Jeroen Overman, Frank Fontaine ... Mathias Francois
A novel molecular strategy to block transcription factor activity using small molecule interference of multiple protein-protein interactions is reported.
Hala Harony-Nicolas, Maya Kay ... Joseph D Buxbaum
The production, validation and study of a novel rat model for Phelan McDermid Syndrome shows an ameliorative effect of oxytocin on both social and attentional deficits.
Janusz Franco-Barraza, Ralph Francescone ... Edna Cukierman
Stromal cell levels and localization of active α5β1-integrin are regulated by desmoplastic extracellular matrix control of αvβ5-integrin signaling, and predict clinical outcomes for pancreatic and renal cancer patients.
Ariana Strandburg-Peshkin, Damien R Farine ... Iain D Couzin
For baboons on the move, habitat features across multiple spatial scales combine with social interactions to impact the movements of individuals, ultimately shaping the structure of the whole group.
David H Burkhardt, Silvi Rouskin ... Carol A Gross
Operonic mRNAs in bacteria are comprised of ORF (open reading frame)-wide units of secondary structure, which are intrinsically distinct between adjacent ORFs and encode a rough blueprint for ORF-specific translation efficiency.
Elena W Adlaf, Ryan J Vaden ... Linda Overstreet-Wadiche
The formation of new neurons in the adult dentate gyrus causes a proportion of cortical neurons to transfer their existing connections to the newborn cells.
SNX6 regulates the distribution of a protein called Homer1b/c to distal dendrites, enabling the latter to stabilize the synapses and thereby support memory formation.
A genetically diverse panel of subject-specific induced pluripotent stem cells models the in vitro susceptibility of cardiac cells to develop a cardiotoxic drug response.
Single and double-knockout mouse models for proteins associated with nodes of Ranvier reveal that a paranodal, spectrin-based lateral diffusion barrier is sufficient to cluster Na+ channels at nodes of Ranvier.
M Rocio Servin-Vences, Mirko Moroni ... Kate Poole
The application of different types of mechanical stimuli to chondrocytes, either by stretching the membrane or deflecting cell-substrate contacts, reveals that there are distinct but overlapping mechanoelectrical transduction pathways in these cells.
The rapid killing of macrophages by Mycobacterium tuberculosis aggregates, and the subsequent proliferation of the bacteria inside the dead cell, leads to a cell death cascade and explains the coupling of necrosis and pathogen growth observed in active disease.
I Lorena Arancibia-Cárcamo, Marc C Ford ... David Attwell
Node of Ranvier length is similar at successive nodes along single myelinated CNS axons, but differs between axons, and could potentially be tuned to adjust the conduction velocity of each axon.
Andreas J Keller, Rachael Houlton ... Fritjof Helmchen
Cortex dynamically regulates the flow of sensory information by suppressing responses of non-relevant stimuli through mechanisms of adaptation, while boosting sensory responses that are behaviorally important.
The Time Point Selection (or TPS) method is a general protocol for determining sampling rates for high throughout time series biological studies, that is efficient, cheap, scalable and works well for several different types of molecular data.
Yap and Taz regulate proliferation and differentiation of Schwann cells, driving radial sorting, myelination and myelin maintenance of peripheral nerves.
Gabriel A Fitzgerald, Christopher Mulligan, Joseph A Mindell
A method for determining how many ions are required to drive transport in an electrogenic secondary active transporter will help understand the mechanisms of bacterial transporters whose structures have been solved.
A method for measuring p300 chromatin occupancy in specific lineages of mouse tissues was used to map endothelial enhancers and to identify previously unrecognized angiogenesis-related sequence motifs.
Two regions of the frontal lobe – the anterior cingulate cortex and, unexpectedly, the dorsolateral prefrontal cortex – show coordinated rhythmic activity during REM sleep.
Simon Erlendsson, Kamil Gotfryd ... Claus J Loland
Solid state NMR is unable to detect any association of substrate to the second binding site, S2, in the extracellular vestibule of the Neurotransmitter:Sodium Symporter LeuT.
A sexually dimorphic transcriptional switch in sensory neurons integrates information about microbial environment and nutritional state to regulate exploratory behavior in C. elegans..
Transport-based high-throughput identification of cargo proteins specific to all 12 human importin-β family nuclear import receptors revealed biological processes that the cargo cohorts of each receptor are involved in.
Masatoshi Nishikawa, Sundar Ram Naganathan ... Stephan W Grill
Combining quantitative biological experiment and physical description of actomyosin cortex reveals a contractile instability in the cortex of C. elegans embryo, and its biochemical control in order to robustly drive morphogenetic events.
A novel methodological framework for cross-frequency coupling and spike-field coherence in multichannel (LFP, EEG, MEG) electrophysiology data reveals new manifestations of coupling dynamics.
The human Origin Replication Complex is shaped as a shallow corkscrew in a classic AAA+ organization reminiscent of clamp loader complexes with highly controlled ATPase activity as exemplified by Meier-Gorlin syndrome mutations.
ATAC-seq, transcriptomics, and transcription factor motif searches collaborate to build a network that regulates gene expression in different cortical layers.
Johanna Ludwigsen, Sabrina Pfennig ... Felix Mueller-Planitz
The N-terminal domain of the chromatin remodeler ISWI contains previously uncharacterized conserved motifs that maintain structure, prevent ATP hydrolysis unless nucleosomes are bound, and confer H4-tail sensitivity without directly competing with the H4 tail.
Radostin Danev, Dimitry Tegunov, Wolfgang Baumeister
Building on previous work in cryo-electron microscopy (Entchev et al, 2015), it shown that a combination of the Volta phase plate and a small amount of defocus can simplify the experimental set-up, increase the data acquisition rate and improve resolution.
The feedback inhibition of T-type calcium channels by intracellular calcium provides new avenues to better decipher the roles of these low-voltage-activated channels in the fine control of calcium signaling events in physiology and pathophysiology.
For brain imaging to be useful despite its limitations in measuring neural activity, the neural code must be smooth both in a traditional sense and functionally.
Building on previous work (Reznik et al., 2016), independent measurements of mitochondrial genome copy number and expression indicate that several solid tumor types suppress respiratory metabolism compared to normal tissue.
The length-dependent growth rate of bacterial flagellar filament is determined by the flagellin loading speed, loading strength and its diffusion process.
Yen-Ping Hsueh, Matthew R Gronquist ... Paul W Sternberg
Genetic and behavior analyses show that Caenorhabditis nematodes are lured to the predator Arthrobotrys oligospora by olfactory mimicry of food and sex cues.
Studies in zebrafish and mouse implicate the PDGF signaling pathway in the communication between the endoderm and the myocardium that drives medial myocardial movement and thereby initiates cardiac morphogenesis.
Experiments in zebrafish reveal a new role for a critical hypothalamic transcription factor, orthopedia, in controlling developmental neuropeptide balance in a discrete oxytocin-producing neuronal circuit whose disrupted development affects social behavior.
Jean M Mulcahy Levy, Shadi Zahedi ... Andrew Thorburn
Pre-clinical and patient data show that inhibition of autophagy with an approved, inexpensive, well-tolerated drug can overcome resistance to BRAFV600E inhibition in multiple brain tumor subtypes with different resistance mechanisms.
The cessation of major anthropogenic disturbances since European colonization in the forests of central Africa leads to a canopy closing, and to the disappearance of certain light-demanding tree species.
Michael J Iannacone, Isabel Beets ... David M Raizen
During sickness, sleep is induced by neuropeptides, which contain an amidated arginine-phenylalanine motif, acting in a neuroendocrine fashion on a G-protein coupled receptor called DMSR-1.
Yayoi Teramoto, Daniel Y Takahashi ... Asif A Ghazanfar
An integrated landscape framework shows how the coordinated changes in vocal apparatus, muscles, nervous system, and social interaction together influence the trajectory of vocal development.
Phenotypic diversity and cell state transition (i.e., acquisition of a CD44+/CD24- cell state or exposure to TGF-beta) can spur intra-tumor genetic heterogeneity and contribute to acquired resistance.
Gregory M Martin, Craig Yoshioka ... Show-Ling Shyng
Single-particle cryo-electron microscopy reveals the first subnanometer structure of ATP-sensitive potassium (KATP) channels, which provides insight into the structural mechanisms of channel assembly and gating.
The structural and functional analysis of the ATP-dependent RNA helicase Prp43 provides insights into the mechanisms of RNA binding and translocation, which could serve as paradigm for all DEAH-box proteins.
Kenji Sugioka, Danielle R Hamill ... Bruce Bowerman
A genetic screen and live cell imaging show that a newly identified coiled-coil protein called SAS-7 is the earliest acting factor in centriole assembly yet identified in the roundworm Caenorhabditis elegans.
Building on previous work (Haldipur et al., 2014), we show that many key mechanisms controlling cerebellar development are likely conserved between mouse and human, and validate our mouse model of Dandy-Walker malformation.
Collin Yvès Ewald, John M Hourihan ... Nancy E Hynes
Genetic analysis reveals NADPH oxidase generated reactive oxygen species as signals to re-establish cellular homeostasis during aging via activating a transcriptional response.
A high-throughput functional validation system for large numbers of candidate disease genes enables in vivo functional testing of specific gene variants.
By modelling organisms that alternate between individual and colonial lifestyles, the well-known Parrondo's paradox can emerge in an ecological setting without the need for stochastic environmental variation.
Grid-cell maps can be aligned to both local and remote reference frames, suggesting that they provide a metric for space beyond the navigationally accessible boundaries of the local environment.
A two-part neural network models reward-based training and provides a unified framework in which to study diverse computations that can be compared to electrophysiological recordings from behaving animals.
Carey D Nadell, Deirdre Ricaurte ... Bonnie L Bassler
The feedback between hydrodynamic flow conditions and biofilm spatial architecture drives competition in P. aeruginosa biofilms, and can explain variation in biofilm production observed among bacteria in natural environments.
High-resolution, large-scale immunohistochemical mouse brain images showing global views of different brain regions, as well as cellular and subcellular details, identified distinct localization of PKA RIβ and RIIβ regulatory subunits that reveal functional differences.
CUT&RUN (Cleavage Under Targets & Release Using Nuclease) profiles antibody-targeted DNA-binding proteins in situ with high resolution and low background, providing a simple, robust and scalable alternative to chromatin immunoprecipitation.
Joshua B Benoit, Aurélien Vigneron ... Brian L Weiss
Insect symbiotic bacteria regulate expression of an odorant binding protein that mediates an evolutionarily conserved hematopoietic pathway crucial for host immune system development and function.
Inês M Tenente, Madeline N Hayes ... David M Langenau
MYF5 and MYOD regulate rhabdomyosaroma growth and tumor-propagating potential, acting more than as passive markers retained from the target cell-of-origin during transformation.
A novel statistical algorithm for mining high-dimensional spike train (count) data for significant spatio-temporal patterns reveals new insights into task and brain area dependent functional organization of neural activity.
The spatial and dynamic properties of self-motion signals are acquired at the first stage of otolith signal transformation, which is in the brainstem and cerebellum, and conserved across brainstem, cerebellar and cortical areas.
Erin L Davies, Kai Lei ... Alejandro Sánchez Alvarado
Anarchic, cycling piwi-1+ embryonic cells gives rise to neoblasts, pluripotent stemcells required for development of all organ systems during S. mediterranea embryogenesis, as well as the maintenance andregeneration of tissues during adulthood.
The spindle checkpoint kinase Mps1 sequentially phosphorylates multiple substrates to amplify checkpoint signals, making the checkpoint highly dependent on Mps1 function and directly responsive to kinetochore-microtubule attachment.
Alison M Devault, Tatum D Mortimer ... Caitlin S Pepperell
Mineralized placental tissue from Late Byzantine Troy enables the detailed reconstruction of genomes of mixed bacterial species responsible for maternal sepsis in the ancient world.
Genetic analyses reveal how CDX2 and BRAF defects seen in serrated colorectal cancer (CRCs), a poor prognosis CRC subset, cooperate in tumorigenesis in humans and in a mouse cancer model.
Zfp106 functions as an RNA binding protein, binds directly to GGGGCC RNA repeats, is required in motor neurons to prevent ALS-like neurodegeneration in mice, and can suppress neurotoxicity in an established fly model of ALS.
Elizabeth A Hubin, Allison Fay ... Elizabeth A Campbell
The essential mycobacterial transcription factor RbpA interacts with promoter DNA and cooperates with another essential transcription factor, CarD, to stimulate the formation of an intermediate leading to the open promoter complex.
Behavioral and synaptic investigations of long-term memory in Aplysia reveal differing roles for DNA methylation, protein synthesis during training and protein synthesis shortly after training with respect to memory consolidation and maintenance.
Geraldine M Clarke, Kirk Rockett ... MalariaGEN Consortium
Increasing levels of glucose-6-phosphate dehydrogenase deficiency are associated with decreasing risk of cerebral malaria, but with increased risk of severe malarial anaemia.
Caleb N Fischer, Eric P Trautman ... Nichole A Broderick
Interactions between fungal and bacterial microbiome members alter Drosophila melanogaster's chemical environment, affecting host behavior and survival.
As the function of membrane proteins is often influenced by its membrane environment the presented combinatorial approach is of great value for the investigation of membrane protein complexes in natural or even manipulated lipid bilayers.
Liku B Tezera, Magdalena K Bielecka ... Paul T Elkington
The bridging of bioengineering and cell culture techniques provides a transformative platform to investigate human biology within a 3-dimensional extracellular matrix over prolonged periods with multiplex readouts.
Analyses of a developmentally regulated Drosophila myofiber remodeling program provide insight into induced autophagy required for T-tubule membrane reorganization, and uncover a conserved Rab2 role in autophagosome-lysosome fusion.
The stoichiometry and mechanism of interactions of the Mis18 complex with M18BP1 was analysed to unveil the molecular basis of new CENP-A deposition during the G1 phase of the cell cycle.
Basket cells expressing parvalbumin or cholecystokinin provide equally effective control of principal neuron activity via their perisomatic synapses in the basal amygdala.
C-terminus mediated inhibition is one emerging modality of intervention for L-type Ca2+ channels, which coordinate multiple motifs to acutely tune Ca2+ current and Ca2+ influx down to the lower limits preset by end-stage Ca2+-dependent inactivation.
Lindsey Araujo, Phillip Khim ... Michael Demetriou
Metabolic switches between oxidative phosphorylation and aerobic glycolysis plus glutaminolysis direct T cell function by altering the flux of glucose and glutamine to N-glycosylation.
APP interacts with KCC2 to limit the latter from tyrosine-phosphorylation and ubiquitination and thus subsequent degradation, revealing a novel molecular pathway in which APP regulates GABAergic signaling and thus inhibition in the hippocampus.
William Menegas, Benedicte M Babayan ... Mitsuko Watabe-Uchida
Dopamine novelty signals are localized in the posterior tail of the striatum along with general salience signals, while dopamine in the ventral striatum reliably encodes reward prediction error.
M Hadi Timachi, Cedric AJ Hutter ... Enrica Bordignon
A heterodimeric exporter exhibits conformational equilibria in the presence of nucleotides, suggesting a unified mechanistic model for the conformational cycle of ABC exporters.
Exploratory growth is a newly discovered mode of Streptomyces growth that it is stimulated by fungi, is pH responsive, and can be communicated to other – physically separated – streptomycetes through airborne compounds.
Pascal Krotee, Jose A Rodriguez ... David S Eisenberg
Atomic structures of hIAPP fibrillar segments, determined using the cryo electron microscopy method MicroED, reveal that strong, stable intermolecular interactions are important features of cytotoxic amyloid proteins.
Formation of a phase-separated interface between homologous chromosomes during meiosis enables regulatory signals to spread in cis over long distances, illuminating the longstanding mystery of crossover interference.
Joshua M Galanter, Christopher R Gignoux ... Noah Zaitlen
An epigenome-wide study shows that ethnic self-identification and genetically determined ancestry both make important independent contributions to DNA methylation levels.
