Steadily growing cells prepare for conditions that demand increased translation by producing excess ribosomes, at the expense of lower steady-state growth rate.
Patterning of the dorsal-ventral axis in zebrafish is mediated by a graded source-sink mechanism in which diffusing BMP, produced from a ventrally biased source, is inhibited by dorsally-produced chordin.
Ernesto Pérez, Jillian L Lindblad, Andreas Bergmann
The oncogenic RasV12 keeps cells mutant for the tumor suppressor scribble in an undead-like condition, which is required for an amplification loop that promotes tumorigenesis.
Brent S Wells, Daniela Pistillo ... Claude Desplan
TGFβ family members instruct a cell fate decision downstream of stochastic signaling in the Drosophila retina to ensure correct pairing between different color photoreceptors for color vision.
Glutamate receptor auxiliary proteins exert their effects on receptor gating through two divergent extracellular loops, explaining subunit specificity and allowing the construction of null versions that form complexes normally but do not modify receptor gating.
Integrative analysis of a specialized metabolic pathway across multiple non-model species illustrates mechanisms of emergence of chemical novelty in plant metabolism.
Michiel van Veen, Elisa Matas-Rico ... Wouter H Moolenaar
GDE3 is a transmembrane GPI-specific phospholipase C that sheds the urokinase receptor (uPAR) from the cell surface resulting in loss of uPAR function in breast cancer cells and reduced tumor growth.
Similar to spontaneous eye blinks perceptual stability, despite small saccades, is related to actively silencing transients in the high-level ends of both ventral and dorsal visual cortices, while activity in low-level visual cortex remains unstable.
Identification and functional characterization of C. elegans luqin-like arginine-tyrosine-NH2 (RYamide) peptides reveal their critical role in feeding-related processes.
Calcium-binding synaptotagmins are involved in ring oligomer formation, which allows synaptotagmins to synchronize neurotransmitter release to Ca2+ influx.
Matthias Pechmann, Matthew A Benton ... Siegfried Roth
In the spider Parasteatoda tepidariorum the transcription factor Ets4 is needed for cumulus integrity, dorsoventral patterning and for the activation of hunchback and twist expression.
PRDM13, a transcriptional repressor, antagonizes activity of basic-helix-loop-helix transcriptional activators and protects the developing spinal cord from aberrant expression of ventral-restricted cell-type regulators to generate the correct composition of neurons in the dorsal spinal cord.
Retrotransposon-derived messenger RNA plays a critical role in rice root development via sequestration of miR171, which suggests a novel trans-acting regulation by transposable elements.
Adam JM Wollman, Sviatlana Shashkova ... Mark C Leake
Transcription factors form clusters independently of the presence of DNA, which regulate target genes as opposed to individual monomers, addressing a longstanding question of how transcription factors can find gene targets so quickly.
The 24 ANK repeats of each ankyrin are inhibited by combinatorial bindings of multiple disordered segments from their tail regions, suggesting a mechanism for differential regulations of membrane target bindings by ankyrins.
The RNA-binding protein Mmi1 targets its own inhibitor Mei2 for ubiquitination by the E3 ubiquitin ligase Not4/Mot2 in order to preserve its role in meiotic mRNA decay during vegetative growth.
Occluding-junctions form a permeability barrier around the hematopoietic niche in Drosophila that controls the production of immune cells in response to infection by shaping the signalling micro-environment produced by the niche.
Biochemical and cell biological analyses reveal that the Astrin-SKAP complex acts to stabilize kinetochore-microtubule interactions through its intrinsic microtubule binding activity and its association with the Ndc80 complex, the core component of the kinetochore-microtubule interface.
Genetic analyses reveal that purely quantitative changes in the relative copy number of chromosomes can be sufficient to disrupt the epigenetic mechanisms that define the cells' differentiated state.
The introduction of rapid diagnostic testing for Plasmodium falciparum infections can explain an increased emergence of diagnostic resistant pfhrp2-deleted parasites in sub-Saharan Africa.
Bárbara Coimbra, Carina Soares-Cunha ... Ana João Rodrigues
LDT-VTA dysfunction induced by prenatal glucocorticoid exposure leads to reward deficits that can be ameliorated by selective optogenetic activation of this circuit.
Short bursts of high-intensity exercise elicit robust improvements in core cognitive abilities, especially in individuals whose genotype is associated with lower cognitive performance.
Patrick Smith, David Willemsen ... Dario Riccardo Valenzano
Resetting a young gut microbiota in middle-aged individuals extends life span and slows aging in the naturally short-lived turquoise killifish, a new vertebrate model organism to study how the microbiota affects the aging process.
The melanocortin-4 receptor knockout mouse exhibits a cardiomyopathy syndrome, which raises concerns about cardiovascular function in patients with the similar loss of function mutations, and perhaps even in the 1 in 1500 patients with heterozygous loss of the gene.
Single molecule fluorescence analysis of spliceosome E complex formation reveals how tuning of U1 binding to the 5' SS facilitates efficient capture of the snRNP by pre-mRNAs.
An innovative inter-subject stimulus-locked brain activation approach uncovers marked topological differences in a brain network of higher-order visual regions in individuals with a congenital impairment in face recognition compared with controls.
In contrast to previous post-mortem or fixed tissue histochemical reports, live calcium and mitochondrial imaging data suggest that the enteric nervous system is not generally affected in Parkinson's disease patients.
Laura González-Méndez, Irene Seijo-Barandiarán, Isabel Guerrero
Direct interaction between Hedgehog-sending and Hedgehog-receiving cytonemes is a fundamental mechanism for morphogen transfer and gradient establishment.
Solute movement in brain extracellular space is determined by solute diffusion, and does not depend on convection or aquaporin-4 expression as predicted by the glymphatic mechanism.
Oriane Blanquie, Jenq-Wei Yang ... Heiko J Luhmann
In the developing mouse, the regional distribution of neuronal apoptosis in the primary motor cortex and primary somatosensory cortex is controlled by sensory-driven and intrinsic electrical activity patterns.
An unbiased transcriptional profiling screen reveals the secreted matrix metalloproteinase MMP-1 is a transcriptional target of the ensheathing glial receptor Draper following acute axon injury in adult Drosophila.
David Florentino Montez, Finnegan J Calabro, Beatriz Luna
The excessive behavioral variability associated with adolescence is the result of greater instability of widespread or global gain signals which produces greater variability in the amplitude of expression of whole-brain states of task-related activity.
Leukemia-Related Protein 16 (LRP16), a member of the macro domain family, plays a crucial role in orchestrating genotoxicity-initiated NF-κB signaling in the colon and the pathophysiological relevance of NF-κB activation induced by LRP16 in colonic cell survival/recovery from extrinsic DNA damage.
Kathleen Greenham, Carmela Rosaria Guadagno ... C Robertson McClung
Coupled physiology and gene expression, measured over a two-day time course, reveals specific time-of-day responses to the early stages of drought in Brassica rapa.
A novel lncRNA (Ephemeron) is connected to known post-transcriptional and epigenetic regulators as part of an integrated machinery, which controls the timely exit from the naïve state of mouse embryonic stem cells.
Coregulators mediate selective interactions between DNA-bound androgen receptor and other transcription factors, which control distinct prostate cancer biology, suggesting disruption of critical interactions in these complexes as a novel therapeutic strategy.
Katherine Amberg-Johnson, Sanjay B Hari ... Ellen Yeh
An unbiased chemical screen identifies the AAA+ membrane metalloprotease FtsH1 as a novel apicoplast biogenesis factor and druggable antimalarial target.
James S Martenson, Tokiwa Yamasaki ... Susumu Tomita
A novel GABAAR assembly pathway that promotes synaptic inhibition is established and provides a molecular explanation for how GABAARs with distinct subunit compositions display distinct subcellular distributions.
Elizabeth R Jerison, Sergey Kryazhimskiy ... Michael M Desai
Substantial heritable genetic variation in adaptability and the pleiotropic consequences of adaptation exists in budding yeast, and can be explained by a combination of fitness and specific segregating alleles.
Michael R Bale, Malamati Bitzidou ... Miguel Maravall
Mice and humans learned to distinguish an arbitrary tactile sequence from other stimuli that differed only in their temporal patterning over hundreds of milliseconds, showing that sequence learning generalises across sensory modalities.
Matthew A Sdano, James M Fulcher ... Christopher P Hill
The tandem SH2 domains of Spt6 use novel mechanisms to bind unexpected phosphorylated serine and threonine residues in the RNA polymerase II linker to recruit Spt6 to sites of transcription and maintain repressive chromatin.
Intersectin counterparts in yeast recruit WASP and WIP to endocytic sites to establish a robust multivalent SH3 domain-PRM interaction network which gives actin assembly onset a switch-like behavior in vivo.
A network, composed of 22 relatives of the Beaten Path and Sidestep immunoglobulin superfamily cell surface proteins, also includes several neuronal Beaten Path subfamily receptors which interact selectively with Sidestep subfamily proteins expressed on peripheral tissues.
Magnetothermal neuromodulation providing quick, tetherless, precise on and off switching of neurons deep in the brain of freely moving animals is orthogonal to optogenetics and a breakthrough in remote modulation techniques.
Fanny Pouyet, Dominique Mouchiroud ... Marie Sémon
Variation in codon usage among functional categories of human genes is not due to selection for translation efficiency, but to differences in intragenic recombination rate, linked to variation in meiotic transcription level.
Sandeep Dembla, Marc Behrendt ... Johannes Oberwinkler
Pro-nociceptive and pro-inflammatory TRPM3 (transient receptor potential melastatin 3) channels, expressed in somatosensory neurons, are inhibited by activation of Gαi-coupled receptors, such as µ-opioid receptors, in vitro and in vivo.
Electrophysiological experiments, Ca2+ imaging, and behavioral studies in mice identify the TRPM3 ion channel as a novel target of G-protein βγ subunits.
A link between chronic stress and organ dysfunction is explained by the gateway reflex, in which brain micro-inflammation at specific vessels establishes a new neural pathway to induce fatal organ failure particularly in gastrointestine and heart.
Laurence Abrami, Tiziano Dallavilla ... F Gisou van der Goot
Cycles of palmitoylation-depalmitoylation by an upstream palmitoyltransferase allow precise tuning of DHHC6 activity, which in turn regulates the abundance and function of key ER proteins involved in protein folding, degradation, ER architecture and calcium homeostasis.
Genetic and cell biological study indicates that germ cells' connectivity serves as a mechanism to increase the sensitivity of germline to DNA damage, protecting the genome of gametes, in the Drosophila testis.
Alexander Muir, Laura V Danai ... Matthew G Vander Heiden
Cell culture models widely used in cancer research do not reflect metabolism in tumors; by altering culture systems to better model tumor metabolism we find that environmental cystine promotes tumor glutamine metabolism.
Efficient targeting of membrane proteins from the endoplasmic reticulum (ER) to the inner nuclear membrane depends on GTP hydrolysis by Atlastin GTPases and their function in maintaining an interconnected topology of the ER network.
Marie MacLennan, Marta García-Cañadas ... Ian R Adams
Post-translational regulation of retrotransposons plays a key role in preventing retrotransposon mobilization in the epigenetically dynamic mouse germline.
BalaT-dependent β-alanine trafficking pathway in retinal pigment cells is critical for maintaining synaptic transmission of photoreceptor neurons in Drosophila.
Daniel Andergassen, Christoph P Dotter ... Quanah J Hudson
Allele-specific expression due to genetic differences, X-chromosome inactivation or genomic imprinting, varies dynamically throughout development, and may be explained by allele-specific differences in stability or the actions of tissue-specific enhancers.
MKLP2 is a divergent molecular motor that has structurally evolved to bind its microtubule track and use the energy of ATP in distinct ways, tuned according to its function in cell division.
Global transcriptome changes, particularly alternative splicing, are highly dynamic the first 2 weeks after birth, and the example of calcineurin A splicing exemplifies the importance of alternative splicing during skeletal muscle development.
Kirill Tokarev, Julia Hyland Bruno ... Henning U Voss
Co-evolution of sexually dimorphic reinforcement systems for song can explain the coexistence of the seemingly contradictory traits of gregariousness and monogamy in social songbirds.
Neurosecretory protein GL, a previously unknown mammalian neuropeptide, is a novel hypothalamic factor which regulates feeding behavior and peripheral lipogenesis in animals.
Targeting the activation of the androgen receptor N-terminal domain by the cochaperone Bag-1L provides a new approach for inhibiting androgen receptor function to treat prostate cancer.
The cellular behaviours that underlie the internalization of the multilayered endoderm anlage in Xenopus laevis link the ancestral mode of vertebrate gastrulation to common, epithelial-based mechanisms of gastrulation in non-vertebrate animals.
Using Drosophila as a model organism shows that neural stem cell proliferation decisions in response to dietary nutrient conditions can be regulated by cell-autonomous lineage factors.
Andrew Santiago-Frangos, Jeliazko R Jeliazkov ... Sarah A Woodson
Modeling and biophysics show that the unstructured acidic tail of the Sm protein Hfq mimics nucleic acid to auto inhibit its chaperone activity, preventing Hfq from being sequestered by inauthentic substrates and providing insight into the evolution of Hfq's chaperone function among bacterial genera.
Embryo-wide quantitative analysis of BMP signaling in zebrafish embryos, combined with a mathematical model-based computational screen, challenges the prevailing model of an antagonist counter-gradient shaping the gastrula BMP morphogen gradient and supports an antagonist sink with BMP diffusion mechanism.
Johanne Le Coq, Marta Camacho-Artacho ... Daniel Lietha
The SHIP2 inositol phosphatase is an important upstream regulator of the Akt signaling pathway, which requires a catalytic core formed by the phosphatase domain tightly packed to a C2 domain for its function.
Pierre Khoueiry, Charles Girardot ... Eileen EM Furlong
Interspecies comparison of transcription factor occupancy during embryogenesis reveals potential co-operative relationships between factors and uncovers the inherent plasticity of developmental enhancers to overcome divergence in transcription factor occupancy.
Young neurons of the adult hippocampus are synaptically activated by a small group of non-overlapping afferent excitatory fibers, due to high synaptic gain and sparse connectivity, important for sparse and orthogonal coding during hippocampal information processing.
Pre-verbal infants demonstrate an implicit sensitivity to interoceptive sensations, which fluctuates spontaneously during emotional processing and guides audiovisual preferences in the environment.
Matthias Lübbert, R Oliver Goral ... Samuel M Young Jr
A novel region in the CaV2.1 α1 subunit regulates coupling of synaptic vesicles to CaV2.1 calcium channels, synaptic vesicle release and docking, and the size of the fast and total releasable pools of synaptic vesicles.
Ganesh V Raj, Gangadhara Reddy Sareddy ... Ratna K Vadlamudi
A novel first-in-class small molecule (ERX-11) that interacts with and disrupts the interactome of the estrogen receptor (ER), blocks the growth of ER-positive breast cancers, including those that are resistant to currently approved hormonal agents.
Mateusz Maciejewski, Eugen Lounkine ... Laszlo Urban
Careful analysis of adverse drug reaction reports reveals noise and biases embedded in this data and allows for systematic mitigation of these effects to produce much more robust understanding of side effects of marketed drugs.
Ivan Larderet, Pauline MJ Fritsch ... Simon G Sprecher
The synaptic connectome of the Drosophila larval visual circuit is the first case of a completely reconstructed visual network in a genetically fully tractable model organism.
Mature axons lose the ability to regenerate because key growth molecules are excluded through changes in vesicle transport, and restoring transport can restore regeneration.
The neural population of the Aplysia's pedal ganglion are a low-dimensional spiral attractor, and the parameters of the attractor directly define the properties of the Aplysia's escape locomotion behaviour.
Population cortical recordings and computational network modeling support a novel mechanism underlying spontaneous UP-DOWN dynamics consisting on non-rhythmic transitions between a silent attractor and a low-rate inhibition-stabilized attractor.
During awake Sharp wave-ripple memory reactivation, hippocampal-cortical representations for movement- versus immobility-associated experiences are reactivated separately.
Agonist and antagonist peptides of the corticotropin-releasing factor receptor type 1 adopt different folds and stabilize distinct conformations of the receptor transmembrane domain, which involves tilting of helices VI and VII around conserved glycine hinges.
Jonathan Strecker, Sonia Stinus ... Daniel Durocher
A sharp transition in the fate of DNA ends with telomere sequences is identified, which suggests a boundary between DNA double-strand breaks and telomeres.
Luis Miguel Díaz-Santín, Natasha Lukoyanova ... Alan CM Cheung
An atomic model of the 3744-residue Tra1 protein reveals multiple transcription activator binding sites, its integration within the SAGA chromatin coactivator complex, and a striking similarity to DNA-repair factor DNA-PKcs.
Functional and mechanistic analyses of cancer cells containing homozygous deletion of TP53 and FXR2 reveal that inhibition of FXR1 blocks cell proliferation in a collateral lethality manner, opening an avenue to develop therapies targeting such cancers.
The utility of split GFP for tissue-specific visualization of ribosomes in live Caenorhabditis elegans demonstrates the link between ribosomes and microtubules.
The development of diet-dependent obesity results in the deterioration of calcium homeostasis in pro-opiomelanocortin-expressing neurons and impaired function of the same neurons.
Shigetomo Suyama, Alexandra Ralevski ... Tamas L Horvath
Neurons in the hypothalamus that promote satiety manifest plasticity of their response to the excitatory transmitter, glutamate, by re-organizing the composition of a specific glutamare receptor.
Suv39h1 chromodomain possesses nucleic acid-binding activity and this activity is coupled with its H3K9 methylation recognition in assembling heterochromatin.
