Kinetic Modeling of cometabolic degradation of ethanethiol and phenol by Ralstonia eutropha

Cometabolism, as a complex phenomenon in microbial world, is a special mechanism for transformation of many compounds of environmental and toxicological significance. Several models have been proposed to describe the cometabolic transformations of non-growth substrates in the absence or presence of growth substrates. In this study, a model was proposed to simulate the degradation kinetics of phenol and ethanethiol (ET) by a pure culture of Ralstonia eutropha, including the effects of cell growth, endogenous cell decay, loss of transformation activity, competitive inhibition between growth and non-growth substrates, and self-inhibition of non-growth substrate. The model parameters were determined independently and were then used for evaluating the applicability of the model by comparing experimental data with model predictions. The model successfully predicted ET transformation and phenol utilization for a wide range of concentrations of ET (0 ～ 40 mg/L) and phenol (0 ～ 100 mg/L).     

Multi-spectroscopic and molecular docking studies on the interaction of neotame with calf thymus DNA

Abstract

In this paper, we have studied the in vitro binding of neotame (NTM), an artificial sweetener, with native calf thymus DNA using different methods including spectrophotometric, spectrofluorometric, competition experiment, circular dichroism (CD), and viscosimetric techniques. From the spectrophotometric studies, the binding constant (K_b) of NTM-DNA was calculated to be 2?×?10³ M^?1. The quenching of the intrinsic fluorescence of NTM in the presence of DNA at different temperatures was also used to calculate binding constants (K_b) as well as corresponding number of binding sites (n). Moreover, the obtained results indicated that the quenching mechanism involves static quenching. By comparing the competitive fluorimetric studies with Hoechst 33258, as a known groove probe, and methylene blue, as a known intercalation probe, and iodide quenching experiments it was revealed that NTM strongly binds in the grooves of the DNA helix, which was further confirmed by CD and viscosimetric studies. In addition, a molecular docking method was employed to further investigate the binding interactions between NTM and DNA, and confirm the obtained results.     

A new heavy lanthanide-dependent DNAzyme displaying strong metal cooperativity and unrescuable phosphorothioate effect

In vitro selection of RNA-cleaving DNAzymes was performed using three heavy lanthanide ions (Ln³⁺): Ho³⁺, Er³⁺ and Tm³⁺. The resulting sequences were aligned together and about half of the library contained a new family of DNAzyme. These DNAzymes have a simple loop structure, and they are active only with the seven heavy Ln³⁺. Among the tested non-lanthanide ions, only Y³⁺ induced cleavage and even Pb²⁺ failed to cleave, suggesting a very high specificity. A representative DNAzyme, Tm7, has a sigmoidal metal binding curve with a Hill coefficient of 3, indicating that three metal ions are involved in the catalytic step. Its pH-rate profile has a slope of 1, suggesting a single deprotonation step is involved in the rate-limiting step. Tm7 has a cleavage rate of 1.6 min⁻¹ at pH 7.8 with 10 μM Er³⁺. Phosphorothioate substitution at the cleavage junction completely inhibits the activity, which cannot be rescued by Cd²⁺ alone, or by a mixture of Er³⁺ and Cd²⁺, suggesting that two interacting metal ions are involved in direct bonding to both non-bridging oxygen atoms. A new model involving three lanthanide ions is proposed based on this study. A biosensor is engineered using Tm7 to detect Dy³⁺ down to 14 nM.     

TipChip: a modular,MEMS‐based platform for experimentation and phenotyping of tip‐growing cells

Large‐scale phenotyping of tip‐growing cells such as pollen tubes has hitherto been limited to very crude parameters such as germination percentage and velocity of growth. To enable efficient and high‐throughput execution of more sophisticated assays, an experimental platform, the TipChip, was developed based on microfluidic and microelectromechanical systems (MEMS) technology. The device allows positioning of pollen grains or fungal spores at the entrances of serially arranged microchannels equipped with microscopic experimental set‐ups. The tip‐growing cells (pollen tubes, filamentous yeast or fungal hyphae) may be exposed to chemical gradients, microstructural features, integrated biosensors or directional triggers within the modular microchannels. The device is compatible with Nomarski optics and fluorescence microscopy. Using this platform, we were able to answer several outstanding questions on pollen tube growth. We established that, unlike root hairs and fungal hyphae, pollen tubes do not have a directional memory. Furthermore, pollen tubes were found to be able to elongate in air, raising the question of how and where water is taken up by the cell. The platform opens new avenues for more efficient experimentation and large‐scale phenotyping of tip‐growing cells under precisely controlled, reproducible conditions.     

Genetic Diversity of Selected Iranian Quinces Using SSRs from Apples and Pears

An Iranian National Quince collection containing 40 quince genotypes, originating from six distinct geographic areas, was screened using 15 SSR markers developed originally for apple and pear genomes. Overall, 13 markers exhibited polymorphism, with an average of 5.36 putative alleles per locus and a mean PIC value of 0.76. An UPGMA analysis divided the quince genotypes into five major clusters. The same results were obtained when the principal coordinates were plotted. The assignment test successfully allocated 83% of individuals into their place of origin. These results agree somewhat with the geographic origin of the quince accessions, and we conclude that geographic isolation leads to considerable genetic differentiation among Iranian quince collections. A significant ratio of transferability with a mean of 87.86% was measured, and we deduced that STMS markers derived from pear and apple have enough potential to detect polymorphism and differentiation in quince.     

Signatures of host–pathogen evolutionary conflict reveal MISTR—A conserved MItochondrial STress Response network

Host–pathogen conflicts leave genetic signatures in genes that are critical for host defense functions. Using these “molecular scars” as a guide to discover gene functions, we discovered a vertebrate-specific MItochondrial STress Response (MISTR) circuit. MISTR proteins are associated with electron transport chain (ETC) factors and activated by stress signals such as interferon gamma (IFNγ) and hypoxia. Upon stress, ultraconserved microRNAs (miRNAs) down-regulate MISTR1(NDUFA4) followed by replacement with paralogs MItochondrial STress Response AntiViral (MISTRAV) and/or MItochondrial STress Response Hypoxia (MISTRH). While cells lacking MISTR1(NDUFA4) are more sensitive to chemical and viral apoptotic triggers, cells lacking MISTRAV or expressing the squirrelpox virus-encoded vMISTRAV exhibit resistance to the same insults. Rapid evolution signatures across primate genomes for MISTR1(NDUFA4) and MISTRAV indicate recent and ongoing conflicts with pathogens. MISTR homologs are also found in plants, yeasts, a fish virus, and an algal virus indicating ancient origins and suggesting diverse means of altering mitochondrial function under stress. The discovery of MISTR circuitry highlights the use of evolution-guided studies to reveal fundamental biological processes.

Host-pathogen conflicts leave genetic signatures in genes that are critical for host defense functions. This study uses these “molecular scars” as a guide to identify a vertebrate-specific mitochondrial stress response circuit that interacts with the electron transport chain and is activated by stress signals such as interferon-gamma and hypoxia.     

Controlled Access under Review: Improving the Governance of Genomic Data Access

In parallel with massive genomic data production, data sharing practices have rapidly expanded over the last decade. To ensure authorized access to data, access review by data access committees (DACs) has been utilized as one potential solution. Here we discuss core elements to be integrated into the fabric of access review by both established and emerging DACs in order to foster fair, efficient, and responsible access to datasets. We particularly highlight the fact that the access review process could be adversely influenced by the potential conflicts of interest of data producers, particularly when they are directly involved in DACs management. Therefore, in structuring DACs and access procedures, possible data withholding by data producers should receive thorough attention.     

The Data Governance Act and the EU's move towards facilitating data sharing

The implementation of the EU General Data Protection Regulation (GDPR) has had significant impacts on biomedical research, often complicating data sharing among researchers. The recently announced proposal for a new EU Data Governance Act is a promising step towards facilitating data sharing, if it can interplay well with the GDPR.Subject Categories: S&S: Ethics

The EU General Data Protection Regulation (GDPR) has affected biomedical research, often complicating data sharing. The recently announced proposal for a new EU Data Governance Act, is a promising step towards facilitating data sharing.

In an attempt to improve and increase data sharing in the EU and to optimize the re‐use of personal and non‐personal data, the European Commission has recently announced the proposal for a new EU Data Governance Act (https://ec.europa.eu/digital‐single‐market/en/news/proposal‐regulation‐european‐data‐governance‐data‐governance‐act). If approved, it will enable the creation and regulation of “secure spaces” where various types of data, including health data, can be shared and re‐used for both commercial and altruistic purposes, including scientific research. The Data Governance Act, within the framework of a European Strategy for Data, (https://ec.europa.eu/info/sites/info/files/communication‐european‐strategy‐dat‐19feb2020_en.pdf), would address some of the shortcomings and drawbacks of the current regulatory framework which holds back sharing and re‐using data for biomedical research purposes.While the proposed Act would apply to all types of personal and non‐personal data, the increasing demand for sharing health data has most likely been a major rationale for this new legislation of data governance. Notably, sharing health and genetic data for scientific research entails an extra layer of complexity, owing to concerns over data protection and privacy when sharing sensitive personal data. Vice versa, there are also concerns in the scientific community over the negative impact of regulatory restrictions on sharing health data in data‐driven biomedical research. The pressing question here is how far the EU’s proposed legislative and policy framework can offset either concerns?