Featured
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Article
| Open AccessRapid response of fly populations to gene dosage across development and generations
While developmental phenotypes are often multigenic and involve environmental inputs, most research approaches involve perturbation of small numbers of genes. Here they use a synthetic evolution approach in Drosophila to show that adding extra copies of bicoid leads to rapid, system-wide phenotypic responses, potentiated by highly polygenic traits such as embryo size.
- Xueying C. Li
- , Lautaro Gandara
- & Justin Crocker
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Article
| Open AccessBreast cancer cell-secreted miR-199b-5p hijacks neurometabolic coupling to promote brain metastasis
Breast cancer metastasis to the brain is rising in prevalence and is an increasingly lethal threat to the patients. Here, the authors show miR-199b-5p, secreted by some breast cancer cells and detected at a higher level in patients with brain metastases, impairs the metabolic coupling between neurons and astrocytes to facilitate development of brain metastasis.
- Xianhui Ruan
- , Wei Yan
- & Shizhen Emily Wang
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Article
| Open AccessControl of artificial membrane fusion in physiological ionic solutions beyond the limits of electroformation
Membrane fusion is crucial for fabricating artificial membranes. Here, the authors present an approach combining electric field with hydraulic pressure to physically control the fusion, enabling tuning of the shape and size of the 3D freestanding lipid bilayers in physiological solutions.
- Bong Kyu Kim
- , Dong-Hyun Kang
- & Tae Song Kim
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Article
| Open AccessGut microbiome remodeling and metabolomic profile improves in response to protein pacing with intermittent fasting versus continuous caloric restriction
Here, in a follow-up of a clinical study, the authors show that protein pacing and intermittent fasting improves gut symptomatology and microbial diversity, as well as reduces visceral fat compared to a heart-healthy, calorie-restricted diet matched for overall energy intake and expenditure in free-living humans.
- Alex E. Mohr
- , Karen L. Sweazea
- & Paul J. Arciero
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Article
| Open AccessLiquid foam improves potency and safety of gene therapy vectors
Gene therapy is a rapidly growing field, but is hindered by efficacy and safety concerns, including those related to delivery methods. Here, inspired by the use of foam in the delivery of pharmaceuticals, Dr. Stephan and colleagues formulated foam as a safe and effective delivery platform for gene therapy.
- K. Fitzgerald
- , S. B. Stephan
- & M. T. Stephan
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Article
| Open AccessDynamics underlie the drug recognition mechanism by the efflux transporter EmrE
Here, the authors reveal the protonation of a single membrane embedded glutamate residue within the homodimer of the efflux transporter EmrE modulates the structure and dynamics in an allosteric manner using NMR spectroscopy.
- Jianping Li
- , Ampon Sae Her
- & Nathaniel J. Traaseth
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Article
| Open AccessMemory CD8 T cells are vulnerable to chronic IFN-γ signals but not to CD4 T cell deficiency in MHCII-deficient mice
Memory CD8+ T cells persist poorly in MHCII-deficient mice. Here the authors show that this CD8+ T cell attrition is not caused by a lack of CD4+ T cell help, as previously proposed, but by chronic IFN-γ signals derived from endogenous colonic CD8+ T cells.
- Ruka Setoguchi
- , Tomoya Sengiku
- & Shohei Hori
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Article
| Open AccessNucleosomal DNA has topological memory
Here, the authors develop Topo-seq to measure the DNA topology (∆Lk) restrained by individual nucleosomes in vivo. They show that nucleosome DNA topology is imprinted by its native chromatin context and persists when the nucleosome is relocated.
- Joana Segura
- , Ofelia Díaz-Ingelmo
- & Joaquim Roca
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Article
| Open AccessMulti-omics in nasal epithelium reveals three axes of dysregulation for asthma risk in the African Diaspora populations
Here, the authors suggest that molecular dysregulation on three axes may play a critical role in asthma within the African Diaspora. RNASeq and DNA methylation data are generated from nasal epithelium including cases and controls from seven different geographic sites.
- Brooke Szczesny
- , Meher Preethi Boorgula
- & Rasika A. Mathias
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Article
| Open AccessA protein sequence-based deep transfer learning framework for identifying human proteome-wide deubiquitinase-substrate interactions
The specificity of protein deubiquitination relies on deubiquitinase-substrate interactions (DSIs). Here, authors leverage evolutionary information from the proteome to predict DSIs, even with an inadequate training dataset.
- Yuan Liu
- , Dianke Li
- & Dong Li
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Article
| Open AccessPhysiochemical interaction between osmotic stress and a bacterial exometabolite promotes plant disease
A single exometabolite produced by an opportunistic bacterial pathogen of the root microbiome enhances host susceptibility to salt stress and promotes plant disease in complex soil systems.
- Felix Getzke
- , Lei Wang
- & Stéphane Hacquard
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Article
| Open AccessSmall body size is associated with increased evolutionary lability of wing skeleton proportions in birds
Birds vary in body mass by many orders of magnitude, but how this effects the evolution of their skeletal proportions is unclear. This study shows that small body size is associated with decreased evolutionary integration between wing bone sizes, facilitating increased evolutionary lability.
- Andrew Orkney
- & Brandon P. Hedrick
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Article
| Open AccessCrykey: Rapid identification of SARS-CoV-2 cryptic mutations in wastewater
Wastewater surveillance has the potential to be used for early detection of new SARS-CoV-2 lineages. Here, the authors present Crykey, a computational method for detecting cryptic SARS-CoV-2 mutations in wastewater that co-occur on the same sequencing read, potentially representing new lineages.
- Yunxi Liu
- , Nicolae Sapoval
- & Lauren B. Stadler
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Article
| Open AccessRegiodivergent biosynthesis of bridged bicyclononanes
Hypericum plants contain complex compounds with promising medicinal properties. Here, the authors report a pair of enzymes catalyzing prenylation and regiodivergent cyclization. The forged scaffolds are characteristic of hyperforin analogs.
- Lukas Ernst
- , Hui Lyu
- & Benye Liu
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Article
| Open AccessLong-read sequencing for 29 immune cell subsets reveals disease-linked isoforms
This paper unveils the complexity of human immune cell splicing, highlighting cell-specific isoforms and establishing connections between alternative splicing and complex traits. These findings have implications for understanding diseases and the evolution of the genome.
- Jun Inamo
- , Akari Suzuki
- & Yuta Kochi
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Article
| Open AccessTAD border deletion at the Kit locus causes tissue-specific ectopic activation of a neighboring gene
Research on the Kit locus shows TAD boundary deletion may or may not trigger ectopic gene activation in different cell types, influenced by active enhancers’ position relative gene promoters.
- Evelyn Kabirova
- , Anastasiya Ryzhkova
- & Nariman Battulin
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Article
| Open AccessAssociations of semaglutide with incidence and recurrence of alcohol use disorder in real-world population
Anecdotal reports from patients prescribed semaglutide describe a reduced desire to drink. Here, the authors show that semaglutide is associated with a 50%-56% reduced risk for both the incidence and recurrence of alcohol use disorder in real-world populations.
- William Wang
- , Nora D. Volkow
- & Rong Xu
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Article
| Open AccessStructure prediction of protein-ligand complexes from sequence information with Umol
Here the authors report the AI system Umol that predicts flexible all-atom structures of protein-ligand complexes from sequence information, advancing AI-driven drug discovery: accurate structures and affinity can be selected from predicted confidence metrics (plDDT).
- Patrick Bryant
- , Atharva Kelkar
- & Frank Noé
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Article
| Open AccessAn isoform quantitative trait locus in SBNO2 links genetic susceptibility to Crohn’s disease with defective antimicrobial activity
Genetic variants in the SBNO2 locus are associated with Crohns’s disease. Here the authors show that those variants cause a cell type and isoform specific effect were transcription of SBNO2 isoform 2 impacts on antimicrobial activity in macrophages providing a plausible gene-mechanism-phenotype model.
- Dominik Aschenbrenner
- , Isar Nassiri
- & Holm H. Uhlig
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Article
| Open AccessStructure and distinct supramolecular organization of a PSII-ACPII dimer from a cryptophyte alga Chroomonas placoidea
The authors report structure of PSII-ACPII from a cryptophyte alga Chroomonas placoidea, providing insights into a distinct supramolecular organization and assembly of antennas in the supercomplex and possible excitation energy transfer pathways.
- Zhiyuan Mao
- , Xingyue Li
- & Guangye Han
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Article
| Open AccessThe low-density lipoprotein receptor and apolipoprotein E associated with CCHFV particles mediate CCHFV entry into cells
This study shows that Crimean-Congo hemorrhagic fever virus (CCHFV) recruits apoE, an exchangeable apolipoprotein that mediates LDL/LDL-R interaction, to promote virion entry via the LDLR. Molecules that down-regulate LDL-R inhibit CCHFV infection.
- Maureen Ritter
- , Lola Canus
- & Solène Denolly
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Perspective
| Open AccessAlternative protein sources: science powered startups to fuel food innovation
Harnessing the potential of considerable food security efforts requires the ability to translate them into commercial applications. In this Perspective, the author explores the alternative protein source start-up landscape.
- Elena Lurie-Luke
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Article
| Open AccessHuman movement and environmental barriers shape the emergence of dengue
Here, using a dynamic modelling approach, the authors find that the spread of dengue through Mexico and Brazil is shaped by specific interactions between human mobility, climate, and the environment. Their models can also be applied to predict future spread in these geographic areas.
- Vinyas Harish
- , Felipe J. Colón-González
- & Oliver J. Brady
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Article
| Open AccessGlioblastoma disrupts cortical network activity at multiple spatial and temporal scales
The precise onset, temporal progression and spatial extent of neuron-tumor crosstalk in brain with Glioblastoma (GBM) are not fully understood. Here authors, using a genetic GBM mouse model, show widespread glutamate accumulation, chronic neural activity disruption between cells and brain areas, depending on tumor expansion rate and genotype with altered tumor and neural activity dynamics when adding glypican6.
- Jochen Meyer
- , Kwanha Yu
- & Jeffrey Noebels
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Article
| Open AccessDynamic movement of the Golgi unit and its glycosylation enzyme zones
The structure of the Golgi and the localization of glycosylation enzymes remain largely elusive. Here, the authors use super-resolution microscopy to show that the Golgi is composed of small dynamic units which have rapidly moving zones of glycosylation enzymes.
- Akihiro Harada
- , Masataka Kunii
- & Akihiko Nakano
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Article
| Open AccessEnhanced surface colonisation and competition during bacterial adaptation to a fungus
Bacterial-fungal interactions can stimulate the production of specialised microbial metabolites. Here, Richter et al. use co-culture experimental evolution to show that the presence of a fungus selects for increased surfactin production in the bacterium Bacillus subtilis, which inhibits fungal growth and facilitates the competitive success of the bacterium.
- Anne Richter
- , Felix Blei
- & Ákos T. Kovács
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Article
| Open AccessProximal protein landscapes of the type I interferon signaling cascade reveal negative regulation by PJA2
Type I IFN is vital for antiviral defense. Here, the authors use TurboID-based proximity labeling to comprehensively map the protein landscapes surrounding core IFN signaling members. Among factors uncovered, PJA2 emerged as a negative regulator of IFN signaling that ubiquitinates the Janus kinases.
- Samira Schiefer
- & Benjamin G. Hale
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Article
| Open AccessHairpin protein partitioning from the ER to lipid droplets involves major structural rearrangements
Lipid droplet (LD) function relies on protein partitioning between the endoplasmic reticulum (ER) and LD. The authors show that UBXD8 adopts distinct conformations in both membranes and undergoes structural rearrangements during ER-to-LD partitioning.
- Ravi Dhiman
- , Rehani S. Perera
- & Bianca Schrul
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Article
| Open AccessProton-coupled transport mechanism of the efflux pump NorA
Efflux pumps confer antibiotic resistance by coupling proton import with drug export. In this work, the authors uncover the proton-coupled transport mechanism for the clinically relevant efflux pump NorA from the pathogenic bacterium S. aureus.
- Jianping Li
- , Yan Li
- & Nathaniel J. Traaseth
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Article
| Open AccessOsSRF8 interacts with OsINP1 and OsDAF1 to regulate pollen aperture formation in rice
At the tetrad stage, OsSRF8 interacts with OsINP1 to promote the formation of aperture plasma membrane protrusion (APMP). Then, the OsINP1-OsSRF8 protein complex recruits OsDAF1 to the APMP site and co-regulate pollen aperture formation in rice.
- Keyi Chen
- , Qiming Wang
- & Jianmin Wan
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Article
| Open AccessShifts in evolutionary lability underlie independent gains and losses of root-nodule symbiosis in a single clade of plants
Kates et al. propose that nitrogen-fixing symbiosis between bacteria and angiosperms has been gained and lost multiple times, based on ancestral reconstructions of nodulation across a deeply sampled, 13,000-species phylogeny, in contrast to a single origin with many losses.
- Heather R. Kates
- , Brian C. O’Meara
- & Ryan A. Folk
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Article
| Open AccessApo and Aβ46-bound γ-secretase structures provide insights into amyloid-β processing by the APH-1B isoform
Incomplete proteolysis of amyloid-β (Aβ) peptides by γ-secretases is linked to Alzheimer’s disease. Using cryo-EM and functional analyses, this study uncovers the γ-secretase – Aβ46 structure and unveils key interactions for efficient Aβ cleavage.
- Ivica Odorčić
- , Mohamed Belal Hamed
- & Rouslan G. Efremov
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Article
| Open AccessSpa2 remodels ADP-actin via molecular condensation under glucose starvation
Here the authors show that Spa2 orchestrates adaptive actin remodelling in budding yeast by dynamically binding ADP-actin and inducing phase separation on F-actin, a crucial response to energy starvation.
- Qianqian Ma
- , Wahyu Surya
- & Yansong Miao
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Article
| Open AccessC5aR1 inhibition reprograms tumor associated macrophages and reverses PARP inhibitor resistance in breast cancer
PARP inhibitors (PARPi) have been approved for the treatment of metastatic triple-negative breast cancer (BC), however resistance and recurrence are often observed. Here, in preclinical models of BRCA1/2 wild type and homologous recombination competent BC, the authors show that C5aR1-positive tumor associated macrophages are associated with PARPi-resistance, suggesting targeting C5aR1 as a therapeutic option.
- Xi Li
- , Alfonso Poire
- & Gordon B. Mills
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Article
| Open AccessStructural domain in the Titin N2B-us region binds to FHL2 in a force-activation dependent manner
Titin N2B unique sequence (N2B-us) is a 572 amino acid sequence that acts as an elastic spring to regulate muscle passive elasticity. Here the authors identify a mechanosensitive structural domain within the titin (N2B-us), and a force-dependent interaction between (N2B-us) and the protein FHL2.
- Yuze Sun
- , Xuyao Liu
- & Jie Yan
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Article
| Open AccessDeciphering bat influenza H18N11 infection dynamics in male Jamaican fruit bats on a single-cell level
Here, Kessler et al use single-cell RNA sequencing of the intestine and mesentery from H18N11 influenza-infected bats to show that viral infection is predominant in leukocytes and causes activation of immune cells and antiviral gene signatures.
- Susanne Kessler
- , Bradly Burke
- & Kevin Ciminski
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Article
| Open AccessExposure to environmental pollutants selects for xenobiotic-degrading functions in the human gut microbiome
In this study, the authors employ metagenomics to explore the impact of environmental pollution on the human gut microbiome using samples from a cohort living in a very polluted area in Southern Italy, showing that pollutants degradation genes are more abundant in subjects with higher blood levels of those specific xenobiotics.
- Francesca De Filippis
- , Vincenzo Valentino
- & Danilo Ercolini
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Article
| Open AccessHuman neutralizing antibodies target a conserved lateral patch on H7N9 hemagglutinin head
Here the authors isolate two human antibodies, H7.HK1 and H7.HK2, that achieve broad and potent neutralization against H7N9 influenza by targeting a distinct lateral patch on the hemagglutinin head, thus making them favorable to complement other antibodies for combination therapy.
- Manxue Jia
- , Hanjun Zhao
- & Xueling Wu
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Article
| Open AccessABA-mediated regulation of rice grain quality and seed dormancy via the NF-YB1-SLRL2-bHLH144 Module
This study revealed an NF-YB1-SLRL2-bHLH144 regulatory module, centered on a key transcription factor SLRL2, that mediates the ABA-regulated amylose content in rice. Furthermore, SLRL2 is also involved in the regulation of rice dormancy
- Jin-Dong Wang
- , Jing Wang
- & Qian-Feng Li
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Article
| Open AccessPixel-wise programmability enables dynamic high-SNR cameras for high-speed microscopy
The researchers present an image sensor that allows every pixel to have independent exposure. It can sample a cell ROI’s fast fluorescence activity with long exposures at different phases, enhancing SNR and temporal resolution for capturing high-speed events.
- Jie Zhang
- , Jonathan Newman
- & Matthew Wilson
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Article
| Open AccessBiodiversity increases resistance of grasslands against plant invasions under multiple environmental changes
Species-rich communities tend to be less vulnerable to species invasions, but whether this is maintained under environmental stress is unclear. This meta-analysis shows that the positive effect of biodiversity on resistance to invasion in grassland plant communities is reduced by drought but increased by warming and multiple global change factors.
- Cai Cheng
- , Zekang Liu
- & Jihua Wu
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Article
| Open AccessSafety outcomes following COVID-19 vaccination and infection in 5.1 million children in England
COVID-19 vaccines reduce the risk of severe disease in young people, but the absolute risk is low, and side effects have been reported. Here, the authors use data on 5–17 year olds in England to assess the overall risk-benefit profile of the vaccines.
- Emma Copland
- , Martina Patone
- & Julia Hippisley-Cox
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Article
| Open AccessLongitudinal viral shedding and antibody response characteristics of men with acute infection of monkeypox virus: a prospective cohort study
Here the authors measure viral load in samples from skin lesions, saliva, oropharynx, and rectum of 77 patients with acute monkeypox virus infection as well as from environmental fomite swabs and show a high seropositivity rate for antibodies against A29L and H3L.
- Yang Yang
- , Shiyu Niu
- & Yingxia Liu
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Article
| Open AccessOrganization of corticocortical and thalamocortical top-down inputs in the primary visual cortex
The organization of top-down inputs in primary visual cortex (V1) remains unclear. Here the authors characterized corticocortical and thalamocortical top-down inputs recruiting V1 neurons with cell-type and layer-specificities, and revealed distinct forms of top-down input processing.
- Yanmei Liu
- , Jiahe Zhang
- & Guofen Ma
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Article
| Open AccessPrimate retina trades single-photon detection for high-fidelity contrast encoding
The neural mechanisms setting the lower limit of conscious visual perception in humans is not fully understood. Here the authors show by correlating human vision experiments and non-human primate retina recordings that primates rely on the retinal ON pathway in perception of the dimmest light increments, and that nonlinear thresholding in this pathway eliminates single photons and neural noise thereby allowing perception of minute differences in light intensity.
- Markku Kilpeläinen
- , Johan Westö
- & Petri Ala-Laurila
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Article
| Open AccessNoninvasive imaging-guided ultrasonic neurostimulation with arbitrary 2D patterns and its application for high-quality vision restoration
Researchers have developed a noninvasive retina prosthesis based on ultrasound for treating blindness. This device uses ultrasound waves to stimulate the retina, creating artificial vision confirmed through behavior tests, offering a safer alternative to invasive treatments.
- Gengxi Lu
- , Chen Gong
- & Qifa Zhou
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Article
| Open AccessAcute and post-acute respiratory complications of SARS-CoV-2 infection: population-based cohort study in South Korea and Japan
Respiratory complications of SARS-CoV-2 infection have been described in the acute (within 30 days) and post-acute (after 30 days) phase. Here, the authors characterise the risk of acute and post-acute respiratory complications of SARS-CoV-2 using population-based data from South Korea and Japan.
- Yujin Choi
- , Hyeon Jin Kim
- & Dong Keon Yon
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Article
| Open AccessPotential decoupling of CO2 and Hg uptake process by global vegetation in the 21st century
The uptake of gaseous elementary mercury by terrestrial vegetation in 2100 is likely to decrease by more than half compared to present-day conditions. This decrease is caused by the reduced stomatal conductance associated with increasing CO2 levels.
- Tengfei Yuan
- , Shaojian Huang
- & Yanxu Zhang
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Article
| Open AccessWhole-soil warming leads to substantial soil carbon emission in an alpine grassland
This study demonstrates that future whole-soil warming has a much stronger effect on soil carbon emission in the alpine grassland ecosystem than what is estimated by previous warming experiments which only warm surface soils mostly.
- Ying Chen
- , Wenkuan Qin
- & Biao Zhu
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