC tumours and determine PTC subtypes that are associated with prognosis and potential targeted therapies.
- Ning Qu
- , Di Chen
- & Rongliang Shi
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Article
| Open AccessHydrophobic mismatch drives self-organization of designer proteins into synthetic membranes
The organization of membrane proteins is critical to cellular function. Here the authors explore how computational protein design, MD simulation, and cell-free systems can be combined to elucidate how membrane-protein hydrophobic mismatch affects protein folding and organization in synthetic lipid membranes.
- Justin A. Peruzzi
- , Jan Steinkühler
- & Neha P. Kamat
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Article
| Open AccessKSNP: a fast de Bruijn graph-based haplotyping tool approaching data-in time cost
Haplotyping is the process of distinguishing alleles inherited together on a chromosome, a crucial step in assembling and interpreting genome sequences. Here, the authors present a computationally efficient haplotype assembly tool for long read sequencing data.
- Qian Zhou
- , Fahu Ji
- & Jue Ruan
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Article
| Open AccessAdaptive expansion of ERVK solo-LTRs is associated with Passeriformes speciation events
Endogenous retroviruses (ERVs) are remnants of ancient viruses embedded in animal DNA. This study found that the solitary long terminal repeats of ERVs in birds, particularly Passeriformes, have evolved to influence gene expression, potentially contributing to adaptive diversification of species.
- Guangji Chen
- , Dan Yu
- & Shaohong Feng
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Article
| Open AccessLDL receptor-related protein 5 selectively transports unesterified polyunsaturated fatty acids to intracellular compartments
The mechanisms transporting fatty acids into the cell are not completely understood. Here, the authors discover a selective transporter for a specific class of lipids, and show its role in regulating neutrophil function during myocardial ischemia-reperfusion injury.
- Wenwen Tang
- , Yi Luan
- & Dianqing Wu
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Article
| Open AccessTeacher-student collaborated multiple instance learning for pan-cancer PDL1 expression prediction from histopathology slides
PDL1 expression is a common biomarker for immunotherapy response in cancer, and it is usually quantified using immunohistochemistry. Here, the authors develop a weakly supervised learning approach combining multiple instance learning and a teacher-student framework to predict PDL1 expression from histopathological imaging.
- Darui Jin
- , Shangying Liang
- & Xiangzhi Bai
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Article
| Open AccessComparative characterization of the infant gut microbiome and their maternal lineage by a multi-omics approach
Here, the authors employ multi-omics on a cohort comprising three generations of family members, showing that fecal microbiota populations, functions, and metabolome of infants vary greatly from their maternal lineage, exhibiting a less diverse microbiota and differences in various metabolite classes including short- and branched-chain fatty acids.
- Tomás Clive Barker-Tejeda
- , Elisa Zubeldia-Varela
- & Alma Villaseñor
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Article
| Open AccessLarge-volume focus control at 10 MHz refresh rate via fast line-scanning amplitude-encoded scattering-assisted holography
This study presents a wavefront shaping scheme to control optical focus in a large 3D space at the unprecedented rate of 30 MHz with micron-scale precision and random accessibility via reallocation of degrees of freedom in spatiotemporal domain.
- Atsushi Shibukawa
- , Ryota Higuchi
- & Mooseok Jang
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Article
| Open AccessHalogen doped graphene quantum dots modulate TDP-43 phase separation and aggregation in the nucleus
Modulating amyloid protein phase separation and fibrilization may help in addressing neurodegenerative diseases. This study demonstrates that halogen-doped graphene quantum dots can modulate these processes in TDP-43 in both nucleus and cytoplasm.
- Hong Zhang
- , Huazhang Guo
- & Bin Dai
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Article
| Open AccessSubcellular pathways through VGluT3-expressing mouse amacrine cells provide locally tuned object-motion-selective signals in the retina
How the spatial distribution of synapses relates to the subcellular integration and transmission of signals is not fully understood. Here authors combine functional and connectomic analysis to map the subcellular flow of information in retinal amacrine cells.
- Karl Friedrichsen
- , Jen-Chun Hsiang
- & Josh L. Morgan
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Article
| Open AccessContext-aware deep learning enables high-efficacy localization of high concentration microbubbles for super-resolution ultrasound localization microscopy
Ultrasound localisation microscopy enables deep tissue microvascular imaging. Here, authors introduce LOCA-ULM, a deep learning pipeline enhancing localisation accuracy in high microbubble concentrations. LOCA-ULM reveals dense cerebrovascular networks and enhances the sensitivity of functional ULM.
- YiRang Shin
- , Matthew R. Lowerison
- & Pengfei Song
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Article
| Open AccessThe CRISPR-Cas13a Gemini System for noncontiguous target RNA activation
CRISPR-Cas13a based methods currently use contiguous target RNA activation, which only enables single-target detection or editing. Here the authors propose a noncontiguous target RNA activation approach which can provide rapid, simultaneous and sensitive detection of two RNAs in a single readout, as well as parallel dual transgene knockdown.
- Hongrui Zhao
- , Yan Sheng
- & Jiaming Hu
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Article
| Open AccessReLo is a simple and rapid colocalization assay to identify and characterize direct protein–protein interactions
Characterising interactions between proteins that are large and poorly soluble remains challenging. Here, the authors describe ReLo, a rapid and versatile eukaryotic cell culture-based method for detecting and studying direct interactions between structurally complex proteins.
- Harpreet Kaur Salgania
- , Jutta Metz
- & Mandy Jeske
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Article
| Open AccessArchaeological and molecular evidence for ancient chickens in Central Asia
The origin and dispersal of the chicken across Eurasia is unclear. Here, the authors examine eggshell fragments from southern Central Asia with paleoproteomics to identify chicken eggshells, suggesting that chickens may have been an important dietary component as early as 400BCE.
- Carli Peters
- , Kristine K. Richter
- & Robert N. Spengler III
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Article
| Open AccessBiomimetic NIR-II fluorescent proteins created from chemogenic protein-seeking dyes for multicolor deep-tissue bioimaging
Near-infrared-I/II fluorescent proteins (NIR-I/II FPs) are crucial for in vivo imaging, but their availability is still scarce. Here, the authors make use of protein-seeking NIR-II dyes as chromophores, which covalently bind to tag proteins and thus creating biomimetic NIR-II FPs.
- Jiajun Xu
- , Ningning Zhu
- & Shoujun Zhu
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Article
| Open AccessPLMSearch: Protein language model powers accurate and fast sequence search for remote homology
Homologous protein search is one of the most commonly used methods for protein analysis. Here, authors propose PLMSearch, a search method that takes only sequences as input and can search millions of protein pairs in seconds while maintaining sensitivity comparable to SOTA structure search methods.
- Wei Liu
- , Ziye Wang
- & Shanfeng Zhu
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Article
| Open AccessTM4SF19-mediated control of lysosomal activity in macrophages contributes to obesity-induced inflammation and metabolic dysfunction
Adipose tissue adapts to overnutrition in a complex process, wherein specialized immune cells remove and replace dysfunctional and stressed adipocytes with new fat cells. Here, the authors show that the deletion of TM4SF19 expressed in lipid-associated macrophages, enhances the clearance of dying adipocytes, thereby improving local and systemic insulin sensitivity as well as energy expenditure.
- Cheoljun Choi
- , Yujin L. Jeong
- & Yun-Hee Lee
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Article
| Open AccessProjective light-sheet microscopy with flexible parameter selection
Projection imaging for multi-cellular samples can be hindered by several factors, including low contrast. Here, the authors propose projective light-sheet imaging with parameter selection (props) of imaging depth, position and viewing angle.
- Bingying Chen
- , Bo-Jui Chang
- & Reto Fiolka
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Article
| Open AccessDELVE: feature selection for preserving biological trajectories in single-cell data
Characteristic genes or proteins driving continuous biological processes are difficult to uncover from noisy single-cell data. Here, authors present DELVE, an unsupervised feature selection method to identify core molecular features driving cell fate decisions.
- Jolene S. Ranek
- , Wayne Stallaert
- & Jeremy E. Purvis
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Article
| Open AccessSpiDe-Sr: blind super-resolution network for precise cell segmentation and clustering in spatial proteomics imaging
Imaging mass cytometry (IMC) is a powerful single-cell resolution platform for targeted spatial proteomics, but it can be constrained by imaging noise and resolution. Here, the authors propose SpiDe-Sr, a super-resolution network embedded with a denoising module for IMC spatial resolution enhancement.
- Rui Chen
- , Jiasu Xu
- & Xianting Ding
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Article
| Open AccessMicroevolution, reinfection and highly complex genomic diversity in patients with sequential isolates of Mycobacterium abscessus
Mycobacterium abscessus is considered an emerging pathogen, given its prevalence in patients with pulmonary diseases, such as cystic fibrosis. Here, authors perform a genomic analysis on sequential isolates obtained from patients with persistent infections of M. abscessus.
- Sergio Buenestado-Serrano
- , Miguel Martínez-Lirola
- & Darío García de Viedma
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Article
| Open AccessBenchtop mesoSPIM: a next-generation open-source light-sheet microscope for cleared samples
The demand to image large biological samples at high resolution requires improvement in current light-sheet microscopy tools. Here, the authors present an improved, benchtop mesoSPIM with a significantly increased field-of-view, improved resolution and improved throughput.
- Nikita Vladimirov
- , Fabian F. Voigt
- & Fritjof Helmchen
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Article
| Open AccessPredicting and improving complex beer flavor through machine learning
Perception and appreciation of food flavour depends on many factors, posing a challenge for effective prediction. Here, the authors combine extensive chemical and sensory analyses of 250 commercial Belgian beers to train machine learning models that enable flavour and consumer appreciation prediction.
- Michiel Schreurs
- , Supinya Piampongsant
- & Kevin J. Verstrepen
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Article
| Open AccessSingle drop cytometry onboard the International Space Station
Real-time lab analysis is key to support clinical research during space missions. Here, the authors show scant test samples can be measured in microgravity using a miniature cytometery-based analyzer, the rHEALTH ONE with specific spaceflight modifications.
- Daniel J. Rea
- , Rachael S. Miller
- & Eugene Y. Chan
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Article
| Open AccessIon mobility-tandem mass spectrometry of mucin-type O-glycans
Currently, only a few specialized labs can characterize O-glycans. The present study couples high-resolution ion mobility spectrometry with tandem mass spectrometry to efficiently identify complex O-glycan structures in clinical samples.
- Leïla Bechtella
- , Jin Chunsheng
- & Kevin Pagel
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Article
| Open AccessFunctional screening in human HSPCs identifies optimized protein-based enhancers of Homology Directed Repair
Here the authors describe a functional screening platform in human stem cells to identify and optimize protein-based gene editing additives that increase homologous directed recombination and have potential to improve gene therapy workflows.
- Juan A. Perez-Bermejo
- , Oghene Efagene
- & Kristen L. Seim
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Article
| Open AccessPrior infection with unrelated neurotropic virus exacerbates influenza disease and impairs lung T cell responses
Co-infections are much less studied than single pathogen infections. Here, the authors show that co-infection with two unrelated viruses, neurotropic Semliki Forest virus and influenza A virus, exacerbates influenza-related lung pathology and prolongs lung virus replication in a mouse model.
- Isabelle Jia-Hui Foo
- , Brendon Y. Chua
- & Lukasz Kedzierski
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Article
| Open AccessPhotoswitchable polyynes for multiplexed stimulated Raman scattering microscopy with reversible light control
Bioimaging with photocontrol and multiplexing capability is vital for studying cellular interactions and dynamics, but multiplexed stimulated Raman scattering (SRS) imaging with reversible photocontrol is elusive. Here, the authors report SRS microscopy with Carbow-switch enabling multiplexed SRS imaging and tracking in live cells with reversible photocontrol and high spatiotemporal selectivity.
- Yueli Yang
- , Xueyang Bai
- & Fanghao Hu
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