PubMed Central (PMC3 - NLM DTD)
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Archive of life sciences journal literature at the U.S. National Institutes of Health (NIH), developed and managed by NIH's National Center for Biotechnology Information (NCBI) in the National Library of Medicine (NLM).
Mostrando recursos 41 - 60 de 184,040
41.
The majority of human genes have regions repeated in other human genes - Britten, Roy J.
Amino acid sequence comparisons have been made between all of 25,193 human proteins with each of the others by using blast software (National Center for Biotechnology Information) and recording the results for regions that are significantly related in sequence, that is, have an expectation of <1 × 103. The results are presented for each amino acid as the number of identical or similar amino acids matched in these aligned regions. This approach avoids summing or dealing directly with the different regions of any one protein that are often related to different numbers and types of other proteins. The results are...
42.
Functional diffusion map: A noninvasive MRI biomarker for early stratification of clinical brain tumor response - Moffat, Bradford A.; Chenevert, Thomas L.; Lawrence, Theodore S.; Meyer, Charles R.; Johnson, Timothy D.; Dong, Qian; Tsien, Christina; Mukherji, Suresh; Quint, Douglas J.; Gebarski, Stephen S.; Robertson, Patricia L.; Junck, Larry R.; Rehemtulla, Alnawaz; Ross, Brian D.
Assessment of radiation and chemotherapy efficacy for brain cancer patients is traditionally accomplished by measuring changes in tumor size several months after therapy has been administered. The ability to use noninvasive imaging during the early stages of fractionated therapy to determine whether a particular treatment will be effective would provide an opportunity to optimize individual patient management and avoid unnecessary systemic toxicity, expense, and treatment delays. We investigated whether changes in the Brownian motion of water within tumor tissue as quantified by using diffusion MRI could be used as a biomarker for early prediction of treatment response in brain cancer...
43.
Escherichia coli K1 polysialic acid O-acetyltransferase gene, neuO, and the mechanism of capsule form variation involving a mobile contingency locus - Deszo, Eric L.; Steenbergen, Susan M.; Freedberg, Darón I.; Vimr, Eric R.
Potential O-acetylation of the sialic acid residues of Escherichia coli K1, groups W-135, Y, and C meningococci, and group B Streptococcus capsular polysaccharides modifies their immunogenicity and susceptibility to glycosidases. Despite the biological importance of O-acetylation, no sialic or polysialic acid O-acetyltransferase has been identified in any system. Here we show that the E. coli K1 O-acetyltransferase encoded by neuO is genetically linked to the endo-neuraminidase tail protein gene of a chromosomal accretion element, designated CUS-3, with homology to lambdoid bacteriophage. Molecular epidemiological analysis established concordance between O-acetyltransferase and CUS-3 in a set of E. coli K1 strains. Deleting neuO...
44.
Molecular organization of the Ndc80 complex, an essential kinetochore component - Wei, Ronnie R.; Sorger, Peter K.; Harrison, Stephen C.
The four-protein Ndc80 complex, an essential kinetochore component conserved from yeast to humans, plays an indispensable role in proper chromosome alignment and segregation during mitosis. In higher eukaryotes, the homologous complex probably resides in the middle domain of the trilaminar kinetochore, linking centromeric heterochromatin with microtubule-associated structures. We have prepared recombinant Ndc80 complex by pairwise coexpression of its components (Ndc80p and Nuf2p; Spc24p and Spc25p) and shown that they form independently stable subcomplexes. Rotary shadowing electron microscopy, combined with limited proteolysis and antibody labeling, demonstrates that the heterotetrameric Ndc80 complex is an ?570-Å-long rod, with globular regions at either end....
45.
Identification of putative noncoding polyadenylated transcripts in Drosophila melanogaster - Tupy, Jonathan L.; Bailey, Adina M.; Dailey, Gina; Evans-Holm, Martha; Siebel, Christian W.; Misra, Sima; Celniker, Susan E.; Rubin, Gerald M.
Analysis of EST and cDNA collections from a number of metazoan species has identified genes encoding long polyadenylated transcripts that do not contain ORFs of lengths typical for protein-encoding mRNAs. Noncoding functions of such polyadenylated transcripts have been elucidated in only a few examples. The corresponding genes neither contain hallmark sequence motifs nor appear to have been conserved across phyla. Thus, it is impossible to systematically identify new members of this class of gene by using sequence homology and traditional gene-finding algorithms that depend on protein-coding potential. Consequently, even their approximate number has not been established for any metazoan genome....
46.
Diverse taxa of cyanobacteria produce ?-N-methylamino-l-alanine, a neurotoxic amino acid - Cox, Paul Alan; Banack, Sandra Anne; Murch, Susan J.; Rasmussen, Ulla; Tien, Georgia; Bidigare, Robert Richard; Metcalf, James S.; Morrison, Louise F.; Codd, Geoffrey A.; Bergman, Birgitta
Cyanobacteria can generate molecules hazardous to human health, but production of the known cyanotoxins is taxonomically sporadic. For example, members of a few genera produce hepatotoxic microcystins, whereas production of hepatotoxic nodularins appears to be limited to a single genus. Production of known neurotoxins has also been considered phylogenetically unpredictable. We report here that a single neurotoxin, ?-N-methylamino-l-alanine, may be produced by all known groups of cyanobacteria, including cyanobacterial symbionts and free-living cyanobacteria. The ubiquity of cyanobacteria in terrestrial, as well as freshwater, brackish, and marine environments, suggests a potential for wide-spread human exposure.
47.
Structure theorems and the dynamics of nitrogen catabolite repression in yeast - Boczko, Erik M.; Cooper, Terrance G.; Gedeon, Tomas; Mischaikow, Konstantin; Murdock, Deborah G.; Pratap, Siddharth; Wells, K. Sam
By using current biological understanding, a conceptually simple, but mathematically complex, model is proposed for the dynamics of the gene circuit responsible for regulating nitrogen catabolite repression (NCR) in yeast. A variety of mathematical structure theorems are described that allow one to determine the asymptotic dynamics of complicated systems under very weak hypotheses. It is shown that these theorems apply to several subcircuits of the full NCR circuit, most importantly to the URE2GLN3 subcircuit that is independent of the other constituents but governs the switching behavior of the full NCR circuit under changes in nitrogen source. Under hypotheses that are...
48.
Reverse recruitment: The Nup84 nuclear pore subcomplex mediates Rap1/Gcr1/Gcr2 transcriptional activation - Menon, Balaraj B.; Sarma, Nayan J.; Pasula, Satish; Deminoff, Stephen J.; Willis, Kristine A.; Barbara, Kellie E.; Andrews, Brenda; Santangelo, George M.
The recruitment model for gene activation presumes that DNA is a platform on which the requisite components of the transcriptional machinery are assembled. In contrast to this idea, we show here that Rap1/Gcr1/Gcr2 transcriptional activation in yeast cells occurs through a large anchored protein platform, the Nup84 nuclear pore subcomplex. Surprisingly, Nup84 and associated subcomplex components activate transcription themselves in vivo when fused to a heterologous DNA-binding domain. The Rap1 coactivators Gcr1 and Gcr2 form an important bridge between the yeast nuclear pore complex and the transcriptional machinery. Nucleoporin activation may be a widespread eukaryotic phenomenon, because it was first...
49.
Linker histone variants control chromatin dynamics during early embryogenesis - Saeki, Hideaki; Ohsumi, Keita; Aihara, Hitoshi; Ito, Takashi; Hirose, Susumu; Ura, Kiyoe; Kaneda, Yasufumi
Complex transitions in chromatin structure produce changes in genome function during development in metazoa. Linker histones, the last component of nucleosomes to be assembled into chromatin, comprise considerably divergent subtypes as compared with core histones. In all metazoa studied, their composition changes dramatically during early embryogenesis concomitant with zygotic gene activation, leading to distinct functional changes that are still poorly understood. Here, we show that early embryonic linker histone B4, which is maternally expressed, is functionally different from somatic histone H1 in influencing chromatin structure and dynamics. We developed a chromatin assembly system with nucleosome assembly protein-1 as a linker...
50.
Evolution and development of facial bone morphology in threespine sticklebacks - Kimmel, Charles B.; Ullmann, Bonnie; Walker, Charline; Wilson, Catherine; Currey, Mark; Phillips, Patrick C.; Bell, Michael A.; Postlethwait, John H.; Cresko, William A.
How do developmental mechanisms evolve to control changing skeletal morphology, the shapes and sizes of individual bones? We address this question with studies of the opercle (OP), a large facial bone that has undergone marked morphological evolution in the ray-finned fish. Attributes for developmental analysis motivated us to examine how OP shape and size evolve and develop in threespine sticklebacks, a model system for understanding vertebrate evolution. We find that when Alaskan anadromous fish take up permanent residence in lakes, they evolve smaller and reshaped OPs. The change is a reduction in the amount of bone laid down along one...
51.
Observing spontaneous branch migration of Holliday junctions one step at a time - McKinney, Sean A.; Freeman, Alasdair D. J.; Lilley, David M. J.; Ha, Taekjip
Genetic recombination occurs between homologous DNA molecules via a four-way (Holliday) junction intermediate. This ancient and ubiquitous process is important for the repair of double-stranded breaks, the restart of stalled replication forks, and the creation of genetic diversity. Once formed, the four-way junction alone can undergo the stepwise exchange of base pairs known as spontaneous branch migration. Conventional ensemble assays, useful for finding average migration rates over long sequences, have been unable to examine the affect of sequence and structure on the migration process. Here, we present a single-molecule spontaneous branch migration assay with single-base pair resolution in a study...
52.
Delayed maturation of receptive field center/surround mechanisms in V2 - Zhang, Bin; Zheng, Jianghe; Watanabe, Ichiro; Maruko, Ichiro; Bi, Hua; Smith, Earl L.; Chino, Yuzo
Neurons in the adult visual cortex are capable of integrating signals over a large area that surrounds their classic receptive field (RF), and this ability of cortical neurons is thought to be intimately involved in perceptual binding. It is not known, however, at what age these long-range signal interactions emerge. Here, we report that qualitatively adult-like center/surround interactions are already present in the primary visual cortex as early as postnatal day 14 in macaque monkeys. However, the RF surrounds of visual area 2 (V2) neurons were largely absent until 4 weeks of age and, as late as 8 weeks of...
53.
Nonmammalian gonadotropin-releasing hormone molecules in the brain of promoter transgenic rats - Parhar, Ishwar S.; Soga, Tomoko; Ogawa, Satoshi; Ogawa, Sonoko; Pfaff, Donald W.; Sakuma, Yasuo
Mammalian gonadotropin-releasing hormone (GnRH1) and nonmammalian immunoreactive GnRH subtypes were examined in transgenic rats carrying an enhanced GFP (EGFP) reporter gene driven by a rat GnRH1 promoter. Double-label immunocytochemistry was performed on EGFP+/GnRH1 brain sections by using antisera against GnRH1, GnRH2 (chicken II), GnRH3 (salmon), or seabream GnRH. EGFP+/GnRH1 neurons were in the septalpreoptic hypothalamus but not in the midbrain, consistent with GnRH1-immunopositive neurons in WT rats. Apparent coexpression of EGFP+/GnRH1 with other GnRH subtypes was observed. All EGFP+ neurons in the septalpreoptic hypothalamus were GnRH1-immunopositive. However, only ?80% of GnRH1-immunopositive neurons were EGFP+, which awaits further elucidation. GnRH subtypes-immunopositive...
54.
An Early Pleistocene hominin mandible from Atapuerca-TD6, Spain - Carbonell, E.; Bermúdez de Castro, J. M.; Arsuaga, J. L.; Allue, E.; Bastir, M.; Benito, A.; Cáceres, I.; Canals, T.; Díez, J. C.; van der Made, J.; Mosquera, M.; Ollé, A.; Pérez-González, A.; Rodríguez, J.; Rodríguez, X. P.; Rosas, A.; Rosell, J.; Sala, R.; Vallverdú, J.; Vergés, J. M.
We present a mandible recovered in 2003 from the Aurora Stratum of the TD6 level of the Gran Dolina site (Sierra de Atapuerca, northern Spain). The specimen, catalogued as ATD6-96, adds to the hominin sample recovered from this site in 19941996, and assigned to Homo antecessor. ATD6-96 is the left half of a gracile mandible belonging to a probably female adult individual with premolars and molars in place. This mandible shows a primitive structural pattern shared with all African and Asian Homo species. However, it is small and exhibits a remarkable gracility, a trait shared only with the Early and...
55.
DNA repair proteins affect the lifecycle of herpes simplex virus 1 - Lilley, Caroline E.; Carson, Christian T.; Muotri, Alysson R.; Gage, Fred H.; Weitzman, Matthew D.
We report that herpes simplex virus 1 (HSV-1) infection can activate and exploit a cellular DNA damage response that aids viral replication in nonneuronal cells. Early in HSV-1 infection, several members of the cellular DNA damage-sensing machinery are activated and accumulate at sites of viral DNA replication. When this cellular response is abrogated, formation of HSV-1 replication centers is retarded, and viral production is compromised. In neurons, HSV-1 replication centers fail to mature, and the DNA damage response is not initiated. These data suggest that the failure of neurons to mount a DNA damage response to HSV-1 may contribute to...
56.
Gene expression profiling reveals molecularly and clinically distinct subtypes of glioblastoma multiforme - Liang, Yu; Diehn, Maximilian; Watson, Nathan; Bollen, Andrew W.; Aldape, Ken D.; Nicholas, M. Kelly; Lamborn, Kathleen R.; Berger, Mitchel S.; Botstein, David; Brown, Patrick O.; Israel, Mark A.
Glioblastoma multiforme (GBM) is the most common form of malignant glioma, characterized by genetic instability, intratumoral histopathological variability, and unpredictable clinical behavior. We investigated global gene expression in surgical samples of brain tumors. Gene expression profiling revealed large differences between normal brain samples and tumor tissues and between GBMs and lower-grade oligodendroglial tumors. Extensive differences in gene expression were found among GBMs, particularly in genes involved in angiogenesis, immune cell infiltration, and extracellular matrix remodeling. We found that the gene expression patterns in paired specimens from the same GBM invariably were more closely related to each other than to any...
57.
Zinc inhibition of ?-aminobutyric acid transporter 4 (GAT4) reveals a link between excitatory and inhibitory neurotransmission - Cohen-Kfir, Einav; Lee, William; Eskandari, Sepehr; Nelson, Nathan
?-Aminobutyric acid (GABA) transporters (GATs) play an important role in inhibitory neurotransmission by clearing synaptically released GABA and by maintaining low resting levels of GABA in synaptic and extrasynaptic regions. In certain brain regions, vesicular zinc is colocalized and coreleased with glutamate and modulates the behavior of a number of channels, receptors, and transporters. We examined the effect of zinc on expressed GATs (GAT1, GAT2, GAT3, and GAT4) in Xenopus laevis oocytes by using tracer flux and electrophysiological methods. We show that zinc is a potent inhibitor of GAT4 (Ki of 3 ?M). Immunolocalization of GAT4 in the hippocampus revealed...
58.
Semipermeable lipid bilayers exhibit diastereoselectivity favoring ribose - Sacerdote, M. G.; Szostak, J. W.
Nutrient uptake by a primitive cell would have been limited by the permeability characteristics of its membrane. We measured the permeabilities of model protocellular membranes to water, five of the six pentoses, and selected aldohexoses, ketohexoses, and three to six carbon alditols by following volume changes of vesicles after the addition of solute to the external medium. Solute hydrophobicities correlated poorly with permeability coefficients within one structural class of compounds. The permeability coefficients of diastereomeric sugars differed by as much as a factor of 10, with ribose being the most permeable aldopentose. Flexible alditols and sugars, sugars biased toward or...
59.
Glutamate induces the rapid formation of spine head protrusions in hippocampal slice cultures - Richards, David A.; Mateos, José Maria; Hugel, Sylvain; de Paola, Vincenzo; Caroni, Pico; Gähwiler, Beat H.; McKinney, R. Anne
Synaptic plasticity at neuronal connections has been well characterized functionally by using electrophysiological approaches, but the structural basis for this phenomenon remains controversial. We have studied the dynamic interactions between presynaptic and postsynaptic structures labeled with FM 4-64 and a membrane-targeted GFP, respectively, in hippocampal slices. Under conditions of reduced neuronal activity (1 ?M tetrodotoxin), we observed extension of glutamate receptor-dependent processes from dendritic spines of CA1 pyramidal cells to presynaptic boutons. The formation of these spine head protrusions is blocked by ?-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonists and by agents that reduce the release of glutamate from presynaptic terminals....
60.
Deletion of PPAR? in adipose tissues of mice protects against high fat diet-induced obesity and insulin resistance - Jones, Julie R.; Barrick, Cordelia; Kim, Kyoung-Ah; Lindner, Jill; Blondeau, Bertrand; Fujimoto, Yuka; Shiota, Masakazu; Kesterson, Robert A.; Kahn, Barbara B.; Magnuson, Mark A.
Peroxisome proliferator-activated receptor ? (PPAR?) plays a crucial role in adipocyte differentiation, glucose metabolism, and other physiological processes. To further explore the role of PPAR? in adipose tissues, we used a Cre/loxP strategy to generate adipose-specific PPAR? knockout mice. These animals exhibited marked abnormalities in the formation and function of both brown and white adipose tissues. When fed a high-fat diet, adipose-specific PPAR? knockout mice displayed diminished weight gain despite hyperphagia, had diminished serum concentrations of both leptin and adiponectin, and did not develop glucose intolerance or insulin resistance. Characterization of in vivo glucose dynamics pointed to improved hepatic glucose...
41.
