Decoding the nucleoid organisation of Bacillus subtilis and Escherichia coli through gene expression data

BACKGROUND: Although the organisation of the bacterial chromosome is an area of active research, little is known yet on that subject. The difficulty lies in the fact that the system is dynamic and difficult to observe directly. The advent of massive hybridisation techniques opens the way to further studies of the chromosomal structure because the genes that are co-expressed, as identified by microarray experiments, probably share some spatial relationship. The use of several independent sets of gene expression data should make it possible to obtain an exhaustive view of the genes co-expression and thus a more accurate image of the structure of the chromosome. RESULTS: For both Bacillus subtilis and Escherichia coli the co-expression of genes varies as a function of the distance between the genes along the chromosome. The long-range correlations are surprising: the changes in the level of expression of any gene are correlated (positively or negatively) to the changes in the expression level of other genes located at well-defined long-range distances. This property is true for all the genes, regardless of their localisation on the chromosome. We also found short-range correlations, which suggest that the location of these co-expressed genes corresponds to DNA turns on the nucleoid surface (14–16 genes). CONCLUSION: The long-range correlations do not correspond to the domains so far identified in the nucleoid. We explain our results by a model of the nucleoid solenoid structure based on two types of spirals (short and long). The long spirals are uncoiled expressed DNA while the short ones correspond to coiled unexpressed DNA

Analyzing stochastic transcription to elucidate the nucleoid's organization.

International audienceABSTRACT: BACKGROUND: The processes of gene transcription, translation, as well as the reactions taking place between gene products, are subject to stochastic fluctuations. These stochastic events are being increasingly examined as it emerges that they can be crucial in the cell's survival. In a previous study we had examined the transcription patterns of two bacterial species (Escherichia coli and Bacillus subtilis) to elucidate the nucleoid's organization. The basic idea is that genes that share transcription patterns, must share some sort of spatial relationship, even if they are not close to each other on the chromosome. We had found that picking any gene at random, its transcription will be correlated with genes at well-defined short- as well as long-range distances, leaving the explanation of the latter an open question. In this paper we study the transcription correlations when the only transcription taking place is stochastic, in other words, no active or "deterministic" transcription takes place. To this purpose we use transcription data of Sinorhizobium meliloti. RESULTS: Even when only stochastic transcription takes place, the co-expression of genes varies as a function of the distance between genes: we observe again the short-range as well as the regular, long-range correlation patterns. CONCLUSION: We explain these latter with a model based on the physical constraints acting on the DNA, forcing it into a conformation of groups of a few successive large and transcribed loops, which are evenly spaced along the chromosome and separated by small, non-transcribed loops. We discuss the question about the link between shared transcription patterns and physiological relationship and come to the conclusion that when genes are distantly placed along the chromosome, the transcription correlation does not imply a physiological relationship

Omental adipocyte hypertrophy relates to coenzyme Q10 redox state and lipid peroxidation in obese women

Occurrence of oxidative stress in white adipose tissues contributes to its dysfunction and the development of obesity-related metabolic complications. Coenzyme Q10 (CoQ10) is the single lipophilic antioxidant synthesized in humans and is essential for electron transport during mitochondrial respiration. To understand the role of CoQ10 in adipose tissue physiology and dysfunction, the abundance of the oxidized and reduced (CoQ10red) isoforms of the CoQ10 were quantified in subcutaneous and omental adipose tissues of women covering the full range of BMI (from 21.5 to 53.2 kg/m2). Lean women displayed regional variations of CoQ10 redox state between the omental and subcutaneous depot, despite similar total content. Obese women had reduced CoQ10red concentrations in the omental depot, leading to increased CoQ10 redox state and higher levels of lipid hydroperoxide. Women with low omental CoQ10 content had greater visceral and subcutaneous adiposity, increased omental adipocyte diameter, and higher circulating interleukin-6 and C-reactive protein levels and were more insulin resistant. The associations between abdominal obesity-related cardiometabolic risk factors and CoQ10 content in the omental depot were abolished after adjustment for omental adipocyte diameter. This study shows that hypertrophic remodeling of visceral fat closely relates to depletion of CoQ10, lipid peroxidation, and inflammation

Pharmacokinetics during therapeutic hypothermia in neonates:from pathophysiology to translational knowledge and physiologically-based pharmacokinetic (PBPK) modeling

Introduction: Perinatal asphyxia (PA) still causes significant morbidity and mortality. Therapeutic hypothermia (TH) is the only effective therapy for neonates with moderate to severe hypoxic-ischemic encephalopathy after PA. These neonates need additional pharmacotherapy, and both PA and TH may impact physiology and, consequently, pharmacokinetics (PK) and pharmacodynamics (PD). Areas covered: This review provides an overview of the available knowledge in PubMed (until November 2022) on the pathophysiology of neonates with PA/TH. In vivo pig models for this setting enable distinguishing the effect of PA versus TH on PK and translating this effect to human neonates. Available asphyxia pig models and methodological considerations are described. A summary of human neonatal PK of supportive pharmacotherapy to improve neurodevelopmental outcomes is provided. Expert opinion: To support drug development for this population, knowledge from clinical observations (PK data, real-world data on physiology), preclinical (in vitro and in vivo (minipig)) data, and molecular and cellular biology insights can be integrated into a predictive physiologically-based PK (PBPK) framework, as illustrated by the I-PREDICT project (Innovative physiology-based pharmacokinetic model to predict drug exposure in neonates undergoing cooling therapy). Current knowledge, challenges, and expert opinion on the future directions of this research topic are provided.</p

Isotopic niches of diadromous fishes inform on interspecific competition in an obstructed catchment

Competition arises when species share a limited resource, but this can be avoided through niche partitioning. Despite the large body of literature on diadromous fishes, very few studies have focused on niche partitioning when competing for resources. Diadromous fishes are suffering a global decline throughout their range in part due to their peculiar life history traits as they migrate from the sea to freshwater to spawn or the reverse. They are particularly sensitive to river fragmentation induced by barriers. Dams for instance are expected to alter the spatial distribution and resource exploitation of diadromous fishes as well as other organisms. Here, we studied the ecological niche of six taxa of diadromous fishes, temporally co-occurring in the same land–sea continuum obstructed by two river dams. We used Bayesian mixing models run on C and N isotopes to infer the various habitats used and the origin of the trophic carbon in muscle and scale tissues of diadromous fishes. Results showed that the sub-adults of Anguilla anguilla, juveniles of Petromyzon marinus, and Salmo trutta exploit mainly the freshwater, or marine part for adults of Lampetra fluviatilis, whereas juveniles of Platichthys flesus and Mugilidae use all the habitats of the land–sea continuum. In the freshwater habitat, the microphytobenthos and biofilm are the main sources of carbon used, while in the marine habitat, the basal carbon sources are more diverse. The analyses of niche overlaps between diadromous fishes demonstrate that the widest isotopic niches, observed for A. anguilla and P. flesus, also have more impact within the community. Results are discussed in terms of intra- and interspecific competition between these diadromous fishes and their generalist/specialist strategies in an obstructed catchment

Swelfe: a detector of internal repeats in sequences and structures

Summary: Intragenic duplications of genetic material have important biological roles because of their protein sequence and structural consequences. We developed Swelfe to find internal repeats at three levels. Swelfe quickly identifies statistically significant internal repeats in DNA and amino acid sequences and in 3D structures using dynamic programming. The associated web server also shows the relationships between repeats at each level and facilitates visualization of the results

France’s proposal for Guidelines about setting Maximum Residue Limits in honey

contribution to session I Regulatory issues Background: Honey is produced in an environment potentially polluted by different sources of contamination, so it is necessary to set Maximum Residue Limits (MRLs). These MRLs should be fixed as low as possible in relation to Good Agricultural Practices (GAPs). The guidance provided in this Draft Working Document gives advice on: • when and for what kind of active substance a MRL has to be set in honey • how to propose a temporary MRL for a given active substance • how to design, prepare and realise supervised residue trials when necessary Results: The proposed approach is based on using the available data before an active substance or product is registered, and is divided into several successive steps, represented in a global decision-making scheme. The MRL will be set depending on the results obtained at each different step. Besides, the applicants will have the choice between different methods to set a provisional MRL in preregistration. Conclusion: The initial proposal was a protocol on field residue trials proposed by Germany. The approach used in this guidance document proposes also other possibilities for fixing MRL without conducting systematically field trials. This proposition will be discussed at European level. Keywords: Regulation 396/2005, MRL, honey, plant protection produc

Emergency department outcome of elderly patients assisted by professional home services, the EPIGER study.

BACKGROUND: For the elderly population living at home, the implementation of professional services tends to mitigate the effect of loss of autonomy and increases their quality of life. While helping in avoiding social isolation, home services could also be associated to different healthcare pathways. For elderly patients, Emergency Departments (EDs) are the main entrance to hospital where previous loss of autonomy is associated to worst hospital outcomes. Part of elderly patients visiting EDs are still admitted to hospital for having difficulties coping at home without presenting any acute medical issue. There is a lack of data concerning elderly patients visiting EDs assisted by home services. Our aim was to compare among elderly patients visiting ED those assisted by professional home services to those who do not in terms of emergency resources' use and patients' outcome. METHODS: A multicenter, prospective cohort study was performed in 124 French EDs during a 24-h period on March 2016.Consecutive patients living at home aged ≥80 years were included. The primary objective was to assess the risk of mortality for patients assisted by professional home services vs. those who were not. Secondary objectives included admission rate and specific admission rate for "having difficulties coping at home". The primary endpoint was in-hospital mortality. Cox proportional-hazards regression model was used to test the association between professional home services and the primary endpoint. Multi variables logistic regressions were performed to assess secondary endpoints. RESULTS: One thousand one hundred sixty-eight patients were included, median age 86(83-89) years old,32% were assisted by professional home services. The overall in-hospital mortality rate was 7%. Assisted patients had more investigations performed. Home services were not associated with increased in-hospital mortality (HR = 1.34;95%CI [0.68-2.67]), nor with the admission rate (OR = 0.92;95%CI [0.65-1.30]). Assisted patients had a lower risk of being admitted for "having difficulties coping at home" (OR = 0.59;95%CI [0.38-0.92]). CONCLUSION: Professional home services which assist one-third of elderly patients visiting EDs, were not associated to lower in-hospital mortality or to an increased admission rate. Assisted patients were associated to a lower risk of being admitted for «having difficulties coping at home».Professional home services could result in avoiding some admissions and their corollary complications. TRIAL REGISTRATION: Clinicaltrial.gov - NCT02900391 , 09/14/2016, retrospectively registered