1-20 von 3207 Publikationen

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      Repair restorations: Questionnaire survey among dentists in the Canton of Zurich, Switzerland 

      Kanzow, Philipp; Dieckmann, Phoebe; Hausdörfer, Tim; Attin, Thomas; Wiegand, Annette; Wegehaupt, Florian J
      Swiss Dental Journal 2017; 127(4) p.300-311
      The aim of this study was to carry out a representative survey on the implementation of and experience with repairs of single-tooth restorations among dentists in the Canton of Zurich, Switzerland. An anonymous questionnaire was sent to all 1,411 dentists registered in the Canton of Zurich; 38.9% of the delivered questionnaires were returned and 35.3% could be evaluated. The statistical analysis comprised Kendall s rank correlation coefficient (tau), Wilcoxon signed-rank tests, and Kruskal-Wallis tests. The level of significance was set at p≤0.05. Repair restorations are frequently made (composite: 98.5%, ceramic: 88.9%, crowns: 86.5%, metal: 54.6%, amalgam: 51.5%). Main indications for repairs were the partial loss of an existing restoration or of the adjacent dental hard substance, while restoration failures due to secondary caries were repaired to a lesser extent. The decision to repair is largely dependent on the size of the defect (90%), the size of the original restoration (63%), and the material of the failed restoration (84%). Repair restorations are most frequently made with composite following adequate conditioning of the repair surface. A majority of the dentists rate the lifespan of repair restorations as reduced in comparison with newly made restorations. In summary, repairs of defective single-tooth restorations are frequently performed by dentists in the Canton of Zurich, Switzerland, and constitute a well-established treatment procedure.
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      Alopecia Universalis following Alemtuzumab Treatment in Multiple Sclerosis: A Barely Recognized Manifestation of Secondary Autoimmunity—Report of a Case and Review of the Literature 

      Zimmermann, Julian; Buhl, Timo; Müller, Marcus
      Frontiers in Neurology 2017; 8: Art. 569
      Secondary autoimmunity is the most frequent adverse event occurring in almost every other alemtuzumab-treated multiple sclerosis patient. We report a case of a patient with relapsing-remitting multiple sclerosis who reported smooth, circular areas of complete hair loss on both thighs 6 months after the second treatment cycle with alemtuzumab. The patient was diagnosed as having alopecia areata (AA). Within 3 months, AA progressed to complete loss of all body hair (alopecia universalis). Current literature rarely connects alemtuzumab with the onset of alopecia of autoimmune origin. Here, we report a little-noticed autoimmune disease affecting the skin, very likely being associated with alemtuzumab. We emphasize the necessity of careful clinical surveillance of alemtuzumab- treated patients for yet undescribed autoimmune diseases.
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      Predictors of mortality and ICD shock therapy in primary prophylactic ICD patients-A systematic review and meta-analysis. 

      Bergau, Leonard; Tichelbäcker, Tobias; Kessel, Barbora; Lüthje, Lars; Fischer, Thomas H.; Friede, Tim; Zabel, Markus
      PloS one 2017; 12(10): Art. e0186387
      BACKGROUND: There is evidence that the benefit of a primary prophylactic ICD therapy is not equal in all patients. PURPOSE: To evaluate risk factors of appropriate shocks and all- cause mortality in patients with a primary prophylactic ICD regarding contemporary studies. DATA SOURCE: PubMed, LIVIVO, Cochrane CENTRAL between 2010 and 2016. STUDY SELECTION: Studies were eligible if at least one of the endpoints of interest were reported. DATA EXTRACTION: All abstracts were independently reviewed by at least two authors. The full text of all selected studies was then analysed in detail. DATA SYNTHESIS: Our search strategy retrieved 608 abstracts. After exclusion of unsuitable studies, 36 papers with a total patient number of 47282 were included in our analysis. All-cause mortality was significantly associated with increasing age (HR 1.41, CI 1.29-1.53), left ventricular function (LVEF; HR 1.21, CI 1.14-1.29), ischemic cardiomyopathy (ICM; HR 1.37, CI 1.14-1.66) and co-morbidities such as impaired renal function (HR 2.30, CI 1.97-2.69). Although, younger age (HR 0.96, CI 0.85-1.09), impaired LVEF (HR 1.26, CI 0.89-1.78) and ischemic cardiomyopathy (HR 2.22, CI 0.83-5.93) were associated with a higher risk of appropriate shocks, none of these factors reached statistical significance. LIMITATIONS: Individual patient data were not available for most studies. CONCLUSION: In this meta-analysis of contemporary clinical studies, all-cause mortality is predicted by a variety of clinical characteristics including LVEF. On the other hand, the risk of appropriate shocks might be associated with impaired LVEF and ischemic cardiomyopathy. Further prospective studies are required to verify risk factors for appropriate shocks other than LVEF to help select appropriate patients for primary prophylactic ICD-therapy.
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      In Vivo Neuromechanics: Decoding Causal Motor Neuron Behavior with Resulting Musculoskeletal Function. 

      Sartori, Massimo; Yavuz, Utku Ş.; Farina, Dario
      Scientific reports 2017; 7(1): Art. 13465
      Human motor function emerges from the interaction between the neuromuscular and the musculoskeletal systems. Despite the knowledge of the mechanisms underlying neural and mechanical functions, there is no relevant understanding of the neuro-mechanical interplay in the neuro-musculo-skeletal system. This currently represents the major challenge to the understanding of human movement. We address this challenge by proposing a paradigm for investigating spinal motor neuron contribution to skeletal joint mechanical function in the intact human in vivo. We employ multi-muscle spatial sampling and deconvolution of high-density fiber electrical activity to decode accurate α-motor neuron discharges across five lumbosacral segments in the human spinal cord. We use complete α-motor neuron discharge series to drive forward subject-specific models of the musculoskeletal system in open-loop with no corrective feedback. We perform validation tests where mechanical moments are estimated with no knowledge of reference data over unseen conditions. This enables accurate blinded estimation of ankle function purely from motor neuron information. Remarkably, this enables observing causal associations between spinal motor neuron activity and joint moment control. We provide a new class of neural data-driven musculoskeletal modeling formulations for bridging between movement neural and mechanical levels in vivo with implications for understanding motor physiology, pathology, and recovery.
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      Reabsorption of iron into acutely damaged rat liver: A role for ferritins 

      Malik, Ihtzaz Ahmed; Wilting, Jörg; Ramadori, Giuliano; Naz, Naila
      World Journal of Gastroenterology 2017; 23(41) p.7347-7358
      AIM To studied iron metabolism in liver, spleen, and serum after acute liver-damage, in relation to surrogate markers for liver-damage and repair. METHODS Rats received intraperitoneal injection of the hepatotoxin thioacetamide (TAA), and were sacrificed regularly between 1 and 96 h thereafter. Serum levels of transaminases and iron were measured using conventional laboratory assays. Liver tissue was used for conventional histology, immunohistology, and iron staining. The expression of acute-phase cytokines, ferritin light chain (FTL), and ferritin heavy chain (FTH) was investigated in the liver by qRT-PCR. Western blotting was used to investigate FTL and FTH in liver tissue and serum. Liver and spleen tissue was also used to determine iron concentrations. RESULTS After a short initial decrease, iron serum concentrations increased in parallel with serum transaminase (aspartate aminotransferase and alanine aminotransferase) levels, which reached a maximum at 48 h, and decreased thereafter. Similarly, after 48 h a significant increase in FTL, and after 72h in FTH was detected in serum. While earliest morphological signs of inflammation in liver were visible after 6 h, increased expression of the two acute-phase cytokines IFN-γ (1h) and IL-1β (3h) was detectable earlier, with maximum values after 12-24 h. Iron concentrations in liver tissue increased steadily between 1 h and 48 h, and remained high at 96 h. In contrast, spleen iron concentrations remained unchanged until 48 h, and increased mildly thereafter (96 h). Although tissue iron staining was negative, hepatic FTL and FTH protein levels were strongly elevated. Our results reveal effects on hepatic iron concentrations after direct liver injury by TAA. The increase of liver iron concentrations may be due to the uptake of a significant proportion of the metal by healthy hepatocytes, and only to a minor extent by macrophages, as spleen iron concentrations do not increase in parallel. The temporary increase of iron, FTH and transaminases in serum is obviously due to their release by damaged hepatocytes. CONCLUSION Increased liver iron levels may be the consequence of hepatocyte damage. Iron released into serum by damaged hepatocytes is obviously transported back and stored via ferritins.
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      Myostatin inhibitors as pharmacological treatment for muscle wasting and muscular dystrophy 

      Saitoh, Masakazu; Ishida, Junichi; Ebner, Nicole; Anker, Stefan D.; Springer, Jochen; Haehling, Stephan von
      Journal of Cachexia, Sarcopenia and Muscle ‐ Clinical Reports 2017; 2(1): Art. e00037
      Myostatin, a member of the transforming growth factor beta (TGF‐β) superfamily that is highly expressed in skeletal muscle, was first described in 1997. It has been known that loss of myostatin function induces an increase in muscle mass in mice, cow, dogs and humans. Therefore, myostatin and its receptor have emerged as a therapeutic target for loss of skeletal muscle such as sarcopenia and cachexia, as well as muscular dystrophies. At the molecular level, myostatin binds to and activates the activin receptor IIB (ActRIIB)/Alk 4/5 complex. Therapeutic approaches therefore are being taken both pre‐clinically and clinically to inhibit the myostatin signaling pathway. Several myostatin inhibitors , including myostatin antibodies, anti‐myostatin peptibody, activin A antibody, soluble (decoy) forms of ActRIIB (ActRⅡB‐Fc), anti‐myostatin adnectin, ActRⅡB antibody have been tested in the last decade. The aim of this review is to present the current knowledge of several myostatin inhibitors as a therapeutic approach for patients with loss of skeletal muscle.
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      Interaction of Excitatory Amino Acid Transporters 1 - 3 (EAAT1, EAAT2, EAAT3) with N-Carbamoylglutamate and N-Acetylglutamate. 

      Burckhardt, Birgitta C.; Burckhardt, Gerhard
      Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2017-10-20; 43(5) p.1907-1916
      BACKGROUND/AIMS: Inborn deficiency of the N-acetylglutamate synthase (NAGS) impairs the urea cycle and causes neurotoxic hyperammonemia. Oral administration of N-carbamoylglutamate (NCG), a synthetic analog of N-acetylglutamate (NAG), successfully decreases plasma ammonia levels in the affected children. Due to structural similarities to glutamate, NCG may be absorbed in the intestine and taken up into the liver by excitatory amino acid transporters (EAATs). METHODS: Using Xenopus laevis oocytes expressing either human EAAT1, 2, or 3, or human sodium-dependent dicarboxylate transporter 3 (NaDC3), transport-associated currents of NAG, NCG, and related dicarboxylates were assayed. RESULTS: L-aspartate and L-glutamate produced saturable inward currents with Km values below 30 µM. Whereas NCG induced a small inward current only in EAAT3 expressing oocytes, NAG was accepted by all EAATs. With EAAT3, the NAG-induced current was sodium-dependent and saturable (Km 409 µM). Oxaloacetate was found as an additional substrate of EAAT3. In NaDC3-expressing oocytes, all dicarboxylates induced much larger inward currents than did L-aspartate and L-glutamate. CONCLUSION: EAAT3 may contribute to intestinal absorption and hepatic uptake of NCG. With respect to transport of amino acids and dicarboxylates, EAAT3 and NaDC3 can complement each other.
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      High mast cell density indicates a longer overall survival in oral squamous cell carcinoma. 

      Brockmeyer, Phillipp; Kling, Alexander; Schulz, Xenia; Perske, Christina; Schliephake, Henning; Hemmerlein, Bernhard
      Scientific reports 2017-11-07; 7(1): Art. 14677
      This study evaluates the effects of tumour-associated mast cells on the prognosis of patients suffering from oral squamous cell carcinoma (OSCC). Tryptase-positive (MCT(+)) and CD117-positive (CD117(+)) mast cells were immunohistochemically evaluated in tissue samples of 118 OSCC patients. Besides, various clinicopathological parameters, the influence of the MCT(+) and CD117(+) mast cell density on overall survival and the incidence of first local recurrence was analysed by Cox regression and competing risk regression. Among all investigated parameters, multiple Cox regression revealed a significant influence of the MCT(+) (cut-off at 14.87 mast cells/mm(2) stroma; p = 0.0027) and CD117(+) mast cell density (cut-off at 33.19 mast cells/mm(2) stroma; p = 0.004), the age at primary diagnosis, and the T and N stage (all p-values < 0.05) on overall survival. Patients with a low mast cell density showed a significantly poorer overall survival rate compared to those with a high mast cell density in the tumour-associated stroma. Competing risk regression revealed a significant influence of the resection status (R) on the incidence of first local recurrence (p = 0.0023). A high mast cell density in the tumour-associated stroma of oral squamous cell carcinoma indicates a longer patient survival.
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      Imaging of neuronal tissues by x-ray diffraction and x-ray fluorescence microscopy: evaluation of contrast and biomarkers for neurodegenerative diseases. 

      Carboni, Eleonora; Nicolas, Jan-David; Töpperwien, Mareike; Stadelmann-Nessler, Christine; Lingor, Paul; Salditt, Tim
      Biomedical optics express 2017-10-01; 8(10) p.4331-4347
      We have used scanning X-ray diffraction (XRD) and X-ray fluorescence (XRF) with micro-focused synchrotron radiation to study histological sections from human substantia nigra (SN). Both XRF and XRD mappings visualize tissue properties, which are inaccessible by conventional microscopy and histology. We propose to use these advanced tools to characterize neuronal tissue in neurodegeneration, in particular in Parkinson's disease (PD). To this end, we take advantage of the recent experimental progress in x-ray focusing, detection, and use automated data analysis scripts to enable quantitative analysis of large field of views. XRD signals are recorded and analyzed both in the regime of small-angle (SAXS) and wide-angle x-ray scattering (WAXS). The SAXS signal was analyzed in view of the local myelin structure, while WAXS was used to identify crystalline deposits. PD tissue scans exhibited increased amounts of crystallized cholesterol. The XRF analysis showed increased amounts of iron and decreased amounts of copper in the PD tissue compared to the control.
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      Expanded and updated data and a query pipeline for iBeetle-Base. 

      Dönitz, Jürgen; Gerischer, Lizzy; Hahnke, Stefan; Pfeiffer, Stefan; Bucher, Gregor
      Nucleic acids research
      The iBeetle-Base provides access to sequence and phenotype information for genes of the beetle Tribolium castaneum. It has been updated including more and updated data and new functions. RNAi phenotypes are now available for >50% of the genes, which represents an expansion of 60% compared to the previous version. Gene sequence information has been updated based on the new official gene set OGS3 and covers all genes. Interoperability with FlyBase has been enhanced: First, gene information pages of homologous genes are interlinked between both databases. Second, some steps of a new query pipeline allow transforming gene lists from either species into lists with related gene IDs, names or GO terms. This facilitates the comparative analysis of gene functions between fly and beetle. The backend of the pipeline is implemented as endpoints of a RESTful interface, such that it can be reused by other projects or tools. A novel online interface allows the community to propose GO terms for their gene of interest expanding the range of animals where GO terms are defined. iBeetle-Base is available at http://ibeetle-base.uni-goettingen.de/.
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      Pain experiences of patients with musculoskeletal pain + central sensitization: A comparative Group Delphi Study. 

      Schäfer, Axel Georg Meender; Joos, Leonie Johanna; Roggemann, Katharina; Waldvogel-Röcker, Kerstin; Pfingsten, Michael; Petzke, Frank
      PloS one 2017; 12(8): Art. e0182207
      OBJECTIVES: Central sensitization (CS) is regarded as an important contributing factor for chronification of musculoskeletal pain (MSP). It is crucial to identify CS, as targeted multimodal treatment may be indicated. The primary objective of this study was therefore to explore pain experience of individuals with MSP+CS in order to gain a better understanding of symptoms in relation to CS from a patient perspective. The secondary objective was to investigate whether pain experiences of patients with MSP+CS differ from those of individuals with neuropathic pain (NP). METHODS: We conducted a comparative Group Delphi Study including patients with MSP+CS and neuropathic pain (NP). 13 guiding questions were used to gather information about sensory discriminatory, affective and associated bodily, mental and emotional phenomena related to the pain experience of patients. Descriptions were categorized using qualitative content analysis. Additionally, patients completed several pain related questionnaires. RESULTS: Nine participants with MSP+CS and nine participants with NP participated. The Delphi procedure revealed three main themes: psycho-emotional factors, bodily factors and environmental factors. Descriptions of patients with MSP+CS showed a complex picture, psycho-emotional factors seem to have a considerable impact on pain provocation, aggravation and relief. Impairments associated with mental ability and psyche affected many aspects of daily life. In contrast, descriptions of patients with NP revealed a rather mechanistic and bodily oriented pain experience. DISCUSSION: Patients with MSP+CS reported distinct features in relation to their pain that were not captured with current questionnaires. Insight in patient's pain experience may help to choose and develop appropriate diagnostic instruments.
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      The Serotonin Receptor Subtype 5b Specifically Interacts with Serotonin Receptor Subtype 1A. 

      Niebert, Sabine; van Belle, Gijsbert J.; Vogelgesang, Steffen; Manzke, Till; Niebert, Marcus
      Frontiers in molecular neuroscience 2017; 10: Art. 299
      Previously, we described the dysregulation of serotonin (5-HT) receptor subtype 5b (5-ht5b) in a mouse model of Rett syndrome (RTT). 5-ht5b has not been extensively studied, so we set out to characterize it in more detail. Unlike common cell surface receptors, 5-ht5b displays no membrane expression, while receptor clusters are located in endosomes. This unusual subcellular localization is at least in part controlled by glycosylation of the N-terminus, with 5-ht5b possessing fewer glycosylation sites than related receptors. We analyzed whether the localization to endosomes has any functional relevance and found that 5-ht5b receptors can specifically interact with 5-HT1A receptors and retain them in endosomal compartments. This interaction reduces 5-HT1A surface expression and is mediated by interactions between the fourth and fifth trans-membrane domain (TMD). This possibly represents a mechanism by which 5-ht5b receptors regulate the activity of other 5-HT receptor.
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      Energetics and mechanism of anion permeation across formate-nitrite transporters. 

      Atkovska, Kalina; Hub, Jochen S.
      Scientific reports 2017-09-20; 7(1): Art. 12027
      Formate-nitrite transporters (FNTs) facilitate the translocation of monovalent polyatomic anions, such as formate and nitrite, across biological membranes. FNTs are widely distributed among pathogenic bacteria and eukaryotic parasites, but they lack human homologues, making them attractive drug targets. The mechanisms and energetics involved in anion permeation across the FNTs have remained largely unclear. Both, channel and transporter mode of function have been proposed, with strong indication of proton coupling to the permeation process. We combine molecular dynamics simulations, quantum mechanical calculations, and pK a calculations, to compute the energetics of the complete permeation cycle of an FNT. We find that anions as such, are not able to traverse the FNT pore. Instead, anion binding into the pore is energetically coupled to protonation of a centrally located histidine. In turn, the histidine can protonate the permeating anion, thereby enabling its release. Such mechanism can accommodate the functional diversity among the FNTs, as it may facilitate both, export and import of substrates, with or without proton co-transport. The mechanism excludes proton leakage via the Grotthuss mechanism, and it rationalises the selectivity for weak acids.
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      Activating de novo mutations in NFE2L2 encoding NRF2 cause a multisystem disorder. 

      Huppke, Peter; Weissbach, Susann; Church, Joseph A.; Schnur, Rhonda; Krusen, Martina; Dreha-Kulaczewski, Steffi; Kühn-Velten, W. Nikolaus; Wolf, Annika; Huppke, Brenda; Millan, Francisca; et al.
      Begtrup, AmberAlmusafri, FatimaThiele, HolgerAltmüller, JanineNürnberg, PeterMüller, MichaelGärtner, Jutta
      Nature communications 2017-10-10; 8(1): Art. 818
      Transcription factor NRF2, encoded by NFE2L2, is the master regulator of defense against stress in mammalian cells. Somatic mutations of NFE2L2 leading to NRF2 accumulation promote cell survival and drug resistance in cancer cells. Here we show that the same mutations as inborn de novo mutations cause an early onset multisystem disorder with failure to thrive, immunodeficiency and neurological symptoms. NRF2 accumulation leads to widespread misregulation of gene expression and an imbalance in cytosolic redox balance. The unique combination of white matter lesions, hypohomocysteinaemia and increased G-6-P-dehydrogenase activity will facilitate early diagnosis and therapeutic intervention of this novel disorder.The NRF2 transcription factor regulates the response to stress in mammalian cells. Here, the authors show that activating mutations in NRF2, commonly found in cancer cells, are found in four patients with a multisystem disorder characterized by immunodeficiency and neurological symptoms.
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      Is cardiac wasting accompanied by skeletal muscle loss in breast cancer patients receiving anticancer treatment? 

      Ishida, Junichi; Saitoh, Masakazu; Springer, Jochen
      Journal of cachexia, sarcopenia and muscle 2017-10; 8(5) p.851-852
      not available
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      The contractile adaption to preload depends on the amount of afterload 

      Schotola, Hanna; Sossalla, Samuel T.; Renner, André; Gummert, Jan; Danner, Bernhard C.; Schott, Peter; Toischer, Karl
      ESC Heart Failure
      Aims The Frank–Starling mechanism (rapid response (RR)) and the secondary slow response (SR) are known to contribute to increases contractile performance. The contractility of the heart muscle is influenced by pre-load and after-load. Because of the effect of pre-load vs. after-load on these mechanisms in not completely understood, we studied the effect in isolated muscle strips. Methods and results Progressive stretch lead to an increase in shortening/force development under isotonic (only pre-load) and isometric conditions (pre- and after-load). Muscle length with maximal function was reached earlier under isotonic (Lmax-isotonic) compared with isometric conditions (Lmax-isometric) in nonfailing rabbit, in human atrial and in failing ventricular muscles. Also, SR after stretch from slack to Lmax-isotonic was comparable under isotonic and isometric conditions (human: isotonic 10 ± 4%, isometric 10 ± 4%). Moreover, a switch from isotonic to isometric conditions at Lmax-isometric showed no SR proving independence of after-load. To further analyse the degree of SR on the total contractile performance at higher pre-load muscles were stretched from slack to 98% Lmax-isometric under isotonic conditions. Thereby, the SR was 60 ± 9% in rabbit and 51 ± 14% in human muscle strips. Conclusions This work shows that the acute contractile response largely depends on the degree and type of mechanical load. Increased filling of the heart elevates pre-load and prolongs the isotonic part of contraction. The reduction in shortening at higher levels of pre-load is thereby partially compensated by the pre-load-induced SR. After-load shifts the contractile curve to a better ‘myofilament function’ by probably influencing thin fibers and calcium sensitivity, but has no effect on the SR.
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      Thirty Minutes of Hypobaric Hypoxia Provokes Alterations of Immune Response, Haemostasis, and Metabolism Proteins in Human Serum. 

      Hinkelbein, Jochen; Jansen, Stefanie; Iovino, Ivan; Kruse, Silvia; Meyer, Moritz; Cirillo, Fabrizio; Drinhaus, Hendrik; Hohn, Andreas; Klein, Corinna; Robertis, Edoardo De; et al.
      Beutner, Dirk
      International journal of molecular sciences 2017-08-31; 18(9): Art. 1882
      Hypobaric hypoxia (HH) during airline travel induces several (patho-) physiological reactions in the human body. Whereas severe hypoxia is investigated thoroughly, very little is known about effects of moderate or short-term hypoxia, e.g. during airline flights. The aim of the present study was to analyse changes in serum protein expression and activation of signalling cascades in human volunteers staying for 30 min in a simulated altitude equivalent to airline travel. After approval of the local ethics committee, 10 participants were exposed to moderate hypoxia (simulation of 2400 m or 8000 ft for 30 min) in a hypobaric pressure chamber. Before and after hypobaric hypoxia, serum was drawn, centrifuged, and analysed by two-dimensional gel electrophoresis (2-DIGE) and matrix-assisted laser desorption/ionization followed by time-of-flight mass spectrometry (MALDI-TOF). Biological functions of regulated proteins were identified using functional network analysis (GeneMania(®), STRING(®), and Perseus(®) software). In participants, oxygen saturation decreased from 98.1 ± 1.3% to 89.2 ± 1.8% during HH. Expression of 14 spots (i.e., 10 proteins: ALB, PGK1, APOE, GAPDH, C1QA, C1QB, CAT, CA1, F2, and CLU) was significantly altered. Bioinformatic analysis revealed an association of the altered proteins with the signalling cascades "regulation of haemostasis" (four proteins), "metabolism" (five proteins), and "leukocyte mediated immune response" (five proteins). Even though hypobaric hypoxia was short and moderate (comparable to an airliner flight), analysis of protein expression in human subjects revealed an association to immune response, protein metabolism, and haemostasis.
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      Specificity of surface EMG recordings for gastrocnemius during upright standing. 

      Vieira, Taian Martins; Botter, Alberto; Muceli, Silvia; Farina, Dario
      Scientific reports 2017-10-16; 7(1): Art. 13300
      The relatively large pick-up volume of surface electrodes has for long motivated the concern that muscles other than that of interest may contribute to surface electromyograms (EMGs). Recent findings suggest however the pick-up volume of surface electrodes may be smaller than previously appreciated, possibly leading to the detection of surface EMGs insensitive to muscle activity. Here we combined surface and intramuscular recordings to investigate how comparably action potentials from gastrocnemius and soleus are represented in surface EMGs detected with different inter-electrode distances. We computed the firing instants of motor units identified from intramuscular EMGs detected from gastrocnemius and soleus while five participants stood upright. We used these instants to trigger and average surface EMGs detected from multiple skin regions along gastrocnemius. Results from 66 motor units (whereof 31 from gastrocnemius) revealed the surface-recorded amplitude of soleus action potentials was 6% of that of gastrocnemius and did not decrease for inter-electrode distances smaller than 4 cm. Gastrocnemius action potentials were more likely detected for greater inter-electrode distances and their amplitude increased steeply up to 5 cm inter-electrode distance. These results suggest that reducing inter-electrode distance excessively may result in the detection of surface EMGs insensitive to gastrocnemius activity without substantial attenuation of soleus crosstalk.
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      Gut bacterial communities of diarrheic patients with indications of Clostridioides difficile infection. 

      Schneider, Dominik; Thürmer, Andrea; Gollnow, Kathleen; Lugert, Raimond; Gunka, Katrin; Groß, Uwe; Daniel, Rolf
      Scientific data 2017-10-17; 4: Art. 170152
      We present bacterial 16S rRNA gene datasets derived from stool samples of 44 patients with diarrhea indicative of a Clostridioides difficile infection. For 20 of these patients, C. difficile infection was confirmed by clinical evidence. Stool samples from patients originating from Germany, Ghana, and Indonesia were taken and subjected to DNA isolation. DNA isolations of stool samples from 35 asymptomatic control individuals were performed. The bacterial community structure was assessed by 16S rRNA gene analysis (V3-V4 region). Metadata from patients and control individuals include gender, age, country, presence of diarrhea, concomitant diseases, and results of microbiological tests to diagnose C. difficile presence. We provide initial data analysis and a dataset overview. After processing of paired-end sequencing data, reads were merged, quality-filtered, primer sequences removed, reads truncated to 400 bp and dereplicated. Singletons were removed and sequences were sorted by cluster size, clustered at 97% sequence similarity and chimeric sequences were discarded. Taxonomy to each operational taxonomic unit was assigned by BLASTn searches against Silva database 123.1 and a table was constructed.
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      Sexual dimorphism of AMBRA1-related autistic features in human and mouse. 

      Mitjans, M.; Begemann, M.; Ju, A.; Dere, E.; Wüstefeld, L.; Hofer, S.; Hassouna, I.; Balkenhol, J.; Oliveira, B.; van der Auwera, S.; et al.
      Tammer, R.Hammerschmidt, K.Völzke, H.Homuth, G.Cecconi, F.Chowdhury, K.Grabe, H.Frahm, J.Boretius, S.Dandekar, T.Ehrenreich, H.
      Translational psychiatry 2017-10-10; 7(10): Art. e1247
      Ambra1 is linked to autophagy and neurodevelopment. Heterozygous Ambra1 deficiency induces autism-like behavior in a sexually dimorphic manner. Extraordinarily, autistic features are seen in female mice only, combined with stronger Ambra1 protein reduction in brain compared to males. However, significance of AMBRA1 for autistic phenotypes in humans and, apart from behavior, for other autism-typical features, namely early brain enlargement or increased seizure propensity, has remained unexplored. Here we show in two independent human samples that a single normal AMBRA1 genotype, the intronic SNP rs3802890-AA, is associated with autistic features in women, who also display lower AMBRA1 mRNA expression in peripheral blood mononuclear cells relative to female GG carriers. Located within a non-coding RNA, likely relevant for mRNA and protein interaction, rs3802890 (A versus G allele) may affect its stability through modification of folding, as predicted by in silico analysis. Searching for further autism-relevant characteristics in Ambra1(+/-) mice, we observe reduced interest of female but not male mutants regarding pheromone signals of the respective other gender in the social intellicage set-up. Moreover, altered pentylentetrazol-induced seizure propensity, an in vivo readout of neuronal excitation-inhibition dysbalance, becomes obvious exclusively in female mutants. Magnetic resonance imaging reveals mild prepubertal brain enlargement in both genders, uncoupling enhanced brain dimensions from the primarily female expression of all other autistic phenotypes investigated here. These data support a role of AMBRA1/Ambra1 partial loss-of-function genotypes for female autistic traits. Moreover, they suggest Ambra1 heterozygous mice as a novel multifaceted and construct-valid genetic mouse model for female autism.
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