Zur Oberkarbonflora in der Bohrung Jessen 1Z/62 bei Wittenberg (Sachsen-Anhalt)

Die Nachuntersuchung der Bohrung Jessen 1 Z/62 im Rahmen der Tiefenkartierung im südöstlichen Sachsen-Anhalt ergab, dass die fossilführenden Schichten zwischen Teufe 1050,40 m und 1202,0 m in das höhere Westfal D eingestuft werden müssen. Damit wird eine Neudefinition der Roitzsch-Formation notwendig. Floristisch kann Stefan nicht belegt werden, ist aber aus lithologischer Sicht höchst wahrscheinlich. Eine paläobotanische Beziehung zum Zwickauer Becken liegt nahe. Paralische Einflüsse in diesem Teilbecken des Saale-Senkungsgebietes zwischen Wittenberg und Torgau sind nicht belegbar. Die Obergrenze des Westfals dürfte bereits bei 1050,40 m und nicht erst bei 1065,30 m Teufe liegen, d.h. erstmalig konnte (sekundär?) rotgefärbtes Westfal D im Bereich der Saale-Senke nachgewiesen werden. The sediments of the drilling Jessen 1Z/62 between 1050,40 m and 1202,0 m are of Westphalian D age. Therefore it is necessary to redefine the so called Roitzsch formation. Stephanian is not verified by plant fossils but is most likely by lithological reasons. Palaeontological relationships to the Zwickau Basin are obvious; therefore paralic influence is unverifiable in this part of the Saale depression between Wittenberg and Torgau. The upper boundary of the Westphalian is located by 1050,40 m, while former authors were opting for the depth of 1065,30 m. So at the first time reddish (secondary coloration) Westphalian D is demonstrated around the Saale depression

Der Erstnachweis von Namur A in der Umgebung von Prettin: Ein Beitrag zur Tiefenkartierung von Sachsen- Anhalt

Die lithologische und paläontologische (paläobotanische) Bewertung von Bohrkernen einschließlich deren geophysikalischen Messergebnissen im Gebiet von Prettin bei Torgau ergab eine stratigraphische Einstufung in das Namur Ae2 (Arnsbergium). Dieses Namur-Alter widerspricht den bisherigen strukturellen Vorstellungen eines Unterrotliegend-Grabens, die damit nicht aufrecht zu erhalten sind. In diesem Raum erstmals nachgewiesene Konglomerate an der Basis des Namurs führen Gerölle, die vermutlich von einem im Liegenden erbohrten Ignimbrit stammen.Lithological and palaeobotanical assessments – including also geophysical measurements – from boreholes in the vicinity of Prettin near Torgau (Sachsen-Anhalt, Germany) indicate a Lower Carboniferous i.e. Namurian Ae2 (Arnsbergium) age. This Namurian age contradicts previous concepts involving the tectonic structure of a rift of Asselian age hypothesized in former publications. Conglomerates from the basis of the Namurian discovered here for the first time have pebbles probably originate from the underlying ignimbrite. This offers important hints about the age of ignimbrites developed in the core

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Impact of infection on proteome-wide glycosylation revealed by distinct signatures for bacterial and viral pathogens

Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection

Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study

BackgroundThe PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice.MethodsFebrile children and controls were recruited on presentation to hospital in 9 European countries 2016-2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed.FindingsOf 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92-5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07-7.59), Group A streptococcus (OR 2.73, 95% CI 1.13-6.09) and E. coli (OR 2.7, 95% CI 1.02-6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11-0.46), influenza B (OR 0.12, 95% CI 0.02-0.37) and RSV (OR 0.16, 95% CI: 0.06-0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23-0.72) and EBV (OR 0.71, 95% CI 0.56-0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively.InterpretationMost febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics.FundingEU Horizon 2020 grant 668303

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Lymphocyte Subsets in HIV-Exposed Uninfected Infants: The Impact of Neonatal Postexposure Prophylaxis With Zidovudine

HIV-exposed, uninfected (HEU) infants receiving neonatal postexposure prophylaxis with zidovudine showed nonsignificant trends of lower CD4 and CD8 T cells as well as CD19 B cells than those who did not, suggesting toxicity that might impact the overall health of HEU children