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In a fluctuating environment, cell populations need to adapt to survive. There are several ways to achieve it, but in general cells take benefit from biological noise to switch to alternative phenotypes, leading to improved fitness in the new environment. This is a known phenomenon that gives rise to phenotypically heterogeneous populations, but the dynamics of the adaptation are still unclear.

Understanding those dynamics is key if one wants to control gene expression in bio-processes in general, but the literature on ways to reproduce population behaviours quantitatively in silico is still nascent; and if a few models are available, they have not been validated based on experimental data.

Therefore, in this work, an existing model was applied and improved to better fit experimental data obtained based on the use of high-throughput, automated, flow cytometry. In particular, a simple model derived from the general model developed by Thattai and Van Oudenaarden was applied to data representing populations of Escherichia coli growing under continuous cultivation conditions. The fluctuating environment for the population was based on a constant feed of glucose, but varying amounts of arabinose in the medium.

The existing model used basal stochastic switching to drive the population diversification. It was found insufficient to reproduce the observed data, and several possible new contributions to the model were therefore devised. Each one was considered independently of the others, thanks to a succession of models, each taking into account a different set of contributions, and fitted as well as possible to the data.

Eventually, it was found that several of those contributions could indeed improve the model for this particular case. Moreover, this work also sheds new lights on two important points that are likely applicable in most systems with heterogeneous cell populations: the growth rates of the different phenotypes need to be considered in details if the population is to be modelled correctly, and representing the switching mechanism adequately is likely often easier and more exact by simulating single cells with a stochastic behaviour, rather than using differential equations.

Phenotypic heterogeneity --- Fluctuating environment --- Segregostat --- Modelling --- Ingénierie, informatique & technologie > Multidisciplinaire, généralités & autres

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Pulmonary arterial hypertension is a severe and progressive disorder affecting the blood vessels in the lungs. Typically, symptoms first appear at around 30–40 years of age and, without treatment, can lead to fatal heart disease within a few years. Genetic studies over the past decade have identified numerous genes that contribute to disease progression but, for many sufferers, the underlying genetic cause remains elusive. The collection of reviews and original research articles contained within this book provide an overview of recent advancements in understanding the genetic risk factors for pulmonary arterial hypertension. We further examine the emerging interplay between genetic variants and clinical outcomes, providing a framework for new treatments and improved patient care.

pulmonary arterial hypertension --- massive parallel sequencing --- NGS --- digenic inheritance --- and genetics --- BMPR2 promoter --- pathogenic variant --- heritable pulmonary arterial hypertension --- genetic analysis --- NGS gene panel --- BMPR2 --- TBX4 --- GDF2 --- EIF2AK4 --- genomics --- pediatrics --- lung disease --- endothelial cells --- smooth muscle cells --- DNA damage --- DNA repair --- expression quantitative trait locus --- eQTL --- blood --- genetics --- exome sequencing --- molecular genetics --- paediatrics --- bone morphogenetic protein receptor type 2 --- heritable --- familial --- estrogen --- estradiol --- penetrance --- gender --- PAH --- forward phenotyping --- forward genetics --- reverse genetics --- reverse phenotyping --- intermediate phenotypes --- whole-genome sequencing --- epigenetic inheritance --- genetic heterogeneity --- phenotypic heterogeneity --- pulmonary hypertension --- bone morphogenetic protein receptor 2 --- signaling --- repurposed drugs --- pharmaceuticals --- miRNA --- clinical trials --- n/a

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The G.B. Elyakov Pacific Institute of Bioorganic Chemistry of the Far-Eastern Branch of the Russian Academy of Sciences (PIBOC FEB RAS) was founded in 1964 in Vladivostok in the Far East of Russia. Over many years, we have been carrying out studies on the natural products of both marine and terrestrial origin. In collaboration with many Russian and foreign scientists, we have investigated many hundreds of diverse biomolecules, including steroids and terpenoids, quinoid compounds and alkaloids, polysaccharides and lipids, enzymes and lectins, proteins, and peptides. The Institute has a collection of marine microorganisms (KMM) PIBOC, which includes more than 4000 strains of marine bacteria and more than 1000 strains of marine fungi. The biological activity of natural compounds is also being studied. This book includes the 14 manuscripts which covered almost all aspects of PIBOC research activity in the fields of bioorganic chemistry, biochemistry, organic synthesis of natural compounds, marine microbiology, and genetic engineering, and we hope it will provide interesting new information for scientists working in these fields.

Research & information: general --- polyhydroxylated steroids --- NMR spectra --- starfish --- Anthenoides laevigatus --- cytotoxicity --- soft agar assay --- kainic acid --- domoic acid --- dysiherbaine --- neodysiherbaine A --- marine bacteria --- whole genome sequence --- porin --- amino acids composition --- bilayer lipid membrane --- pore-forming activity --- spatial structure --- phlorotannins --- phlorethols --- anticancer activity --- colorectal cancer --- radiosensitizer --- radiotherapy --- 1,4-naphthoquinones --- quinoid compounds --- thioglycosides --- quinone-sugar conjugates --- cytotoxic activity --- antibiotic activity --- histochrome --- echinochrome A --- oxidative degradation --- HPLC–DAD–MS --- NMR --- actinoporin --- sea anemone --- Heteractis crispa --- anti-migratory activity --- glycosphingolipids --- cerebrosides --- peroxidation products --- structure elucidation --- allylic thioether --- ESI-MS --- GC-MS --- mass spectra --- glass sponge --- isomalabaricanes --- Stelletta sp. --- marine sponge --- terpenoid --- Cobetia amphilecti --- Cobetia litoralis --- Cobetia pacifica --- Cobetia marina --- Cobetia crustatorum --- identification markers --- alkaline phosphatase PhoA --- lanosterol 14-alpha demethylase --- flavonoids --- enzyme inhibition --- surface plasmon resonance --- spectral titration --- molecular docking --- Zobellia --- genomes --- polysaccharide lyase family 7 --- alginate utilization system --- paralogs --- orthologs --- recombinant phospholipase A1 --- Yersinia pseudotuberculosis --- inclusion bodies --- fusion protein --- green fluorescent protein --- porin gene expression --- antibiotic stress --- phenotypic heterogeneity --- n/a --- HPLC-DAD-MS

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The G.B. Elyakov Pacific Institute of Bioorganic Chemistry of the Far-Eastern Branch of the Russian Academy of Sciences (PIBOC FEB RAS) was founded in 1964 in Vladivostok in the Far East of Russia. Over many years, we have been carrying out studies on the natural products of both marine and terrestrial origin. In collaboration with many Russian and foreign scientists, we have investigated many hundreds of diverse biomolecules, including steroids and terpenoids, quinoid compounds and alkaloids, polysaccharides and lipids, enzymes and lectins, proteins, and peptides. The Institute has a collection of marine microorganisms (KMM) PIBOC, which includes more than 4000 strains of marine bacteria and more than 1000 strains of marine fungi. The biological activity of natural compounds is also being studied. This book includes the 14 manuscripts which covered almost all aspects of PIBOC research activity in the fields of bioorganic chemistry, biochemistry, organic synthesis of natural compounds, marine microbiology, and genetic engineering, and we hope it will provide interesting new information for scientists working in these fields.

Research & information: general --- polyhydroxylated steroids --- NMR spectra --- starfish --- Anthenoides laevigatus --- cytotoxicity --- soft agar assay --- kainic acid --- domoic acid --- dysiherbaine --- neodysiherbaine A --- marine bacteria --- whole genome sequence --- porin --- amino acids composition --- bilayer lipid membrane --- pore-forming activity --- spatial structure --- phlorotannins --- phlorethols --- anticancer activity --- colorectal cancer --- radiosensitizer --- radiotherapy --- 1,4-naphthoquinones --- quinoid compounds --- thioglycosides --- quinone-sugar conjugates --- cytotoxic activity --- antibiotic activity --- histochrome --- echinochrome A --- oxidative degradation --- HPLC-DAD-MS --- NMR --- actinoporin --- sea anemone --- Heteractis crispa --- anti-migratory activity --- glycosphingolipids --- cerebrosides --- peroxidation products --- structure elucidation --- allylic thioether --- ESI-MS --- GC-MS --- mass spectra --- glass sponge --- isomalabaricanes --- Stelletta sp. --- marine sponge --- terpenoid --- Cobetia amphilecti --- Cobetia litoralis --- Cobetia pacifica --- Cobetia marina --- Cobetia crustatorum --- identification markers --- alkaline phosphatase PhoA --- lanosterol 14-alpha demethylase --- flavonoids --- enzyme inhibition --- surface plasmon resonance --- spectral titration --- molecular docking --- Zobellia --- genomes --- polysaccharide lyase family 7 --- alginate utilization system --- paralogs --- orthologs --- recombinant phospholipase A1 --- Yersinia pseudotuberculosis --- inclusion bodies --- fusion protein --- green fluorescent protein --- porin gene expression --- antibiotic stress --- phenotypic heterogeneity --- polyhydroxylated steroids --- NMR spectra --- starfish --- Anthenoides laevigatus --- cytotoxicity --- soft agar assay --- kainic acid --- domoic acid --- dysiherbaine --- neodysiherbaine A --- marine bacteria --- whole genome sequence --- porin --- amino acids composition --- bilayer lipid membrane --- pore-forming activity --- spatial structure --- phlorotannins --- phlorethols --- anticancer activity --- colorectal cancer --- radiosensitizer --- radiotherapy --- 1,4-naphthoquinones --- quinoid compounds --- thioglycosides --- quinone-sugar conjugates --- cytotoxic activity --- antibiotic activity --- histochrome --- echinochrome A --- oxidative degradation --- HPLC-DAD-MS --- NMR --- actinoporin --- sea anemone --- Heteractis crispa --- anti-migratory activity --- glycosphingolipids --- cerebrosides --- peroxidation products --- structure elucidation --- allylic thioether --- ESI-MS --- GC-MS --- mass spectra --- glass sponge --- isomalabaricanes --- Stelletta sp. --- marine sponge --- terpenoid --- Cobetia amphilecti --- Cobetia litoralis --- Cobetia pacifica --- Cobetia marina --- Cobetia crustatorum --- identification markers --- alkaline phosphatase PhoA --- lanosterol 14-alpha demethylase --- flavonoids --- enzyme inhibition --- surface plasmon resonance --- spectral titration --- molecular docking --- Zobellia --- genomes --- polysaccharide lyase family 7 --- alginate utilization system --- paralogs --- orthologs --- recombinant phospholipase A1 --- Yersinia pseudotuberculosis --- inclusion bodies --- fusion protein --- green fluorescent protein --- porin gene expression --- antibiotic stress --- phenotypic heterogeneity