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https://www.readbyqxmd.com/read/29142109/the-ndc80-complex-targets-bod1-to-human-mitotic-kinetochores
#1
Katharina Schleicher, Michael Porter, Sara Ten Have, Ramasubramanian Sundaramoorthy, Iain M Porter, Jason R Swedlow
Regulation of protein phosphatase activity by endogenous protein inhibitors is an important mechanism to control protein phosphorylation in cells. We recently identified Biorientation defective 1 (Bod1) as a small protein inhibitor of protein phosphatase 2A containing the B56 regulatory subunit (PP2A-B56). This phosphatase controls the amount of phosphorylation of several kinetochore proteins and thus the establishment of load-bearing chromosome-spindle attachments in time for accurate separation of sister chromatids in mitosis...
November 2017: Open Biology
https://www.readbyqxmd.com/read/29142108/growth-and-size-control-during-development
#2
REVIEW
Jannik Vollmer, Fernando Casares, Dagmar Iber
The size and shape of organs are characteristic for each species. Even when organisms develop to different sizes due to varying environmental conditions, such as nutrition, organ size follows species-specific rules of proportionality to the rest of the body, a phenomenon referred to as allometry. Therefore, for a given environment, organs stop growth at a predictable size set by the species's genotype. How do organs stop growth? How can related species give rise to organs of strikingly different size? No definitive answer has been given to date...
November 2017: Open Biology
https://www.readbyqxmd.com/read/29142107/is-inflammatory-micronucleation-the-key-to-a-successful-anti-mitotic-cancer-drug
#3
REVIEW
T J Mitchison, J Pineda, J Shi, S Florian
Paclitaxel is a successful anti-cancer drug that kills cancer cells in two-dimensional culture through perturbation of mitosis, but whether it causes tumour regression by anti-mitotic actions is controversial. Drug candidates that specifically target mitosis, including inhibitors of kinesin-5, AurkA, AurkB and Plk1, disappointed in the clinic. Current explanations for this discrepancy include pharmacokinetic differences and hypothetical interphase actions of paclitaxel. Here, we discuss post-mitotic micronucleation as a special activity of taxanes that might explain their higher activity in solid tumours...
November 2017: Open Biology
https://www.readbyqxmd.com/read/29142106/soluble-a%C3%AE-aggregates-can-inhibit-prion-propagation
#4
Claire J Sarell, Emma Quarterman, Daniel C-M Yip, Cassandra Terry, Andrew J Nicoll, Jonathan D F Wadsworth, Mark A Farrow, Dominic M Walsh, John Collinge
Mammalian prions cause lethal neurodegenerative diseases such as Creutzfeldt-Jakob disease (CJD) and consist of multi-chain assemblies of misfolded cellular prion protein (PrP(C)). Ligands that bind to PrP(C) can inhibit prion propagation and neurotoxicity. Extensive prior work established that certain soluble assemblies of the Alzheimer's disease (AD)-associated amyloid β-protein (Aβ) can tightly bind to PrP(C), and that this interaction may be relevant to their toxicity in AD. Here, we investigated whether such soluble Aβ assemblies might, conversely, have an inhibitory effect on prion propagation...
November 2017: Open Biology
https://www.readbyqxmd.com/read/29142105/the-nde1-genomic-locus-can-affect-treatment-of-psychiatric-illness-through-gene-expression-changes-related-to-microrna-484
#5
Nicholas J Bradshaw, Liisa Ukkola-Vuoti, Maiju Pankakoski, Amanda B Zheutlin, Alfredo Ortega-Alonso, Minna Torniainen-Holm, Vishal Sinha, Sebastian Therman, Tiina Paunio, Jaana Suvisaari, Jouko Lönnqvist, Tyrone D Cannon, Jari Haukka, William Hennah
Genetic studies of familial schizophrenia in Finland have observed significant associations with a group of biologically related genes, DISC1, NDE1, NDEL1, PDE4B and PDE4D, the 'DISC1 network'. Here, we use gene expression and psychoactive medication use data to study their biological consequences and potential treatment implications. Gene expression levels were determined in 64 individuals from 18 families, while prescription medication information has been collected over a 10-year period for 931 affected individuals...
November 2017: Open Biology
https://www.readbyqxmd.com/read/29142104/constraints-on-lateral-gene-transfer-in-promoting-fimbrial-usher-protein-diversity-and-function
#6
Christopher J Stubenrauch, Gordon Dougan, Trevor Lithgow, Eva Heinz
Fimbriae are long, adhesive structures widespread throughout members of the family Enterobacteriaceae. They are multimeric extrusions, which are moved out of the bacterial cell through an integral outer membrane protein called usher. The complex folding mechanics of the usher protein were recently revealed to be catalysed by the membrane-embedded translocation and assembly module (TAM). Here, we examine the diversity of usher proteins across a wide range of extraintestinal (ExPEC) and enteropathogenic (EPEC) Escherichia coli, and further focus on a so far undescribed chaperone-usher system, with this usher referred to as UshC...
November 2017: Open Biology
https://www.readbyqxmd.com/read/29118273/correction-to-interactions-of-the-bacillus-subtilis-dnae-polymerase-with-replisomal-proteins-modulate-its-activity-and-fidelity
#7
Vasileios Paschalis, Emmanuelle Le Chatelier, Matthew Green, François Képès, Panos Soultanas, Laurent Janniere
No abstract text is available yet for this article.
November 2017: Open Biology
https://www.readbyqxmd.com/read/29118272/beyond-cancer-genes-colorectal-cancer-as-robust-intrinsic-states-formed-by-molecular-interactions
#8
Ruoshi Yuan, Suzhan Zhang, Jiekai Yu, Yanqin Huang, Demin Lu, Runtan Cheng, Sui Huang, Ping Ao, Shu Zheng, Leroy Hood, Xiaomei Zhu
Colorectal cancer (CRC) has complex pathological features that defy the linear-additive reasoning prevailing in current biomedicine studies. In pursuing a mechanistic understanding behind such complexity, we constructed a core molecular-cellular interaction network underlying CRC and investigated its nonlinear dynamical properties. The hypothesis and modelling method has been developed previously and tested in various cancer studies. The network dynamics reveal a landscape of several attractive basins corresponding to both normal intestinal phenotype and robust tumour subtypes, identified by their different molecular signatures...
November 2017: Open Biology
https://www.readbyqxmd.com/read/29118271/heparin-bound-chemokine-cxcl8-monomer-and-dimer-are-impaired-for-cxcr1-and-cxcr2-activation-implications-for-gradients-and-neutrophil-trafficking
#9
Prem Raj B Joseph, Kirti V Sawant, Krishna Rajarathnam
Chemokine CXCL8 plays a pivotal role in host immune response by recruiting neutrophils to the infection site. CXCL8 exists as monomers and dimers, and mediates recruitment by interacting with glycosaminoglycans (GAGs) and activating CXCR1 and CXCR2 receptors. How CXCL8 monomer and dimer interactions with both receptors and GAGs mediate trafficking is poorly understood. In particular, both haptotactic (mediated by GAG-bound chemokine) and chemotactic (mediated by soluble chemokine) gradients have been implicated, and whether it is the free or the GAG-bound CXCL8 monomer and/or dimer that activates the receptor remains unknown...
November 2017: Open Biology
https://www.readbyqxmd.com/read/29118270/upregulation-of-pir-gene-expression-induced-by-human-papillomavirus-e6-and-e7-in-epithelial-oral-and-cervical-cells
#10
Diego Carrillo, Juan P Muñoz, Hernán Huerta, Gabriel Leal, Alejandro Corvalán, Oscar León, Gloria M Calaf, Ulises Urzúa, Enrique Boccardo, Julio C Tapia, Francisco Aguayo
The hallmark of high-risk human papillomavirus (HR-HPV)-related carcinogenesis is E6 and E7 oncogene overexpression. The aim of this work was to characterize epithelial oral and cervical cancer cells that express HR-HPV E6 and E7 oncoproteins. Transcriptomic assay using DNA microarrays revealed that PIR gene expression was detected in oral cells in an HR-HPV E6/E7-dependent manner. In addition, PIR was overexpressed in HPV-positive SiHa and Ca Ski cells, whereas it was undetectable in HPV-negative C33A cells...
November 2017: Open Biology
https://www.readbyqxmd.com/read/29118269/genetic-architecture-and-regulatory-impact-on-hepatic-microrna-expression-linked-to-immune-and-metabolic-traits
#11
Siriluck Ponsuksili, Nares Trakooljul, Frieder Hadlich, Fiete Haack, Eduard Murani, Klaus Wimmers
Regulation of microRNA (miRNA) expression contributes to a wide range of target gene expression and phenotypes. The miRNA expression in the liver, the central metabolic organ, was examined in 209 pigs, and integrated with haematological and clinical biomarkers of metabolic and overall health, mRNA-target expression levels and single-nucleotide polymorphism (SNP) genotypes. The expression levels of 426 miRNA species correlated with plasma haematological or biochemical traits (r² = |0.19-0.45|, false discovery rate < 5%)...
November 2017: Open Biology
https://www.readbyqxmd.com/read/29093212/legionella-pneumophila-csra-regulates-a-metabolic-switch-from-amino-acid-to-glycerolipid-metabolism
#12
Ina Häuslein, Tobias Sahr, Pedro Escoll, Nadine Klausner, Wolfgang Eisenreich, Carmen Buchrieser
Legionella pneumophila CsrA plays a crucial role in the life-stage-specific expression of virulence phenotypes and metabolic activity. However, its exact role is only partly known. To elucidate how CsrA impacts L. pneumophila metabolism we analysed the CsrA depended regulation of metabolic functions by comparative (13)C-isotopologue profiling and oxygen consumption experiments of a L. pneumophila wild-type (wt) strain and its isogenic csrA(-) mutant. We show that a csrA(-) mutant has significantly lower respiration rates when serine, alanine, pyruvate, α-ketoglutarate or palmitate is the sole carbon source...
November 2017: Open Biology
https://www.readbyqxmd.com/read/29093211/cellular-v-atpase-is-required-for-virion-assembly-compartment-formation-in-human-cytomegalovirus-infection
#13
Jonathan Pavelin, Dominique McCormick, Stephen Chiweshe, Saranya Ramachandran, Yao-Tang Lin, Finn Grey
Successful generation of virions from infected cells is a complex process requiring orchestrated regulation of host and viral genes. Cells infected with human cytomegalovirus (HCMV) undergo a dramatic reorganization of membrane organelles resulting in the formation of the virion assembly compartment, a process that is not fully understood. Here we show that acidification of vacuoles by the cellular v-ATPase is a crucial step in the formation of the virion assembly compartment and disruption of acidification results in mis-localization of virion components and a profound reduction in infectious virus levels...
November 2017: Open Biology
https://www.readbyqxmd.com/read/29093210/statistical-methods-to-detect-pleiotropy-in-human-complex-traits
#14
REVIEW
Sophie Hackinger, Eleftheria Zeggini
In recent years pleiotropy, the phenomenon of one genetic locus influencing several traits, has become a widely researched field in human genetics. With the increasing availability of genome-wide association study summary statistics, as well as the establishment of deeply phenotyped sample collections, it is now possible to systematically assess the genetic overlap between multiple traits and diseases. In addition to increasing power to detect associated variants, multi-trait methods can also aid our understanding of how different disorders are aetiologically linked by highlighting relevant biological pathways...
November 2017: Open Biology
https://www.readbyqxmd.com/read/29070612/predicting-virus-emergence-amid-evolutionary-noise
#15
REVIEW
Jemma L Geoghegan, Edward C Holmes
The study of virus disease emergence, whether it can be predicted and how it might be prevented, has become a major research topic in biomedicine. Here we show that efforts to predict disease emergence commonly conflate fundamentally different evolutionary and epidemiological time scales, and are likely to fail because of the enormous number of unsampled viruses that could conceivably emerge in humans. Although we know much about the patterns and processes of virus evolution on evolutionary time scales as depicted in family-scale phylogenetic trees, these data have little predictive power to reveal the short-term microevolutionary processes that underpin cross-species transmission and emergence...
October 2017: Open Biology
https://www.readbyqxmd.com/read/29070611/solution-structure-of-cxcl13-and-heparan-sulfate-binding-show-that-gag-binding-site-and-cellular-signalling-rely-on-distinct-domains
#16
Yoan R Monneau, Lingjie Luo, Nehru Viji Sankaranarayanan, Balaji Nagarajan, Romain R Vivès, Françoise Baleux, Umesh R Desai, Fernando Arenzana-Seidedos, Hugues Lortat-Jacob
Chemokines promote directional cell migration through binding to G-protein-coupled receptors, and as such are involved in a large array of developmental, homeostatic and pathological processes. They also interact with heparan sulfate (HS), the functional consequences of which depend on the respective location of the receptor- and the HS-binding sites, a detail that remains elusive for most chemokines. Here, to set up a biochemical framework to investigate how HS can regulate CXCL13 activity, we solved the solution structure of CXCL13...
October 2017: Open Biology
https://www.readbyqxmd.com/read/29070610/mitochondrial-determinants-of-mammalian-longevity
#17
Yasuhiro Kitazoe, Masami Hasegawa, Masashi Tanaka, Midori Futami, Junichiro Futami
Current ageing theories are far from satisfactory because of the many determinants involved in ageing. The well-known rate-of-living theory assumes that the product (lifetime energy expenditure, LEE) of maximum lifespan (MLS) and mass-specific basal metabolic rate (msBMR) is approximately constant. Although this theory provides a significant inverse correlation between msBMR and MLS as a whole for mammals, it remains problematic for two reasons. First, several interspecies studies within respective orders (typically within rodents) have shown no inverse relationships between msBMR and MLS...
October 2017: Open Biology
https://www.readbyqxmd.com/read/29021216/multiple-interactions-are-involved-in-a-highly-specific-association-of-the-mod-mdg4-67-2-isoform-with-the-su-hw-sites-in-drosophila
#18
Larisa Melnikova, Margarita Kostyuchenko, Varvara Molodina, Alexander Parshikov, Pavel Georgiev, Anton Golovnin
The best-studied Drosophila insulator complex consists of two BTB-containing proteins, the Mod(mdg4)-67.2 isoform and CP190, which are recruited to the chromatin through interactions with the DNA-binding Su(Hw) protein. It was shown previously that Mod(mdg4)-67.2 is critical for the enhancer-blocking activity of the Su(Hw) insulators and it differs from more than 30 other Mod(mdg4) isoforms by the C-terminal domain required for a specific interaction with Su(Hw) only. The mechanism of the highly specific association between Mod(mdg4)-67...
October 2017: Open Biology
https://www.readbyqxmd.com/read/29021215/dual-role-of-the-chromatin-binding-factor-phf13-in-the-pre-and-post-integration-phases-of-hiv-1-replication
#19
Stephan Hofmann, Sandra Dehn, Ramona Businger, Sebastian Bolduan, Martha Schneider, Zeger Debyser, Ruth Brack-Werner, Michael Schindler
Viruses interact with multiple host cell factors. Some of these are required to promote viral propagation, others have roles in inhibiting infection. Here, we delineate the function of the cellular factor PHF13 (or SPOC1), a putative HIV-1 restriction factor. Early in the HIV-1 replication cycle PHF13 increased the number of integrated proviral copies and the number of infected cells. However, after HIV-1 integration, high levels of PHF13 suppressed viral gene expression. The antiviral activity of PHF13 is counteracted by the viral accessory protein Vpr, which mediates PHF13 degradation...
October 2017: Open Biology
https://www.readbyqxmd.com/read/29021214/casein-kinase-ii-phosphorylation-of-cyclin-f-at-serine-621-regulates-the-lys48-ubiquitylation-e3-ligase-activity-of-the-scf-cyclin-f-complex
#20
Albert Lee, Stephanie L Rayner, Alana De Luca, Serene S L Gwee, Marco Morsch, Vinod Sundaramoorthy, Hamideh Shahheydari, Audrey Ragagnin, Bingyang Shi, Shu Yang, Kelly L Williams, Emily K Don, Adam K Walker, Katharine Y Zhang, Justin J Yerbury, Nicholas J Cole, Julie D Atkin, Ian P Blair, Mark P Molloy, Roger S Chung
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that is characterized by progressive weakness, paralysis and muscle loss often resulting in patient death within 3-5 years of diagnosis. Recently, we identified disease-linked mutations in the CCNF gene, which encodes the cyclin F protein, in cohorts of patients with familial and sporadic ALS and frontotemporal dementia (FTD) (Williams KL et al 2016 Nat. Commun.7, 11253. (doi:10.1038/ncomms11253)). Cyclin F is a part of a Skp1-Cul-F-box (SCF) E3 ubiquitin-protein ligase complex and is responsible for ubiquitylating proteins for degradation by the proteasome...
October 2017: Open Biology
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