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Science signaling podcast: 15 july 2008.

Science Signaling — Sat, 19 Jul 2008 12:38:30 +0100

Science Signaling Podcast: 15 July 2008.

Sci Signal. 2008;1(28):pc6

Authors: Foley JF, Vanhook AM

This conversation is about research highlighted in the Editors' Choice summary titled, "Macrophages Go Back to School." The highlighted articles are T. Hagemann, T. Lawrence, I. McNeish, K. A. Charles, H. Kulbe, R. G. Thompson, S. C. Robinson, F. R. Balkwill, "Re-educating" tumor-associated macrophages by targeting NF-kappaB. J. Exp. Med. 205, 1261-1268 (2008), and C. H. Y. Fong, M. Bebien, A. Didierlaurent, R. Nebauer, T. Hussell, D. Broide, M. Karin, T. Lawrence, An antiinflammatory role for IKKbeta through the inhibition of "classical" macrophage activation. J. Exp. Med. 205, 1269-1276 (2008). (Length: 11 min; file size: 5.00 MB; file format: mp3; location: http://podcasts.aaas.org/science_signaling/ScienceSignaling_080715.mp3).

PMID: 18632550 [PubMed - as supplied by publisher]

(Source: Science Signaling)

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Ethanol's molecular targets.

Science Signaling — Sat, 19 Jul 2008 12:38:30 +0100

Ethanol's molecular targets.

Sci Signal. 2008;1(28):re7

Authors: Harris RA, Trudell JR, Mihic SJ

Ethanol produces a wide variety of behavioral and physiological effects in the body, but exactly how it acts to produce these effects is still poorly understood. Although ethanol was long believed to act nonspecifically through the disordering of lipids in cell membranes, proteins are at the core of most current theories of its mechanisms of action. Although ethanol affects various biochemical processes such as neurotransmitter release, enzyme function, and ion channel kinetics, we are only beginning to understand the specific molecular sites to which ethanol molecules bind to produce these myriad effects. For most effects of ethanol characterized thus far, it is unknown whether the protein whose function is being studied actually binds ethanol, or if alcohol is instead binding to another protein that then indirectly affects the functioning of the protein being studied. In this Review, we describe criteria that should be considered when identifying alcohol binding sites and highlight a number of proteins for which there exists considerable molecular-level evidence for distinct ethanol binding sites.

PMID: 18632551 [PubMed - in process]

(Source: Science Signaling)

A highly sensitive resonance scattering assay for immunoglobulin m using ag(i)–hydroquinone–immunonanogold catalytic reaction

Plasmonics — Thu, 17 Jul 2008 06:39:56 +0100

Abstract Ten-nanometer nanogold showed the strongest catalytic effect on the particle reaction between Ag(I) and hydroquinone to form nanosilver particles that exhibited the strongest resonance scattering (RS) peak at 350 nm. The enhanced RS intensity was linear to the nanogold concentration in the range of 30–5,700 nM Au. The nanogold was used to label goat antihuman immunoglobulin M (GIgM) to obtain an immunonanogold probe (AuGIgM) for immunoglobulin M (IgM). Based on the nanogold-labeled immunoreaction between IgM and AuGIgM, centrifugation, and AuGIgM–Ag(I)–hydroquinone nanocatalytic reaction, a highly sensitive and selective immunonanogold-catalytic Ag particle RS assay for 0.2–300 ng mL−1 IgM was proposed, with a detection limit of 0.1 ng mL−1. This assay was simple and sensitive and was applied to assay IgM in serum samples, with satisfactory results. Content Type Journal ArticleDOI 10.1007/s11468-008-9060-4Authors Xiaoling Wei, Guangxi University School of Chemistry and Chemical Engineering Nanning 530004 ChinaMingjing Zou, Guangxi Normal University Guangxi Key Laboratory of Environmental Engineering, Protection, and Assessment Guilin 541004 ChinaZhiliang Jiang, Guangxi Normal University Guangxi Key Laboratory of Environmental Engineering, Protection, and Assessment Guilin 541004 ChinaQingye Liu, Guangxi Normal University Guangxi Key Laboratory of Environmental Engineering, Protection, and Assessment Guilin 541004 ChinaGuiqing Wen, Guangxi Normal University Guangxi Key Laboratory of Environmental Engineering, Protection, and Assessment Guilin 541004 China Journal PlasmonicsOnline ISSN 1557-1963Print ISSN 1557-1955 (Source: Plasmonics)

A review of an ultrafast and sensitive bioassay platform technology: microwave-accelerated metal-enhanced fluorescence

Plasmonics — Thu, 17 Jul 2008 06:39:54 +0100

Abstract Since the publication of our first paper on the microwave-accelerated metal-enhanced fluorescence (MAMEF) bioassay platform technology in 2005 (Aslan and Geddes, Anal Chem 77:8057–8067, 2005), we have been repeatedly asked to comment on the advantages of “microwave heating” with plasmonic nanostructures over conventional heating for bioassays by many of our colleagues in the community. We note that one can find a couple of review articles, one by Mingos (Gabriel et al., Chem Soc Rev 27:213–223, 1998) and another by Thostenson and Chou (Manufacturing 30:1055–1071, 1999), summarizing the fundamentals and several applications of microwave processing of chemical compounds and composite materials, respectively. These review articles also present a direct comparison of microwave heating with conventional heating with respect to the processing of materials and microwave-assisted synthesis of chemical compounds. In this review article, we seek to remind the reader of the fundamentals of microwave heating and the interactions of microwaves with chemical and biological materials relevant to our recent work on bioassays, rather than repeating the information provided in the above-mentioned very informative reviews. We also summarize our work on MAMEF-based bioassays where we use plasmonic nanostructures to additionally plasmon-enhance fluorescence signatures. Content Type Journal ArticleDOI 10.1007/s11468-008-9059-xAuthors Kadir Aslan, University of Maryland Biotechnology Institute Institute of Fluorescence, Laboratory for Advanced Medical Plasmonics, and Laboratory for Advanced Fluorescence Spectroscopy, Medical Biotechnology Center 725 West Lombard St Baltimore MD 21201 USAChris D. Geddes, University of Maryland Biotechnology Institute Institute of Fluorescence, Laboratory for Advanced Medical Plasmonics, and Laboratory for Advanced Fluorescence Spectroscopy, Medical Biotechnology Center 725 West Lombard St Baltimore MD 21201 USA Journal PlasmonicsOnline ISSN 1557-1963Print ISSN 1557-1955 (Source: Plasmonics)

Hepatic gap junctions in the hepatocarcinogen-resistant drh rat

Histochemistry and Cell Biology — Thu, 17 Jul 2008 05:57:01 +0100

Abstract Although the gap junction or connexin (Cx) is considered to be a tumor-suppressor, it is also required for tumor promotion. Therefore, we examined hepatic gap junctions in hepatocarcinogen-resistant (DRH) rats. Specifically, we investigated gap junction structure and Cx32 expression during normal conditions and in response to a hepatocarcinogen, 3′-methyl-4-dimethylaminoazobenzene (3′-MeDAB). On a basal diet without 3′-MeDAB, hepatic gap junctions and Cx32 protein expression were greater in DRH rats than in control Donryu rats, as evidenced by morphometry, immunohistochemistry and immunoblotting. On a diet containing 3′-MeDAB, gap junctions and expressed Cx32 were increased significantly in Donryu rats, but not in DRH rats. In this condition, Donryu rats lost weight but DRH rats increased relative liver weight. After 3′-MeDAB treatment, cathepsin D expression in hepatocytes was significantly increased only in Donryu rats, indicating that DRH rats were less susceptible to 3′-MeDAB. The abundance of mitogen-activated protein kinase, some constituent of which might be associated with the degree of Cx protein phosphorylation, was reduced to a greater extent in Donryu than in DRH rats after 3′-MeDAB treatment. The resistance of DRH rats to carcinogenesis may be due partially to their stabilized gap junctions, which could coordinate metabolic coupling to evade 3′-MeDAB toxicity. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00418-008-0473-0Authors Takahiro Gotow, Koshien University Laboratory of Cell Biology, College of Nutrition 10-1 Momijigaoka Takarazuka Hyogo 665-0006 JapanMotoko Shiozaki, Osaka University Graduate School of Medicine and Health Science Department of Molecular Pathology 1-7 Yamadaoka Suita Osaka 565-0871 JapanTaneaki Higashi, Koshien University Laboratory of Biochemistry, College of Nutrition Takarazuka Hyogo 665-0006 JapanKentaro Yoshimura, Interdisciplinary School of Medicine and Engineering, University of Yamanashi Department of Anatomy and Cell Biology 1110 Shimo-Kateau Chuo-shi Yamanashi 409-3898 JapanMasahiro Shibata, Niigata University Graduate School of Medical and Dental Sciences Division of Gross Anatomy and Morphogenesis 1-757 Asahimachi Niigata 951-8510 JapanEiki Kominami, Juntendo University School of Medicine Department of Biochemistry 2-1-1 Hongo, Bunkyo-ku Tokyo 113-8421 JapanYasuo Uchiyama, Juntendo University School of Medicine Department of Cell Biology and Neuroscience 2-1-1 Hongo, Bunkyo-ku Tokyo 113-8421 Japan Journal Histochemistry and Cell BiologyOnline ISSN 1432-119XPrint ISSN 0948-6143 (Source: Histochemistry and Cell Biology)

Tlr9 is expressed in idiopathic interstitial pneumonia and its activation promotes in vitro myofibroblast differentiation

Histochemistry and Cell Biology — Thu, 17 Jul 2008 05:57:01 +0100

Abstract Infectious diseases can be cofactors in idiopathic interstitial pneumonias (IIP) pathogenesis; recent data suggests that toll-like receptors 9 (TLR9) ligands contribute to experimental chronic tissue remodeling. Real-time TAQMAN and immunohistochemical analysis of IIP normal surgical lung biopsies (SLBs), primary fibroblast lines grown from both IIP and normal SLBs indicate that TLR9 is prominently and differentially expressed in a disease-specific manner. TLR9 expression was increased in biopsies from patients with IIP compared with normal lung biopsies and its expression is localized to areas of marked interstitial fibrosis. TLR9 in fibroblasts appeared to be increased by profibrotic Th2 cytokines (IL-4 and IL-13) and this was true in fibroblasts cultured from the most severe form of IIP, idiopathic pulmonary fibrosis (IPF) SLBs, in non-specific interstitial pneumonia fibroblast lines, and in normal fibroblasts. Finally, confocal microscopy studies have shown that TLR9 activation by its synthetic agonist CpG-ODN significantly increased the expression of alpha smooth muscle actin, the main marker of myofibroblast differentiation. These data indicate that TLR9 expression may drive the abnormal tissue healing response in severe forms of IIP and its activation can have a key role in myofibroblast differentiation promoting the progression of disease during the terminal phase of IPF. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00418-008-0466-zAuthors A. Meneghin, University of Michigan Medical School Department of Pathology Room 4710, BSRB, 109 Zina Pitcher Pl Ann Arbor MI 48109-2200 USAE. S. Choi, University of Michigan Medical Center Department of Microbiology and Immunology Ann Arbor MI 48109 USAH. L. Evanoff, University of Michigan Medical School Department of Pathology Room 4710, BSRB, 109 Zina Pitcher Pl Ann Arbor MI 48109-2200 USAS. L. Kunkel, University of Michigan Medical School Department of Pathology Room 4710, BSRB, 109 Zina Pitcher Pl Ann Arbor MI 48109-2200 USAF. J. Martinez, University of Michigan Medical Center Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine Ann Arbor MI 48109 USAK. R. Flaherty, University of Michigan Medical Center Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine Ann Arbor MI 48109 USAG. B. Toews, University of Michigan Medical Center Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine Ann Arbor MI 48109 USAC. M. Hogaboam, University of Michigan Medical School Department of Pathology Room 4057, BSRB, 109 Zina Pitcher Pl Ann Arbor MI 48109-2200 USA Journal Histochemistry and Cell BiologyOnline ISSN 1432-119XPrint ISSN 0948-6143 (Source: Histochemistry and Cell Biology)

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Pkc isoenzymes differentially modulate thrombin effect on mapk-dependent rpe proliferation.

Bioscience Reports — Thu, 17 Jul 2008 04:00:00 +0100

PKC isoenzymes differentially modulate thrombin effect on MAPK-dependent RPE proliferation.

Biosci Rep. 2008 Jul 17;

Authors: Palma-Nicolas JP, López E, López-Colomé AM

Thrombin signaling through protease-activated receptor-1 (PAR-1) is involved in cellular processes such as proliferation, differentiation and cell survival. Following eye traumatic injury, thrombin signaling may participate in disorders such as proliferative vitreoretinopathy (PVR), a human eye disease characterized by the uncontrolled proliferation, transdifferentiation and migration of otherwise quiescent retinal pigment epithelium cells (RPE). PARs activate the Ras/Raf/MEK/ERK mitogen-activated protein kinase pathway (MAPK) through the activation of alpha/betagamma heterotrimeric G proteins, and the downstream stimulation of the PLC-beta/PKC and PI3K signaling axis. We examined the molecular signaling involved in thrombin-induced RPE cell proliferation, using rat RPE cells in culture as a model system for PVR pathogenesis. Results showed that thrombin activation of PAR1 induces RPE cell proliferation through the Ras-independent activation of the Raf/MEK/ERK1/2 MAPK signaling cascade. Pharmacological analysis revealed that the activation of "conventional" PKC isoforms is essential for proliferation, although thrombin-induced phosphorylation of ERK1/2 requires the activation of atypical PKCzeta by PI3K. Consistently, thrombin-induced ERK1/2 activation and RPE proliferation were totally prevented by PI3K or PKCzeta inhibition. These results suggest that thrombin induces RPE cell proliferation by the joint activation of PLC-dependent and atypical PKC isoforms and the Ras-independent downstream stimulation of the Raf/MEK/ERK1/2 MAPK cascade. This is the first report demonstrating directly thrombin-induced ERK phosphorylation in RPE, and the involvement of atypical PKC-zeta- in this process.

PMID: 18636965 [PubMed - as supplied by publisher]

(Source: Bioscience Reports)

The mitochondrial pool of free amino acids reflects the composition of mitochondrial-dna encoded proteins: indication for a post-translational quality control for protein synthesis.

Bioscience Reports — Thu, 17 Jul 2008 04:00:00 +0100

The mitochondrial pool of free amino acids reflects the composition of mitochondrial-DNA encoded proteins: indication for a post-translational quality control for protein synthesis.

Biosci Rep. 2008 Jul 17;

Authors: Ross-Inta C, Tsai CY, Giulivi C

Mitochondria can synthesize a limited number of proteins encoded by mtDNA by using its own biosynthetic machinery, whereas most of the proteins are imported from the cytosol. It could be hypothesized that the mitochondrial pool of amino acids follows the frequency of amino acids in mtDNA-encoded proteins or alternatively, the profile is the result of the participation of amino acids in pathways other than protein synthesis (e.g. heme biosynthesis, aminotransferase reactions). These hypotheses were tested by evaluating the pool of free amino acids and derivatives in highly-coupled, purified liver mitochondria obtained from rats fed a nutritionally adequate diet for growth. Our results indicated that the pool mainly reflects the amino acid composition of mtDNA-encoded proteins suggesting that there is a posttranslational control of protein synthesis. This conclusion was supported by the following findings: one, correlation between the concentration of free amino acids in the matrix and the frequency of abundance of amino acids in mtDNA-encoded proteins; two, the similar ratios of essential-to-nonessential amino acids in mtDNA-encoded proteins and mitochondrial pool of amino acids; three, lack of a correlation between codon usage or tRNA levels and amino acid concentrations. Quantitative information on the mammalian mitochondrial content of amino acids, such as that presented in this report, along with functional studies will help us better understand the pathogenesis of mitochondrial diseases or the biochemical implications in mitochondrial metabolism.

PMID: 18636966 [PubMed - as supplied by publisher]

(Source: Bioscience Reports)

Identification of c-terminal neighbours of amino acid residues without an aliphatic (13)c (gamma) as an aid to nmr assignments in proteins.

Journal of Bimolecular NMR — Thu, 17 Jul 2008 04:00:00 +0100

Identification of C-terminal neighbours of amino acid residues without an aliphatic (13)C (gamma) as an aid to NMR assignments in proteins.

J Biomol NMR. 2008 Jul 17;

Authors: Barnwal RP, Rout AK, Atreya HS, Chary KV

We propose a methodology that uses GFT (3,2)D CB(CACO)NNH experiment to rapidly collect the data and readily identify six amino acid residue types (Ala, Asn, Asp, Cys, Gly and Ser) in any given protein. Further, the experiment can distinguish the redox state of Cys residues. The proposed experiment in its two forms will have wide range of applications in resonance assignment strategies and structure determination of proteins.

PMID: 18633715 [PubMed - as supplied by publisher]

(Source: Journal of Bimolecular NMR)

Fractal parameters and vascular networks: facts & artifacts

Theoretical Biology and Medical Modelling — Thu, 17 Jul 2008 04:00:00 +0100

Background: Several fractal and non-fractal parameters have been considered for the quantitative assessment of the vascular architecture, using a variety of test specimens and of computational tools. The fractal parameters have the advantage of being scale invariant, i.e. to be independent of the magnification and resolution of the images to be investigated, making easier the comparison among different setups and experiments. Results: The success of several commercial and/or free codes in computing the fractal parameters has been tested on well known exact models. Based on such a preliminary study, we selected the code Frac-lac in order to analyze images obtained by visualizing the angiogenetic process occurring in chick Chorio Allontoic Membranes (CAM), assumed to be paradigmatic of a realistic 2D vascular network. Among the parameters investigated, the fractal dimension Df proved to be the most robust estimator for CAM vascular networks. Moreover, only Df was able to discriminate between effective and elusive increases in vascularization after drug-induced angiogenic stimulations on CAMs. Conclusion: The fractal dimension Df is likely to be the most promising tool for monitoring the effectiveness of anti-angiogenic therapies in various clinical contexts. (Source: Theoretical Biology and Medical Modelling)

Microrna profile in peripheral blood t cells of patients with primary biliary cirrhosis

Clinical Science — Thu, 17 Jul 2008 04:00:00 +0100

MicroRNAs (miRNAs) are non-coding RNAs that powerfully regulate gene expression at the post-transcriptional level, which have critical functions across various biological processes but there are few published studies in autoimmune disease. Primary biliary cirrhosis (PBC) is a typical autoimmune disease. In this study, the relative expression of 328 mature miRNA genes was explored in the peripheral blood of PBC patients using an oligonucleotide array platform. Twenty-three miRNAs in the array were found to be lowly expressed and 2 showed high levels of expression in the peripheral blood of PBC patients. Especially the expression of miR-let-7b, miR-346, miR-17-5p and miR-346 was low. Expression of several miRNAs was validated using Northern blot analysis. The proliferation and secretion of IFN-γ of autoantigen PDC-E2 specific T cells transfected with anti-let-7b, anti-miR-346, anti-miR-17-5p, and pre-miR-129 were significantly higher than that of the healthy control group. Potential targets of validated miRNAs included TNFRSF21 and IL6. This study provides insight into PBC pathogenesis. (Source: Clinical Science)

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Combined computational study of mechanical behaviour and drug delivery from a porous, hydroxyapatite-based bone graft.

Biomechanics and Modeling in Mechanobiology — Thu, 17 Jul 2008 04:00:00 +0100

Combined computational study of mechanical behaviour and drug delivery from a porous, hydroxyapatite-based bone graft.

Biomech Model Mechanobiol. 2008 Jul 17;

Authors: Galbusera F, Bertolazzi L, Balossino R, Dubini G

This paper presents a numerical model of a porous, hydroxyapatite-based bone graft also suitable as a drug delivery device. The graft was positioned in different sites and with different porosities inside a human femur model. The structural analyses were carried out to verify the graft mechanical strength, using the Tsai-Wu criterion, and the maximum porosity at which static failure does not occur. A local stress shielding risk was also calculated as the ratio between the bone stress in the intact condition and the stress after implantation of the graft. Drug release kinetics was calculated by means of the finite element method. High porosity grafts were found to fail in all implantation sites. Lower porosity grafts showed to have adequate strength if implanted in some positions, while provided insufficient resistance for other implantation sites. Drug release kinetics was found to be strongly dependent both on the porosity of the graft and the bone density near the bone-graft interface.

PMID: 18629559 [PubMed - as supplied by publisher]

(Source: Biomechanics and Modeling in Mechanobiology)

Dna palindromes and disease

NIGMS - Results — Wed, 16 Jul 2008 19:56:28 +0100

NIGMS-funded biologists have found a link between DNA sequence palindromes and replication delays, which can trigger chromosome breaks. (Source: NIGMS - Results)

Mutant testis cells pass themselves on

NIGMS - Results — Wed, 16 Jul 2008 19:53:09 +0100

NIGMS-funded biologists have shown that testis cells carrying a mutation for Apert's syndrome have a survival advantage. (Source: NIGMS - Results)

Artificial skin fact sheet

NIGMS - What's New — Tue, 15 Jul 2008 16:30:52 +0100

(Source: NIGMS - What's New)

Trauma and shock fact sheet

NIGMS - What's New — Tue, 15 Jul 2008 16:30:34 +0100

(Source: NIGMS - What's New)

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Burns fact sheet

NIGMS - What's New — Tue, 15 Jul 2008 16:30:12 +0100

(Source: NIGMS - What's New)

Notice of intent to publish a request for applications for research on causal factors and interventions that promote and support the careers of women in biomedical and behavioral research

NIGMS - What's New — Tue, 15 Jul 2008 14:40:27 +0100

(Source: NIGMS - What's New)

A catalog of mitochondrial proteins

NIGMS - Results — Tue, 15 Jul 2008 12:56:44 +0100

An NIGMS-funded team has compiled a "parts list" for mitochondria, the cell's powerhouses, enhancing understanding of mitochondrial biology and disease. (Source: NIGMS - Results)

High-resolution pyrimidine- and ribose-specific 4d hcch-cosy spectra of rna using the filter diagonalization method.

Journal of Bimolecular NMR — Tue, 15 Jul 2008 04:00:00 +0100

High-resolution pyrimidine- and ribose-specific 4D HCCH-COSY spectra of RNA using the filter diagonalization method.

J Biomol NMR. 2008 Jul 15;

Authors: Douglas JT, Latham MP, Armstrong GS, Bendiak B, Pardi A

The NMR spectra of nucleic acids suffer from severe peak overlap, which complicates resonance assignments. 4D NMR experiments can overcome much of the degeneracy in 2D and 3D spectra; however, the linear increase in acquisition time with each new dimension makes it impractical to acquire high-resolution 4D spectra using standard Fourier transform (FT) techniques. The filter diagonalization method (FDM) is a numerically efficient algorithm that fits the entire multi-dimensional time-domain data to a set of multi-dimensional oscillators. Selective 4D constant-time HCCH-COSY experiments that correlate the H5-C5-C6-H6 base spin systems of pyrimidines or the H1'-C1'-C2'-H2' spin systems of ribose sugars were acquired on the (13)C-labeled iron responsive element (IRE) RNA. FDM-processing of these 4D experiments recorded with only 8 complex points in the indirect dimensions showed superior spectral resolution than FT-processed spectra. Practical aspects of obtaining optimal FDM-processed spectra are discussed. The results here demonstrate that FDM-processing can be used to obtain high-resolution 4D spectra on a medium sized RNA in a fraction of the acquisition time normally required for high-resolution, high-dimensional spectra.

PMID: 18626775 [PubMed - as supplied by publisher]

(Source: Journal of Bimolecular NMR)

Human genetic variation fact sheet

NIGMS - What's New — Mon, 14 Jul 2008 19:47:29 +0100

(Source: NIGMS - What's New)

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Discovery of novel non-peptide thrombopoietin mimetic compounds that induce megakaryocytopoiesis.

Bioscience Reports — Mon, 14 Jul 2008 04:00:00 +0100

Discovery of novel non-peptide thrombopoietin mimetic compounds that induce megakaryocytopoiesis.

Biosci Rep. 2008 Jul 14;

Authors: Yamane N, Takahashi K, Tanaka Y, Kato K, Takayama M, Ohyabu N, Shiota T, Takenaka H, Yoshida Y, Hara S, Murashi T, Nakamura E, Nishitani Y, Ishizaki J, Yamane S, Nagata K, Koizumi K, Yutsudo T, Suzuki R, Itoh T, Takemoto H

We have identified a series of novel non-peptide compounds that activate the thrombopoietin-dependent cell line Ba/F3-huMPL. The compounds stimulated proliferation of Ba/F3-huMPL in the absence of other growth factors, but did not promote proliferation of the thrombopoietin-independent parent cell line Ba/F3. The thrombopoietin mimetic compounds elicited signal transduction responses comparable to recombinant human thrombopoietin, such as tyrosine phosphorylation of the thrombopoietin receptor, janus kinase (JAK) 2, tyrosine kinase 2 (Tyk2), signal transducer and activator of transcription (STAT) 3, STAT5, mitogen-activated protein (MAP) kinases, phospholipase Cgamma (PLCgamma), growth factor receptor-bound protein 2 (Grb2), SHC, Vav, Cbl, and src homology 2 protein tyrosine phosphatase 2 (SHPTP2) and increased the number of CD41+ cells (megakaryocyte lineage) in cultures of human CD34+ bone marrow cells (hematopoietic stem cells). These findings suggest that this series of compounds are novel agonists of the human thrombopoietin receptor and are possible lead compounds for the generation of anti-thrombocytopenia drugs.

PMID: 18620546 [PubMed - as supplied by publisher]

(Source: Bioscience Reports)

Substrate specificity and structural insight of human aminoadipate aminotransferase/kynurenine aminotransferase ii.

Bioscience Reports — Mon, 14 Jul 2008 04:00:00 +0100

Substrate specificity and structural insight of human aminoadipate aminotransferase/kynurenine aminotransferase II.

Biosci Rep. 2008 Jul 14;

Authors: Han Q, Cai T, Tagle DA, Robinson H, Li J

Kynurenine aminotransferase II (KAT-II) has been considered a primary enzyme in brain for catalyzing the transamination of kynurenine to kynurenic acid (KYNA) that is the only known endogenous antagonist of N-methyl-D-aspartate receptor. The enzyme also catalyzes the transamination of aminoadipate to alpha-ketoadipate; therefore it was initially named aminoadipate aminotransferase (AADAT). A number of reports dealing with biochemical and functional aspects of this enzyme exist in the literature, but a systematic assessment of KAT II in terms of its substrate profile and kinetic properties is absent. This study concerns the biochemical and structural characterization of a human KAT II/AADAT. Substrate screening of human KAT II revealed that the enzyme had very broad substrate specificity, was capable of catalyzing the transamination of 16 out of 24 tested amino acids and utilized all 16 tested alpha-keto acids as amino group acceptors. Its broad substrate specificity contrasts to previous reports about KAT II. Kinetic analysis of human KAT II revealed its catalytic efficiency to individual amino group donors and acceptors, which provides a basis to pin point its primary substrates. Structural analysis of human KAT II complex with alpha-ketoglutaric acid revealed the conformation change of an N-terminal fraction, residues 15-33, is able to adapt different size substrates, which provides a structural basis explaining its broad substrate specificity.

PMID: 18620547 [PubMed - as supplied by publisher]

(Source: Bioscience Reports)

A structural constitutive model for the human lens capsule.

Biomechanics and Modeling in Mechanobiology — Sun, 13 Jul 2008 04:00:00 +0100

A structural constitutive model for the human lens capsule.

Biomech Model Mechanobiol. 2008 Jul 13;

Authors: Burd HJ

Published data on the mechanical performance of the human lens capsule when tested under uniaxial and biaxial conditions are reviewed. It is concluded that two simple phenomenological constitutive models (namely a linear elastic model and a Fung-type hyperelastic model) are unable to provide satisfactory representations of the mechanical behaviour of the capsule for both of these loading conditions. The possibility of resolving these difficulties using a structural constitutive model for the capsule, of a form that is inspired by the network of collagen IV filaments that exist within the lens capsule, is explored. The model is implemented within a rectangular periodic cell. Prescribed stretches are imposed on the periodic cell and the network is allowed to deform in a non-affine manner. The performance of the constitutive model correlates well with previously published test data. One possible application of the model is in the development of a multi-scale analysis of the mechanics of the human lens capsule.

PMID: 18622755 [PubMed - as supplied by publisher]

(Source: Biomechanics and Modeling in Mechanobiology)

Temperature effects on the aerobic metabolism of glycogen-accumulating organisms

Biotechnology and Bioengineering — Sun, 13 Jul 2008 04:00:00 +0100

Short-term temperature effects on the aerobic metabolism of glycogen-accumulating organisms (GAO) were investigated within a temperature range from 10 to 40°C. Candidatus Competibacter Phosphatis, known GAO, were the dominant microorganisms in the enriched culture comprising 93 ± 1% of total bacterial population as indicated by fluorescence in situ hybridization (FISH) analysis. Between 10 and 30°C, the aerobic stoichiometry of GAO was insensitive to temperature changes. Around 30°C, the optimal temperature for most of the aerobic kinetic rates was found. At temperatures higher than 30°C, a decrease on the aerobic stoichiometric yields combined with an increase on the aerobic maintenance requirements were observed. An optimal overall temperature for both anaerobic and aerobic metabolisms of GAO appears to be found around 30°C. Furthermore, within a temperature range (10-30°C) that covers the operating temperature range of most of domestic wastewater treatment systems, GAOs aerobic kinetic rates exhibited a medium degree of dependency on temperature ([thetas] = 1.046-1.090) comparable to that of phosphorus accumulating organisms (PAO). We conclude that GAO do not have metabolic advantages over PAO concerning the effects of temperature on their aerobic metabolism, and competitive advantages are due to anaerobic processes. Biotechnol. Bioeng. © 2008 Wiley Periodicals, Inc. (Source: Biotechnology and Bioengineering)

A catalog of mitochondria proteins

NIGMS - Results — Fri, 11 Jul 2008 19:17:47 +0100

An NIGMS-funded team has compiled a "parts list" for mitochondria, the cell's powerhouses, enhancing understanding of mitochondrial biology and disease. (Source: NIGMS - Results)

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The cytoplasmic tail of muc1: a very busy place.

Science Signaling — Fri, 11 Jul 2008 13:13:11 +0100

The cytoplasmic tail of MUC1: a very busy place.

Sci Signal. 2008;1(27):pe35

Authors: Carson DD

The role of mucin 1 (MUC1) in protecting epithelia from microbial infection, enzymatic digestion, and other irritants has been appreciated for some time. In addition, MUC1 serves as a barrier to embryo implantation. MUC1 is highly abundant in many tumors in which its role in barrier function may serve to protect cells from the host immune system, whereas MUC1 is less abundant in certain other cells-for example, in trophoblasts and hematopoietic cells. Most of the functions of MUC1 depend upon its large, extracellular ectodomain. Nonetheless, a series of studies have demonstrated a surprisingly diverse role for the small, highly conserved cytoplasmic domain of MUC1 in intracellular signaling. These intracellular activities have potential roles in the physiology of both malignant and nonmalignant cells.

PMID: 18612140 [PubMed - in process]

(Source: Science Signaling)

Tissue inhibitors of metalloproteinases in cell signaling: metalloproteinase-independent biological activities.

Science Signaling — Fri, 11 Jul 2008 13:13:11 +0100

Tissue inhibitors of metalloproteinases in cell signaling: metalloproteinase-independent biological activities.

Sci Signal. 2008;1(27):re6

Authors: Stetler-Stevenson WG

Over the past 20 years, the tissue inhibitors of metalloproteinases (TIMPs) have been implicated in direct regulation of cell growth and apoptosis. However, the mechanisms of these effects have been controversial. Recent work by several laboratories has identified specific signaling pathways and cell surface binding partners for members of the TIMP family. TIMP-2 binding to the integrin alpha(3)beta(1) is the first description of a cell surface receptor for a TIMP family member. TIMP-2 has been shown to induce gene expression, to promote G(1) cell cycle arrest, and to inhibit cell migration. TIMP-1 binding to CD63 inhibits cell growth and apoptosis. These new findings suggest that TIMPs are multifunctional and can act either directly through cell surface receptors or indirectly through modulation of protease activity to direct cell fate. The emerging concept is that TIMPs function in a contextual fashion so that the mechanism of action depends on the tissue microenvironment.

PMID: 18612141 [PubMed - in process]

(Source: Science Signaling)

Distribution of prolyl oligopeptidase in the mouse whole-body sections and peripheral tissues

Histochemistry and Cell Biology — Fri, 11 Jul 2008 06:55:08 +0100

Abstract Prolyl oligopeptidase (POP) is a serine endopeptidase that hydrolyses proline-containing peptides shorter than 30-mer, including many bioactive peptides. The distribution of POP in the brain has been studied but little is known about the distribution of peripheral POP. We used immunohistochemistry to localize POP in mouse whole-body sections and at the cellular level in peripheral tissues. Furthermore, we used a POP activity assay to reveal the associations between POP protein and its enzymatic activity. The highest POP protein densities were found in brain, kidney, testis and thymus, but in the liver the amounts of POP protein were small. There were remarkable differences between the distribution of POP protein and activity. The highest POP activities were found in the liver and testis while kidney had the lowest activity. In peripheral tissues, POP was present in various cell types both in the cytoplasm and nucleus of the cells, in contrast to the brain where no nuclear localization was detected. These findings support the proposed role of POP in cell proliferation in peripheral tissues. The dissociation of the distribution of POP protein and its enzymatic activity points to nonhydrolytic functions of POP and to strict endogenous regulation of POP activity. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00418-008-0468-xAuthors Timo T. Myöhänen, University of Kuopio Department of Pharmacology and Toxicology P.O. Box 1627 70211 Kuopio FinlandJarkko I. Venäläinen, University of Kuopio Department of Pharmacology and Toxicology P.O. Box 1627 70211 Kuopio FinlandJ. Arturo García-Horsman, University of Helsinki Division of Pharmacology and Toxicology, Faculty of Pharmacy Viikinkaari 5E P.O. Box 56 00014 Helsinki FinlandMarjo Piltonen, University of Helsinki Division of Pharmacology and Toxicology, Faculty of Pharmacy Viikinkaari 5E P.O. Box 56 00014 Helsinki FinlandPekka T. Männistö, University of Helsinki Division of Pharmacology and Toxicology, Faculty of Pharmacy Viikinkaari 5E P.O. Box 56 00014 Helsinki Finland Journal Histochemistry and Cell BiologyOnline ISSN 1432-119XPrint ISSN 0948-6143 (Source: Histochemistry and Cell Biology)

Maldi imaging mass spectrometry for direct tissue analysis: a new frontier for molecular histology

Histochemistry and Cell Biology — Fri, 11 Jul 2008 06:55:06 +0100

Abstract Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is a powerful tool for investigating the distribution of proteins and small molecules within biological systems through the in situ analysis of tissue sections. MALDI-IMS can determine the distribution of hundreds of unknown compounds in a single measurement and enables the acquisition of cellular expression profiles while maintaining the cellular and molecular integrity. In recent years, a great many advances in the practice of imaging mass spectrometry have taken place, making the technique more sensitive, robust, and ultimately useful. In this review, we focus on the current state of the art of MALDI-IMS, describe basic technological developments for MALDI-IMS of animal and human tissues, and discuss some recent applications in basic research and in clinical settings. Content Type Journal ArticleCategory ReviewDOI 10.1007/s00418-008-0469-9Authors Axel Walch, Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) Institute of Pathology Ingolstädter Landstraße 1 85764 Neuherberg GermanySandra Rauser, Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) Institute of Pathology Ingolstädter Landstraße 1 85764 Neuherberg GermanySören-Oliver Deininger, Bruker Daltonik GmbH Bremen GermanyHeinz Höfler, Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) Institute of Pathology Ingolstädter Landstraße 1 85764 Neuherberg Germany Journal Histochemistry and Cell BiologyOnline ISSN 1432-119XPrint ISSN 0948-6143 (Source: Histochemistry and Cell Biology)

Use of dual section mrna in situ hybridisation/immunohistochemistry to clarify gene expression patterns during the early stages of nephron development in the embryo and in the mature nephron of the adult mouse kidney

Histochemistry and Cell Biology — Fri, 11 Jul 2008 06:55:05 +0100

Abstract The kidney is the most complex organ within the urogenital system. The adult mouse kidney contains in excess of 8,000 mature nephrons, each of which can be subdivided into a renal corpuscle and 14 distinct tubular segments. The histological complexity of this organ can make the clarification of the site of gene expression by in situ hybridisation difficult. We have defined a panel of seven antibodies capable of identifying the six stages of early nephron development, the tubular nephron segments and the components of the renal corpuscle within the embryonic and adult mouse kidney. We have analysed in detail the protein expression of Wt1, Calb1 Aqp1, Aqp2 and Umod using these antibodies. We have then coupled immunohistochemistry with RNA in situ hybridisation in order to precisely identify the expression pattern of different genes, including Wnt4, Umod and Spp1. This technique will be invaluable for examining at high resolution, the structure of both the developing and mature nephron where standard in situ hybridisation and histological techniques are insufficient. The use of this technique will enhance the expression analyses of genes which may be involved in nephron formation and the function of the mature nephron in the mouse. Content Type Journal ArticleCategory Original PaperDOI 10.1007/s00418-008-0454-3Authors Kylie Georgas, University of Queensland Institute for Molecular Bioscience St Lucia QLD 4072 AustraliaBree Rumballe, University of Queensland Institute for Molecular Bioscience St Lucia QLD 4072 AustraliaLorine Wilkinson, University of Queensland Institute for Molecular Bioscience St Lucia QLD 4072 AustraliaHan Sheng Chiu, University of Queensland Institute for Molecular Bioscience St Lucia QLD 4072 AustraliaEmmanuelle Lesieur, University of Queensland Institute for Molecular Bioscience St Lucia QLD 4072 AustraliaThierry Gilbert, University of Queensland Institute for Molecular Bioscience St Lucia QLD 4072 AustraliaMelissa H. Little, University of Queensland Institute for Molecular Bioscience St Lucia QLD 4072 Australia Journal Histochemistry and Cell BiologyOnline ISSN 1432-119XPrint ISSN 0948-6143 (Source: Histochemistry and Cell Biology)

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Histological assessment of cellular half-life in tissues in vivo

Histochemistry and Cell Biology — Fri, 11 Jul 2008 06:55:04 +0100

Abstract The assessment of cellular half-life is of fundamental importance for cell biology and biomedicine. Here, we show that cellular half-life in tissues can be histologically measured under steady state conditions in vivo by analyzing the loss of 5-bromo-2′-deoxyuridine (BrdU)-labeled cells over time after withdrawal of long-term BrdU labeling. To achieve efficient continuous cell labeling, we implanted BrdU-containing subcutaneous slow-release pellets into 12-month-old male Fischer 344 rats, delivering BrdU at a dose of 75 mg/kg per day over 1 (n = 20) or 3 weeks (n = 20). Four to five rats each were killed directly after the labeling or 1, 3, and 7 weeks post-labeling. Cellular half-life after withdrawal of BrdU was analyzed by nonlinear regression analysis of the labeling index, using a model of one-phase exponential decay. We initially validated our technique in the duodenum, where we determined a half-life of 2.4 days for crypt cells. Next, we applied this method to other tissues, and found a half-life of 2.2 weeks for cardiac endothelial cells, and of 5–6 days for pancreatic duct cells. In conclusion, we believe that this novel approach is an important step forward in the histological assessment of cellular half-life. Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/s00418-008-0470-3Authors Reinhold G. Erben, University of Veterinary Medicine Department of Biomedical Sciences, Institute of Pathophysiology Veterinaerplatz 1 1210 Vienna AustriaKathrin I. Odörfer, University of Veterinary Medicine Department of Biomedical Sciences, Institute of Pathophysiology Veterinaerplatz 1 1210 Vienna AustriaMichael Siebenhütter, Ludwig Maximilians University Institute of Animal Physiology Veterinaerstrasse 13 80539 Munich GermanyKarin Weber, Ludwig Maximilians University Institute of Animal Physiology Veterinaerstrasse 13 80539 Munich GermanySonja Rohleder, Ludwig Maximilians University Institute of Animal Physiology Veterinaerstrasse 13 80539 Munich Germany Journal Histochemistry and Cell BiologyOnline ISSN 1432-119XPrint ISSN 0948-6143 (Source: Histochemistry and Cell Biology)

A. fulgidus srp54 m-domain.

Journal of Bimolecular NMR — Fri, 11 Jul 2008 04:00:00 +0100

A. fulgidus SRP54 M-domain.

J Biomol NMR. 2008 Jul 11;

Authors: Ilangovan U, Bhuiyan SH, Hinck CS, Hoyle JT, Pakhomova ON, Zwieb C, Hinck AP

PMID: 18618268 [PubMed - as supplied by publisher]

(Source: Journal of Bimolecular NMR)

Revisiting the relation between species diversity and information theory.

Acta Biotheoretica — Fri, 11 Jul 2008 04:00:00 +0100

Revisiting the Relation Between Species Diversity and Information Theory.

Acta Biotheor. 2008 Jul 11;

Authors: Camargo JA

The Shannon information function (H) has been extensively used in ecology as a statistic of species diversity. Yet, the use of Shannon diversity index has also been criticized, mainly because of its ambiguous ecological interpretation and because of its relatively great sensitivity to the relative abundances of species in the community. In my opinion, the major shortcoming of the traditional perspective (on the possible relation of species diversity with information theory) is that species need for an external receiver (the scientist or ecologist) to exist and transmit information. Because organisms are self-catalized replicating structures that can transmit genotypic information to offspring, it should be evident that any single species has two possible states or alternatives: to be or not to be. In other words, species have no need for an external receiver since they are their own receivers. Therefore, the amount of biological information (at the species scale) in a community with one only species would be [Formula: see text] species, and not [Formula: see text] bits as in the traditional perspective. Moreover, species diversity appears to be a monotonic increasing function of [Formula: see text] (or S) when all species are equally probable (S being species richness), and not a function of [Formula: see text] as in the traditional perspective. To avoid the noted shortcoming, we could use 2(H) (instead of H) for calculating species diversity and species evenness (= 2(H)/S). However, owing to the relatively great sensitivity of H to the relative abundances of species in the community, the value of species dominance (= 1 - 2(H)/S) is unreasonably high when differences between dominant and subordinate species are considerable, thereby lowering the value of species evenness and diversity. This unsatisfactory behaviour is even more evident for Simpson index and related algorithms. I propose the use of other statistics for a better analysis of community structure, their relationship being: species evenness + species dominance = 1; species diversity x species uniformity = 1; and species diversity = species richness x species evenness.

PMID: 18618269 [PubMed - as supplied by publisher]

(Source: Acta Biotheoretica)

National institute of allergy and infectious diseases, nih

Springer Biomedical Sciences titles — Thu, 10 Jul 2008 23:40:34 +0100

Volume 1: Frontiers in Research series: Infectious Disease For over 50 years, the mission of the National Institute of Allergy and Infectious Diseases (NIAID) has been to conduct and support basic and applied research to better understand, treat, and prevent infectious, immunologic, and allergic diseases with the ultimate goal of improving the health of individuals in the United States and around the world. As part of its mission to foster ... (Source: Springer Biomedical Sciences titles)

Reelin glycoprotein

Springer Biomedical Sciences titles — Thu, 10 Jul 2008 23:04:42 +0100

Structure, Biology and Roles in Health and Disease Reelin glycoprotein is a major secretory protein with important roles in embryogenesis and during adult life. Reelin gene mutations or deficiency of the protein product cause abnormal cortical development and reelin signaling impairment in brain. Since the first discovery of the reelin mutant mouse in 1951 by Falconer, and later discovery of the gene for reelin in 1995, there has ... (Source: Springer Biomedical Sciences titles)

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Fly cells reveal host genes required for flu infection

NIGMS - Results — Thu, 10 Jul 2008 17:41:53 +0100

NIGMS-funded biologists have demonstrated a rapid way to identify host factors needed for a virus to infect a cell. (Source: NIGMS - Results)

How molecular motor works

NIGMS - Results — Thu, 10 Jul 2008 17:39:49 +0100

NIGMS-funded researchers have discovered that molecular motors in the cell work by detecting minor changes in force. (Source: NIGMS - Results)

Ion channels caught in opening act

NIGMS - Results — Thu, 10 Jul 2008 17:37:41 +0100

An NIGMS-funded study used unique methods to study how ion channels respond to voltage changes to open and close. (Source: NIGMS - Results)

Key molecule lets microbes produce greenhouse gases

NIGMS - Results — Thu, 10 Jul 2008 17:35:46 +0100

A 12-year effort funded by NIGMS sheds light on how microbes produce carbon dioxide and methane, offering insights for improving industrial processes. (Source: NIGMS - Results)

Ribosome display selection of a metal-binding motif from an artificial peptide library

Biotechnology and Bioengineering — Thu, 10 Jul 2008 04:00:00 +0100

A new ribosome display system was applied for the in vitro selection of a metal-binding motif from an artificial peptide library. The display system consisted of an mRNA-associating protein, a ribosome, and mRNA. The protein part of this display system was designed to provide a random peptide library and to stabilize the ribosome display. The random peptide library was newly designed to isolate stable metal-binding motifs. We employed the system for in vitro selection and found several new proteins and peptides that bind Co(II)-immobilized resin and Co(II)-complex, respectively. This newly developed system can be conveniently applied to the in vitro selection of peptide aptamers. Biotechnol. Bioeng. © 2008 Wiley Periodicals, Inc. (Source: Biotechnology and Bioengineering)

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Molecular imaging i

Springer Biomedical Sciences titles — Wed, 09 Jul 2008 23:07:33 +0100

series: Handbook of Experimental Pharmacology The aim of this textbook of molecular imaging is to provide an up to date review of this rapidly growing field and to discuss basic methodological aspects necessary for the interpretation of experimental and clinical results. Emphasis is placed on the interplay of imaging technology and probe development, since the physical properties of the imaging approach need to be closely ... (Source: Springer Biomedical Sciences titles)

Molecular imaging ii

Springer Biomedical Sciences titles — Wed, 09 Jul 2008 23:06:09 +0100

Rna technologies in cardiovascular medicine and research

Springer Biomedical Sciences titles — Wed, 09 Jul 2008 23:05:06 +0100

Cardiovascular disease is the number one cause of death worldwide. In 2005 17.5 million people, representing 30% of all global deaths, died of cardiovascular disease. For this reason every effort needs to be made to improve the early diagnosis and treatment procedures for combating this disease. This book - edited by Professors Erdmann and Barciszewski, both internationally recognised experts ... (Source: Springer Biomedical Sciences titles)

The role of microtubules in cell biology, neurobiology, and oncology

Springer Biomedical Sciences titles — Wed, 09 Jul 2008 23:04:39 +0100

series: Cancer Drug Discovery and Development The family of proteins called the tubulin and the microtubules they form when they aggregate are extremely important in the cell and, as we are increasingly learning, important in diseases that afflict so many. This field of investigation is a testament to how important both basic and clinical sciences are in understanding disease mechanisms and making inroads into therapies. ... (Source: Springer Biomedical Sciences titles)

Tools for germplasm cryopreservation (sttr [r41/r42])

NIGMS - What's New — Wed, 09 Jul 2008 22:15:04 +0100

(Source: NIGMS - What's New)

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Rna interacts with promoters to regulate genes

NIGMS - Results — Wed, 09 Jul 2008 17:16:55 +0100

NIGMS-funded researchers have discovered that RNA can interact with the non-coding part of a gene, apparently to regulate when it's turned on. (Source: NIGMS - Results)

Engineering an ecosystem

NIGMS Computing Life — Wed, 09 Jul 2008 15:00:00 +0100

New research is unveiling predator-prey interactions in a place much smaller than the Serengeti--a petri dish. (Source: NIGMS Computing Life)

Genetics medical officer

NIGMS Feedback Loop — Tue, 08 Jul 2008 18:53:00 +0100

The Division of Genetics and Developmental Biology is recruiting a human/medical geneticist with an M.D. or M.D./Ph.D. degree, clinical genetics experience, independent research experience, and a knowledge of the NIH peer review and grants processes. Read more. (Source: NIGMS Feedback Loop)

Nigms rss feeds

NIGMS Feedback Loop — Tue, 08 Jul 2008 18:53:00 +0100

Really Simple Syndication (RSS) is used to distribute news as it's published. Read more. (Source: NIGMS Feedback Loop)