Aeshna vercanica sp. nov. from Iran with a new insight into the Aeshna cyanea-group (Odonata: Aeshnidae)

Aeshna vercanica sp. nov. is described and illustrated. The male holotype and four male paratypes were collected on 15-vii-2013 in the Hyrcanian forest of the Alborz Mountains, Mazandaran province, northwestern Iran. A specimen collected on 29-vi-2002 in the Talysh Hills, Lankoran area, Azerbaijan, also belongs to the new species. In July 2014 the species, including females, was recorded again at the type locality and additionally ca 400 km further east in Golestan province. Males are similar to Aeshna cyanea in the structure of genitalia and terminalia but differ in head morphology, pterostigma length, colour pattern, and behaviour. Females have small abdominal blue or turquoise postero-median dorsal spots which are absent on S9 and S10, thin green antehumeral stripes, a less robust appearance than females of A. cyanea, and are more slender and longer. The range of A. vercanica sp. nov. covers the Hyrcanian forest along the southern margin of the Caspian Sea. Analysis of the barcoding COI sequence of DNA confirmed that A. vercanica sp. nov. is separated from A. cyanea by a genetic distance of ca 4%. The ITS gave a similar result. A haplotype map could not derive A. vercanica sp. nov. directly from A. cyanea. They are thus related but different species, and we suggest the common ancestor lived in pre-Pleistocene times. Analysis of A. cyanea specimens from across its range also revealed a western clade from the Maghreb to Central Europe. Populations from the Caucasus to Eastern Europe were polytomous, a common scenario for post-glacial invaders. A molecular comparison of the species pair A. juncea and A. subarctica showed these to be even more closely related than A. cyanea and A. vercanica sp. nov

Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors

We analyzed a multi-drug resistant (MR) HIV-1 re- verse transcriptase (RT), subcloned from a patient- derived subtype CRF02 AG, harboring 45 amino acid exchanges, amongst them four thymidine analog mutations (TAMs) relevant for high-level AZT (azi- dothymidine) resistance by AZTMP excision (M41L, D67N, T215Y, K219E) as well as four substitutions of the AZTTP discrimination pathway (A62V, V75I, F116Y and Q151M). In addition, K65R, known to an- tagonize AZTMP excision in HIV-1 subtype B was present. Although MR-RT harbored the most signif- icant amino acid exchanges T215Y and Q151M of each pathway, it exclusively used AZTTP discrimi- nation, indicating that the two mechanisms are mu- tually exclusive and that the Q151M pathway is ob- viously preferred since it confers resistance to most nucleoside inhibitors. A derivative was created, ad- ditionally harboring the TAM K70R and the rever- sions M151Q as well as R65K since K65R antago- nizes excision. MR-R65K-K70R-M151Q was compe- tent of AZTMP excision, whereas other combinations thereof with only one or two exchanges still pro- moted discrimination. To tackle the multi-drug resis- tance problem, we tested if the MR-RTs could still be inhibited by RNase H inhibitors. All MR-RTs exhibited similar sensitivity toward RNase H inhibitors be- longing to different inhibitor classes, indicating the importance of developing RNase H inhibitors further as anti-HIV drugs

A multi-criteria decision support for optimal instrumentation in scoliosis spine surgery

In adolescent idiopathic scoliosis, the selection of an optimal instrumentation configuration for correcting a specific spinal deformity is a challenging combinatorial problem. Current methods mostly rely on surgeons' expertise, which has been shown to lead to different treatment strategies for the same patients. In this work, a mathematical model of the human spine derived from in-vitro experimentally-obtained data was used to simulate the biomechanical behavior of the spine under the application of corrective forces and torques. The corrective forces and torques were optimized based on the particle swarm optimization algorithm for each combinatorially possible instrumentation strategy. Finally, a multi-criteria decision support for optimal instrumentation in scoliosis spine surgery has been proposed and applied to five patient data sets exhibiting similar spinal deformities according to two commonly used classification systems. Results indicated that the classification of the spinal deformities based on the current standardized clinical classifications systems is not a sufficient condition for recommending selective fusion of spinal motion segments. In addition, the particle swarm optimization algorithm was successfully applied to solve a realistic interdisciplinary clinical problem in a patient-specific fashion. The proposed method enables a better understanding of the biomechanical behavior of spinal structures and has the potential to become a standard tool in preoperative plannin

Visibility, framing and importance: Images of the EU in Japan and South Korea

Addressing an under-researched theme of international images and perceptions of the EU, this paper scrutinizes the framings of the Union endorsed in the news media and expressed by the general public in the two East Asian OECD countries – Japan and South Korea. Conclusions indicate that the EU’s importance and presence is often underestimated in the region, and frequently seen in terms of ‘economic muscle’ only. The empirical data comes from a trans-national comparative research project, sponsored by the Asia-Europe foundation (ASEF). The research framework is interdisciplinary, drawing resources from critical discourse analysis, media and image studies, EU scholarship and political scienc

Microfluidic acini-on-chip platforms as a tool to study bacterial lung exposure

Bacterial invasion of the respiratory system leads to complex immune responses involving many cell types. In the alveolar regions, the first line of defense includes the alveolar epithelium, secreted surfactant, alveolar lining fluid and alveolar macrophages. The epithelium consists of alveolar type I and type II cells. Both cell types are known to have immuno-modulatory functions characterized by the secretion of pro-inflammatory cytokines. Epithelial in vitro models offer attractive platforms to investigate biological functionality, but have typically relied on traditional well plate assays that come short of mimicking the complexity of the airway environment and do not capture physiological flows or relevant anatomical features. In the last decade, microfluidics have gained significant momentum in laying the foundations for constructing in vitro models that mimic physiologically-relevant organ functions. Here we propose to use acinus-on-chip platforms that mimic more closely native acinar microflows at true scale in a multi-generation alveolated tree. Acinar chips are cultured with human Alveolar Epithelial Lentivirus immortalized (hAELVi) cells at an air-liquid interface (ALI); such cells show alveolar type I like characteristics and maintained barrier function, leading to high trans-epithelial electrical resistance (TEER) in analogy to primary cells harvested from human tissue. To model bacterial infection, i.e. a strong stimulator of the innate arm of the immune system, lipopolysaccharides (LPS) will be used. LPS is a major outer surface membrane protein expressed on Gram-negative bacteria. The alveolar epithelium is exposed to LPS-laden aerosols and cell response is monitored mainly by secretion of pro-inflammatory cytokines. Our acinus-on-chip allows quantitative on-line measurements of alveolar barrier function, absorption kinetics and immunologically relevant responses, giving further insight to the role played by type I alveolar cells in lung immunity. Please click Additional Files below to see the full abstract

Origin of isotopic diversity among carbonaceous chondrites

Carbonaceous chondrites are some of the most primitive meteorites and derive from planetesimals that formed a few million years after the beginning of the solar system. Here, using new and previously published Cr, Ti, and Te isotopic data, we show that carbonaceous chondrites exhibit correlated isotopic variations that can be accounted for by mixing among three major constituents having distinct isotopic compositions, namely refractory inclusions, chondrules, and CI chondrite-like matrix. The abundances of refractory inclusions and chondrules are coupled and systematically decrease with increasing amount of matrix. We propose that these correlated abundance variations reflect trapping of chondrule precursors, including refractory inclusions, in a pressure maximum in the disk, which is likely related to the water ice line and the ultimate formation location of Jupiter. The variable abundance of refractory inclusions/chondrules relative to matrix is the result of their distinct aerodynamical properties resulting in differential delivery rates and their preferential incorporation into chondrite parent bodies during the streaming instability, consistent with the early formation of matrix-poor and the later accretion of matrix-rich carbonaceous chondrites. Our results suggest that chondrules formed locally from isotopically heterogeneous dust aggregates which themselves derive from a wide area of the disk, implying that dust enrichment in a pressure trap was an important step to facilitate the accretion of carbonaceous chondrite parent bodies or, more generally, planetesimals in the outer solar system.Comment: 12 pages, 4 figures, 1 table. Accepted for publication in ApJ

Genetic defects of GDF6 in the zebrafish out of sight mutant and in human eye developmental anomalies

Contains fulltext : 88522.pdf (publisher's version ) (Open Access)BACKGROUND: The size of the vertebrate eye and the retina is likely to be controlled at several stages of embryogenesis by mechanisms that affect cell cycle length as well as cell survival. A mutation in the zebrafish out of sight (out) locus results in a particularly severe reduction of eye size. The goal of this study is to characterize the outm233 mutant, and to determine whether mutations in the out gene cause microphthalmia in humans. RESULTS: In this study, we show that the severe reduction of eye size in the outm233 mutant is caused by a mutation in the zebrafish gdf6a gene. Despite the small eye size, the overall retinal architecture appears largely intact, and immunohistochemical studies confirm that all major cell types are present in outm233 retinae. Subtle cell fate and patterning changes are present predominantly in amacrine interneurons. Acridine orange and TUNEL staining reveal that the levels of apoptosis are abnormally high in outm233 mutant eyes during early neurogenesis. Mutation analysis of the GDF6 gene in 200 patients with microphthalmia revealed amino acid substitutions in four of them. In two patients additional skeletal defects were observed. CONCLUSIONS: This study confirms the essential role of GDF6 in the regulation of vertebrate eye size. The reduced eye size in the zebrafish outm233 mutant is likely to be caused by a transient wave of apoptosis at the onset of neurogenesis. Amino acid substitutions in GDF6 were detected in 4 (2%) of 200 patients with microphthalmia. In two patients different skeletal defects were also observed, suggesting pleitrophic effects of GDF6 variants. Parents carrying these variants are asymptomatic, suggesting that GDF6 sequence alterations are likely to contribute to the phenotype, but are not the sole cause of the disease. Variable expressivity and penetrance suggest a complex non-Mendelian inheritance pattern where other genetic factors may influence the outcome of the phenotype

Structured implementation of digital, systematically updated guideline recommendations for enhanced adherence in schizophrenia (SISYPHOS) — protocol of a cluster-randomized trial

BACKGROUND: Despite high acceptance rates in the field, the implementation of the 2019 published German evidence and consensus-based S3 guideline is unsatisfactory. This study aims to assess the superiority of an adaptive online version with a better visualization of the recommendations in terms of guideline conformity, application of shared decision making, and digital health expertise compared to the classic pdf print version of the guideline. METHODS: The study is a multicenter, controlled, cluster-randomized trial with two arms: one arm investigating the implementation of the German schizophrenia guideline in form of a digital format (intervention group using the evidence ecosystem MAGICapp), the other arm in form of the classic print pdf version (control group). Physicians and psychologists working in specialized hospitals will be included in the study. The guideline-knowledge before and after the intervention is defined as primary outcome measure. Secondary endpoints include digital health expertise and application of shared decision making. DISCUSSION: This is the first study evaluating if an adaptive-digital version of the schizophrenia guideline is superior to the classic pdf print version. Therefore, the guideline is digitally prepared in the evidence-ecosystem MAGICapp, which covers the whole process of the development of a living guideline. We intend to use the results of the cluster-randomized trial for developing the German S3 guideline for schizophrenia in form of a living guideline in future. TRIAL REGISTRATION: The study is registered (10 May 2022) in the German Clinical Trials Register (DRKS) and the WHO International Clinical Trials Registry Platform (ICTRP) under registration number DRKS00028895. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-022-06749-0

Expression profiling of hypothetical genes in Desulfovibrio vulgaris leads to improved functional annotation

Hypothetical (HyP) and conserved HyP genes account for >30% of sequenced bacterial genomes. For the sulfate-reducing bacterium Desulfovibrio vulgaris Hildenborough, 347 of the 3634 genes were annotated as conserved HyP (9.5%) along with 887 HyP genes (24.4%). Given the large fraction of the genome, it is plausible that some of these genes serve critical cellular roles. The study goals were to determine which genes were expressed and provide a more functionally based annotation. To accomplish this, expression profiles of 1234 HyP and conserved genes were used from transcriptomic datasets of 11 environmental stresses, complemented with shotgun LC–MS/MS and AMT tag proteomic data. Genes were divided into putatively polycistronic operons and those predicted to be monocistronic, then classified by basal expression levels and grouped according to changes in expression for one or multiple stresses. One thousand two hundred and twelve of these genes were transcribed with 786 producing detectable proteins. There was no evidence for expression of 17 predicted genes. Except for the latter, monocistronic gene annotation was expanded using the above criteria along with matching Clusters of Orthologous Groups. Polycistronic genes were annotated in the same manner with inferences from their proximity to more confidently annotated genes. Two targeted deletion mutants were used as test cases to determine the relevance of the inferred functional annotations