Featured
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Article
| Open AccessAlpha-glucans from bacterial necromass indicate an intra-population loop within the marine carbon cycle
Phytoplankton blooms provoke bacterioplankton blooms, from which bacterial biomass (necromass) is released via zooplankton grazing and viral lysis. Here, Beidler et al. show that the bacterial biomass, including alpha-glucan polysaccharides generated from the consumption of algal organic matter, is reused by microbes in vitro and during a diatom-dominated bloom.
- Irena Beidler
- , Nicola Steinke
- & Thomas Schweder
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Article
| Open AccessThree-dimensional liquid metal-based neuro-interfaces for human hippocampal organoids
Providing a suitable multi-electrode array (MEA) for free-floating neural organoids is a great challenge. Here, authors present a mesh soft stretchable MEA for recording neural signals in human hippocampal organoids derived from induced pluripotent stem cells.
- Yan Wu
- , Jinhao Cheng
- & Xingyu Jiang
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Article
| Open AccessLoCoHD: a metric for comparing local environments of proteins
The techniques available for comparing protein structures do not focus directly on the chemical nature of residue environments. Here, authors describe a computational method that can capture both the spatial and chemical dissimilarities of residue surroundings.
- Zsolt Fazekas
- , Dóra K. Menyhárd
- & András Perczel
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Article
| Open AccessDeep mutational scanning reveals a correlation between degradation and toxicity of thousands of aspartoacylase variants
The details of how the protein folding and degradation systems collaborate to combat potentially toxic non-native proteins are unknown. Here the authors perform systematic studies of missense and nonsense variants of the cytosolic aspartoacylase, ASPA, where loss-of-function variants are linked to Canavan disease.
- Martin Grønbæk-Thygesen
- , Vasileios Voutsinos
- & Rasmus Hartmann-Petersen
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Article
| Open AccessOxidative photocatalysis on membranes triggers non-canonical pyroptosis
Oxidative damage to intracellular membrane proteins is critical to cells. Here, the authors use a water-oxidizing photocatalyst, generating ∙OH even under hypoxia, to show that membrane-specific protein oxidation triggers pyroptosis via non-canonical inflammasomes.
- Chaiheon Lee
- , Mingyu Park
- & Tae-Hyuk Kwon
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Article
| Open AccessMicrofibril-associated glycoprotein 4 forms octamers that mediate interactions with elastogenic proteins and cells
Microfibrillar-associated protein 4 (MFAP4) is involved in fibrotic and cardiovascular diseases. Wozny et al. reveal structural aspects mediating MFAP4 octamer formation critical for its interaction with elastogenic proteins and cells.
- Michael R. Wozny
- , Valentin Nelea
- & Dieter P. Reinhardt
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Article
| Open AccessStructural and dynamic insights into the activation of the μ-opioid receptor by an allosteric modulator
Here, the authors utilise NMR and cryo-EM to characterise the binding of an allosteric modulator to μ-opioid receptor (MOR), revealing modulator binding can potentiate receptor activation by altering the conformational dynamics in the core region of MOR.
- Shun Kaneko
- , Shunsuke Imai
- & Ichio Shimada
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Article
| Open AccessMethylation of ESCRT-III components regulates the timing of cytokinetic abscission
Methylation of CHMP2B regulates abscission timing by modulating ESCRT-III dynamics during cytokinesis. This methylation also plays a role in HIV-1 budding, highlighting the broader significance of ESCRT-III methylation.
- Aurélie Richard
- , Jérémy Berthelet
- & Souhila Medjkane
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Article
| Open AccessMultiscale modelling of chromatin 4D organization in SARS-CoV-2 infected cells
In this work, the authors apply polymer models to reconstruct the 3D structure of the genome during SARS-CoV-2 infection and examine how the virus impacts key mechanisms of chromatin organization.
- Andrea M. Chiariello
- , Alex Abraham
- & Mario Nicodemi
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Article
| Open AccessAnalysis of early intermediate states of the nitrogenase reaction by regularization of EPR spectra
Here, the authors characterize selenium and sulphur incorporated FeMo cofactors of the catalytic MoFe protein component from Azotobacter vinelandii under turnover conditions using EPR.
- Lorenz Heidinger
- , Kathryn Perez
- & Erik Schleicher
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Article
| Open AccessCoordinated wound responses in a regenerative animal-algal holobiont
The term ‘holobiont’ refers to a multicellular organism and its microbial symbionts. Whether and how symbionts react to host injury and how cellular responses are integrated across species remain unexplored. Here, the authors report a deeply conserved animal regeneration regulatory program that links molecular networks across species in an animal-algal holobiont.
- Dania Nanes Sarfati
- , Yuan Xue
- & Bo Wang
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Article
| Open AccessMapping of mitogen and metabolic sensitivity in organoids defines requirements for human hepatocyte growth
Human hepatocytes remain hard to grow in vitro. Here, the authors temporally map the early stages of organoid growth initiated from fetal and adult hepatocytes, leveraging this knowledge to design maturation and improved expansion conditions.
- Delilah Hendriks
- , Benedetta Artegiani
- & Hans Clevers
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Article
| Open AccessNonuniform and pathway-specific laminar processing of spatial frequencies in the primary visual cortex of primates
The uniformity of laminar processing in a cortex remains not fully understood. Here authors show that high spatial frequency stimuli elicit distinct active patterns across V1 layers, arising from multiple mechanisms involving M and P pathways.
- Tian Wang
- , Weifeng Dai
- & Dajun Xing
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Article
| Open AccessThe structural basis for 2′−5′/3′−5′-cGAMP synthesis by cGAS
Here, the authors provide structural and biochemical data describing the mechanism through which cGAS synthesizes 2′−5′/3′−5′-cGAMP.
- Shuai Wu
- , Sandra B. Gabelli
- & Jungsan Sohn
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Article
| Open AccessGene editing for latent herpes simplex virus infection reduces viral load and shedding in vivo
The main challenge for anti-HSV therapy is to target latent virus in ganglionic neurons. Here, the authors report a well-tolerated anti-HSV gene editing approach against HSV which targets latent HSV genomes and leads to reductions of ganglionic viral loads, and viral shedding upon reactivation in mouse models.
- Martine Aubert
- , Anoria K. Haick
- & Keith R. Jerome
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Article
| Open AccessThe basal forebrain to lateral habenula circuitry mediates social behavioral maladaptation
Maladaptive fear is linked to many neuropsychiatric disorders, while its neural basis is not fully understood. Here, the authors show that the hyperactivity of the basal forebrain to lateral habenula glutamatergic circuit is crucial for social fear behavior.
- Jun Wang
- , Qian Yang
- & Han Xu
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Article
| Open AccessTargeting bacterial nickel transport with aspergillomarasmine A suppresses virulence-associated Ni-dependent enzymes
Aspergillomarasmine A (AMA) chelates metal ions such as Zn2+ and Ni2+, which are essential for the activity of enzymes that are important for virulence of several pathogens. Here, Sychantha et al. show that AMA inhibits bacterial Ni2+ uptake and Ni-dependent enzymes, and reduces bacterial virulence in an animal infection model.
- David Sychantha
- , Xuefei Chen
- & Gerard D. Wright
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Article
| Open AccessMammographic density mediates the protective effect of early-life body size on breast cancer risk
Mammographic density is known to be linked to breast cancer risk. Here, the authors use Mendelian randomization to estimate the effects of childhood body size and age at menarche on density phenotypes and breast cancer risk.
- Marina Vabistsevits
- , George Davey Smith
- & Eleanor Sanderson
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Article
| Open AccessDynamic microvilli sculpt bristles at nanometric scale
Bristleworms possess dedicated cells that can synthesize highly stereotypical bristles with sub-micrometric precision. Here, Ikeda and colleagues shed light on the underlying dynamics of cellular protrusions, revealing an extension-disassembly cycle that resembles a 3D printer.
- Kyojiro N. Ikeda
- , Ilya Belevich
- & Florian Raible
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Article
| Open AccessPlatelets favor the outgrowth of established metastases
It is unclear if platelets regulate the growth of established metastases. Using syngeneic mouse models of metastasis, the authors show that platelets support the outgrowth of established metastases via immune suppression, and that targeting the platelet-specific receptor GPVI, efficiently reduces established metastases, providing a promising therapeutic avenue for inhibiting cancer metastasis.
- Maria J. Garcia-Leon
- , Cristina Liboni
- & Jacky G. Goetz
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Article
| Open AccessA cell-free nutrient-supplemented perfusate allows four-day ex vivo metabolic preservation of human kidneys
As demand for organ transplants exceeds availability there has been an unmet need to extend preservation of deceased donor kidneys. Here, the authors show that a cell-free nutrient-supplemented perfusate allows 4-day preservation of human kidneys using spatially resolved lipidomics and metabolomics.
- Marlon J. A. de Haan
- , Marleen E. Jacobs
- & Ton J. Rabelink
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Article
| Open AccessRelationship between HLA genetic variations, COVID-19 vaccine antibody response, and risk of breakthrough outcomes
Human leucocyte antigens are important in the adaptive immune response. Here, the authors use data from the UK Biobank linked to electronic health records to investigate the association between genetic variation in HLA alleles and antibody responses to SARS-CoV-2 vaccination and breakthrough COVID-19 outcomes.
- Junqing Xie
- , Beatriz Mothe
- & Daniel Prieto Alhambra
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Article
| Open AccessStructural basis of human NOX5 activation
NADPH oxidase 5 (NOX5) is activated by Ca2+ signaling, catalyzing superoxide production by transferring electrons from intracellular NADPH to extracellular oxygen. Here the authors uncover the molecular basis of NOX5 activation and electron transfer.
- Chenxi Cui
- , Meiqin Jiang
- & Ji Sun
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Article
| Open AccessEnhancing genome editing in hPSCs through dual inhibition of DNA damage response and repair pathways
Precise genome editing is crucial. Here the authors demonstrate that dual inhibition of p53-mediated cell death and distinct activation of the DNA damage repair system upon DNA damage by cytosine base editor (CBE) or prime editor (PE) additively enhanced editing efficiency in hPSCs.
- Ju-Chan Park
- , Yun-Jeong Kim
- & Hyuk-Jin Cha
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Article
| Open AccessStructural insights into drug transport by an aquaglyceroporin
Pentamidine and melarsoprol are drugs used to treat sleeping sickness caused by Trypanosoma brucei. Here, authors present cryo-EM structures of TbAQP2 with molecular dynamic simulations, revealing mechanisms shaping substrate specificity and drug permeation.
- Wanbiao Chen
- , Rongfeng Zou
- & Chongyuan Wang
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Article
| Open AccessThe greenbeard gene tgrB1 regulates altruism and cheating in Dictyostelium discoideum
Greenbeards encode perceptible signals, signal recognition ability, and altruism towards others displaying the signal. This study shows that activation of the greenbeard receptor gene tgrB1 increases altruism and inactivation causes kin-specific cheating in the social amoeba Dictyostelium discoideum.
- Mariko Katoh-Kurasawa
- , Peter Lehmann
- & Gad Shaulsky
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Article
| Open AccessDetection of Anaplasma and Ehrlichia bacteria in humans, wildlife, and ticks in the Amazon rainforest
In this study, the authors detect diverse Ehrlichia and Anaplasma bacteria in samples from Amazonian wildlife, humans and ticks that are mostly distinct from pathogens detected in the Northern Hemisphere and that might indicate emerging health hazards from tick-borne diseases in the Amazon rainforests.
- Marie Buysse
- , Rachid Koual
- & Olivier Duron
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Article
| Open AccessRegulation of cerebral blood flow boosts precise brain targeting of vinpocetine-derived ionizable-lipidoid nanoparticles
Despite advances in active drug-targeting for blood-brain barrier penetration, challenges related to brain biodistribution, and drug accumulation persist. Here the authors show a molecular library design centered on cyclic tertiary amine compounds and develop a self-enhanced brain-targeted nucleic acid delivery system inspired by the neuroprotective properties of vinpocetine.
- Xufei Bian
- , Ling Yang
- & Chong Li
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Article
| Open AccessAn integrated multi-omics approach reveals polymethoxylated flavonoid biosynthesis in Citrus reticulata cv. Chachiensis
Citrus reticulata cv. Chachiensis (CRC) is used in traditional Chinese medicine to treat various ailments. Here Wen et al. provide genomic, transcriptomic and metabolomic resources for CRC and propose a possible biosynthetic pathway for bioactive components.
- Jiawen Wen
- , Yayu Wang
- & Huan Liu
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Article
| Open AccessEffects of SPI1-mediated transcriptome remodeling on Alzheimer’s disease-related phenotypes in mouse models of Aβ amyloidosis
Although SPI1 gene was identified as a risk factor for Alzheimer’s disease, its role in the disease remains unclear. Here, the authors show that decreasing SPI1 level exacerbates disease symptoms, whereas increasing its level ameliorates phenotypes.
- Byungwook Kim
- , Luke Child Dabin
- & Jungsu Kim
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Article
| Open AccessCerebellar Purkinje cells in male macaques combine sensory and motor information to predict the sensory consequences of active self-motion
Neural basis of the sensory suppression signal required to cancel peripheral vestibular input is not fully understood. Here authors show that cerebellar Purkinje cells combine sensory and motor information to predict the sensory consequences of active self-motion, thereby establishing how vestibular reafference is distinguished to cancel self-generated sensory input.
- Omid A. Zobeiri
- & Kathleen E. Cullen
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Article
| Open AccessHigh-confidence 3D template matching for cryo-electron tomography
Enabling visual proteomics with high-confidence 3D template matching (TM) in CryoET. 3D TM precisely localizes macromolecular complexes, individual subunits, and different functional states in situ, revealing molecular interactions within cells.
- Sergio Cruz-León
- , Tomáš Majtner
- & Gerhard Hummer
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Article
| Open AccessMolecular basis of bacterial DSR2 anti-phage defense and viral immune evasion
The defense-associated sirtuin 2 (DSR2) system protects bacteria from phages by depleting NAD+. Here, authors elucidate the molecular mechanisms underlying DSR2 assembly, activation, and inhibition, providing important insights into bacterial anti-phage defense.
- Jiafeng Huang
- , Keli Zhu
- & Ang Gao
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Article
| Open AccessMutational dissection of a hole hopping route in a lytic polysaccharide monooxygenase (LPMO)
Lytic polysaccharide monooxygenases (LPMOs) are mono copper enzymes with outstanding industrial applicability. Here, the authors investigate the “hole hopping” mechanism in a bacterial LPMO and show that a strictly conserved tryptophan is critical for radical formation and hole transference, as well as reveal a correlation between the efficiency of hole transference and enzyme performance under oxidative stress.
- Iván Ayuso-Fernández
- , Tom Z. Emrich-Mills
- & Vincent G. H. Eijsink
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Article
| Open AccessGenetic and functional diversity of β-N-acetylgalactosamine-targeting glycosidases expanded by deep-sea metagenome analysis
Four β-N-acetylgalactosaminidase gene families were identified via deep-sea metagenome analysis. The biochemical and structural characterization of the aforementioned enzymes revealed their functional diversity and monophyletic evolutionary history.
- Tomomi Sumida
- , Satoshi Hiraoka
- & Takuro Nunoura
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Article
| Open AccessTemperature alters the predator-prey size relationships and size-selectivity of Southern Ocean fish
Using prey size measurements from ten Southern Ocean lanternfish species sampled across >10° of latitude, this study shows that higher temperatures were associated with smaller fish and an overall decrease in the size of fish relative to their prey. Ocean warming may therefore alter the diversity and size structuring of trophic interactions, reducing the stability of marine ecosystems.
- Patrick Eskuche-Keith
- , Simeon L. Hill
- & Eoin J. O’Gorman
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Article
| Open AccessMultimodal binding and inhibition of bacterial ribosomes by the antimicrobial peptides Api137 and Api88
Proline-rich antimicrobial peptides (PrAMPs) inhibit bacterial protein biosynthesis. Here, the authors show that the honey-bee derived PrAMPs Api137 and Api88 inhibit bacterial ribosomes through multiple mechanisms, promising for drug development.
- Simon M. Lauer
- , Maren Reepmeyer
- & Ralf Hoffmann
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Article
| Open AccessFragment ion intensity prediction improves the identification rate of non-tryptic peptides in timsTOF
Immunopeptidomics is crucial for the discovery of potential immunotherapy and vaccine candidates. Here, the authors generate a ground truth timsTOF dataset to fine-tune the deep learning model Prosit, improving peptide-spectrum match rescoring by up to 3-fold during immunopeptide identification.
- Charlotte Adams
- , Wassim Gabriel
- & Kurt Boonen
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Article
| Open AccessUnveiling the A-to-I mRNA editing machinery and its regulation and evolution in fungi
A-to-I editing in animals is catalyzed by enzymes of the Adenosine Deaminase Acting on RNA family, orthologues of which do not exist in fungi. Here, Feng et al. characterise the enzymes involved in A-to-I mRNA editing in Fusarium graminearum.
- Chanjing Feng
- , Kaiyun Xin
- & Huiquan Liu
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Article
| Open AccessAn integrated technology for quantitative wide mutational scanning of human antibody Fab libraries
Limited experimental platforms exist for assessing quantitative sequence-function relationships for multiple antibodies. Here, authors develop a deep-sequencing based technology called MAGMA-seq, that determines the quantitative properties of antibody libraries.
- Brian M. Petersen
- , Monica B. Kirby
- & Timothy A. Whitehead
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Article
| Open AccessMultiplexed bulk and single-cell RNA-seq hybrid enables cost-efficient disease modeling with chimeric organoids
IPSC-derived organoids model diseases. Multiplexed coculture and demultiplexing natural genetic barcodes aid in studying genetic effects. Here, authors introduce Vireo-bulk to deconvolve bulk RNA-seq data, quantify donor abundance and identify differentially expressed genes.
- Chen Cheng
- , Gang Wang
- & Jin Zhang
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Article
| Open AccessThree concurrent mechanisms generate gene copy number variation and transient antibiotic heteroresistance
Bacterial heteroresistance is a medically relevant phenotype where small antibiotic-resistant subpopulations coexist within predominantly susceptible bacterial populations. Here, Nicoloff et al. describe how three different mechanisms that increase the copy number of resistance genes can lead to unstable and transient heteroresistance.
- Hervé Nicoloff
- , Karin Hjort
- & Helen Wang
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Article
| Open AccessDiscovering allatostatin type-C receptor specific agonists
Pesticides safeguard crops against pest infestations and mitigate associated risks. In this work, the authors develop a pesticide targeting AlstR-C of T.pityocampa pests, showing promising results without harming other insects, and advancing the development of GPCR-targeted pesticides for insect control.
- Kübra Kahveci
- , Mustafa Barbaros Düzgün
- & Necla Birgul Iyison
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Article
| Open AccessTFPI from erythroblasts drives heme production in central macrophages promoting erythropoiesis in polycythemia
The role of coagulation system in erythropoiesis is not clear. Here, the authors report that an anticoagulant protein TFPI from erythroblasts directs central macrophages to synthesize heme, which in turn promotes erythropoiesis in bone marrow.
- Jun-Kai Ma
- , Li-Da Su
- & Xin-Jiang Lu
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Article
| Open AccessPretreatment with IL-15 and IL-18 rescues natural killer cells from granzyme B-mediated apoptosis after cryopreservation
Natural killer (NK) cells are assessed for various therapies, but sub-optimal cryopreservation dampens their clinical feasibility. Here the authors show that pretreating human NK cells with IL-15/IL-18 prior to cryopreservation improves NK cell post-thaw viability and functions, potentially via anti-apoptosis gene induction and granzyme B degranulation.
- Abdulla Berjis
- , Deeksha Muthumani
- & Neil C. Sheppard
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Article
| Open AccessRegulation of Myc transcription by an enhancer cluster dedicated to pluripotency and early embryonic expression
MYC regulates numerous genes involved in cell growth and proliferation. Here, Li-Bao et al. study the DNA regions that regulate Myc transcription in early mouse embryos and pluripotent stem cells. They report a specific region with independent modules dedicated to discrete temporal and spatial phases of Myc expression.
- Lin Li-Bao
- , Covadonga Díaz-Díaz
- & Miguel Torres
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Article
| Open AccessSpatial mapping of hepatic ER and mitochondria architecture reveals zonated remodeling in fasting and obesity
Hepatocytes are central for maintaining metabolic homeostasis during nutritional transitions. Here, we show that the structural remodelling of hepatic organelles is part of hepatocytes’ metabolic plasticity to adapt to cycles of fasting/feeding and this process is zonated in the liver.
- Güneş Parlakgül
- , Song Pang
- & Ana Paula Arruda
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Article
| Open AccessA nascent riboswitch helix orchestrates robust transcriptional regulation through signal integration
Here the authors unveil an intermediate state during the folding of the manganese riboswitch from L. lactis. This transient state allows the integration of multiple cellular signals including RNA polymerase pausing and transcription factor NusA.
- Adrien Chauvier
- , Shiba S. Dandpat
- & Nils G. Walter
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Article
| Open AccessFused in sarcoma (FUS) inhibits milk production efficiency in mammals
Efficient milk production in mammals confers advantages by facilitating the transmission of energy from mother to offspring. However, the factors for establishing the efficiency in mammals are unknown. Here, the authors identify FUS as a regulator of efficient milk production in mammals.
- Haili Shao
- , Jipeng Huang
- & Baowei Jiao
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