English Journal

New aspects and strategies for methane mitigation from ruminants.

Kumar S, Choudhury PK, Carro MD, Griffith GW, Dagar SS, Puniya M, Calabro S, Ravella SR, Dhewa T, Upadhyay RC, Sirohi SK, Kundu SS, Wanapat M, Puniya AK.Author information Dairy Microbiology Division, National Dairy Research Institute, Karnal, 132001, India.AbstractThe growing demand for sustainable animal production is compelling researchers to explore the potential approaches to reduce emissions of greenhouse gases from livestock that are mainly produced by enteric fermentation. Some potential solutions, for instance, the use of chemical inhibitors to reduce methanogenesis, are not feasible in routine use due to their toxicity to ruminants, inhibition of efficient rumen function or other transitory effects. Strategies, such as use of plant secondary metabolites and dietary manipulations have emerged to reduce the methane emission, but these still require extensive research before these can be recommended and deployed in the livestock industry sector. Furthermore, immunization vaccines for methanogens and phages are also under investigation for mitigation of enteric methanogenesis. The increasing knowledge of methanogenic diversity in rumen, DNA sequencing technologies and bioinformatics have paved the way for chemogenomic strategies by targeting methane producers. Chemogenomics will help in finding target enzymes and proteins, which will further assist in the screening of natural as well chemical inhibitors. The construction of a methanogenic gene catalogue through these approaches is an attainable objective. This will lead to understand the microbiome function, its relation with the host and feeds, and therefore, will form the basis of practically viable and eco-friendly methane mitigation approaches, while improving the ruminant productivity.
Applied microbiology and biotechnology.Appl Microbiol Biotechnol.2014 Jan;98(1):31-44. doi: 10.1007/s00253-013-5365-0. Epub 2013 Nov 19.
The growing demand for sustainable animal production is compelling researchers to explore the potential approaches to reduce emissions of greenhouse gases from livestock that are mainly produced by enteric fermentation. Some potential solutions, for instance, the use of chemical inhibitors to reduce
PMID 24247990

High-resolution chemical dissection of a model eukaryote reveals targets, pathways and gene functions.

Hoepfner D1, Helliwell SB2, Sadlish H2, Schuierer S2, Filipuzzi I2, Brachat S2, Bhullar B2, Plikat U2, Abraham Y2, Altorfer M2, Aust T2, Baeriswyl L2, Cerino R2, Chang L2, Estoppey D2, Eichenberger J2, Frederiksen M2, Hartmann N2, Hohendahl A2, Knapp B2, Krastel P2, Melin N2, Nigsch F2, Oakeley EJ2, Petitjean V2, Petersen F2, Riedl R2, Schmitt EK2, Staedtler F2, Studer C2, Tallarico JA3, Wetzel S2, Fishman MC3, Porter JA3, Movva NR2.Author information 1Novartis Institutes for BioMedical Research, Novartis Campus, CH-4056 Basel, Switzerland. Electronic address: dominic.hoepfner@novartis.com.2Novartis Institutes for BioMedical Research, Novartis Campus, CH-4056 Basel, Switzerland.3Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, MA 02139, USA.AbstractDue to evolutionary conservation of biology, experimental knowledge captured from genetic studies in eukaryotic model organisms provides insight into human cellular pathways and ultimately physiology. Yeast chemogenomic profiling is a powerful approach for annotating cellular responses to small molecules. Using an optimized platform, we provide the relative sensitivities of the heterozygous and homozygous deletion collections for nearly 1800 biologically active compounds. The data quality enables unique insights into pathways that are sensitive and resistant to a given perturbation, as demonstrated with both known and novel compounds. We present examples of novel compounds that inhibit the therapeutically relevant fatty acid synthase and desaturase (Fas1p and Ole1p), and demonstrate how the individual profiles facilitate hypothesis-driven experiments to delineate compound mechanism of action. Importantly, the scale and diversity of tested compounds yields a dataset where the number of modulated pathways approaches saturation. This resource can be used to map novel biological connections, and also identify functions for unannotated genes. We validated hypotheses generated by global two-way hierarchical clustering of profiles for (i) novel compounds with a similar mechanism of action acting upon microtubules or vacuolar ATPases, and (ii) an un-annotated ORF, YIL060w, that plays a role in respiration in the mitochondria. Finally, we identify and characterize background mutations in the widely used yeast deletion collection which should improve the interpretation of past and future screens throughout the community. This comprehensive resource of cellular responses enables the expansion of our understanding of eukaryotic pathway biology.
Microbiological research.Microbiol Res.2013 Dec 1. pii: S0944-5013(13)00193-6. doi: 10.1016/j.micres.2013.11.004. [Epub ahead of print]
Due to evolutionary conservation of biology, experimental knowledge captured from genetic studies in eukaryotic model organisms provides insight into human cellular pathways and ultimately physiology. Yeast chemogenomic profiling is a powerful approach for annotating cellular responses to small mole
PMID 24360837

Laulimalide and peloruside A inhibit mitosis of Saccharomyces cerevisiae by preventing microtubule depolymerisation-dependent steps in chromosome separation and nuclear positioning.

Best HA, Matthews JH, Heathcott RW, Hanna R, Leahy DC, Coorey NV, Bellows DS, Atkinson PH, Miller JH.Author information Centre for Biodiscovery, School of Biological Sciences, Victoria University of Wellington, Kelburn Parade, Kelburn, Wellington, 6011, New Zealand. john.h.miller@vuw.ac.nz.AbstractThe activity and mechanism of action of two microtubule-stabilising agents, laulimalide and peloruside A, were investigated in Saccharomyces cerevisiae. In contrast to paclitaxel, both compounds displayed growth inhibitory activity in yeast with wild type TUB2 and were susceptible to the yeast pleiotropic drug efflux pumps, as evidenced by the increased sensitivity of a pump transcription factor knockout strain, pdr1Δpdr3Δ. Laulimalide (IC50=3.7 μM) was 5-fold more potent than peloruside A (IC50=19 μM) in this knockout strain. Bud index assays and flow cytometry revealed a G2/M block as seen in mammalian cells subsequent to treatment with these compounds. Furthermore, peloruside A treatment caused an increase in the number of cells with polymerised spindle microtubules. These results indicate an anti-mitotic action of both compounds with tubulin the likely target. This conclusion was supported by laulimalide and peloruside chemogenomic profiling using a yeast deletion library in the pdr1Δpdr3Δ background. The chemogenomic profiles of these compounds indicate that, in contrast to microtubule destabilising agents like nocodazole and benomyl, laulimalide and peloruside A inhibit mitotic processes that are reliant on microtubule depolymerisation, consistent with their ability to stabilise microtubules. Gene deletion strains hypersensitive to laulimalide and peloruside A represent possible targets for drugs that can synergize with microtubule stabilising agent and be of potential use in combination therapy for the treatment of cancer or other diseases.
Molecular bioSystems.Mol Biosyst.2013 Nov;9(11):2842-52. doi: 10.1039/c3mb70211a.
The activity and mechanism of action of two microtubule-stabilising agents, laulimalide and peloruside A, were investigated in Saccharomyces cerevisiae. In contrast to paclitaxel, both compounds displayed growth inhibitory activity in yeast with wild type TUB2 and were susceptible to the yeast pleio
PMID 24056987

Japanese Journal

Applicability domain of active learning in chemical probe identification: Convergence in learning from non-specific compounds and decision rule clarification

Polash Ahsan Habib,Nakano Takumi,Takeda Shunichi,Brown J. B.
Molecules 24(15), 2019-08-01
… In this article, we challenge active learning's ability to predict inhibitory bioactivity profiles of selective compounds when learning from chemogenomic features found in non-selective ligand-target pairs. … this data volume is consistent with prior chemogenomic active learning studies despite the increased difficulty from chemical biology experimental settings used here. …
NAID 120006712779

Classifiers and their Metrics Quantified

Brown J. B.
Molecular Informatics 37(1-2), 2018-01
その人工知能は本当に信頼できるのか？ --人工知能の性能を正確に評価する方法を開発--. 京都大学プレスリリース. 2018-03-05.
NAID 120006406833

Active learning for computational chemogenomics

Reker Daniel,Schneider Petra,Schneider Gisbert,Brown JB
Future Medicinal Chemistry 9(4), 381-402, 2017-03
… Results/methodology: We assessed active learning for protein/target family-wide chemogenomic modeling by replicate experiment. … Conclusion: Chemogenomic active learning identifies small subsets of ligand–target interactions in a large screening database that lead to knowledge discovery and highly predictive models. …
NAID 120005997743

Related Pictures

Chemogenomic data search with Chemical Chemogenomics and orthology‐based design Figure 1. CPI-Predictor cover diverse chemogenomic targets are labelled with a ionic Transporters Na+ | Leaders in and computational chemogenomic method (B Figure 2: Yeast chemogenomic platform that to small molecules using chemogenomic