Diagnostic performance of the specific uptake size index for semi-quantitative analysis of I-123-FP-CIT SPECT: harmonized multi-center research setting versus typical clinical single-camera setting

Introduction: The specific uptake size index (SUSI) of striatal FP-CIT uptake is independent of spatial resolution in the SPECT image, in contrast to the specific binding ratio (SBR). This suggests that the SUSI is particularly appropriate for multi-site/multi-camera settings in which camera-specific effects increase inter-subject variability of spatial resolution. However, the SUSI is sensitive to inter-subject variability of striatum size. Furthermore, it might be more sensitive to errors of the estimate of non-displaceable FP-CIT binding. This study compared SUSI and SBR in the multi-site/multi-camera (MULTI) setting of a prospective multi-center study and in a mono-site/mono-camera (MONO) setting representative of clinical routine. Methods: The MULTI setting included patients with Parkinson’s disease (PD, n = 438) and healthy controls (n = 207) from the Parkinson Progression Marker Initiative. The MONO setting included 122 patients from routine clinical patient care in whom FP-CIT SPECT had been performed with the same double-head SPECT system according to the same acquisition and reconstruction protocol. Patients were categorized as “neurodegenerative” (n = 84) or “non-neurodegenerative” (n = 38) based on follow-up data. FP-CIT SPECTs were stereotactically normalized to MNI space. SUSI and SBR were computed for caudate, putamen, and whole striatum using unilateral ROIs predefined in MNI space. SUSI analysis was repeated in native patient space in the MONO setting. The area (AUC) under the ROC curve for identification of PD/“neurodegenerative” cases was used as performance measure. Results: In both settings, the highest AUC was achieved by the putamen (minimum over both hemispheres), independent of the semi-quantitative method (SUSI or SBR). The putaminal SUSI provided slightly better performance with ROI analysis in MNI space compared to patient space (AUC = 0.969 vs. 0.961, p = 0.129). The SUSI (computed in MNI space) performed slightly better than the SBR in the MULTI setting (AUC = 0.993 vs. 0.991, p = 0. 207) and slightly worse in the MONO setting (AUC = 0.969 vs. AUC = 0.976, p = 0.259). There was a trend toward larger AUC difference between SUSI and SBR in the MULTI setting compared to the MONO setting (p = 0.073). Variability of voxel intensity in the reference region was larger in misclassified cases compared to correctly classified cases for both SUSI and SBR (MULTI setting: p = 0.007 and p = 0.012, respectively). Conclusions: The SUSI is particularly useful in MULTI settings. SPECT images should be stereotactically normalized prior to SUSI analysis. The putaminal SUSI provides better diagnostic performance than the SUSI of the whole striatum. Errors of the estimate of non-displaceable count density in the reference region can cause misclassification by both SUSI and SBR, particularly in borderline cases. These cases might be identified by visual checking FP-CIT uptake in the reference region for particularly high variability

Molecular cloning, expression analysis and assignment of the porcine tumor necrosis factor superfamily member 10 gene (TNFSF10) to SSC13q34 -> q36 by fluorescence in situ hybridization and radiation hybrid mapping

We have cloned the complete coding region of the porcine TNFSF10 gene. The porcine TNFSF10 cDNA has an ORF of 870 nucleotides and shares 85 % identity with human TNFSF10, and 75% and 72% identity with rat and mouse Tnfsf10 coding sequences, respectively. The deduced porcine TNFSF10 protein consists of 289 amino acids with the calculated molecular mass of 33.5 kDa and a predicted pI of 8.15. The amino acid sequence similarities correspond to 86, 72 and 70% when compared with human, rat and mouse sequences, respectively. Nor-them blot analysis detected TNFSF10-specific transcripts (similar to 1.7 kb) in various organs of a 10-week-old pig, suggesting ubiquitous expression. Real-time RT-PCR studies of various organs from fetal (days 73 and 98) and postnatal stages (two weeks, eight months) demonstrated developmental and tissue-specific regulation of TNFSF10 mRNA abundance. The chromosomal location of the porcine TNFSF10 gene was determined by FISH of a specific BAC clone to metaphase chromosomes. This TNFSF10 BAC clone has been assigned to SSC13q34 -> q36. Additionally, the localization of the TNFSF10 gene was verified by RH mapping on the porcine IMpRH panel. Copyright (c) 2005S. KargerAG, Basel

ATF4 Is an Oxidative Stress–Inducible, Prodeath Transcription Factor in Neurons in Vitro and in Vivo

Oxidative stress is pathogenic in neurological diseases, including stroke. The identity of oxidative stress-inducible transcription factors and their role in propagating the death cascade are not well known. In an in vitro model of oxidative stress, the expression of the bZip transcription factor activating transcription factor 4 (ATF4) was induced by glutathione depletion and localized to the promoter of a putative death gene in neurons. Germline deletion of ATF4 resulted in a profound reduction in oxidative stress-induced gene expression and resistance to oxidative death. In neurons, ATF4 modulates an early, upstream event in the death pathway, as resistance to oxidative death by ATF4 deletion was associated with decreased consumption of the antioxidant glutathione. Forced expression of ATF4 was sufficient to promote cell death and loss of glutathione. In ATF4(-/-) neurons, restoration of ATF4 protein expression reinstated sensitivity to oxidative death. In addition, ATF4(-/-) mice experienced significantly smaller infarcts and improved behavioral recovery as compared with wild-type mice subjected to the same reductions in blood flow in a rodent model of ischemic stroke. Collectively, these findings establish ATF4 as a redox-regulated, prodeath transcriptional activator in the nervous system that propagates death responses to oxidative stress in vitro and to stroke in vivo

The origin of the [C II] emission in the S140 PDRs - new insights from HIFI

Using Herschel's HIFI instrument we have observed [C II] along a cut through S140 and high-J transitions of CO and HCO+ at two positions on the cut, corresponding to the externally irradiated ionization front and the embedded massive star forming core IRS1. The HIFI data were combined with available ground-based observations and modeled using the KOSMA-tau model for photon dominated regions. Here we derive the physical conditions in S140 and in particular the origin of [C II] emission around IRS1. We identify three distinct regions of [C II] emission from the cut, one close to the embedded source IRS1, one associated with the ionization front and one further into the cloud. The line emission can be understood in terms of a clumpy model of photon-dominated regions. At the position of IRS1, we identify at least two distinct components contributing to the [C II] emission, one of them a small, hot component, which can possibly be identified with the irradiated outflow walls. This is consistent with the fact that the [C II] peak at IRS1 coincides with shocked H2 emission at the edges of the outflow cavity. We note that previously available observations of IRS1 can be well reproduced by a single-component KOSMA-tau model. Thus it is HIFI's unprecedented spatial and spectral resolution, as well as its sensitivity which has allowed us to uncover an additional hot gas component in the S140 region.Comment: accepted for publication in Astronomy and Astrophysics (HIFI special issue

Swabian MOSES 2021: An interdisciplinary field campaign for investigating convective storms and their event chains

The Neckar Valley and the Swabian Jura in southwest Germany comprise a hotspot for severe convective storms, causing tens of millions of euros in damage each year. Possible reasons for the high frequency of thunderstorms and the associated event chain across compartments were investigated in detail during the hydro-meteorological field campaign Swabian MOSES carried out between May and September 2021. Researchers from various disciplines established more than 25 temporary ground-based stations equipped with state-of-the-art in situ and remote sensing observation systems, such as lidars, dual-polarization X- and C-band Doppler weather radars, radiosondes including stratospheric balloons, an aerosol cloud chamber, masts to measure vertical fluxes, autosamplers for water probes in rivers, and networks of disdrometers, soil moisture, and hail sensors. These fixed-site observations were supplemented by mobile observation systems, such as a research aircraft with scanning Doppler lidar, a cosmic ray neutron sensing rover, and a storm chasing team launching swarmsondes in the vicinity of hailstorms. Seven Intensive Observation Periods (IOPs) were conducted on a total of 21 operating days. An exceptionally high number of convective events, including both unorganized and organized thunderstorms such as multicells or supercells, occurred during the study period. This paper gives an overview of the Swabian MOSES (Modular Observation Solutions for Earth Systems) field campaign, briefly describes the observation strategy, and presents observational highlights for two IOPs

Bradykinin and adenosine receptors mediate desflurane induced postconditioning in human myocardium: role of reactive oxygen species

BACKGROUND: Desflurane during early reperfusion has been shown to postcondition human myocardium, in vitro. We investigated the role of adenosine and bradykinin receptors, and generation of radical oxygen species in desflurane-induced postconditioning in human myocardium. METHODS: We recorded isometric contraction of human right atrial trabeculae hanged in an oxygenated Tyrode's solution (34 degrees Celsius, stimulation frequency 1 Hz). After a 30-min hypoxic period, desflurane 6% was administered during the first 5 min of reoxygenation. Desflurane was administered alone or with pretreatment of N-mercaptopropionylglycine, a reactive oxygen species scavenger, 8-(p-Sulfophenyl)theophylline, an adenosine receptor antagonist, HOE140, a selective B2 bradykinin receptor antagonist. In separate groups, adenosine and bradykinin were administered during the first minutes of reoxygenation alone or in presence of N-mercaptopropionylglycine. The force of contraction of trabeculae was recorded continuously. Developed force at the end of a 60-min reoxygenation period was compared (mean +/- standard deviation) between the groups by a variance analysis and post hoc test. RESULTS: Desflurane 6% (84 +/- 6% of baseline) enhanced the recovery of force after 60-min of reoxygenation as compared to control group (51 +/- 8% of baseline, P < 0.0001). N-mercaptopropionylglycine (54 +/- 3% of baseline), 8-(p-Sulfophenyl)theophylline (62 +/- 9% of baseline), HOE140 (58 +/- 6% of baseline) abolished desflurane-induced postconditioning. Adenosine (80 +/- 9% of baseline) and bradykinin (83 +/- 4% of baseline) induced postconditioning (P < 0.0001 vs control), N-mercaptopropionylglycine abolished the beneficial effects of adenosine and bradykinin (54 +/- 8 and 58 +/- 5% of baseline, respectively). CONCLUSIONS: In vitro, desflurane-induced postconditioning depends on reactive oxygen species production, activation of adenosine and bradykinin B2 receptors. And, the cardioprotective effect of adenosine and bradykinin administered at the beginning of reoxygenation, was mediated, at least in part, through ROS production

FoxO and Stress Responses in the Cnidarian Hydra vulgaris

Background: In the face of changing environmental conditions, the mechanisms underlying stress responses in diverse organisms are of increasing interest. In vertebrates, Drosophila, and Caenorhabditis elegans, FoxO transcription factors mediate cellular responses to stress, including oxidative stress and dietary restriction. Although FoxO genes have been identified in early-arising animal lineages including sponges and cnidarians, little is known about their roles in these organisms. Methods/Principal Findings: We have examined the regulation of FoxO activity in members of the well-studied cnidarian genus Hydra. We find that Hydra FoxO is expressed at high levels in cells of the interstitial lineage, a cell lineage that includes multipotent stem cells that give rise to neurons, stinging cells, secretory cells and gametes. Using transgenic Hydra that express a FoxO-GFP fusion protein in cells of the interstitial lineage, we have determined that heat shock causes localization of the fusion protein to the nucleus. Our results also provide evidence that, as in bilaterian animals, Hydra FoxO activity is regulated by both Akt and JNK kinases. Conclusions: These findings imply that basic mechanisms of FoxO regulation arose before the evolution of bilaterians an

Massively Parallel RNA Sequencing Identifies a Complex Immune Gene Repertoire in the lophotrochozoan Mytilus edulis

The marine mussel Mytilus edulis and its closely related sister species are distributed world-wide and play an important role in coastal ecology and economy. The diversification in different species and their hybrids, broad ecological distribution, as well as the filter feeding mode of life has made this genus an attractive model to investigate physiological and molecular adaptations and responses to various biotic and abiotic environmental factors. In the present study we investigated the immune system of Mytilus, which may contribute to the ecological plasticity of this species. We generated a large Mytilus transcriptome database from different tissues of immune challenged and stress treated individuals from the Baltic Sea using 454 pyrosequencing. Phylogenetic comparison of orthologous groups of 23 species demonstrated the basal position of lophotrochozoans within protostomes. The investigation of immune related transcripts revealed a complex repertoire of innate recognition receptors and downstream pathway members including transcripts for 27 toll-like receptors and 524 C1q domain containing transcripts. NOD-like receptors on the other hand were absent. We also found evidence for sophisticated TNF, autophagy and apoptosis systems as well as for cytokines. Gill tissue and hemocytes showed highest expression of putative immune related contigs and are promising tissues for further functional studies. Our results partly contrast with findings of a less complex immune repertoire in ecdysozoan and other lophotrochozoan protostomes. We show that bivalves are interesting candidates to investigate the evolution of the immune system from basal metazoans to deuterostomes and protostomes and provide a basis for future molecular work directed to immune system functioning in Mytilus