Perspective
|
Open Access
Featured
-
-
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
-
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
-
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
-
Article
| Open Accessβ-lactamase expression induces collateral sensitivity in Escherichia coli
In this work, authors show that β-lactamase enzymes not only confer antibiotic resistance but also increase susceptibility to other antibiotics.
- Cristina Herencias
- , Laura Álvaro-Llorente
- & Jerónimo Rodríguez-Beltrán
-
Article
| Open AccessMicrobiome and epigenetic variation in wild fish with low genetic diversity
Species with low genetic diversity have limited capacity to adapt to environmental change. This study finds that the skin microbiome and non-genetic (epigenetic) modifications of the DNA represent additional sources of variation that could help low diversity fish survive environmental challenges.
- Ishrat Z. Anka
- , Tamsyn M. Uren Webster
- & Sofia Consuegra
-
Article
| Open AccessNeuromodulatory subcortical nucleus integrity is associated with white matter microstructure, tauopathy and APOE status
The isodendritic core is a group of neuromodulatory nuclei with diffuse projections. Here the authors describe associations between the microstructural integrity of the isodendritic core and whole-brain white matter in humans, and its relationship to Apolipoprotein-E4 carrier status.
- Alfie Wearn
- , Stéfanie A. Tremblay
- & R. Nathan Spreng
-
Article
| Open AccessFate of telomere entanglements is dictated by the timing of anaphase midregion nuclear envelope breakdown
Telomeric entanglements arising from stalled telomeric replication forks can cause mitotic catastrophe in dividing cells. Here, the authors show that resolution of such entanglements in fission yeast requires rapid exposure of the DNA to the cytoplasm during anaphase.
- Rishi Kumar Nageshan
- , Raquel Ortega
- & Julia Promisel Cooper
-
Article
| Open AccessPotent activity of polymyxin B is associated with long-lived super-stoichiometric accumulation mediated by weak-affinity binding to lipid A
Polymyxins are last-resort antibiotics targeting lipid A in the gram-negative outer membrane. Here, the authors use surface plasmon resonance-based kinetics to reveal a three-state mechanism governing superstoichiometric accumulation of polymyxins.
- Kerry R. Buchholz
- , Mike Reichelt
- & John G. Quinn
-
Article
| Open AccessDormant origin firing promotes head-on transcription-replication conflicts at transcription termination sites in response to BRCA2 deficiency
BRCA2 has essential roles in suppressing genome instability at stalled replication forks, but how this is achieved remains unclear. Here, the authors apply Okazaki-fragment sequencing to predict sites of genomic instability caused by head-on transcription-replication conflicts upon BRCA2 loss.
- Liana Goehring
- , Sarah Keegan
- & Tony T. Huang
-
Article
| Open AccessSororin is an evolutionary conserved antagonist of WAPL
Cohesin functions must be tightly regulated. Here Prusén Mota et al. show that the cohesin regulator SORORIN is conserved beyond the animal kingdom and they provide the first organismal in vivo evidence that SORORIN antagonizes WAPL.
- Ignacio Prusén Mota
- , Marta Galova
- & Peter Schlögelhofer
-
Article
| Open AccessAnti-PD-1 cis-delivery of low-affinity IL-12 activates intratumoral CD8+T cells for systemic antitumor responses
IL-12 has been shown to enhance the efficacy of anti-PD-1 therapy, but this has been hampered by issues with toxicity and poor delivery to the tumour site. In this study, the authors generate an anti-PD-1 antibody/IL-12 fusion protein for specific targeting of IL-12 to tumour sites, resulting in potent anti-tumour immunity with limited toxicity.
- Zhuangzhi Zou
- , Jiao Shen
- & Hua Peng
-
Article
| Open AccessGeneration of nanobodies from transgenic ‘LamaMice’ lacking an endogenous immunoglobulin repertoire
Nanobodies are normally made from immunized camelids, Ig transgenic mice or synthetic libraries. In this study, the authors introduce the llama Ig heavy chain locus into mice lacking this locus, thereby generating a line in which nanobodies can be made by direct immunization in the absence of an endogenous antibody repertoire.
- Thomas Eden
- , Alessa Z. Schaffrath
- & Friedrich Koch-Nolte
-
Article
| Open AccessIL-6 inhibition prevents costimulation blockade-resistant allograft rejection in T cell-depleted recipients by promoting intragraft immune regulation in mice
The use of CTLA4-Ig fusion proteins in transplantation remains limited due to co-stimulation blockade-resistant rejection (CBRR). In this study, the authors demonstrate that IL-6 blockade reduces CBRR in murine cardiac transplants in the context of T cell-depleting induction regimens and CTLA4-Ig treatment.
- Moritz Muckenhuber
- , Konstantinos Mengrelis
- & Thomas Wekerle
-
Article
| Open AccessTransfer of modified gut viromes improves symptoms associated with metabolic syndrome in obese male mice
With metabolic syndrome links to gut microbiome imbalance, authors show that transplantation of modified lean fecal donor viromes alleviate metabolic syndrome symptoms in obese mice.
- Xiaotian Mao
- , Sabina Birgitte Larsen
- & Torben Sølbeck Rasmussen
-
Article
| Open AccessInstantly adhesive and ultra-elastic patches for dynamic organ and wound repair
Bioadhesive materials and patches are promising alternatives to surgical sutures and staples but many existing bioadhesives do not meet the functional requirements of current surgical procedures. Here the authors present a tissue adhesive, stretchable and rapid photo-projection compatible translational patch material which is able to deliver therapeutics.
- Parth Chansoria
- , Ameya Chaudhari
- & Juliane Nguyen
-
Article
| Open AccessPPIA dictates NRF2 stability to promote lung cancer progression
Despite being an established oncogenic driver of non-small cell lung cancer (NSCLC), therapies targeting NRF2 hyperactivation are lacking. Here, the authors identify peptidylprolyl isomerase A (PPIA) as a mediator of NRF2 stability and demonstrate the efficacy of targeting this interaction with cyclosporin A in preclinical models of NSCLC.
- Weiqiang Lu
- , Jiayan Cui
- & Jin Huang
-
Article
| Open AccessNeutrophils and galectin-3 defend mice from lethal bacterial infection and humans from acute respiratory failure
This study reports training by lipopolysaccharide to expand neutrophils expressing the anti-bacterial galectin-3 protein defending mice from a lethal bacterial infection, a similar signature associated with survivors of respiratory failure in humans.
- Sudipta Das
- , Tomasz W. Kaminski
- & Prabir Ray
-
Article
| Open AccessIdentification and validation of a blood- based diagnostic lipidomic signature of pediatric inflammatory bowel disease
Diagnostic blood-based biomarkers of pediatric IBD are limited. Here, the authors demonstrate a diagnostic lipidomic signature, comprising only of two molecular lipids. Translation of this signature into a scalable test has the potential to support clinical decision making.
- Samira Salihovic
- , Niklas Nyström
- & Jonas Halfvarson
-
Article
| Open AccessHighly biased agonism for GPCR ligands via nanobody tethering
Activated GPCRs signal through multiple pathways. Ligands that signal through a single pathway are highly valued. The authors demonstrate that tethering ligands to receptors via conjugation with binding nanobodies enables pathway-specific signaling.
- Shivani Sachdev
- , Brendan A. Creemer
- & Ross W. Cheloha
-
Article
| Open AccessPeripheral apoptosis and limited clonal deletion during physiologic murine B lymphocyte development
Self-tolerance is established during B cell development but the contribution of clonal deletion, receptor editing, anergy and apoptosis is debated. Here we show that although apoptosis does occur in a high proportion of transitional B cells after exiting the bone marrow, the reactivity of apoptotic B cells does not differ from that of viable cells, which argues against apoptosis as major mechanism to eliminate self-reactive and polyreactive clones.
- Mikala JoAnn Simpson
- , Anna Minh Newen
- & Christian Thomas Mayer
-
Article
| Open AccessEngineering natural microbiomes toward enhanced bioremediation by microbiome modeling
Engineering natural microbiomes for biotechnological applications remains challenging. Here, the authors present a combinatory top-down and bottom-up framework to engineer natural microbiomes for the construction of function-enhanced synthetic microbiomes.
- Zhepu Ruan
- , Kai Chen
- & Xihui Xu
-
Article
| Open AccessStructural basis for human mitochondrial tRNA maturation
Mitochondrial tRNAs are less structurally stable than nuclear tRNAs, and their maturation pathway is unique. Here, the authors reveal how human mitochondrial precursor tRNAs are recognised, processed, methylated and prepared for full functionality in mitochondrial translation.
- Vincent Meynier
- , Steven W. Hardwick
- & Carine Tisné
-
Article
| Open AccessDiffusion-based deep learning method for augmenting ultrastructural imaging and volume electron microscopy
This study presents EMDiffuse, a software suite based on diffusion models which augments electron microscopy imaging. EMDiffuse enhances electron microscopy images and enables isotropic reconstruction of volume electron microscopy data, suitable for investigating biological nanostructures.
- Chixiang Lu
- , Kai Chen
- & Haibo Jiang
-
Article
| Open AccessIκBα controls dormancy in hematopoietic stem cells via retinoic acid during embryonic development
Hematopoietic stem cells are generated during development, though how and when they become dormant long term-HSCs remains unclear. Here they show that retinoic acid receptor levels are regulated by a IκBα-PRC2 axis in HSCs, and that IκBα KO mice have HSCs that are fewer in number, but functionally and molecularly more dormant.
- Roshana Thambyrajah
- , Maria Maqueda
- & Anna Bigas
-
Article
| Open AccessNutrient levels control root growth responses to high ambient temperature in plants
This study shows root growth increases in high temperature in multiple plant species along with reduced plant nitrogen (N) and phosphorus (P). This growth response is abolished by low N and P environments and mediated via the HY5-NRT1.1 gene module.
- Sanghwa Lee
- , Julia Showalter
- & Wolfgang Busch
-
Article
| Open AccessCo-aggregation with Apolipoprotein E modulates the function of Amyloid-β in Alzheimer’s disease
Here the authors connect inherited Apolipoprotein E genotype with the risk of developing Alzheimer’s disease by demonstrating how, in an isoform- and lipidation-specific way, apoE modulates the aggregation, clearance and toxicity of Amyloid-beta.
- Zengjie Xia
- , Emily E. Prescott
- & Suman De
-
Article
| Open AccessArea postrema neurons mediate interleukin-6 function in cancer cachexia
Elevation of IL-6 during cancer progression has been shown to drive cancer cachexia, however, while brain dysfunction has been reported, the underlying mechanism is unclear. Here, the authors identify neurons in the area postrema as a mediator of peripheral IL-6 in preclinical models of cancer cachexia.
- Qingtao Sun
- , Daniëlle van de Lisdonk
- & Bo Li
-
Article
| Open AccessInherited C-terminal TREX1 variants disrupt homology-directed repair to cause senescence and DNA damage phenotypes in Drosophila, mice, and humans
Variants of the 3′−5′ exonuclease TREX1 can cause retinal vasculopathy with cerebral leukoencephalopathy (RVCL). Here, the authors show that RVCL-associated TREX1 variants trigger DNA damage in humans, mice, and Drosophila, and render cells more vulnerable to DNA damage inducing agents.
- Samuel D. Chauvin
- , Shoichiro Ando
- & Jonathan J. Miner
-
Article
| Open AccessAn axonemal intron splicing program sustains Plasmodium male development
Guan et al. identify a male gametocyte-specific RNA-binding protein RBPm1 in the malaria parasite. RBPm1 controls the intron splicing of axonemal genes. RBPm1- deficient parasites fail to assemble the axoneme for male gametogenesis and thus mosquito transmission of Plasmodium.
- Jiepeng Guan
- , Peijia Wu
- & Jing Yuan
-
Article
| Open AccessA persistent variant telomere sequence in a human pedigree
A variant telomerase template demonstrates that human telomeres can tolerate significant degeneracy and remain functional. Once incorporated by telomerase, variant sequences can influence telomere length dynamics.
- Angela M. Hinchie
- , Samantha L. Sanford
- & Jonathan K. Alder
-
Article
| Open AccessDevelopment and deployment of a histopathology-based deep learning algorithm for patient prescreening in a clinical trial
Here, the authors develop a deep-learning algorithm to predict biomarkers from histopathological imaging in advanced urothelial cancer patients. This method detects suitable patients for targeted therapy clinical trials with a significant reduction in molecular testing, providing cost and time savings in real-world clinical settings.
- Albert Juan Ramon
- , Chaitanya Parmar
- & Kristopher A. Standish
-
Article
| Open AccessStructural conversion of the spidroin C-terminal domain during assembly of spider silk fibers
The mechanical properties of spider silk are a consequence of the structural organisation of proteins known as spidroins. Here the authors investigate the structure of the fibers formed by a C-terminal domain of a major spidroin: the study elucidates the mechanisms by which spidroins are transformed from soluble form into a fiber.
- Danilo Hirabae De Oliveira
- , Vasantha Gowda
- & My Hedhammar
-
Article
| Open AccessTwo noncompeting human neutralizing antibodies targeting MPXV B6 show protective effects against orthopoxvirus infections
There are limited therapeutics available for treatment of mpox. In this study, the authors identify two non-competing human neutralizing monoclonal antibodies with protective effects against orthopoxvirus infection in a mouse model and structurally resolve the targeted epitope within the MPXV B6 protein.
- Runchu Zhao
- , Lili Wu
- & Qihui Wang
-
Article
| Open AccessA multidimensional selective landscape drives adaptive divergence between and within closely related Phlox species
Selection drives divergence between species, contributing to speciation, while simultaneously favoring extensive diversity that is maintained across populations within a species. This study demonstrates how the selection landscape is complex and multidimensional across three species of Phlox flowers.
- Benjamin E. Goulet-Scott
- , Matthew C. Farnitano
- & Robin Hopkins
-
Article
| Open AccessCircular single-stranded DNA as a programmable vector for gene regulation in cell-free protein expression systems
Protein expression vectors in cell-free systems mainly rely on double-stranded DNA and single-stranded RNA. Here, authors use circular single-stranded DNA as a programmable vector for gene regulation in a cell-free expression system by identifying its expression pathways.
- Zhijin Tian
- , Dandan Shao
- & Jie Song
-
Article
| Open AccessDeep brain stimulation of symptom-specific networks in Parkinson’s disease
Different motor symptoms respond variably to deep brain stimulation in Parkinson’s Disease. Rajamani et al. suggest that this variability may be due to tremor, bradykinesia, rigidity, and axial symptoms being associated with a gradient of brain circuits.
- Nanditha Rajamani
- , Helen Friedrich
- & Andreas Horn
-
Article
| Open AccessEvolved histone tail regulates 53BP1 recruitment at damaged chromatin
Histone H2AX is a central regulator in DNA repair. Here, the authors show that the H2AX C-terminal linker mediates recruitment of 53BP1, a mechanism which evolved to function independently of the canonical phospho-ubiquitin axis important for DNA repair regulation.
- Jessica L. Kelliher
- , Melissa L. Folkerts
- & Justin W. Leung
-
Article
| Open AccessThe peptidase DA1 cleaves and destabilizes WUSCHEL to control shoot apical meristem size
The transcription factor WUSCHEL is essential for stem cell function, but factors that directly modulate WUS stability are unclear. This work discovers that the peptidase DA1 cleaves and destabilizes WUS to control shoot apical meristem size.
- Guicai Cui
- , Yu Li
- & Yunhai Li
-
Article
| Open AccessAtomistic mechanism of coupling between cytosolic sensor domain and selectivity filter in TREK K2P channels
The TREK K2P channel activity is dynamically regulated by protein kinase-dependent signaling pathways involved in the development of various human diseases. Here, the authors report how phosphorylation at the proximal C-terminus induces allosteric deactivation of the selectivity filter gate.
- Berke Türkaydin
- , Marcus Schewe
- & Han Sun
-
Article
| Open AccessConformations of Bcs1L undergoing ATP hydrolysis suggest a concerted translocation mechanism for folded iron-sulfur protein substrate
How folded proteins are translocated across membranes is unknown for eukaryotes. Here, the authors propose a concerted translocation mechanism used by the AAA-ATPase Bcs1 to retro-translocate fully folded Rieske iron-sulfur protein across mitochondrial inner membrane.
- Jingyu Zhan
- , Allison Zeher
- & Di Xia
-
Article
| Open AccessNanoscale cellular organization of viral RNA and proteins in SARS-CoV-2 replication organelles
The precise cellular localization of the SARS-CoV-2 RNA and replication partners has been elusive. Here, the authors use super-resolution fluorescence microscopy and specific labeling to reveal the nanoscale structure of viral replication organelles.
- Leonid Andronov
- , Mengting Han
- & W. E. Moerner
-
Article
| Open AccessGlobal biogeography of microbes driving ocean ecological status under climate change
Zhang et al. propose the ecological status of the ocean by considering microbial diversity, structure, and biogeochemical potential. Ecological status of 32.44% surface ocean will change due to climate change in 2100, assuming no policy intervention.
- Zhenyan Zhang
- , Qi Zhang
- & Haifeng Qian
-
Article
| Open AccessA theory of evolutionary dynamics on any complex population structure reveals stem cell niche architecture as a spatial suppressor of selection
Evolutionary models can help understand how the spatial arrangement of a population shapes its evolutionary dynamics. This study presents such a method and shows that the spatial architectures of stem cell populations in bone marrow are suppressors of selection, hinting at a potential evolutionary design.
- Yang Ping Kuo
- , César Nombela-Arrieta
- & Oana Carja
-
Article
| Open AccessAplp1 interacts with Lag3 to facilitate transmission of pathologic α-synuclein
Pathologic α-synuclein spreads from cell-to-cell through binding to the lymphocyteactivation gene 3 (Lag3). Here, the authors demonstrate that the amyloid β precursor-like protein 1 (Aplp1) interacts with Lag3 and facilitates the binding, internalization, transmission, and toxicity of pathologic α-synuclein.
- Xiaobo Mao
- , Hao Gu
- & Ted M. Dawson
-
Article
| Open AccessUniversal paramyxovirus vaccine design by stabilizing regions involved in structural transformation of the fusion protein
There is a lack of vaccines for prevention of human respirovirus 3 (RV3) infection. Bakkers et al. report the design of a stabilized RV3 preF protein vaccine candidate that induces strong neutralizing antibodies and protective responses in small animal models.
- Johannes P. M. Langedijk
- , Freek Cox
- & Mark J. G. Bakkers
-
Article
| Open AccessRepresentation of genomic intratumor heterogeneity in multi-region non-small cell lung cancer patient-derived xenograft models
Patient-derived xenografts are important tools for cancer drug development. Here, the authors develop models from 22 non-small cell lung cancer patients. They show genomic differences between models created from different spatial regions of tumours and a bottleneck on model establishment.
- Robert E. Hynds
- , Ariana Huebner
- & Charles Swanton
-
Article
| Open AccessThe real-time infection hospitalisation and fatality risk across the COVID-19 pandemic in England
The severity of SARS-CoV-2 infection varied over the course of the pandemic due to factors such as changes in variant characteristics and population immunity from previous infection or vaccination. Here, the authors estimate infection hospitalisation and infection fatality rates in England over time from the start of the pandemic until March 2023.
- Thomas Ward
- , Martyn Fyles
- & Christopher E. Overton
-
Article
| Open AccessIntrinsic and synaptic determinants of receptive field plasticity in Purkinje cells of the mouse cerebellum
How each mechanism of plasticity contributes to memory formation is not fully understood. Here the authors show that plasticity of intrinsic excitability exerts permissive control over the coupling of synaptic weight to neuronal output, as shown in Purkinje cells using two-photon microscopy. Non-synaptic plasticity emerges as an independent player in learning.
- Ting-Feng Lin
- , Silas E. Busch
- & Christian Hansel
-
Article
| Open AccessThe thioredoxin system determines CHK1 inhibitor sensitivity via redox-mediated regulation of ribonucleotide reductase activity
The clinical application of inhibitors targeting checkpoint kinase 1 (CHK1) is challenged by limited efficacy. Here, the authors identify that thioredoxin (Trx) system inhibition mediates sensitivity to CHK1 inhibitor via regulating the activity of ribonucleotide reductase, demonstrating the synergistic effect of CHK1 inhibitor and inhibitors targeting Trx system in lung cancer models.
- Chandra Bhushan Prasad
- , Adrian Oo
- & Junran Zhang
Browse narrower subjects
- Biochemistry
- Biological techniques
- Biophysics
- Biotechnology
- Cancer
- Cell biology
- Chemical biology
- Computational biology and bioinformatics
- Developmental biology
- Drug discovery
- Ecology
- Evolution
- Genetics
- Immunology
- Microbiology
- Molecular biology
- Neuroscience
- Physiology
- Plant sciences
- Psychology
- Stem cells
- Structural biology
- Systems biology
- Zoology