The Slavonic tradition of the quaestiones ad antiochum ducem : the conflated nature of Cod. Pragensis Slav. IX F 15

The late fourteenth-century Codex Pragensis slav. IX F 15 is a key witness to the textual tradition of the Slavonic Quaestiones ad Antiochum ducem as it contains an almost complete set of questions-and-answers (133 QA’s). It is argued, however, that this corpus is the result of a conflation of two distinct versions of the Quaestiones, viz. redaction T and version X. Redaction T, found in five Moscou manuscripts (15th-16th c.), is the result of a revision of the Slavonic Quaestiones based on the consultation of a Greek exemplar: both the structure (viz. the number and sequence of the QA’s) and the textual particulars of the Greek Quaestiones found in Codex Oxoniensis Bodleianus gr. Auct. F.4.07 are shown to be in almost perfect agreement with the Slavonic T-witnesses. Version X is much more enigmatic; apparently, QA’s from this further unknown text version were introduced in the Prague codex to complement the T-redaction’s corpus of 120 QA’s

Erwinia oleae sp. nov., isolated from olive knots caused by Pseudomonas savastanoi pv. savastanoi

Three endophytic bacterial isolates were obtained in Italy from olive knots caused by Pseudomonas savastanoi pv. savastanoi. Phenotypic tests in combination with 16S rRNA gene sequence analysis indicated a phylogenetic position of these isolates in the genus Erwinia or Pantoea, and revealed two other strains with highly similar 16S rRNA gene sequences (> 99 %), CECT 5262 and CECT 5264, obtained in Spain from olive knots. Rep-PCR DNA fingerprinting of the five strains from olive knots with BOX, ERIC and REP primers revealed three groups of profiles that were highly similar to each other. Multilocus sequence analysis (MLSA) based on concatenated partial atpD, gyrB, infB and rpoB gene sequences, indicated that the strains constitute a single novel species in the genus Erwinia. The strains showed general phenotypic characteristic of Erwinia, and whole genome DNA-DNA hybridization data confirmed they represent a single novel Erwinia species. The strains showed a DNA G+C base composition ranging from 54.7 to 54.9 mol%. They could be discriminated from the phylogenetically related Erwinia species by their ability to utilise potassium gluconate, L-rhamnose and D-arabitol, but not glycerol, inositol and D-sorbitol. The name Erwinia oleae (type strain DAPP-PG 531T = LMG 25322T = DSM 23398T) is proposed for this new taxon

Marinomonas brasilensis sp. nov., isolated from the coral Mussismilia hispida, and reclassification of Marinomonas basaltis as a later heterotypic synonym of Marinomonas communis

A Gram-negative, aerobic bacterium, designated strain R-40503(T), was isolated from mucus of the reef-builder coral Mussismilia hispida, located in the Sao Sebastiao Channel, Sao Paulo, Brazil. Phylogenetic analyses revealed that strain R-40503(T) belongs to the genus Marinomonas. The 16S rRNA gene sequence similarity of R-40503(T) was above 97% with the type strains of Marinomonas vaga, M. basaltis, M. communis and M. pontica, and below 97% with type strains of the other Marinomonas species. Strain R-40503(T) showed less than 35% DNA-DNA hybridization (DDH) with the type strains of the phylogenetically closest Marinomonas species, demonstrating that it should be classified into a novel species. Amplified fragment length polymorphism (AFLP), chemotaxonomic and phenotypic analyses provided further evidence for the proposal of a novel species. Concurrently, a close genomic relationship between M. basaltis and M. communis was observed. The type strains of these two species showed 78% DDH and 63% AFLP pattern similarity. Their phenotypic features were very similar, and their DNA G+C contents were identical (46.3 mol%). Collectively, these data demonstrate unambiguously that Marinomonas basaltis is a later heterotypic synonym of Marinomonas communis. Several phenotypic features can be used to discriminate between Marinomonas species. The novel strain R-40503(T) is clearly distinguishable from its neighbours. For instance, it shows oxidase and urease activity, utilizes L-asparagine and has the fatty acid C(12:1) 3-OH but lacks C(10:0) and C(12:0). The name Marinomonas brasilensis sp. nov. is proposed, with the type strain R-40503(T) (=R-278(T) =LMG 25434(T) =CAIM 1459(T)). The DNA G+C content of strain R-40503(T) is 46.5 mol%

Synergistic Effects of Six Chronic Disease Pairs on Decreased Physical Activity: The SMILE Cohort Study

Little is known about whether and how two chronic diseases interact with each other in modifying the risk of physical inactivity. The aim of the present study is to identify chronic disease pairs that are associated with compliance or noncompliance with the Dutch PA guideline recommendation and to study whether specific chronic disease pairs indicate an extra effect on top of the effects of the diseases individually. Cross-sectional data from 3,386 participants of cohort study SMILE were used and logistic regression analysis was performed to study the joint effect of the two diseases of each chronic disease pair for compliance with the Dutch PA guideline. For six chronic disease pairs, patients suffering from both diseases belonging to these disease pairs in question show a higher probability of noncompliance to the Dutch PA guideline, compared to what one would expect based on the effects of each of the two diseases alone. These six chronic disease pairs were chronic respiratory disease and severe back problems; migraine and inflammatory joint disease; chronic respiratory disease and severe kidney disease; chronic respiratory disease and inflammatory joint disease; inflammatory joint disease and rheumatoid arthritis; and rheumatoid arthritis and osteoarthritis of the knees, hips, and hands

Disease Combinations Associated with Physical Activity Identified: The SMILE Cohort Study

In the search of predictors of inadequate physical activity, an investigation was conducted into the association between multimorbidity and physical activity (PA). So far the sum of diseases used as a measure of multimorbidity reveals an inverse association. How specific combinations of chronic diseases are associated with PA remains unclear. The objective of this study is to identify clusters of multimorbidity that are associated with PA. Cross-sectional data of 3,386 patients from the 2003 wave of the Dutch cohort study SMILE were used. Ward's agglomerative hierarchical clustering was executed to establish multimorbidity clusters. Chi-square statistics were used to assess the association between clusters of chronic diseases and PA, measured in compliance with the Dutch PA guideline. The highest rate of PA guideline compliance was found in patients the majority of whom suffer from liver disease, back problems, rheumatoid arthritis, osteoarthritis, and inflammatory joint disease (62.4%). The lowest rate of PA guideline compliance was reported in patients with heart disease, respiratory disease, and diabetes mellitus (55.8%). Within the group of people with multimorbidity, those suffering from heart disease, respiratory disease, and/or diabetes mellitus may constitute a priority population as PA has proven to be effective in the prevention and cure of all three disorders

Efficient mouse transgenesis using Gateway-compatible ROSA26 locus targeting vectors and F1 hybrid ES cells

The ability to rapidly and efficiently generate reliable Cre/loxP conditional transgenic mice would greatly complement global high-throughput gene targeting initiatives aimed at identifying gene function in the mouse. We report here the generation of Cre/loxP conditional ROSA26-targeted ES cells within 3–4 weeks by using Gateway® cloning to build the target vectors. The cDNA of the gene of interest can be expressed either directly by the ROSA26 promoter providing a moderate level of expression or by a CAGG promoter placed in the ROSA26 locus providing higher transgene expression. Utilization of F1 hybrid ES cells with exceptional developmental potential allows the production of germ line transmitting, fully or highly ES cell-derived mice by aggregation of cells with diploid embryos. The presented streamlined procedures accelerate the examination of phenotypical consequences of transgene expression. It also provides a unique tool for comparing the biological activity of polymorphic or splice variants of a gene, or products of different genes functioning in the same or parallel pathways in an overlapping manner

Efficacy and Safety of Panitumumab in Patients With RAF/RAS-Wild-Type Glioblastoma: Results From the Drug Rediscovery Protocol

BACKGROUND: The prognosis of malignant primary high-grade brain tumors, predominantly glioblastomas, is poor despite intensive multimodality treatment options. In more than 50% of patients with glioblastomas, potentially targetable mutations are present, including rearrangements, altered splicing, and/or focal amplifications of epidermal growth factor receptor (EGFR) by signaling through the RAF/RAS pathway. We studied whether treatment with the clinically available anti-EGFR monoclonal antibody panitumumab provides clinical benefit for patients with RAF/RAS-wild-type (wt) glioblastomas in the Drug Rediscovery Protocol (DRUP). METHODS: Patients with progression of treatment refractory RAF/RASwt glioblastoma were included for treatment with panitumumab in DRUP when measurable according to RANO criteria. The primary endpoints of this study are clinical benefit (CB: defined as confirmed objective response [OR] or stable disease [SD] ≥ 16 weeks) and safety. Patients were enrolled using a Simon-like 2-stage model, with 8 patients in stage 1 and up to 24 patients in stage 2 if at least 1 in 8 patients had CB in stage 1. RESULTS: Between 03-2018 and 02-2022, 24 evaluable patients were treated. CB was observed in 5 patients (21%), including 2 patients with partial response (8.3%) and 3 patients with SD ≥ 16 weeks (12.5%). After median follow-up of 15 months, median progression-free survival and overall survival were 1.7 months (95% CI 1.6-2.1 months) and 4.5 months (95% CI 2.9-8.6 months), respectively. No unexpected toxicities were observed. CONCLUSIONS: Panitumumab treatment provides limited CB in patients with recurrent RAF/RASwt glioblastoma precluding further development of this therapeutic strategy

A first AFLP-based genetic linkage map for brine shrimp Artemia franciscana and its application in mapping the sex locus

We report on the construction of sex-specific linkage maps, the identification of sex-linked markers and the genome size estimation for the brine shrimp Artemia franciscana. Overall, from the analysis of 433 AFLP markers segregating in a 112 full-sib family we identified 21 male and 22 female linkage groups (2n = 42), covering 1,041 and 1,313 cM respectively. Fifteen putatively homologous linkage groups, including the sex linkage groups, were identified between the female and male linkage map. Eight sex-linked AFLP marker alleles were inherited from the female parent, supporting the hypothesis of a WZ-ZZ sex-determining system. The haploid Artemia genome size was estimated to 0.93 Gb by flow cytometry. The produced Artemia linkage maps provide the basis for further fine mapping and exploring of the sex-determining region and are a possible marker resource for mapping genomic loci underlying phenotypic differences among Artemia species