Calycomorphotria hydatis gen. nov., sp. nov., a novel species in the family Planctomycetaceae with conspicuous subcellular structures

A novel strain belonging to the family Planctomycetaceae, designated V22$^{T}$, was isolated from sediment of a seawater fish tank in Braunschweig, Germany. The isolate forms pink colonies on solid medium and displays common characteristics of planctomycetal strains, such as division by budding, formation of rosettes, a condensed nucleoid and presence of crateriform structures and fimbriae. Unusual invaginations of the cytoplasmic membrane and filamentous putative cytoskeletal elements were observed in thin sections analysed by transmission electron microscopy. Strain V22$^{T}$ is an aerobic heterotroph showing optimal growth at 30 °C and pH 8.5. During laboratory cultivations, strain V22$^{T}$ reached generation times of 10 h (maximal growth rate of 0.069 h$^{-1}$). Its genome has a size of 5.2 Mb and a G + C content of 54.9%. Phylogenetically, the strain represents a novel genus and species in the family Planctomycetaceae, order Planctomycetales, class Planctomycetia. We propose the name Calycomorphotria hydatis gen. nov., sp. nov. for the novel taxon, represented by the type strain V22$^{T}$ (DSM 29767$^{T}$ = LMG 29080$^{T}$)

deFuse: An Algorithm for Gene Fusion Discovery in Tumor RNA-Seq Data

Gene fusions created by somatic genomic rearrangements are known to play an important role in the onset and development of some cancers, such as lymphomas and sarcomas. RNA-Seq (whole transcriptome shotgun sequencing) is proving to be a useful tool for the discovery of novel gene fusions in cancer transcriptomes. However, algorithmic methods for the discovery of gene fusions using RNA-Seq data remain underdeveloped. We have developed deFuse, a novel computational method for fusion discovery in tumor RNA-Seq data. Unlike existing methods that use only unique best-hit alignments and consider only fusion boundaries at the ends of known exons, deFuse considers all alignments and all possible locations for fusion boundaries. As a result, deFuse is able to identify fusion sequences with demonstrably better sensitivity than previous approaches. To increase the specificity of our approach, we curated a list of 60 true positive and 61 true negative fusion sequences (as confirmed by RT-PCR), and have trained an adaboost classifier on 11 novel features of the sequence data. The resulting classifier has an estimated value of 0.91 for the area under the ROC curve. We have used deFuse to discover gene fusions in 40 ovarian tumor samples, one ovarian cancer cell line, and three sarcoma samples. We report herein the first gene fusions discovered in ovarian cancer. We conclude that gene fusions are not infrequent events in ovarian cancer and that these events have the potential to substantially alter the expression patterns of the genes involved; gene fusions should therefore be considered in efforts to comprehensively characterize the mutational profiles of ovarian cancer transcriptomes

EuReCa ONE—27 Nations, ONE Europe, ONE Registry A prospective one month analysis of out-of-hospital cardiac arrest outcomes in 27 countries in Europe

AbstractIntroductionThe aim of the EuReCa ONE study was to determine the incidence, process, and outcome for out of hospital cardiac arrest (OHCA) throughout Europe.MethodsThis was an international, prospective, multi-centre one-month study. Patients who suffered an OHCA during October 2014 who were attended and/or treated by an Emergency Medical Service (EMS) were eligible for inclusion in the study. Data were extracted from national, regional or local registries.ResultsData on 10,682 confirmed OHCAs from 248 regions in 27 countries, covering an estimated population of 174 million. In 7146 (66%) cases, CPR was started by a bystander or by the EMS. The incidence of CPR attempts ranged from 19.0 to 104.0 per 100,000 population per year. 1735 had ROSC on arrival at hospital (25.2%), Overall, 662/6414 (10.3%) in all cases with CPR attempted survived for at least 30 days or to hospital discharge.ConclusionThe results of EuReCa ONE highlight that OHCA is still a major public health problem accounting for a substantial number of deaths in Europe.EuReCa ONE very clearly demonstrates marked differences in the processes for data collection and reported outcomes following OHCA all over Europe. Using these data and analyses, different countries, regions, systems, and concepts can benchmark themselves and may learn from each other to further improve survival following one of our major health care events

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Investigation of the Iron–Peroxo Complex in the Fenton Reaction: Kinetic Indication, Decay Kinetics, and Hydroxyl Radical Yields

The Fenton reaction describes the reaction of Fe­(II) with hydrogen peroxide. Several researchers proposed the formation of an intermediate iron–peroxo complex but experimental evidence for its existence is still missing. The present study investigates formation and lifetime of this intermediate at various conditions such as different Fe­(II)-concentrations, absence vs presence of a hydroxyl radical scavenger (dimethyl sulfoxide, DMSO), and different pH values. Obtained results indicate that the iron–peroxo complex is formed under all experimental conditions. Based on these data, stability of the iron–peroxo complex could be examined. At pH 3 regardless of [Fe­(II)]₀ decay rates for the iron–peroxo complex of about 50 s^–1 were determined in absence and presence of DMSO. Without DMSO and [Fe­(II)]₀ = 300 μM variation of pH yielded decay rates of about 70 s^–1 for pH 1 and 2 and of about 50 s^–1 at pH 3 and 4. Hence, the iron–peroxo complex becomes more stable with increasing pH. Furthermore, pH-dependent hydroxyl radical yields were determined to investigate whether the increasing stability of the intermediate complex may indicate a different reaction of the iron–peroxo complex which might yield Fe­(IV) instead of hydroxyl radical formation as suggested in literature. However, it was found that hydroxyl radicals were produced proportionally to the Fe­(II)-concentration

Calycomorphotria hydatis gen. nov., sp. nov., a novel species in the family Planctomycetaceae with conspicuous subcellular structures.

A novel strain belonging to the family Planctomycetaceae, designated V22T, was isolated from sediment of a seawater fish tank in Braunschweig, Germany. The isolate forms pink colonies on solid medium and displays common characteristics of planctomycetal strains, such as division by budding, formation of rosettes, a condensed nucleoid and presence of crateriform structures and fimbriae. Unusual invaginations of the cytoplasmic membrane and filamentous putative cytoskeletal elements were observed in thin sections analysed by transmission electron microscopy. Strain V22T is an aerobic heterotroph showing optimal growth at 30 °C and pH 8.5. During laboratory cultivations, strain V22T reached generation times of 10 h (maximal growth rate of 0.069 h-1). Its genome has a size of 5.2 Mb and a G + C content of 54.9%. Phylogenetically, the strain represents a novel genus and species in the family Planctomycetaceae, order Planctomycetales, class Planctomycetia. We propose the name Calycomorphotria hydatis gen. nov., sp. nov. for the novel taxon, represented by the type strain V22T (DSM 29767T = LMG 29080T)

Modulating the Barrier Function of Human Alveolar Epithelial (hAELVi) Cell Monolayers as a Model of Inflammation.

The incidence of inflammatory lung diseases such as acute respiratory distress syndrome (ARDS) remains an important problem, particularly in the present time with the Covid-19 pandemic. However, an adequate in vitro test system to monitor the barrier function of the alveolar epithelium during inflammation and for assessing anti-inflammatory drugs is urgently needed. Therefore, we treated human Alveolar Epithelial Lentivirus-immortalised cells (hAELVi cells) with the pro-inflammatory cytokines TNF-α (25 ng/ml) and IFN-γ (30 ng/ml), in the presence or absence of hydrocortisone (HC). While TNF-α and IFN-γ are known to reduce epithelial barrier properties, HC could be expected to protect the barrier function and result in an anti-inflammatory effect. We investigated the impact of anti-inflammatory/inflammatory treatment on transepithelial electrical resistance (TEER) and the apparent permeability coefficient (P app ) of the low permeability marker sodium fluorescein (NaFlu). After incubating hAELVi cells for 48 hours with a combination of TNF-α and IFN-γ, there was a significant decrease in TEER and a significant increase in the P app . The presence of HC maintained the TEER values and barrier properties, so that no significant P app change was observed. By using hAELVi cells to study anti-inflammatory drugs in vitro, the need for animal experiments could be reduced and pulmonary drug development accelerated