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91.
LC8 is present in various molecular complexes. However, its role in these complexes remains unclear. We discovered that although LC8 is a subunit of the radial spoke (RS) complex in Chlamydomonas flagella, it was undetectable in the RS precursor that is converted into the mature RS at the tip of elongating axonemes. Interestingly, LC8 dimers bound in tandem to the N-terminal region of a spoke phosphoprotein, RS protein 3 (RSP3), that docks RSs to axonemes. LC8 enhanced the binding of RSP3 N-terminal fragments to purified axonemes. Likewise, the N-terminal fragments extracted from axonemes contained LC8 and putative spoke-docking proteins. Lastly, perturbations of RSP3's LC8-binding sites resulted in asynchronous flagella with hypophosphorylated RSP3 and defective associations between LC8, RSs, and axonemes. We propose that at the tip of flagella, an array of LC8 dimers binds to RSP3 in RS precursors, triggering phosphorylation, stalk base formation, and axoneme targeting. These multiple effects shed new light on fundamental questions about LC8-containing complexes and axoneme assembly. 相似文献
92.
Mariana Brait Myriam Loyo Eli Rosenbaum Kimberly L. Ostrow Alina Markova Silvana Papagerakis Marianna Zahurak Steven M. Goodman Martha Zeiger David Sidransky Christopher B. Umbricht Mohammad O. Hoque 《Epigenetics》2012,7(7):710-719
Our aim was to comprehensively analyze promoter hypermethylation of a panel of novel and known methylation markers for thyroid neoplasms and to establish their relationship with BRAF mutation and clinicopathologic parameters of thyroid cancer. A cohort of thyroid tumors, consisting of 44 cancers and 44 benign thyroid lesions, as well as 15 samples of adjacent normal thyroid tissue, was evaluated for BRAF mutation and promoter hypermethylation. Genes for quantitative methylation specific PCR (QMSP) were selected by a candidate gene approach. Twenty-two genes were tested: TSHR, RASSF1A, RARβ2, DAPK, hMLH1, ATM, S100, p16, CTNNB1, GSTP1, CALCA, TIMP3, TGFßR2, THBS1, MINT1, CTNNB1, MT1G, PAK3, NISCH, DCC, AIM1 and KIF1A. The PCR-based “mutector assay” was used to detect BRAF mutation. All p values reported are two sided. Considerable overlap was seen in the methylation markers among the different tissue groups. Significantly higher methylation frequency and level were observed for KIF1A and RARß2 in cancer samples compared with benign tumors. A negative correlation between BRAF mutation and RASSF1A methylation, and a positive correlation with RARß2 methylation were observed in accordance with previous results. In addition, positive correlation with TIMP3 and a marginal correlation with DCC methylation were observed. The present study constitutes a comprehensive promoter methylation profile of thyroid neoplasia and shows that results must be analyzed in a tissue-specific manner to identify clinically useful methylation markers. Integration of genetic and epigenetic changes in thyroid cancer will help identify relevant biologic pathways that drive its development. 相似文献
93.
Susann Rosenbaum Robert Ringseis Sonja Hillen Sabrina Becker Georg Erhardt Gerald Reiner Klaus Eder 《Comparative biochemistry and physiology. Part D, Genomics & proteomics》2012,7(4):370-381
The present study aimed to explore the lactation-induced changes in hepatic gene expression in sows (Sus scrofa) during lactation. Using a porcine whole-genome microarray a total of 632 differentially expressed genes in the liver of lactating compared to non-lactating sows could be identified. Enrichment analysis revealed that the differentially expressed genes were mainly involved in fatty acid metabolism, pyruvate metabolism, glutathione metabolism, glycine, serine and threonine metabolism, citrate cycle, glycerophospholipid metabolism, PPAR signaling, and focal adhesion. The most striking observation with respect to intermediary metabolism was that genes involved in fatty acid catabolism, the catabolism of gluconeogenic amino acids, the citrate cycle and the respiratory chain were up-regulated in the liver of sows during lactation. With respect to immune response, it could be demonstrated that genes encoding acute phase proteins and genes involved in tissue repair were up-regulated and genes encoding adhesion molecules were down-regulated in the liver of sows during lactation. The results indicate that energy-generating pathways and pathways involved in the delivery of gluconeogenic substrates are induced in sow liver during lactation. The alterations of expression of genes encoding proteins involved in immune response suggest that lactation in sows may cause an adaptive immune response that possibly counteracts hepatic inflammation. 相似文献
94.
Anita Murray Salvatore Cerchio Robert McCauley Curt S. Jenner Yvette Razafindrakoto Douglas Coughran Shannon McKay Howard Rosenbaum 《Marine Mammal Science》2012,28(1):E41-E57
Comparing humpback whale song from different breeding assemblages can reveal similarities in song due to acoustically interacting males, and therefore indirectly test whether males from different breeding sites are mixing. Northern Hemisphere song comparisons illustrated that whales within ocean basins share similar songs and are subpopulations within a larger population, whereas whales in different ocean basins are isolated populations and therefore do not share songs. During the 2006 breeding season, recordings were collected in Madagascar and Western Australia, and were compared visually plus aurally. Both regions shared one theme, whereas each region had four and six private themes, respectively. This study had a substantially low number of shared themes. The co‐occurrence of one theme was interpreted as an indication of limited exchange between these breeding assemblages, and we speculate that limited song similarity is due to inter‐oceanic interactions. Male(s) from an Indian Ocean breeding group could be exposed to novel song when they geographically overlap, and acoustically interact, with males from a different ocean basin. Novel song could induce rapid temporal changes as new song content is incorporated, thereby minimizing song similarities between that breeding group and other Indian Ocean breeding groups that were not exposed to the novel song. 相似文献
95.
Guinée Jeroen B. Koning Arjan de Pennington David W. Rosenbaum Ralph Hauschild Michael Olsen Stig I. Molander Sverker Bachmann Till M. Pant Rana 《The International Journal of Life Cycle Assessment》2004,9(5):320-326
Goal, Scope and Background The EU 5th framework project OMNIITOX will develop models calculating characterisation factors for assessing the potential toxic impacts
of chemicals within the framework of LCA. These models will become accessible through a web-based information system. The
key objective of the OMNIITOX project is to increase the coverage of substances by such models. In order to reach this objective,
simpler models which need less but available data, will have to be developed while maintaining scientific quality. Methods.
Experience within the OMNIITOX project has taught that data availability and quality are crucial issues for calculating characterisation
factors. Data availability determines whether calculating characterisation factors is possible at all, whereas data quality
determines to what extent the resulting characterisation factors are reliable. Today, there is insufficient knowledge and/or
resources to have high data availability as well as high data quality and high model quality at the same time.
Results The OMNIITOX project is developing two inter-related models in order to be able to provide LCA impact assessment characterisation
factors for toxic releases for as broad a range of chemicals as possible: 1) A base model representing a state-of-the-art
multimedia model and 2) a simple model derived from the base model using statistical tools. Discussion. A preliminary decision
tree for using the OMNIITOX information system (IS) is presented. The decision tree aims to illustrate how the OMNIITOX IS
can assist an LCA practitioner in finding or deriving characterisation factors for use in life cycle impact assessment of
toxic releases.
Conclusions and Outlook Data availability and quality are crucial issues when calculating characterisation factors for the toxicity impact categories.
The OMNIITOX project is developing a tiered model approach for this. It is foreseen that a first version of the base model
will be ready in late summer of 2004, whereas a first version of the simple base model is expected a few months later. 相似文献
96.
Allison Kraus Jody Groenendyk Karen Bedard Troy A. Baldwin Karl-Heinz Krause Michel Dubois-Dauphin Jason Dyck Erica E. Rosenbaum Lawrence Korngut Nansi J. Colley Simon Gosgnach Douglas Zochodne Kathryn Todd Luis B. Agellon Marek Michalak 《The Journal of biological chemistry》2010,285(24):18928-18938
Calnexin is a molecular chaperone and a component of the quality control of the secretory pathway. We have generated calnexin gene-deficient mice (cnx−/−) and showed that calnexin deficiency leads to myelinopathy. Calnexin-deficient mice were viable with no discernible effects on other systems, including immune function, and instead they demonstrated dysmyelination as documented by reduced conductive velocity of nerve fibers and electron microscopy analysis of sciatic nerve and spinal cord. Myelin of the peripheral and central nervous systems of cnx−/− mice was disorganized and decompacted. There were no abnormalities in neuronal growth, no loss of neuronal fibers, and no change in fictive locomotor pattern in the absence of calnexin. This work reveals a previously unrecognized and important function of calnexin in myelination and provides new insights into the mechanisms responsible for myelin diseases. 相似文献
97.
R T Crow B Rosenbaum R Smith Y Guo K S Ramos G A Sulikowski 《Bioorganic & medicinal chemistry letters》1999,9(12):1663-1666
Landomycin A was found to inhibit the uptake of [3H]thymidine into DNA in murine smooth muscle cells indicating decreased DNA synthesis. Subsequent studies showed that landomycin A inhibits cell cycle progression. 相似文献
98.
Treating obesity has proven to be an intractable challenge, in part, due to the difficulty of maintaining reduced weight. In our previous studies of in-patient obese subjects, we have shown that leptin repletion following a 10% or greater weight loss reduces many of the metabolic (decreased energy expenditure, sympathetic nervous system tone, and bioactive thyroid hormones) and behavioral (delayed satiation) changes that favor regain of lost weight. FMRI studies of these same subjects have shown leptin-sensitive increases in activation of the right hypothalamus and reduced activation of the cingulate, medial frontal and parahippocampal gryi, following weight loss, in response to food stimuli. In the present study, we expanded our cohort of in-patient subjects and employed psychophysiological interaction (PPI) analysis to examine changes in the functional connectivity of the right hypothalamus. During reduced-weight maintenance with placebo injections, the functional connectivity of the hypothalamus increased with visual areas and the dorsal anterior cingulate (dorsal ACC) in response to food cues, consistent with higher sensitivity to food. During reduced-weight maintenance with leptin injections, however, the functional connectivity of the right hypothalamus increased with the mid-insula and the central and parietal operculae, suggesting increased coupling with the interoceptive system, and decreased with the orbital frontal cortex, frontal pole and the dorsal ACC, suggesting a down-regulated sensitivity to food. These findings reveal neural mechanisms that may underlie observed changes in sensitivity to food cues in the obese population during reduced-weight maintenance and leptin repletion. 相似文献
99.
M. Asunción Durá Eva Rosenbaum Amédé Larabi Frank Gabel Frédéric M. D. Vellieux Bruno Franzetti 《Molecular microbiology》2009,72(1):26-40
The structure of a 468 kDa peptidase complex from the hyperthermophile Pyrococcus horikoshii has been solved at 1.9 Å resolution. The monomer contains the M42 peptidase typical catalytic domain, and a dimerization domain that allows the formation of dimers that assemble as a 12-subunit self-compartmentalized tetrahedron, similar to those described for the TET peptidases. The biochemical analysis shows that the enzyme is cobalt-activated and cleaves peptides by a non-processive mechanism. Consequently, this protein represents the third TET peptidase complex described in P. horikoshii , thereby called PhTET3. It is a lysyl aminopeptidase with a strong preference for basic residues, which are poorly cleaved by PhTET1 and PhTET2. The structural analysis of PhTET3 and its comparison with PhTET1 and PhTET2 unravels common features explaining the general mode of action of the TET molecular machines as well as differences that can be associated with strong substrate discriminations. The question of the stability of the TET assemblies under extreme temperatures has been addressed. PhTET3 displays its maximal activity at 95°C and small-angle neutron scattering experiments at 90°C demonstrate the absence of quaternary structure alterations after extensive incubation times. In conclusion, PhTETs are complementary peptide destruction machines that may play an important role in the metabolism of P. horikoshii . 相似文献
100.