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  • 1
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    Applying ecological resistance and resilience to dissect bacterial antibiotic responses (2018)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2018
    Description: 〈p〉An essential property of microbial communities is the ability to survive a disturbance. Survival can be achieved through resistance, the ability to absorb effects of a disturbance without a notable change, or resilience, the ability to recover after being perturbed by a disturbance. These concepts have long been applied to the analysis of ecological systems, although their interpretations are often subject to debate. Here, we show that this framework readily lends itself to the dissection of the bacterial response to antibiotic treatment, where both terms can be unambiguously defined. The ability to tolerate the antibiotic treatment in the short term corresponds to resistance, which primarily depends on traits associated with individual cells. In contrast, the ability to recover after being perturbed by an antibiotic corresponds to resilience, which primarily depends on traits associated with the population. This framework effectively reveals the phenotypic signatures of bacterial pathogens expressing extended-spectrum β-lactamases (ESBLs) when treated by a β-lactam antibiotic. Our analysis has implications for optimizing treatment of these pathogens using a combination of a β-lactam and a β-lactamase (Bla) inhibitor. In particular, our results underscore the need to dynamically optimize combination treatments based on the quantitative features of the bacterial response to the antibiotic or the Bla inhibitor.〈/p〉
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Potent and selective small-molecule MCL-1 inhibitors demonstrate on-target cancer cell killing activity as single agents and in combination with ABT-263 (navitoclax) (2015)
    Springer Nature
    Details
    Publication Date: 2015-01-16
    Description: Potent and selective small-molecule MCL-1 inhibitors demonstrate on-target cancer cell killing activity as single agents and in combination with ABT-263 (navitoclax) Cell Death and Disease 6, e1590 (January 2015). doi:10.1038/cddis.2014.561 Authors: J D Leverson, H Zhang, J Chen, S K Tahir, D C Phillips, J Xue, P Nimmer, S Jin, M Smith, Y Xiao, P Kovar, A Tanaka, M Bruncko, G S Sheppard, L Wang, S Gierke, L Kategaya, D J Anderson, C Wong, J Eastham-Anderson, M J C Ludlam, D Sampath, W J Fairbrother, I Wertz, S H Rosenberg, C Tse, S W Elmore & A J Souers
    Electronic ISSN: 2041-4889
    Topics: Biology , Medicine
    Published by Springer Nature
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  • 3
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    Distinct sensory representations of wind and near-field sound in the Drosophila brain (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-03-13
    Description: Behavioural responses to wind are thought to have a critical role in controlling the dispersal and population genetics of wild Drosophila species, as well as their navigation in flight, but their underlying neurobiological basis is unknown. We show that Drosophila melanogaster, like wild-caught Drosophila strains, exhibits robust wind-induced suppression of locomotion in response to air currents delivered at speeds normally encountered in nature. Here we identify wind-sensitive neurons in Johnston's organ, an antennal mechanosensory structure previously implicated in near-field sound detection (reviewed in refs 5 and 6). Using enhancer trap lines targeted to different subsets of Johnston's organ neurons, and a genetically encoded calcium indicator, we show that wind and near-field sound (courtship song) activate distinct populations of Johnston's organ neurons, which project to different regions of the antennal and mechanosensory motor centre in the central brain. Selective genetic ablation of wind-sensitive Johnston's organ neurons in the antenna abolishes wind-induced suppression of locomotion behaviour, without impairing hearing. Moreover, different neuronal subsets within the wind-sensitive population respond to different directions of arista deflection caused by air flow and project to different regions of the antennal and mechanosensory motor centre, providing a rudimentary map of wind direction in the brain. Importantly, sound- and wind-sensitive Johnston's organ neurons exhibit different intrinsic response properties: the former are phasically activated by small, bi-directional, displacements of the aristae, whereas the latter are tonically activated by unidirectional, static deflections of larger magnitude. These different intrinsic properties are well suited to the detection of oscillatory pulses of near-field sound and laminar air flow, respectively. These data identify wind-sensitive neurons in Johnston's organ, a structure that has been primarily associated with hearing, and reveal how the brain can distinguish different types of air particle movements using a common sensory organ.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755041/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755041/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yorozu, Suzuko -- Wong, Allan -- Fischer, Brian J -- Dankert, Heiko -- Kernan, Maurice J -- Kamikouchi, Azusa -- Ito, Kei -- Anderson, David J -- R01 DC002780/DC/NIDCD NIH HHS/ -- T32 GM007737/GM/NIGMS NIH HHS/ -- T32 GM007737-30/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Mar 12;458(7235):201-5. doi: 10.1038/nature07843.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology 216-76, California Institute of Technology, Pasadena, California 91125, USA. yorozu@caltech.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19279637" target="_blank"〉PubMed〈/a〉
    Keywords: *Air Movements ; Animals ; Auditory Perception/*physiology ; Behavior, Animal/physiology ; Drosophila melanogaster/*physiology ; Electrophysiological Phenomena/physiology ; Mechanoreceptors/physiology ; Sensory Receptor Cells/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 4
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    Genetic dissection of an amygdala microcircuit that gates conditioned fear (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-11-12
    Description: The role of different amygdala nuclei (neuroanatomical subdivisions) in processing Pavlovian conditioned fear has been studied extensively, but the function of the heterogeneous neuronal subtypes within these nuclei remains poorly understood. Here we use molecular genetic approaches to map the functional connectivity of a subpopulation of GABA-containing neurons, located in the lateral subdivision of the central amygdala (CEl), which express protein kinase C-delta (PKC-delta). Channelrhodopsin-2-assisted circuit mapping in amygdala slices and cell-specific viral tracing indicate that PKC-delta(+) neurons inhibit output neurons in the medial central amygdala (CEm), and also make reciprocal inhibitory synapses with PKC-delta(-) neurons in CEl. Electrical silencing of PKC-delta(+) neurons in vivo suggests that they correspond to physiologically identified units that are inhibited by the conditioned stimulus, called CEl(off) units. This correspondence, together with behavioural data, defines an inhibitory microcircuit in CEl that gates CEm output to control the level of conditioned freezing.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597095/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597095/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haubensak, Wulf -- Kunwar, Prabhat S -- Cai, Haijiang -- Ciocchi, Stephane -- Wall, Nicholas R -- Ponnusamy, Ravikumar -- Biag, Jonathan -- Dong, Hong-Wei -- Deisseroth, Karl -- Callaway, Edward M -- Fanselow, Michael S -- Luthi, Andreas -- Anderson, David J -- 1 R01 MH085082-01A1/MH/NIMH NIH HHS/ -- R01 MH063912/MH/NIMH NIH HHS/ -- R01 MH063912-09/MH/NIMH NIH HHS/ -- R01 MH063912-09S1/MH/NIMH NIH HHS/ -- R01 MH063912-10/MH/NIMH NIH HHS/ -- R01 MH085082/MH/NIMH NIH HHS/ -- R01 MH085082-01A1/MH/NIMH NIH HHS/ -- RC2 NS069464/NS/NINDS NIH HHS/ -- RC2 NS069464-01/NS/NINDS NIH HHS/ -- RC2 NS069464-02/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Nov 11;468(7321):270-6. doi: 10.1038/nature09553.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology 216-76, California Institute of Technology, Pasadena, California 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21068836" target="_blank"〉PubMed〈/a〉
    Keywords: Amygdala/anatomy & histology/cytology/enzymology/*physiology ; Animals ; Axonal Transport ; Cells, Cultured ; Conditioning, Classical/*physiology ; Fear/*physiology ; Female ; Freezing Reaction, Cataleptic ; Genetic Techniques ; Humans ; Male ; Mice ; Mice, Transgenic ; Neural Inhibition/*physiology ; Neural Pathways/cytology/enzymology/*physiology ; Neurons/enzymology/metabolism ; Protein Kinase C-delta/deficiency/genetics/metabolism ; Synapses/metabolism ; gamma-Aminobutyric Acid/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 5
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    Membrane depolarization induces p140trk and NGF responsiveness, but not p75LNGFR, in MAH cells (1992)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1992-07-17
    Description: Nerve growth factor (NGF) is required for the maturation and survival of sympathetic neurons, but the mechanisms controlling expression of the NGF receptor in developing neuroblasts have not been defined. MAH cells, an immortalized sympathoadrenal progenitor cell line, did not respond to NGF and expressed neither low-affinity NGF receptor (p75) nor p140trk messenger RNAs. Depolarizing concentrations of potassium chloride, but none of a variety of growth factors, induced expression of p140trk but not p75 messenger RNA. A functional response to NGF was acquired by MAH cells under these conditions, suggesting that expression of p75 is not essential for this response. Depolarization also permitted a relatively high proportion of MAH cells to develop and survive as neurons in fibroblast growth factor and NGF. These data establish a relation between electrical activity and neurotrophic factor responsiveness in developing neurons, which may operate in the functioning of the mature nervous system as well.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Birren, S J -- Verdi, J M -- Anderson, D J -- NS23476/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1992 Jul 17;257(5068):395-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology, California Institute of Technology, Pasadena 91125.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1321502" target="_blank"〉PubMed〈/a〉
    Keywords: Blotting, Northern ; Cell Line ; Cell Line, Transformed ; Cell Membrane/*physiology ; Dose-Response Relationship, Drug ; Membrane Potentials ; Nerve Growth Factors/*biosynthesis ; Neurons/*metabolism/*physiology ; Potassium Chloride/pharmacology ; Proto-Oncogene Proteins/*biosynthesis ; RNA, Messenger/*biosynthesis ; Receptor, trkA ; Receptors, Cell Surface/*biosynthesis ; Receptors, Nerve Growth Factor ; Signal Transduction ; Time Factors ; Tretinoin/pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 6
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    The valine and lysine residues in the conserved FxVTxK motif are important for the function of phylogenetically distant plant cellulose synthases (2016)
    Oxford University Press
    Details
    Publication Date: 2016-03-31
    Description: Cellulose synthases (CESAs) synthesize the β-1,4-glucan chains that coalesce to form cellulose microfibrils in plant cell walls. In addition to a large cytosolic (catalytic) domain, CESAs have eight predicted transmembrane helices (TMHs). However, analogous to the structure of BcsA, a bacterial CESA, predicted TMH5 in CESA may instead be an interfacial helix. This would place the conserved FxVTxK motif in the plant cell cytosol where it could function as a substrate-gating loop as occurs in BcsA. To define the functional importance of the CESA region containing FxVTxK, we tested five parallel mutations in Arabidopsis thaliana CESA1 and Physcomitrella patens CESA5 in complementation assays of the relevant cesa mutants. In both organisms, the substitution of the valine or lysine residues in FxVTxK severely affected CESA function. In Arabidopsis roots, both changes were correlated with lower cellulose anisotropy, as revealed by Pontamine Fast Scarlet. Analysis of hypocotyl inner cell wall layers by atomic force microscopy showed that two altered versions of Atcesa1 could rescue cell wall phenotypes observed in the mutant background line. Overall, the data show that the FxVTxK motif is functionally important in two phylogenetically distant plant CESAs. The results show that Physcomitrella provides an efficient model for assessing the effects of engineered CESA mutations affecting primary cell wall synthesis and that diverse testing systems can lead to nuanced insights into CESA structure–function relationships. Although CESA membrane topology needs to be experimentally determined, the results support the possibility that the FxVTxK region functions similarly in CESA and BcsA.
    Print ISSN: 0959-6658
    Electronic ISSN: 1460-2423
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 7
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    Applying ecological resistance and resilience to dissect bacterial antibiotic responses (2018)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2018-12-06
    Description: An essential property of microbial communities is the ability to survive a disturbance. Survival can be achieved through resistance, the ability to absorb effects of a disturbance without a notable change, or resilience, the ability to recover after being perturbed by a disturbance. These concepts have long been applied to the analysis of ecological systems, although their interpretations are often subject to debate. Here, we show that this framework readily lends itself to the dissection of the bacterial response to antibiotic treatment, where both terms can be unambiguously defined. The ability to tolerate the antibiotic treatment in the short term corresponds to resistance, which primarily depends on traits associated with individual cells. In contrast, the ability to recover after being perturbed by an antibiotic corresponds to resilience, which primarily depends on traits associated with the population. This framework effectively reveals the phenotypic signatures of bacterial pathogens expressing extended-spectrum β-lactamases (ESBLs) when treated by a β-lactam antibiotic. Our analysis has implications for optimizing treatment of these pathogens using a combination of a β-lactam and a β-lactamase (Bla) inhibitor. In particular, our results underscore the need to dynamically optimize combination treatments based on the quantitative features of the bacterial response to the antibiotic or the Bla inhibitor.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 8
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    Scalable control of mounting and attack by Esr1+ neurons in the ventromedial hypothalamus (2014)
    Nature Publishing Group (NPG)
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    Publication Date: 2014-04-18
    Description: Social behaviours, such as aggression or mating, proceed through a series of appetitive and consummatory phases that are associated with increasing levels of arousal. How such escalation is encoded in the brain, and linked to behavioural action selection, remains an unsolved problem in neuroscience. The ventrolateral subdivision of the murine ventromedial hypothalamus (VMHvl) contains neurons whose activity increases during male-male and male-female social encounters. Non-cell-type-specific optogenetic activation of this region elicited attack behaviour, but not mounting. We have identified a subset of VMHvl neurons marked by the oestrogen receptor 1 (Esr1), and investigated their role in male social behaviour. Optogenetic manipulations indicated that Esr1(+) (but not Esr1(-)) neurons are sufficient to initiate attack, and that their activity is continuously required during ongoing agonistic behaviour. Surprisingly, weaker optogenetic activation of these neurons promoted mounting behaviour, rather than attack, towards both males and females, as well as sniffing and close investigation. Increasing photostimulation intensity could promote a transition from close investigation and mounting to attack, within a single social encounter. Importantly, time-resolved optogenetic inhibition experiments revealed requirements for Esr1(+) neurons in both the appetitive (investigative) and the consummatory phases of social interactions. Combined optogenetic activation and calcium imaging experiments in vitro, as well as c-Fos analysis in vivo, indicated that increasing photostimulation intensity increases both the number of active neurons and the average level of activity per neuron. These data suggest that Esr1(+) neurons in VMHvl control the progression of a social encounter from its appetitive through its consummatory phases, in a scalable manner that reflects the number or type of active neurons in the population.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4098836/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4098836/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Hyosang -- Kim, Dong-Wook -- Remedios, Ryan -- Anthony, Todd E -- Chang, Angela -- Madisen, Linda -- Zeng, Hongkui -- Anderson, David J -- 1F32HD055198-01/HD/NICHD NIH HHS/ -- 1K99NS074077/NS/NINDS NIH HHS/ -- R01 MH085082/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 May 29;509(7502):627-32. doi: 10.1038/nature13169. Epub 2014 Apr 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Division of Biology and Biological Engineering 156-29, California Institute of Technology, Pasadena, California 91125, USA [2] Howard Hughes Medical Institute, Pasadena, California 91125, USA. ; Computation and Neural Systems, California Institute of Technology, Pasadena, California 91125, USA. ; Division of Biology and Biological Engineering 156-29, California Institute of Technology, Pasadena, California 91125, USA. ; Allen Institute for Brain Science, Seattle, Washington 98103, USA. ; 1] Division of Biology and Biological Engineering 156-29, California Institute of Technology, Pasadena, California 91125, USA [2] Howard Hughes Medical Institute, Pasadena, California 91125, USA [3] Computation and Neural Systems, California Institute of Technology, Pasadena, California 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24739975" target="_blank"〉PubMed〈/a〉
    Keywords: Aggression/*physiology ; Animals ; Estrogen Receptor alpha/*metabolism ; Female ; Integrases/genetics/metabolism ; Male ; Mice ; Neurons/*metabolism ; Optogenetics ; Sexual Behavior, Animal/*physiology ; Ventromedial Hypothalamic Nucleus/*cytology/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
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    Functional identification of an aggression locus in the mouse hypothalamus (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-02-11
    Description: Electrical stimulation of certain hypothalamic regions in cats and rodents can elicit attack behaviour, but the exact location of relevant cells within these regions, their requirement for naturally occurring aggression and their relationship to mating circuits have not been clear. Genetic methods for neural circuit manipulation in mice provide a potentially powerful approach to this problem, but brain-stimulation-evoked aggression has never been demonstrated in this species. Here we show that optogenetic, but not electrical, stimulation of neurons in the ventromedial hypothalamus, ventrolateral subdivision (VMHvl) causes male mice to attack both females and inanimate objects, as well as males. Pharmacogenetic silencing of VMHvl reversibly inhibits inter-male aggression. Immediate early gene analysis and single unit recordings from VMHvl during social interactions reveal overlapping but distinct neuronal subpopulations involved in fighting and mating. Neurons activated during attack are inhibited during mating, suggesting a potential neural substrate for competition between these opponent social behaviours.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075820/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075820/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lin, Dayu -- Boyle, Maureen P -- Dollar, Piotr -- Lee, Hyosang -- Lein, E S -- Perona, Pietro -- Anderson, David J -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Feb 10;470(7333):221-6. doi: 10.1038/nature09736.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology 216-76, California Institute of Technology, 1201 East California Boulevard, Pasadena, California 91125, USA. dayu.lin@nyumc.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21307935" target="_blank"〉PubMed〈/a〉
    Keywords: Aggression/*physiology ; Animals ; Electric Stimulation ; Electrophysiology ; Female ; Gene Expression Regulation ; Genes, fos/genetics ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Neural Inhibition/genetics/physiology ; Neural Pathways/physiology ; Neurons/physiology ; Sexual Behavior, Animal/physiology ; Ventromedial Hypothalamic Nucleus/anatomy & ; histology/*cytology/metabolism/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
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    Sensitivity to antitubulin chemotherapeutics is regulated by MCL1 and FBW7 (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-03-04
    Description: Microtubules have pivotal roles in fundamental cellular processes and are targets of antitubulin chemotherapeutics. Microtubule-targeted agents such as Taxol and vincristine are prescribed widely for various malignancies, including ovarian and breast adenocarcinomas, non-small-cell lung cancer, leukaemias and lymphomas. These agents arrest cells in mitosis and subsequently induce cell death through poorly defined mechanisms. The strategies that resistant tumour cells use to evade death induced by antitubulin agents are also unclear. Here we show that the pro-survival protein MCL1 (ref. 3) is a crucial regulator of apoptosis triggered by antitubulin chemotherapeutics. During mitotic arrest, MCL1 protein levels decline markedly, through a post-translational mechanism, potentiating cell death. Phosphorylation of MCL1 directs its interaction with the tumour-suppressor protein FBW7, which is the substrate-binding component of a ubiquitin ligase complex. The polyubiquitylation of MCL1 then targets it for proteasomal degradation. The degradation of MCL1 was blocked in patient-derived tumour cells that lacked FBW7 or had loss-of-function mutations in FBW7, conferring resistance to antitubulin agents and promoting chemotherapeutic-induced polyploidy. Additionally, primary tumour samples were enriched for FBW7 inactivation and elevated MCL1 levels, underscoring the prominent roles of these proteins in oncogenesis. Our findings suggest that profiling the FBW7 and MCL1 status of tumours, in terms of protein levels, messenger RNA levels and genetic status, could be useful to predict the response of patients to antitubulin chemotherapeutics.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wertz, Ingrid E -- Kusam, Saritha -- Lam, Cynthia -- Okamoto, Toru -- Sandoval, Wendy -- Anderson, Daniel J -- Helgason, Elizabeth -- Ernst, James A -- Eby, Mike -- Liu, Jinfeng -- Belmont, Lisa D -- Kaminker, Josh S -- O'Rourke, Karen M -- Pujara, Kanan -- Kohli, Pawan Bir -- Johnson, Adam R -- Chiu, Mark L -- Lill, Jennie R -- Jackson, Peter K -- Fairbrother, Wayne J -- Seshagiri, Somasekar -- Ludlam, Mary J C -- Leong, Kevin G -- Dueber, Erin C -- Maecker, Heather -- Huang, David C S -- Dixit, Vishva M -- CA043540/CA/NCI NIH HHS/ -- CA80188/CA/NCI NIH HHS/ -- England -- Nature. 2011 Mar 3;471(7336):110-4. doi: 10.1038/nature09779.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Early Discovery Biochemistry, Genentech, South San Francisco, California 94080, USA. ingrid@gene.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21368834" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis/drug effects ; Cell Cycle Proteins/genetics/*metabolism ; Cell Line ; Cell Line, Tumor ; Cell Transformation, Neoplastic/drug effects ; Drug Resistance, Neoplasm ; F-Box Proteins/genetics/*metabolism ; Fibroblasts ; Humans ; Mice ; Mitosis/drug effects ; Myeloid Cell Leukemia Sequence 1 Protein ; Paclitaxel/pharmacology ; Pharmacogenetics ; Phosphorylation/drug effects ; Polyploidy ; Proteasome Endopeptidase Complex/metabolism ; Protein Binding/drug effects ; Proto-Oncogene Proteins c-bcl-2/deficiency/genetics/*metabolism ; RNA, Messenger/genetics/metabolism ; Tubulin/*metabolism ; Tubulin Modulators/*pharmacology ; Ubiquitin-Protein Ligases/deficiency/genetics/*metabolism ; Vincristine/pharmacology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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