Featured
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Article
| Open AccessImportance of social inequalities to contact patterns, vaccine uptake, and epidemic dynamics
Contact patterns influence the spread of infectious diseases, but mathematical models of epidemics typically only account for age differences in contacts. Here, the authors investigate the importance of other sociodemographic characteristics in shaping contact patterns and vaccine uptake using survey data from Hungary.
- Adriana Manna
- , Júlia Koltai
- & Márton Karsai
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Article
| Open AccessGut microbiota produces biofilm-associated amyloids with potential for neurodegeneration
The microbiota of the intestinal tract is considered a large biofilm formed by myriads bacteria that have a considerable impact in health and disease. Here, the authors show that biofilm-associated proteins from intestinal microbiota form amyloid-like structures that exacerbate alpha-synuclein pathologies.
- Ariadna Fernández-Calvet
- , Leticia Matilla-Cuenca
- & Jaione Valle
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Article
| Open AccessTDP-43 proteinopathy in ALS is triggered by loss of ASRGL1 and associated with HML-2 expression
Amyotrophic Lateral Sclerosis is characterized by TDP-43 proteinopathy in the brain. Here, the authors find TDP-43 aggregation might be mediated by the loss of Asparaginase-like 1, an enzyme that degrades detrimental isoaspartates and is downregulated by the endogenous retrovirus HML-2.
- Marta Garcia-Montojo
- , Saeed Fathi
- & Avindra Nath
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Article
| Open AccessZero-shot learning enables instant denoising and super-resolution in optical fluorescence microscopy
The authors introduce ZS-DeconvNet, an unsupervised computational super-resolution method for multiple types of microscopes, that enhances image resolution by more than 1.5 times over the diffraction limit with 10 times lower fluorescence than regular superresolution imaging conditions.
- Chang Qiao
- , Yunmin Zeng
- & Qionghai Dai
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Article
| Open AccessExtracellular modulation of TREK-2 activity with nanobodies provides insight into the mechanisms of K2P channel regulation
K2P channels are important regulators of cellular electrical activity. Here the authors show how nanobody fragments can be used to detect and modulate TREK2 K2P channel activity to provide insight into the mechanism of gating.
- Karin E. J. Rödström
- , Alexander Cloake
- & Stephen J. Tucker
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Article
| Open AccessMagnetic voluntary head-fixation in transgenic rats enables lifespan imaging of hippocampal neurons
Head-fixation system is widely used in neuroscience research but has limitations in application due to restraint. Here the authors developed a magnetic voluntary head-fixation system that allows stable rat hippocampal imaging during complex behaviors.
- P. Dylan Rich
- , Stephan Yves Thiberge
- & David W. Tank
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Article
| Open AccessOptogenetic activation of dorsal raphe serotonin neurons induces brain-wide activation
The dorsal raphe nucleus (DRN) is a major source of serotonergic projections to brain-wide targets. Here the authors use optogenetics and fMRI to investigate brain-wide responses to activation of the DRN serotonergic pathway.
- Hiro Taiyo Hamada
- , Yoshifumi Abe
- & Kenji Doya
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Article
| Open AccessPhysiological basis for atmospheric methane oxidation and methanotrophic growth on air
Atmospheric methane-oxidizing bacteria constitute the sole biological sink for atmospheric methane. Here, Schmider et al. assess the ability and strategies of seven methanotrophic species to grow with air as sole energy, carbon, and nitrogen source, showing that these bacteria can grow on the trace concentrations of methane, carbon monoxide, and hydrogen present in air.
- Tilman Schmider
- , Anne Grethe Hestnes
- & Alexander T. Tveit
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Article
| Open AccessSevere drought exposure in utero associates to children’s epigenetic age acceleration in a global climate change hot spot
The study suggests a positive association between in utero drought exposure and faster biological aging in children in a global climate change hot spot. Drought experienced during pregnancy may reduce life expectancy.
- Xi Qiao
- , Bilinda Straight
- & Belinda L. Needham
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Article
| Open AccessFOXC1 regulates endothelial CD98 (LAT1/4F2hc) expression in retinal angiogenesis and blood-retina barrier formation
FOXC1 transcription factor plays a role in vascular development, but its mechanism is not well defined. Here, the authors show FOXC1 regulates retinal angiogenesis by promoting CD98 amino acid transporter expression to activate mTOR signalling, and also by promoting blood-retina barrier formation.
- Teena Bhakuni
- , Pieter R. Norden
- & Tsutomu Kume
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Article
| Open AccessMechanically robust and personalized silk fibroin-magnesium composite scaffolds with water-responsive shape-memory for irregular bone regeneration
The regeneration of critical-size bone defects, especially those with irregular shapes, remains a clinical challenge. Here, the authors report a shape-memory, tailorable, self-adaptive and bioactive silk fibroin/magnesium composite scaffold that can quickly match irregular defects by simple trimming and lead to good interface integration.
- Zhinan Mao
- , Xuewei Bi
- & Yufeng Zheng
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Article
| Open AccessSerological evidence of zoonotic filovirus exposure among bushmeat hunters in Guinea
In a serological analysis, Bore et al. utilise serum samples, collected from a cohort of individuals associated with bushmeat hunting and butchering, in the forested region of Guinea, a region close to the epicentre of the 2013–2016 West Africa Ebola virus disease epidemic.
- Joseph Akoi Boré
- , Joseph W. S. Timothy
- & Miles W. Carroll
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Article
| Open AccessGeologically younger ecosystems are more dependent on soil biodiversity for supporting function
This study demonstrates that soil BEF relationships diminish during long-term pedogenesis, highlighting the importance of soil biodiversity in sustaining multiple ecosystem functions in younger, drier soils.
- Jiao Feng
- , Yu-Rong Liu
- & Manuel Delgado-Baquerizo
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Article
| Open AccessThe vacuolar fusion regulated by HOPS complex promotes hyphal initiation and penetration in Candida albicans
The transition between yeast and hyphae is crucial for the pathogenicity of Candida albicans. Here, Liu et al. show that vacuole fusion is active during hyphal extension and that large vacuoles increase the mechanical forces of hyphae penetrating into organs.
- Yu Liu
- , Ruina Wang
- & Lan Yan
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| Open AccessThe great escape: a Shigella effector unlocks the septin cage
Shigella, an important human pathogen, can secrete effector proteins to invade host cells and evade mechanisms of cell-autonomous immunity. In a new manuscript published in Nature Communications, Xian et al. report that the Shigella kinase effector OspG promotes the ubiquitination of septin cytoskeletal proteins to evade cage entrapment.
- Ana T. López-Jiménez
- , Gizem Özbaykal Güler
- & Serge Mostowy
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Article
| Open AccessInterplay between Mg2+ and Ca2+ at multiple sites of the ryanodine receptor
Skeletal ryanodine receptor controls calcium mobilization indispensable for muscle contraction. Here, authors combine cryo-EM and molecular dynamics to uncover the structural basis of the intricate regulation of this channel by calcium and magnesium.
- Ashok R. Nayak
- , Warin Rangubpit
- & Montserrat Samsó
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Article
| Open AccessMAPP unravels frequent co-regulation of splicing and polyadenylation by RNA-binding proteins and their dysregulation in cancer
Here the authors apply the Motif Activity on Pre-mRNA Processing (MAPP) tool to standard RNA sequencing data, thereby unravelling the co-regulation of splicing and polyadenylation by RNA-binding proteins and their dysregulation in cancer.
- Maciej Bak
- , Erik van Nimwegen
- & Andreas J. Gruber
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Article
| Open AccessPost-translational modification-dependent oligomerization switch in regulation of global transcription and DNA damage repair during genotoxic stress
Here the authors show that the human transcription elongation factor AF9, part of Super Elongation Complex (SEC), undergoes oligomerization which can be reverted by post-translational modification in regulation of global transcription.
- Prathama Talukdar
- , Sujay Pal
- & Debabrata Biswas
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Article
| Open AccessJag1/2 maintain esophageal homeostasis and suppress foregut tumorigenesis by restricting the basal progenitor cell pool
Dysregulation of basal progenitor cells induces esophageal tumorigenesis but the underlying mechanism is less explored. Here, the authors show that Jag1/2 deficiency promotes expansion of basal progenitor cells, leading to reduced squamous epithelial differentiation and enhanced formation of squamous cell carcinoma in the foregut.
- Haidi Huang
- , Yu Jiang
- & Yongchun Zhang
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Article
| Open AccessProteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis
MAPK-driven tumorigenesis is often related to epithelial dedifferentiation but the regulatory mechanism is less clear. Here, the authors show that MAPK activation upregulates USP15 to promote deubiquitylation and stability of TBX3, a transcription factor implicated in thyroid development and differentiation, driving tumorigenesis in a BRAFV600E thyroid tumor model.
- Zhenlei Zhang
- , Yufan Wu
- & Li Zhao
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Article
| Open AccessOctyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways
The use of oncolytic viruses as a therapy for cancer is limited by mechanisms inhibiting viral replication in the tumor. Here, the authors show that a chemical derivative of itaconate, 4-octyl itaconate, increases oncolytic virus VSVΔ51 efficacy in various cancer models, through decreasing antiviral immunity.
- Naziia Kurmasheva
- , Aida Said
- & David Olagnier
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Article
| Open AccessMacro-scale relationship between body mass and timing of bird migration
Clarifying migration timing and how it links with underlying drivers is essential to understanding bird migration. This study finds body mass affects the timing of both spring and autumn migration, while environmental factors mainly affect the timing of spring migration.
- Xiaodan Wang
- , Marius Somveille
- & Zhijun Ma
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Article
| Open AccessNuclear actin structure regulates chromatin accessibility
Intranuclear actin contributes to nuclear structure. Inducing actin remodeling within the nucleus regulates chromatin accessibility, and is associated with phenotypic outcomes in mesenchymal stem cells. As such, dynamic actin remodeling may modulate gene expression.
- Buer Sen
- , Zhihui Xie
- & Janet Rubin
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Article
| Open AccessStructures of H5N1 influenza polymerase with ANP32B reveal mechanisms of genome replication and host adaptation
The authors demonstrate how avian H5N1 influenza A virus polymerase interacts with human ANP32B to facilitate the replication of the viral genetic information in mammalian hosts, revealing insights into cross-species transmission.
- Ecco Staller
- , Loïc Carrique
- & Ervin Fodor
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Article
| Open AccessMicrobial adaptation to spaceflight is correlated with bacteriophage-encoded functions
Viruses that infect bacteria shape microbial communities. Here, authors show that this may hold for bacteria isolated from the International Space Station, with spacefaring viruses correlated to host adaptation to the spaceflight environment.
- Iris Irby
- & Jared T. Broddrick
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Article
| Open AccessStructure and genome editing of type I-B CRISPR-Cas
Here the authors present two cryo-EM structures of the Synechocystis sp. PCC 6714 (Syn) type I-B Cascade, revealing the molecular mechanisms that underlie RNA-directed Cascade assembly, target DNA recognition and local conformational changes of the effector complex upon R-loop formation.
- Meiling Lu
- , Chenlin Yu
- & Yibei Xiao
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Article
| Open AccessCryo-EM structures of the human Elongator complex at work
Here the authors determined several cryo-EM structures of the human Elongator complex, which modifies anticodons of tRNAs. The structural work is complemented by functional analyses to understand this clinically relevant cellular machine at the molecular level.
- Nour-el-Hana Abbassi
- , Marcin Jaciuk
- & Sebastian Glatt
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Article
| Open AccessAn antiplasmid system drives antibiotic resistance gene integration in carbapenemase-producing Escherichia coli lineages
It has been predicted that mobilization of resistance genes from plasmid to chromosome is selected by an antibiotic pressure. Here, authors discover an antiplasmid system promoting the chromosomal integration of the carbapenemase gene blaOXA-48.
- Pengdbamba Dieudonné Zongo
- , Nicolas Cabanel
- & Isabelle Rosinski-Chupin
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Article
| Open AccessTRIM25 predominately associates with anti-viral stress granules
Different environmental stressors induce different subtypes of stress granules (SGs), and each of them presumably have distinct functions. Here the authors provide a framework for understanding the compositional and functional heterogeneity of SGs, and see that TRIM25 mainly associates with anti-viral SGs.
- Zehua Shang
- , Sitao Zhang
- & Da Jia
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Article
| Open AccessThree stepwise pH progressions in stratum corneum for homeostatic maintenance of the skin
Previous studies of the skin have suggested a neutral-to-acidic pH gradient in the outermost layer. Here, the authors perform quantitative intravital pH imaging of the stratum corneum, the outermost epidermal layer, and demonstrate three distinct pH zones - rather than a gradient - with different biological functions.
- Keitaro Fukuda
- , Yoshihiro Ito
- & Masayuki Amagai
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Article
| Open AccessA non-canonical visual cortical-entorhinal pathway contributes to spatial navigation
Neural circuitry conveying visual information to the medial entorhinal cortex (MEC), a crucial region for spatial cognition, is not fully understood. Here, the authors report a direct pathway from the secondary visual cortex to MEC layer 5a in mice and its involvement in memory-guided navigation, thus revealing a role of deep MEC in sensory information transmission.
- Qiming Shao
- , Ligu Chen
- & Guangfu Wang
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Article
| Open AccessIRE1α determines ferroptosis sensitivity through regulation of glutathione synthesis
The endoplasmic reticulum (ER) is a major site of lipid peroxidation during ferroptosis. Here authors show that the ER protein IRE1α determines ferroptosis induction via regulating glutathione synthesis independent of the unfolded protein response.
- Dadi Jiang
- , Youming Guo
- & Albert C. Koong
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Article
| Open AccessCEA-CD3 bispecific antibody cibisatamab with or without atezolizumab in patients with CEA-positive solid tumours: results of two multi-institutional Phase 1 trials
Cibisatamab is a T-cell bispecific antibody targeting the carcinoembryonic antigen (CEA) on tumor cells and CD3 epsilon chain on T cells. Here the authors report the results of two clinical trials of cibisatamab as monotherapy (NCT02324257) and in combination with atezolizumab (anti-PD-L1; NCT02650713) in patients with CEA-positive solid tumors.
- Neil H. Segal
- , Ignacio Melero
- & Guillem Argilés
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Article
| Open AccessHepatocytes differentiate into intestinal epithelial cells through a hybrid epithelial/mesenchymal cell state in culture
Hepatocytes dedifferentiate into progenitor-like cells in culture. Here, authors elucidate the dynamics and mechanisms of hepatocyte dedifferentiation and find an unexpected differentiation potential of hepatocytes into intestinal epithelial cells.
- Shizuka Miura
- , Kenichi Horisawa
- & Atsushi Suzuki
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Article
| Open AccessRisk assessment of a highly pathogenic H5N1 influenza virus from mink
In 2023, a highly pathogenic H5N1 virus caused an outbreak in mink. In the ferret model of influenza, the virus exhibits limited airborne transmissibility and high virulence. These findings indicate heightened pandemic potential of these viruses.
- Katherine H. Restori
- , Kayla M. Septer
- & Troy C. Sutton
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Article
| Open AccessComparison of intramyocellular lipid metabolism in patients with diabetes and male athletes
Endurance athletes and sedentary type 2 diabetes patients swapped their lifestyle for 8 weeks. Athletes store and utilise saturated fat intensely for performant physical activity, and type 2 diabetes patients reversed their dysmetabolic lipid state after endurance training.
- Alice M. Mezincescu
- , Amelia Rudd
- & Dana Dawson
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Article
| Open AccessCD5L as a promising biological therapeutic for treating sepsis
Authors explore the utility of CD5L for treating experimental sepsis. CD5L deficiency exacerbates experimental sepsis. Conversely, administration of recombinant CD5L in WT mice augments neutrophil function, enhances bacterial control, and mitigates inflammation, leading to substantial improvements in disease outcomes.
- Liliana Oliveira
- , M. Carolina Silva
- & Alexandre M. Carmo
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Article
| Open AccessMolecular fingerprinting of biological nanoparticles with a label-free optofluidic platform
Biosensing tools to detect multiple analytes in a high-throughput manner are still hindered by many limitations. Here, the authors present a label-free optofluidic platform integrating digital holography and microfluidics for analyte detection, allowing for the fingerprinting of heterogenous biological samples.
- Alexia Stollmann
- , Jose Garcia-Guirado
- & Romain Quidant
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Article
| Open AccessSustained bacterial N2O reduction at acidic pH
Microbial reduction of nitrous oxide to dinitrogen is considered negligible under acidic conditions. However, Guang He et al. show that a co-culture of two bacterial species derived from acidic tropical forest soil can reduce nitrous oxide at pH 4.5.
- Guang He
- , Gao Chen
- & Frank E. Löffler
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Article
| Open AccessCell-mediated cytotoxicity within CSF and brain parenchyma in spinal muscular atrophy unaltered by nusinersen treatment
Cell-mediated cytotoxicity observed in untreated SMA patients’ CSF and brain parenchyma. Spatial transcriptomic and multiplex immunohistochemistry linked cytotoxicity near affected motoneurons. Nusinersen treatment showed no impact on this profile.
- I-Na Lu
- , Phyllis Fung-Yi Cheung
- & Gerd Meyer zu Horste
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Article
| Open AccessDisentangling oncogenic amplicons in esophageal adenocarcinoma
Esophageal adenocarcinoma is characterised by frequent amplifications in oncogenes. Here, the authors use short- and long-read sequencing approaches to analyze primary tumor samples and tumour-derived organoids and to investigate the mechanisms underlying complex amplifications.
- Alvin Wei Tian Ng
- , Dylan Peter McClurg
- & Rebecca C. Fitzgerald
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Article
| Open AccessQuantifying 3′UTR length from scRNA-seq data reveals changes independent of gene expression
While gene expression analysis is commonly performed, 3′UTR length analysis is limited due to technical challenges. Here the authors provide an open-access analysis pipeline for scRNA-seq data to simultaneously quantify gene expression and 3′UTR length.
- Mervin M. Fansler
- , Sibylle Mitschka
- & Christine Mayr
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Article
| Open AccessGRouNdGAN: GRN-guided simulation of single-cell RNA-seq data using causal generative adversarial networks
Benchmarking GRN inference methods remains a challenge. Here, authors present GRouNdGAN, a causal generative model that imposes a user-defined GRN in its architecture to simulate realistic single-cell data, bridging the gap between synthetic and biological data benchmarks of GRN inference methods.
- Yazdan Zinati
- , Abdulrahman Takiddeen
- & Amin Emad
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Article
| Open AccessEnzyme-assisted high throughput sequencing of an expanded genetic alphabet at single base resolution
The expansion of the genetic code with synthetic nucleotides has broadened our ability to evolve DNA as a functional material, but we lack analytical tools for the expanded alphabet. Here the authors demonstrate an enzyme-assisted method for the sequencing of six-letter DNA.
- Bang Wang
- , Kevin M. Bradley
- & Steven A. Benner
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Article
| Open AccessDouble-negative B cells and DNASE1L3 colocalise with microbiota in gut-associated lymphoid tissue
Intestinal homeostasis is maintained by interactions between the gut-associated lymphoid tissue and the resident flora. Here Montorsi et al use multiplexed single cell omics to describe double negative type 2 B cells and DNASE1L3-expressing dendritic cells that interact and associate with microbiota on the human gut antigenic front line.
- Lucia Montorsi
- , Michael J. Pitcher
- & Jo Spencer
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Article
| Open AccessTransfer learning enables identification of multiple types of RNA modifications using nanopore direct RNA sequencing
Simultaneous profiling of multiple RNA modifications is a promising yet understudied field of research. Here, authors develop a transferable deep learning framework capable of detecting multiple types of RNA modifications in single nanopore sequencing sample.
- You Wu
- , Wenna Shao
- & Xiang Yu
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Article
| Open AccessSystematic dissection of tumor-normal single-cell ecosystems across a thousand tumors of 30 cancer types
Single-cell sequencing has enabled detailed analyses of the tumour microenvironment (TME). Here, the authors perform an integrative analysis of the TME using single-cell and spatial transcriptomics data from over a thousand tumours across thirty cancer types, identifying interferon-enriched community states predictive of immunotherapeutic responses.
- Junho Kang
- , Jun Hyeong Lee
- & Jong-Eun Park
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Article
| Open AccessTranscription stress at telomeres leads to cytosolic DNA release and paracrine senescence
Cellular senescence and the process of transcription are intimately linked, yet the mechanisms involved remain unclear. Here the authors show that a defect in TFIIS leads to telomere dysfunction, genome instability and the release of vesicles that induce senescence to neighboring cells.
- Athanasios Siametis
- , Kalliopi Stratigi
- & George A. Garinis
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Article
| Open AccessDrosophila Evi5 is a critical regulator of intracellular iron transport via transferrin and ferritin interactions
Vesicle transport ensures cargo delivery to cellular targets. Here, Soltani et al. show that Drosophila Evi5, a multiple sclerosis risk gene in humans, controls vesicular transport of iron-bound transferrins and physically interacts with ferritin.
- Sattar Soltani
- , Samuel M. Webb
- & Kirst King-Jones
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