The Pro-Inflammatory Deletion Allele of the NF-κB1 Polymorphism Is Characterized by a Depletion of Subunit p50 in Sepsis

The functionally important NF-κB1 promoter polymorphism (−94ins/delATTG) significantly shapes inflammation and impacts the outcome of sepsis. However, exploratory studies elucidating the molecular link of this genotype-dependent pattern are lacking. Accordingly, we analyzed lipopolysaccharide-stimulated peripheral blood mononuclear cells from both healthy volunteers (n = 20) and septic patients (n = 10). All individuals were genotyped for the −94ins/delATTG NF-κB1 promoter polymorphism. We found a diminished nuclear activity of the NF-κB subunit p50 in ID/DD genotypes after 48 h of lipopolysaccharide stimulation compared to II genotypes (p = 0.025). This was associated with higher TNF-α (p = 0.005) and interleukin 6 concentrations (p = 0.014) and an increased production of mitochondrial radical oxygen species in ID/DD genotypes (p = 0.001). Although ID/DD genotypes showed enhanced activation of mitochondrial biogenesis, they still had a significantly diminished cellular ATP content (p = 0.046) and lower mtDNA copy numbers (p = 0.010) compared to II genotypes. Strikingly, these findings were mirrored in peripheral blood mononuclear cells taken from septic patients. Our results emphasize the crucial aspect of considering NF-κB subunits in sepsis. We showed here that the deletion allele of the NF-κB1 (−94ins/delATTG) polymorphism was associated with the lower nuclear activity of subunit p50, which, in turn, was associated with aggravated inflammation and mitochondrial dysfunction.     

Automatic classifier selection for non-experts

Choosing a suitable classifier for a given dataset is an important part of developing a pattern recognition system. Since a large variety of classification algorithms are proposed in literature, non-experts do not know which method should be used in order to obtain good classification results on their data. Meta-learning tries to address this problem by recommending promising classifiers based on meta-features computed from a given dataset. In this paper, we empirically evaluate five different categories of state-of-the-art meta-features for their suitability in predicting classification accuracies of several widely used classifiers (including Support Vector Machines, Neural Networks, Random Forests, Decision Trees, and Logistic Regression). Based on the evaluation results, we have developed the first open source meta-learning system that is capable of accurately predicting accuracies of target classifiers. The user provides a dataset as input and gets an automatically created high-performance ready-to-use pattern recognition system in a few simple steps. A user study of the system with non-experts showed that the users were able to develop more accurate pattern recognition systems in significantly less development time when using our system as compared to using a state-of-the-art data mining software.     

Diverse nearest neighbors queries using linear skylines

k-nearest neighbor (k-NN) queries are well-known and widely used in a plethora of applications. However, in the original definition of k-NN queries there is no concern regarding diversity of the answer set with respect to the user’s interests. For instance, travelers may be looking for touristic sites that are close to where they are, but that would also lead them to see different parts of the city. Likewise, if one is looking for restaurants close by, it may be more interesting to learn about restaurants of different categories or ethnicities which are nonetheless relatively close. The interesting novel aspect of this type of query is that there are two competing criteria to be optimized: closeness and diversity. We propose two approaches that leverage the notion of linear skyline queries in order to find the k diverse nearest neighbors within a radius r from a given query point, or (k, r)-DNNs for short. Our proposed approaches return a relatively small set containing all optimal solutions for any linear combination of the weights a user could give to the two competing criteria, and we consider three different notions of diversity: spatial, categorical and angular. Our experiments, varying a number of parameters and exploring synthetic and real datasets, in both Euclidean space and road networks, respectively, show that our approaches are several orders of magnitude faster than a straightforward approach.     

An Overview of the Latest Metabolomics Studies on Atopic Eczema with New Directions for Study

Atopic eczema (AE) is an inflammatory skin disorder affecting approximately 20% of children worldwide and early onset can lead to asthma and allergies. Currently, the mechanisms of the disease are not fully understood. Metabolomics, the analysis of small molecules in the skin produced by the host and microbes, opens a window to observe the mechanisms of the disease which then may lead to new drug targets for AE treatment. Here, we review the latest advances in AE metabolomics, highlighting both the lipid and non-lipid molecules, along with reviewing the metabolites currently known to reside in the skin.     

Long COVID: Association of Functional Autoantibodies against G-Protein-Coupled Receptors with an Impaired Retinal Microcirculation

Long COVID (LC) describes the clinical phenotype of symptoms after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diagnostic and therapeutic options are limited, as the pathomechanism of LC is elusive. As the number of acute SARS-CoV-2 infections was and is large, LC will be a challenge for the healthcare system. Previous studies revealed an impaired blood flow, the formation of microclots, and autoimmune mechanisms as potential factors in this complex interplay. Since functionally active autoantibodies against G-protein-coupled receptors (GPCR-AAbs) were observed in patients after SARS-CoV-2 infection, this study aimed to correlate the appearance of GPCR-AAbs with capillary microcirculation. The seropositivity of GPCR-AAbs was measured by an established cardiomyocyte bioassay in 42 patients with LC and 6 controls. Retinal microcirculation was measured by OCT–angiography and quantified as macula and peripapillary vessel density (VD) by the Erlangen-Angio Tool. A statistical analysis yielded impaired VD in patients with LC compared to the controls, which was accentuated in female persons. A significant decrease in macula and peripapillary VD for AAbs targeting adrenergic β2-receptor, MAS-receptor angiotensin-II-type-1 receptor, and adrenergic α1-receptor were observed. The present study might suggest that a seropositivity of GPCR-AAbs can be linked to an impaired retinal capillary microcirculation, potentially mirroring the systemic microcirculation with consecutive clinical symptoms.     

Sheet metal forming of piezoceramic-metal-laminar structures—Simulation and experimental analysis

Adaptive systems with piezoelectric components offer significant opportunities for the active control of dynamic behaviour. Vibration and acoustics control as well as structural health monitoring are also possible. However ineffective production technologies prevent industrial applications. The authors are therefore proposing the integration of piezo-modules inside a double-layer sheet. The use of semi-cured adhesive avoids shear-forces being transferred to the piezo-modules during forming. After forming the adhesive will cure and the transfer of piezoelectric strain to the sheet is made possible. A detailed finite-element-model incorporating the electro-mechanical characteristics of the piezo-modules has been developed. The simulation results were validated experimentally.     

Diagenetic transformation of dissolved organic nitrogen compounds under contrasting sedimentary redox conditions in the Black Sea

Remineralization of organic matter in reactive marine sediments releases nutrients and dissolved organic matter (DOM) into the ocean. Here we focused on the molecular-level characterization of DOM by high-resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) in sediment pore waters and bottom waters from contrasting redox regimes in the northern Black Sea with particular emphasis on nitrogen-bearing compounds to derive an improved understanding of the molecular transformations involved in nitrogen release. The number of nitrogen-bearing molecules is generally higher in pore waters than in bottom waters. This suggests intensified degradation of nitrogen-bearing precursor molecules such as proteins in anoxic sediments: No significant difference was observed between sediments deposited under oxic vs anoxic conditions (average O/C ratios of 0.55) suggesting that the different organic matter quality induced by contrasting redox conditions does not impact protein diagenesis in the subseafloor. Compounds in the pore waters were on average larger, less oxygenated, and had a higher number of unsaturations. Applying a mathematical model, we could show that the assemblages of nitrogen-bearing molecular formulas are potential products of proteinaceous material that was transformed by the following reactions: (a) hydrolysis and deamination, both reducing the molecular size and nitrogen content of the products and intermediates; (b) oxidation and hydration of the intermediates; and (c) methylation and dehydration.     

Influence of genotype,harvest time and plant part on polyphenolic composition of globe artichoke [Cynara cardunculus L. var. scolymus (L.) Fiori]

Globe artichoke is an ancient herbaceous plant native to the Mediterranean Basin. The edible part of the plant (head) is particularly rich in polyphenols, whose therapeutic properties are well documented. A field experiment was conducted in Sicily (south Italy) to examine the influence of genotype and harvest time on the polyphenol content and profile of different head parts. The concentrations of 19 phenolic compounds were determined by HPLC-DAD-ESI/MSⁿ analysis. It was observed that individual phenolic substances were preferentially accumulated in specific head parts and genotypes. Apigenin 7-O-glucuronide was found to be the major flavonoid, with 6298 mg kg⁻¹ DM in ‘Romanesco clone C3’ receptacle, whereas chlorogenic acid represented the main caffeoylquinic acid, reaching 14841 mg kg⁻¹ DM in the inner bracts of ‘Violetto di Sicilia’. Our findings prove also the influence of climatic conditions on the phenolic profile and thus suggest giving specific consideration to harvest time.     

The explanatory power of citations: a new approach to unpacking impact in science

Scientometrics - Citation analysis has been applied to map the landscape of scientific disciplines and to assess the impact of publications. However, it is limited in that it assumes all citations...