Inference of ancient whole genome duplications and the evolution of the gene duplication and loss rate.

Mol Biol Evol. 2019 Apr 19;:

Authors: Zwaenepoel A, Van de Peer Y

Abstract
Gene tree - species tree reconciliation methods have been employed for studying ancient whole genome duplication (WGD) events across the eukaryotic tree of life. Most approaches have relied on using maximum likelihood trees and the maximum parsimony reconciliation thereof to count duplication events on specific branches of interest in a reference species tree. Such approaches do not account for uncertainty in the gene tree and reconciliation, or do so only heuristically. The effects of these simplifications on the inference of ancient WGDs are unclear. In particular the effects of variation in gene duplication and loss rates across the species tree have not been considered. Here, we developed a full probabilistic approach for phylogenomic reconciliation based WGD inference, accounting for both gene tree and reconciliation uncertainty using a method based on the principle of amalgamated likelihood estimation. The model and methods are implemented in a maximum likelihood and Bayesian setting and account for variation of duplication and loss rate across the species tree, using methods inspired by phylogenetic divergence time estimation. We applied our newly developed framework to ancient WGDs in land plants and investigate the effects of duplication and loss rate variation on reconciliation and gene count based assessment of these earlier proposed WGDs.

PMID: 31004147 [PubMed - as supplied by publisher]

Simple fluorometric-based assay of antibiotic effectiveness for Acinetobacter baumannii biofilms.

Sci Rep. 2019 Apr 19;9(1):6300

Authors: Wannigama DL, Hurst C, Pearson L, Saethang T, Singkham-In U, Luk-In S, Storer RJ, Chatsuwan T

Abstract
Despite strengthened antimicrobial therapy, biofilm infections of Acinetobacter baumannii are associated with poor prognosis and limited therapeutic options. Assessing antibiotics on planktonic bacteria can result in failure against biofilm infections. Currently, antibiotics to treat biofilm infections are administered empirically, usually without considering the susceptibility of the biofilm objectively before beginning treatment. For effective therapy to resolve biofilm infections it is essential to assess the efficacy of commonly used antibiotics against biofilms. Here, we offer a robust and simple assay to assess the efficacy of antibiotics against biofilms. In the present work, we carefully optimized the incubation time, detection range, and fluorescence reading mode for resazurin-based viability staining of biofilms in 96-well-plates and determined minimal biofilm eradication concentrations (MBECs) for A. baumannii isolates from patients with chronic infection. By applying this assay, we demonstrated that antibiotic response patterns varied uniquely within the biofilm formation of various clinical samples. MBEC-50 and 75 have significant discriminatory power over minimum inhibitory concentrations for planktonic suspensions to differentiate the overall efficiency of an antibiotic to eradicate a biofilm. The present assay is an ideal platform on which to assess the efficacy of antibiotics against biofilms in vitro to pave the way for more effective therapy.

PMID: 31004100 [PubMed - in process]

How Ca2+ influx is attenuated in the heart during a "fight or flight" response.

J Gen Physiol. 2019 Apr 19;:

Authors: Bazmi M, Escobar AL

PMID: 31004065 [PubMed - as supplied by publisher]

36 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

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These pubmed results were generated on 2019/04/20

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"systems biology"

These pubmed results were generated on 2019/04/19

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30 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2019/04/18

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37 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2019/04/17

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31 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2019/04/17

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58 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2019/04/16

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51 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2019/04/16

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In vitro anti-glioblastoma activity of L-valine derived boroxazolidones.

Eur J Pharmacol. 2019 Apr 11;:

Authors: Viswanathan A, Sebastianelli G, Brown K, Raunio J, Sipilä V, Yli-Harja O, Candeias NR, Kandhavelu M

Abstract
In the present study, a series of L-valine derived boroxazolidones, previously synthesized and reported to have residual activity in a human epithelial cell line, have been evaluated in vitro for their anti-glioblastoma activity. A boroxazolidone derivative containing 2,4-difluorophenyl moieties (6) was found to have higher cytotoxicity than the standard drug, Temozolomide (TMZ). Compound 6 was found to exhibit dose-dependent growth inhibitory effects with an IC50 of 49 μM and 53 μM for LN229 and SNB19 cells, respectively. Additionally, 6 was assessed for its role in apoptosis, caspase 3/7 activation and oxidative stress in SNB19 and LN229 cells. SNB19 cells treated with 6 showed 45.3% apoptosis in the population, while TMZ had 24.7%. In LN229 cells, the percentage of apoptotic cells treated with compound 6 and TMZ were the same. Both 6 and TMZ induced apoptosis through the activation of caspase 3/7 in SNB19 and LN229 cells. Interestingly, 6 exhibited a higher effectivity in promoting reactive oxygen species production in LN229, while it was 6-fold less in SNB19. Boroxazolidone-treated GBM cell lines increased reactive oxygen species production, suggesting that such species may be interlinked with the observed programmed cell death. Additionally, the treatment of both GBM cell lines with 6 led to G2/M phase arrest. The magnitude of anti-GBM effect of 6 is significantly higher than the known chemotherapeutic agent TMZ. This work further demonstrates the anticancer properties of L-valine derived boroxazolidones, adding another potential derivative to the collection of promising chemotherapeutic agents for GBM treatment.

PMID: 30981767 [PubMed - as supplied by publisher]

Drp1/Fis1 interaction mediates mitochondrial dysfunction in septic cardiomyopathy.

J Mol Cell Cardiol. 2019 Apr 11;:

Authors: Haileselassie B, Mukherjee R, Joshi AU, Napier BA, Massis LM, Ostberg NP, Queliconi BB, Monack D, Bernstein D, Mochly-Rosen D

Abstract
Mitochondrial dysfunction is a key contributor to septic cardiomyopathy. Although recent literature implicates dynamin related protein 1 (Drp1) and its mitochondrial adaptor fission 1 (Fis1) in the development of pathologic fission and mitochondrial failure in neurodegenerative disease, little is known about the role of Drp1/Fis1 interaction in the context of sepsis-induced cardiomyopathy. Our study tests the hypothesis that Drp1/Fis1 interaction is a major driver of sepsis-mediated pathologic fission, leading to mitochondrial dysfunction in the heart.
METHODS: H9C2 cardiomyocytes were treated with lipopolysaccharide (LPS) to evaluate changes in mitochondrial membrane potential, oxidative stress, cellular respiration, and mitochondrial morphology. Balb/c mice were treated with LPS, cardiac function was measured by echocardiogaphy, and mitochondrial morphology determined by electron microscopy (EM). Drp1/Fis1 interaction was inhibited by P110 to determine whether limiting mitochondrial fission can reduce LPS-induced oxidative stress and cardiac dysfunction.
RESULTS: LPS-treated H9C2 cardiomyocytes demonstrated a decrease in mitochondrial respiration followed by an increase in mitochondrial oxidative stress and a reduction in membrane potential. Inhibition of Drp1/Fis1 interaction with P110 attenuated LPS-mediated cellular oxidative stress and preserved membrane potential. In vivo, cardiac dysfunction in LPS-treated mice was associated with increased mitochondrial fragmentation. Treatment with P110 reduced cardiac mitochondrial fragmentation, prevented decline in cardiac function, and reduced mortality.
CONCLUSIONS: Sepsis decreases cardiac mitochondrial respiration and membrane potential while increasing oxidative stress and inducing pathologic fission. Treatment with P110 was protective in both in vitro and in vivo models of septic cardiomyopathy, suggesting a key role of Drp1/Fis1 interaction, and a potential target to reduce its morbidity and mortality.

PMID: 30981733 [PubMed - as supplied by publisher]

Synthesis and evaluation of histamine H3 receptor ligand based on lactam scaffold as agents for treating neuropathic pain.

Bioorg Med Chem Lett. 2019 Apr 08;:

Authors: Dou F, Cao X, Jing P, Wu C, Zhang Y, Chen Y, Zhang G

Abstract
The synthesis and H3 receptor ligand of a new series of lactam derivatives are reported. The new compounds were evaluated in vitro in H3 and H1 receptor-binding assays. The structure-activity relationship led us to the promising derivative 2-methyl-7-(3-morpholinopropoxy)-3,4-dihydroisoquinolin-1(2H)-one (11). The compound with highest affinity and greatest selectivity were further profiled, In addition, compound 11 exerted dose-dependent anti-nociceptive effects in the formalin test. These characteristics suggested that the potent and selective compound 11 could be a potent candidate for pain treatment.

PMID: 30981577 [PubMed - as supplied by publisher]

Spontaneous preterm labour that leads to preterm birth: An update and personal reflection.

Placenta. 2019 Mar 25;:

Authors: Lamont RF

Abstract
OBJECTIVE: The objective was to provide an update of progress made over time (including personal reflection) of our attempts to reduce the mortality and morbidity associated with spontaneous preterm labour that leads to preterm birth.
METHODS: An experienced and evidence based approach was taken to provide an overview of progress made over a generation (∼40 years) in our understanding of spontaneous preterm labour.
RESULTS: It is evident that we have made significant progress in our understanding of the aetiology, the measurement of the burden, the basic science, systems biology and mechanical pathways of the preterm parturition syndrome. We have better ways of predicting, preventing and managing spontaneous preterm labour than existed a generation ago.
CONCLUSIONS: The profile of spontaneous preterm labour that leads to preterm birth, thanks to organisations such as the March of Dimes, WHO and PREBIC is much more evident than before. However, while we have come a long way, we must not be complacent, and clinicians and basic scientists must continue to work in harmony, while recruiting and encouraging young investigators to join the effort to improve survival and handicap in what is one of the Great Obstetric Syndromes.

PMID: 30981438 [PubMed - as supplied by publisher]

11 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

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These pubmed results were generated on 2019/04/14

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These pubmed results were generated on 2019/04/13

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"systems biology"

These pubmed results were generated on 2019/04/12

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"systems biology"

These pubmed results were generated on 2019/04/12

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31 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2019/04/11

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29 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2019/04/11

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.