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https://www.readbyqxmd.com/read/30232099/quantifying-the-phosphorylation-timescales-of-receptor-ligand-complexes-a-markovian-matrix-analytic-approach
#1
M López-García, M Nowicka, C Bendtsen, G Lythe, S Ponnambalam, C Molina-París
Cells interact with the extracellular environment by means of receptor molecules on their surface. Receptors can bind different ligands, leading to the formation of receptor-ligand complexes. For a subset of receptors, called receptor tyrosine kinases, binding to ligand enables sequential phosphorylation of intra-cellular residues, which initiates a signalling cascade that regulates cellular function and fate. Most mathematical modelling approaches employed to analyse receptor signalling are deterministic, especially when studying scenarios of high ligand concentration or large receptor numbers...
September 19, 2018: Open Biology
https://www.readbyqxmd.com/read/30232098/reduction-of-leucocyte-cell-surface-disulfide-bonds-during-immune-activation-is-dynamic-as-revealed-by-a-quantitative-proteomics-workflow-sh-iq
#2
Monika Stegmann, A Neil Barclay, Clive Metcalfe
Communication through cell surface receptors is crucial for maintaining immune homeostasis, coordinating the immune response and pathogen clearance. This is dependent on the interaction of cell surface receptors with their ligands and requires functionally active conformational states. Thus, immune cell function can be controlled by modulating the structure of either the receptor or the ligand. Reductive cleavage of labile disulfide bonds can mediate such an allosteric change, resulting in modulation of the immune system by a hitherto little studied mechanism...
September 19, 2018: Open Biology
https://www.readbyqxmd.com/read/30209039/tales-from-the-crypt-intestinal-niche-signals-in-tissue-renewal-plasticity-and-cancer
#3
REVIEW
Maureen Spit, Bon-Kyoung Koo, Madelon M Maurice
Rapidly renewing tissues such as the intestinal epithelium critically depend on the activity of small-sized stem cell populations that continuously generate new progeny to replace lost and damaged cells. The complex and tightly regulated process of intestinal homeostasis is governed by a variety of signalling pathways that balance cell proliferation and differentiation. Accumulating evidence suggests that stem cell control and daughter cell fate determination is largely dictated by the microenvironment. Here, we review recent developments in the understanding of intestinal stem cell dynamics, focusing on the roles, mechanisms and interconnectivity of prime signalling pathways that regulate stem cell behaviour in intestinal homeostasis...
September 12, 2018: Open Biology
https://www.readbyqxmd.com/read/30209038/periodontal-cell-mechanotransduction
#4
REVIEW
Sasanka S Chukkapalli, Tanmay P Lele
The periodontium is a structurally and functionally complex tissue that facilitates the anchorage of teeth in jaws. The periodontium consists of various cell types including stem cells, fibroblasts and epithelial cells. Cells of the periodontium are constantly exposed to mechanical stresses generated by biological processes such as the chewing motions of teeth, by flows generated by tongue motions and by forces generated by implants. Mechanical stresses modulate the function of cells in the periodontium, and may play a significant role in the development of periodontal disease...
September 12, 2018: Open Biology
https://www.readbyqxmd.com/read/30185603/synaptic-dysfunction-in-neurodegenerative-and-neurodevelopmental-diseases-an-overview-of-induced-pluripotent-stem-cell-based-disease-models
#5
REVIEW
Era Taoufik, Georgia Kouroupi, Ourania Zygogianni, Rebecca Matsas
Synaptic dysfunction in CNS disorders is the outcome of perturbations in physiological synapse structure and function, and can be either the cause or the consequence in specific pathologies. Accumulating data in the field of neuropsychiatric disorders, including autism spectrum disorders, schizophrenia and bipolar disorder, point to a neurodevelopmental origin of these pathologies. Due to a relatively early onset of behavioural and cognitive symptoms, it is generally acknowledged that mental illness initiates at the synapse level...
September 2018: Open Biology
https://www.readbyqxmd.com/read/30185602/emerging-approaches-for-detection-of-methylation-sites-in-rna
#6
REVIEW
Anna Ovcharenko, Andrea Rentmeister
RNA methylations play a significant regulatory role in diverse biological processes. Although the transcriptome-wide discovery of unknown RNA methylation sites is essential to elucidate their function, the development of a bigger variety of detection approaches is desirable for multiple reasons. Many established detection methods for RNA modifications heavily rely on the specificity of the respective antibodies. Thus, the development of antibody-independent transcriptome-wide methods is beneficial. Even the antibody-independent high-throughput sequencing-based methods are liable to produce false-positive or false-negative results...
September 2018: Open Biology
https://www.readbyqxmd.com/read/30185601/structural-insights-into-the-functional-diversity-of-the-cdk-cyclin-family
#7
REVIEW
Daniel J Wood, Jane A Endicott
Since their characterization as conserved modules that regulate progression through the eukaryotic cell cycle, cyclin-dependent protein kinases (CDKs) in higher eukaryotic cells are now also emerging as significant regulators of transcription, metabolism and cell differentiation. The cyclins, though originally characterized as CDK partners, also have CDK-independent roles that include the regulation of DNA damage repair and transcriptional programmes that direct cell differentiation, apoptosis and metabolic flux...
September 2018: Open Biology
https://www.readbyqxmd.com/read/30158322/correction-to-shape-form-function-and-leishmania-pathogenicity-from-textbook-descriptions-to-biological-understanding
#8
Jack Sunter, Keith Gull
No abstract text is available yet for this article.
August 2018: Open Biology
https://www.readbyqxmd.com/read/30135239/a-unified-view-of-spatio-temporal-control-of-mitotic-entry-polo-kinase-as-the-key
#9
REVIEW
Lionel Pintard, Vincent Archambault
The Polo kinase is an essential regulator of cell division. Its ability to regulate multiple events at distinct subcellular locations and times during mitosis is remarkable. In the last few years, a much clearer mechanistic understanding of the functions and regulation of Polo in cell division has emerged. In this regard, the importance of coupling changes in activity with changes in localization is striking, both for Polo itself and for its upstream regulators. This review brings together several new pieces of the puzzle that are gradually revealing how Polo is regulated, in space and time, to enable its functions in the early stages of mitosis in animal cells...
August 2018: Open Biology
https://www.readbyqxmd.com/read/30135238/immune-responses-to-dengue-virus-in-the-skin
#10
REVIEW
Abhay P S Rathore, Ashley L St John
Dengue virus (DENV) causes infection in humans and current estimates place 40% of the world population at risk for contracting disease. There are four DENV serotypes that induce a febrile illness, which can develop into a severe and life-threatening disease in some cases, characterized primarily by vascular dysregulation. As a mosquito-borne infection, the skin is the initial site of DENV inoculation and also where primary host immune responses are initiated. This review discusses the early immune response to DENV in the skin by both infection target cells such as dendritic cells and by immune sentinels such as mast cells...
August 2018: Open Biology
https://www.readbyqxmd.com/read/30135237/spatial-organization-of-different-sigma-factor-activities-and-c-di-gmp-signalling-within-the-three-dimensional-landscape-of-a-bacterial-biofilm
#11
Gisela Klauck, Diego O Serra, Alexandra Possling, Regine Hengge
Bacterial biofilms are large aggregates of cells embedded in an extracellular matrix of self-produced polymers. In macrocolony biofilms of Escherichia coli , this matrix is generated in the upper biofilm layer only and shows a surprisingly complex supracellular architecture. Stratified matrix production follows the vertical nutrient gradient and requires the stationary phase σ S (RpoS) subunit of RNA polymerase and the second messenger c-di-GMP. By visualizing global gene expression patterns with a newly designed fingerprint set of Gfp reporter fusions, our study reveals the spatial order of differential sigma factor activities, stringent control of ribosomal gene expression and c-di-GMP signalling in vertically cryosectioned macrocolony biofilms...
August 2018: Open Biology
https://www.readbyqxmd.com/read/30111590/leader-of-the-sac-molecular-mechanisms-of-mps1-ttk-regulation-in-mitosis
#12
REVIEW
Spyridon T Pachis, Geert J P L Kops
Discovered in 1991 in a screen for genes involved in spindle pole body duplication, the monopolar spindle 1 (Mps1) kinase has since claimed a central role in processes that ensure error-free chromosome segregation. As a result, Mps1 kinase activity has become an attractive candidate for pharmaceutical companies in the search for compounds that target essential cellular processes to eliminate, for example, tumour cells or pathogens. Research in recent decades has offered many insights into the molecular function of Mps1 and its regulation...
August 2018: Open Biology
https://www.readbyqxmd.com/read/30111589/mouse-models-in-the-era-of-large-human-tumour-sequencing-studies
#13
REVIEW
J R de Ruiter, L F A Wessels, J Jonkers
Cancer is a complex disease in which cells progressively accumulate mutations disrupting their cellular processes. A fraction of these mutations drive tumourigenesis by affecting oncogenes or tumour suppressor genes, but many mutations are passengers with no clear contribution to tumour development. The advancement of DNA and RNA sequencing technologies has enabled in-depth analysis of thousands of human tumours from various tissues to perform systematic characterization of their (epi)genomes and transcriptomes in order to identify (epi)genetic changes associated with cancer...
August 2018: Open Biology
https://www.readbyqxmd.com/read/30089658/conserved-temporal-ordering-of-promoter-activation-implicates-common-mechanisms-governing-the-immediate-early-response-across-cell-types-and-stimuli
#14
Annalaura Vacca, Masayoshi Itoh, Hideya Kawaji, Erik Arner, Timo Lassmann, Carsten O Daub, Piero Carninci, Alistair R R Forrest, Yoshihide Hayashizaki, Stuart Aitken, Colin A Semple
The promoters of immediate early genes (IEGs) are rapidly activated in response to an external stimulus. These genes, also known as primary response genes, have been identified in a range of cell types, under diverse extracellular signals and using varying experimental protocols. Whereas genomic dissection on a case-by-case basis has not resulted in a comprehensive catalogue of IEGs, a rigorous meta-analysis of eight genome-wide FANTOM5 CAGE (cap analysis of gene expression) time course datasets reveals successive waves of promoter activation in IEGs, recapitulating known relationships between cell types and stimuli: we obtain a set of 57 (42 protein-coding) candidate IEGs possessing promoters that consistently drive a rapid but transient increase in expression over time...
August 2018: Open Biology
https://www.readbyqxmd.com/read/30068568/reproducibility-of-academic-preclinical-translational-research-lessons-from-the-development-of-hedgehog-pathway-inhibitors-to-treat-cancer
#15
REVIEW
Tom Curran
Academic translational research is growing at a great pace at a time in which questions have been raised about the reproducibility of preclinical findings. The development of Hedgehog (HH) pathway inhibitors for the treatment of cancer over the past two decades offers a case study for understanding the root causes of failure to predict clinical outcomes arising from academic preclinical translational research. Although such inhibitors were once hoped to be efficacious in up to 25% of human cancer, clinical studies showed responses only in basal cell carcinoma and the HH subtype of medulloblastoma...
August 2018: Open Biology
https://www.readbyqxmd.com/read/30068567/implications-of-dimeric-activation-of-pde6-for-rod-phototransduction
#16
Trevor D Lamb, Martin Heck, Timothy W Kraft
We examine the implications of a recent report providing evidence that two transducins must bind to the rod phosphodiesterase to elicit significant hydrolytic activity. To predict the rod photoreceptor's electrical response, we use numerical simulation of the two-dimensional diffusional contact of interacting molecules at the surface of the disc membrane, and then we use the simulated PDE activity as the driving function for the downstream reaction cascade. The results account for a number of aspects of rod phototransduction that have previously been puzzling...
August 2018: Open Biology
https://www.readbyqxmd.com/read/30068566/it-takes-two-transducins-to-activate-the-cgmp-phosphodiesterase-6-in-retinal-rods
#17
Bilal M Qureshi, Elmar Behrmann, Johannes Schöneberg, Justus Loerke, Jörg Bürger, Thorsten Mielke, Jan Giesebrecht, Frank Noé, Trevor D Lamb, Klaus Peter Hofmann, Christian M T Spahn, Martin Heck
Among cyclic nucleotide phosphodiesterases (PDEs), PDE6 is unique in serving as an effector enzyme in G protein-coupled signal transduction. In retinal rods and cones, PDE6 is membrane-bound and activated to hydrolyse its substrate, cGMP, by binding of two active G protein α-subunits (Gα*). To investigate the activation mechanism of mammalian rod PDE6, we have collected functional and structural data, and analysed them by reaction-diffusion simulations. Gα* titration of membrane-bound PDE6 reveals a strong functional asymmetry of the enzyme with respect to the affinity of Gα* for its two binding sites on membrane-bound PDE6 and the enzymatic activity of the intermediary 1 : 1 Gα* · PDE6 complex...
August 2018: Open Biology
https://www.readbyqxmd.com/read/30068565/cell-polarity-having-and-making-sense-of-direction-on-the-evolutionary-significance-of-the-primary-cilium-centrosome-organ-in-metazoa
#18
REVIEW
Michel Bornens
Cell-autonomous polarity in Metazoans is evolutionarily conserved. I assume that permanent polarity in unicellular eukaryotes is required for cell motion and sensory reception, integration of these two activities being an evolutionarily constrained function. Metazoans are unique in making cohesive multicellular organisms through complete cell divisions. They evolved a primary cilium/centrosome (PC/C) organ, ensuring similar functions to the basal body/flagellum of unicellular eukaryotes, but in different cells, or in the same cell at different moments...
August 2018: Open Biology
https://www.readbyqxmd.com/read/30045886/who-are-you-subdistal-appendages-of-centriole
#19
REVIEW
Rustem Uzbekov, Irina Alieva
This review summarizes data that assign morphological, biochemical and functional characteristics of two types of structures that are associated with centrioles: distal appendages and subdistal appendages. The description of centriole subdistal appendages is often a matter of confusion, both due to the numerous names used to describe these structures and because of their variability among species and cell types. Thus, we have summarized our current knowledge in this review. We conclude that distal appendages and subdistal appendages are fundamentally different in composition and function in the cell...
July 2018: Open Biology
https://www.readbyqxmd.com/read/30045885/loss-of-runx1-function-results-in-b-cell-immunodeficiency-but-not-t-cell-in-adult-zebrafish
#20
Yali Chi, Zhibin Huang, Qi Chen, Xiaojie Xiong, Kemin Chen, Jin Xu, Yiyue Zhang, Wenqing Zhang
Transcription factor RUNX1 holds an integral role in multiple-lineage haematopoiesis and is implicated as a cofactor in V(D)J rearrangements during lymphocyte development. Runx1 deficiencies resulted in immaturity and reduction of lymphocytes in mice. In this study, we found that runx1W84X/W84X mutation led to the reduction and disordering of B cells, as well as the failure of V(D)J rearrangements in B cells but not T cells, resulting in antibody-inadequate-mediated immunodeficiency in adult zebrafish. By contrast, T cell development was not affected...
July 2018: Open Biology
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