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https://www.readbyqxmd.com/read/28544778/differential-regulation-of-protein-tyrosine-kinase-signaling-by-dock-and-the-ptp61f-variants
#1
Lee F Willoughby, Jan Manent, Kirsten Allan, Han Lee, Marta Portela, Florian Wiede, Coral Warr, Tzu-Ching Meng, Tony Tiganis, Helena E Richardson
Tyrosine phosphorylation-dependent signalling is coordinated by the opposing actions of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). There is a growing list of adaptor proteins that interact with PTPs and facilitate the dephosphorylation of substrates. The extent to which any given adaptor confers selectivity for any given substrate in vivo remains unclear. Here we have taken advantage of Drosophila melanogaster as a model organism to explore the influence of the SH3/SH2 adaptor protein Dock on the abilities of the membrane (PTP61Fm)- and nuclear (PTP61Fn)-targeted variants of PTP61F (the Drosophila othologue of the mammalian enzymes PTP1B and TCPTP respectively) to repress PTK signaling pathways in vivo...
May 23, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28542380/more-oxygen-during-development-enhanced-flight-performance-but-not-thermal-tolerance-of-drosophila-melanogaster
#2
Shayan Shiehzadegan, Jacqueline Le Vinh Thuy, Natalia Szabla, Michael J Angilletta, John M VandenBrooks
High temperatures can stress animals by raising the oxygen demand above the oxygen supply. Consequently, animals under hypoxia could be more sensitive to heating than those exposed to normoxia. Although support for this model has been limited to aquatic animals, oxygen supply might limit the heat tolerance of terrestrial animals during energetically demanding activities. We evaluated this model by studying the flight performance and heat tolerance of flies (Drosophila melanogaster) acclimated and tested at different concentrations of oxygen (12%, 21%, and 31%)...
2017: PloS One
https://www.readbyqxmd.com/read/28542178/uncovering-direct-and-indirect-molecular-determinants-of-chromatin-loops-using-a-computational-integrative-approach
#3
Raphaël Mourad, Lang Li, Olivier Cuvier
Chromosomal organization in 3D plays a central role in regulating cell-type specific transcriptional and DNA replication timing programs. Yet it remains unclear to what extent the resulting long-range contacts depend on specific molecular drivers. Here we propose a model that comprehensively assesses the influence on contacts of DNA-binding proteins, cis-regulatory elements and DNA consensus motifs. Using real data, we validate a large number of predictions for long-range contacts involving known architectural proteins and DNA motifs...
May 23, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28537903/amyloid-precursor-like-protein-1-promotes-jnk-mediated-cell-migration-in-drosophila
#4
Xingjun Wang, Ying Sun, Shilong Han, Chenxi Wu, Yeqing Ma, Yu Zhao, Yingyao Shao, Yujun Chen, Lingzhi Kong, Wenzhe Li, Fan Zhang, Lei Xue
The amyloid precursor like protein-1 (APLP1) is a member of the amyloid precursor protein (APP) family in mammals. While many studies have been focused on the pathologic role of APP in Alzheimer's disease, the physiological functions of APLP1 have remained largely elusive. Here we report that ectopic expression of APLP1 in Drosophila induces cell migration, which is suppressed by the loss of JNK signaling and enhanced by the gain of JNK signaling. APLP1 activates JNK signaling through phosphorylation of JNK, which up-regulates the expression of matrix metalloproteinase MMP1 required for basement membranes degradation and promotes actin remodeling essential for cell migration...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28536147/hormone-dependent-control-of-developmental-timing-through-regulation-of-chromatin-accessibility
#5
Christopher M Uyehara, Spencer L Nystrom, Matthew J Niederhuber, Mary Leatham-Jensen, Yiqin Ma, Laura A Buttitta, Daniel J McKay
Specification of tissue identity during development requires precise coordination of gene expression in both space and time. Spatially, master regulatory transcription factors are required to control tissue-specific gene expression programs. However, the mechanisms controlling how tissue-specific gene expression changes over time are less well understood. Here, we show that hormone-induced transcription factors control temporal gene expression by regulating the accessibility of DNA regulatory elements. Using the Drosophila wing, we demonstrate that temporal changes in gene expression are accompanied by genome-wide changes in chromatin accessibility at temporal-specific enhancers...
May 23, 2017: Genes & Development
https://www.readbyqxmd.com/read/28520783/effect-of-n-terminal-region-of-nuclear-drosophila-melanogaster-small-heat-shock-protein-dmhsp27-on-function-and-quaternary-structure
#6
Mohamed Taha Moutaoufik, Geneviève Morrow, Stéphanie Finet, Robert M Tanguay
The importance of the N-terminal region (NTR) in the oligomerization and chaperone-like activity of the Drosophila melanogaster small nuclear heat shock protein DmHsp27 was investigated by mutagenesis using size exclusion chromatography and native gel electrophoresis. Mutation of two sites of phosphorylation in the N-terminal region, S58 and S75, did not affect the oligomerization equilibrium or the intracellular localization of DmHsp27 when transfected into mammalian cells. Deletion or mutation of specific residues within the NTR region delineated a motif (FGFG) important for the oligomeric structure and chaperone-like activity of this sHsp...
2017: PloS One
https://www.readbyqxmd.com/read/28516957/asxl2-is-essential-for-haematopoiesis-and-acts-as-a-haploinsufficient-tumour-suppressor-in-leukemia
#7
Jean-Baptiste Micol, Alessandro Pastore, Daichi Inoue, Nicolas Duployez, Eunhee Kim, Stanley Chun-Wei Lee, Benjamin H Durham, Young Rock Chung, Hana Cho, Xiao Jing Zhang, Akihide Yoshimi, Andrei Krivtsov, Richard Koche, Eric Solary, Amit Sinha, Claude Preudhomme, Omar Abdel-Wahab
Additional sex combs-like (ASXL) proteins are mammalian homologues of additional sex combs (Asx), a regulator of trithorax and polycomb function in Drosophila. While there has been great interest in ASXL1 due to its frequent mutation in leukemia, little is known about its paralog ASXL2, which is frequently mutated in acute myeloid leukemia patients bearing the RUNX1-RUNX1T1 (AML1-ETO) fusion. Here we report that ASXL2 is required for normal haematopoiesis with distinct, non-overlapping effects from ASXL1 and acts as a haploinsufficient tumour suppressor...
May 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28509532/nanodiamonds-mediate-oral-delivery-of-proteins-for-stem-cell-activation-and-intestinal-remodeling-in-drosophila
#8
Xingjie Hu, Xiaojiao Li, Min Yin, Ping Li, Ping Huang, Lihua Wang, Yiguo Jiang, Hui Wang, Nan Chen, Chunhai Fan, Haiyun Song
Introduction of exogenous biomacromolecules into living systems is of great interest in genome editing, cancer immunotherapy, and stem cell reprogramming. Whereas current strategies generally depend on nucleic acids transfection, direct delivery of functional proteins that provides enhanced specificity, increased safety, and fast and temporal regulation is highly desirable. Nevertheless, intracellular delivery of intact and bioactive proteins, especially in vivo, remains poorly explored. In this study, we developed a nanodiamonds (NDs)-based protein delivery system in cultured cells and in Drosophila that showed high adsorption, high efficiency, and effective cytosolic release of fully functional proteins...
May 23, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28508872/actin-stress-fiber-organization-promotes-cell-stiffening-and-proliferation-of-pre-invasive-breast-cancer-cells
#9
Sandra Tavares, André Filipe Vieira, Anna Verena Taubenberger, Margarida Araújo, Nuno Pimpao Martins, Catarina Brás-Pereira, António Polónia, Maik Herbig, Clara Barreto, Oliver Otto, Joana Cardoso, José B Pereira-Leal, Jochen Guck, Joana Paredes, Florence Janody
Studies of the role of actin in tumour progression have highlighted its key contribution in cell softening associated with cell invasion. Here, using a human breast cell line with conditional Src induction, we demonstrate that cells undergo a stiffening state prior to acquiring malignant features. This state is characterized by the transient accumulation of stress fibres and upregulation of Ena/VASP-like (EVL). EVL, in turn, organizes stress fibres leading to transient cell stiffening, ERK-dependent cell proliferation, as well as enhancement of Src activation and progression towards a fully transformed state...
May 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28502613/generation-of-a-targeted-expression-system-for-branchless-and-characterization-of-novel-cellular-expression-patterns-of-the-gene-in-drosophila
#10
Lijuan Du, Amy Zhou, Akshay Patel, Mishal Rao, Kelsey Anderson, Sougata Roy
Fibroblast growth factors (FGF) are essential signaling proteins that regulate diverse cellular functions in developmental and metabolic processes. In Drosophila, the FGF homolog, branchless (bnl) is expressed in a dynamic and spatiotemporally restricted pattern to induce branching morphogenesis of the trachea, which expresses the Bnl-receptor, breathless (btl). Here we have developed a new strategy to determine bnl- expressing cells and study their interactions with the btl-expressing cells in the range of tissue patterning during Drosophila development...
May 11, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28500755/enhanced-fib-sem-systems-for-large-volume-3d-imaging
#11
C Shan Xu, Kenneth J Hayworth, Zhiyuan Lu, Patricia Grob, Ahmed M Hassan, José G García-Cerdán, Krishna K Niyogi, Eva Nogales, Richard J Weinberg, Harald F Hess
Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) can automatically generate 3D images with superior z-axis resolution, yielding data that needs minimal image registration and related post-processing. Obstacles blocking wider adoption of FIB-SEM include slow imaging speed and lack of long-term system stability, which caps the maximum possible acquisition volume. Here we present techniques that accelerate image acquisition while greatly improving FIB-SEM reliability, allowing the system to operate for months and generating continuously imaged volumes > 10(6) µm(3)...
May 13, 2017: ELife
https://www.readbyqxmd.com/read/28497117/rna-interference-restricts-rift-valley-fever-virus-in-multiple-insect-systems
#12
Isabelle Dietrich, Stephanie Jansen, Gamou Fall, Stephan Lorenzen, Martin Rudolf, Katrin Huber, Anna Heitmann, Sabine Schicht, El Hadji Ndiaye, Mick Watson, Ilaria Castelli, Benjamin Brennan, Richard M Elliott, Mawlouth Diallo, Amadou A Sall, Anna-Bella Failloux, Esther Schnettler, Alain Kohl, Stefanie C Becker
The emerging bunyavirus Rift Valley fever virus (RVFV) is transmitted to humans and livestock by a large number of mosquito species. RNA interference (RNAi) has been characterized as an important innate immune defense mechanism used by mosquitoes to limit replication of positive-sense RNA flaviviruses and togaviruses; however, little is known about its role against negative-strand RNA viruses such as RVFV. We show that virus-specific small RNAs are produced in infected mosquito cells, in Drosophila melanogaster cells, and, most importantly, also in RVFV vector mosquitoes...
May 2017: MSphere
https://www.readbyqxmd.com/read/28492538/drosophila-caspase-activity-is-required-independently-of-apoptosis-to-produce-active-tnf-eiger-during-nociceptive-sensitization
#13
Juyeon Jo, Seol Hee Im, Daniel T Babcock, Srividya C Iyer, Felona Gunawan, Daniel N Cox, Michael J Galko
Tumor necrosis factor (TNF) signaling is required for inflammatory nociceptive (pain) sensitization in Drosophila and vertebrates. Nociceptive sensitization in Drosophila larvae following UV-induced tissue damage is accompanied by epidermal apoptosis and requires epidermal-derived TNF/Eiger and the initiator caspase, Dronc. Major gaps remain regarding TNF function in sensitization, including the relationship between apoptosis/tissue damage and TNF production, the downstream signaling in this context, and the target genes that modulate nociceptive behaviors...
May 11, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28490633/single-particle-electron-microscopy-structure-of-udp-glucose-glycoprotein-glucosyltransferase-suggests-a-selectivity-mechanism-for-misfolded-proteins
#14
Daniel Calles-Garcia, Meng Yang, Naoto Soya, Roberto Melero, Marie Ménade, Yukishige Ito, Javier Vargas, Gergely L Lukacs, Justin M Kollman, Guennadi Kozlov, Kalle Gehring
The enzyme UDP-glucose:glycoprotein glucosyltransferase (UGGT) mediates quality control of glycoproteins in the endoplasmic reticulum by attaching glucose to N-linked glycan of misfolded proteins. As a sensor, UGGT ensures that misfolded proteins are recognized by the lectin chaperones and do not leave the secretory pathway. The structure of UGGT and the mechanism of its selectivity for misfolded proteins have been unknown for 25 years. Here, we used negative-stain electron microscopy and small-angle X-ray scattering to determine the structure of UGGT from Drosophila melanogaster at 18 Å resolution...
May 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28485098/production-of-a-fungal-furocoumarin-by-a-polyketide-synthase-gene-cluster-confers-the-chemo-resistance-of-neurospora-crassa-to-the-predation-by-fungivorous-arthropods
#15
Yanxia Zhao, Jianing Ding, Weihua Yuan, Jinjin Huang, Wenxiu Huang, Yan Wang, Weifa Zheng
The formation of sexual fruiting bodies and production of polyketides are believed to be the most important strategies for fungal survival in environmental insults. In Neurospora crassa, the backbone gene of polyketide synthase gene cluster 6 (pks-6), which is expressed at lower level under vegetative growth, is highly expressed during perithecia development. Intriguingly, deletion of pks-6 does not affect perithecia maturation. How the expression of pks-6 correlates with fungal sexual development remains to be established...
May 9, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28469030/manipulation-of-feeding-regime-alters-sexual-dimorphism-for-lifespan-and-reduces-sexual-conflict-in-drosophila-melanogaster
#16
Elizabeth M L Duxbury, Wayne G Rostant, Tracey Chapman
Sexual dimorphism for lifespan (SDL) is widespread, but poorly understood. A leading hypothesis, which we test here, is that strong SDL can reduce sexual conflict by allowing each sex to maximize its sex-specific fitness. We used replicated experimental evolution lines of the fruit fly, Drosophila melanogaster, which had been maintained for over 360 generations on either unpredictable 'Random' or predictable 'Regular' feeding regimes. This evolutionary manipulation of feeding regime led to robust, enhanced SDL in Random over control, Regular lines...
May 17, 2017: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/28469022/flightin-maintains-myofilament-lattice-organization-required-for-optimal-flight-power-and-courtship-song-quality-in-drosophila
#17
Samya Chakravorty, Bertrand C W Tanner, Veronica Lee Foelber, Hien Vu, Matthew Rosenthal, Teresa Ruiz, Jim O Vigoreaux
The indirect flight muscles (IFMs) of Drosophila and other insects with asynchronous flight muscles are characterized by a crystalline myofilament lattice structure. The high-order lattice regularity is considered an adaptation for enhanced power output, but supporting evidence for this claim is lacking. We show that IFMs from transgenic flies expressing flightin with a deletion of its poorly conserved N-terminal domain (fln(ΔN62) ) have reduced inter-thick filament spacing and a less regular lattice. This resulted in a decrease in flight ability by 33% and in skinned fibre oscillatory power output by 57%, but had no effect on wingbeat frequency or frequency of maximum power output, suggesting that the underlying actomyosin kinetics is not affected and that the flight impairment arises from deficits in force transmission...
May 17, 2017: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/28457869/satellite-repeats-identify-x-chromatin-for-dosage-compensation-in-drosophila-melanogaster-males
#18
Sonal S Joshi, Victoria H Meller
A common feature of sex chromosomes is coordinated regulation of X-linked genes in one sex. Drosophila melanogaster males have one X chromosome, whereas females have two. The resulting imbalance in gene dosage is corrected by increased expression from the single X chromosome of males, a process known as dosage compensation. In flies, compensation involves recruitment of the male-specific lethal (MSL) complex to X-linked genes and modification of chromatin to increase expression. The extraordinary selectivity of the MSL complex for the X chromosome has never been explained...
May 22, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28448633/a-commensal-streptococcus-hijacks-a-pseudomonas-aeruginosa-exopolysaccharide-to-promote-biofilm-formation
#19
Jessica A Scoffield, Dingyu Duan, Fan Zhu, Hui Wu
Pseudomonas aeruginosa causes devastating chronic pulmonary infections in cystic fibrosis (CF) patients. Although the CF airway is inhabited by diverse species of microorganisms interlaced within a biofilm, many studies focus on the sole contribution of P. aeruginosa pathogenesis in CF morbidity. More recently, oral commensal streptococci have been identified as cohabitants of the CF lung, but few studies have explored the role these bacteria play within the CF biofilm. We examined the interaction between P...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28446593/creating-cell-type-specific-mutants-by-enhancer-mutagenesis
#20
Stephen Crews
Cell signaling plays an essential role in development, and knowledge of the identities of the cells sending the signal is critical. This can be a challenge, since signaling pathways and ligands are commonly used at multiple times and in multiple cell types during development. One solution to this problem is to create cell type-specific mutants using CRISPR/Cas9 to mutate enhancers that control different patterns of expression. In this issue of Genes & Development, Rogers and colleagues (pp. 634-638) provide the first use of this method in Drosophila to solve a long-standing issue in patterning of the embryonic central nervous system...
April 1, 2017: Genes & Development
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