Diagnostische Bedeutung der alkalischen Phosphatase und ihrer Isoenzyme im Blutserum von Kühen

Die alkalische Phosphatase (AP) ist in Form von verschiedenen Isoenzymen in fast allen Geweben und Flüssigkeiten des Organismus vorhanden. Durch die Auftrennung der Gesamt-AP in ihre Isoenzyme ist eine Lokalisation von krankhaften Prozessen möglich. Da in der Veterinärmedizin die AP-Isoenzymdiagnostik bisher nicht praktisch zum Einsatz kommt, wurde in der vorliegenden Arbeit die Aussagekraft der Isoenzym-Aktivitäten bei verschiedenen Krankheitsbildern und die Eignung dieses Verfahren für den Einsatz in Klinik und Praxis untersucht. Die Untersuchungen wurden an insgesamt 106 Rindern durchgeführt. 25 gesunde Rinder bildeten eine Kontrollgruppe. 69 an Diarrhoe erkrankte Kühe wurden gemäß ihrer Primärerkrankung in 6 Gruppen eingeteilt: Labmagenverlagerung nach links (LMV li) (n=28), Labmagenverlagerung nach rechts (LMV re) (n=20), Enteritis (n=5), Strangulationsileus (n=4), Labmagenulcera (n=5) und Endometritis / Mastitis (n=7). Zwei weitere Gruppen bildeten Rinder mit einer Leberfunktionsstörung (n=20) und Rinder mit einer hochgradigen Aktivitätserhöhung der Gesamt-AP ≥ 300 U/l (n=12). Zudem wurden Blutproben vom Tag der Aufnahme und der Entlassung verglichen. Die AP-Isoenzyme im Blutserum wurden mit Hilfe des Testkits HYDRAGEL ISO-PAL K20 der Firma Sebia, Fulda elektrophoretisch auf Agarosegel aufgetrennt in die Leber-1-, Leber-2-, Knochen- und intestinalen Isoenzyme. Außerdem wurden bestimmt: Gesamt-Alkalische-Phosphatase, Glutamat-Dehydrogenase, Aspartat-Amino-Transferase (ASAT), Gamma-Glutamyl-Transferase, Alanin-Amino-Trans-ferase, Gesamtbilirubin, Gesamteiweiß, Harnstoff, Beta-Hydroxybuttersäure, Cholesterol, Calcium, anorganisches Phosphat und Leukozyten. Bei den gesunden Kühen beträgt die mediane Aktivität der Gesamt-AP 122 U/l, die der intestinalen AP 22,7 U/l und die der Leber-1-AP 51,0 U/l. Bei den Kühen mit Diarrhoe ist die intestinale AP-Aktivität bei Erkrankung signifikant erhöht (M=28,2 U/l). Bei der Unterteilung in verschiedene Erkrankungen weist sie bei den Tieren mit Strangulationsileus eine signifikant höhere Aktivität als bei den anderen Krankheiten auf (M=71,4 U/l). Die Gesamt-AP-Aktivität ist jedoch in keinem Fall signifikant erhöht und gibt somit keinen Hinweis auf einen Aktivitätsanstieg der intestinalen AP. Nach Abklingen der Diarrhoe ist die Wiederherstellung der Darmfunktion anhand einer Normalisierung der intestinalen AP-Aktivität nachvoll-ziehbar, da zwischen den gesunden Kühen und den rekonvaleszenten Tieren (M=24,2 U/l) kein signifikanter Unterschied besteht. Jedoch lässt die Aktivität des intestinalen Isoenzyms keine Rückschlüsse auf die zu Grunde liegende Grund-erkrankung zu, weil auch bei den anderen Erkrankungen ähnlich hohe Aktivitäten der intestinalen AP wie beim Ileus existieren. Auffällig ist auch eine Hypocholesterolämie bei den Kühen mit LMV li (M=1,86 mmol/l), LMV re (M=1,92 mmol/l) und besonders bei den Tieren mit Ileus (M=1,36 mmol/l) gegenüber den Gesunden (M=3,45 mmol/l). Die Untersuchung von Gesamt-AP-Aktivität und Leber-1-AP-Aktivität bei den Patien-ten mit einer Leberfunktionsstörung ergibt, dass der Grad der Erhöhung dieser Parameter einen Rückschluss auf die Schwere der Erkrankung zulässt. Bei den später verstorbenen Kühen sind für die Gesamt-AP (M=178 U/l) und für das Leber-1-Isoenzym (M=116,5 U/l) die hochgradigsten Aktivitätsanstiege zu verzeichnen. Eine Prognose hinsichtlich des Ausgangs der Erkrankung ist allerdings nicht zu treffen, weil keine signifikanten Aktivitätsunterschiede zwischen Kühen mit Exitus letalis und Heilung bestehen. Aber die ASAT-Aktivitäten (M=278,1 U/l) und die Bilirubinkonzen-trationen (M=20,5 µmol/l) sind bei den Tieren mit Exitus letalis deutlich höher als bei den rekonvaleszenten Kühen (M=145,6 U/l bzw. 12,5 µmol/l) und sind somit prognostisch verwertbar. Auf Grund dieser Ergebnisse erscheint die Aussagekraft der AP-Isoenzymdiagnostik als zu gering, um diese Methodik in Praxis und Klinik zur Zeit anzuwenden

Fluxes, Vacua, and Tadpoles meet Landau-Ginzburg and Fermat

Type IIB flux vacua based on Landau-Ginzburg models without K\"ahler deformations provide fully-controlled insights into the non-geometric and strongly-coupled string landscape. We show here that supersymmetric flux configurations at the Fermat point of the $1^9$ model, which were found long-time ago to saturate the orientifold tadpole, leave a number of massless fields, which however are not all flat directions of the superpotential at higher order. More generally, the rank of the Hessian of the superpotential is compatible with a suitably formulated tadpole conjecture for all fluxes that we found. Moreover, we describe new infinite families of supersymmetric 4d $\mathcal{N}=1$ Minkowski and AdS vacua and confront them with several other swampland conjectures.Comment: 37 pages, 1 figur

Roiu paisjärve tervendamise eeltööd – limnoloogiline hinnang

Uuring lähtub veekogude tervendamisel üldisest EL Veepoliitika Raamdirektiivi eesmärgist, mille järgi peavad siseveekogud saavutama hea ökoloogilise seisundi. Siseveekogude seisund on hea või väga hea, kui vee-ökosüsteemi esmasproduktsioon ja lagundamine on tasakaalus. Sellest lähtudes on oluline hinnata ideaalvariandis kogu elustikku, setete koostist, levikut, toitesoolade sisebilanssi, välisbilanssi ja veebilanssi. Roiu paisjärv on tehisveekogu, pindalalt (5,5 ha) ja mahult väike. Seepärast koguti setteproove kolmest punktist, planktoni ja vee omaduste proovid ühest punktist. Seevastu taimi uuriti üle kogu järve. EMÜ PKI Limnoloogiakeskus pole Roiu paisjärve varem uurinud. Seepärast on suurt rõhku pööratud inventuurile. Töös kirjeldatakse veekogu, esitatakse eripärad, funktsioneerimise peamised mõjurid, liikide seisund, veekogu ökoloogiline seisund. Hinnatakse koormustaluvust. Uuringu raames uuritakse kõiki paisjärve sissevoole, mis võivad olla oluliseks surveteguriks paisjärve seisundile. Lisaks tuleb tuvastada sissevooludest paisjärve suunatav reostuskoormus ning anda soovitused nende mõju vähendamiseks. Antakse järve seisundi tervendamiseks soovitused. Töödest võtsid osa järgmised EMÜ PKI Limnoloogiakeskuse töötajad: prof. I. Ott; PhD. H. Timm; PhD. H. Tammert; MSc. K. Saar; BSc. R. Laarmaa; MSc. M. Lehtpuu; MSc. T. Krause; MSc. A. Palm; MSc. M. Sepp, K. Ott; PhD. E.-J. Haberman

Kurepalu paisjärve tervendamise eeltööd – limnoloogiline hinnang

Uuring lähtub veekogude tervendamisel üldisest EL Veepoliitika Raamdirektiivi eesmärgist, mille järgi peavad siseveekogud saavutama hea ökoloogilise seisundi. Siseveekogude seisund on hea või väga hea, kui vee-ökosüsteemi esmasproduktsioon ja lagundamine on tasakaalus. Sellest lähtudes on oluline hinnata ideaalvariandis kogu elustikku, setete koostist, levikut, toitesoolade sisebilanssi, välisbilanssi ja veebilanssi. Kurepalu paisjärv on tehisveekogu, pindalalt (13,7 ha) ja mahult väike, veevahetus intensiivne, seepärast koguti setteproove kolmest punktist, planktoni ja vee omaduste proovid ühest punktist. Seevastu taimi uuriti üle kogu järve. EMÜ PKI Limnoloogiakeskus pole Kurepalu paisjärve varem uurinud. Seepärast on suurt rõhku pööratud inventuurile. Töös kirjeldatakse veekogu, esitatakse eripärad, funktsioneerimise peamised mõjurid, liikide seisund, veekogu ökoloogiline seisund. Hinnatakse koormustaluvust. Uuringu raames uuritakse paisjärve sissevoole, mis võivad olla oluliseks surveteguriks paisjärve seisundile. Lisaks tuleb tuvastada sissevooludest paisjärve suunatav reostuskoormus ning anda soovitused nende mõju vähendamiseks. Antakse järve seisundi tervendamiseks soovitused. Töödest võtsid osa järgmised EMÜ PKI Limnoloogiakeskuse töötajad: prof. I. Ott; PhD. H. Timm; PhD. H. Tammert; MSc. K. Saar; BSc. R. Laarmaa; MSc. M. Lehtpuu; MSc. T. Krause; MSc. A. Palm; MSc. M. Sepp, K. Ott; PhD. E.-J. Haberman

Afferent Visual Pathway Affection in Patients with PMP22 Deletion-Related Hereditary Neuropathy with Liability to Pressure Palsies

Background The PMP22 gene encodes a protein integral to peripheral myelin. Its deletion leads to hereditary neuropathy with liability to pressure palsies (HNPP). PMP22 is not expressed in the adult central nervous system, but previous studies suggest a role in CNS myelin development. The objective of this study was to identify potential structural and functional alterations in the afferent visual system in HNPP patients. Methods Twenty HNPP patients and 18 matched healthy controls (HC) were recruited in a cross-sectional study. Participants underwent neurological examination including visual acuity, visual evoked potential (VEP) examination, optical coherence tomography (OCT), and magnetic resonance imaging with calculation of brain atrophy, regarding grey and white matter, and voxel based morphometry (VBM), in addition answered the National Eye Institute’s 39-item Visual Functioning Questionnaire (NEI- VFQ). Thirteen patients and 6 HC were additionally examined with magnetic resonance spectroscopy (MRS). Results All patients had normal visual acuity, but reported reduced peripheral vision in comparison to HC in the NEI-VFQ (p = 0.036). VEP latency was prolonged in patients (P100 = 103.7±5.7 ms) in comparison to healthy subjects (P100 = 99.7±4.2 ms, p = 0.007). In OCT, peripapillary retinal nerve fiber layer thickness RNFL was decreased in the nasal sector (90.0±15.5 vs. 101.8±16.5, p = 0.013), and lower nasal sector RNFL correlated with prolonged VEP latency (Rho = -0.405, p = 0.012). MRS revealed reduced tNAA (731.4±45.4 vs. 814.9±62.1, p = 0.017) and tCr (373.8±22.2 vs. 418.7±31.1, p = 0.002) in the visual cortex in patients vs. HC. Whole brain volume, grey and white matter volume, VBM and metabolites in a MRS sensory cortex control voxel did not differ significantly between patients and HC. Conclusion PMP22 deletion leads to functional, metabolic and macro- structural alterations in the afferent visual system of HNPP patients. Our data suggest a functional relevance of these changes for peripheral vision, which warrants further investigation and confirmation

Two alanine aminotranferases link mitochondrial glycolate oxidation to the major photorespiratory pathway in Arabidopsis and rice

The major photorespiratory pathway in higher plants is distributed over chloroplasts, mitochondria, and peroxisomes. In this pathway, glycolate oxidation takes place in peroxisomes. It was previously suggested that a mitochondrial glycolate dehydrogenase (GlcDH) that was conserved from green algae lacking leaf-type peroxisomes contributes to photorespiration in Arabidopsis thaliana. Here, the identification of two Arabidopsis mitochondrial alanine:glyoxylate aminotransferases (ALAATs) that link glycolate oxidation to glycine formation are described. By this reaction, the mitochondrial side pathway produces glycine from glyoxylate that can be used in the glycine decarboxylase (GCD) reaction of the major pathway. RNA interference (RNAi) suppression of mitochondrial ALAAT did not result in major changes in metabolite pools under standard conditions or enhanced photorespiratroy flux, respectively. However, RNAi lines showed reduced photorespiratory CO2 release and a lower CO2 compensation point. Mitochondria isolated from RNAi lines are incapable of converting glycolate to CO2, whereas simultaneous overexpression of GlcDH and ALAATs in transiently transformed tobacco leaves enhances glycolate conversion. Furthermore, analyses of rice mitochondria suggest that the side pathway for glycolate oxidation and glycine formation is conserved in monocotyledoneous plants. It is concluded that the photorespiratory pathway from green algae has been functionally conserved in higher plants

Disentangling dyskinesia from parkinsonism in motor structures of patients with schizophrenia

Patients with schizophrenia frequently suffer from motor abnormalities, but underlying alterations in neuroarchitecture remain unclear. Here, we aimed to disentangle dyskinesia from parkinsonism in motor structures of patients with schizophrenia and to assess associated molecular architecture. We measured grey matter of motor regions and correlated volumetric estimates with dyskinesia and parkinsonism severity. Associations with molecular architecture were identified by cross-modal spatial correlations between ensuing maps of abnormality-related volume alterations and neurotransmitter maps from healthy populations. Both phenomena were linked to (specific) striatal and basal forebrain reductions as well as to D1 receptor density. Dyskinesia also manifested in cerebellar decrease, while parkinsonism was associated with less motor cortex volume. The parkinsonism-related brain pattern was additionally associated with 5-HT1A/2A and µ-opioid receptors distribution. Findings suggest the need to develop psychopharmacological compounds that display not only selectivity for receptor subtypes but also anatomical selectivity for alleviating dyskinesia without worsening parkinsonism and vice versa

Spinocerebellar ataxia type 14: refining clinicogenetic diagnosis in a rare adult‐onset disorder

Objectives: Genetic variant classification is a challenge in rare adult-onset disorders as in SCA-PRKCG (prior spinocerebellar ataxia type 14) with mostly private conventional mutations and nonspecific phenotype. We here propose a refined approach for clinicogenetic diagnosis by including protein modeling and provide for confirmed SCA-PRKCG a comprehensive phenotype description from a German multi-center cohort, including standardized 3D MR imaging. Methods: This cross-sectional study prospectively obtained neurological, neuropsychological, and brain imaging data in 33 PRKCG variant carriers. Protein modeling was added as a classification criterion in variants of uncertain significance (VUS). Results: Our sample included 25 cases confirmed as SCA-PRKCG (14 variants, thereof seven novel variants) and eight carriers of variants assigned as VUS (four variants) or benign/likely benign (two variants). Phenotype in SCA-PRKCG included slowly progressive ataxia (onset at 4-50 years), preceded in some by early-onset nonprogressive symptoms. Ataxia was often combined with action myoclonus, dystonia, or mild cognitive-affective disturbance. Inspection of brain MRI revealed nonprogressive cerebellar atrophy. As a novel finding, a previously not described T2 hyperintense dentate nucleus was seen in all SCA-PRKCG cases but in none of the controls. Interpretation: In this largest cohort to date, SCA-PRKCG was characterized as a slowly progressive cerebellar syndrome with some clinical and imaging features suggestive of a developmental disorder. The observed non-ataxia movement disorders and cognitive-affective disturbance may well be attributed to cerebellar pathology. Protein modeling emerged as a valuable diagnostic tool for variant classification and the newly described T2 hyperintense dentate sign could serve as a supportive diagnostic marker of SCA-PRKCG

Airborne DNA reveals predictable spatial and seasonal dynamics of fungi.

Fungi are among the most diverse and ecologically important kingdoms in life. However, the distributional ranges of fungi remain largely unknown as do the ecological mechanisms that shape their distributions1,2. To provide an integrated view of the spatial and seasonal dynamics of fungi, we implemented a globally distributed standardized aerial sampling of fungal spores3. The vast majority of operational taxonomic units were detected within only one climatic zone, and the spatiotemporal patterns of species richness and community composition were mostly explained by annual mean air temperature. Tropical regions hosted the highest fungal diversity except for lichenized, ericoid mycorrhizal and ectomycorrhizal fungi, which reached their peak diversity in temperate regions. The sensitivity in climatic responses was associated with phylogenetic relatedness, suggesting that large-scale distributions of some fungal groups are partially constrained by their ancestral niche. There was a strong phylogenetic signal in seasonal sensitivity, suggesting that some groups of fungi have retained their ancestral trait of sporulating for only a short period. Overall, our results show that the hyperdiverse kingdom of fungi follows globally highly predictable spatial and temporal dynamics, with seasonality in both species richness and community composition increasing with latitude. Our study reports patterns resembling those described for other major groups of organisms, thus making a major contribution to the long-standing debate on whether organisms with a microbial lifestyle follow the global biodiversity paradigms known for macroorganisms4,5