Lineage commitment of hematopoietic stem cells and progenitors: insights from recent single cell and lineage tracing technologies.

Exp Hematol. 2020 Jul 09;:

Authors: Loughran S, Haas S, Wilkinson AC, Klein A, Brand M

Abstract
Blood production is essential to maintain human health, and even small perturbations in hematopoiesis can cause disease. Hematopoiesis has therefore been the focus of much research for many years. Experiments determining the lineage potentials of hematopoietic stem and progenitor cells (HSPCs) in vitro and after transplantation revealed a hierarchy of progenitor cell states, where differentiating cells undergo lineage commitment - a series of irreversible changes that progressively restrict their potential. New technologies have recently been developed that allow for a more detailed analysis of the molecular states and fates of differentiating HSPCs. Proteomic and lineage-tracing approaches, alongside single cell transcriptomic analyses have recently helped to reveal the biological complexity underlying lineage commitment during hematopoiesis. Recent insights from these new technologies were presented by Drs. Marjorie Brand and Allon Klein in the Summer 2019 ISEH Webinar, and are discussed in this Perspective.

PMID: 32653531 [PubMed - as supplied by publisher]

Computational insights into tetracyclines as inhibitors against SARS-CoV-2 Mpro via combinatorial molecular simulation calculations.

Life Sci. 2020 Jul 09;:118080

Authors: Bharadwaj S, Lee KE, Dwivedi VD, Kang SG

Abstract
The COVID-19 pandemic raised by SARS-CoV-2 is a public health emergency. However, lack of antiviral drugs and vaccine against human coronaviruses demands a concerted approach to challenge the SARS-CoV-2 infection. Under limited resource and urgency, combinatorial computational approaches to identify the potential inhibitor from known drugs could be applied against risen COVID-19 pandemic. Thereof, this study attempted to purpose the potent inhibitors from the approved drug pool against SARS-CoV-2 main protease (Mpro). To circumvent the issue of lead compound from available drugs as antivirals, antibiotics with broad spectrum of viral activity, i.e. doxycycline, tetracycline, demeclocycline, and minocycline were chosen for molecular simulation analysis against native ligand N3 inhibitor in SARS-CoV-2 Mpro crystal structure. Molecular docking simulation predicted the docking score >-7 kcal/mol with significant intermolecular interaction at the catalytic dyad (His41 and Cys145) and other essential substrate binding residues of SARS-CoV-2 Mpro. The best ligand conformations were further studied for complex stability and intermolecular interaction profiling with respect to time under 100 ns classical molecular dynamics simulation, established the significant stability and interactions of selected antibiotics by comparison to N3 inhibitor. Based on combinatorial molecular simulation analysis, doxycycline and minocycline were selected as potent inhibitor against SARS-CoV-2 Mpro which can used in combinational therapy against SARS-CoV-2 infection.

PMID: 32653520 [PubMed - as supplied by publisher]

Phylogenetic relationships in the genus Cheracebus (Callicebinae, Pitheciidae).

Am J Primatol. 2020 Jul 11;:e23167

Authors: Carneiro J, Sampaio I, Lima T, Silva-Júnior JS, Farias I, Hrbek T, Valsecchi J, Boubli J, Schneider H

Abstract
Cheracebus is a new genus of New World primate of the family Pitheciidae, subfamily Callicebinae. Until recently, Cheracebus was classified as the torquatus species group of the genus Callicebus. The genus Cheracebus has six species: C. lucifer, C. lugens, C. regulus, C. medemi, C. torquatus, and C. purinus, which are all endemic to the Amazon biome. Before the present study, there had been no conclusive interpretation of the phylogenetic relationships among most of the Cheracebus species. The present study tests the monophyly of the genus and investigates the relationships among the different Cheracebus species, based on DNA sequencing of 16 mitochondrial and nuclear markers. The phylogenetic analyses were based on Maximum Likelihood, Bayesian Inference, and multispecies coalescent approaches. The divergence times and genetic distances between the Cheracebus taxa were also estimated. The analyses confirmed the monophyly of the genus and a well-supported topology, with the following arrangement: ((C. torquatus, C. lugens), (C. lucifer (C. purinus, C. regulus))). A well-differentiated clade was also identified within part of the geographic range of C. lugens, which warrants further investigation to confirm its taxonomic status.

PMID: 32652664 [PubMed - as supplied by publisher]

Proteomic analysis of wheat contrasting genotypes reveals the interplay between primary metabolic and regulatory pathways in anthers under drought stress.

J Proteomics. 2020 Jul 08;:103895

Authors: Mehri N, Fotovat R, Mirzaei M, Fard EM, Parsamatin P, Hasan MT, Wu Y, Ghaffari MR, Salekdeh GH

Abstract
Reproductive stage is very sensitive to various forms of environmental stresses such as drought stress. The proteomic analysis of anther during pollen development in response to drought stress was performed using a label-free quantitative shotgun proteomic technique to define the underlying molecular principles in two contrasting wheat genotypes Shiraz (susceptible) and D-10 (tolerant). Drought stress resulted in around two-fold decline in seed setting capacity and pollen viability in the Shiraz genotype compared to D-10. A Partial Least Square Discriminant Analysis (PLS-DA) of proteomic data revealed the abundance of 131 differentially abundant proteins significantly contributing in separation of drought tolerant and susceptible genotypes under normal and stress conditions. Proteins involved in cellular respiration, carbohydrate metabolism, RNA metabolism, and vesicle trafficking showed completely different responses in two genotypes. These proteins may maintain hexose pool and energy level and control regulation of transcription and transport. Furthermore, different members of functional groups such as protein biosynthesis and degradation, chromatin organization, and cytoskeleton dynamics were differentially abundant in response to stress in both genotypes which suggest their function in both genotypes to maintain minimum pollen viability/ fertility under drought stress. In conclusion, our findings revealed various metabolic and regulatory pathways underlying survival strategies required for pollen fertility and viability. SIGNIFICANCE: Drought caused by global climate change decreases cereal grain productivity worldwide. Yield losses due to water stress have been reported for major small grain cereal including wheat. Our findings highlighted the importance of key proteins in wheat adaptation to drought stress at reproductive stage. The obtained data showed that differentially abundant proteins in drought tolerant wheat genotype was remarkably associated with cellular respiration, carbohydrate metabolism, RNA metabolism, and vesicle trafficking. These results revealed fundamental data to elucidate the complexity of pollen fertility and viability under drought stress condition in wheat.

PMID: 32652220 [PubMed - as supplied by publisher]

Correction: A DNA methylation clock associated with age-related illnesses and mortality is accelerated in men with combat PTSD.

Mol Psychiatry. 2020 Jul 10;:

Authors: Yang R, Wu GWY, Verhoeven JE, Gautam A, Reus VI, Kang JI, Flory JD, Abu-Amara D, PTSD Systems Biology Consortium, Hood L, Doyle FJ, Yehuda R, Marmar CR, Jett M, Hammamieh R, Mellon SH, Wolkowitz OM

Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.

PMID: 32651479 [PubMed - as supplied by publisher]

Genomic insights of body plan transitions from bilateral to pentameral symmetry in Echinoderms.

Commun Biol. 2020 Jul 10;3(1):371

Authors: Li Y, Omori A, Flores RL, Satterfield S, Nguyen C, Ota T, Tsurugaya T, Ikuta T, Ikeo K, Kikuchi M, Leong JCK, Reich A, Hao M, Wan W, Dong Y, Ren Y, Zhang S, Zeng T, Uesaka M, Uchida Y, Li X, Shibata TF, Bino T, Ogawa K, Shigenobu S, Kondo M, Wang F, Chen L, Wessel G, Saiga H, Cameron RA, Livingston B, Bradham C, Wang W, Irie N

Abstract
Echinoderms are an exceptional group of bilaterians that develop pentameral adult symmetry from a bilaterally symmetric larva. However, the genetic basis in evolution and development of this unique transformation remains to be clarified. Here we report newly sequenced genomes, developmental transcriptomes, and proteomes of diverse echinoderms including the green sea urchin (L. variegatus), a sea cucumber (A. japonicus), and with particular emphasis on a sister group of the earliest-diverged echinoderms, the feather star (A. japonica). We learned that the last common ancestor of echinoderms retained a well-organized Hox cluster reminiscent of the hemichordate, and had gene sets involved in endoskeleton development. Further, unlike in other animal groups, the most conserved developmental stages were not at the body plan establishing phase, and genes normally involved in bilaterality appear to function in pentameric axis development. These results enhance our understanding of the divergence of protostomes and deuterostomes almost 500 Mya.

PMID: 32651448 [PubMed - as supplied by publisher]

Analysis of the photoheterotrophic assimilation of valerate and associated PHA production by Rs. rubrum.

Appl Environ Microbiol. 2020 Jul 10;:

Authors: Bayon-Vicente G, Zarbo S, Deutschbauer A, Wattiez R, Leroy B

Abstract
Purple non-sulfur bacteria are increasingly regarded for industrial applications in bioplastics, pigment and biomass production. In order to optimize the yield of future biotechnological processes, the assimilation of different carbon sources by Rhodospirillum rubrum (Rs. rubrum) has to be understood. As they are released from several fermentation processes, volatile fatty acids (VFAs) represent a promising carbon source in the development of circular industrial applications. To obtain an exhaustive characterization of the photoheterotrophic metabolism of Rs. rubrum in the presence of valerate, we combined phenotypic, proteomic and genomic approaches. We obtained evidence that valerate is cleaved into acetyl-CoA and propionyl-CoA and depends on the presence of bicarbonate ions. Genomic and enzyme inhibition data showed that a functional methylmalonyl-CoA pathway is essential. Our proteomic data showed that the photoheterotrophic assimilation of valerate induces an intracellular redox stress which is accompanied by an increased abundance of phasins (the main proteins present in PHA granules). Finally, we observed a significant increase in the production of the copolymer P(HB-co-HV) presenting an outstanding (more than 80%) percentage of HV monomer. Moreover, an increase in the PHA content was obtained when bicarbonate ions were progressively added to the medium. The experimental conditions used in this study suggest that the redox imbalance is responsible for PHA production. These findings also reinforce the idea that PNSB are suitable for PHA production through another strategy than the well-known feast and famine process.Importance The use and the littering of plastics represent major issues that humanity has to face. Polyhydroxyalkanoates (PHAs) are good candidates for the replacement of oil-based plastics as they exhibit comparable physicochemical properties but are biobased and biodegradable. However, the current industrial production of PHAs is curbed by the production costs, which are mainly linked to the carbon source. Volatile fatty acids issued from the fermentation processes constitute interesting carbon sources as they are cheap and easily available. Among them, valerate is gaining interest regarding the ability of many bacteria to produce a copolymer of PHAs. Here, we describe the photoheterotrophic assimilation of valerate by Rhodospirillum rubrum, a purple non-sulfur bacterium mainly known for its metabolic versatility. Using a knowledge based optimization process, we display a new strategy for the improvement of PHA production, paving the way for the use of Rhodospirillum rubrum in industrial processes.

PMID: 32651203 [PubMed - as supplied by publisher]

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