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J Gsponer

Antonio N Calabrese, Scott M Jackson, Lynsey N Jones, Oliver Beckstein, Florian Heinkel, Joerg Gsponer, David Sharples, Marta Sans, Maria Kokkinidou, Arwen R Pearson, Sheena E Radford, Alison E Ashcroft, Peter J F Henderson
Cys accessibility and quantitative intact mass spectrometry (MS) analyses have been devised to study the topological transitions of Mhp1, the membrane protein for sodium-linked transport of hydantoins from Microbacterium liquefaciens. Mhp1 has been crystallized in three forms (outward-facing open, outward-facing occluded with substrate bound, and inward-facing open). We show that one natural cysteine residue, Cys327, out of three, has an enhanced solvent accessibility in the inward-facing (relative to the outward-facing) form...
September 5, 2017: Analytical Chemistry
D Juskevicius, T Lorber, J Gsponer, V Perrina, C Ruiz, F Stenner-Liewen, S Dirnhofer, A Tzankov
Recurrences of diffuse large B-cell lymphomas (DLBCL) result in significant morbidity and mortality, but their underlying genetic and biological mechanisms are unclear. Clonal relationship in DLBCL relapses so far is mostly addressed by the investigation of immunoglobulin (IG) rearrangements, therefore, lacking deeper insights into genome-wide lymphoma evolution. We studied mutations and copy number aberrations in 20 paired relapsing and 20 non-relapsing DLBCL cases aiming to test the clonal relationship between primaries and relapses to track tumors' genetic evolution and to investigate the genetic background of DLBCL recurrence...
December 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Nancy N Fang, Gerard T Chan, Mang Zhu, Sophie A Comyn, Avinash Persaud, Raymond J Deshaies, Daniela Rotin, Joerg Gsponer, Thibault Mayor
The heat-shock response is a complex cellular program that induces major changes in protein translation, folding and degradation to alleviate toxicity caused by protein misfolding. Although heat shock has been widely used to study proteostasis, it remained unclear how misfolded proteins are targeted for proteolysis in these conditions. We found that Rsp5 and its mammalian homologue Nedd4 are important E3 ligases responsible for the increased ubiquitylation induced by heat stress. We determined that Rsp5 ubiquitylates mainly cytosolic misfolded proteins upon heat shock for proteasome degradation...
December 2014: Nature Cell Biology
C Wetterauer, M Weibel, J R Gsponer, T Vlajnic, T Zellweger, S Bütikofer, G Müller, H Püschel, A Bachmann, T C Gasser, L Bubendorf, C A Rentsch
The reported incidental prostate cancer prevalence rates at radical cystoprostatectomy cover a range from 4 to 60 %. We investigated the influence of the histopathological work-up on prostate cancer prevalence rates. We identified 114 patients who had undergone cystoprostatectomy for bladder cancer between 2000 and 2012. Complete histopathological assessment was defined as follows: (i) complete embedding of the prostate gland, (ii) sectioning of 15 or more prostate sections, and (iii) processing as whole mount slides...
December 2014: Virchows Archiv: An International Journal of Pathology
Robin van der Lee, Marija Buljan, Benjamin Lang, Robert J Weatheritt, Gary W Daughdrill, A Keith Dunker, Monika Fuxreiter, Julian Gough, Joerg Gsponer, David T Jones, Philip M Kim, Richard W Kriwacki, Christopher J Oldfield, Rohit V Pappu, Peter Tompa, Vladimir N Uversky, Peter E Wright, M Madan Babu
No abstract text is available yet for this article.
July 9, 2014: Chemical Reviews
J R Gsponer, M Braun, V J Scheble, T Zellweger, A Bachmann, S Perner, T Vlajnic, M Srivastava, S H Tan, A Dobi, I A Sesterhenn, S Srivastava, L Bubendorf, C Ruiz
BACKGROUND: Approximately half of the prostate carcinomas are characterized by a chromosomal rearrangement fusing the androgen-regulated gene TMPRSS2 to the oncogenic ETS transcription factor ERG. Aim of this study was to comprehensively analyze the role and impact of the ERG rearrangement and protein expression on the progression to castration-resistant (CR) disease. METHODS: We used a tissue microarray (TMA) constructed from 114 hormone naive (HN) and 117 CR PCs...
June 2014: Prostate Cancer and Prostatic Diseases
Dorita Avila, Keri N Althoff, Catrina Mugglin, Kara Wools-Kaloustian, Manuel Koller, François Dabis, Denis Nash, Thomas Gsponer, Somnuek Sungkanuparph, Catherine McGowan, Margaret May, David Cooper, Cleophas Chimbetete, Marcelo Wolff, Ann Collier, Hamish McManus, Mary-Ann Davies, Dominique Costagliola, Brenda Crabtree-Ramirez, Romanee Chaiwarith, Angela Cescon, Morna Cornell, Lameck Diero, Praphan Phanuphak, Adrien Sawadogo, Jochen Ehmer, Serge P Eholie, Patrick C K Li, Matthew P Fox, Neel R Gandhi, Elsa González, Christopher K C Lee, Christopher J Hoffmann, Andrew Kambugu, Olivia Keiser, Rossana Ditangco, Hans Prozesky, Fiona Lampe, Nagalingeswaran Kumarasamy, Mari Kitahata, Emmanuel Lugina, Rita Lyamuya, Saphonn Vonthanak, Valeria Fink, Antonella d'Arminio Monforte, Paula Mendes Luz, Yi-Ming A Chen, Albert Minga, Jordi Casabona, Albert Mwango, Jun Y Choi, Marie-Louise Newell, Elizabeth A Bukusi, Kapella Ngonyani, Tuti P Merati, Juliana Otieno, Mwebesa B Bosco, Sam Phiri, Oon T Ng, Kathryn Anastos, Jürgen Rockstroh, Ignacio Santos, Shinichi Oka, Geoffrey Somi, Christoph Stephan, Ramon Teira, Deo Wabwire, Gilles Wandeler, Andrew Boulle, Peter Reiss, Robin Wood, Benjamin H Chi, Carolyn Williams, Jonathan A Sterne, Matthias Egger
OBJECTIVE: To describe the CD4 cell count at the start of combination antiretroviral therapy (cART) in low-income (LIC), lower middle-income (LMIC), upper middle-income (UMIC), and high-income (HIC) countries. METHODS: Patients aged 16 years or older starting cART in a clinic participating in a multicohort collaboration spanning 6 continents (International epidemiological Databases to Evaluate AIDS and ART Cohort Collaboration) were eligible. Multilevel linear regression models were adjusted for age, gender, and calendar year; missing CD4 counts were imputed...
January 1, 2014: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Gilles Wandeler, Florian Gerber, Julia Rohr, Benjamin H Chi, Catherine Orrell, Cleophas Chimbetete, Hans Prozesky, Andrew Boulle, Christopher J Hoffmann, Thomas Gsponer, Matthew P Fox, Marcel Zwahlen, Matthias Egger
BACKGROUND: There is debate over using tenofovir or zidovudine alongside lamivudine in second-line antiretroviral therapy (ART) following stavudine failure. We analysed outcomes in cohorts from South Africa, Zambia and Zimbabwe METHODS: Patients aged ≥16 years who switched from a first-line regimen including stavudine to a ritonavir-boosted lopinavir-based second-line regimen with lamivudine or emtricitabine and zidovudine or tenofovir in seven ART programmes in southern Africa were included...
2014: Antiviral Therapy
Dokyun Na, Mushfiqur Rouf, Cahir J O'Kane, David C Rubinsztein, Jörg Gsponer
BACKGROUND: Neurodegenerative diseases (NDs) are characterized by the progressive loss of neurons in the human brain. Although the majority of NDs are sporadic, evidence is accumulating that they have a strong genetic component. Therefore, significant efforts have been made in recent years to not only identify disease-causing genes but also genes that modify the severity of NDs, so-called genetic modifiers. To date there exists no compendium that lists and cross-links genetic modifiers of different NDs...
November 14, 2013: BMC Medical Genomics
Claudia Solis, Juan J Torres, Natalia Gsponer, Carlos Previtali, Rodrigo Palacios, Hernán Montejano, Carlos Chesta
We report herein a study on photoinduced electron transfer (eT) and energy transfer (ET) processes occurring between 9-methylanthracene-acrylate (A) and N,N-dimethylaniline-acrylate (D) derivatives incorporated into polymeric nanoparticles (NP). Five types of NPs were synthesized: PAD0, PAD25, PAD75, PD25, and PD75. All NPs are composed of a crosslinked polymer matrix of methyl methacrylate and ethylene glycol dimethacrylate. In addition, PAD0, PAD25 and PAD75 contain low doping levels of A. For PAD25 and PAD75, 25% and 75% of the mole fraction of methyl methacrylate is replaced by D, respectively...
December 2013: Photochemical & Photobiological Sciences
Anders R Kristensen, Joerg Gsponer, Leonard J Foster
External perturbations, by forcing cells to adapt to a new environment, often elicit large-scale changes in gene expression resulting in an altered proteome that improves the cell's fitness in the new conditions. Steady-state levels of a proteome depend on transcription, the levels of transcripts, translation and protein degradation but system-level contribution that each of these processes make to the final protein expression change has yet to be explored. We therefore applied a systems biology approach to characterize the regulation of protein expression during cellular differentiation using quantitative proteomics...
2013: Molecular Systems Biology
M Schomaker, T Gsponer, J Estill, M Fox, A Boulle
Loss to follow-up (LTFU) is a common problem in many epidemiological studies. In antiretroviral treatment (ART) programs for patients with human immunodeficiency virus (HIV), mortality estimates can be biased if the LTFU mechanism is non-ignorable, that is, mortality differs between lost and retained patients. In this setting, routine procedures for handling missing data may lead to biased estimates. To appropriately deal with non-ignorable LTFU, explicit modeling of the missing data mechanism is needed. This can be based on additional outcome ascertainment for a sample of patients LTFU, for example, through linkage to national registries or through survey-based methods...
January 15, 2014: Statistics in Medicine
Juan J Torres, Natalia Gsponer, Cristina L Ramírez, D Mariano A Vera, Hernán A Montejano, Carlos A Chesta
A comprehensive study on the enantioseparation of racemic bis[1-phenylethyl]amine (PEA) on a series of molecularly imprinted polymers (MIPs) prepared using the chiral functional monomer (S)-2-(2-methyl-acryloylamino)-3-phenyl propionic acid (MAPP) is reported. MIP-R, MIP-S and MIP-RS, were synthesized separately by imprinting the pure enantiomers (R-, S-PEA) and racemic PEA, respectively, MAPP, EDGMA as crosslinker and chloroform as the porogen. It was found that all MIPs prepared were able to resolve the PEA racemate...
November 30, 2012: Journal of Chromatography. A
Emma J Griffiths, Guanggan Hu, Bettina Fries, Mélissa Caza, Joyce Wang, Joerg Gsponer, Marcellene A Gates-Hollingsworth, Thomas R Kozel, Louis De Repentigny, James W Kronstad
The interaction of Cryptococcus neoformans with phagocytic cells of the innate immune system is a key step in disseminated disease leading to meningoencephalitis in immunocompromised individuals. Transcriptional profiling of cryptococcal cells harvested from cell culture medium or from macrophages found differential expression of metabolic and other functions during fungal adaptation to the intracellular environment. We focused on the ACL1 gene for ATP-citrate lyase, which converts citrate to acetyl-CoA, because this gene showed elevated transcript levels in macrophages and because of the importance of acetyl-CoA as a central metabolite...
December 2012: Molecular Microbiology
Anders R Kristensen, Joerg Gsponer, Leonard J Foster
Interactomes are often measured using affinity purification-mass spectrometry (AP-MS) or yeast two-hybrid approaches, but these methods do not provide stoichiometric or temporal information. We combine quantitative proteomics and size-exclusion chromatography to map 291 coeluting complexes. This method allows mapping of an interactome to the same depth and accuracy as AP-MS with less work and without overexpression or tagging. The use of triplex labeling enables monitoring of interactome rearrangements.
September 2012: Nature Methods
Katja Scheffler, Markus Krohn, Tina Dunkelmann, Jan Stenzel, Bruno Miroux, Saleh Ibrahim, Oliver von Bohlen Und Halbach, Hans-Jochen Heinze, Lary C Walker, Jörg A Gsponer, Jens Pahnke
Several lines of evidence link mutations and deletions in mitochondrial DNA (mtDNA) and its maternal inheritance to neurodegenerative diseases in the elderly. Age-related mutations of mtDNA modulate the tricarboxylic cycle enzyme activity, mitochondrial oxidative phosphorylation capacity and oxidative stress response. To investigate the functional relevance of specific mtDNA polymorphisms of inbred mouse strains in the proteostasis regulation of the brain, we established novel mitochondrial congenic mouse lines of Alzheimer's disease (AD)...
August 2012: Acta Neuropathologica
Jennifer M Bui, Jörg Gsponer, Michele Vendruscolo, Christopher M Dobson
The functions of proteins depend on the dynamical behavior of their native states on a wide range of timescales. To investigate these dynamics in the case of the small protein Gbeta1, we analyzed molecular dynamics simulations with the model-free approach of nuclear magnetic relaxation. We found amplitudes of fast timescale motions (sub-tau(c), where tau(c) is the rotational correlation time) consistent with S(2) obtained from spin relaxation measurements as well as amplitudes of slow timescale motions (supra-tau(c)) in quantitative agreement with S(2) order parameters derived from residual dipolar coupling measurements...
November 4, 2009: Biophysical Journal
Jörg Gsponer, M Madan Babu
The Publisher regrets that this article is an accidental duplication of an article that has already been published, doi:10.1016/j.pbiomolbio.2009.03.001.The duplicate article has therefore been withdrawn.
April 2, 2009: Progress in Biophysics and Molecular Biology
Joerg Gsponer, Harri Hopearuoho, Andrea Cavalli, Christopher M Dobson, Michele Vendruscolo
An accurate description of hydrogen bonds is essential to identify the determinants of protein stability and function as well as folding and misfolding behavior. We describe a method of using J couplings through hydrogen bonds as ensemble-averaged restraints in molecular dynamics simulations. Applications to the cases of ubiquitin and protein G show that these scalar couplings provide powerful structural information that, when used through the methodology that we present here, enables the description of the geometry and energetics of hydrogen bonds with an accuracy approaching that of high-resolution X-ray structures...
November 29, 2006: Journal of the American Chemical Society
G Settanni, J Gsponer, A Caflisch
The experimentally well-established folding mechanism of the src-SH3 domain, and in particular the phi-value analysis of its transition state, represents a sort of testing table for computational investigations of protein folding. Here, parallel molecular dynamics simulations of the src-SH3 domain have been performed starting from denatured conformations. By rescuing and restarting only trajectories approaching the folding transition state, an ensemble of conformations was obtained with a completely structured central beta-sheet and a native-like packing of residues Ile-110, Ala-121, and Ile-132...
March 2004: Biophysical Journal
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