journal
MENU ▼
Read by QxMD icon Read
search

ELife

journal
https://www.readbyqxmd.com/read/28447937/il17-factors-are-early-regulators-in-the-gut-epithelium-during-inflammatory-response-to-vibrio-in-the-sea-urchin-larva
#1
Katherine M Buckley, Eric Chun Hei Ho, Taku Hibino, Catherine S Schrankel, Nicholas W Schuh, Guizhi Wang, Jonathan Patrick Rast
IL17 cytokines are central mediators of mammalian immunity. In vertebrates, these factors derive from diverse cellular sources. Sea urchins share a molecular heritage with chordates that includes the IL17 system. Here, we characterize the role of epithelial expression of IL17 in the larval gut-associated immune response. The purple sea urchin genome encodes ten IL17 subfamilies (35 genes) and two IL17 receptors. Most of these subfamilies are conserved throughout echinoderms. Two IL17 subfamilies are sequentially strongly upregulated and attenuated in the gut epithelium in response to bacterial disturbance...
April 27, 2017: ELife
https://www.readbyqxmd.com/read/28447936/ppp1r15a-mediated-dephosphorylation-of-eif2%C3%AE-is-unaffected-by-sephin1-or-guanabenz
#2
Ana Crespillo-Casado, Joseph E Chambers, Peter M Fischer, Stefan J Marciniak, David Ron
Dephosphorylation of translation initiation factor 2 (eIF2α) terminates signalling in the mammalian integrated stress response (ISR) and has emerged as a promising target for modifying the course of protein misfolding diseases. The [(o-chlorobenzylidene)amino]guanidines (Guanabenz and Sephin1) have been proposed to exert protective effects against misfolding by interfering with eIF2α-P dephosphorylation through selective disruption of a PP1-PPP1R15A holophosphatase complex. Surprisingly, they proved inert in vitro affecting neither stability of the PP1-PPP1R15A complex nor substrate-specific dephosphorylation...
April 27, 2017: ELife
https://www.readbyqxmd.com/read/28447935/host-selected-mutations-converging-on-a-global-regulator-drive-an-adaptive-leap-by-bacteria-to-symbiosis
#3
Molly Sabrina Pankey, Randi L Foxall, Ian M Ster, Lauren A Perry, Brian M Schuster, Rachel A Donner, Matthew Coyle, Vaughn S Cooper, Cheryl A Whistler
Host immune and physical barriers protect against pathogens but also impede the establishment of essential symbiotic partnerships. To reveal mechanisms by which beneficial organisms adapt to circumvent host defenses, we experimentally evolved ecologically distinct bioluminescent Vibrio fischeri through Euprymna scolopes squid light organs. Serial squid passaging of bacteria produced eight distinct mutations in the binK sensor kinase gene that conferred an exceptional selective advantage demonstrated through both empirical and theoretical analysis...
April 27, 2017: ELife
https://www.readbyqxmd.com/read/28443815/molecular-mechanism-of-voltage-dependent-potentiation-of-kcnh-potassium-channels
#4
William N Zagotta, Gucan Dai
EAG-like (ELK) voltage-gated potassium channels are abundantly expressed in the brain. These channels exhibit a behavior called voltage-dependent potentiation (VDP), which appears to be a specialization to dampen the hyperexitability of neurons. VDP manifests as a potentiation of current amplitude, hyperpolarizing shift in voltage sensitivity, and slowing of deactivation in response to a depolarizing prepulse. Here we show that VDP of D. rerio ELK channels involves the structural interaction between the intracellular N-terminal eag domain and C-terminal CNBHD...
April 26, 2017: ELife
https://www.readbyqxmd.com/read/28440746/dual-interaction-of-scaffold-protein-tim44-of-mitochondrial-import-motor-with-channel-forming-translocase-subunit-tim23
#5
See-Yeun Ting, Nicholas L Yan, Brenda A Schilke, Elizabeth A Craig
Proteins destined for the mitochondrial matrix are targeted to the inner membrane Tim17/23 translocon by their presequences. Inward movement is driven by the matrix-localized, Hsp70-based motor. The scaffold Tim44, interacting with the matrix face of the translocon, recruits other motor subunits and binds incoming presequence. The basis of these interactions and their functional relationships remains unclear. Using site-specific in vivo crosslinking and genetic approaches in Saccharomyces cerevisiae, we found that both domains of Tim44 interact with the major matrix-exposed loop of Tim23, with the C-terminal domain (CTD) binding Tim17 as well...
April 25, 2017: ELife
https://www.readbyqxmd.com/read/28440220/rapid-evolution-of-the-human-mutation-spectrum
#6
Kelley Harris, Jonathan K Pritchard
DNA is a remarkably precise medium for copying and storing biological information. This high fidelity results from the action of hundreds of genes involved in replication, proofreading, and damage repair. Evolutionary theory suggests that in such a system, selection has limited ability to remove genetic variants that change mutation rates by small amounts or in specific sequence contexts. Consistent with this, using SNV variation as a proxy for mutational input, we report here that mutational spectra differ substantially among species, human continental groups and even some closely-related populations...
April 25, 2017: ELife
https://www.readbyqxmd.com/read/28436820/srna-mediated-activation-of-gene-expression-by-inhibition-of-5-3-exonucleolytic-mrna-degradation
#7
Sylvain Durand, Frédérique Braun, Anne-Catherine Helfer, Pascale Romby, Ciarán Condon
Post-transcriptional control by small regulatory RNA (sRNA) is critical for rapid adaptive processes. sRNAs can directly modulate mRNA degradation in Proteobacteria without interfering with translation. However, Firmicutes have a fundamentally different set of ribonucleases for mRNA degradation and whether sRNAs can regulate the activity of these enzymes is an open question. We show that Bacillus subtilis RoxS, a major trans-acting sRNA shared with Staphylococus aureus, prevents degradation of the yflS mRNA, encoding a malate transporter...
April 24, 2017: ELife
https://www.readbyqxmd.com/read/28436819/insight-into-the-evolution-of-microbial-metabolism-from-the-deep-branching-bacterium-thermovibrio-ammonificans
#8
Donato Giovannelli, Stefan M Sievert, Michael Hügler, Stephanie Markert, Dörte Becher, Thomas Schweder, Costantino Vetriani
Anaerobic thermophiles inhabit relic environments that resemble the early Earth. However, the lineage of these modern organisms co-evolved with our planet. Hence, these organisms carry both ancestral and acquired genes and serve as models to reconstruct early metabolism. Based on comparative genomic and proteomic analyses, we identified two distinct groups of genes in Thermovibrio ammonificans: the first codes for enzymes that do not require oxygen and use substrates of geothermal origin; the second appears to be a more recent acquisition, and may reflect adaptations to cope with the rise of oxygen on Earth...
April 24, 2017: ELife
https://www.readbyqxmd.com/read/28432790/single-molecule-visualization-of-fast-polymerase-turnover-in-the-bacterial-replisome
#9
Jacob S Lewis, Lisanne M Spenkelink, Slobodan Jergic, Elizabeth A Wood, Enrico Monachino, Nicholas P Horan, Karl E Duderstadt, Michael M Cox, Andrew Robinson, Nicholas E Dixon, Antoine M van Oijen
The Escherichia coli DNA replication machinery has been used as a road map to uncover design rules that enable DNA duplication with high efficiency and fidelity. Although the enzymatic activities of the replicative DNA Pol III are well understood, its dynamics within the replisome are not. Here we test the accepted view that the Pol III holoenzyme remains stably associated within the replisome. We use in vitro single-molecule assays with fluorescently labeled polymerases to demonstrate that the Pol III* complex (holoenzyme lacking the β2 sliding clamp), is rapidly exchanged during processive DNA replication...
April 22, 2017: ELife
https://www.readbyqxmd.com/read/28432789/probing-protein-flexibility-reveals-a-mechanism-for-selective-promiscuity
#10
Nicolas A Pabon, Carlos J Camacho
Many eukaryotic regulatory proteins adopt distinct bound and unbound conformations, and use this structural flexibility to bind specifically to multiple partners. However, we lack an understanding of how an interface can select some ligands, but not others. Here, we present a molecular dynamics approach to identify and quantitatively evaluate the interactions responsible for this selective promiscuity. We apply this approach to the anti-cancer target PD-1 and its ligands PD-L1 and PD-L2. We discover that while unbound PD-1 exhibits a hard-to-drug hydrophilic interface, conserved specific triggers encoded in the cognate ligands activate a promiscuous binding pathway that reveals a flexible hydrophobic binding cavity...
April 22, 2017: ELife
https://www.readbyqxmd.com/read/28432788/structure-of-fam20a-reveals-a-pseudokinase-featuring-unique-disulfide-pattern-and-inverted-atp-binding
#11
Jixin Cui, Qinyu Zhu, Hui Zhang, Michael A Cianfrocco, Andres E Leschziner, Jack E Dixon, Junyu Xiao
Mutations in FAM20A cause tooth enamel defects known as Amelogenesis Imperfecta (AI) and renal calcification. We previously showed that Fam20A is a secretory pathway pseudokinase and allosterically activates the physiological casein kinase Fam20C to phosphorylate secreted proteins important for biomineralization (Cui et al., 2015). Here we report the nucleotide-free and ATP-bound structures of Fam20A. Fam20A exhibits a distinct disulfide bond pattern mediated by a unique insertion region. Loss of this insertion due to abnormal mRNA splicing interferes with the structure and function of Fam20A, resulting in AI...
April 22, 2017: ELife
https://www.readbyqxmd.com/read/28432787/presynaptic-morphology-and-vesicular-composition-determine-vesicle-dynamics-in-mouse-central-synapses
#12
Laurent Guillaud, Dimitar Dimitrov, Tomoyuki Takahashi
Transport of synaptic vesicles (SVs) in nerve terminals is thought to play essential roles in maintenance of neurotransmission. To identify factors modulating SV movements, we performed real-time imaging analysis of fluorescently labeled SVs in giant calyceal and conventional hippocampal terminals. Compared with small hippocampal terminals, SV movements in giant calyceal terminals were faster, longer and kinetically more heterogeneous. Morphological maturation of giant calyceal terminals was associated with an overall reduction in SV mobility and displacement heterogeneity...
April 22, 2017: ELife
https://www.readbyqxmd.com/read/28432786/the-comprehensive-connectome-of-a-neural-substrate-for-on-motion-detection-in-drosophila
#13
Shin-Ya Takemura, Aljoscha Nern, Dmitri B Chklovskii, Louis K Scheffer, Gerald M Rubin, Ian A Meinertzhagen
Analysing computations in neural circuits often uses simplified models because the actual neuronal implementation is not known. For example, a problem in vision, how the eye detects image motion, has long been analysed using Hassenstein-Reichardt (HR) detector or Barlow-Levick (BL) models. These both simulate motion detection well, but the exact neuronal circuits undertaking these tasks remain elusive. We reconstructed a comprehensive connectome of the circuits of Drosophila's motion-sensing T4 cells using a novel EM technique...
April 22, 2017: ELife
https://www.readbyqxmd.com/read/28432785/phosphorylation-of-irhom2-at-the-plasma-membrane-controls-mammalian-tace-dependent-inflammatory-and-growth-factor-signalling
#14
Adam Graham Grieve, Hongmei Xu, Ulrike Künzel, Paul Bambrough, Boris Sieber, Matthew Freeman
Proteolytic cleavage and release from the cell surface of membrane-tethered ligands is an important mechanism of regulating intercellular signalling. TACE is a major shedding protease, responsible for the liberation of the inflammatory cytokine TNFα and ligands of the epidermal growth factor receptor. iRhoms, catalytically inactive members of the rhomboid-like superfamily, have been shown to control the ER-to-Golgi transport and maturation of TACE. Here, we reveal that iRhom2 remains associated with TACE throughout the secretory pathway, and is stabilised at the cell surface by this interaction...
April 22, 2017: ELife
https://www.readbyqxmd.com/read/28425917/tapbpr-bridges-udp-glucose-glycoprotein-glucosyltransferase-1-onto-mhc-class-i-to-provide-quality-control-in-the-antigen-presentation-pathway
#15
Andreas Neerincx, Clemens Hermann, Robin Antrobus, Andy van Hateren, Huan Cao, Nico Trautwein, Stefan Stevanović, Tim Elliott, Janet E Deane, Louise H Boyle
Recently we revealed that TAPBPR is a peptide exchange catalyst important for optimal peptide selection by MHC class I molecules. Here we asked if any other co-factors associate with TAPBPR which would explain its effect on peptide selection. We identify an interaction between TAPBPR and UDP-glucose:glycoprotein glucosyltransferase 1 (UGT1), a folding sensor in the calnexin/calreticulin quality control cycle known to regenerate the Glc1Man9GlcNAc2 moiety on glycoproteins. Our results suggest the formation of a multimeric complex, dependent on a conserved cysteine at position 94 in TAPBPR, in which TAPBPR promotes the association of UGT1 with peptide-receptive class I molecules...
April 20, 2017: ELife
https://www.readbyqxmd.com/read/28425916/combined-alk-and-mdm2-inhibition-increases-antitumor-activity-and-overcomes-resistance-in-human-alk-mutant-neuroblastoma-cell-lines-and-xenograft-models
#16
Hui Qin Wang, Ensar Halilovic, Xiaoyan Li, Jinsheng Liang, Yichen Cao, Daniel P Rakiec, David A Ruddy, Sebastien Jeay, Jens U Wuerthner, Noelito Timple, Shailaja Kasibhatla, Nanxin Li, Juliet A Williams, William R Sellers, Alan Huang, Fang Li
The efficacy of ALK inhibitors in patients with ALK-mutant neuroblastoma is limited, highlighting the need to improve their effectiveness in these patients. To this end we sought to develop a combination strategy to enhance the antitumor activity of ALK inhibitor monotherapy in human neuroblastoma cell lines and xenograft models expressing activated ALK. Herein, we report that combined inhibition of ALK and MDM2 induced a complementary set of anti-proliferative and pro-apoptotic proteins. Consequently, this combination treatment synergistically inhibited proliferation of TP53 wild-type neuroblastoma cells harboring ALK amplification or mutations in vitro, and resulted in complete and durable responses in neuroblastoma xenografts derived from these cells...
April 20, 2017: ELife
https://www.readbyqxmd.com/read/28425915/competition-between-histone-and-transcription-factor-binding-regulates-the-onset-of-transcription-in-zebrafish-embryos
#17
Shai R Joseph, Máté Pálfy, Lennart Hilbert, Mukesh Kumar, Jens Karschau, Vasily Zaburdaev, Andrej Shevchenko, Nadine L Vastenhouw
Upon fertilization, the genome of animal embryos remains transcriptionally inactive until the maternal-to-zygotic transition. At this time, the embryo takes control of its development and transcription begins. How the onset of zygotic transcription is regulated remains unclear. Here, we show that a dynamic competition for DNA binding between nucleosome-forming histones and transcription factors regulates zebrafish genome activation. Taking a quantitative approach, we found that the concentration of non-DNA bound core histones sets the time for the onset of transcription...
April 20, 2017: ELife
https://www.readbyqxmd.com/read/28425914/epstein-barr-virus-ensures-b-cell-survival-by-uniquely-modulating-apoptosis-at-early-and-late-times-after-infection
#18
Alexander M Price, Joanne Dai, Quentin Bazot, Luv Patel, Pavel A Nikitin, Reza Djavadian, Peter S Winter, Cristina A Salinas, Ashley Perkins Barry, Kris C Wood, Eric C Johannsen, Anthony Letai, Martin J Allday, Micah A Luftig
Latent Epstein-Barr virus (EBV) infection is causally linked to several human cancers. EBV expresses viral oncogenes that promote cell growth and inhibit the apoptotic response to uncontrolled proliferation. The EBV oncoprotein LMP1 constitutively activates NFB and is critical for survival of EBV-immortalized B cells. However, during early infection EBV induces rapid B cell proliferation with low levels of LMP1 and little apoptosis. Therefore, we sought to define the mechanism of survival in the absence of LMP1/NFB early after infection...
April 20, 2017: ELife
https://www.readbyqxmd.com/read/28425913/loss-of-dnmt3a-and-dnmt3b-does-not-affect-epidermal-homeostasis-but-promotes-squamous-transformation-through-ppar-%C3%AE
#19
Lorenzo Rinaldi, Alexandra Avgustinova, Mercé Martin, Debayan Datta, Guiomar Solanas, Neus Prats, Salvador Aznar Benitah
The DNA methyltransferase Dnmt3a suppresses tumorigenesis in models of leukemia and lung cancer. Conversely, deregulation of Dnmt3b is thought to generally promote tumorigenesis. However, the role of Dnmt3a and Dnmt3b in many types of cancer remains undefined. Here we show that Dnmt3a and Dnmt3b are dispensable for homeostasis of the murine epidermis. However, loss of Dnmt3a-but not Dnmt3b-increases the number of carcinogen-induced squamous tumors, without affecting tumor progression. Only upon combined deletion of Dnmt3a and Dnmt3b, squamous carcinomas become more aggressive and metastatic...
April 20, 2017: ELife
https://www.readbyqxmd.com/read/28425912/how-spatial-release-from-masking-may-fail-to-function-in-a-highly-directional-auditory-system
#20
Norman Lee, Andrew C Mason
Spatial release from masking (SRM) occurs when spatial separation between a signal and masker decreases masked thresholds. The mechanically-coupled ears of Ormia ochracea are specialized for hyperacute directional hearing, but the possible role of SRM, or whether such specializations exhibit limitations for sound source segregation, is unknown. We recorded phonotaxis to a cricket song masked by band-limited noise. With a masker, response thresholds increased and localization was diverted away from the signal and masker...
April 20, 2017: ELife
journal
journal
43971
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"