Micromonospora schwarzwaldensis sp. nov., a producer of telomycin, isolated from soil

A Gram-positive, spore-forming actinomycete strain (HKI0641T) was isolated from a soil sample collected in the Black Forest, Germany. During a screening for antimicrobial natural products this bacterium was identified as a producer of the antibiotic telomycin. Morphological characteristics and chemotaxonomic data suggested that the strain belongs to the genus Micromonospora. The peptidoglycan contains meso-diaminopimelic acid, and the fatty acid profile consists predominantly of anteiso-C15:0, iso-C15:0, iso-C16:0 and C16:0. MK-10(H4), MK-10(H2) and MK-10 were identified as the major menaquinones. To determine the taxonomic positioning of strain HKI0641T, we computed a binary tanglegram of two rooted phylogenetic trees that were based upon 16S rRNA and gyrB gene sequences, respectively. The comparative analysis of the two common classification methods strongly supported the phylogenetic affiliation with the genus Micromonospora, but it also revealed discrepancies in the assignment at the level of the genomic species. 16S rRNA gene sequence analysis identified M. coxensis DSM 45161T (99.1%) and M. marina DSM 45555T (99.0%) as the nearest taxonomic neighbours, whereas the gyrB sequence of strain HKI0641T indicated a closer relationship to M. aurantiaca DSM 43813T (95.1%). By means of DNA-DNA hybridization experiments, it was possible to resolve this issue and to clearly differentiate strain HKI0641T from other Micromonospora species. The type strains of the aforementioned Micromonospora species could be further distinguished from strain HKI0641T by several phenotypic properties, such as colony colour, NaCl tolerance and the utilization of carbon sources. The isolate was therefore assigned to a new species, for which the name Micromonospora schwarzwaldensis sp. nov. is proposed. The type strain is HKI0641T (= DSM 45708T = CIP 110415T).Fil: Vela Gurovic, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Instituto de Química del Sur; Argentina. Hans-Knöll-Institute; AlemaniaFil: Müller, Sebastian. Hans-Knöll-Institute; AlemaniaFil: Domin, Nicole. Hans-Knöll-Institute; AlemaniaFil: Seccareccia, Ivana. Hans-Knöll-Institute; AlemaniaFil: Nietzsche, Sandor. University Hospital Jena; AlemaniaFil: Martin, Karin. Hans-Knöll-Institute; AlemaniaFil: Nett, Markus. Hans-Knöll-Institute; Alemani

Information System for Error Report Management

Tato bakalářská práce se věnuje problematice testování softwarových aplikací a jejich údržbě.Záměrem této práce je vytvořit aplikaci, která bude pomocným nástrojem nejen při testovánísoftwarových výrobků, ale i při následném provozu a údržbě softwaru. Jedná se onástroj, jehož hlavním úkolem je umožnit jak samotným testerům, tak i koncovým uživatelůmpatřičné aplikace evidovat nalezené problémy a chyby. Jednotlivé chyby je následněmožné spravovat. Jelikož aplikace bude využívána také veřejnými uživateli testované či používanéaplikace, kteří jsou různého věku a schopností, byl by při vývoji kladen důraz najednoduchost ovládání.This bachelor thesis inquires the problematics of software testing and software maintenance.Motivation is to create an application, that would be a helpful tool not only for testingsoftware applications, but also for future software maintenance. This application is a tool,which main purpose is to allow registration of problems and errors not only to the testers,but also to the public end-users of a particular application. Those individual problems canbe managed using this system. Because the application will be used also by public end-usersof a particular application who very differ of age and skill, there is an emphasis on ease ofuse and intuitivness of the system.

Down-modulation of functional ventral striatum activation for emotional face stimuli in patients with insula damage

Insula damage results in substantial impairments in facial emotion recognition. In particular, left hemispheric damage appears to be associated with poorer recognition of aversively rated facial expressions. Functional imaging can provide information on differences in the processing of these stimuli in patients with insula lesions when compared to healthy matched controls (HCs). We therefore investigated 17 patients with insula lesions in the chronic stage following stroke and 13 HCs using a passive-viewing task with pictures of facial expressions testing the blood oxygenation dependent (BOLD) effect in predefined regions of interest (ROIs). We expected a decrease in functional activation in an area modulating emotional response (left ventral striatum) but not in the facial recognition areas in the left inferior fusiform gyrus. Quantification of BOLD-response in ROIs but also voxel-based statistics confirmed this hypothesis. The voxel-based analysis demonstrated that the decrease in BOLD in the left ventral striatum was driven by left hemispheric damaged patients (n = 10). In our patient group, insula activation was strongly associated with the intensity rating of facial expressions. In conclusion, the combination of performance testing and functional imaging in patients following circumscribed brain damage is a challenging method for understanding emotion processing in the human brain

Structural Alterations in the Corpus Callosum Are Associated with Suicidal Behavior in Women with Borderline Personality Disorder

Structural alterations in the corpus callosum (CC), the major white matter tract connecting functionally related brain regions in the two hemispheres, have been shown to be associated with emotional instability, impulsivity and suicidality in various mental disorders. To explore whether structural alterations of the CC would be similarly associated with emotional instability, impulsivity and suicidality in borderline personality disorder (BPD), we used diffusion tensor imaging (DTI) to assess the structural integrity of the CC in 21 BPD and 20 healthy control (HC) participants. Our hypothesis-driven analyses revealed a positive correlation between BPD participants’ suicidal behavior and fractional anisotropy (FA) in the splenium and genu of the CC and a negative correlation between BPD participants’ suicidal behavior and mean diffusivity (MD) in the splenium of CC. Our exploratory analyses suggested that suicidal BPD participants showed less FA and more MD in these regions than HC participants but that non-suicidal BPD participants showed similar FA and MD in these regions as HC participants. Taken together, our findings suggest an association between BPD participants’ suicidal behavior and structural alterations in regions of the CC that are connected with brain regions implicated in emotion regulation and impulse control. Structural alterations of the CC may, thus, account for deficits in emotion regulation and impulse control that lead to suicidal behavior in BPD. However, these findings should be considered as preliminary until replicated and extended in future studies that comprise larger samples of suicidal and non-suicidal BPD participants

Predicting Training Gain for a 3 Week Period of Arm Ability Training in the Subacute Stage After Stroke

Background: Biomarkers for gains of evidence based interventions for upper limb motor training in the subacute stage following stroke have rarely been described. Information about these parameters might help to identify patients who benefit from specific interventions and to determine individually expected behavioral gains for a certain period of therapy.Objective: To evaluate predictors for hand motor outcome after arm ability training in the subacute stage after stroke selected from known potentially relevant parameters (initial motor strength, structural integrity of the pyramidal tract and functional motor cortex integrity).Methods: We applied the arm ability training (AAT) over 3 weeks to a subpopulation of stroke patients with mild arm paresis, i.e., in 14 patients on average 4 weeks after stroke. The following biomarkers were measured before therapy onset: grip strength on the affected hand, transcranial magnetic stimulation recruitment curve steepness over the primary motor hand area [slope ratio between the ipsilesional hemisphere (IH) and contralesional hemisphere (CH)], and diffusion weighted MRI fractional anisotropy (FA) in the posterior limb of the internal capsule (PLIC; determined as a lateralization index between IH and CH). Outcome was assessed as the AATgain (percentage improvement over training). The “Test d'Evaluation des Membres Supérieurs de Personnes Âgées” (TEMPA) was assessed before and after training to test for possible associations of AAT with activity of daily living.Results: A stepwise linear regression identified the lateralization index of PLIC FA as the only significant predictor for AAT-gain (R2 = 0.519; P = 0.029). AAT-gain was positively associated (r = 0.59; P = 0.028) with improvement in arm function during daily activities (TEMPA).Conclusions: While all mildly affected patients achieved a clinically relevant therapeutic effect, pyramidal tract integrity nevertheless had a modifying role for clinical benefit

Global functional connectivity reorganization reflects cognitive processing speed deficits and fatigue in multiple sclerosis

Background and purpose Cognitive impairment (CI) in multiple sclerosis (MS) is associated with bidirectional changes in resting‐state centrality measures. However, practicable functional magnetic resonance imaging (fMRI) biomarkers of CI are still lacking. The aim of this study was to assess the graph‐theory‐based degree rank order disruption index (kD) and its association with cognitive processing speed as a marker of CI in patients with MS (PwMS) in a secondary cross‐sectional fMRI analysis. Methods Differentiation between PwMS and healthy controls (HCs) using kD and its correlation with CI (Symbol Digit Modalities Test) was compared to established imaging biomarkers (regional degree, volumetry, diffusion‐weighted imaging, lesion mapping). Additional associations were assessed for fatigue (Fatigue Scale for Motor and Cognitive Functions), gait and global disability. Results Analysis in 56 PwMS and 58 HCs (35/27 women, median age 45.1/40.5 years) showed lower kD in PwMS than in HCs (median −0.30/−0.06, interquartile range 0.55/0.54; p = 0.009, Mann–Whitney U test), yielding acceptable yet non‐superior differentiation (area under curve 0.64). kD and degree in medial prefrontal cortex (MPFC) correlated with CI (kD/MPFC Spearman's ρ = 0.32/−0.45, p = 0.019/0.001, n = 55). kD also explained fatigue (ρ = −0.34, p = 0.010, n = 56) but neither gait nor disability. Conclusions kD is a potential biomarker of CI and fatigue warranting further validation

Juvenile Myoclonic Epilepsy Shows Potential Structural White Matter Abnormalities: A TBSS Study

Background: Several studies on patients with juvenile myoclonic epilepsy (JME) showed widespread white matter (WM) abnormalities in the brain. The aim of this study was to investigate potential structural abnormalities in JME patients (1) compared to healthy controls, (2) among JME subgroups with or without photoparoxysmal responses (PPR), and (3) in correlation with clinical variables.Methods: A selection of 31 patients with JME (12 PPR positive) and 27 age and gender matched healthy controls (HC) were studied at a tertiary epilepsy center. Fractional anisotropy (FA) was calculated and intergroup differences analyzed using Tract Based Spatial Statistics (TBSS).Results: Compared to HC the JME group showed reduced FA widespread and bilateral in the longitudinal fasciculus, inferior fronto-occipital fasciculus, corticospinal tract, anterior and posterior thalamic radiation, corona radiata, corpus callosum, cingulate gyrus and external capsule (p < 0.01). Subgroup analysis revealed no significant differences of WM alterations between PPR positive and negative patients and with clinical and epilepsy-related factors.Conclusions: Widespread microstructural abnormalities among patients with JME have been identified.Prior findings of frontal and thalamofrontal microstructural abnormalities have been confirmed. Additionally, microstructural abnormalities were found in widespread extra-frontal regions that may help to validate pathophysiological concepts of JME

Regulation of Neuron Survival through an Intersectin-Phosphoinositide 3'-Kinase C2 -AKT Pathway

While endocytosis attenuates signals from plasma membrane receptors, recent studies suggest that endocytosis also serves as a platform for the compartmentalized activation of cellular signaling pathways. Intersectin (ITSN) is a multidomain scaffolding protein that regulates endocytosis and has the potential to regulate various biochemical pathways through its multiple, modular domains. To address the biological importance of ITSN in regulating cellular signaling pathways versus in endocytosis, we have stably silenced ITSN expression in neuronal cells by using short hairpin RNAs. Decreasing ITSN expression dramatically increased apoptosis in both neuroblastoma cells and primary cortical neurons. Surprisingly, the loss of ITSN did not lead to major defects in the endocytic pathway. Yeast two-hybrid analysis identified class II phosphoinositide 3′-kinase C2β (PI3K-C2β) as an ITSN binding protein, suggesting that ITSN may regulate a PI3K-C2β-AKT survival pathway. ITSN associated with PI3K-C2β on a subset of endomembrane vesicles and enhanced both basal and growth factor-stimulated PI3K-C2β activity, resulting in AKT activation. The use of pharmacological inhibitors, dominant negatives, and rescue experiments revealed that PI3K-C2β and AKT were epistatic to ITSN. This study represents the first demonstration that ITSN, independent of its role in endocytosis, regulates a critical cellular signaling pathway necessary for cell survival

Monitoring HSVtk suicide gene therapy: the role of [18F]FHPG membrane transport

Favourable pharmacokinetics of the prodrug are essential for successful HSVtk/ganciclovir (GCV) suicide gene therapy. [F-18] FHPG PET might be a suitable technique to assess the pharmacokinetics of the prodrug GCV noninvasively, provided that [F-18] FHPG mimics the behaviour of GCV. Since membrane transport is an important aspect of the pharmacokinetics of the prodrug, we investigated the cellular uptake mechanism of [F-18] FHPG in an HSVtk expressing C6 rat glioma cell line and in tumour- bearing rats. The nucleoside transport inhibitors dipyridamol, NBMPR and 2- chloroadenosine did not significantly affect the [F-18] FHPG uptake in vitro. Thymidine and uridine significantly decreased [F-18] FHPG uptake by 84 and 58%, respectively, but an enzyme assay revealed that this decline was due to inhibition of the HSVtk enzyme rather than membrane transport. Nucleobase transport inhibitors, thymine and adenine, caused a 58 and 55% decline in tracer uptake, respectively. In vivo, the ratio of [F-18] FHPG uptake in C6tk and C6 tumours decreased from 3.070.5 to 1.070.2 after infusion of adenine. Thus, in our tumour model, [F-18] FHPG transport exclusively occurred via purine nucleobase transport. In this respect, FHPG does not resemble GCV, which is predominantly taken up via the nucleoside transporter, but rather acyclovir, which is also taken up via the purine nucleobase carrier

Complete genome sequence of the filamentous gliding predatory bacterium Herpetosiphon aurantiacus type strain (114-95T)

Herpetosiphon aurantiacus Holt and Lewin 1968 is the type species of the genus Herpetosiphon, which in turn is the type genus of the family Herpetosiphonaceae, type family of the order Herpetosiphonales in the phylum Chloroflexi. H. aurantiacus cells are organized in filaments which can rapidly glide. The species is of interest not only because of its rather isolated position in the tree of life, but also because Herpetosiphon ssp. were identified as predators capable of facultative predation by a wolf pack strategy and of degrading the prey organisms by excreted hydrolytic enzymes. The genome of H. aurantiacus strain 114-95T is the first completely sequenced genome of a member of the family Herpetosiphonaceae. The 6,346,587 bp long chromosome and the two 339,639 bp and 99,204 bp long plasmids with a total of 5,577 protein-coding and 77 RNA genes was sequenced as part of the DOE Joint Genome Institute Program DOEM 2005