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https://www.readbyqxmd.com/read/28098558/platelet-derived-growth-factor-pdgf-signaling-directs-cardiomyocyte-movement-toward-the-midline-during-heart-tube-assembly
#1
Joshua Bloomekatz, Reena Singh, Owen Wj Prall, Ariel C Dunn, Megan Vaughan, Chin-San Loo, Richard P Harvey, Deborah Yelon
Communication between neighboring tissues plays a central role in guiding organ morphogenesis. During heart tube assembly, interactions with the adjacent endoderm control the medial movement of cardiomyocytes, a process referred to as cardiac fusion. However, the molecular underpinnings of this endodermal-myocardial relationship remain unclear. Here, we show an essential role for platelet-derived growth factor receptor alpha (Pdgfra) in directing cardiac fusion. Mutation of pdgfra disrupts heart tube assembly in both zebrafish and mouse...
January 18, 2017: ELife
https://www.readbyqxmd.com/read/28098557/length-dependent-flagellar-growth-of-vibrio-alginolyticus-revealed-by-real-time-fluorescent-imaging
#2
Meiting Chen, Ziyi Zhao, Jin Yang, Kai Peng, Matthew A B Baker, Fan Bai, Chien-Jung Lo
Bacterial flagella are extracellular filaments that drive swimming in bacteria. During its assembly, flagellins are transported unfolded through the central channel in the flagellum to the growing tip. Here we applied in vivo fluorescent imaging to monitor in real time the Vibrio alginolyticus polar flagella growth. The flagellar growth rate is found to be highly length-dependent. Initially, the flagellum grows at a constant rate (50nm/min) when shorter than 1500nm. The growth rate decays sharply when the flagellum grows longer...
January 18, 2017: ELife
https://www.readbyqxmd.com/read/28098556/genetic-defects-in-%C3%AE-spectrin-and-tau-sensitize-c-elegans-axons-to-movement-induced-damage-via-torque-tension-coupling
#3
Michael Krieg, Jan Stühmer, Juan G Cueva, Richard Fetter, Kerri A Spliker, Daniel Cremers, Kang Shen, Alexander R Dunn, Miriam B Goodman
Our bodies are in constant motion and so are the neurons that invade each tissue. Motion-induced neuron deformation and damage are associated with several neurodegenerative conditions. Here, we investigated the question of how the neuronal cytoskeleton protects axons and dendrites from mechanical stress, exploiting mutations in UNC-70 β-spectrin, PTL-1 tau/MAP2-like and MEC-7 β-tubulin proteins in Caenorhabditis elegans. We found that mechanical stress induces supercoils and plectonemes in the sensory axons of spectrin and tau double mutants...
January 18, 2017: ELife
https://www.readbyqxmd.com/read/28094761/homeodomain-protein-otp-affects-developmental-neuropeptide-switching-in-oxytocin-neurons-associated-with-a-long-term-effect-on-social-behavior
#4
Einav Wircer, Janna Blechman, Nataliya Borodovsky, Michael Tsoory, Ana Rita Nunes, Rui F Oliveira, Gil Levkowitz
Proper response to stress and social stimuli depends on orchestrated development of hypothalamic neuronal circuits. Here we address the effects of the developmental transcription factor orthopedia (Otp) on hypothalamic development and function. We show that developmental mutations in the zebrafish paralogous gene otpa but not otpb affect both stress response and social preference. These behavioral phenotypes were associated with developmental alterations in oxytocinergic (OXT) neurons. Thus, otpa and otpb differentially regulate neuropeptide switching in a newly identified subset of OXT neurons that co-express the corticotropin-releasing hormone (CRH)...
January 17, 2017: ELife
https://www.readbyqxmd.com/read/28092268/phenotypic-outcomes-in-mouse-and-human-foxc1-dependent-dandy-walker-cerebellar-malformation-suggest-shared-mechanisms
#5
Parthiv Haldipur, Derek Dang, Kimberly A Aldinger, Olivia K Janson, Fabien Guimiot, Homa Adle-Biasette, William B Dobyns, Joseph R Siebert, Rosa Russo, Kathleen J Millen
FOXC1 loss contributes to Dandy-Walker malformation (DWM), a common human cerebellar malformation.  Previously we found that complete Foxc1 loss leads to aberrations in proliferation, neuronal differentiation and migration in the embryonic mouse cerebellum (Haldipur et al., 2014). We now demonstrate that hypomorphic Foxc1 mutant mice have granule and Purkinje cell abnormalities causing subsequent disruptions in postnatal cerebellar foliation and lamination. Particularly striking is the presence of a partially formed posterior lobule echoing the posterior vermis DW "tail sign" observed in human imaging studies...
January 16, 2017: ELife
https://www.readbyqxmd.com/read/28092267/cryo-em-structure-of-the-atp-sensitive-potassium-channel-illuminates-mechanisms-of-assembly-and-gating
#6
Gregory M Martin, Craig Yoshioka, Emily A Rex, Jonathan F Fay, Qing Xie, Matthew R Whorton, James Z Chen, Show-Ling Shyng
KATP channels are metabolic sensors that couple cell energetics to membrane excitability. In pancreatic β-cells, channels formed by SUR1 and Kir6.2 regulate insulin secretion and are the targets of antidiabetic sulfonylureas. Here, we used cryo-EM to elucidate structural basis of channel assembly and gating. The structure, determined in the presence of ATP and the sulfonylurea glibenclamide, at ~6Å resolution reveals a closed Kir6.2 tetrameric core with four peripheral SUR1s each anchored to a Kir6.2 by its N-terminal transmembrane domain (TMD0)...
January 16, 2017: ELife
https://www.readbyqxmd.com/read/28092266/tgf-%C3%AE-reduces-dna-ds-break-repair-mechanisms-to-heighten-genetic-diversity-and-adaptability-of-cd44-cd24-cancer-cells
#7
Debjani Pal, Anja Pertot, Nitin H Shirole, Zhan Yao, Naishitha Anaparthy, Tyler Garvin, Hilary Cox, Kenneth Chang, Fred Rollins, Jude Kendall, Leyla Edwards, Vijay A Singh, Gary C Stone, Michael C Schatz, James Hicks, Gregory Hannon, Raffaella Sordella
Many lines of evidence have indicated that both genetic and non-genetic determinants can contribute to intra-tumor heterogeneity and influence cancer outcomes. Among the best described sub-population of cancer cells generated by non-genetic mechanisms are cells characterized by a CD44+/CD24- cell surface marker profile. Here, we report that human CD44+/CD24- cancer cells are genetically highly unstable due to intrinsic defects in their DNA repair capabilities. In fact, in CD44+/CD24- cells constitutive activation of the TGF-beta axis was both necessary and sufficient to reduce the expression of genes that are critical in coordinating DNA damage repair mechanisms...
January 16, 2017: ELife
https://www.readbyqxmd.com/read/28092265/the-fibronectin-synergy-site-re-enforces-cell-adhesion-and-mediates-a-crosstalk-between-integrin-classes
#8
Maria Benito-Jardón, Sarah Klapproth, Irene Gimeno-LLuch, Tobias Petzold, Mitasha Bharadwaj, Daniel J Müller, Gabriele Zuchtriegel, Christoph A Reichel, Mercedes Costell
Fibronectin (FN), a major extracellular matrix component, enables integrin-mediated cell adhesion via binding of α5β1, αIIbβ3 and αv-class integrins to an RGD-motif. An additional linkage for α5 and αIIb is the synergy site located in close proximity to the RGD motif. We report that mice with a dysfunctional FN-synergy motif (FNsyn/syn) suffer from surprisingly mild platelet adhesion and bleeding defects due to delayed thrombus formation after vessel injury. Additional loss of β3 integrins dramatically aggravates the bleedings and severely compromises smooth muscle cell coverage of the vasculature leading to embryonic lethality...
January 16, 2017: ELife
https://www.readbyqxmd.com/read/28092264/centriolar-sas-7-acts-upstream-of-spd-2-to-regulate-centriole-assembly-and-pericentriolar-material-formation
#9
Kenji Sugioka, Danielle R Hamill, Joshua B Lowry, Marie E McNeely, Molly Enrick, Alyssa C Richter, Lauren E Kiebler, James R Priess, Bruce Bowerman
The centriole/basal body is a eukaryotic organelle that plays essential roles in cell division and signaling. Among five known core centriole proteins, SPD-2/Cep192 is the first recruited to the site of daughter centriole formation and regulates the centriolar localization of the other components in C. elegans and in humans. However, the molecular basis for SPD-2 centriolar localization remains unknown. Here we describe a new centriole component, the coiled-coil protein SAS-7, as a regulator of centriole duplication, assembly and elongation...
January 16, 2017: ELife
https://www.readbyqxmd.com/read/28092263/transcription-leads-to-pervasive-replisome-instability-in-bacteria
#10
Sarah Mangiameli, Christopher N Merrikh, Paul A Wiggins, Houra Merrikh
The canonical model of DNA replication describes a highly-processive and largely continuous process by which the genome is duplicated. This continuous model is based upon in vitro reconstitution and in vivo ensemble experiments. Here, we characterize the replisome-complex stoichiometry and dynamics with single-molecule resolution in bacterial cells. Strikingly, the stoichiometries of the replicative helicase, DNA polymerase, and clamp loader complexes are consistent with the presence of only one active replisome in a significant fraction of cells (>40%)...
January 16, 2017: ELife
https://www.readbyqxmd.com/read/28092262/vocal-development-in-a-waddington-landscape
#11
Yayoi Teramoto, Daniel Takahashi, Philip Holmes, Asif A Ghazanfar
Vocal development is the adaptive coordination of the vocal apparatus, muscles, the nervous system, and social interaction. Here, we use a quantitative framework based on optimal control theory and Waddington's landscape metaphor to provide an integrated view of this process. With a biomechanical model of the marmoset monkey vocal apparatus and behavioral developmental data, we show that only the combination of the developing vocal tract, vocal apparatus muscles and nervous system can fully account for the patterns of vocal development...
January 16, 2017: ELife
https://www.readbyqxmd.com/read/28092261/structural-insights-into-the-mechanism-of-the-deah-box-rna-helicase-prp43
#12
Marcel J Tauchert, Jean-Baptiste Fourmann, Reinhard Lührmann, Ralf Ficner
The DEAH-box helicase Prp43 is a key player in pre-mRNA splicing as well as the maturation of rRNAs. The exact modus operandi of Prp43 and of all other spliceosomal DEAH-box RNA helicases is still elusive. Here, we report crystal structures of Prp43 complexes in different functional states and the analysis of structure-based mutants providing insights into the unwinding and loading mechanism of RNAs. The Prp43•ATP-analog•RNA complex shows the localization of the RNA inside a tunnel formed by the two RecA-like and C-terminal domains...
January 16, 2017: ELife
https://www.readbyqxmd.com/read/28084994/flow-environment-and-matrix-structure-interact-to-determine-spatial-competition-in-pseudomonas-aeruginosa-biofilms
#13
Carey D Nadell, Deirdre Ricaurte, Jing Yan, Knut Drescher, Bonnie Bassler
Bacteria often live in biofilms, which are microbial communities surrounded by a secreted extracellular matrix. Here, we demonstrate that hydrodynamic flow and matrix organization interact to shape competitive dynamics in Pseudomonas aeruginosa biofilms. Irrespective of initial frequency, in competition with matrix mutants, wild type cells always increase in relative abundance in planar microfluidic devices under simple flow regimes. By contrast, in microenvironments with complex, irregular flow profiles - which are common in natural environments - wild type matrix-producing and isogenic non-producing strains can coexist...
January 13, 2017: ELife
https://www.readbyqxmd.com/read/28084993/nomadic-colonial-life-strategies-enable-paradoxical-survival-and-growth-despite-habitat-destruction
#14
Zong Xuan Tan, Kang Hao Cheong
Organisms often exhibit behavioral or phenotypic diversity to improve population fitness in the face of environmental variability. When each behavior or phenotype is individually maladaptive, alternating between these losing strategies can counter-intuitively result in population persistence--an outcome similar to Parrondo's paradox. Instead of the capital or history dependence that characterize traditional Parrondo games, most ecological models which exhibit such paradoxical behavior depend on the presence of exogenous environmental variation...
January 13, 2017: ELife
https://www.readbyqxmd.com/read/28084992/framing-of-grid-cells-within-and-beyond-navigation-boundaries
#15
Francesco Savelli, J D Luck, James J Knierim
Grid cells represent an ideal candidate to investigate the allocentric determinants of the brain's cognitive map. Most studies of grid cells emphasized the roles of geometric boundaries within the navigational range of the animal. Behaviors such as novel route-taking between local environments indicate the presence of additional inputs from remote cues beyond the navigational borders. To investigate these influences, we recorded grid cells as rats explored an open-field platform in a room with salient, remote cues...
January 13, 2017: ELife
https://www.readbyqxmd.com/read/28084991/reward-based-training-of-recurrent-neural-networks-for-cognitive-and-value-based-tasks
#16
H Francis Song, Guangyu R Yang, Xiao-Jing Wang
Trained neural network models, which exhibit features of neural activity recorded from behaving animals, may provide insights into the circuit mechanisms of cognitive functions through systematic analysis of network activity and connectivity. However, in contrast to the graded error signals commonly used to train networks through supervised learning, animals learn from reward feedback on definite actions through reinforcement learning. Reward maximization is particularly relevant when optimal behavior depends on an animal's internal judgment of confidence or subjective preferences...
January 13, 2017: ELife
https://www.readbyqxmd.com/read/28084990/high-throughput-in-vivo-functional-validation-of-candidate-congenital-heart-disease-genes-in-drosophila
#17
Jun-Yi Zhu, Yulong Fu, Margaret Nettleton, Adam Richman, Zhe Han
Genomic sequencing has implicated large numbers of genes and de novo mutations as potential disease risk factors. A high throughput in vivo model system is needed to validate gene associations with pathology. We developed a Drosophila-based functional system to screen candidate disease genes identified from Congenital Heart Disease (CHD) patients. 134 genes were tested in the Drosophila heart using RNAi-based gene silencing. Quantitative analyses of multiple cardiac phenotypes demonstrated essential structural, functional, and developmental roles for more than 70 genes, including a subgroup encoding histone H3K4 modifying proteins...
January 13, 2017: ELife
https://www.readbyqxmd.com/read/28079521/isoform-specific-subcellular-localization-and-function-of-protein-kinase-a-identified-by-mosaic-imaging-of-mouse-brain
#18
Ronit Ilouz, Varda Lev-Ram, Eric A Bushong, Travis L Stiles, Dinorah Friedmann-Morvinski, Christopher Douglas, Geoffrey Goldberg, Mark H Ellisman, Susan S Taylor
Protein kinase A (PKA) plays critical roles in neuronal function that are mediated by different regulatory (R) subunits. Deficiency in either RIβ or RIIβ subunits results in distinct neuronal phenotypes. Although RIβ contributes to synaptic plasticity, it is the least studied isoform. Using isoform-specific antibodies we generated high-resolution large-scale immunohistochemical mosaic images of mouse brain that provide global views of several brain regions, including the hippocampus and cerebellum. The isoforms concentrate in discrete brain regions and we then zoom-in to show distinct patterns of subcellular localization...
January 12, 2017: ELife
https://www.readbyqxmd.com/read/28079019/an-efficient-targeted-nuclease-strategy-for-high-resolution-mapping-of-dna-binding-sites
#19
Peter J Skene, Steven Henikoff
We describe Cleavage Under Targets and Release Using Nuclease (CUT&RUN), a chromatin profiling strategy in which antibody-targeted controlled cleavage by micrococcal nuclease releases specific protein-DNA complexes into the supernatant for paired-end DNA sequencing. Unlike Chromatin Immunoprecipitation (ChIP), which fragments and solubilizes total chromatin, CUT&RUN is performed in situ, allowing for both quantitative high-resolution chromatin mapping and probing of the local chromatin environment. When applied to yeast and human nuclei, CUT&RUN yielded precise transcription factor profiles while avoiding cross-linking and solubilization issues...
January 12, 2017: ELife
https://www.readbyqxmd.com/read/28072391/braf-v600e-cooperates-with-cdx2-inactivation-to-promote-serrated-colorectal-tumorigenesis
#20
Naoya Sakamoto, Ying Feng, Carmine Stolfi, Yuki Kurosu, Maranne Green, Jeffry Lin, Megan Green, Kazuhiro Sentani, Wataru Yasui, Martin McMahon, Karin M Hardiman, Jason R Spence, Nobukatsu Horita, Joel K Greenson, Rork Kuick, Kathy R Cho, Eric R Fearon
While 20-30% of colorectal cancers (CRCs) may arise from precursors with serrated glands, only 8-10% of CRCs manifest serrated morphology at diagnosis. Markers for distinguishing CRCs arising from 'serrated' versus 'conventional adenoma' precursors are lacking. We studied 36 human serrated CRCs and found CDX2 loss or BRAF mutations in ~60% of cases and often together (p= .04). CDX2(Null)/BRAF(V600E) expression in adult mouse intestinal epithelium led to serrated morphology tumors (including carcinomas) and BRAF(V600E) potently interacted with CDX2 silencing to alter gene expression...
January 10, 2017: ELife
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