Förderzeitraum 2015
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- D-1221-2009 (1)
Background
Fibromyalgia syndrome (FMS) is a chronic condition characterized by widespread pain and associated symptoms. We investigated cerebral activation in FMS patients by functional near-infrared spectroscopy (fNIRS).
Methods
Two stimulation paradigms were applied: a) painful pressure stimulation at the dorsal forearm; b) verbal fluency test (VFT). We prospectively recruited 25 FMS patients, ten patients with unipolar major depression (MD) without pain, and 35 healthy controls. All patients underwent neurological examination and all subjects were investigated with questionnaires (pain, depression, FMS, empathy).
Results
FMS patients had lower pressure pain thresholds than patients with MD and controls (p < 0.001) and reported higher pain intensity (p < 0.001). Upon unilateral pressure pain stimulation fNIRS recordings revealed increased bilateral cortical activation in FMS patients compared to controls (p < 0.05). FMS patients also displayed a stronger contralateral activity over the dorsolateral prefrontal cortex in direct comparison to patients with MD (p < 0.05). While all three groups performed equally well in the VFT, a frontal deficit in cortical activation was only found in patients with depression (p < 0.05). Performance and cortical activation correlated negatively in FMS patients (p < 0.05) and positively in patients with MD (p < 0.05).
Conclusion
Our data give further evidence for altered central nervous processing in patients with FMS and the distinction between FMS and MD.
Background
Chronic hyperglycemia (CHG) with HbA1c as an indicator affects postoperative mortality and morbidity after coronary artery bypass grafting surgery (CABG). Acute kidney injury (AKI) is one of the frequent postoperative complications after CABG impacting short-and long-term outcomes. We investigated the association between CHG and postoperative incidence of AKI in CABG patients with and without history of diabetes mellitus (DM).
Methods
This cohort study consecutively enrolled patients undergoing CABG in 2009 at the department for cardiovascular surgery. CHG was defined as HbA1c ≥ 6.0 %. Patients with advanced chronic kidney disease (CKD) were excluded. The incidence of postoperative AKI and its association with CHG was analyzed by univariate and multivariate logistic regression modeling.
Results
Three-hundred-seven patients were analyzed. The incidence of AKI was 48.2 %. Patients with CHG (n = 165) were more likely to be female and had greater waist circumference as well as other comorbid conditions, such as smoking, history of DM, CKD, hypertension, pulmonary hypertension, and chronic obstructive pulmonary disease (all p ≤ 0.05). Preoperative eGFR, atrial fibrillation (AF), history of DM and CHG were associated with an increased risk of postoperative AKI in univariate analyses. In multivariate modelling, history of DM as well as preoperative eGFR and AF lost significance, while age, CHG and prolonged OP duration (p < 0.05) were independently associated with postoperative AKI.
Conclusions
Our results suggest that CHG defined on a single measurement of HbA1c ≥ 6.0 % was associated with the incidence of AKI after CABG. This finding might implicate that treatment decisions, including the selection of operative strategies, could be based on HbA1c measurement rather than on a recorded history of diabetes.
LINC complexes are evolutionarily conserved nuclear envelope bridges, physically connecting the nucleus to the peripheral cytoskeleton. They are pivotal for dynamic cellular and developmental processes, like nuclear migration, anchoring and positioning, meiotic chromosome movements and maintenance of cell polarity and nuclear shape. Active nuclear reshaping is a hallmark of mammalian sperm development and, by transducing cytoskeletal forces to the nuclear envelope, LINC complexes could be vital for sperm head formation as well. We here analyzed in detail the behavior and function of Sun4, a bona fide testis-specific LINC component. We demonstrate that Sun4 is solely expressed in spermatids and there localizes to the posterior nuclear envelope, likely interacting with Sun3/Nesprin1 LINC components. Our study revealed that Sun4 deficiency severely impacts the nucleocytoplasmic junction, leads to mislocalization of other LINC components and interferes with the formation of the microtubule manchette, which finally culminates in a globozoospermia-like phenotype. Together, our study provides direct evidence for a critical role of LINC complexes in mammalian sperm head formation and male fertility.
It has been demonstrated that verbal context information alters the neural processing of ambiguous faces such as faces with no apparent facial expression. In social anxiety, neutral faces may be implicitly threatening for socially anxious individuals due to their ambiguous nature, but even more so if these neutral faces are put in self-referential negative contexts. Therefore, we measured event-related brain potentials (ERPs) in response to neutral faces which were preceded by affective verbal information (negative, neutral, positive). Participants with low social anxiety (LSA; n = 23) and high social anxiety (HSA; n = 21) were asked to watch and rate valence and arousal of the respective faces while continuous EEG was recorded. ERP analysis revealed that HSA showed elevated P100 amplitudes in response to faces, but reduced structural encoding of faces as indexed by reduced N170 amplitudes. In general, affective context led to an enhanced early posterior negativity (EPN) for negative compared to neutral facial expressions. Moreover, HSA compared to LSA showed enhanced late positive potentials (LPP) to negatively contextualized faces, whereas in LSA this effect was found for faces in positive contexts. Also, HSA rated faces in negative contexts as more negative compared to LSA. These results point at enhanced vigilance for neutral faces regardless of context in HSA, while structural encoding seems to be diminished (avoidance). Interestingly, later components of sustained processing (LPP) indicate that LSA show enhanced visuocortical processing for faces in positive contexts (happy bias), whereas this seems to be the case for negatively contextualized faces in HSA (threat bias). Finally, our results add further new evidence that top-down information in interaction with individual anxiety levels can influence early-stage aspects of visual perception.
Marine sponge–associated actinomycetes are considered as promising sources for the discovery of novel biologically active compounds. In the present study, a total of 64 actinomycetes were isolated from 12 different marine sponge species that had been collected offshore the islands of Milos and Crete, Greece, eastern Mediterranean. The isolates were affiliated to 23 genera representing 8 different suborders based on nearly full length 16S rRNA gene sequencing. Four putatively novel species belonging to genera Geodermatophilus, Microlunatus, Rhodococcus and Actinomycetospora were identified based on a 16S rRNA gene sequence similarity of < 98.5% to currently described strains. Eight actinomycete isolates showed bioactivities against Trypanosma brucei brucei TC221 with half maximal inhibitory concentration (IC50) values <20 μg/mL. Thirty four isolates from the Milos collection and 12 isolates from the Crete collection were subjected to metabolomic analysis using high resolution LC-MS and NMR for dereplication purposes. Two isolates belonging to the genera Streptomyces (SBT348) and Micromonospora (SBT687) were prioritized based on their distinct chemistry profiles as well as their anti-trypanosomal activities. These findings demonstrated the feasibility and efficacy of utilizing metabolomics tools to prioritize chemically unique strains from microorganism collections and further highlight sponges as rich source for novel and bioactive actinomycetes.
Mining Genomes of Three Marine Sponge-Associated Actinobacterial Isolates for Secondary Metabolism
(2015)
Here, we report the draft genome sequences of three actinobacterial isolates, Micromonospora sp. RV43, Rubrobacter sp. RV113, and Nocardiopsis sp. RV163 that had previously been isolated from Mediterranean sponges. The draft genomes were analyzed for the presence of gene clusters indicative of secondary metabolism using antiSMASH 3.0 and NapDos pipelines. Our findings demonstrated the chemical richness of sponge-associated actinomycetes and the efficacy of genome mining in exploring the genomic potential of sponge-derived actinomycetes.
CD1d molecules are MHC class I-like molecules that present glycolipids to iNKT cells. The highly conserved interaction between CD1d:α-Galactosylceramide (αGC) complexes and the iNKT TCR not only defines this population of αβ T cells but can also be used for its direct identification. Therefore, CD1d oligomers are a widely used tool for iNKT cell related investigations. To this end, the lipid chains of the antigen have to be inserted into the hydrophobic pockets of the CD1d binding cleft, often with help of surfactants. In this study, we investigated the influence of different surfactants (Triton X-100, Tween 20, Tyloxapol) on in vitro loading of CD1d molecules derived from four different species (human, mouse, rat and cotton rat) with αGC and derivatives carrying modifications of the acyl-chain (DB01-1, PBS44) and a 6-acetamido-6-deoxy-addition at the galactosyl head group (PBS57). We also compared rat CD1d dimers with tetramers and staining of an iNKT TCR transductant was used as readout for loading efficacy. The results underlined the importance of CD1d loading efficacy for proper analysis of iNKT TCR binding and demonstrated the necessity to adjust loading conditions for each oligomer/glycolipid combination. The efficient usage of surfactants as a tool for CD1d loading was revealed to be species-specific and depending on the origin of the CD1d producing cells. Additional variation of surfactant-dependent loading efficacy between tested glycolipids was influenced by the acyl-chain length and the modification of the galactosyl head group with PBS57 showing the least dependence on surfactants and the lowest degree of species-dependent differences.
To investigate the usefulness of pain-related evoked potentials (PREP) elicited by electrical stimulation for the identification of small fiber involvement in patients with mixed fiber neuropathy (MFN). Eleven MFN patients with clinical signs of large fiber impairment and neuropathic pain and ten healthy controls underwent clinical and electrophysiological evaluation. Small fiber function, electrical conductivity and morphology were examined by quantitative sensory testing (QST), PREP, and skin punch biopsy. MFN was diagnosed following clinical and electrophysiological examination (chronic inflammatory demyelinating neuropathy: n = 6; vasculitic neuropathy: n = 3; chronic axonal neuropathy: n = 2). The majority of patients with MFN characterized their pain by descriptors that mainly represent C-fiber-mediated pain. In QST, patients displayed elevated cold, warm, mechanical, and vibration detection thresholds and cold pain thresholds indicative of MFN. PREP amplitudes in patients correlated with cold (p < 0.05) and warm detection thresholds (p < 0.05). Burning pain and the presence of par-/dysesthesias correlated negatively with PREP amplitudes (p < 0.05). PREP amplitudes correlating with cold and warm detection thresholds, burning pain, and par-/dysesthesias support employing PREP amplitudes as an additional tool in conjunction with QST for detecting small fiber impairment in patients with MFN.