Unravelling microalgal-bacterial interactions in aquatic ecosystems through 16S co-occurrence networks

Microalgae and bacteria have a wide spectrum of associations in aquatic environments. Since their interactions can directly influence global carbon and nutrient cycling, understanding these associations help us evaluate their influence on ecosystem productivity. Algal biodiversity is large, and bacterial associations have been characterised for a small fraction of them. While experiments based on algal-bacterial co-culturing are commonly used to infer interactions, deciphering all associations present in nature through such methods is impractical and approaches based on co-occurrence network analysis can help infer associations. In this study, we used microbial co-occurrence networks built from Earth microbiome project 16S metabarcoding data to detect microalgal-bacterial associations in aquatic environments. We analysed marine and freshwater environments to understand what groups of bacteria are tightly co-occurring with different algal groups in both aquatic environments, to see patterns of interactions, and to evaluate the overall use of co-occurrence networks to infer meaningful algal-bacterial interactions. In line with expectations from co-culturing work, our results show that the phyla Proteobacteria and Bacteroidetes are the major bacterial associates of microalgae and the co-occurring bacteria may be specific to the algal host. From the independent analysis of environments, we also show that sample origin may be an important determinant of these interactions. By unravelling previously established microalgal-bacterial links as well as identifying a range of previously unknown interactions, we show that co-occurrence network analysis is a promising hypothesis-generating framework to study microalgal-bacterial interactions that can guide future research into the functional nature of interactions.

THE PROPHET MUHAMMAD AND THE QURAN

Based on an independent analysis of artifacts, ancestral tree and astronomical phenomena related to the deeds, life and death of the Prophet Muhammad, as well as historical evidence of the first appearance and legal use of the Quran in the life of Muslims, the author drew conclusions about the integration of several historical figures of the VII and XII centuries into the personality of the Prophet Muhammad. They became Khagan Kubrat, aka Emperor Heraclius, the Arabian Prophet or Caliph of the Rashidun Caliphs and the true Prophet Muhammad, who lived in 1090–1052. The Quran was created in 1130–1152. The proposed interpretation does not undermine the canons of the faith of Islam, but establishes the truth.

MULTITRAIT ANALYSIS EXPANDS GENETIC RISK FACTORS IN CARDIOEMBOLIC STROKE

Background and Purpose: The genetic architecture of cardioembolic stroke (CES) is still poorly understood. Atrial fibrillation (AF) is the main cause of CES, with which it shares heritability. We aimed to discover novel loci associated with CES by performing a Multitrait Analysis of the GWAS (MTAG) with atrial fibrillation genetic data. Methods: For the MTAG analysis we used the MEGASTROKE cohort, which comprises European patients with CES and controls (n=362,661) and an AF cohort composed of 1,030,836 subjects. Regional genetic pleiotropy of the significant results was explored using an alternative Bayesian approach with GWAS-pairwise method. A replication was performed in an independent European cohort comprising 9,105 subjects using a Genome Wide Association Study (GWAS). Results: MTAG-CES analysis revealed 40 novel and significant loci (p-value<5x10-8) associated with CES, four of which had not previously been associated with AF. A significant replication was assessed for eight novel loci: CAV1, IGF1R, KIAA1755, NEURL1, PRRX1, SYNE2, TEX41 and WIPF1, showing a p-value<0.05 in the CES vs controls independent analysis. KIAA1755, a locus not previously described associated with AF. Interestingly, 51 AF risk loci were not associated with CES according to GWAS-pairwise analysis. Gene Ontology (GO) analysis revealed that these exclusive AF genes from the 51 loci participate in processes related mainly to cardiac development, whereas genes associated with AF and CES participate mainly in muscle contraction and the conduction of electrical impulses. Conclusions: We found eight new loci associated with CES. In addition, this study provides novel insights into the pathogenesis of CES, highlighting multiple candidate genes for future functional experiments.

Harmonizing Commercial and Investment Arbitration: Conflict Dynamics

This article provides an independent analysis of the scope and extent of arbitration under investment agreements, and the implications of the possible convergence in the process of harmonization of international commercial arbitration law.The successful settlement of any dispute depends on the compatibility of the nature of the dispute with the technique to which it is submitted for resolution. In the last decade, there was a constant increase in the number of disputes that were subjected to arbitration and a major chunk of those disputes covered a comparatively new but known area called international investment law. With economic globalization allowing the free flow of foreign direct investment (FDI) in and out of a country, the existing regulatory framework in international law to standardize investment liberalization is often seen as ineffective, hence the consequent disputes. Here, arbitration offers a suitable framework for the amicable settlement of commercial disputes covering investment agreements with the assistance of bilateral or multilateral agreements between the states. Preferential trade agreements pertaining to investment often contain an arbitration clause for the settlement of future disputes between parties. At this juncture, one may find that there exists a fundamental dilemma in ascertaining the true nature of investment arbitration and how it is different from commercial arbitration. For example, the protection being offered to human rights under the purview of investment arbitration may generate doubts in the minds of investment arbitrators. In commercial arbitration, divergences in a pluralistic order become particularly relevant whereas the diverse legal cultures supported by individual constitutional frameworks have a direct impact on investment arbitration due to their practical application. The article also discusses the need for harmonized rules governing arbitration procedures while maintaining the functional dissimilarities between commercial and investment arbitration.

A Novel Approach for Quantifying the Pharmacological Activity of T-Cell Engagers Utilizing In Vitro Time Course Experiments and Streamlined Data Analysis

CD3-bispecific antibodies are a new class of immunotherapeutic drugs against cancer. The pharmacological activity of CD3-bispecifics is typically assessed through in vitro assays of cancer cell lines co-cultured with human peripheral blood mononuclear cells (PBMCs). Assay results depend on experimental conditions such as incubation time and the effector-to-target cell ratio, which can hinder robust quantification of pharmacological activity. In order to overcome these limitations, we developed a new, holistic approach for quantification of the in vitro dose–response relationship. Our experimental design integrates a time-independent analysis of the dose–response across different time points as an alternative to the static, “snap-shot” analysis based on a single time point commonly used in dose–response assays. We show that the potency values derived from static in vitro experiments depend on the incubation time, which leads to inconsistent results across multiple assays and compounds. We compared the potency values from the time-independent analysis with a model-based approach. We find comparably accurate potency estimates from the model-based and time-independent analyses and that the time-independent analysis provides a robust quantification of pharmacological activity. This approach may allow for an improved head-to-head comparison of different compounds and test systems and may prove useful for supporting first-in-human dose selection.

Halo-independent analysis of direct dark matter detection through electron scattering

Sub-GeV mass dark matter particles whose collisions with nuclei would not deposit sufficient energy to be detected, could instead be revealed through their interaction with electrons. Analyses of data from direct detection experiments usually require assuming a local dark matter halo velocity distribution. In the halo-independent analysis method, properties of this distribution are instead inferred from direct dark matter detection data, which allows then to compare different data without making any assumption on the uncertain local dark halo characteristics. This method has so far been developed for and applied to dark matter scattering off nuclei. Here we demonstrate how this analysis can be applied to scattering off electrons.

A model-independent analysis of $$b{\rightarrow }s\mu ^{+}\mu ^{-}$$transitions with GAMBIT ’s FlavBit

The search for flavour-changing neutral current effects in B-meson decays is a powerful probe of physics beyond the Standard Model. Deviations from SM behaviour are often quantified by extracting the preferred values of the Wilson coefficients of an operator product expansion. We use the module of the package to perform a simultaneous global fit of the Wilson coefficients $$C_7$$ C 7 , $$C_9$$ C 9 , and $$C_{10}$$ C 10 using a combination of all current data on $$b{\rightarrow }s\mu ^{+}\mu ^{-}$$ b → s μ + μ - transitions. We further extend previous analyses by accounting for the correlated theoretical uncertainties at each point in the Wilson coefficient parameter space, rather than deriving the uncertainties from a Standard Model calculation. We find that the best fit deviates from the SM value with a significance of 6.6$$\sigma $$ σ . The largest deviation is associated with a vector coupling of muons to b and s quarks.

Solving the electron and muon $$g-2$$ anomalies in $$Z'$$ models

We consider simultaneous explanations of the electron and muon $$g-2$$ g - 2 anomalies through a single $$Z'$$ Z ′ of a $$U(1)'$$ U ( 1 ) ′ extension to the Standard Model (SM). We first perform a model-independent analysis of the viable flavour-dependent $$Z'$$ Z ′ couplings to leptons, which are subject to various strict experimental constraints. We show that only a narrow region of parameter space with an MeV-scale $$Z'$$ Z ′ can account for the two anomalies. Following the conclusions of this analysis, we then explore the ability of different classes of $$Z'$$ Z ′ models to realise these couplings, including the SM$$+U(1)'$$ + U ( 1 ) ′ , the N-Higgs Doublet Model$$+U(1)'$$ + U ( 1 ) ′ , and a Froggatt–Nielsen style scenario. In each case, the necessary combination of couplings cannot be obtained, owing to additional relations between the $$Z'$$ Z ′ couplings to charged leptons and neutrinos induced by the gauge structure, and to the stringency of neutrino scattering bounds. Hence, we conclude that no $$U(1)'$$ U ( 1 ) ′ extension can resolve both anomalies unless other new fields are also introduced. While most of our study assumes the Caesium $$(g-2)_e$$ ( g - 2 ) e measurement, our findings in fact also hold in the case of the Rubidium measurement, despite the tension between the two.