NDR kinase Orb6 prevents RNP granule assembly and translational repression by promoting Sts5 association with 14-3-3 protein Rad24 to spatially control polarized cell growth.
Stephen W Eichhorn, Alexander O Subtelny ... David P Bartel
Profiling of mRNA poly(A)-tail lengths and translational efficiencies provides new insights into posttranscriptional gene regulation in early Drosophila development.
Eph receptor signaling commonly excludes migrating embryonic cells from regions of high ligand density; however, in sea urchin embryos pigmented immunocytes are attracted to regions expressing high levels of Ephrin.
Daichi Nozaki, Atsushi Yokoi ... Jean-Jacques Orban de Xivry
Noninvasive brain stimulation can artificially tag and retrieve human motor memories by altering the background activity patterns of the sensorimotor cortex.
Bacteria use the transcription factor binding region of their transcription activator-like effectors to hijack host basal transcription factor to cause rice diseases by activating host susceptibility genes.
John M Nicoludis, Bennett E Vogt ... Rachelle Gaudet
Clustered and non-clustered protocadherins form antiparallel homodimers in which distinct regions of the extended interface demonstrate a division of labor between driving affinity and determining specificity.
Victoria E Pedanou, Stéphane Gobeil ... Michael R Green
A large-scale RNA interference screen uncovers a new transcriptional regulatory program involving the histone H3 demethylase KDM3A, which mediates detachment-induced apoptosis (anoikis) in breast epithelial cells.
Dawn Z Eichenfield, Ty Dale Troutman ... Christopher K Glass
Combinatorial signaling leads to transcription factor co-localization at Rev-erb sensitive enhancers, enabling a diversified cellular response to complex stimuli.
Yishan Sun, Sergiu P Paşca ... Ricardo E Dolmetsch
A human cellular model of a prototypical form of intractable childhood epilepsy supports selective impairment of inhibitory neurons as a key pathophysiological mechanism.
Two related DNA replication initiation proteins contribute to the decision of whether to enter a new round of the cell division cycle or enter into a period of proliferative quiescence.
Dorothy P Schafer, Christopher T Heller ... Beth Stevens
In mouse models of Rett Syndrome, global loss of the Mecp2 gene induces microglia to engulf excess synapses, while microglia-specific loss or gain of Mecp2 has little impact on disease.
Cerebellar Purkinje neurons use a multiplexed simple spike code combining synchrony/spike time and firing rate, with each component encoding distinct information about movements such as motion onset timing and kinematics.
Height in early adulthood is an indicator that integrates across different dimensions of sustainable human development with links to health and longevity, nutrition, education and economic productivity.
The nuclear protein Sam68 plays a role in the genotoxic stress-initiated "nuclear to cytoplasmic" activation of NF-κB and is involved in the development and survival of colon cancer.
An integrative model of coordinated crawling in fruit fly maggots links neuromuscular dynamics to body-substrate mechanics in the presence of proprioceptive feedback.
Activity in the pedunculopontine tegmental nucleus reflects the choices and outcomes of previous trials in a decision making task, and affects upcoming choices.
Nicholas B Last, Ludmila Kolmakova-Partensky ... Christopher Miller
Combining crystal structures with single-pore analysis of Fluc-family fluoride channel mutants demonstrates that Fluc channels have two separate fluoride ion permeation pathways within the channel complex.
Two natural cooling agents activate the cold-activated channel TRPM8 via two opposite mechanisms, evoking distinct electrical responses in cold-sensitive neurons.
Catherine A Hartzell, Katarzyna I Jankowska ... Richard S Lewis
By restricting actin polymerization to the perimeter of the immune synapse and promoting depolymerization, calcium influx drives centripetal actin flow, which confines CRAC channels and the endoplasmic reticulum to the synapse center.
The link between the activity of large populations of cortical neurons and single neuron responses is examined in primates using a new optical-genetic method.
Christopher P Arnold, M Shane Merryman ... Alejandro Sánchez Alvarado
An innate immune system signaling pathway in planarians has a dual role: it enhances apoptosis during bacterial infection, but represses apoptosis during tissue regeneration in the absence of infection.
Building on previous work (Aso et al., 2014a; Aso et al., 2014b), cell-type-specific drivers and optogenetics are used to control the local release of dopamine and reveal that distinct learning rules are implemented in parallel memory units.
Chiara M Eandi, Hugo Charles Messance ... Florian Sennlaub
IL-1β release from macrophages might be responsible for the unexplained cone segment loss in retinal degenerative diseases that are associated with subretinal inflammation, such as retinitis pigmentosa or geographic atrophy.
Lars Plate, Christina B Cooley ... Jeffery W Kelly
Small molecule proteostasis regulators that activate the unfolded protein response transcription factor ATF6 reduce the secretion of amyloid disease-associated proteins.
The auditory cortex temporarily stores task-relevant information by persistently changed neuronal activity of single neurons and of neuronal populations.
The transcription machinery is required for the disassembly of the promoter-proximal H2A.Z nucleosome, contributing to the constitutive histone turnover at yeast promoters.
Ciara M Gallagher, Carolina Garri ... Peter Walter
Ceapins enable selective pharmacological inhibition of the cytoprotective transcriptional response to endoplasmic reticulum stress through ATF6α without affecting other branches of the unfolded protein response.
Fluorescence detected sedimentation velocity offers a new method for studying heterogeneous protein interactions in solution by exploiting characteristic temporal signal modulations of photoswitchable fluorescent proteins.
Marc Chevalier, Natalia Toporikova ... Muriel Thoby-Brisson
Pacemaker neurons are present in the preBötC circuitry of mouse embryos and their role in driving respiratory network activity changes during the critical period immediately before birth.
A fully synthetic library of humanized single domain antibodies yields in vitro high affinity antibodies usable in cell biology and translational projects.
In keratinocytes, the BRAF and RAF1 proteins work independently to balance the activity of mitogenic and stress kinase cascades and uphold the mechanical and immunological barrier functions of the epidermis.
New biophysical methods and analyses visualize in real-time a chain of coordinated single-molecular events on a living cell, enabling the inner workings of a mechanoreceptor important to biology to be elucidated.
Convergent transcription and stalling of transcription are enriched at DNA breakpoints found in acute lymphoblastic leukemia and associate with DNA structures and sequences that mediate genetic instability.
Small molecule inhibitors identified in a biophysical high-throughout screening assay confirm the importance of the interaction between single-stranded DNA and the protein RAD52 for the survival of BRCA2-depleted cells.
Maria N Zanetti, Oscar D Bello ... Shyam S Krishnakumar
A model for synchronous neurotransmitter release suggests that when not in the presence of calcium ions, Synaptotagmin proteins form ring-like structures between the vesicle and plasma membrane that prevent spontaneous fusion.
Clonal tracing in vivo and quantitative modeling in silico reveal a unique mode of tissue growth and structural remodeling of the biliary system, providing an insight into the cellular basis for robust liver regeneration.
A combination of optogenetics and 2-photon calcium imaging reveals spatial prerequisites for non-linear synaptic summation within a defined cortical connection.
When Rhesus monkeys plan reaching movements of which they are not fully confident, a particular area of the brain represents both the chosen action as well as alternate movements, perhaps as an aid for error correction or learning.
David M Pigott, Anoushka I Millear ... Simon I Hay
Building on previous work (Pigott et al. 2014), estimates of areas of potential transmission of Ebola virus are revised and updated to provide a contemporary map for use by researchers and policymakers.
Though generally considered a transcriptional repressor, Wiz may also function as a transcriptional activator in the mouse brain and is required for normal behaviour.
James D Joseph, Beatrice Darimont ... Jeffrey H Hager
GDC-0810 is a novel, orally bioavailable SERD that exhibits robust pre-clinical activity in models of ER+ breast cancer, including models of tamoxifen resistance, and those that express the ERα mutations, ER.Y537S and ER.D538G.
Christopher Chidley, Sunia A Trauger ... Erin K O'Shea
An unbiased genetic screen in human cells shows that the molecular target of a natural product with promising anticancer activity is a membrane phospholipid.
Birds that see ultraviolet light tune the sensitivity of their short-wavelength photoreceptors with colored filters to maximize the number of colors they can see.
Yoshitaka Kawasoe, Toshiki Tsurimoto ... Tatsuro S Takahashi
Biochemical analysis in Xenopus egg extracts reveals that the MutSα mismatch sensor retains the DNA-bound replication clamp to maintain a post-replicative temporal window permissive to strand-specific repair of mismatches.
TOR kinase guides the transition of plant stem cells from the dormant embryonic state to the active adult state by integrating light and metabolic signals.
The extra dimensions in protein sequence space open up indirect paths of adaptation and alleviate the constraint on the selective accessibility to high fitness genotypes.
New hybrid structure determination methods leveraging the inherent biophysical properties of a macromolecule through molecular dynamics simulations provide accurate and cost-efficient ways of achieving atomic structures from high resolution cryo-electron density maps.
Neural oscillations are a necessary consequence of efficient coding of sensory signals by a spiking neural network, limited by synaptic delays and noise.
Maximilian Joesch, David Mankus ... Joshua R Sanes
A new pipeline of electron microscopy techniques reduces the time required to visualize genetically targeted neurons and their connections by two orders of magnitude.
The tumor suppressor p53 prevents tumor cell growth by employing a small RNA called miR-139-5p to inhibit the activity of an tumorigenic protein, cAMP-specific phosphodiesterase 4D.
A stochastic model of phyllotaxis can explain the striking irregularities observed in the spiral patterns of plants and predicts that perturbation patterns provide key information about the underlying biochemical mechanisms.
Emma Watson, Viridiana Olin-Sandoval ... Albertha JM Walhout
The roundworm C. elegans transcriptionally activates five genes comprising an alternate propionate breakdown pathway when dietary vitamin B12 is low or when the canonical pathway is compromised.
Christine E Cho, Chantal Brueggemann ... Cornelia I Bargmann
Odor conditioning induces two changes in olfactory neurons: non-associative sensory adaptation to odor history, and associative, bidirectional changes in behavioral output that are oppositely regulated in aversive and appetitive learning.
Novel brainstem organotypic cultures that generate rhythmic respiratory motor activity reveal the neural networks that control breathing and a new pathway in the hypercapnic response.
Microbial genetics and biophysical analyses provide insight into an evolutionarily conserved bile salt receptor complex used by pathogenic bacteria to sense their environment.
Claire E Stelly, Matthew B Pomrenze ... Hitoshi Morikawa
Enhanced glutamatergic synaptic plasticity in mesolimbic dopaminergic neurons may contribute to repeatedly stressed rats becoming more vulnerable to addiction.
Karmel A Allison, Eniko Sajti ... Christopher K Glass
Pre-existing enhancers interpret T cell signaling strength in an analogue manner to direct quantitative changes in gene expression within the context of an overall digital response.
Shanna L Resendez, Piper C Keyes ... Brandon J Aragona
The neural mechanisms that underlie the maintenance of social bonds between prairie voles suggest that social support networks may be a powerful way of treating addiction.
Human proteins that add or remove the methyladenosine modification of cellular RNA, or recognize methylated RNA significantly affect HIV-1 infection or viral protein synthesis in cells, suggesting an important role for HIV-1 RNA methylation in regulating viral replication.
Glucocorticoid receptor directly regulates the transcriptional activity of peroxisome proliferator-activated alpha (PPARα) before birth in anticipation of the sudden shifts in the postnatal nutrient source and metabolic demands.
