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Nucleotide sequence of the feline retroviral oncogene v-fms shows unexpected homology with oncogenes encoding tyrosine-specific protein kinases.

The nucleotide sequence encoding the transforming polyprotein of the McDonough strain of feline sarcoma virus was determined. This sequence includes 231 nucleotides specifying a leader peptide, 1,377 nucleotides encoding most of the feline leukemia virus-derived gag gene, and 2,969 nucleotides representing the viral transforming gene v-fms. A single open reading frame was predicted to encode a fusion polyprotein of 160,000 daltons (P160gag-fms). Fourteen potential sites for glycosylation were predicted within the v-fms-encoded portion of the protein, consistent with previous observations that the primary translation product is rapidly glycosylated. The presence of hydrophobic signal peptides within the amino-terminal leader sequence and in the middle of the v-fms-encoded moiety suggests that the transforming glycoprotein becomes oriented with its amino terminus within the lumen of the rough endoplasmic reticulum and its carboxyl terminus protruding across the membrane of the rough endoplasmic reticulum into the cytoplasm. The latter portion of the protein shows unexpected homology to tyrosine-specific protein kinases encoded by several of the known retroviral oncogenes.

Amino Acid Sequence↗

Evidence for selection as a mechanism in the concerted evolution of Lycopersicon esculentum (tomato) genes encoding the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase.

The nuclear gene sequences encoding RBCS, the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (EC 4.1.1.39) from several plants show extensive interspecific divergence but little intraspecific divergence, suggesting that these genes are evolving in concert within a genome. In this study, the nucleotide sequences of two tomato (Lycopersicon esculentum) RBCS genes and a cDNA clone containing the entire coding region of a third tomato RBCS gene were determined. The three genes, designated Rbcs-1, Rbcs-2A, and Rbcs-3A, each belong to a different one of the three RBCS loci in the tomato genome. The nucleotide sequence of Rbcs-1 differs from that of Rbcs-2A and Rbcs-3A by 13.9% and 13.1%, respectively. Rbcs-2A and Rbcs-3A differ from each other by 10.7%. A recently published RBCS gene sequence from tobacco (Nicotiana tabacum) [Mazur, B. J. & Chui, C.-F. (1985) Nucleic Acids Res. 13, 2373-2386] differs by 10.6% and 11.3% from Rbcs-2A and Rbcs-3A, respectively, and by 15.0% from Rbcs-1. Thus the tobacco gene seems to be phylogenetically as closely related to the tomato genes Rbcs-2A and Rbcs-3A as the latter two are to each other, and more closely related to them than Rbcs-1 is. However, the mature part of the polypeptide encoded by the tobacco RBCS gene differs by five and six amino acids from the corresponding region in the polypeptides encoded by Rbcs-2A and Rbcs-3A, respectively, while these two tomato RBCS polypeptides differ from each other in the mature part by a single amino acid. Rbcs-1, whose nucleotide sequence shows higher divergence from both the tobacco RBCS gene and Rbcs-2A and Rbcs-3A, encodes a polypeptide whose mature part differs by eight amino acids from the corresponding region in the tobacco polypeptide but only by three and four amino acids from the corresponding regions of Rbcs-2A- and Rbcs-3A-encoded polypeptides, respectively. Thus, it appears that in the tomato selection has maintained near uniformity of the coding information in the portion of the RBCS genes encoding the mature polypeptides.

Amino Acid Sequence↗

Transcript encoded on the opposite strand of the human steroid 21-hydroxylase/complement component C4 gene locus.

The gene encoding human adrenal steroid 21-hydroxylase (P450c21) and its highly similar pseudogene are duplicated in tandem with the two genes encoding the fourth component of human serum hemolytic complement (C4). This 60-kilobase gene complex, which lies within the major histocompatibility complex on the short arm of human chromosome 6, has been studied in considerable detail because genetic disorders in steroid 21-hydroxylation and in C4 are common. We have cloned a cDNA encoded by a previously unidentified gene in this region. This gene lies on the strand of DNA opposite from the strand containing the P450c21 and C4 genes, and it overlaps the last exon of P450c21. The newly identified gene encodes mRNAs of 3.5 and 1.8 kilobases that are expressed in the adrenal and in a Leydig cell tumor but are not expressed in nonsteroidogenic tissues. The sequence of the longest cDNA (2.7 kilobases) shows no similarity to known sequences available in two computerized data bases. The 5' end of this sequence is characterized by three repeats, each encoding about 100 amino acids flanked by potential sites for proteolytic cleavage. Although numerous studies have shown that gene deletions causing congenital adrenal hyperplasia occur in this region, none of these gene deletions extends into this newly identified gene, suggesting that it encodes an essential function.

Amino Acid Sequence↗

The plastid genome of Cryptomonas phi encodes an hsp70-like protein, a histone-like protein, and an acyl carrier protein.

The plastid genome of Cryptomonas phi, a cryptomonad alga, contains three genes that have not previously been found in any organellar genome. Each of these genes encodes a functional class of organellar gene product not previously reported. The first gene, dnaK, encodes a polypeptide of the hsp70 heat shock protein family. The predicted amino acid sequence of the DnaK protein is 54% identical to that of the Escherichia coli hsp70 protein (DnaK), 50-53% identical to that of two nucleus-encoded mitochondrial hsp70 proteins, and 43-46% identical to that of several eukaryotic cytoplasmic members of the hsp70 protein family. The second gene, hlpA, encodes a polypeptide resembling bacterial histone-like proteins. The predicted amino acid sequence of the HlpA protein is 25-53% identical to that of several bacterial histone-like proteins, and the identity increases to 39-76% over a conserved region corresponding to the long arm that binds DNA. The third gene, acpA, encodes an acyl carrier protein, which is a key cofactor in the synthesis and metabolism of fatty acids. Its predicted amino acid sequence is 36-59% identical to that of eubacterial and plant chloroplast (nucleus-encoded) acyl carrier proteins.

Acyl Carrier Protein↗

Identification of a yeast artificial chromosome clone encoding an accessory factor for the human interferon gamma receptor: evidence for multiple accessory factors.

Human chromosomes 6 and 21 are both necessary to confer sensitivity to human interferon gamma (Hu-IFN-gamma), as measured by the induction of human HLA class I antigen. Human chromosome 6 encodes the receptor for Hu-IFN-gamma, and human chromosome 21 encodes accessory factors for generating biological activity through the Hu-IFN-gamma receptor. A small region of human chromosome 21 that is responsible for encoding such factors was localized with hamster-human somatic cell hybrids carrying an irradiation-reduced fragment of human chromosome 21. The cell line with the minimum chromosome 21-specific DNA is Chinese hamster ovary 3x1S. To localize the genes further, 10 different yeast artificial chromosome clones from six different loci in the vicinity of the 3x1S region were fused to a human-hamster hybrid cell line (designated 16-9) that contains human chromosome 6q (supplying the Hu-IFN-gamma receptor) and the human HLA-B7 gene. These transformed 16-9 cells were assayed for induction of class I HLA antigens upon treatment with Hu-IFN-gamma. Here we report that a 540-kb yeast artificial chromosome encodes the necessary species-specific factor(s) and can substitute for human chromosome 21 to reconstitute the Hu-IFN-gamma-receptor-mediated induction of class I HLA antigens. However, the factor encoded on the yeast artificial chromosome does not confer antiviral protection against encephalomyocarditis virus, demonstrating that an additional factor encoded on human chromosome 21 is required for the antiviral activity.

Animals↗

An intron-encoded protein assists RNA splicing of multiple similar introns of different bacterial genes.

Four group II introns were found in an unusually intron-rich dnaN gene (encoding the beta subunit of DNA polymerase III) of the cyanobacterium Trichodesmium erythraeum, and they have strong similarities to two introns of the RIR gene (encoding ribonucleotide reductase) of the same organism. Of these six introns, only the RIR-3 intron encodes a maturase protein and showed efficient RNA splicing when expressed in Escherichia coli cells. The other five introns do not encode a maturase protein and did not show RNA splicing in E. coli. But these maturase-less introns showed efficient RNA splicing when the RIR-3 intron-encoded maturase protein was co-expressed from a freestanding gene in the same cell. These findings demonstrated that an intron-encoded protein could function as a general maturase for multiple introns of different genes. Major implications may include an intron-mediated co-regulation of the different genes and a resemblance of the evolutionary origin of spliceosomal introns.

Alternative Splicing↗

Adult age differences in memory: effects of distinctive and common encodings.

To clarify the role of encoding distinctiveness and encoding cue utilization in age-related memory differences, young and elderly adults were instructed either to generate distinctive or common adjectives for 40 nouns and given 3 study-recall trials for the nouns, both with no cues and with the adjectives that they had generated as cues. Their retention was compared with that of a control group that had rated the nouns for abstractness. Elderly adults were as likely as young adults to generate distinctive adjectives, but were less likely than young adults to generate common adjectives when instructed to do so. In both age groups, common adjective encodings produced superior free recall and distinctive adjective encodings produced superior cued recall. The results suggest that (1) elderly adults are as capable as young adults of generating distinctive encoding context cues when instructed to do so, and (2) age-related encoding differences occur in the processing of distinctive properties of the stimulus items themselves rather than in the utilization of cues generated during study.

Adult↗

The neuroimaging of long-term memory encoding processes.

There needs to be more crosstalk between the lesion and functional neuroimaging memory literatures. This is illustrated by a discussion of episode and fact encoding. The lesion literature suggests several hypotheses about which brain regions underlie the storage of episode and fact information, which can be explored by functional neuroimaging. These hypotheses have been underexplored because neuroimaging studies of encoding have been insufficiently hypothesis-driven and have not controlled encoding-related processes sufficiently well to allow clear interpretations of results to be made. Nevertheless, there is good evidence that certain kinds of associative encoding and/or consolidation are sufficient to activate the medial temporal lobes, and preliminary evidence that some kinds of associative priming may reduce activation of this region. It remains to be proved that attentional orienting to certain kinds of novel information activates the medial temporal lobes. Evidence is growing that the HERA model, developed from neuroimaging rather than lesion data, requires modification and that frontal cortex encoding activations are probably caused by executive processes that are important in effortful memory processing. Neuroimaging studies allow the detection of encoding-related activations in previously unexpected brain regions (e.g. parietal lobes) and, in turn, these findings can be explored with lesion studies.

Brain↗

Myocardial fiber orientation mapping using reduced encoding diffusion tensor imaging.

A precise knowledge of the myocardial fiber architecture is essential to accurately understand and interpret cardiac electrical and mechanical functions. Diffusion tensor imaging has been used to noninvasively and quantitatively characterize myocardial fiber orientations. However, because the approach necessitates diffusion to be measured in multiple encoding directions and frequently at multiple weighting levels, the required data set size may present a limitation on its acquisition time efficiency. Applying the principles of reduced encoding imaging (REI), four basic reconstruction schemes, keyhole using direct substitution, keyhole with baseline correction, symmetrically encoded REI with generalized-series reconstruction (RIGR), and asymmetrically encoded RIGR, are evaluated in terms of their accuracy in diffusion tensorfiber orientation mapping of excised myocardial samples. Results show that the performances of all REI schemes, at approximately 50% reduced encoding, are at least comparable with that of a control experiment consisting of proportionally reduced number of full k-space images. Moreover, although performances of the symmetrically and asymmetrically encoded RIGR schemes are similar, both methods provide significant improvements over the control experiment and the direct-substitution keyhole technique. These findings demonstrate the potential of the general REI methodology for diffusion tensor imaging and pave the way for modified schemes involving rapid imaging sequences or alternative k-space sampling strategies to achieve even better data acquisition time efficiency and performance.

Analysis of Variance↗

Expression and alternative processing of a chicken gene encoding both growth hormone-releasing hormone and pituitary adenylate cyclase-activating polypeptide.

The chicken growth hormone-releasing hormone (GRF) gene was isolated, sequenced, and characterized. In addition, three different mRNAs were isolated from juvenile and adult brain. The first cDNA encoded for a GRF(1-46), the second cDNA encoded for a GRF(1-43) due to a sliding intron boundary, and the third skipped exon four and encoded only GRF(33-46). We also determined that juvenile chicken mRNA encoding GRF is expressed in the brain and gonads, but not in the pituitary, heart, liver, kidney, crop, small intestine, large intestine, eye, and muscle. This gene is also interesting in terms of evolution because another neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), is encoded within the same gene (grf/pacap) in chicken, but on a separate gene (pacap) in mammals. We showed previously that these two neuropeptides were encoded in the same cDNA in fish, but the present evidence in chicken suggests a gene duplication in stem mammals.

Alternative Splicing↗

Brain systems for encoding and retrieval of auditory-verbal memory. An in vivo study in humans.

Long-term auditory-verbal memory comprises, at a neuropsychological level, a number of distinct cognitive processes. In the present study we determined the brain systems engaged during encoding (experiment 1) and retrieval (experiment 2) of episodic auditory-verbal material. In the separate experiments, PET measurements of regional cerebral blood flow (rCBF), an index of neural activity, were performed in normal volunteers during either the encoding or the retrieval of paired word associates. In experiment 1, a dual task interference paradigm was used to isolate areas involved in episodic encoding from those which would be concurrently activated by other cognitive processes associated with the presentation of paired associates, notably priming. In experiment 2, we used the cued retrieval of paired associates from episodic or from semantic memory in order to isolate the neural correlates of episodic memories. Encoding of episodic memory was associated with activation of the left prefrontal cortex and the retrosplenial area of the cingulate cortex, while retrieval from episodic memory was associated with activation of the precuneus bilaterally and of the right prefrontal cortex. These results are compatible with the patterns of activation reported in a previous PET memory experiment in which encoding and retrieval were studied concurrently. They also indicate that separate brain systems are engaged during the encoding and retrieval phases of episodic auditory-verbal memory. Retrieval from episodic memory engages a different, but overlapping, system to that engaged by retrieval from semantic memory, a finding that lends functional anatomical support to this neuropsychological distinction.

Adult↗

The functional roles of prefrontal cortex in episodic memory. I. Encoding.

Functional neuroimaging studies of episodic memory consistently report an association between memory encoding operations and left prefrontal cortex (PFC) activation. Encoding-related activation has been described in dorsolateral, ventrolateral and anterior prefrontal regions. We tested the hypothesis that a specific component of this left PFC activation reflects organizational processes necessary for optimal memory encoding. Subjects underwent PET scans while learning auditorily presented word lists under dual task conditions. The degree to which they were required to organize word lists semantically was systematically varied across three experimental conditions. A task in which words were already organized produced the least degree of left PFC activity whereas a task requiring subjects to generate an organizational structure was associated with maximal activity in this region. This activation was localized to a region just above the inferior frontal sulcus. The functional specificity of this increased activity for organizational processes was tested using a concurrent distracting task known to disrupt these processes. Distraction resulted in a significant attenuation of this activation during the task emphasizing organizational processes but not other encoding tasks. In contrast, the distraction task resulted in reduced activity in a more ventral/anterior PFC region expressed equally for all memory tasks. The findings indicate that a key function of left dorsolateral PFC at encoding relates specifically to the use of executive processes necessary for the creation of an organizational structure. Activity in more ventral and anterior left PFC regions would appear to reflect a less specific component of episodic memory encoding.

Adult↗

Mood states modulate activity in semantic brain areas during emotional word encoding.

It is controversially discussed whether or not mood-congruent recall (i.e., superior recall for mood-congruent material) reflects memory encoding processes or reduces to processes during retrieval. We therefore investigated the neurophysiological correlates of mood-dependent memory during emotional word encoding. Event-related potentials (ERPs) were recorded while participants in good or bad mood states encoded words of positive and negative valence. Words were either complete or had to be generated from fragments. Participants had to memorize words for subsequent recall. Mood-congruent recall tended to be largest in good mood for generated words. Starting at 200 ms, mood-congruent ERP effects of word valence were obtained in good, but not in bad mood. Only for good mood, source analysis revealed valence-related activity in ventral temporal cortex and for generated words also in prefrontal cortex. These areas are known to be involved in semantic processing. Our findings are consistent with the view that mood-congruent recall depends on the activation of mood-congruent semantic knowledge during encoding. Incoming stimuli are more readily transformed according to stored knowledge structures in good mood particularly during generative encoding tasks. The present results therefore show that mood-congruent memory originates already during encoding and cannot be reduced to strategic processes during retrieval.

Adult↗

Recollection and the reinstatement of encoding-related cortical activity.

The neural correlates of episodic memory retrieval ("recollection") differ according to the type of information contained in the recollected episode. Such content-specific recollection effects have been hypothesized to reflect the reinstatement of processes or representations active during encoding. Using event-related functional magnetic resonance imaging, we evaluated this hypothesis by directly contrasting the neural activity elicited during the encoding and subsequent recollection of words studied with one of 2 encoding tasks. Study words appearing on pictures of scenes required imagining the word's referent at any location within the scene, whereas words appearing on a blank background required generating a sentence that incorporated the word. On a later memory test, the neural correlates of recollection were operationalized by contrasting the activity elicited during correct "remember" versus "know" responses. Recollected words from the "scene" task elicited activity in regions of left occipital cortex and anterior fusiform gyrus that overlapped regions where encoding-related activity was greater for the scene than sentence task. Conversely, activity elicited by words recollected from the "sentence" task overlapped with a region of ventromedial frontal cortex where encoding-related activity was greater for the sentence task. These content-specific associations between encoding- and recollection-related neural activity strongly support the reinstatement hypothesis of episodic retrieval.

Adolescent↗

A sea urchin gene encoding dystrophin-related proteins.

The gene which is defective in Duchenne muscular dystrophy (DMD) is the largest known gene. The product of the gene in muscle, dystrophin, is a 427 kDa protein. The same gene encodes at least six additional products: two non-muscle dystrophin isoforms transcribed from promoters located in the 5'-end region of the gene and four smaller proteins transcribed from internal promoters located further downstream. Several other genes, encoding evolutionarily related proteins, have been identified. These include a structurally very similar gene in vertebrates encoding utrophin (DRP1), which is closely related to dystrophin, and a number of small and simple genes in vertebrates or invertebrates encoding proteins similar to some of the small products of the DMD gene. We have isolated a sea urchin gene showing very strong sequence and structural homology with the DMD and utrophin genes. Sequence and intron/exon structure similarities suggest that this gene is related to a precursor of both the DMD gene and the gene encoding utrophin. The sea urchin gene has the unique complex structure of the DMD gene. There is at least one, and possibly more, product(s) transcribed from internal promoters, as well as a large product of >300 kDa containing at least three of the four major domains of dystrophin. The small product seems to be evolutionarily related to Dp116, one of the small products of the human DMD gene. Partial characterization of this gene helped us to construct an evolutionary tree connecting the vertebrate dystrophin gene family with related genes in invertebrates. The constructed evolutionary tree also implies that the vertebrate small and simple structured gene encoding a Dp71-like protein, called DRP2 , evolved from the dystrophin/utrophin ancestral large and complex gene by a duplication of only a small part of the gene.

Amino Acid Sequence↗

Identification of 17 Pseudomonas aeruginosa sRNAs and prediction of sRNA-encoding genes in 10 diverse pathogens using the bioinformatic tool sRNAPredict2.

sRNAs are small, non-coding RNA species that control numerous cellular processes. Although it is widely accepted that sRNAs are encoded by most if not all bacteria, genome-wide annotations for sRNA-encoding genes have been conducted in only a few of the nearly 300 bacterial species sequenced to date. To facilitate the efficient annotation of bacterial genomes for sRNA-encoding genes, we developed a program, sRNAPredict2, that identifies putative sRNAs by searching for co-localization of genetic features commonly associated with sRNA-encoding genes. Using sRNAPredict2, we conducted genome-wide annotations for putative sRNA-encoding genes in the intergenic regions of 11 diverse pathogens. In total, 2759 previously unannotated candidate sRNA loci were predicted. There was considerable range in the number of sRNAs predicted in the different pathogens analyzed, raising the possibility that there are species-specific differences in the reliance on sRNA-mediated regulation. Of 34 previously unannotated sRNAs predicted in the opportunistic pathogen Pseudomonas aeruginosa, 31 were experimentally tested and 17 were found to encode sRNA transcripts. Our findings suggest that numerous genes have been missed in the current annotations of bacterial genomes and that, by using improved bioinformatic approaches and tools, much remains to be discovered in 'intergenic' sequences.

Computational Biology↗

Molecular evolution of the Paramyxoviridae and Rhabdoviridae multiple-protein-encoding P gene.

Presented here is an analysis of the molecular evolutionary dynamics of the P gene among 76 representative sequences of the Paramyxoviridae and Rhabdoviridae RNA virus families. In a number of Paramyxoviridae taxa, as well as in vesicular stomatitis viruses of the Rhabdoviridae, the P gene encodes multiple proteins from a single genomic RNA sequence. These products include the phosphoprotein (P), as well as the C and V proteins. The complexity of the P gene makes it an intriguing locus to study from an evolutionary perspective. Amino acid sequence alignments of the proteins encoded at the P and N loci were used in independent phylogenetic reconstructions of the Paramyxoviridae and Rhabdoviridae families. P-gene-coding capacities were mapped onto the Paramyxoviridae phylogeny, and the most parsimonious path of multiple-coding-capacity evolution was determined. Levels of amino acid variation for Paramyxoviridae and Rhabdoviridae P-gene-encoded products were also analyzed. Proteins encoded in overlapping reading frames from the same nucleotides have different levels of amino acid variation. The nucleotide architecture that underlies the amino acid variation was determined in order to evaluate the role of selection in the evolution of the P gene overlapping reading frames. In every case, the evolution of one of the proteins encoded in the overlapping reading frames has been constrained by negative selection while the other has evolved more rapidly. The integrity of the overlapping reading frame that represents a derived state is generally maintained at the expense of the ancestral reading frame encoded by the same nucleotides. The evolution of such multicoding sequences is likely a response by RNA viruses to selective pressure to maximize genomic information content while maintaining small genome size. The ability to evolve such a complex genomic strategy is intimately related to the dynamics of the viral quasispecies, which allow enhanced exploration of the adaptive landscape.

Evolution, Molecular↗

Encoding, memory, and thought disorder in schizophrenia and mania.

Schizophrenic (n = 24) and manic (n = 20) inpatients were compared with a normal comparison sample (n = 10) on memory and encoding performance for both self- and other-generated speech. It was found that the level of encoding, as indexed by the level of organization present in the recalled speech, predicted memory performance for both schizophrenic and normal samples. Schizophrenics were less effective at encoding than normals, although the relationship between level of encoding and memory performance was similar for both samples. For the manic patients, however, clinically rated thought disorder predicted memory performance better than encoding performance. It appeared that thought disorder specifically disrupted recall performance, with less of an effect on encoding. These relationships, as well as the lack of a significant relationship between thought disorder and task performance in the schizophrenics, are discussed in terms of their implications for later research in the area of information processing in psychotic patients.

Adult↗