Nature Biotechnology

People.

Publication Date: 2010 Mar PMID: 20212492
Authors:
Journal: Nat Biotechnol

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The importance of foreign-born talent for US innovation.

Publication Date: 2010 Mar PMID: 20212491
Authors: No, Y. - Walsh, J. P.
Journal: Nat Biotechnol

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What is flux balance analysis?

Publication Date: 2010 Mar PMID: 20212490
Authors: Orth, J. D. - Thiele, I. - Palsson, B. O.
Journal: Nat Biotechnol

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Research highlights.

Publication Date: 2010 Mar PMID: 20212489
Authors: Elsner, M. - Defrancesco, L. - Mak, C.
Journal: Nat Biotechnol

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Grass genomics on the wild side.

Publication Date: 2010 Mar PMID: 20212488
Authors: Mak, C.
Journal: Nat Biotechnol

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Navigating genomic maps of cancer cells.

Publication Date: 2010 Mar PMID: 20212487
Authors: van der Brug, M. P. - Wahlestedt, C.
Journal: Nat Biotechnol

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Cellular targets for influenza drugs.

Publication Date: 2010 Mar PMID: 20212486
Authors: Min, J. Y. - Subbarao, K.
Journal: Nat Biotechnol

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Targeting leukemia stem cells.

Publication Date: 2010 Mar PMID: 20212485
Authors: Mikkola, H. K. - Radu, C. G. - Witte, O. N.
Journal: Nat Biotechnol

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Genetic therapy for spinal muscular atrophy.

Publication Date: 2010 Mar PMID: 20212484
Authors: Mackenzie, A.
Journal: Nat Biotechnol

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Recent patent applications in DNA diagnostics.

Publication Date: 2010 Mar PMID: 20212483
Authors:
Journal: Nat Biotechnol

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Patenting biotech beyond the central dogma.

Publication Date: 2010 Mar PMID: 20212482
Authors: Wu, G.
Journal: Nat Biotechnol

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Lost in migration.

Publication Date: 2010 Mar PMID: 20212481
Authors: Mack, G. S. - Marshall, A.
Journal: Nat Biotechnol

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Why FDA recruitment of 'critics' is a problem.

Publication Date: 2010 Mar PMID: 20212480
Authors: Miller, H. I.
Journal: Nat Biotechnol

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Genetic exceptionalism.

Publication Date: 2010 Mar PMID: 20212479
Authors: Bains, W.
Journal: Nat Biotechnol

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Reply to Oversulfated chondroitin sulfate is not the sole contaminant in heparin.

Publication Date: 2010 Mar PMID: 20212478
Authors:
Journal: Nat Biotechnol

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Oversulfated chondroitin sulfate is not the sole contaminant in heparin.

Publication Date: 2010 Mar PMID: 20212477
Authors: Pan, J. - Qian, Y. - Zhou, X. - Pazandak, A. - Frazier, S. B. - Weiser, P. - Lu, H. - Zhang, L.
Journal: Nat Biotechnol

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The lengthening handshake.

Publication Date: 2010 Mar PMID: 20212476
Authors: Osborne, R.
Journal: Nat Biotechnol

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One year in-Obama's biotech scorecard.

Publication Date: 2010 Mar PMID: 20212475
Authors: Fox, J. L.
Journal: Nat Biotechnol

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Patent income tax slashed.

Publication Date: 2010 Mar PMID: 20212474
Authors: Mullard, A.
Journal: Nat Biotechnol

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Resuscitated deCODE refocuses on diagnostics.

Publication Date: 2010 Mar PMID: 20212473
Authors: Ratner, M.
Journal: Nat Biotechnol

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Abbott hit with record fine.

Publication Date: 2010 Mar PMID: 20212472
Authors: Francisco, M.
Journal: Nat Biotechnol

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Brazil boosts bioscience.

Publication Date: 2010 Mar PMID: 20212471
Authors: Neto, R. B.
Journal: Nat Biotechnol

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RNAi delivery shop.

Publication Date: 2010 Mar PMID: 20212470
Authors: Latefi, N.
Journal: Nat Biotechnol

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Chinese institute makes bold sequencing play.

Publication Date: 2010 Mar PMID: 20212469
Authors: Fox, J. - Kling, J.
Journal: Nat Biotechnol

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Biotechs go virtual.

Publication Date: 2010 Mar PMID: 20212468
Authors: Aldridge, S.
Journal: Nat Biotechnol

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Melanoma vaccine for dogs.

Publication Date: 2010 Mar PMID: 20212467
Authors: Elvidge, S.
Journal: Nat Biotechnol

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Ride 'n Drive on government waste.

Publication Date: 2010 Mar PMID: 20212466
Authors:
Journal: Nat Biotechnol

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US biodefense contracts continue to lure biotechs.

Publication Date: 2010 Mar PMID: 20212465
Authors: Shaffer, C.
Journal: Nat Biotechnol

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GSK/Sirtris compounds dogged by assay artifacts.

Publication Date: 2010 Mar PMID: 20212464
Authors: Schmidt, C.
Journal: Nat Biotechnol

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Monsanto's alfalfa reaches Supreme Court.

Publication Date: 2010 Mar PMID: 20212463
Authors: Dickinson, B.
Journal: Nat Biotechnol

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Ark's gene therapy stumbles at the finish line.

Publication Date: 2010 Mar PMID: 20212462
Authors: Mitchell, P.
Journal: Nat Biotechnol

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H1N1dsight is a wonderful thing.

Publication Date: 2010 Mar PMID: 20212461
Authors:
Journal: Nat Biotechnol

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America's got talent-can it keep it?

Publication Date: 2010 Mar PMID: 20212460
Authors:
Journal: Nat Biotechnol

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Isotopic labeling of terminal amines in complex samples identifies protein N-termini and protease cleavage products.

Publication Date: 2010 Mar PMID: 20208520
Authors: Kleifeld, O. - Doucet, A. - Auf dem Keller, U. - Prudova, A. - Schilling, O. - Kainthan, R. K. - Starr, A. E. - Foster, L. J. - Kizhakkedathu, J. N. - Overall, C. M.
Journal: Nat Biotechnol

Effective proteome-wide strategies that distinguish the N-termini of proteins from the N-termini of their protease cleavage products would accelerate identification of the substrates of proteases with broad or unknown specificity. Our approach, named terminal amine isotopic labeling of substrates (TAILS), addresses this challenge by using dendritic polyglycerol aldehyde polymers that remove tryptic and C-terminal peptides. We analyze unbound naturally acetylated, cyclized or labeled N-termini from proteins and their protease cleavage products by tandem mass spectrometry, and use peptide isotope quantification to discriminate between the substrates of the protease of interest and the products of background proteolysis. We identify 731 acetylated and 132 cyclized N-termini, and 288 matrix metalloproteinase (MMP)-2 cleavage sites in mouse fibroblast secretomes. We further demonstrate the potential of our strategy to link proteases with defined biological pathways in complex samples by analyzing mouse inflammatory bronchoalveolar fluid and showing that expression of the poorly defined breast cancer protease MMP-11 in MCF-7 human breast cancer cells cleaves both endoplasmin and the immunomodulator and apoptosis inducer galectin-1.

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Harnessing chaperone-mediated autophagy for the selective degradation of mutant huntingtin protein.

Publication Date: 2010 Mar PMID: 20190739
Authors: Bauer, P. O. - Goswami, A. - Wong, H. K. - Okuno, M. - Kurosawa, M. - Yamada, M. - Miyazaki, H. - Matsumoto, G. - Kino, Y. - Nagai, Y. - Nukina, N.
Journal: Nat Biotechnol

Huntington's Disease (HD) is a dominantly inherited pathology caused by the accumulation of mutant huntingtin protein (HTT) containing an expanded polyglutamine (polyQ) tract. As the polyglutamine binding peptide 1 (QBP1) is known to bind an expanded polyQ tract but not the polyQ motif found in normal HTT, we selectively targeted mutant HTT for degradation by expressing a fusion molecule comprising two copies of QBP1 and copies of two different heat shock cognate protein 70 (HSC70)-binding motifs in cellular and mouse models of HD. Chaperone-mediated autophagy contributed to the specific degradation of mutant HTT in cultured cells expressing the construct. Intrastriatal delivery of a virus expressing the fusion molecule ameliorated the disease phenotype in the R6/2 mouse model of HD. Similar adaptor molecules comprising HSC70-binding motifs fused to an appropriate structure-specific binding agent(s) may have therapeutic potential for treating diseases caused by misfolded proteins other than those with expanded polyQ tracts.

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Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN.

Publication Date: 2010 Mar PMID: 20190738
Authors: Foust, K. D. - Wang, X. - McGovern, V. L. - Braun, L. - Bevan, A. K. - Haidet, A. M. - Le, T. T. - Morales, P. R. - Rich, M. M. - Burghes, A. H. - Kaspar, B. K.
Journal: Nat Biotechnol

Spinal muscular atrophy (SMA), the most common autosomal recessive neurodegenerative disease affecting children, results in impaired motor neuron function. Despite knowledge of the pathogenic role of decreased survival motor neuron (SMN) protein levels, efforts to increase SMN have not resulted in a treatment for patients. We recently demonstrated that self-complementary adeno-associated virus 9 (scAAV9) can infect approximately 60% of motor neurons when injected intravenously into neonatal mice. Here we use scAAV9-mediated postnatal day 1 vascular gene delivery to replace SMN in SMA pups and rescue motor function, neuromuscular physiology and life span. Treatment on postnatal day 5 results in partial correction, whereas postnatal day 10 treatment has little effect, suggesting a developmental period in which scAAV9 therapy has maximal benefit. Notably, we also show extensive scAAV9-mediated motor neuron transduction after injection into a newborn cynomolgus macaque. This demonstration that scAAV9 traverses the blood-brain barrier in a nonhuman primate emphasizes the clinical potential of scAAV9 gene therapy for SMA.

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Directed evolution of a magnetic resonance imaging contrast agent for noninvasive imaging of dopamine.

Publication Date: 2010 Mar PMID: 20190737
Authors: Shapiro, M. G. - Westmeyer, G. G. - Romero, P. A. - Szablowski, J. O. - Kuster, B. - Shah, A. - Otey, C. R. - Langer, R. - Arnold, F. H. - Jasanoff, A.
Journal: Nat Biotechnol

The development of molecular probes that allow in vivo imaging of neural signaling processes with high temporal and spatial resolution remains challenging. Here we applied directed evolution techniques to create magnetic resonance imaging (MRI) contrast agents sensitive to the neurotransmitter dopamine. The sensors were derived from the heme domain of the bacterial cytochrome P450-BM3 (BM3h). Ligand binding to a site near BM3h's paramagnetic heme iron led to a drop in MRI signal enhancement and a shift in optical absorbance. Using an absorbance-based screen, we evolved the specificity of BM3h away from its natural ligand and toward dopamine, producing sensors with dissociation constants for dopamine of 3.3-8.9 muM. These molecules were used to image depolarization-triggered neurotransmitter release from PC12 cells and in the brains of live animals. Our results demonstrate the feasibility of molecular-level functional MRI using neural activity-dependent sensors, and our protein engineering approach can be generalized to create probes for other targets.

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Induction of cell cycle entry eliminates human leukemia stem cells in a mouse model of AML.

Publication Date: 2010 Mar PMID: 20160717
Authors: Saito, Y. - Uchida, N. - Tanaka, S. - Suzuki, N. - Tomizawa-Murasawa, M. - Sone, A. - Najima, Y. - Takagi, S. - Aoki, Y. - Wake, A. - Taniguchi, S. - Shultz, L. D. - Ishikawa, F.
Journal: Nat Biotechnol

Cancer stem cells have been proposed to be important for initiation, maintenance and recurrence of various malignancies, including acute myeloid leukemia (AML). We have previously reported that CD34(+)CD38(-) human primary AML stem cells residing in the endosteal region of the bone marrow are relatively chemotherapy resistant. Using a NOD/SCID/IL2rgamma(null) mouse model of human AML, we now show that the AML stem cells in the endosteal region are cell cycle quiescent and that these stem cells can be induced to enter the cell cycle by treatment with granulocyte colony-stimulating factor (G-CSF). In combination with cell cycle-dependent chemotherapy, G-CSF treatment significantly enhances induction of apoptosis and elimination of human primary AML stem cells in vivo. The combination therapy leads to significantly increased survival of secondary recipients after transplantation of leukemia cells compared with chemotherapy alone.

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Nutrient-sensitized screening for drugs that shift energy metabolism from mitochondrial respiration to glycolysis.

Publication Date: 2010 Mar PMID: 20160716
Authors: Gohil, V. M. - Sheth, S. A. - Nilsson, R. - Wojtovich, A. P. - Lee, J. H. - Perocchi, F. - Chen, W. - Clish, C. B. - Ayata, C. - Brookes, P. S. - Mootha, V. K.
Journal: Nat Biotechnol

Most cells have the inherent capacity to shift their reliance on glycolysis relative to oxidative metabolism, and studies in model systems have shown that targeting such shifts may be useful in treating or preventing a variety of diseases ranging from cancer to ischemic injury. However, we currently have a limited number of mechanistically distinct classes of drugs that alter the relative activities of these two pathways. We screen for such compounds by scoring the ability of >3,500 small molecules to selectively impair growth and viability of human fibroblasts in media containing either galactose or glucose as the sole sugar source. We identify several clinically used drugs never linked to energy metabolism, including the antiemetic meclizine, which attenuates mitochondrial respiration through a mechanism distinct from that of canonical inhibitors. We further show that meclizine pretreatment confers cardioprotection and neuroprotection against ischemia-reperfusion injury in murine models. Nutrient-sensitized screening may provide a useful framework for understanding gene function and drug action within the context of energy metabolism.

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