Deacylation of Calcium-Dependent Antibiotics from Streptomyces violaceoruber in Co-culture with Streptomyces sp. MG7-G1

When Streptomyces violaceoruber grows together with Streptomyces sp. MG7-G1, it reacts with strongly induced droplet production on its aerial mycelium. Initially the metabolite profile of droplets from S. violaceoruber in co-culture with Streptomyces sp. MG7-G1 was compared to samples from S. violaceoruber in single-culture by using high-performance liquid chromatography-mass spectrometry (HPLC-MS). Then, the exudate from agar plates of co-cultures and single cultures (after freezing and thawing) was also analysed. Several compounds were only observed when S. violaceoruber was grown in co-culture. Based on their high-resolution ESI mass spectra and their comparable retention times to the calcium-dependent antibiotics (CDAs) produced by S. violaceoruber, the new compounds were suspected to be deacylated calcium-dependent antibiotics (daCDAs), lacking the 2,3-epoxyhexanoyl residue of CDAs. This was verified by detailed analysis of the MS/MS spectra of the daCDAs in comparison to the CDAs. The major CDA compounds present in calcium ion-supplemented agar medium of co-cultures were daCDAs, thus suggesting that Streptomyces sp. MG7-G1 expresses a deacylase that degrades CDAs.     

Support Vector machine and duration-aware conditional random field for identification of spatio-temporal activity patterns by combined indoor positioning and heart rate sensors

Tracking the spatio-temporal activity is highly relevant for domains like security, health, and quality management. Since animal welfare became a topic in politics and legislation locomotion patterns of livestock have received increasing interest. In contrast to the monitoring of pedestrians cattle activity tracking poses special challenges to both sensors and data analysis. Interesting states are not directly observable by a single sensor. In addition, sensors must be accepted by cattle and need to be robust enough to cope with a rough environment. In this article, we introduce the novel combination of heart rate and positioning sensors. Attached to neck and chest they are less interfering than accelerometers at the ankles. Exploiting the potential of such combined sensor system that records locomotion and non-spatial information from the heart rate sensor however is challenging. We introduce a novel two level method for the activity tracking focused on the duration and sequence of activity states. We combine Support Vector Machine (SVM) with Conditional Random Field (CRF) and extend Conditional Random fields by an explicit representation of duration. The SVM characterizes local activity states, whereas the CRF addresses sequences of local states to sequences incorporating spatial and non-spatial contextual knowledge. This combination provides a reliable and comprehensive identification of defined activity patterns, as well as their chronology and durations, suitable for the integration in an activity data base. This data base is used to extract physiological parameters and promises insights into internal states such as fitness, well-being and stress. Interestingly we were able to demonstrate a significant correlation between resting pulse rate and the day of pregnancy.     

Robustness of an aerobic metabolically vinyl chloride degrading bacterial enrichment culture

Degradation of the lower chlorinated ethenes is crucial to the application of natural attenuation or in situ bioremediation on chlorinated ethene contaminated sites. Recently, within mixtures of several chloroethenes as they can occur in contaminated groundwater inhibiting effects on aerobic chloroethene degradation have been shown. The current study demonstrated that metabolic vinyl chloride (VC) degradation by an enrichment culture originating from groundwater was not affected by an equimolar concentration (50 μM) of cis-1,2-dichloroethene (cDCE). Only cDCE concentrations at a ratio of 2.4:1 (initial cDCE to VC concentration) caused minor inhibition of VC degradation. Furthermore, the degradation of VC was not affected by the presence of trans-1,2-dichloroethene (tDCE), 1,1-dichloroethene (1,1-DCE), trichloroethene (TCE), and tetrachloroethene (PCE) in equimolar concentrations (50 μM). Only cDCE and tDCE were cometabolically degraded in small amounts. The VC-degrading culture demonstrated a broad pH tolerance from 5 to 9 with an optimum between 6 and 7. Results also showed that the culture could degrade VC concentrations up to 1,800 μM (110 mg/L).     

Exploring cognitive style and task-specific preferences for process representations

Process models describe someone’s understanding of processes. Processes can be described using unstructured, semi-formal or diagrammatic representation forms. These representations are used in a variety of task settings, ranging from understanding processes to executing or improving processes, with the implicit assumption that the chosen representation form will be appropriate for all task settings. We explore the validity of this assumption by examining empirically the preference for different process representation forms depending on the task setting and cognitive style of the user. Based on data collected from 120 business school students, we show that preferences for process representation formats vary dependent on application purpose and cognitive styles of the participants. However, users consistently prefer diagrams over other representation formats. Our research informs a broader research agenda on task-specific applications of process modeling. We offer several recommendations for further research in this area.     

Gene expression changes in a transgenic mouse model overexpressing human wildtype and mutant torsinA

Primary torsion dystonia is an autosomal-dominantly inherited, neurodevelopmental movement disorder caused by a GAG deletion (ΔGAG) in the DYT1 gene, encoding torsinA. This mutation is responsible for approximately 70% of cases of early-onset primary torsion dystonia. The function of wildtype torsinA is still unknown, and it is unsolved how the deletion in the DYT1 gene contributes to the development of the disease. To better understand the molecular processes involved in torsinA pathology, we used genome-wide oligonucleotide microarrays to characterize gene expression patterns in the striatum of mouse models overexpressing the human wildtype and mutant torsinA. By this approach we were able to detect gene expression changes that seem to be specific for torsinA pathology. We found an impact of torsinA, independent from genotype, on vesicle trafficking, exocytosis, and neurotransmitter release in our mouse model. In addition, we were able to identify several new pathways and processes involved in the development of the nervous system that are affected by wildtype and mutant torsinA. Furthermore, we have striking evidence from our gene expression data that glutamate receptor mediated synaptic plasticity in the striatum is the affected underlying cellular process for impaired motor learning in human ΔGAG torsinA transgenic mice.     

Office task effects on comfort and body dynamics in five dynamic office chairs

In the present study, we investigated the effect of office tasks on posture and movements in field settings, and the comfort rating for chair characteristics and correlation with type of task. The tasks studied were: computer work, telephoning, desk work and conversation. Postures, movements, chair part inclinations and comfort rating data were collected from 12 subjects. Computer work showed the lowest physical activity, together with upright trunk and head position and low backrest inclination. Conversation shows the highest activity of head legs and low back together with the highest cervical spine extension. In contrast, desk work provoked the most cervical spine flexion and showed the second lowest activity. The telephoning tasks showed medium activity and the highest kyphosis. Conversation showed the highest backrest inclination. Positive comfort relations were found for computer work and a "swing system" chair, for telephoning and an active longitudinal seat rotation, and for desk work and a chair with a three-dimensionally moveable seat.     

Analyses of circRNA Expression throughout the Light-Dark Cycle Reveal a Strong Regulation of Cdr1as,Associated with Light Entrainment in the SCN

Circular RNAs (circRNAs) are a large class of relatively stable RNA molecules that are highly expressed in animal brains. Many circRNAs have been associated with CNS disorders accompanied by an aberrant wake-sleep cycle. However, the regulation of circRNAs in brain homeostasis over daily light-dark (LD) cycles has not been characterized. Here, we aim to quantify the daily expression changes of circRNAs in physiological conditions in healthy adult animals. Using newly generated and public RNA-Seq data, we monitored circRNA expression throughout the 12:12 h LD cycle in various mouse brain regions. We identified that Cdr1as, a conserved circRNA that regulates synaptic transmission, is highly expressed in the suprachiasmatic nucleus (SCN), the master circadian pacemaker. Despite its high stability, Cdr1as has a very dynamic expression in the SCN throughout the LD cycle, as well as a significant regulation in the hippocampus following the entry into the dark phase. Computational integration of different public datasets predicted that Cdr1as is important for regulating light entrainment in the SCN. We hypothesize that the expression changes of Cdr1as in the SCN, particularly during the dark phase, are associated with light-induced phase shifts. Importantly, our work revises the current beliefs about natural circRNA stability and suggests that the time component must be considered when studying circRNA regulation.     

Circulating miR-200 Family and CTCs in Metastatic Breast Cancer before,during, and after a New Line of Systemic Treatment

The extracellular circulating microRNA (miR)-200 regulates epithelial-mesenchymal transition and, thus, plays an essential role in the metastatic cascade and has shown itself to be a promising prognostic and predictive biomarker in metastatic breast cancer (MBC). Expression levels of the plasma miR-200 family were analyzed in relationship to systemic treatment, circulating tumor cells (CTC) count, progression-free survival (PFS), and overall survival (OS). Expression of miR-200a, miR-200b, miR-200c, miR-141, and miR-429, and CTC status (CTC-positive ≥ 5 CTC/7.5 mL) was assessed in 47 patients at baseline (BL), after the first completed cycle of a new line of systemic therapy (1C), and upon the progression of disease (PD). MiR-200a, miR-200b, and miR-141 expression was reduced at 1C compared to BL. Upon PD, all miR-200s were upregulated compared to 1C. At all timepoints, the levels of miR-200s were elevated in CTC-positive versus CTC-negative patients. Further, heightened miR-200s expression and positive CTC status were associated with poorer OS at BL and 1C. In MBC patients, circulating miR-200 family members decreased after one cycle of a new line of systemic therapy, were elevated during PD, and were indicative of CTC status. Notably, increased levels of miR-200s and elevated CTC count correlated with poorer OS and PFS. As such, both are promising biomarkers for optimizing the clinical management of MBC.     

No Neuromuscular Side-Effects of Scopolamine in Sensorimotor Control and Force-Generating Capacity Among Parabolic Fliers

Scopolamine is used to counteract motion sickness in parabolic flight (PF) experiments. Although the drug’s anticholinergic properties effectively impede vomiting, recent studies document other sensory side-effects in the central nervous system that may considerably influence sensorimotor performance. This study aimed to quantify such effects in order to determine if they are of methodological and operational significance for sensorimotor control. Ten subjects of a PF campaign received a weight-sex-based dose of a subcutaneous scopolamine injection. Sensorimotor performance was recorded before medication, 20min, 2h and 4h after injection in four space-relevant paradigms: balance control in one-leg stance with eyes open (protocol 1) and closed as well as force-generating capacity in countermovement jumps and hops (protocol 2). Postural sway, forces and joint angles were recorded. Neuromuscular control was assessed by electromyography and peripheral nerve stimulation; H-reflexes and M-waves were used to monitor spinal excitability of the Ia afferent reflex circuitry and maximal motor output. (1) H-reflex amplitudes, latencies and functional reflexes remained unchanged after scopolamine injection. (2) M-waves, neuromuscular activation intensities and antagonistic muscle coordination did not change with scopolamine administration. (3) Balance performance and force-generating capacity were not impeded by scopolamine. We found no evidence for changes in sensorimotor control in response to scopolamine injection. Sensory processing of daily relevant reflexes, spinal excitability, maximal motor output and performance parameters were not sensitive to the medication. We conclude that scopolamine administration can be used to counteract motion sickness in PF without methodological and operational concerns or interference regarding sensorimotor skills associated with neuromuscular control.