TY  - JOUR
A1  - Muthalagu, Nathiya
A1  - Junttila, Melissa R.
A1  - Wiese, Kathrin E.
A1  - Wolf, Elmar
A1  - Morton, Jennifer
A1  - Bauer, Barbara
A1  - Evan, Gerard I.
A1  - Eilers, Martin
A1  - Murphy, Daniel J.
T1  - BIM Is the Primary Mediator of MYC-Induced Apoptosis in Multiple Solid Tissues
JF  - Cell Reports
N2  - MYC is one of the most frequently overexpressed oncogenes in human cancer, and even modestly deregulated MYC can initiate ectopic proliferation in many postmitotic cell types in vivo. Sensitization of cells to apoptosis limits MYC's oncogenic potential. However, the mechanism through which MYC induces apoptosis is controversial. Some studies implicate p19ARF-mediated stabilization of p53, followed by induction of proapoptotic BH3 proteins NOXA and PUMA, whereas others argue for direct regulation of BH3 proteins, especially BIM. Here, we use a single experimental system to systematically evaluate the roles of p19ARF and BIM during MYC-induced apoptosis, in vitro, in vivo, and in combination with a widely used chemotherapeutic, doxorubicin. We find a common specific requirement for BIM during MYC-induced apoptosis in multiple settings, which does not extend to the p53-responsive BH3 family member PUMA, and find no evidence of a role for p19ARF during MYC-induced apoptosis in the tissues examined.
KW  - ARF tumor-suppressor induced lymphomagenes
KW  - BCL-X-L P53
KW  - C-MYC PUMA
KW  - in-vivo expression
KW  - cell-cycle arrest cancer therapy
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115370
VL  - 8
IS  - 5
ER  - 
TY  - JOUR
A1  - Pamir, Evren
A1  - Szyszka, Paul
A1  - Scheiner, Ricarda
A1  - Nawrot, Martin P.
T1  - Rapid learning dynamics in individual honeybees during classical conditioning
JF  - Frontiers in Behavioral Neuroscience
N2  - Associative learning in insects has been studied extensively by a multitude of classical conditioning protocols. However, so far little emphasis has been put on the dynamics of learning in individuals. The honeybee is a well-established animal model for learning and memory. We here studied associative learning as expressed in individual behavior based on a large collection of data on olfactory classical conditioning (25 datasets, 3298 animals). We show that the group-averaged learning curve and memory retention score confound three attributes of individual learning: the ability or inability to learn a given task, the generally fast acquisition of a conditioned response (CR) in learners, and the high stability of the CR during consecutive training and memory retention trials. We reassessed the prevailing view that more training results in better memory performance and found that 24 h memory retention can be indistinguishable after single-trial and multiple-trial conditioning in individuals. We explain how inter-individual differences in learning can be accommodated within the Rescorla Wagner theory of associative learning. In both data-analysis and modeling we demonstrate how the conflict between population-level and single-animal perspectives on learning and memory can be disentangled.
KW  - sucrose sensitivity
KW  - sucrose responsiveness
KW  - learning curve
KW  - bees
KW  - apis mellifera
KW  - single-trial learning
KW  - classical conditioning
KW  - Rescorla-Wagner model
KW  - proboscis extension response (PER)
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115365
SN  - 1662-5153
VL  - 8
IS  - 313
ER  - 
TY  - JOUR
A1  - Stellamanns, Eric
A1  - Uppaluri, Sravanti
A1  - Hochstetter, Axel
A1  - Heddergott, Niko
A1  - Engstler, Markus
A1  - Pfohl, Thomas
T1  - Optical trapping reveals propulsion forces, power generation and motility efficiency of the unicellular parasites Trypanosoma brucei brucei
JF  - Scientific Reports
N2  - Unicellular parasites have developed sophisticated swimming mechanisms to survive in a wide range of environments. Cell motility of African trypanosomes, parasites responsible for fatal illness in humans and animals, is crucial both in the insect vector and the mammalian host. Using millisecond-scale imaging in a microfluidics platform along with a custom made optical trap, we are able to confine single cells to study trypanosome motility. From the trapping characteristics of the cells, we determine the propulsion force generated by cells with a single flagellum as well as of dividing trypanosomes with two fully developed flagella. Estimates of the dissipative energy and the power generation of single cells obtained from the motility patterns of the trypanosomes within the optical trap indicate that specific motility characteristics, in addition to locomotion, may be required for antibody clearance. Introducing a steerable second optical trap we could further measure the force, which is generated at the flagellar tip. Differences in the cellular structure of the trypanosomes are correlated with the trapping and motility characteristics and in consequence with their propulsion force, dissipative energy and power generation.
KW  - African Trypanosomes
KW  - components
KW  - bacteria
KW  - brain
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115348
SN  - 2045-2322
VL  - 4
IS  - 6515
ER  - 
TY  - JOUR
A1  - Bensaad, Karim
A1  - Favaro, Elena
A1  - Lewis, Caroline A.
A1  - Peck, Barrie
A1  - Lord, Simon
A1  - Collins, Jennifer M.
A1  - Pinnick, Katherine E.
A1  - Wigfield, Simon
A1  - Buffa, Francesca M.
A1  - Li, Ji-Liang
A1  - Zhang, Qifeng
A1  - Wakelam, Michael J. O.
A1  - Karpe, Fredrik
A1  - Schulze, Almut
A1  - Harris, Adrian L.
T1  - Fatty Acid Uptake and Lipid Storage Induced by HIF-1 alpha Contribute to Cell Growth and Survival after Hypoxia-Reoxygenation
JF  - Cell Reports
N2  - An in vivo model of antiangiogenic therapy allowed us to identify genes upregulated by bevacizumab treatment, including Fatty Acid Binding Protein 3 (FABP3) and FABP7, both of which are involved in fatty acid uptake. In vitro, both were induced by hypoxia in a hypoxia-inducible factor-1 alpha (HIF-1 alpha)-dependent manner. There was a significant lipid droplet (LD) accumulation in hypoxia that was time and O-2 concentration dependent. Knockdown of endogenous expression of FABP3, FABP7, or Adipophilin (an essential LD structural component) significantly impaired LD formation under hypoxia. We showed that LD accumulation is due to FABP3/7-dependent fatty acid uptake while de novo fatty acid synthesis is repressed in hypoxia. We also showed that ATP production occurs via beta-oxidation or glycogen degradation in a cell-type-dependent manner in hypoxia-reoxygenation. Finally, inhibition of lipid storage reduced protection against reactive oxygen species toxicity, decreased the survival of cells subjected to hypoxia-reoxygenation in vitro, and strongly impaired tumorigenesis in vivo.
KW  - inducible factor-I
KW  - binding protein
KW  - triglyceride accumulation
KW  - cancer cell
KW  - complex-III
KW  - beta-oxidation
KW  - metabolism
KW  - lipogenesis
KW  - proliferation
KW  - resistance
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115162
SN  - 2211-1247
VL  - 9
IS  - 1
ER  - 
TY  - JOUR
A1  - Akhoon, Bashir A.
A1  - Singh, Krishna P.
A1  - Varshney, Megha
A1  - Gupta, Shishir K.
A1  - Shukla, Yogeshwar
A1  - Gupta, Shailendra K.
T1  - Understanding the Mechanism of Atovaquone Drug Resistance in Plasmodium falciparum Cytochrome b Mutation Y268S Using Computational Methods
JF  - PLOS ONE
N2  - The rapid appearance of resistant malarial parasites after introduction of atovaquone (ATQ) drug has prompted the search for new drugs as even single point mutations in the active site of Cytochrome b protein can rapidly render ATQ ineffective. The presence of Y268 mutations in the Cytochrome b (Cyt b) protein is previously suggested to be responsible for the ATQ resistance in Plasmodium falciparum (P. falciparum). In this study, we examined the resistance mechanism against ATQ in P. falciparum through computational methods. Here, we reported a reliable protein model of Cyt bc1 complex containing Cyt b and the Iron-Sulphur Protein (ISP) of P. falciparum using composite modeling method by combining threading, ab initio modeling and atomic-level structure refinement approaches. The molecular dynamics simulations suggest that Y268S mutation causes ATQ resistance by reducing hydrophobic interactions between Cyt bc1 protein complex and ATQ. Moreover, the important histidine contact of ATQ with the ISP chain is also lost due to Y268S mutation. We noticed the induced mutation alters the arrangement of active site residues in a fashion that enforces ATQ to find its new stable binding site far away from the wild-type binding pocket. The MM-PBSA calculations also shows that the binding affinity of ATQ with Cyt bc1 complex is enough to hold it at this new site that ultimately leads to the ATQ resistance.
KW  - molecular-dynamics simulations
KW  - HIV-1 protease
KW  - structure prediction
KW  - saccharomyces cerevisiae
KW  - I-tasser
KW  - inhibitors
KW  - binding
KW  - malaria
KW  - complex
KW  - protein-protein interactions
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-114882
VL  - 9
IS  - 10
ER  - 
TY  - JOUR
A1  - Senecal, Jean-Luc
A1  - Isabelle, Catherine
A1  - Fritzler, Marvin J.
A1  - Targoff, Ira N.
A1  - Goldstein, Rose
A1  - Gagne, Michel
A1  - Raynauld, Jean-Pierre
A1  - Joyal, France
A1  - Troyanov, Yves
A1  - Dabauvalle, Marie-Christine
T1  - An Autoimmune Myositis-Overlap Syndrome Associated With Autoantibodies to Nuclear Pore Complexes Description and Long-Term Follow-up of the Anti-Nup Syndrome
JF  - Medicine
N2  - Autoimmune myositis encompasses various myositis-overlap syndromes, each being identified by the presence of serum marker autoantibodies. We describe a novel myositis-overlap syndrome in 4 patients characterized by the presence of a unique immunologic marker, autoantibodies to nuclear pore complexes. The clinical phenotype was characterized by prominent myositis in association with erosive, anti-CCP, and rheumatoid factor-positive arthritis, trigeminal neuralgia, mild interstitial lung disease, Raynaud phenomenon, and weight loss. The myositis was typically chronic, relapsing, and refractory to corticosteroids alone, but remitted with the addition of a second immuno-modulating drug. There was no clinical or laboratory evidence for liver disease. The prognosis was good with 100% long-term survival (mean follow-up 19.5 yr). By indirect immunofluorescence on HEp-2 cells, sera from all 4 patients displayed a high titer of antinuclear autoantibodies (ANA) with a distinct punctate peripheral (rim) fluorescent pattern of the nuclear envelope characteristic of nuclear pore complexes. Reactivity with nuclear pore complexes was confirmed by immunoelectron microscopy. In a cohort of 100 French Canadian patients with autoimmune myositis, the nuclear pore complex fluorescent ANA pattern was restricted to these 4 patients (4%). It was not observed in sera from 393 adult patients with systemic sclerosis (n = 112), mixed connective tissue disease (n = 35), systemic lupus (n = 94), rheumatoid arthritis (n = 45), or other rheumatic diseases (n = 107), nor was it observed in 62 normal adults. Autoantibodies to nuclear pore complexes were predominantly of IgG isotype. No other IgG autoantibody markers for defined connective tissue diseases or overlap syndromes were present, indicating a selective and highly focused immune response. In 3 patients, anti-nuclear pore complex autoantibody titers varied in parallel with myositis activity, suggesting a pathogenic link to pathophysiology. The nuclear pore complex proteins, that is, nucleoporins (nup), recognized by these sera were heterogeneous and included Nup358/RanBP2 (n = 2 patients), Nup90 (n = 1), Nup62 (n = 1), and gp210 (n = 1). Taken together the data suggest that nup autoantigens themselves drive the anti-nup autoimmune response. Immunogenetically, the 4 patients shared the DQA1*0501 allele associated with an increased risk for autoimmune myositis. In conclusion, we report an apparent novel subset of autoimmune myositis in our population of French Canadian patients with connective tissue diseases. This syndrome is recognized by the presence of a unique immunologic marker, autoantibodies to nuclear pore complexes that react with nups, consistent with an "anti-nupsyndrome.''
KW  - idiopathic inflammatory myopathies
KW  - primary biliary-cirrhosis
KW  - transfer RNA-synthetases
KW  - major histocompatibility complex
KW  - systemic sclerosis
KW  - French-Canadian patients
KW  - protein
KW  - predictive factors
KW  - envelope
KW  - antibodies
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-114829
SN  - 0025-7974
VL  - 93
IS  - 24
ER  - 
TY  - JOUR
A1  - Hudson, Lawrence N.
A1  - Newbold, Tim
A1  - Contu, Sara
A1  - Hill, Samantha L. L.
A1  - Lysenko, Igor
A1  - De Palma, Adriana
A1  - Phillips, Helen R. P.
A1  - Senior, Rebecca A.
A1  - Bennett, Dominic J.
A1  - Booth, Hollie
A1  - Choimes, Argyrios
A1  - Correia, David L. P.
A1  - Day, Julie
A1  - Echeverria-Londono, Susy
A1  - Garon, Morgan
A1  - Harrison, Michelle L. K.
A1  - Ingram, Daniel J.
A1  - Jung, Martin
A1  - Kemp, Victoria
A1  - Kirkpatrick, Lucinda
A1  - Martin, Callum D.
A1  - Pan, Yuan
A1  - White, Hannah J.
A1  - Aben, Job
A1  - Abrahamczyk, Stefan
A1  - Adum, Gilbert B.
A1  - Aguilar-Barquero, Virginia
A1  - Aizen, Marcelo
A1  - Ancrenaz, Marc
A1  - Arbelaez-Cortes, Enrique
A1  - Armbrecht, Inge
A1  - Azhar, Badrul
A1  - Azpiroz, Adrian B.
A1  - Baeten, Lander
A1  - Báldi, András
A1  - Banks, John E.
A1  - Barlow, Jos
A1  - Batáry, Péter
A1  - Bates, Adam J.
A1  - Bayne, Erin M.
A1  - Beja, Pedro
A1  - Berg, Ake
A1  - Berry, Nicholas J.
A1  - Bicknell, Jake E.
A1  - Bihn, Jochen H.
A1  - Böhning-Gaese, Katrin
A1  - Boekhout, Teun
A1  - Boutin, Celine
A1  - Bouyer, Jeremy
A1  - Brearley, Francis Q.
A1  - Brito, Isabel
A1  - Brunet, Jörg
A1  - Buczkowski, Grzegorz
A1  - Buscardo, Erika
A1  - Cabra-Garcia, Jimmy
A1  - Calvino-Cancela, Maria
A1  - Cameron, Sydney A.
A1  - Cancello, Eliana M.
A1  - Carrijo, Tiago F.
A1  - Carvalho, Anelena L.
A1  - Castro, Helena
A1  - Castro-Luna, Alejandro A.
A1  - Cerda, Rolando
A1  - Cerezo, Alexis
A1  - Chauvat, Matthieu
A1  - Clarke, Frank M.
A1  - Cleary, Daniel F. R.
A1  - Connop, Stuart P.
A1  - D'Aniello, Biagio
A1  - da Silva, Pedro Giovani
A1  - Darvill, Ben
A1  - Dauber, Jens
A1  - Dejean, Alain
A1  - Diekötter, Tim
A1  - Dominguez-Haydar, Yamileth
A1  - Dormann, Carsten F.
A1  - Dumont, Bertrand
A1  - Dures, Simon G.
A1  - Dynesius, Mats
A1  - Edenius, Lars
A1  - Elek, Zoltán
A1  - Entling, Martin H.
A1  - Farwig, Nina
A1  - Fayle, Tom M.
A1  - Felicioli, Antonio
A1  - Felton, Annika M.
A1  - Ficetola, Gentile F.
A1  - Filgueiras, Bruno K. C.
A1  - Fonte, Steve J.
A1  - Fraser, Lauchlan H.
A1  - Fukuda, Daisuke
A1  - Furlani, Dario
A1  - Ganzhorn, Jörg U.
A1  - Garden, Jenni G.
A1  - Gheler-Costa, Carla
A1  - Giordani, Paolo
A1  - Giordano, Simonetta
A1  - Gottschalk, Marco S.
A1  - Goulson, Dave
A1  - Gove, Aaron D.
A1  - Grogan, James
A1  - Hanley, Mick E.
A1  - Hanson, Thor
A1  - Hashim, Nor R.
A1  - Hawes, Joseph E.
A1  - Hébert, Christian
A1  - Helden, Alvin J.
A1  - Henden, John-André
A1  - Hernández, Lionel
A1  - Herzog, Felix
A1  - Higuera-Diaz, Diego
A1  - Hilje, Branko
A1  - Horgan, Finbarr G.
A1  - Horváth, Roland
A1  - Hylander, Kristoffer
A1  - Horváth, Roland
A1  - Isaacs-Cubides, Paola
A1  - Ishitani, Mashiro
A1  - Jacobs, Carmen T.
A1  - Jaramillo, Victor J.
A1  - Jauker, Birgit
A1  - Jonsell, Matts
A1  - Jung, Thomas S.
A1  - Kapoor, Vena
A1  - Kati, Vassiliki
A1  - Katovai, Eric
A1  - Kessler, Michael
A1  - Knop, Eva
A1  - Kolb, Annette
A1  - Körösi, Àdám
A1  - Lachat, Thibault
A1  - Lantschner, Victoria
A1  - Le Féon, Violette
A1  - LeBuhn, Gretchen
A1  - Légaré, Jean-Philippe
A1  - Letcher, Susan G.
A1  - Littlewood, Nick A.
A1  - López-Quintero, Carlos A.
A1  - Louhaichi, Mounir
A1  - Lövei, Gabor L.
A1  - Lucas-Borja, Manuel Esteban
A1  - Luja, Victor H.
A1  - Maeto, Kaoru
A1  - Magura, Tibor
A1  - Mallari, Neil Aldrin
A1  - Marin-Spiotta, Erika
A1  - Marhall, E. J. P.
A1  - Martínez, Eliana
A1  - Mayfield, Margaret M.
A1  - Mikusinski, Gregorz
A1  - Milder, Jeffery C.
A1  - Miller, James R.
A1  - Morales, Carolina L.
A1  - Muchane, Mary N.
A1  - Muchane, Muchai
A1  - Naidoo, Robin
A1  - Nakamura, Akihiro
A1  - Naoe, Shoji
A1  - Nates-Parra, Guiomar
A1  - Navarerete Gutierrez, Dario A.
A1  - Neuschulz, Eike L.
A1  - Noreika, Norbertas
A1  - Norfolk, Olivia
A1  - Noriega, Jorge Ari
A1  - Nöske, Nicole M.
A1  - O'Dea, Niall
A1  - Oduro, William
A1  - Ofori-Boateng, Caleb
A1  - Oke, Chris O.
A1  - Osgathorpe, Lynne M.
A1  - Paritsis, Juan
A1  - Parrah, Alejandro
A1  - Pelegrin, Nicolás
A1  - Peres, Carlos A.
A1  - Persson, Anna S.
A1  - Petanidou, Theodora
A1  - Phalan, Ben
A1  - Philips, T. Keith
A1  - Poveda, Katja
A1  - Power, Eileen F.
A1  - Presley, Steven J.
A1  - Proença, Vânia
A1  - Quaranta, Marino
A1  - Quintero, Carolina
A1  - Redpath-Downing, Nicola A.
A1  - Reid, J. Leighton
A1  - Reis, Yana T.
A1  - Ribeiro, Danilo B.
A1  - Richardson, Barbara A.
A1  - Richardson, Michael J.
A1  - Robles, Carolina A.
A1  - Römbke, Jörg
A1  - Romero-Duque, Luz Piedad
A1  - Rosselli, Loreta
A1  - Rossiter, Stephen J.
A1  - Roulston, T'ai H.
A1  - Rousseau, Laurent
A1  - Sadler, Jonathan P.
A1  - Sáfián, Szbolcs
A1  - Saldaña-Vásquez, Romeo A.
A1  - Samnegård, Ulrika
A1  - Schüepp, Christof
A1  - Schweiger, Oliver
A1  - Sedlock, Jodi L.
A1  - Shahabuddin, Ghazala
A1  - Sheil, Douglas
A1  - Silva, Fernando A. B.
A1  - Slade, Eleanor
A1  - Smith-Pardo, Allan H.
A1  - Sodhi, Navjot S.
A1  - Somarriba, Eduardo J.
A1  - Sosa, Ramón A.
A1  - Stout, Jane C.
A1  - Struebig, Matthew J.
A1  - Sung, Yik-Hei
A1  - Threlfall, Caragh G.
A1  - Tonietto, Rebecca
A1  - Tóthmérész, Béla
A1  - Tscharntke, Teja
A1  - Turner, Edgar C.
A1  - Tylianakis, Jason M.
A1  - Vanbergen, Adam J.
A1  - Vassilev, Kiril
A1  - Verboven, Hans A. F.
A1  - Vergara, Carlos H.
A1  - Vergara, Pablo M.
A1  - Verhulst, Jort
A1  - Walker, Tony R.
A1  - Wang, Yanping
A1  - Watling, James I.
A1  - Wells, Konstans
A1  - Williams, Christopher D.
A1  - Willig, Michael R.
A1  - Woinarski, John C. Z.
A1  - Wolf, Jan H. D.
A1  - Woodcock, Ben A.
A1  - Yu, Douglas W.
A1  - Zailsev, Andreys
A1  - Collen, Ben
A1  - Ewers, Rob M.
A1  - Mace, Georgina M.
A1  - Purves, Drew W.
A1  - Scharlemann, Jörn P. W.
A1  - Pervis, Andy
T1  - The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts
JF  - Ecology and Evolution
N2  - Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - ). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
KW  - urban-rural gradient
KW  - instensively managed farmland
KW  - Mexican coffee plantations
KW  - Bombus Spp. Hymenoptera
KW  - bumblebee nest density
KW  - data sharing
KW  - land use
KW  - habitat destruction
KW  - global change
KW  - land-use change
KW  - plant community composition
KW  - Northeastern Costa Rica
KW  - dung beetle coleoptera
KW  - bird species richness
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-114425
VL  - 4
IS  - 24
ER  - 
TY  - JOUR
A1  - Rozycka, Miroslawa
A1  - Wojtas, Magdalena
A1  - Jakob, Michal
A1  - Stigloher, Christian
A1  - Grzeszkowiak, Mikolaj
A1  - Mazur, Maciej
A1  - Ozyhar, Andrzej
T1  - Intrinsically Disordered and Pliable Starmaker-Like Protein from Medaka (Oryzias latipes) Controls the Formation of Calcium Carbonate Crystals
JF  - PLOS ONE
N2  - Fish otoliths, biominerals composed of calcium carbonate with a small amount of organic matrix, are involved in the functioning of the inner ear. Starmaker (Stm) from zebrafish (Danio rerio) was the first protein found to be capable of controlling the formation of otoliths. Recently, a gene was identified encoding the Starmaker-like (Stm-l) protein from medaka (Oryzias latipes), a putative homologue of Stm and human dentine sialophosphoprotein. Although there is no sequence similarity between Stm-l and Stm, Stm-l was suggested to be involved in the biomineralization of otoliths, as had been observed for Stm even before. The molecular properties and functioning of Stm-l as a putative regulatory protein in otolith formation have not been characterized yet. A comprehensive biochemical and biophysical analysis of recombinant Stm-l, along with in silico examinations, indicated that Stm-l exhibits properties of a coil-like intrinsically disordered protein. Stm-l possesses an elongated and pliable structure that is able to adopt a more ordered and rigid conformation under the influence of different factors. An in vitro assay of the biomineralization activity of Stm-l indicated that Stm-l affected the size, shape and number of calcium carbonate crystals. The functional significance of intrinsically disordered properties of Stm-l and the possible role of this protein in controlling the formation of calcium carbonate crystals is discussed.
KW  - circular-dichroism
KW  - unstructured proteins
KW  - olyelectrolyte domains
KW  - modulating
KW  - biominarlization proteins
KW  - nacreous layer formation
KW  - alpha-helical structure
KW  - dye stains-all
KW  - polyelectrolyte domains
KW  - phosphorylation sites
KW  - procambarus-clarkii
KW  - secondary structure
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-114251
SN  - 1932-6203
VL  - 9
IS  - 12
ER  - 
TY  - JOUR
A1  - Remmele, Christian W.
A1  - Xian, Yibo
A1  - Albrecht, Marco
A1  - Faulstich, Michaela
A1  - Fraunholz, Martin
A1  - Heinrichs, Elisabeth
A1  - Dittrich, Marcus T.
A1  - Müller, Tobias
A1  - Reinhardt, Richard
A1  - Rudel, Thomas
T1  - Transcriptional landscape and essential genes of Neisseria gonorrhoeae
N2  - The WHO has recently classified Neisseria gonorrhoeae as a super-bacterium due to the rapid spread of antibiotic resistant derivatives and an overall dramatic increase in infection incidences. Genome sequencing has identified potential genes, however, little is known about the transcriptional organization and the presence of non-coding RNAs in gonococci. We performed RNA sequencing to define the transcriptome and the transcriptional start sites of all gonococcal genes and operons. Numerous new transcripts including 253 potentially non-coding RNAs transcribed from intergenic regions or antisense to coding genes were identified. Strikingly, strong antisense transcription was detected for the phase-variable opa genes coding for a family of adhesins and invasins in pathogenic Neisseria, that may have regulatory functions. Based on the defined transcriptional start sites, promoter motifs were identified. We further generated and sequenced a high density Tn5 transposon library to predict a core of 827 gonococcal essential genes, 133 of which have no known function. Our combined RNA-Seq and Tn-Seq approach establishes a detailed map of gonococcal genes and defines the first core set of essential gonococcal genes.
KW  - Neisseria gonorrhoeae
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-113676
ER  - 
TY  - JOUR
A1  - Linder, Bastian
A1  - Hirmer, Anja
A1  - Gal, Andreas
A1  - Rüther, Klaus
A1  - Bolz, Hanno Jörn
A1  - Winkler, Christoph
A1  - Laggerbauer, Bernhard
A1  - Fischer, Utz
T1  - Identification of a PRPF4 Loss-of-Function Variant That Abrogates U4/U6.U5 Tri-snRNP Integration and Is Associated with Retinitis Pigmentosa
N2  - Pre-mRNA splicing by the spliceosome is an essential step in the maturation of nearly all human mRNAs. Mutations in six spliceosomal proteins, PRPF3, PRPF4, PRPF6, PRPF8, PRPF31 and SNRNP200, cause retinitis pigmentosa (RP), a disease characterized by progressive photoreceptor degeneration. All splicing factors linked to RP are constituents of the U4/U6.U5 tri-snRNP subunit of the spliceosome, suggesting that the compromised function of this particle may lead to RP. Here, we report the identification of the p.R192H variant of the tri-snRNP factor PRPF4 in a patient with RP. The mutation affects a highly conserved arginine residue that is crucial for PRPF4 function. Introduction of a corresponding mutation into the zebrafish homolog of PRPF4 resulted in a complete loss of function in vivo. A series of biochemical experiments suggested that p.R192H disrupts the binding interface between PRPF4 and its interactor PRPF3. This interferes with the ability of PRPF4 to integrate into the tri-snRNP, as shown in a human cell line and in zebrafish embryos. These data suggest that the p.R192H variant of PRPF4 represents a functional null allele. The resulting haploinsufficiency of PRPF4 compromises the function of the tri-snRNP, reinforcing the notion that this spliceosomal particle is of crucial importance in the physiology of the retina.
KW  - zebrafish
KW  - embryos
KW  - immunoprecipitation
KW  - arginine
KW  - messenger RNA
KW  - spliceosomes
KW  - mutation
KW  - RNA splicing
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-113663
ER  -