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| Open AccessKSHV infection of B cells primes protective T cell responses in humanized mice
Kaposi sarcoma associated herpesvirus (KSHV) and Epstein Barr virus often co-infect hosts and some malignancies, such as primary effusion lymphoma, are typically arising from dual-infected cells. Here authors recapitulate dual infection in a humanized mouse model, and find that under these conditions, an efficient and specific CD8+ T cell response is mounted against the lytic KSHV antigen K6.
- Nicole Caduff
- , Lisa Rieble
- & Christian Münz
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Article
| Open Accessm6a methylation orchestrates IMP1 regulation of microtubules during human neuronal differentiation
RNA-binding proteins play a pivotal role during neurodevelopment. Here, the authors show that m6A RNA methylation directs IGF2BP1/IMP1 protein to a set of mRNA targets, regulating a network of microtubule factors during neuronal differentiation.
- Pierre Klein
- , Marija Petrić Howe
- & Andres Ramos
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Article
| Open AccessPNPLA3 is a triglyceride lipase that mobilizes polyunsaturated fatty acids to facilitate hepatic secretion of large-sized very low-density lipoprotein
The PNPLA3 gene is associated with fatty liver disease. Here, the authors define a role for PNPLA3 as a polyunsaturated triglyceride lipase that maintains the balance between hepatic triglyceride storage and secretion.
- Scott M. Johnson
- , Hanmei Bao
- & Jun Liu
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Article
| Open AccessStructural basis of promoter recognition by Staphylococcus aureus RNA polymerase
Here, Yuan, Liu, and Xu et al. report cryo-EM structures of Staphylococcus aureus RNAP-promoter open complexes, highlighting distinct interactions of σA and σB with their cognate promoters.
- Linggang Yuan
- , Qingyang Liu
- & Yu Feng
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Article
| Open AccessPre-hypertrophic chondrogenic enhancer landscape of limb and axial skeleton development
Chondrocyte differentiation controls skeleton development and stature. Here, the authors map mouse fetal chondrocyte enhancers, highlighting their role in controlling bone genes and connecting stature to non-coding variants overlapping these enhancers.
- Fabrice Darbellay
- , Anna Ramisch
- & Guillaume Andrey
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Article
| Open AccessUltrasound-mediated delivery of doxorubicin to the brain results in immune modulation and improved responses to PD-1 blockade in gliomas
Ultrasound-mediated blood-brain barrier opening has been exploited to improve drug delivery in the brain. Here the authors show that low-intensity pulsed ultrasound in combination with intravenous injection of microbubbles enhances the delivery of doxorubicin and anti-PD1 in gliomas, improving anti-tumor immune responses.
- Víctor A. Arrieta
- , Andrew Gould
- & Adam M. Sonabend
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Article
| Open AccessHigh-throughput screening unveils nitazoxanide as a potent PRRSV inhibitor by targeting NMRAL1
There are limited prevention or treatment options for PRRSV. Here, the authors identified nitazoxanide as a promising inhibitor of PRRSV and demonstrate its antiviral efficacy in reducing PRRSV replication and transmission in vivo.
- Zhanding Cui
- , Jinlong Liu
- & Zengjun Lu
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Article
| Open AccessCentral transcriptional regulator controls photosynthetic growth and carbon storage in response to high light
Researchers identify unique transcriptional regulation that controls photosynthetic response, growth and biochemical carbon storage in high light for two variants of the same algae species, offering a glimpse into diel control of plant and crop yields.
- Seth Steichen
- , Arnav Deshpande
- & Lieve M. L. Laurens
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Article
| Open AccessA single-cell and spatial RNA-seq database for Alzheimer’s disease (ssREAD)
A systematic collection for single-cell and spatial transcriptomics is critical for in-depth analysis and novel discovery in AD. Here, authors show ssREAD which covers over 7 million cells and 381 spatial samples from human and mouse, providing a comprehensive resource for AD research.
- Cankun Wang
- , Diana Acosta
- & Qin Ma
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Article
| Open AccessGlobal critical soil moisture thresholds of plant water stress
Using systematic satellite observations of land surface temperature and soil moisture during soil dry-downs, the spatially-explicit global distribution of the critical soil moisture threshold of plant water stress and its drivers is uncovered.
- Zheng Fu
- , Philippe Ciais
- & William K. Smith
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Article
| Open AccessThe hippocampus dissociates present from past and future goals
It is unclear how the brain prioritizes goals. Here, the authors show that the mental timestamps assigned to goals guide their dissociation along the anterior-posterior parts of the hippocampus, extending its long axis system to include temporal goal organization.
- Alison Montagrin
- , Denise E. Croote
- & Daniela Schiller
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Article
| Open AccessGenetic determinants of host- and virus-derived insertions for hepatitis E virus replication
In this study, the authors identify genetic insertions in the population of hepatitis E virus analyzed in serum samples of a patient with ribavirin treatment failure. They show that these genomic rearrangements promote viral replication without affecting ribavirin sensitivity.
- Michael Hermann Wißing
- , Toni Luise Meister
- & Daniel Todt
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Article
| Open AccessSpectro-temporal acoustical markers differentiate speech from song across cultures
What features distinguish speech from song? Here, the authors show that consistent acoustical spectro-temporal features are sufficient to distinguish speech and song across different societies throughout the world.
- Philippe Albouy
- , Samuel A. Mehr
- & Robert J. Zatorre
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Article
| Open AccessSingle-cell transcriptomic atlas reveals increased regeneration in diseased human inner ear balance organs
Loss of inner ear hair cells leads to permanent hearing loss and balance dysfunction. Whether human utricular cells regenerate is unknown. Here, the authors present a single-cell resource of utricular cells from organ donors and schwannoma patients and describe transcriptional changes during homeostasis and in response to damage.
- Tian Wang
- , Angela H. Ling
- & Alan G. Cheng
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Article
| Open AccessDevelopment and organization of the retinal orientation selectivity map
The functional organization rules of retinal orientation are not fully understood. Here the authors show that orientation detection, a crucial task for visual perception, is organized in the mouse retina along concentric axes, and that this organization develops even in the absence of visual experience or patterned spontaneous activity.
- Dominic J. Vita
- , Fernanda S. Orsi
- & Alexandre Tiriac
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Article
| Open AccessTau propagation in the brain olfactory circuits is associated with smell perception changes in aging
The role of olfactory pathways in the development of neurodegeneration in Alzheimer’s disease is not well understood. Here, the authors show odor identification deficits are predictive of tau accumulation and progression in olfactory pathways, and that tau spreads from medial temporal lobe structures towards the olfactory system.
- Ibai Diez
- , Laura Ortiz-Terán
- & Jorge Sepulcre
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Article
| Open AccessA machine learning contest enhances automated freezing of gait detection and reveals time-of-day effects
The absence of an objective way of assessing freezing of gait in Parkinson’s Disease hinders research and care. A machine-learning contest using wearable sensor data delivered detection algorithms with high precision and identified time-of-day effects.
- Amit Salomon
- , Eran Gazit
- & Jeffrey M. Hausdorff
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Article
| Open AccessSingle-cell analysis reveals a subpopulation of adipose progenitor cells that impairs glucose homeostasis
Adipose tissue harbors functionally distinct progenitor cell subsets. Using scRNAseq and functional assays, we disclose a pathogenic adipose progenitor subset, which impairs glycose homeostasis through the construction of a detrimental niche.
- Hongdong Wang
- , Yanhua Du
- & Yan Bi
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Article
| Open AccessOxime-functionalized anti-insecticide fabric reduces insecticide exposure through dermal and nasal routes, and prevents insecticide-induced neuromuscular-dysfunction and mortality
Exposition to insecticides can be dangerous. Here, authors developed an oxime-fabric body suit and facemask that chemically deactivate insecticides and prevent insecticide-induced lethal effects, offering an affordable solution for farmer safety.
- Mahendra K. Mohan
- , Ketan Thorat
- & Praveen Kumar Vemula
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Article
| Open AccessPm57 from Aegilops searsii encodes a tandem kinase protein and confers wheat powdery mildew resistance
Powdery mildew is a devastating disease that affects global wheat production. Here, the authors report the cloning of the Aegilops searsii-derived powdery mildew resistance gene Pm57 that encodes a tandem kinase protein.
- Yue Zhao
- , Zhenjie Dong
- & Wenxuan Liu
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Article
| Open AccessMicrobiota regulates the TET1-mediated DNA hydroxymethylation program in innate lymphoid cell differentiation
The epigenetic program underlying the differentiation of innate lymphoid cell precursors (ILCPs) into innate lymphoid cell (ILC) subsets remains poorly understood. Here the authors show genome-wide distribution of the DNA methylation and hydroxymethylation in murine ILC subsets and at postnatal stage, gut microbiota contributes to the downregulation of TET1 level, resulting in an expansion of ILC1s.
- Xusheng Zhang
- , Xintong Gao
- & Shuo Wang
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Article
| Open AccessCoexistence of state, choice, and sensory integration coding in barrel cortex LII/III
It is an open question whether choice signals in primary sensory areas have a causal influence on an animal’s perception. Here, the authors show that early sensory representations in the neocortex can be selectively manipulated to bias perception during discrimination behavior.
- Pierre-Marie Gardères
- , Sébastien Le Gal
- & Florent Haiss
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Article
| Open AccessPlanum temporale asymmetry in newborn monkeys predicts the future development of gestural communication’s handedness
The planum temporale is a key structure in the human language network. Here the authors show that planum temporale asymmetry at birth in baboons predicts the development of communicative right-hand use, which suggests some common features in the wiring of communicative properties between species.
- Yannick Becker
- , Romane Phelipon
- & Adrien Meguerditchian
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Article
| Open AccessTargeting dependency on a paralog pair of CBP/p300 against de-repression of KREMEN2 in SMARCB1-deficient cancers
Loss of SMARCB1 has been identified in a number of cancers. Here, the authors report a paralog pair of CBP and p300 as a synthetic lethal target in SMARCB1-deficient cancers. Simultaneous inhibitors of CBP/p300 could be therapeutic agents for SMARCB1-deficient cancers.
- Mariko Sasaki
- , Daiki Kato
- & Hideaki Ogiwara
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Article
| Open AccessFBXO7 ubiquitinates PRMT1 to suppress serine synthesis and tumor growth in hepatocellular carcinoma
How serine synthesis is regulated in cancer remains to be further explored. Here the authors identify FBXO7, an E3 ubiquitin ligase, inhibits serine synthesis in hepatocellular carcinoma by promoting ubiquitination and degradation of PRMT1 methyltransferase.
- Li Luo
- , Xingyun Wu
- & Kui Wang
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Article
| Open AccessGeneral mechanisms of task engagement in the primate frontal cortex
Intrinsic motivational fluctuation can lead to complete disengagement in the real world. Here, the authors built a model predicting such behaviors and examined neural activity as macaques spontaneously disengage, identifying a network of frontal regions regulating engagement and motivation.
- Jan Grohn
- , Nima Khalighinejad
- & Nils Kolling
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Article
| Open AccessA candidate sex determination locus in amphibians which evolved by structural variation between X- and Y-chromosomes
Genetic mechanisms of sex determination are still unknown in most amphibians. This study elucidates a mechanism behind amphibian sex determination by uncovering a sex-determining locus (bod1l gene and a Y-specific non-coding RNA, ncRNA-Y) in European green toads (Bufo(tes) viridis) which initiates male development.
- Heiner Kuhl
- , Wen Hui Tan
- & Matthias Stöck
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Article
| Open AccessZebrafish Avatar-test forecasts clinical response to chemotherapy in patients with colorectal cancer
Zebrafish patient-derived xenograft models (zAvatar) can be used to study cancer biology as well as to predict patient clinical outcomes and response to therapies. Here, in a cohort of 55 patients with colorectal cancer, the authors report that the zAvatar-test can predict response to chemotherapy and clinical outcome with 91% accuracy.
- Bruna Costa
- , Marta F. Estrada
- & Rita Fior
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Article
| Open AccessBactericidal effect of tetracycline in E. coli strain ED1a may be associated with ribosome dysfunction
The human gut contains diverse bacterial strains that are beneficial/critical for health. Here, the authors compare the response of human gut and laboratory E. coli strains to the antibiotic tetracycline in molecular detail and find a severe dysfunction of protein synthesis only in the gut strain.
- Iskander Khusainov
- , Natalie Romanov
- & Martin Beck
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Article
| Open AccessThe manganese transporter SLC39A8 links alkaline ceramidase 1 to inflammatory bowel disease
The metal transporter SLC39A8 is linked to blood manganese (Mn) levels and inflammatory bowel diseases (IBD). Here, the authors show that loss of SLC39A8 impairs intestinal Mn absorption and epithelial integrity, suggesting potential therapeutic strategies targeting alkaline ceramidase 1 for IBD patients with SLC39A8 deficiency.
- Eun-Kyung Choi
- , Thekkelnaycke M. Rajendiran
- & Young Ah Seo
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Article
| Open AccessPostmortem imaging reveals patterns of medial temporal lobe vulnerability to tau pathology in Alzheimer’s disease
Using high-resolution ex vivo MRI and serial histology, Ravikumar et al. characterise 3D tau spread across histologically defined medial temporal lobe subregions thus providing a postmortem reference for in vivo studies on early Alzheimer’s disease.
- Sadhana Ravikumar
- , Amanda E. Denning
- & Paul A. Yushkevich
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Article
| Open AccessSupramolecular assembly activated single-molecule phosphorescence resonance energy transfer for near-infrared targeted cell imaging
Phosphorescence resonance energy transfer systems have potential in light-harvesting and bioimaging, but host-guest systems are rarely explored. Here, the authors report the development of a macrocyclic host-guest system for targeted cell imaging.
- Xiaolu Zhou
- , Xue Bai
- & Yu Liu
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Article
| Open AccessStructure and mechanism of the K+/H+ exchanger KefC
Intracellular potassium (K+) homeostasis is achieved by activity of both ion channels and transporters. Here, the authors report structures of E. coli glutathione (GSH)-gated K+ efflux transporter KefC with bound K+ and conclude that the ion-binding site is adapted for binding a dehydrated ion.
- Ashutosh Gulati
- , Surabhi Kokane
- & David Drew
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Article
| Open AccessPlants interfere with non-self recognition of a phytopathogenic fungus via proline accumulation to facilitate mycovirus transmission
Mycoviruses are obligate parasites of fungi. Here, Hai et al. show that mycoviruses can induce hypovirulence in the fungus Sclerotinia, and plants infected by Sclerotinia facilitate the transmission of these mycoviruses, thereby helping the plants defend against Sclerotinia.
- Du Hai
- , Jincang Li
- & Jiatao Xie
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Article
| Open AccessOrthogonal proteogenomic analysis identifies the druggable PA2G4-MYC axis in 3q26 AML
The overexpression of the ecotropic viral integration site-1 gene (EVI1/MECOM) marks the most lethal acute myeloid leukemia subgroup carrying 3q26 abnormalities. Here, pan-histone deacetylase inhibitors are identified as potent repressors of EVI1 and PA2G4 as a druggable target.
- Matteo Marchesini
- , Andrea Gherli
- & Giovanni Roti
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Article
| Open AccessAngiogenesis is uncoupled from osteogenesis during calvarial bone regeneration
Fractured long bones regenerate through osteo-angiogenic coupling, but how calvarial bone healing occurs is not yet clear. Here they show that regenerating blood vessels separate from co-migrating progenitors in calvarial bones, resulting in osteoblasts mineralizing a previously vascularized lesion.
- M. Gabriele Bixel
- , Kishor K. Sivaraj
- & Ralf H. Adams
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Article
| Open AccessBurkholderia pseudomallei BipD modulates host mitophagy to evade killing
The selective degradation of mitochondria by autophagy is essential for cell homeostasis. Here, Nan et al show that the effector protein BipD, secreted by Burkholderia pseudomallei, is able to modulate host mitophagy to promote its survival.
- Dongqi Nan
- , Chenglong Rao
- & Qian Li
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Article
| Open AccessFTO deficiency in older livers exacerbates ferroptosis during ischaemia/reperfusion injury by upregulating ACSL4 and TFRC
Transplanted older livers are prone to injury through unclear mechanisms, precluding effective treatment development. Here, the authors show that decreased FTO expression in older livers inhibits Acsl4 and Tfrc mRNA stability in an m6A-dependent manner, increasing cell death in older donor livers.
- Rong Li
- , Xijing Yan
- & Yang Yang
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Article
| Open AccessDownregulation of rhodopsin is an effective therapeutic strategy in ameliorating peripherin-2-associated inherited retinal disorders
Due to the abundance of pathogenic variants in Peripherin-2, causing peripherin-2-associated inherited retinal disorders, and the lack of any approved treatment, it is imperative to identify an effective therapeutic strategy. Here the authors show that reducing rhodopsin levels improves retinal function and structure and decreases inflammatory responses.
- Christian T. Rutan Woods
- , Mustafa S. Makia
- & Muayyad R. Al-Ubaidi
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Article
| Open AccessControl of a gene transfer agent cluster in Caulobacter crescentus by transcriptional activation and anti-termination
This study reveals that in the alpha-proteobacterium, Caulobacter crescent, a two-tier regulation by transcriptional activation and anti-termination coordinates the synthesis of phage-like Gene Transfer Agents (GTA) particles.
- Ngat T. Tran
- & Tung B. K. Le
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Article
| Open AccessSystematic evaluation of fMRI data-processing pipelines for consistent functional connectomics
The effects of different choices on preprocessing pipelines for functional connectomics remain unclear. Here, the authors systematically evaluate a multitude of pipelines on resting-state fMRI, revealing a number of optimal pipelines for functional brain network analysis.
- Andrea I. Luppi
- , Helena M. Gellersen
- & Emmanuel A. Stamatakis
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Article
| Open AccessBacteriophage defends murine gut from Escherichia coli invasion via mucosal adherence
Authors profile the antimicrobial activity of an Escherichia coli bacteriophage (in vivo and in vitro), isolated from chicken faeces.
- Jiaoling Wu
- , Kailai Fu
- & Fang Tang
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Article
| Open AccessFairer AI in ophthalmology via implicit fairness learning for mitigating sexism and ageism
Biased medical artificial intelligence systems pose significant potential risks to achieving fair and equitable healthcare. Here, we demonstrate a fairer ophthalmology AI that mitigates sexism and ageism through implicit fairness learning.
- Weimin Tan
- , Qiaoling Wei
- & Chen Zhao
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Article
| Open AccessSemaglutide ameliorates cardiac remodeling in male mice by optimizing energy substrate utilization through the Creb5/NR4a1 axis
Semaglutide is used for glucose control and weight reduction. Here, the authors show that it enhances myocardial metabolism by targeting Creb5/NR4a1, protecting against cardiac remodeling and offering a therapeutic approach for heart failure through metabolic regulation.
- Yu-Lan Ma
- , Chun-Yan Kong
- & Qi-Zhu Tang
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Article
| Open AccessSphingosine d18:1 promotes nonalcoholic steatohepatitis by inhibiting macrophage HIF-2α
Non-alcoholic steatohepatitis has with few well-defined biomarkers or clinically effective treatments but is promoted by inflammation. Here, the authors find an active lipid [So(d18:1)] that is significantly changed in patients and promotes inflammation by directly inhibiting macrophage HIF-2α.
- Jialin Xia
- , Hong Chen
- & Yanli Pang
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Perspective
| Open AccessBottlenecks in biobased approaches to plastic degradation
The way we generate and treat plastic waste is a key consideration in the transition from a take-make-waste model to a truly circular economy. Here, authors discuss their views on how biotechnology could contribute to solving the plastic problem, and the barriers we need to overcome to make such approaches a reality.
- Amelia R. Bergeson
- , Ashli J. Silvera
- & Hal S. Alper
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Article
| Open AccessCooperative growth in microbial communities is a driver of multistability
This study explores alternative stable states in microbial communities. Focusing on a respiratory tract community of 6 species, the authors identified four distinct stable states that are predicted to be driven by cooperative growth. The findings contrast with the common association between competitive interactions and multistability in microbial communities.
- William Lopes
- , Daniel R. Amor
- & Jeff Gore
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Article
| Open AccessLipid unsaturation promotes BAX and BAK pore activity during apoptosis
BAX and BAK are proapoptotic proteins that directly mediate mitochondrial outer membrane permeabilization (MOMP). Here, lipidomics and other data provide insight on how local lipid environment affects BAX and BAK function during apoptosis, suggesting that unsaturated lipids promote BAX pore activity.
- Shashank Dadsena
- , Rodrigo Cuevas Arenas
- & Ana J. García-Sáez
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Article
| Open AccessPulmonary maternal immune activation does not cross the placenta but leads to fetal metabolic adaptation
Maternal immune activation during pregnancy can negatively impact the developing fetus. Here, applying multi-omics (RNA-seq, phosphoproteomics and lipidomics) and imaging, the authors show that while maternal immune activation induces strong innate response in maternal organs it does not extend through the placenta but leads to fetal metabolic changes.
- Signe Schmidt Kjølner Hansen
- , Robert Krautz
- & Albin Sandelin
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