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Differential Splicing of Skipped Exons Predicts Drug Response in Cancer Cell lines

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Genomics, Proteomics & Bioinformatics 2021年第6期19卷 901-912页

作者： Edward Simpson steven Chen Jill l.Reiter Yunlong liu Center for Computational Biology and Bioinformatics Indiana University School of MedicineIndianapolisIN 46202USA Department of BioHealth Informatics School of Informatics and ComputingIndiana University-Purdue University IndianapolisIndianapolisIN 46202USA Department of Medical and Molecular Genetics Indiana University School of MedicineIndianapolisIN 46202USA

Alternative splicing of pre-mRNA transcripts is an important regulatory mechanism that increases the diversity of gene products in *** studies have linked specific transcript isoforms to altered drug response in cancer;however,few algorithms have incorporated splicing information into drug response *** this study,we evaluated whether basal-level splicing information could be used to predict drug sensitivity by constructing doxorubicin-sensitivity classification models with splicing and expression *** detailed splicing differences between sensitive and resistant cell lines by implementing quasi-binomial generalized linear modeling(QBGlM)and found altered inclusion of 277 skipped *** additionally conducted RNA-binding protein(RBP)binding motif enrichment and differential ex-pression analysis to characterize cis-and trans-acting elements that potentially influence doxorubicin response-mediating splicing *** results showed that a classification model built with skipped exon data exhibited strong predictive *** discovered an association between differentially spliced events and epithelial-mesenchymal transition(EMT)and observed motif enrichment,as well as differential expression of RBFOX and ElAVl RBP family *** work demonstrates the potential of incorporating splicing data into drug response algorithms and the utility of a QBGlM approach for fast,scalable identification of relevant splicing differences between large groups of samples.

关键词： Alternative splicing Transcript isoform Splicing regulation Drug sensitivity Precision medicine

Myxomycetes associated with grasslands of the western central United States

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Fungal Diversity 2013年第2期59卷 147-158页

作者： Adam W.Rollins steven l.Stephenson Department of Biology Lincoln Memorial UniversityHarrogateTN 37752USA Department of Biological Sciences University of ArkansasFayettevilleAR 72701USA

The assemblages of myxomycetes associated with the three types of temperate grasslands(tall grass,mixed grass and short grass)found across the western central United States were examined by collecting samples for isolation of these organisms from nine study *** consisted of two types of ground litter,two types of aerial litter(dead but still attached plant parts)and *** were brought back to the laboratory and used to prepare a series of moist chamber *** cultures yielded 1,301 collections of myxomycetes representing 59 species in 18 *** collections could be identified only to genus and one in particular(lepidoderma sp.)appears to be an undescribed *** spectabile was recorded for the first time in North ***,only eight species(Badhamia melanospora,Didymium anellus,***,***,Perichaena depressa,Physarum cinereum,***,and Stemonitis fusca)were recovered from all nine study sites and thus are considered to represent a core component of the myxomycete biota of temperate grasslands.

关键词： Community ecology Ecological distribution Grasslands Microhabitat Myxogastrids

ASSESSMENT OF OPTICAl ClEARING AGENTS USING REFlECTANCE-MODE CONFOCAl SCANNING lASER MICROSCOPY

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Journal of Innovative Optical Health Sciences 2010年第3期3卷 183-188页

作者： RAVIKANT SAMATHAM KEVIN G.PHIllIPS steven l.JACQUES Departments of Dermatology and Biomedical Engineering Oregon Health and Science University 3303 SW Bond Avenue PortlandOR 97239USA

The mechanism of action of clearing agents to improve optical imaging of mouse skin during reflectance-mode confocal microscopy was *** dermal side of excised dorsal mouse skin was exposed for one hour to saline,glycerin,or 80% DMSO,then the clearing agent was removed and the dermis placed against a glass cover slip through which a confocal microscope measured reflectance at 488 nm *** untreated control was also *** axial attenuation of reflectance signal,R(z_(f))versus increasing depth of focus zf behaved as R=ρexp(−μz_(f) 2G),where ρ is tissue reflectivity and μ is attenuation[cm^(−1)].The factor 2G accounts for the in/out path of photons,and the numerical aperture of the *** ρ,μ data were mapped to values of scattering coefficient(μ_(s)[cm^(−1)])and anisotropy of scattering(g).Images showed that glycerin significantly increased the g of dermis from about 0.7 to about 0.99,with little change in the μ_(s) of dermis at about 300cm^(−1).DMSO and saline had only slight and inconsistent effects on g and μ_(s).

关键词： Optical properties skin anisotropy

Species in lichen-forming fungi:balancing between conceptual and practical considerations,and between phenotype and phylogenomics

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Fungal Diversity 2021年第4期109卷 99-154页

作者： Robert lücking steven D.leavitt David l.Hawksworth Botanischer Garten Und Botanisches Museum Freie Universität BerlinKönigin-Luise-Str.6-814195 BerlinGermany Department of Biology Brigham Young University4102 Life Science BuildingProvoUT 84602USA M.l.Bean life Science Museum Brigham Young University1115 MLBMProvoUT 84602USA Department of life Sciences The Natural History MuseumLondon SW75BDUK Comparative Plant and Fungal Biology Royal Botanic GardensKewRichmond TW92ABSurreyUK

lichens are symbiotic associations resulting from interactions among fungi(primary and secondary mycobionts),algae and/or cyanobacteria(primary and secondary photobionts),and specific elements of the bacterial microbiome associated with the lichen *** question of what is a species,both concerning the lichen as a whole and its main fungal component,the primary mycobiont,has faced many challenges throughout history and has reached new dimensions with the advent of molecular phylogenetics and *** this paper,we briefly revise the definition of lichens and the scientific and vernacular naming conventions,concluding that the scientific,latinized name usually associated with lichens invariably refers to the primary mycobiont,whereas the vernacular name encompasses the entire *** the same lichen mycobiont may produce different phenotypes when associating with different photobionts or growing in axenic culture,this discrete variation does not warrant the application of different scientific names,but must follow the principle"one fungus=one name".Instead,broadly agreed informal designations should be used for such discrete morphologies,such as chloromorph and cyanomorph for lichens formed by the same mycobiont but with either green algae or *** taxonomic recognition of species in lichen-forming fungi is not different from other fungi and conceptual and nomenclatural approaches follow the same *** identify a number of current challenges and provide recommendations to address *** delimitation in lichen-forming fungi should not be tailored to particular species concepts but instead be derived from empirical evidence,applying one or several of the following principles in what we call the lPR approach:lineage(l)coherence ***(phylogenetic component),phenotype(P)coherence ***(morphological component),and/or reproductive(R)compatibility ***(biological component).Species hypotheses can be e

关键词： Alpha taxonomy Beta taxonomy Biological species concept Cora Cryptic speciation Fungal farmers Gamma taxonomy Infraspecies lichens as ecosystems Machine learning Morphological species concept One fungus=one name Photomorph Phylogenetic species concept Species pair concept Thamnolia

Endoproteolytic cleavage as a molecular switch regulating and diversifying prion protein function

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Neural Regeneration Research 2016年第2期11卷 238-239页

作者： Cathryn l.Haigh steven J.Collins Department of Medicine (Royal Melbourne Hospital) The University of Melbourne

The prion protein（Pr P）,through misfolding,is widely known for its causative role in prion diseases,which are transmissible neurodegenerative diseases of humans and *** is still no defined function assigned to Pr P,especially in the central nervous system,despite many studies in this *** functions are protean and include signal transduction,neuroprotection,neurogenesis,neuritogenesis,metal-ion homeostasis,memory formation and consolidation,as well as circadian rhythms（Nicolas et al.,2009）.

关键词： molecular cleavage Endoproteolytic

Reinforcement learning-driven local transactive energy market fordistributed energy resources

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能源与人工智能(英文) 2022年第2期8卷 162-176页

作者： steven Zhang Daniel May Mustafa Gül Petr Musilek Electrical and Computer Engineering University of AlbertaCanada Civil and Environmental Engineering University of AlbertaCanada

local energy markets are emerging as a tool for coordinating generation, storage, and consumption of energyfrom distributed resources. In combination with automation, they promise to provide an effective energymanagement framework that is fair and brings system-level savings. The cooperative–competitive natureof energy markets calls for multi-agent based automation with learning energy trading agents. However,depending on the dynamics of the agent–environment interaction, this approach may yield unintended behaviorof market participants. Thus, the design of market mechanisms suitable for reinforcement learning agentsmust take into account this interplay. This article introduces autonomous local energy exchange (AlEX) asan experimental framework that combines multi-agent learning and double auction mechanism. Participantsdetermine their internal price signals and make energy management decisions through market interactions,rather than relying on predetermined external price signals. The main contribution of this article is examinationof compatibility between specific market elements and independent learning agents. Effects of different marketproperties are evaluated through simulation experiments, and the results are used for determine a suitablemarket design. The results show that market truthfulness maintains demand-response functionality, while weakbudget balancing provides a strong reinforcement signal for the learning agents. The resulting agent behavioris compared with two baselines: net billing and time-of-use rates. The AlEX-based pricing is more responsiveto fluctuations in the community net load compared to the time-of-use. The more accurate accounting ofrenewable energy usage reduced bills by a median 38.8% compared to net billing, confirming the ability tobetter facilitate demand response.

关键词： Transactive energy Demand response Distributed energy resources(DER) DER integration local energy market Reinforcement learning

Variation in floral form of CRISPR knock-outs of the poplar homologs of lEAFY and AGAMOUS after FT heat-induced early flowering

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Horticulture Research 2023年第8期10卷 183-193页

作者： Amy l.Klocko Estefania Elorriaga Cathleen Ma steven H.Strauss Department of Biology University of Colorado Colorado SpringsColorado SpringsCO 80918USA Department of Forest Ecosystems and Society Oregon State UniversityCorvallisOR 97331USA

Plant migration and gene flow from genetically modified or exotic trees to nearby lands or by crossing with wild relatives is a major public and regulatory *** genetic strategies exist to mitigate potential gene flow;however,the long delay in onset of flow-ering is a severe constraint to research *** used heat-induced FT overexpression to speed assessment of the expected floral phenotypes after CRISPR knockout of poplar homologs of the key floral genes,lEAFY and *** selected events with previously characterized CRISPR-Cas9 induced biallelic changes then re-transformed them with the Arabidopsis thaliana FlOWERING lOCUS T(AtFT)gene under control of either a strong constitutive promoter or a heat-inducible *** successfully obtained flowering in both a male and female clone of poplar,observing a wide range of inflorescence and floral forms among flowers,ramets,and insertion ***,flowers obtained from the selected lFY and AG targeted events were consistent with what would be predicted for loss-of-function of these ***-targeted events showed small catkins with leaf-like organs,AG-targeted events had nested floral organs consistent with reduction in floral determinacy and absence of well-formed carpels or *** findings demonstrate the great developmental plasticity of Populus flowers during genetically accelerated flowering,which may be of horticultural *** also provide an informative early view of floral phenotypes and apparent sterility from knockouts of both these gene targets.

关键词： AGAMOUS flowers organs

Tissue engineering of skin and regenerative medicine for wound care

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Burns & Trauma 2018年第1期6卷 1-10页

作者： steven T.Boyce Andrea l.lalley Department of Surgery University of CincinnatiP.O.Box 670558CincinnatiOhio 45267-0558USA Research Department Shriners Hospitals for ChildrenCincinnatiOhioUSA

Engineering of biologic skin substitutes has progressed over time from individual applications of skin cells, or biopolymer scaffolds, to combinations of cells and scaffolds for treatment, healing, and closure of acute and chronic skin wounds. Skin substitutes may be categorized into three groups: acellular scaffolds, temporary substitutes containing allogeneic skin cells, and permanent substitutes containing autologous skin cells. Combined use of acellular dermal substitutes with permanent skin substitutes containing autologous cells has been shown to provide definitive wound closure in burns involving greater than 90% of the total body surface area. These advances have contributed to reduced morbidity and mortality from both acute and chronic wounds but, to date, have failed to replace all of the structures and functions of the skin. Among the remaining deficiencies in cellular or biologic skin substitutes are hypopigmentation, absence of stable vascular and lymphatic networks, absence of hair follicles, sebaceous and sweat glands, and incomplete innervation. Correction of these deficiencies depends on regulation of biologic pathways of embryonic and fetal development to restore the full anatomy and physiology of uninjured skin. Elucidation and integration of developmental biology into future models of biologic skin substitutes promises to restore complete anatomy and physiology, and further reduce morbidity from skin wounds and scar. This article offers a review of recent advances in skin cell thrapies and discusses the future prospects in cutaneous regeneration.

关键词： Burns Cell therapy Skin substitute Tissue engineering Wound closure Scar Regenerative medicine

Genetic down-regulation of gibberellin results in semi-dwarf poplar but few non-target effects on chemical resistance and tolerance to defoliation

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Journal of Plant Ecology 2019年第1期12卷 124-136页

作者： Christine Buhl steven H.Strauss Richard l.lindroth Department of Entomology University of Wisconsin-Madison1630 Linden DriveMadisonWI 53706USA Department of Forest Ecosystems and Society Oregon State University321 Richardson HallCorvallisOR 97331USA Present address:2600 State Street SalemOR 97310USA

Aims Plant stature can be strongly modified via regulation of endog-enous levels and signalling of the plant hormone gibberellin(GA).Down-regulation of GA can produce semi-dwarf tree varieties with improved qualities such as reduced susceptibility to wind damage,enhanced root growth and more compact ***,these modifications may have unintended,non-target consequences for defence against herbivores,via either of two mechanisms:(i)reduced biomass production may cause trade-offs with chemical resistance traits,as predicted by the growth-differentiation balance hypothesis,and(ii)altered biomass allocation to either roots or pho-tosynthetic tissues may affect regrowth potential and thus tolerance to *** We studied GA down-regulated(GE)and non-transgenic wild-type hybrid poplar(Populus alba×***)in an outdoor,above-ground common garden and defoliated half of all replicate trees to simulate *** then quantified the independent and inter-active effects of genotype and defoliation on growth and chemical resistance-related traits,including phenolic glycosides(PGs),con-densed tannin and *** also calculated tolerance to defo-liation as the differential in relative growth between undefoliated and defoliated *** Findings Our results indicate that two of the four GA down-regulated geno-types had significantly reduced stem height,basal diameter,vol-ume(d2h),total biomass and increased allocation to leaves relative to the wild *** of those two genotypes also had reduced allocation to *** and sometimes both of these same two genotypes also had at least 20%lower levels of condensed tannins and PGs and similar increases in lignin and ***,as calculated by the differential in relative growth between unde-foliated and defoliated trees,was similar among all experimental ***,two GE genotypes flushed fewer leaves in response to defoliation relative to the wild *** results indi-cate

关键词： genetic modification gibberellic acid Populus pest susceptibility tolerance resistance