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Article
| Open AccessImpact of secretin receptor homo-dimerization on natural ligand binding
GPCRs can form functionally important dimers. Here, authors study impact of dimerization of the secretin receptor on peptide ligand binding and show high receptor conformational dynamics that facilitate G protein recruitment and activation.
- Kaleeckal G. Harikumar
- , Sarah J. Piper
- & Laurence J. Miller
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Article
| Open AccessAutophagy-deficient macrophages exacerbate cisplatin-induced mitochondrial dysfunction and kidney injury via miR-195a-5p-SIRT3 axis
Tubulointerstitial inflammation occurs frequently in acute kidney injury (AKI), and Mφ autophagy is a known contributor to inflammation-related diseases. Here, Yuan et al. show that Mφ autophagy deficiency induces systemic inflammation, impairs mitochondria, and worsens kidney injury in AKI mice.
- Yujia Yuan
- , Longhui Yuan
- & Yanrong Lu
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Article
| Open AccessAngle between DNA linker and nucleosome core particle regulates array compaction revealed by individual-particle cryo-electron tomography
Here, using cryo-ET, the 3D structures of individual nucleosome particles were characterized to observe changes under varying ionic strengths and in the presence of protein H1, revealing key regulatory roles in chromatin organization dynamics.
- Meng Zhang
- , César Díaz-Celis
- & Gang Ren
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Article
| Open AccessA comprehensive benchmarking with interpretation and operational guidance for the hierarchy of topologically associating domains
TAD hierarchy demonstrates cell-to-cell variability, leading to the development of numerous callers. Here, authors present a comprehensive benchmark of TAD hierarchy callers and introduce the ‘air conditioner’ model to illustrate TAD hierarchy’s role in transcription.
- Jingxuan Xu
- , Xiang Xu
- & Hebing Chen
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Article
| Open AccessIlluminating the function of the orphan transporter, SLC22A10, in humans and other primates
Orphan transporters can be found in over 20 families in the SLC superfamily. Here, the authors show that human SLC22A10 is a unitary pseudogene due to a fixed missense mutation, P220; while in great apes, its orthologs transport sex steroid conjugates.
- Sook Wah Yee
- , Luis Ferrández-Peral
- & Kathleen M. Giacomini
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Article
| Open AccessDevelopment of a nucleoside-modified mRNA vaccine against clade 2.3.4.4b H5 highly pathogenic avian influenza virus
Highly pathogenic avian influenza viruses from H5 clade 2.3.4.4b are circulating widely in birds and have recently caused large outbreaks in mammals. Here, Furey et al. develop a clade 2.3.4.4b HA-expressing mRNA-LNP vaccine and show that it elicits strong protective immune responses in mice and ferrets.
- Colleen Furey
- , Gabrielle Scher
- & Scott E. Hensley
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Article
| Open AccessThe patatin-like protein PlpD forms structurally dynamic homodimers in the Pseudomonas aeruginosa outer membrane
The Omp85 superfamily is a widely distributed class of outer membrane proteins found in Gram-negative bacteria, mitochondria and chloroplasts. Here the authors show that PlpD has a different structure and topology than other Omp85 proteins that have been studied.
- Sarah E. Hanson
- , Tyrone Dowdy
- & Harris D. Bernstein
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Article
| Open AccessA rationally designed miniature of soluble methane monooxygenase enables rapid and high-yield methanol production in Escherichia coli
Soluble methane monooxygenase (sMMO) is a potentially value biocatalyst, but production of active recombinant sMMO is very challenging. Here the authors report the rational design and construction of a catalytically active miniature sMMO which enables high-yield production of methanol in E. coli.
- Yeonhwa Yu
- , Yongfan Shi
- & Jeewon Lee
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Article
| Open AccessIn-depth organic mass cytometry reveals differential contents of 3-hydroxybutanoic acid at the single-cell level
Comprehensive single-cell metabolic profiling is critical for revealing phenotypic heterogeneity and elucidating the molecular mechanisms underlying biological processes. Here, the authors establish a novel single-cell metabolomics platform for in-depth organic mass cytometry.
- Shaojie Qin
- , Yi Zhang
- & Yu Bai
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Article
| Open AccessReduction of specific enterocytes from loss of intestinal LGR4 improves lipid metabolism in mice
How LGR4 impacts nutrition absorption and energy homeostasis is unknown. Here, the authors show that LGR4 loss in the intestinal epithelium decreases the proportion of enterocytes selective for long-chain fatty acid absorption, reducing lipid absorption and improving lipid and glucose metabolism.
- Yuan Liang
- , Chao Luo
- & Yue Yin
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Article
| Open AccessSingle-cell and spatial transcriptomics analysis of non-small cell lung cancer
Myeloid cell populations play a critical role in lung cancer progression. Here, the authors use scRNA-seq and spatial transcriptomics to identify changes in the phenotype of macrophages within the tumour microenvironment.
- Marco De Zuani
- , Haoliang Xue
- & Ana Cvejic
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Article
| Open AccessTranslation initiation factor eIF1.2 promotes Toxoplasma stage conversion by regulating levels of key differentiation factors
Wang et al. show that Toxoplasma gondii translation initiation factor eIF1.2 is critical for acute to chronic stage transition during infection, underscoring the importance of protein translation in controlling stage differentiation.
- Fengrong Wang
- , Michael J. Holmes
- & Vern B. Carruthers
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Article
| Open AccessAn integrated spatio-temporal view of riverine biodiversity using environmental DNA metabarcoding
Using intensive eDNA sampling in space and time across five rivers in Europe and North America, this study shows that eDNA gives relevant information on freshwater diversity and ecology across broad taxonomic groups, and with limited downstream transport. The findings demonstrate that eDNA is vital for freshwater biodiversity monitoring in a time of anthropogenic change.
- William Bernard Perry
- , Mathew Seymour
- & Simon Creer
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Article
| Open AccessCompound mortality impacts from extreme temperatures and the COVID-19 pandemic
Extreme weather and pandemics are classified as two of the most serious risks facing the UK in its National Risk Register. Here, the authors investigate the compound mortality impacts of extreme high and low temperatures and COVID-19 in England and Wales.
- Y. T. Eunice Lo
- , Dann M. Mitchell
- & Antonio Gasparrini
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Article
| Open AccessFar-East Asian Toxoplasma isolates share ancestry with North and South/Central American recombinant lineages
The population genome structure of Asian Toxoplasma remains incompletely understood. This study analyzes intercontinental genomic admixture in 17 isolates from Japan and China, providing insights into the evolution of parasites and their impact on public health.
- Fumiaki Ihara
- , Hisako Kyan
- & Masahiro Yamamoto
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Article
| Open AccessPrediction of Klebsiella phage-host specificity at the strain level
Bacterial viruses (phages) are promising alternatives to treat antibiotic-resistant bacterial infections, but finding matching phages against bacteria of interest is challenging. Here, Boeckaerts et al. present a machine learning approach that predicts phage-bacteria pairs at the strain level for Klebsiella pathogens.
- Dimitri Boeckaerts
- , Michiel Stock
- & Yves Briers
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Article
| Open AccessEnvironmental conditions associated with initial northern expansion of anatomically modern humans
Past global human migration was the result of environmental and cultural factors. Here, the authors develop a statistical approach that combines archaeological, genetic, and palaeoclimate data to identify regional environmental conditions facilitating population expansion routes in northern Eurasia and the Americas.
- Frédérik Saltré
- , Joël Chadœuf
- & Corey J. A. Bradshaw
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Article
| Open AccessHippocampal sharp-wave ripples correlate with periods of naturally occurring self-generated thoughts in humans
Whether and how sharp-wave ripples (SWRs) accompany mental states that are less closely linked to events in the immediate environment are not fully understood. Here authors recorded SWRs from hippocampus of 10 epilepsy patients for up to 15 days with experience sampling. SWR rates showed circadian fluctuation and were associated with self-generated thoughts such as mind wandering.
- Takamitsu Iwata
- , Takufumi Yanagisawa
- & Haruhiko Kishima
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Review Article
| Open AccessControlled oxygen delivery to power tissue regeneration
This review explores the role of oxygen and its delivery via engineered biomaterials in a plethora of physiological processes. This piece emphasises on the application of advanced oxygen delivery strategies, as well as discussing advances in oxygen-generating materials and oxygen-perfusing devices.
- Elizabeth Zoneff
- , Yi Wang
- & Lilith M. Caballero-Aguilar
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Article
| Open AccessCystine-knot peptide inhibitors of HTRA1 bind to a cryptic pocket within the active site region
Here the authors use phage display to develop cystine-knot peptides that inhibit the trimeric serine protease HTRA1. Structural and biochemical characterisation uncovered binding of the peptides to a cryptic pocket that locked the active site in a noncompetent state.
- Yanjie Li
- , Yuehua Wei
- & Daniel Kirchhofer
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Article
| Open AccessA modular framework for multi-scale tissue imaging and neuronal segmentation
Tools to segment cellular and sub-cellular neuronal structures can be hindered by high neuronal density and low signal-to-noise in thick samples. Here, the authors present SENPAI, a framework for imaging and segmenting neurons from conventional and super-resolution microscopy of clarified brain tissues.
- Simone Cauzzo
- , Ester Bruno
- & Nicola Vanello
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Article
| Open AccessRevealing the mechanism and function underlying pairwise temporal coupling in collective motion
It is known that spatially localized interactions can give rise to self-organized collective motion. Here, by studying pairwise interactions in juvenile zebrafish, authors reveal the role of reciprocal temporal coupling and find that temporal coordination considerably improves spatial responsiveness, such as reacting to changes in the direction of motion of a partner.
- Guy Amichay
- , Liang Li
- & Iain D. Couzin
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Article
| Open AccessIntegrating cryo-OrbiSIMS with computational modelling and metadynamics simulations enhances RNA structure prediction at atomic resolution
Conventional structural biology techniques are limited in deciphering complex RNA structures and dynamic interactions. Here the authors show an integrated approach that combines cryogenic OrbiSIMS (cryo-OrbiSIMS) with computational methods for modelling RNA structures at atomic resolution.
- Shannon Ward
- , Alex Childs
- & Aditi N. Borkar
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Article
| Open AccessDNA methylation-based high-resolution mapping of long-distance chromosomal interactions in nucleosome-depleted regions
Here, the authors present MTAC, a method to map chromosomal interactions in budding yeast. By applying MTAC to various viewpoints, they find that most of the long-distance chromosomal interactions detected by MTAC reflect tethering by the nuclear pore complexes.
- Yi Li
- , James Lee
- & Lu Bai
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Article
| Open AccessIntegrating human endogenous retroviruses into transcriptome-wide association studies highlights novel risk factors for major psychiatric conditions
Duarte et al. report that common genetic variants linked to psychiatric disorders influence the regulation of ancient retroviruses integrated into the genome. This suggests ancient viruses acquired millions of years ago may have shaped modern human brain function.
- Rodrigo R. R. Duarte
- , Oliver Pain
- & Timothy R. Powell
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Article
| Open AccessArtificial intelligence enables precision diagnosis of cervical cytology grades and cervical cancer
Cervical screening is a key method for detecting cervical cancer, but is limited by pathologist detection. Here, the authors use artificial intelligence to predict cytology grades from whole slide images.
- Jue Wang
- , Yunfang Yu
- & Herui Yao
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Article
| Open AccessDual-mode harvest solar energy for photothermal Cu2-xSe biomineralization and seawater desalination by biotic-abiotic hybrid
Biotic-abiotic photosynthetic systems hold great promise to innovate solar-driven chemical transformation. Here, the authors construct a biotic-abiotic hybrid system composed of Shewanella oneidensis MR-1 and biogenic Se0 nanoparticles for photothermal Cu2-xSe biomineralization and then for seawater desalination.
- Sheng-Lan Gong
- , YangChao Tian
- & Li-Jiao Tian
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Article
| Open AccessLocalized and global representation of prior value, sensory evidence, and choice in male mouse cerebral cortex
The extent to which brains employ Bayesian principles remains unclear. Here, the authors provide evidence suggesting that neurons in the medial prefrontal cortex represent the modulation of reward expectation (i.e., prior values) with incoming sensory inputs to compute confidence values.
- Kotaro Ishizu
- , Shosuke Nishimoto
- & Akihiro Funamizu
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Article
| Open AccessAbrupt onset of intensive human occupation 44,000 years ago on the threshold of Sahul
Archaeological and genetic evidence suggest differing scenarios for human migration out of Africa. Here, the authors present archaeological evidence of intense occupation in Wallacea from 44 thousand years ago, suggesting that this occupation obscured genetic evidence of earlier dispersals.
- Ceri Shipton
- , Mike W. Morley
- & Sue O’Connor
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Perspective
| Open AccessRediscovery of mononuclear phagocyte system blockade for nanoparticle drug delivery
Temporal blockade of the mononuclear phagocyte system is an approach to enhance the therapeutic efficiency of nanocarrier drug-delivery systems but the broad applicability is hindered by the complexity of optimisation and management of potential side effects. Here, the authors review the development of this technique and show its efficiency using meta-analysis of the published data and discuss essential features for its successful translation to clinic.
- Ivan V. Zelepukin
- , Konstantin G. Shevchenko
- & Sergey M. Deyev
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Article
| Open AccessPost-COVID conditions following COVID-19 vaccination: a retrospective matched cohort study of patients with SARS-CoV-2 infection
The impact of COVID-19 vaccination on post-COVID conditions is not well understood. Here, the authors use electronic health record data from a network of eight integrated healthcare systems in the United States to compare rates of post-COVID conditions in those with and without vaccination.
- Debbie E. Malden
- , In-Lu Amy Liu
- & Sara Y. Tartof
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Article
| Open AccessCellular structure of dinosaur scales reveals retention of reptile-type skin during the evolutionary transition to feathers
The evolution of feathers is associated with the evolution of related skin microstructures. Here, the authors demonstrate that Psittacosaurus, a non-avian feathered dinosaur, retained scaled skin like its ancestors in body regions lacking feathers.
- Zixiao Yang
- , Baoyu Jiang
- & Maria E. McNamara
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Article
| Open AccessParental experiences orchestrate locust egg hatching synchrony by regulating nuclear export of precursor miRNA
The parental experience exerts a profound impact on offspring phenotypes. Zhu et al. find that in locusts the population density of parents regulates the hatching synchrony of progeny eggs via the FOXN1-PTBP1/XPO5 pathway, facilitating the nuclear export of precursor miRNA in the oocytes.
- Ya′nan Zhu
- , Jing He
- & Le Kang
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Article
| Open AccessHuman CD4-binding site antibody elicited by polyvalent DNA prime-protein boost vaccine neutralizes cross-clade tier-2-HIV strains
Here the authors isolate monoclonal antibody HmAb64 from a healthy volunteer who received an experimental polyvalent DNA prime-protein boost HIV vaccine, and show that it’s specific for the CD4 binding site and neutralizes cross-subtype HIV isolates including several tier-2 viruses.
- Shixia Wang
- , Kun-Wei Chan
- & Shan Lu
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Article
| Open AccessReceptor-like cytoplasmic kinases of different subfamilies differentially regulate SOBIR1/BAK1-mediated immune responses in Nicotiana benthamiana
Cell-surface receptors form the front line of plant immunity. Here, the authors show that the RLP co-receptors SOBIR1 and BAK1 directly phosphorylate each other, leading to activation of the immune receptor complex in which RLCKs are differentially required for production of reactive oxygen species that play a role in resistance against Phytophthora palmivora.
- Wen R. H. Huang
- , Ciska Braam
- & Matthieu H. A. J. Joosten
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Article
| Open AccessIntegrative multi-region molecular profiling of primary prostate cancer in men with synchronous lymph node metastasis
While it is known that localised prostate cancer is characterised by clonal heterogeneity, the clonal origin of synchronous lymph node (LN) metastases remains poorly understood. Here, the authors analyse the clonal origin of LN metastases in prostate cancer patients using multi-region sequencing.
- Udit Singhal
- , Srinivas Nallandhighal
- & Simpa S. Salami
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Article
| Open AccessDeterminants of gastric cancer immune escape identified from non-coding immune-landscape quantitative trait loci
The role of non-coding mutations in cancer progression and immune evasion needs to be further explored. Here, the authors investigate the potential of common somatic and germline 3′ untranslated region variants in predicting response to immunotherapy in gastric patients.
- Christos Miliotis
- , Yuling Ma
- & Ioannis S. Vlachos
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Article
| Open AccessCiliary tip actin dynamics regulate photoreceptor outer segment integrity
Photoreceptor outer segment abnormalities cause retinitis pigmentosa, a form of blindness. Here, authors show that the disease-associated gene RPGR regulates actin-mediated outer segment turnover through its interaction with the actin severer, cofilin.
- Roly Megaw
- , Abigail Moye
- & Pleasantine Mill
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Article
| Open AccessA potent Henipavirus cross-neutralizing antibody reveals a dynamic fusion-triggering pattern of the G-tetramer
There are no approved interventions for Hendra or Nipah viruses. Here, the authors isolate a G glycoprotein-specific antibody with cross-neutralizing and in vivo protective activities, and structurally resolve its binding pattern to the G protein.
- Pengfei Fan
- , Mengmeng Sun
- & Sandra Chiu
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Article
| Open AccessNeuroprotective gap-junction-mediated bystander transformations in the adult zebrafish spinal cord after injury
The mechanisms underlying the zebrafish spinal cord’s impressive innate ability to regenerate after traumatic insults remain largely unknown. Here, the authors show that spinal neurons enact an essential neuron-to-neuron neuroprotective strategy to safeguard cell survival and support the zebrafish’s regeneration process.
- Andrea Pedroni
- , Yu-Wen E. Dai
- & Konstantinos Ampatzis
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Article
| Open AccessThe SUN-family protein Sad1 mediates heterochromatin spatial organization through interaction with histone H2A-H2B
Here authors identify the interaction between the SUN-family protein Sad1 and histone H2A-H2B in S. pombe, and reveal the roles of the Sad1-histone interaction in the association of heterochromatin with the nuclear envelope and heterochromatin silencing.
- Wenqi Sun
- , Qianhua Dong
- & Yong Chen
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Article
| Open AccessOsMAPK6 phosphorylation and CLG1 ubiquitylation of GW6a non-additively enhance rice grain size through stabilization of the substrate
OsMAPK6 and CLG1, respectively, target GW6a for phosphorylation and ubiquitylation to favor the substrate stabilization using a different mechanism from prior reports, and the corresponding genetic axes operate non-additively to regulate seed size.
- Chen Bai
- , Gao-Jie Wang
- & Xian-Jun Song
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Article
| Open AccessPost-resolution macrophages shape long-term tissue immunity and integrity in a mouse model of pneumococcal pneumonia
The post-resolution phase of inflammation is not simply a linear path towards cessation of immune response but rather a regulated process involving fluctuating immune activity. Here authors show a pivotal role for post-resolution macrophages in driving a wave of T cell recruitment and activation via prostaglandin E2 and α-integrin signalling during the resolution phase of murine pneumococcal pneumonia.
- Karen T. Feehan
- , Hannah E. Bridgewater
- & Derek W. Gilroy
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Article
| Open AccessMultiregional transcriptomics identifies congruent consensus subtypes with prognostic value beyond tumor heterogeneity of colorectal cancer
Intratumoral heterogeneity has been documented in multiple cancer types, and can be linked to treatment resistance. Here, the authors analyse multiregional samples from colorectal cancers and show gene expression subtypes which are less vulnerable to heterogeneity and may partly contribute to differential patient survival.
- Jonas Langerud
- , Ina A. Eilertsen
- & Anita Sveen
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Article
| Open AccessCell of origin epigenetic priming determines susceptibility to Tet2 mutation
HSC mutations lead to diverse clonal hematopoiesis outcomes. This study shows how epigenetic traits can predispose clones for dominance. Sox4 increases sensitivity to Tet2 KO, offering insights into variable phenotypes despite identical mutations.
- Giulia Schiroli
- , Vinay Kartha
- & David T. Scadden
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Article
| Open AccessProdrug-conjugated tumor-seeking commensals for targeted cancer therapy
The chemotherapeutic efficacy of prodrug is limited by its cancer-targeting ability. Here this group reports an engineered commensal Lactobacillus plantarum strain with anticancer prodrugs loading on the surface for nasopharyngeal carcinoma cell-targeting and growth inhibition.
- Haosheng Shen
- , Changyu Zhang
- & Matthew Wook Chang
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Article
| Open AccessSelf-organization of modular activity in immature cortical networks
How the cortex forms spatially structured modules during development is poorly understood. Here, the authors show that activity in early developing cortex is self-organized though local-excitation and lateral inhibition.
- Haleigh N. Mulholland
- , Matthias Kaschube
- & Gordon B. Smith
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Article
| Open AccessAstrocytic ALKBH5 in stress response contributes to depressive-like behaviors in mice
The regulatory mechanism and function of astrocytic epigenetic effects on depression remain to be explored. Here, the authors show astrocytic ALKBH5 contributes to depressive-like behaviors via the m6A RNA methylation of GLT-1.
- Fang Guo
- , Jun Fan
- & Xiong Cao
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Article
| Open AccessHeliorhodopsin-mediated light-modulation of ABC transporter
Here, authors classify genes flanking the Heliorhodopsin (HeR)-encoding genes and identify highly conserved residues for protein–protein interactions, revealing a function of HeR as regulatory rhodopsin for multidrug resistance.
- Shin-Gyu Cho
- , Ji-Hyun Kim
- & Kwang-Hwan Jung
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