TY  - JOUR
A1  - Abu-Halima, Masood
A1  - Häusler, Sebastian
A1  - Backes, Christina
A1  - Fehlmann, Tobias
A1  - Staib, Claudia
A1  - Nestel, Sigrun
A1  - Nazarenko, Irina
A1  - Meese, Eckart
A1  - Keller, Andreas
T1  - Micro-ribonucleic acids and extracellular vesicles repertoire in the spent culture media is altered in women undergoing \(In\) \(Vitro\) Fertilization
JF  - Scientific Reports
N2  - MicroRNAs (miRNAs) are class of small RNA molecules with major impact on gene regulation. We analyzed the potential of miRNAs secreted from pre-implantation embryos into the embryonic culture media as biomarkers to predict successful pregnancy. Using microarray analysis, we profiled the miRNome of the 56 spent culture media (SCM) after embryos transfer and found a total of 621 miRNAs in the SCM. On average, we detected 163 miRNAs in SCM of samples with failed pregnancies, but only 149 SCM miRNAs of embryos leading to pregnancies. MiR-634 predicted an embryo transfer leading to a positive pregnancy with an accuracy of 71% and a sensitivity of 85%. Among the 621 miRNAs, 102 (16.4%) showed a differential expression between positive and negative outcome of pregnancy with miR-29c-3p as the most significantly differentially expressed miRNA. The number of extracellular vehicles was lower in SCM with positive outcomes (3.8 × 10\(^9\)/mL EVs), as compared to a negative outcome (7.35 × 10\(^9\)/mL EVs) possibly explaining the reduced number of miRNAs in the SCM associated with failed pregnancies. The analysis of the miRNome in the SCM of couples undergoing fertility treatment lays the ground towards development of biomarkers to predict successful pregnancy and towards understanding the role of embryonic miRNAs found in the SCM.
KW  - Medicine
KW  - miRNAs
KW  - Molecular biology
KW  - Non-coding RNAs
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173632
VL  - 7
ER  - 
TY  - JOUR
A1  - Bousquet, J.
A1  - Onorato, G. L.
A1  - Bachert, C.
A1  - Barbolini, M.
A1  - Bedbrook, A.
A1  - Bjermer, L.
A1  - Correia de Sousa, J.
A1  - Chavannes, N. H.
A1  - Cruz, A. A.
A1  - De Manuel Keenoy, E.
A1  - Devillier, P.
A1  - Fonseca, J.
A1  - Hun, S.
A1  - Kostka, T.
A1  - Hellings, P. W.
A1  - Illario, M.
A1  - Ivancevich, J. C.
A1  - Larenas-Linnemann, D.
A1  - Millot-Keurinck, J.
A1  - Ryan, D.
A1  - Samolinski, B.
A1  - Sheikh, A.
A1  - Yorgancioglu, A.
A1  - Agache, I.
A1  - Arnavielhe, S.
A1  - Bewick, M.
A1  - Annesi-Maesano, I.
A1  - Anto, J. M.
A1  - Bergmann, K. C.
A1  - Bindslev-Jensen, C.
A1  - Bosnic-Anticevich, S.
A1  - Bouchard, J.
A1  - Caimmi, D. P.
A1  - Camargos, P.
A1  - Canonica, G. W.
A1  - Cardona, V.
A1  - Carriazo, A. M.
A1  - Cingi, C.
A1  - Cogan, E.
A1  - Custovic, A.
A1  - Dahl, R.
A1  - Demoly, P.
A1  - De Vries, G.
A1  - Fokkens, W. J.
A1  - Fontaine, J. F.
A1  - Gemicioğlu, B.
A1  - Guldemond, N.
A1  - Gutter, Z.
A1  - Haahtela, T.
A1  - Hellqvist-Dahl, B.
A1  - Jares, E.
A1  - Joos, G.
A1  - Just, J.
A1  - Khaltaev, N.
A1  - Keil, T.
A1  - Klimek, L.
A1  - Kowalski, M. L.
A1  - Kull, I.
A1  - Kuna, P.
A1  - Kvedariene, V.
A1  - Laune, D.
A1  - Louis, R.
A1  - Magnan, A.
A1  - Malva, J.
A1  - Mathieu-Dupas, E.
A1  - Melén, E.
A1  - Menditto, E.
A1  - Morais-Almeida, M.
A1  - Mösges, R.
A1  - Mullol, J.
A1  - Murray, R.
A1  - Neffen, H.
A1  - O'Hehir, R.
A1  - Palkonen, S.
A1  - Papadopoulos, N. G.
A1  - Passalacqua, G.
A1  - Pépin, J. L.
A1  - Portejoie, F.
A1  - Price, D.
A1  - Pugin, B.
A1  - Raciborski, F.
A1  - Simons, F. E. R.
A1  - Sova, M.
A1  - Spranger, O.
A1  - Stellato, C.
A1  - Todo Bom, A.
A1  - Tomazic, P. V.
A1  - Triggiani, M.
A1  - Valero, A.
A1  - Valovirta, E.
A1  - VandenPlas, O.
A1  - Valiulis, A.
A1  - van Eerd, M.
A1  - Ventura, M. T.
A1  - Wickmann, M.
A1  - Young, I.
A1  - Zuberbier, T.
A1  - Zurkuhlen, A.
A1  - Senn, A.
T1  - CHRODIS criteria applied to the MASK (MACVIA-ARIA Sentinel NetworK) Good Practice in allergic rhinitis: a SUNFRAIL report
JF  - Clinical and Translational Allergy
N2  - A Good Practice is a practice that works well, produces good results, and is recommended as a model. MACVIA-ARIA Sentinel Network (MASK), the new Allergic Rhinitis and its Impact on Asthma (ARIA) initiative, is an example of a Good Practice focusing on the implementation of multi-sectoral care pathways using emerging technologies with real life data in rhinitis and asthma multi-morbidity. The European Union Joint Action on Chronic Diseases and Promoting Healthy Ageing across the Life Cycle (JA-CHRODIS) has developed a checklist of 28 items for the evaluation of Good Practices. SUNFRAIL (Reference Sites Network for Prevention and Care of Frailty and Chronic Conditions in community dwelling persons of EU Countries), a European Union project, assessed whether MASK is in line with the 28 items of JA-CHRODIS. A short summary was proposed for each item and 18 experts, all members of ARIA and SUNFRAIL from 12 countries, assessed the 28 items using a Survey Monkey-based questionnaire. A visual analogue scale (VAS) from 0 (strongly disagree) to 100 (strongly agree) was used. Agreement equal or over 75% was observed for 14 items (50%). MASK is following the JA-CHRODIS recommendations for the evaluation of Good Practices.
KW  - Medicine
KW  - Rhinitis
KW  - Asthma
KW  - CHRODIS
KW  - ARIA
KW  - MASK
KW  - Sunfrail
KW  - Good Practices
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173527
VL  - 2017
IS  - 7
ER  - 
TY  - JOUR
A1  - Kuznetsov, Nikolai V.
A1  - Almuzzaini, Bader
A1  - Kritikou, Joanna S.
A1  - Baptista, Marisa A. P.
A1  - Oliveira, Mariana M. S.
A1  - Keszei, Marton
A1  - Snapper, Scott B.
A1  - Percipalle, Piergiorgio
A1  - Westerberg, Lisa S.
T1  - Nuclear Wiskott-Aldrich syndrome protein co-regulates T cell factor 1-mediated transcription in T cells
JF  - Genome Medicine
N2  - Background
The Wiskott–Aldrich syndrome protein (WASp) family of actin-nucleating factors are present in the cytoplasm and in the nucleus. The role of nuclear WASp for T cell development remains incompletely defined.

Methods
We performed WASp chromatin immunoprecipitation and deep sequencing (ChIP-seq) in thymocytes and spleen CD4\(^+\) T cells.

Results
WASp was enriched at genic and intergenic regions and associated with the transcription start sites of protein-coding genes. Thymocytes and spleen CD4\(^+\) T cells showed 15 common WASp-interacting genes, including the gene encoding T cell factor (TCF)12. WASp KO thymocytes had reduced nuclear TCF12 whereas thymocytes expressing constitutively active WASp\(^{L272P}\) and WASp\(^{I296T}\) had increased nuclear TCF12, suggesting that regulated WASp activity controlled nuclear TCF12. We identify a putative DNA element enriched in WASp ChIP-seq samples identical to a TCF1-binding site and we show that WASp directly interacted with TCF1 in the nucleus.

Conclusions
These data place nuclear WASp in proximity with TCF1 and TCF12, essential factors for T cell development.
KW  - Medicine
KW  - WASp
KW  - T cells
KW  - ChIP-seq
KW  - Wiskott-Aldrich syndrome
KW  - TCF1
KW  - TCF12
KW  - Nucleus
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173486
VL  - 9
ER  - 
TY  - JOUR
A1  - Wohlfarth, Carolin
A1  - Schmitteckert, Stefanie
A1  - Härtle, Janina D.
A1  - Houghton, Lesley A.
A1  - Dweep, Harsh
A1  - Fortea, Marina
A1  - Assadi, Ghazaleh
A1  - Braun, Alexander
A1  - Mederer, Tanja
A1  - Pöhner, Sarina
A1  - Becker, Philip P.
A1  - Fischer, Christine
A1  - Granzow, Martin
A1  - Mönnikes, Hubert
A1  - Mayer, Emeran A.
A1  - Sayuk, Gregory
A1  - Boeckxstaens, Guy
A1  - Wouters, Mira M.
A1  - Simrén, Magnus
A1  - Lindberg, Greger
A1  - Ohlsson, Bodil
A1  - Schmidt, Peter Thelin
A1  - Dlugosz, Aldona
A1  - Agreus, Lars
A1  - Andreasson, Anna
A1  - D'Amato, Mauro
A1  - Burwinkel, Barbara
A1  - Bermejo, Justo Lorenzo
A1  - Röth, Ralph
A1  - Lasitschka, Felix
A1  - Vicario, Maria
A1  - Metzger, Marco
A1  - Santos, Javier
A1  - Rappold, Gudrun A.
A1  - Martinez, Cristina
A1  - Niesler, Beate
T1  - miR-16 and miR-103 impact 5-HT4 receptor signalling and correlate with symptom profile in irritable bowel syndrome
JF  - Scientific Reports
N2  - Irritable bowel syndrome (IBS) is a gut-brain disorder involving alterations in intestinal sensitivity and motility. Serotonin 5-HT4 receptors are promising candidates in IBS pathophysiology since they regulate gut motor function and stool consistency, and targeted 5-HT4R selective drug intervention has been proven beneficial in subgroups of patients. We identified a single nucleotide polymorphism (SNP) (rs201253747) c.*61 T > C within the 5-HT4 receptor gene \(HTR4\) to be predominantly present in diarrhoea-IBS patients (IBS-D). It affects a binding site for the miR-16 family and miR-103/miR-107 within the isoforms \({HTR4b/i}\) and putatively impairs \(HTR4\) expression. Subsequent miRNA profiling revealed downregulation of miR-16 and miR-103 in the jejunum of IBS-D patients correlating with symptoms. \(In\) \(vitro\) assays confirmed expression regulation via three 3′UTR binding sites. The novel isoform \(HTR4b\_2\) lacking two of the three miRNA binding sites escapes miR-16/103/107 regulationin SNP carriers. We provide the first evidence that \(HTR4\) expression is fine-tuned by miRNAs, and that this regulation is impaired either by the SNP c.*61 T > C or bydiminished levels of miR-16 and miR-103 suggesting that \(HTR4\) might be involved in the development of IBS-D.
KW  - Medicine
KW  - Gene regulation
KW  - Irritable bowel syndrome
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173478
VL  - 7
ER  - 
TY  - JOUR
A1  - Grünblatt, Edna
A1  - Oneda, Beatrice
A1  - Ekici, Arif B.
A1  - Ball, Juliane
A1  - Geissler, Julia
A1  - Uebe, Steffen
A1  - Romanos, Marcel
A1  - Rauch, Anita
A1  - Walitza, Susanne
T1  - High resolution chromosomal microarray analysis in paediatric obsessive-compulsive disorder
JF  - BMC Medical Genomics
N2  - Background
Obsessive-Compulsive Disorder (OCD) is a common and chronic disorder in which a person has uncontrollable, reoccurring thoughts and behaviours. It is a complex genetic condition and, in case of early onset (EO), the patients manifest a more severe phenotype, and an increased heritability. Large (>500 kb) copy number variations (CNVs) previously associated with autism and schizophrenia have been reported in OCD. Recently, rare CNVs smaller than 500 kb overlapping risk loci for other neurodevelopmental conditions have also been reported in OCD, stressing the importance of examining CNVs of any size range. The aim of this study was to further investigate the role of rare and small CNVs in the aetiology of EO-OCD.

Methods
We performed high-resolution chromosomal microarray analysis in 121 paediatric OCD patients and in 124 random controls to identify rare CNVs (>50 kb) which might contribute to EO-OCD.

Results
The frequencies and the size of the observed rare CNVs in the patients did not differ from the controls. However, we observed a significantly higher frequency of rare CNVs affecting brain related genes, especially deletions, in the patients (OR = 1.98, 95% CI 1.02–3.84; OR = 3.61, 95% CI 1.14–11.41, respectively). Similarly, enrichment-analysis of CNVs gene content, performed with three independent methods, confirmed significant clustering of predefined genes involved in synaptic/brain related functional pathways in the patients but not in the controls. In two patients we detected \(de-novo\) CNVs encompassing genes previously associated with different neurodevelopmental disorders \(\textit{NRXN1, ANKS1B, UHRF1BP1}\)).

Conclusions
Our results further strengthen the role of small rare CNVs, particularly deletions, as susceptibility factors for paediatric OCD.
KW  - Medicine
KW  - OCD
KW  - CNV
KW  - Enrichment analysis
KW  - De-novo
KW  - Early-onset
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172791
VL  - 10
IS  - 68
ER  - 
TY  - JOUR
A1  - Fröhlich, M.
A1  - Pinart, M.
A1  - Keller, T.
A1  - Reich, A.
A1  - Cabieses, B.
A1  - Hohmann, C.
A1  - Postma, D. S.
A1  - Bousquet, J.
A1  - Antó, J. M.
A1  - Keil, T.
A1  - Roll, S.
T1  - Is there a sex-shift in prevalence of allergic rhinitis and comorbid asthma from childhood to adulthood? A meta-analysis
JF  - Clinical and Translational Allergy
N2  - Background: Allergic rhinitis and asthma as single entities affect more boys than girls in childhood but more females in adulthood. However, it is unclear if this prevalence sex-shift also occurs in allergic rhinitis and concurrent asthma. Thus, our aim was to compare sex-specifc differences in the prevalence of coexisting allergic rhinitis and asthma in childhood, adolescence and adulthood.

Methods: Post-hoc analysis of systematic review with meta-analysis concerning sex-specific prevalence of allergic rhinitis. Using random-effects meta-analysis, we assessed male–female ratios for coexisting allergic rhinitis and asthma in children (0–10 years), adolescents (11–17) and adults (> 17). Electronic searches were performed using MEDLINE and EMBASE for the time period 2000–2014. We included population-based observational studies, reporting coexisting allergic rhinitis and asthma as outcome stratifed by sex. We excluded non-original or non-population-based studies, studies with only male or female participants or selective patient collectives.

Results: From a total of 6539 citations, 10 studies with a total of 93,483 participants met the inclusion criteria. The male–female ratios (95% CI) for coexisting allergic rhinitis and asthma were 1.65 (1.52; 1.78) in children (N = 6 studies), 0.61 (0.51; 0.72) in adolescents (N = 2) and 1.03 (0.79; 1.35) in adults (N = 2). Male–female ratios for allergic rhinitis only were 1.25 (1.19; 1.32, N = 5) in children, 0.80 (0.71; 0.89, N = 2) in adolescents and 0.98 (0.74; 1.30, N = 2) in adults, respectively.

Conclusions: The prevalence of coexisting allergic rhinitis and asthma shows a clear male predominance in childhood and seems to switch to a female predominance in adolescents. This switch was less pronounced for allergic rhinitis only.
KW  - Medicine
KW  - Allergic rhinitis
KW  - Asthma
KW  - Multimorbidity
KW  - Prevalence
KW  - Systematic review
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172508
VL  - 7
ER  - 
TY  - JOUR
A1  - Rueegg, Corina S.
A1  - Kriemler, Susi
A1  - Zuercher, Simeon J.
A1  - Schindera, Christina
A1  - Renner, Andrea
A1  - Hebestreit, Helge
A1  - Meier, Christian
A1  - Eser, Prisca
A1  - von der Weid, Nicolas X.
T1  - A partially supervised physical activity program for adult and adolescent survivors of childhood cancer (SURfit): study design of a randomized controlled trial [NCT02730767]
JF  - BMC Cancer
N2  - Background: Beyond survival of nowadays >80%, modern childhood cancer treatment strives to preserve long-term health and quality of life. However, the majority of today’s survivors suffer from short- and long-term adverse effects such as cardiovascular and pulmonary diseases, obesity, osteoporosis, fatigue, depression, and reduced physical fitness and quality of life. Regular exercise can play a major role to mitigate or prevent such late-effects. Despite this, there are no data on the effects of regular exercise in childhood cancer survivors from randomized controlled trials (RCTs). \(Primary\) \(outcome\) of the current RCT is therefore the effect of a 12-months exercise program on a composite cardiovascular disease risk score in childhood cancer survivors. \(Secondary\) \(outcomes\) are single cardiovascular disease risk factors, glycaemic control, bone health, body composition, physical fitness, physical activity, quality of life, mental health, fatigue and adverse events (safety).

Methods: A total of 150 childhood cancer survivors aged ≥16 years and diagnosed ≥5 years prior to the study are recruited from Swiss paediatric oncology clinics. Following the baseline assessments patients are randomized 1:1 into an intervention and control group. Thereafter, they are seen at month 3, 6 and 12 for follow-up assessments. The intervention group is asked to add ≥2.5 h of intense physical activity/week, including 30 min of strength building and 2 h of aerobic exercises. In addition, they are told to reduce screen time by 25%. Regular consulting by physiotherapists, individual web-based activity diaries, and pedometer devices are used as motivational tools for the intervention group. The control group is asked to keep their physical activity levels constant.

Discussion: The results of this study will show whether a partially supervised exercise intervention can improve cardiovascular disease risk factors, bone health, body composition, physical activity and fitness, fatigue, mental health and quality of life in childhood cancer survivors. If the program will be effective, all relevant information of the SURfit physical activity intervention will be made available to interested clinics that treat and follow-up childhood cancer patients to promote exercise in their patients.
KW  - Medicine
KW  - Randomized controlled trial
KW  - Physical activity
KW  - Exercise intervention
KW  - Childhood cancer survivors
KW  - Late-effects
KW  - Cardiovascular disease
KW  - Bone health
KW  - Body composition
KW  - Physical fitness
KW  - Quality of life
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172497
VL  - 17
ER  - 
TY  - JOUR
A1  - Eisele, Marion
A1  - Boczor, Sigrid
A1  - Rakebrandt, Anja
A1  - Blozik, Eva
A1  - Trader, Jens-Martin
A1  - Stork, Stefan
A1  - Herrmann-Lingen, Christoph
A1  - Scherer, Martin
T1  - General practitioners' awareness of depressive symptomatology is not associated with quality of life in heart failure patients - cross-sectional results of the observational RECODE-HF Study
JF  - BMC Family Practice
N2  - Background
Depression is a common comorbidity in patients with chronic heart failure (HF) and linked to a wider range of symptoms which, in turn, are linked to a decreased health-related quality of life (HRQOL). Treatment of depression might improve HRQOL but detecting depression is difficult due to the symptom overlap between HF and depression. Therefore, clinical guidelines recommend to routinely screen for depression in HF patients. No studies have so far investigated the treatment after getting aware of a depressive symptomatology and its correlation with HRQOL in primary care HF patients. Therefore, we examined the factors linked to depression treatment and those linked to HRQOL in HF patients. We hypothesized that GPs’ awareness of depressive symptomatology was associated with depression treatment and HRQOL in HF patients.

Methods
For this observational study, HF patients were recruited in primary care practices and filled out a questionnaire including PHQ-9 and HADS. A total of 574 patients screened positive for depressive symptomatology. Their GPs were interviewed by phone regarding the patients’ comorbidities and potential depression treatment. Descriptive and regression analysis were performed.

Results
GPs reported various types of depression treatments (including dialogue/counselling by the GP him/herself in 31.8% of the patients). The reported rates differed considerably between GP-reported initiated treatment and patient-reported utilised treatment regarding psychotherapy (16.4% vs. 9.5%) and pharmacotherapy (61.2% vs. 30.3%). The GPs' awareness of depressive symptomatology was significantly associated with the likelihood of receiving pharmacotherapy (OR 2.8; p < 0.001) but not psychotherapy. The patient’s HRQOL was not significantly associated with the GPs' awareness of depression.

Conclusion
GPs should be aware of the gap between GP-initiated and patient-utilised depression treatments in patients with chronic HF, which might lead to an undersupply of depression treatment. It remains to be investigated why GPs’ awareness of depressive symptomatology is not linked to patients’ HRQOL. We hypothesize that GPs are aware of cases with reduced HRQOL (which improves under depression treatment) and unaware of cases whose depression do not significantly impair HRQOL, resulting in comparable levels of HRQOL in both groups. This hypothesis needs to be further investigated.
KW  - Medicine
KW  - Depression
KW  - Heart failure
KW  - Recognition of depression
KW  - Quality of life
KW  - Depression treatment
KW  - Observational study
KW  - Primary care
KW  - Healthcare research
KW  - Depressive symptomatology
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172445
VL  - 18
ER  - 
TY  - JOUR
A1  - Westermann, Alexander J.
A1  - Barquist, Lars
A1  - Vogel, Jörg
T1  - Resolving host-pathogen interactions by dual RNA-seq
JF  - PLoS Pathogens
N2  - The transcriptome is a powerful proxy for the physiological state of a cell, healthy or diseased. As a result, transcriptome analysis has become a key tool in understanding the molecular changes that accompany bacterial infections of eukaryotic cells. Until recently, such transcriptomic studies have been technically limited to analyzing mRNA expression changes in either the bacterial pathogen or the infected eukaryotic host cell. However, the increasing sensitivity of high-throughput RNA sequencing now enables “dual RNA-seq” studies, simultaneously capturing all classes of coding and noncoding transcripts in both the pathogen and the host. In the five years since the concept of dual RNA-seq was introduced, the technique has been applied to a range of infection models. This has not only led to a better understanding of the physiological changes in pathogen and host during the course of an infection but has also revealed hidden molecular phenotypes of virulence-associated small noncoding RNAs that were not visible in standard infection assays. Here, we use the knowledge gained from these recent studies to suggest experimental and computational guidelines for the design of future dual RNA-seq studies. We conclude this review by discussing prospective applications of the technique.
KW  - Medicine
KW  - RNA sequencing
KW  - Salmonellosis
KW  - Transcriptome analysis
KW  - Gene expression
KW  - Bacterial pathogens
KW  - Salmonella
KW  - Host cells
KW  - Lysis (medicine)
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171921
VL  - 13
IS  - 2
ER  - 
TY  - JOUR
A1  - Sander, Bodo
A1  - Xu, Wenshan
A1  - Eilers, Martin
A1  - Popov, Nikita
A1  - Lorenz, Sonja
T1  - A conformational switch regulates the ubiquitin ligase HUWE1
JF  - eLife
N2  - The human ubiquitin ligase HUWE1 has key roles in tumorigenesis, yet it is unkown how its activity is regulated. We present the crystal structure of a C-terminal part of HUWE1, including the catalytic domain, and reveal an asymmetric auto-inhibited dimer. We show that HUWE1 dimerizes in solution and self-associates in cells, and that both occurs through the crystallographic dimer interface. We demonstrate that HUWE1 is inhibited in cells and that it can be activated by disruption of the dimer interface. We identify a conserved segment in HUWE1 that counteracts dimer formation by associating with the dimerization region intramolecularly. Our studies reveal, intriguingly, that the tumor suppressor p14ARF binds to this segment and may thus shift the conformational equilibrium of HUWE1 toward the inactive state. We propose a model, in which the activity of HUWE1 underlies conformational control in response to physiological cues—a mechanism that may be exploited for cancer therapy.
KW  - Medicine
KW  - Structural Biology
KW  - Molecular Biophysics
KW  - HUWE1
KW  - HECT Ligase
KW  - Ubiquitin
KW  - P14ARF
KW  - X-Ray Chrystallography
KW  - Enzyme Regulation
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171862
VL  - 6
ER  - 
TY  - JOUR
A1  - Triphan, Simon M. F.
A1  - Jobst, Bertram J.
A1  - Anjorin, Angela
A1  - Sedlaczek, Oliver
A1  - Wolf, Ursula
A1  - Terekhov, Maxim
A1  - Hoffmann, Christian
A1  - Ley, Sebastian
A1  - Düber, Christoph
A1  - Biederer, Jürgen
A1  - Kauczor, Hans-Ulrich
A1  - Jakob, Peter M.
A1  - Wielpütz, Mark O.
T1  - Reproducibility and comparison of oxygen-enhanced T\(_1\) quantification in COPD and asthma patients
JF  - PLoS ONE
N2  - T\(_1\) maps have been shown to yield useful diagnostic information on lung function in patients with chronic obstructive pulmonary disease (COPD) and asthma, both for native T\(_1\) and ΔT\(_1\), the relative reduction while breathing pure oxygen. As parameter quantification is particularly interesting for longitudinal studies, the purpose of this work was both to examine the reproducibility of lung T\(_1\) mapping and to compare T\(_1\) found in COPD and asthma patients using IRSnapShotFLASH embedded in a full MRI protocol. 12 asthma and 12 COPD patients (site 1) and further 15 COPD patients (site 2) were examined on two consecutive days. In each patient, T\(_1\) maps were acquired in 8 single breath-hold slices, breathing first room air, then pure oxygen. Maps were partitioned into 12 regions each to calculate average values. In asthma patients, the average T\(_{1,RA}\) = 1206ms (room air) was reduced to T\(_{1,O2}\) = 1141ms under oxygen conditions (ΔT\(_1\) = 5.3%, p < 5⋅10\(^{−4})\), while in COPD patients both native T\(_{1,RA}\) = 1125ms was significantly shorter (p < 10\(^{−3})\) and the relative reduction to T\(_{1,O2}\) = 1081ms on average ΔT\(_1\) = 4.2%(p < 10\(^{−5}\)). On the second day, with T\(_{1,RA}\) = 1186ms in asthma and T\(_{1,RA}\) = 1097ms in COPD, observed values were slightly shorter on average in all patient groups. ΔT\(_1\) reduction was the least repeatable parameter and varied from day to day by up to 23% in individual asthma and 30% in COPD patients. While for both patient groups T\(_1\) was below the values reported for healthy subjects, the T\(_1\) and ΔT\(_1\) found in asthmatics lies between that of the COPD group and reported values for healthy subjects, suggesting a higher blood volume fraction and better ventilation. However, it could be demonstrated that lung T\(_1\) quantification is subject to notable inter-examination variability, which here can be attributed both to remaining contrast agent from the previous day and the increased dependency of lung T\(_1\) on perfusion and thus current lung state.
KW  - Medicine
KW  - Chronic obstrusive pulmonary disease
KW  - Asthma
KW  - Oxygen
KW  - Magnetic resonance imaging
KW  - Breathing
KW  - Pulmonary imaging
KW  - Protons
KW  - Diagnostic medicine
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171833
VL  - 12
IS  - 2
ER  - 
TY  - JOUR
A1  - Fassnacht, Martin
A1  - Johanssen, Sarah
A1  - Allolio, Bruno
T1  - Statements Cannot Be Substantiated : In Reply
JF  - Deutsches Ärzteblatt International
N2  - No abstract available.
KW  - Medicine
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-142597
VL  - 108
IS  - 19
ER  - 
TY  - JOUR
A1  - Nell, Manuel
A1  - Burgkart, Rainer H.
A1  - Gradl, Guntmar
A1  - von Eisenhart-Rothe, Rüdiger
A1  - Schaeffeler, Christoph
A1  - Trappe, Dennis
A1  - Prazeres da Costa, Clarissa
A1  - Gradinger, Reiner
A1  - Kirchhoff, Chlodwig
T1  - Primary extrahepatic alveolar echinococcosis of the lumbar spine and the psoas muscle
JF  - Annals of Clinical Microbiology and Antimicrobials
N2  - Alveolar echinococcosis (AE) of human being caused by Echinococcus multilocularis is a rare but important zoonosis especially in tempered zones of middle Europe and Northern America with endemic character in many countries. Due to the long incubation period, various clinical manifestations, critical prognosis, and outcome AE presents a serious and severe disease. The primary focus of infection is usually the liver. Although secondary affection of visceral organs is possible extrahepatic AE is highly uncommon. Moreover, the involvement of bone and muscle presents with an even lower incidence. In the literature numerous cases on hepatic AE have been reported. However, extrahepatic AE involving bones and/or muscles was described very rarely. We report a case of an 80-year-old man with primary extrahepatic alveolar Echinococcosis of the lumbar spine and the psoas muscle. The etiology, diagnosis, differential diagnoses, treatment options and outcome of this rare disease are discussed in context with the current literature.
KW  - Medicine
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-141796
VL  - 10
IS  - 13
ER  -