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https://www.readbyqxmd.com/read/27927008/microrna-296-5p-promotes-invasiveness-through-downregulation-of-nerve-growth-factor-receptor-and-caspase-8
#1
Hong Lee, Chang Hoon Shin, Hye Ree Kim, Kyung Hee Choi, Hyeon Ho Kim
Glioblastomas (GBM) are very difficult to treat and their aggressiveness is one of the main reasons for this as well as for the frequent recurrences. MicroRNAs posttranscriptionally regulate their target genes through interaction between their seed sequence and 3'UTR of the target mRNAs. We previously reported that miR-296-3p is regulated by neurofibromatosis 2 (NF2) and enhances the invasiveness of GBM cells via SOCS2/STAT3. In this study, we investigated whether miR-296-5p, which originates from the same precursor miRNA as miR-296-3p, can increase the invasiveness of GBM cells...
December 8, 2016: Molecules and Cells
https://www.readbyqxmd.com/read/27926980/role-and-regulation-of-p27-in-neuronal-apoptosis
#2
Surbhi Jaiswal, Pushkar Sharma
It is necessary for the cell cycle machinery of neurons to be suppressed to promote differentiation and maintenance of their terminally differentiated state. Reactivation of the cell cycle in response to neurotoxic insults leads to neuronal cell death and some cell cycle related proteins contribute to the process. p27 kip1 (p27), an inhibitor of Cyclin Dependent Kinases (CDKs), prevents unwarranted CDK activation. In the present study, we have elucidated a novel mechanism via which p27 promotes apoptosis of neurons stimulated by neurotoxic amyloid peptide Aβ42 (Amyloid β1-42 peptide)...
December 7, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27926943/the-mouse-cytomegalovirus-gene-m42-targets-surface-expression-of-the-protein-tyrosine-phosphatase-cd45-in-infected-macrophages
#3
Nadine Thiel, Kirsten A Keyser, Niels A W Lemmermann, Jennifer D Oduro, Karen Wagner, Carina Elsner, Anne Halenius, Tihana Lenac Roviš, Melanie M Brinkmann, Stipan Jonjić, Luka Cicin-Sain, Martin Messerle
The receptor-like protein tyrosine phosphatase CD45 is expressed on the surface of cells of hematopoietic origin and has a pivotal role for the function of these cells in the immune response. Here we report that following infection of macrophages with mouse cytomegalovirus (MCMV) the cell surface expression of CD45 is drastically diminished. Screening of a set of MCMV deletion mutants allowed us to identify the viral gene m42 of being responsible for CD45 down-modulation. Moreover, expression of m42 independent of viral infection upon retroviral transduction of the RAW264...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926928/an-interactome-centered-protein-discovery-approach-reveals-novel-components-involved-in-mitosome-function-and-homeostasis-in-giardia-lamblia
#4
Samuel Rout, Jon Paulin Zumthor, Elisabeth M Schraner, Carmen Faso, Adrian B Hehl
Protozoan parasites of the genus Giardia are highly prevalent globally, and infect a wide range of vertebrate hosts including humans, with proliferation and pathology restricted to the small intestine. This narrow ecological specialization entailed extensive structural and functional adaptations during host-parasite co-evolution. An example is the streamlined mitosomal proteome with iron-sulphur protein maturation as the only biochemical pathway clearly associated with this organelle. Here, we applied techniques in microscopy and protein biochemistry to investigate the mitosomal membrane proteome in association to mitosome homeostasis...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926919/plasmodium-falciparum-infection-status-among-children-with-schistosoma-in-sub-saharan-africa-a-systematic-review-and-meta-analysis
#5
Abraham Degarege, Dawit Degarege, Emir Veledar, Berhanu Erko, Mathieu Nacher, Consuelo M Beck-Sague, Purnima Madhivanan
BACKGROUND: It has been suggested that Schistosoma infection may be associated with Plasmodium falciparum infection or related reduction in haemoglobin level, but the nature of this interaction remains unclear. This systematic review synthesized evidence on the relationship of S. haematobium or S. mansoni infection with the occurrence of P. falciparum malaria, Plasmodium density and related reduction in haemoglobin level among children in sub-Saharan Africa (SSA). METHODOLOGY/PRINCIPAL FINDINGS: A systematic review in according with PRISMA guidelines was conducted...
December 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27926916/elevated-temperature-and-allelopathy-impact-coral-recruitment
#6
Raphael Ritson-Williams, Cliff Ross, Valerie J Paul
As climate change continues to alter seawater temperature and chemistry on a global scale, coral reefs show multiple signs of degradation. One natural process that could facilitate the recovery of reef ecosystems is coral recruitment, which can be influenced by the benthic organisms in a local habitat. We experimentally tested both a global stressor (increased seawater temperature) and a local stressor (exposure to microcolin A, a natural product from a common marine benthic cyanobacterium) to determine how these stressors impacted coral larval sublethal stress, survival and settlement...
2016: PloS One
https://www.readbyqxmd.com/read/27926877/ptbp1-and-ptbp2-serve-both-specific-and-redundant-functions-in-neuronal-pre-mrna-splicing
#7
John K Vuong, Chia-Ho Lin, Min Zhang, Liang Chen, Douglas L Black, Sika Zheng
Families of alternative splicing regulators often contain multiple paralogs presumed to fulfill different functions. Polypyrimidine tract binding proteins PTBP1 and PTBP2 reprogram developmental pre-mRNA splicing in neurons, but how their regulatory networks differ is not understood. To compare their targeting, we generated a knockin allele that conditionally expresses PTBP1. Bred to a Ptbp2 knockout, the transgene allowed us to compare the developmental and molecular phenotypes of mice expressing only PTBP1, only PTBP2, or neither protein in the brain...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926874/multivalent-histone-and-dna-engagement-by-a-phd-brd-pwwp-triple-reader-cassette-recruits-zmynd8-to-k14ac-rich-chromatin
#8
Pavel Savitsky, Tobias Krojer, Takao Fujisawa, Jean-Philippe Lambert, Sarah Picaud, Chen-Yi Wang, Erin K Shanle, Krzysztof Krajewski, Hans Friedrichsen, Alexander Kanapin, Colin Goding, Matthieu Schapira, Anastasia Samsonova, Brian D Strahl, Anne-Claude Gingras, Panagis Filippakopoulos
Elucidation of interactions involving DNA and histone post-translational-modifications (PTMs) is essential for providing insights into complex biological functions. Reader assemblies connected by flexible linkages facilitate avidity and increase affinity; however, little is known about the contribution to the recognition process of multiple PTMs because of rigidity in the absence of conformational flexibility. Here, we resolve the crystal structure of the triple reader module (PHD-BRD-PWWP) of ZMYND8, which forms a stable unit capable of simultaneously recognizing multiple histone PTMs while presenting a charged platform for association with DNA...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926873/foxa1-directs-h3k4-monomethylation-at-enhancers-via-recruitment-of-the-methyltransferase-mll3
#9
Kamila M Jozwik, Igor Chernukhin, Aurelien A Serandour, Sankari Nagarajan, Jason S Carroll
FOXA1 is a pioneer factor that binds to enhancer regions that are enriched in H3K4 mono- and dimethylation (H3K4me1 and H3K4me2). We performed a FOXA1 rapid immunoprecipitation mass spectrometry of endogenous proteins (RIME) screen in ERα-positive MCF-7 breast cancer cells and found histone-lysine N-methyltransferase (MLL3) as the top FOXA1-interacting protein. MLL3 is typically thought to induce H3K4me3 at promoter regions, but recent findings suggest it may contribute to H3K4me1 deposition. We performed MLL3 chromatin immunoprecipitation sequencing (ChIP-seq) in breast cancer cells, and MLL3 was shown to occupy regions marked by FOXA1 occupancy and H3K4me1 and H3K4me2...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926869/robust-asymmetric-localization-of-planar-polarity-proteins-is-associated-with-organization-into-signalosome-like-domains-of-variable-stoichiometry
#10
Helen Strutt, Jessica Gamage, David Strutt
In developing epithelia, the core planar polarity proteins physically interact with each other and localize asymmetrically at opposite cell ends, forming intercellular complexes that link the polarity of neighboring cells. Using quantitative imaging to examine the composition of the core protein complex in vivo, we find that complex composition is unexpectedly plastic. The transmembrane proteins Frizzled and Flamingo form a stoichiometric nucleus in the complex, while the relative levels of the other four core proteins can vary independently...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926868/cmyc-regulates-the-size-of-the-premigratory-neural-crest-stem-cell-pool
#11
Laura Kerosuo, Marianne E Bronner
The neural crest is a transient embryonic population that originates within the central nervous system (CNS) and then migrates into the periphery and differentiates into multiple cell types. The mechanisms that govern neural crest stem-like characteristics and self-renewal ability are poorly understood. Here, we show that the proto-oncogene cMyc is a critical factor in the chick dorsal neural tube, where it regulates the size of the premigratory neural crest stem cell pool. Loss of cMyc dramatically decreases the number of emigrating neural crest cells due to reduced self-renewal capacity, increased cell death, and shorter duration of the emigration process...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926858/g-protein-coupled-receptor-2-interacting-protein-1-controls-stalk-cell-fate-by-inhibiting-delta-like-4-notch1-signaling
#12
Syamantak Majumder, GuoFu Zhu, Xiangbin Xu, Sharon Senchanthisai, Dongyang Jiang, Hao Liu, Chao Xue, Xiaoqun Wang, Heidi Coia, Zhaoqiang Cui, Elaine M Smolock, Richard T Libby, Bradford C Berk, Jinjiang Pang
The spatiotemporal localization and expression of Dll4 are critical for sprouting angiogenesis. However, the related mechanisms are poorly understood. Here, we show that G-protein-coupled receptor-kinase interacting protein-1 (GIT1) is a robust endogenous inhibitor of Dll4-Notch1 signaling that specifically controls stalk cell fate. GIT1 is highly expressed in stalk cells but not in tip cells. GIT1 deficiency remarkably enhances Dll4 expression and Notch1 signaling, resulting in impaired retinal sprouting angiogenesis, which can be rescued by treatment with the Notch inhibitor or Dll4 neutralizing antibody...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926854/structural-characterization-and-statistical-mechanical-model-of-epidermal-patterns
#13
Duyu Chen, Wen Yih Aw, Danelle Devenport, Salvatore Torquato
In proliferating epithelia of mammalian skin, cells of irregular polygon-like shapes pack into complex, nearly flat two-dimensional structures that are pliable to deformations. In this work, we employ various sensitive correlation functions to quantitatively characterize structural features of evolving packings of epithelial cells across length scales in mouse skin. We find that the pair statistics in direct space (correlation function) and Fourier space (structure factor) of the cell centroids in the early stages of embryonic development show structural directional dependence (statistical anisotropy), which is a reflection of the fact that cells are stretched, which promotes uniaxial growth along the epithelial plane...
December 6, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27926846/alamethicin-supramolecular-organization-in-lipid-membranes-from-19-f-solid-state-nmr
#14
Evgeniy S Salnikov, Jesus Raya, Marta De Zotti, Ekaterina Zaitseva, Cristina Peggion, Gema Ballano, Claudio Toniolo, Jan Raap, Burkhard Bechinger
Alamethicins (ALMs) are antimicrobial peptides of fungal origin. Their sequences are rich in hydrophobic amino acids and strongly interact with lipid membranes, where they cause a well-defined increase in conductivity. Therefore, the peptides are thought to form transmembrane helical bundles in which the more hydrophilic residues line a water-filled pore. Whereas the peptide has been well characterized in terms of secondary structure, membrane topology, and interactions, much fewer data are available regarding the quaternary arrangement of the helices within lipid bilayers...
December 6, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27926845/membrane-bound-alpha-synuclein-clusters-induce-impaired-lipid-diffusion-and-increased-lipid-packing
#15
Aditya Iyer, Nathalie Schilderink, Mireille M A E Claessens, Vinod Subramaniam
The aggregation of membrane-bound α-synuclein (αS) into oligomers and/or amyloid fibrils has been suggested to cause membrane damage in in vitro model phospholipid membrane systems and in vivo. In this study, we investigate how αS interactions that precede the formation of well-defined aggregates influence physical membrane properties. Using three truncated variants of αS with different aggregation propensities and comparable phospholipid membrane binding affinities we show, using fluorescence recovery after photobleaching (FRAP) and fluorescence anisotropy measurements, that formation of αS clusters on supported lipid bilayers (SLBs) impairs lateral lipid diffusion and increases lipid packing beneath the αS clusters...
December 6, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27926842/intact-telopeptides-enhance-interactions-between-collagens
#16
Marjan Shayegan, Tuba Altindal, Evan Kiefl, Nancy R Forde
Collagen is the fundamental structural component of a wide range of connective tissues and of the extracellular matrix. It undergoes self-assembly from individual triple-helical proteins into well-ordered fibrils, a process that is key to tissue development and homeostasis, and to processes such as wound healing. Nucleation of this assembly is known to be slowed considerably by pepsin removal of short nonhelical regions that flank collagen's triple helix, known as telopeptides. Using optical tweezers to perform microrheology measurements, we explored the changes in viscoelasticity of solutions of collagen with and without intact telopeptides...
December 6, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27926840/calcium-dependent-structural-dynamics-of-a-spin-labeled-ryr-peptide-bound-to-calmodulin
#17
Cheng Her, Jesse E McCaffrey, David D Thomas, Christine B Karim
We have used chemical synthesis, electron paramagnetic resonance (EPR), and circular dichroism to detect and analyze the structural dynamics of a ryanodine receptor (RyR) peptide bound to calmodulin (CaM). The skeletal muscle calcium release channel RyR1 is activated by Ca(2+)-free CaM and inhibited by Ca(2+)-bound CaM. To probe the structural mechanism for this regulation, wild-type RyRp and four spin-labeled derivatives were synthesized, each containing the nitroxide probe 2,2,6,6-tetramethyl-piperidine-1-oxyl-4-amino-4-carboxylic acid substituted for a single amino acid...
December 6, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27926839/circular-dichroism-spectroscopy-of-collagen-fibrillogenesis-a-new-use-for-an-old-technique
#18
Kathryn E Drzewiecki, Daniel R Grisham, Avanish S Parmar, Vikas Nanda, David I Shreiber
Type-I collagen assembles in a stepwise, hierarchic fashion from the folding of the triple helix to the assembly of fibrils into fibers. The mature assembled fibers are crucial for tissue structure and mechanics, cell interactions, and other functions in vivo. Although triple helix folding can be followed with the use of optical methods such as circular dichroism (CD) spectroscopy, fibrillogenesis is typically measured by alternative methods such as turbidity, rheology, and microscopy. Together, these approaches allow for investigation of the mechanical properties and architectures of collagen-based scaffolds and excised tissues...
December 6, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27926836/probing-small-molecule-binding-to-unfolded-polyprotein-based-on-its-elasticity-and-refolding
#19
Ricksen S Winardhi, Qingnan Tang, Jin Chen, Mingxi Yao, Jie Yan
Unfolded protein, a disordered structure found before folding of newly synthesized protein or after protein denaturation, is a substrate for binding by many cellular factors such as heat-stable proteins, chaperones, and many small molecules. However, it is challenging to directly probe such interactions in physiological solution conditions because proteins are largely in their folded state. In this work we probed small molecule binding to mechanically unfolded polyprotein using sodium dodecyl sulfate (SDS) as an example...
December 6, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27926833/conformational-plasticity-in-the-transsynaptic-neurexin-cerebellin-glutamate-receptor-adhesion-complex
#20
Shouqiang Cheng, Alpay B Seven, Jing Wang, Georgios Skiniotis, Engin Özkan
Synaptic specificity is a defining property of neural networks. In the cerebellum, synapses between parallel fiber neurons and Purkinje cells are specified by the simultaneous interactions of secreted protein cerebellin with pre-synaptic neurexin and post-synaptic delta-type glutamate receptors (GluD). Here, we determined the crystal structures of the trimeric C1q-like domain of rat cerebellin-1, and the first complete ectodomain of a GluD, rat GluD2. Cerebellin binds to the LNS6 domain of α- and β-neurexin-1 through a high-affinity interaction that involves its highly flexible N-terminal domain...
December 6, 2016: Structure
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