Control of mitochondrial structure and function by the Yorkie/YAP oncogenic pathway.
AuthorsNagaraj R, Gururaja-Rao S, Jones KT, Slattery M, Negre N, Braas D, Christofk H, White KP, Mann R, Banerjee U,
JournalGenes Dev
PubMed ID22925885
Mitochondrial structure and function are highly dynamic, but the potential roles for cell signaling pathways in influencing these properties are not fully understood. Reduced mitochondrial function has been shown to cause cell cycle arrest, and a direct role of signaling pathways in controlling mitochondrial function during development and disease is ... More
Nonequilibrium dynamics of helix reorganization observed by transient 2D IR spectroscopy.
AuthorsTucker MJ, Abdo M, Courter JR, Chen J, Brown SP, Smith AB, Hochstrasser RM,
Journal
PubMed ID24106309
'The relaxation of helical structures very close to equilibrium is observed via transient 2D IR spectroscopy. An initial distribution of synthetically distorted helices having an unnatural bridge linking the 10th and 12th residues of an alanine-rich a-helix is released to evolve into the equilibrium distribution of a-helix conformations. The bridge ... More
De novo identification of VRC01 class HIV-1-neutralizing antibodies by next-generation sequencing of B-cell transcripts.
AuthorsZhu J, Wu X, Zhang B, McKee K, O'Dell S, Soto C, Zhou T, Casazza JP, Mullikin JC, Kwong PD, Mascola JR, Shapiro L, Becker J, Benjamin B, Blakesley R, Bouffard G, Brooks S, Coleman H, Dekhtyar M, Gregory M, Guan X, Gupta J, Han J, Hargrove A, Ho SL, Johnson T, Legaspi R, Lovett S, Maduro Q, Masiello C, Maskeri B, McDowell J, Montemayor C, Mullikin J, Park M, Riebow N, Schandler K, Schmidt B, Sison C, Stantripop M, Thomas J, Thomas P, Vemulapalli M, Young A,
Journal
PubMed ID24106303
'Next-generation sequencing of antibody transcripts provides a wealth of data, but the ability to identify function-specific antibodies solely on the basis of sequence has remained elusive. We previously characterized the VRC01 class of antibodies, which target the CD4-binding site on gp120, appear in multiple donors, and broadly neutralize HIV-1. Antibodies ... More
Model-driven optimization of multicomponent self-assembly processes.
'Here, we report an engineering approach toward multicomponent self-assembly processes by developing a methodology to circumvent spurious, metastable assemblies. The formation of metastable aggregates often hampers self-assembly of molecular building blocks into the desired nanostructures. Strategies are explored to master the pathway complexity and avoid off-pathway aggregates by optimizing the ... More
Evidence for supernova injection into the solar nebula and the decoupling of r-process nucleosynthesis.
AuthorsBrennecka GA, Borg LE, Wadhwa M,
Journal
PubMed ID24101483
'The isotopic composition of our Solar System reflects the blending of materials derived from numerous past nucleosynthetic events, each characterized by a distinct isotopic signature. We show that the isotopic compositions of elements spanning a large mass range in the earliest formed solids in our Solar System, calcium-aluminum-rich inclusions (CAIs), ... More
Identification and grafting of a unique peptide-binding site in the Fab framework of monoclonal antibodies.
AuthorsDonaldson JM, Zer C, Avery KN, Bzymek KP, Horne DA, Williams JC,
Journal
PubMed ID24101516
'Capitalizing on their extraordinary specificity, monoclonal antibodies (mAbs) have become one of the most reengineered classes of biological molecules. A major goal in many of these engineering efforts is to add new functionality to the parental mAb, including the addition of cytotoxins and imaging agents for medical applications. Herein, we ... More
Expanded therapeutic potential in activity space of next-generation 5-nitroimidazole antimicrobials with broad structural diversity.
AuthorsMiyamoto Y, Kalisiak J, Korthals K, Lauwaet T, Cheung DY, Lozano R, Cobo ER, Upcroft P, Upcroft JA, Berg DE, Gillin FD, Fokin VV, Sharpless KB, Eckmann L,
Journal
PubMed ID24101497
'Metronidazole and other 5-nitroimidazoles (5-NI) are among the most effective antimicrobials available against many important anaerobic pathogens, but evolving resistance is threatening their long-term clinical utility. The common 5-NIs were developed decades ago, yet little 5-NI drug development has since taken place, leaving the true potential of this important drug ... More
Structures of the flax-rust effector AvrM reveal insights into the molecular basis of plant-cell entry and effector-triggered immunity.
AuthorsVe T, Williams SJ, Catanzariti AM, Rafiqi M, Rahman M, Ellis JG, Hardham AR, Jones DA, Anderson PA, Dodds PN, Kobe B,
Journal
PubMed ID24101475
'Fungal and oomycete pathogens cause some of the most devastating diseases in crop plants, and facilitate infection by delivering a large number of effector molecules into the plant cell. AvrM is a secreted effector protein from flax rust (Melampsora lini) that can internalize into plant cells in the absence of ... More
Allosteric regulation of SERCA by phosphorylation-mediated conformational shift of phospholamban.
'The membrane protein complex between the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and phospholamban (PLN) controls Ca(2+) transport in cardiomyocytes, thereby modulating cardiac contractility. ß-Adrenergic-stimulated phosphorylation of PLN at Ser-16 enhances SERCA activity via an unknown mechanism. Using solid-state nuclear magnetic resonance spectroscopy, we mapped the physical interactions between SERCA and both ... More
Tracking the establishment of local endemic populations of an emergent enteric pathogen.
AuthorsHolt KE, Thieu Nga TV, Thanh DP, Vinh H, Kim DW, Vu Tra MP, Campbell JI, Hoang NV, Vinh NT, Minh PV, Thuy CT, Nga TT, Thompson C, Dung TT, Nhu NT, Vinh PV, Tuyet PT, Phuc HL, Lien NT, Phu BD, Ai NT, Tien NM, Dong N, Parry CM, Hien TT, Farrar JJ, Parkhill J, Dougan G, Thomson NR, Baker S,
Journal
PubMed ID24082120
'Shigella sonnei is a human-adapted pathogen that is emerging globally as the dominant agent of bacterial dysentery. To investigate local establishment, we sequenced the genomes of 263 Vietnamese S. sonnei isolated over 15 y. Our data show that S. sonnei was introduced into Vietnam in the 1980s and has undergone ... More
Xenopus laevis Tadpoles Can Regenerate Neural Retina Lost after Physical Excision but Cannot Regenerate Photoreceptors Lost through Targeted Ablation.
AuthorsLee DC, Hamm LM, Moritz OL,
JournalInvest Ophthalmol Vis Sci
PubMed ID23425694
'To determine whether the Xenopus laevis retina is capable of regenerating photoreceptor cells lost through apoptotic cell death in an inducible transgenic X. laevis model of retinitis pigmentosa (RP). Acute rod photoreceptor apoptosis was induced in transgenic X. laevis expressing drug-inducible caspase 9. We subsequently monitored the ability of the ... More
Lanthanide near infrared imaging in living cells with Yb3+ nano metal organic frameworks.
AuthorsFoucault-Collet A, Gogick KA, White KA, Villette S, Pallier A, Collet G, Kieda C, Li T, Geib SJ, Rosi NL, Petoud S,
Journal
PubMed ID24108356
We have created unique near-infrared (NIR)-emitting nanoscale metal-organic frameworks (nano-MOFs) incorporating a high density of Yb(3+) lanthanide cations and sensitizers derived from phenylene. We establish here that these nano-MOFs can be incorporated into living cells for NIR imaging. Specifically, we introduce bulk and nano-Yb-phenylenevinylenedicarboxylate-3 (nano-Yb-PVDC-3), a unique MOF based on ... More
Mammalian cells preferentially internalize hydrogel nanodiscs over nanorods and use shape-specific uptake mechanisms.
AuthorsAgarwal R, Singh V, Jurney P, Shi L, Sreenivasan SV, Roy K,
Journal
PubMed ID24101456
Size, surface charge, and material compositions are known to influence cell uptake of nanoparticles. However, the effect of particle geometry, i.e., the interplay between nanoscale shape and size, is less understood. Here we show that when shape is decoupled from volume, charge, and material composition, under typical in vitro conditions, ... More
DNA conformations in mismatch repair probed in solution by X-ray scattering from gold nanocrystals.
AuthorsHura GL, Tsai CL, Claridge SA, Mendillo ML, Smith JM, Williams GJ, Mastroianni AJ, Alivisatos AP, Putnam CD, Kolodner RD, Tainer JA,
Journal
PubMed ID24101514
DNA metabolism and processing frequently require transient or metastable DNA conformations that are biologically important but challenging to characterize. We use gold nanocrystal labels combined with small angle X-ray scattering to develop, test, and apply a method to follow DNA conformations acting in the Escherichia coli mismatch repair (MMR) system ... More
Regulation of estrogen receptor a by histone methyltransferase SMYD2-mediated protein methylation.
AuthorsZhang X, Tanaka K, Yan J, Li J, Peng D, Jiang Y, Yang Z, Barton MC, Wen H, Shi X,
Journal
PubMed ID24101509
Estrogen receptor alpha (ERa) is a ligand-activated transcription factor. Upon estrogen stimulation, ERa recruits a number of coregulators, including both coactivators and corepressors, to the estrogen response elements, modulating gene activation or repression. Most coregulator complexes contain histone-modifying enzymes to control ERa target gene expression in an epigenetic manner. In ... More
GBP-1 acts as a tumor suppressor in colorectal cancer cells.
AuthorsBritzen-Laurent N, Lipnik K, Ocker M, Naschberger E, Schellerer VS, Croner RS, Vieth M, Waldner M, Steinberg P, Hohenadl C, Stürzl M,
JournalCarcinogenesis
PubMed ID23042300
The human guanylate-binding protein 1 (GBP-1) is among the proteins the most highly induced by interferon-? (IFN-?) in every cell type investigated as yet. In vivo, GBP-1 expression is associated with the presence of inflammation and has been observed in autoimmune diseases, inflammatory bowel diseases (IBD) and cancer. In colorectal ... More
Calcium channel TRPV6 as a potential therapeutic target in estrogen receptor-negative breast cancer.
AuthorsPeters AA, Simpson PT, Bassett JJ, Lee JM, Da Silva L, Reid LE, Song S, Parat MO, Lakhani SR, Kenny PA, Roberts-Thomson SJ, Monteith GR,
JournalMol Cancer Ther
PubMed ID22807578
Calcium signaling is a critical regulator of cell proliferation. Elevated expression of calcium channels and pumps is a characteristic of some cancers, including breast cancer. We show that the plasma membrane calcium channel TRPV6, which is highly selective for Ca(2+), is overexpressed in some breast cancer cell lines. Silencing of ... More
PTEN inhibition improves wound healing in lung epithelia through changes in cellular mechanics that enhance migration.
AuthorsMihai C, Bao S, Lai JP, Ghadiali SN, Knoell DL,
JournalAm J Physiol Lung Cell Mol Physiol
PubMed ID22037358
The phosphoinositide-3 kinase/Akt pathway is a vital survival axis in lung epithelia. We previously reported that inhibition of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a major suppressor of this pathway, results in enhanced wound repair following injury. However, the precise cellular and biomechanical mechanisms responsible for increased ... More
High mobility group box-1 (HMGB1; amphoterin) is required for zebrafish brain development.
Hmgb1 (high mobility group box-1; amphoterin) is highly expressed in brain during early development of vertebrate and nonvertebrate species. However, its role in brain development remains elusive. Here we have cloned the zebrafish Hmgb1 and specifically manipulated Hmgb1 expression using injection of morpholino antisense oligonucleotides or Hmgb1 cRNA. The HMGB1 ... More
ORAI1-mediated calcium influx in lactation and in breast cancer.
AuthorsMcAndrew D, Grice DM, Peters AA, Davis FM, Stewart T, Rice M, Smart CE, Brown MA, Kenny PA, Roberts-Thomson SJ, Monteith GR,
JournalMol Cancer Ther
PubMed ID21224390
The entry of calcium into the mammary epithelial cell from the maternal plasma (i.e., calcium influx mechanisms) during lactation is poorly understood. As alterations in calcium channels and pumps are a key feature of some cancers, including breast cancer, understanding these calcium influx pathways may have significance beyond mammary biology. ... More
Phosphorylation of Ku dictates DNA double-strand break (DSB) repair pathway choice in S phase.
Authors
JournalNucleic Acids Res
PubMed ID26712563
UV-triggered p21 degradation facilitates damaged-DNA replication and preserves genomic stability.
Authors
JournalNucleic Acids Res
PubMed ID23723248
Targeting Interleukin-1β Protects from Aortic Aneurysms Induced by Disrupted Transforming Growth Factor β Signaling.
Authors
JournalImmunity
PubMed ID29150241
Modulation of oligodendrocyte generation during a critical temporal window after NG2 cell division.
Authors
JournalNat Neurosci
PubMed ID25262495
Impairment of Angiogenesis by Fatty Acid Synthase Inhibition Involves mTOR Malonylation.
Authors
JournalCell Metab
PubMed ID30146486
Editing DNA Methylation in the Mammalian Genome.
Authors
JournalCell
PubMed ID27662091
Developmental broadening of inhibitory sensory maps.
Authors
JournalNat Neurosci
PubMed ID28024159
Mitochondria-Endoplasmic Reticulum Contacts in Reactive Astrocytes Promote Vascular Remodeling.
Authors
JournalCell Metab
PubMed ID32220306
Cell-Intrinsic Control of Interneuron Migration Drives Cortical Morphogenesis.
Authors
JournalCell
PubMed ID29474907
Simultaneous binding of Guidance Cues NET1 and RGM blocks extracellular NEO1 signaling.