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Active protection by bacteriophages T3 and T7 against E. coli B- and K-specific restriction of their DNA.

The bacteriophages T3 and T7 are not modified and restricted by E. coli strains with different host specificity (E. coli B, K, O) in vivo. The phages code for a gene product with the ability to overcome classical restriction (ocr): ocr- mutants are subject to modification and restriction via DNA methylation vs cleavage. The T3 genome possesses recognition sites for the restriction endonuclease R.EcoB which, unless the DNA is B-specifically modified, trigger 5-7 DNA cleavages. The ocr gene function of T3 and T7 is located within the gene 0.3 region of these phages and is not identical with the sam (SAMase) function of T3. The mechanism of ocr protection remains unclear, while it is certain that this protection by the gene 0.3 protein is exerted in the infected cell and not through "over-all" modification in the preceding growth cycle of the phage.

Adenosylmethionine Decarboxylase↗

Deoxynucleotide sequence of an insect cDNA codes for an unreported member of the Chironomus thummi globin family.

Synthetic oligonucleotides served as probes to isolate insect globin clones from a Chironomus thummi cDNA bank. The cDNA insert of one clone (pC-S9) was completely sequenced by the dideoxy termination procedure. Beginning at the 5' end of the coding region, the 584 base pair sequence encodes most of an N-terminal hydrophobic signal sequence and the complete sequence for a mature secreted globin, and contains a polyadenylation recognition site 3' to an appropriate stop codon. The inferred amino acid sequence is that of an unreported variant of hemoglobin VIIB. Based on the number of differences between Hb VIIB chains, the pC-S9 gene has been evolutionarily independent longer than the other (two) members of the globin VIIB subfamily.

Amino Acid Sequence↗

Selective visual interference with right hemisphere performance in verbal recall. A divided field study.

Three experiments were performed in normal subjects to find out whether interhemispheric functional asymmetries in oral recall of meaningless trigrams of consonants, laterally presented through a tachistoscope, were affected by the subsequent presentation and the immediate recall of visual (verbal and geometrical) vs auditory information. It was shown that the visual presentation of after-target information brought about a right hemisphere disadvantage, which did not occur when the additional information was presented auditorily. The results are consistent with the view that, as to visually presented letters, the right hemisphere processing systems run along a physical code.

Adult↗

Monoclonality in human T-cell disorders.

The genes coding for the T-cell antigen receptor have recently been cloned. They have proven to be invaluable tools for the study of the molecular mechanisms governing T-cell recognition of foreign antigens associated with histocompatibility antigens. In addition, they have also provided sensitive means of detecting clonal cell populations and determining cell lineage. In this review we describe the general organisation of these genes, the results of their utilization in the analysis of hematological pathologies, and discuss the possible implications of the involvement of these genes in translocations observed in certain T-cell malignancies.

Humans↗

Adaptive norm-based coding of facial identity.

Identification of a face is facilitated by adapting to its computationally opposite identity, suggesting that the average face functions as a norm for coding identity [Leopold, D. A., O'Toole, A. J., Vetter, T., & Blanz, V. (2001). Prototype-referenced shape encoding revealed by high-level aftereffects. Nature Neuroscience, 4, 89-94; Leopold, D. A., Rhodes, G., Müller, K. -M., & Jeffery, L. (2005). The dynamics of visual adaptation to faces. Proceedings of the Royal Society of London, Series B, 272, 897-904]. Crucially, this interpretation requires that the aftereffect is selective for the opposite identity, but this has not been convincingly demonstrated. We demonstrate such selectivity, observing a larger aftereffect for opposite than non-opposite adapt-test pairs that are matched on perceptual contrast (dissimilarity). Component identities were also harder to detect in morphs of opposite than non-opposite face pairs. We propose an adaptive norm-based coding model of face identity.

Adaptation, Physiological↗

Targeting mRNA to regulate iron and oxygen metabolism.

A family of non-coding sequences in the mRNA (iso-IREs [iron-responsive elements]) regulate synthesis of key proteins in animal iron and oxidative metabolism such as ferritin and mitochondrial aconitase. Differential recognition between iso-IREs and iso-IRPs (iron regulatory proteins) regulates the translation or degradation of the IRE-containing mRNAs. IREs are hairpin loop structures with an internal loop/bulge or bulge that influence the binding of the iso-IRPs. The iso-IRPs have sequence homology to the aconitases and at least one IRP can be converted to an aconitase. Signals that target the iso-IRE/iso-IRP interactions in mRNA include environmental iron, O2, nitric oxide, H2O2, ascorbate, growth factors, and protein kinase C-dependent IRP phosphorylation. Iso-IRE structural specificity suggests a means of pharmacologically targeting mRNA function with chemicals such as Fe-bleomycin and other transition metal complexes that could be extended to other mRNAs with specific structures. With the iso-IRE/iso-IRP system, nature has evolved coordinated combinatorial control of iron and oxygen metabolism that may exemplify control of mRNAs in other metabolic pathways, viral reproduction, and oncogenesis.

Animals↗

A MutS-based protein chip for detection of DNA mutations.

This paper describes a new protein chip method for detection of single-base mismatches and unpaired bases of DNA, using a genetic fusion molecular system Trx-His6-Linker peptide-Strep-tagII-Linker peptide-MutS (THLSLM). The THLSLM coding sequence was constructed by attaching Strep-tag II and mutS gene to pET32a (+) sequentially with insertion of a linker peptide coding sequence before and behind Strep-tagII gene, respectively. THLSLM was expressed in E. coli AD494 (DE3) and purified using Ni(2+)-chelation affinity resin. THLSLM retained both mismatch recognition activity and streptavidin binding affinity. THLSLM was then immobilized on the chip matrix coated with streptavidin through the Strep-tag II-streptavidin binding reaction. The resulting protein chip was used to detect the mismatched and unpaired mutations in the synthesized oligonucleotides, as well as a single-base mutation in rpoB gene from Mycobacterium tuberculosis, with high specificity. The method could potentially serve as a platform to develop the high-throughput technology for screening and analysis of genetic mutations.

Adenosine Triphosphatases↗

The type 1 growth factor receptor family: new ligands and receptors and their role in breast cancer.

The type 1 family of growth factor receptors, which consist of the epidermal growth factor receptor, c-erbB-2, c-erbB-3, and c-erbB-4, are expressed in normal breast ductal epithelial cells and in some breast cancers. Nine genes have now been identified which code for ligands. In some cases the genes are spliced into a series of proteins which differ in structure, but all retain an EGF-like element responsible for receptor recognition. The EGF receptor is expressed in normal breast and in some cancers, but is apparently reduced in expression in other cases. Cancers with EGF receptors appear to represent a greater threat to patients as in most studies they are associated with a shorter time to relapse and overall survival. The c-erbB-2 protein is overexpressed at very high levels in about one fifth of breast cancers and is indicative of poor prognosis. Other cancers may express lesser degrees of overexpression but it is not clear if this is biologically or clinically significant. The c-erbB-3 protein is expressed in normal breast epithelial cells and has been reported to be present at high levels in some cancers but at normal levels or at lower than normal levels in some others. The limited studies to date suggest that when measured on its own c-erbB-3 expression is not predictive. c-erbB-4 is also expressed in normal breast and in some cancers but no studies have yet been performed to address whether it is associated with disease behaviour. In the future it is likely that a greater understanding of the function of this complex family of interacting proteins will assist in gaining the maximum predictive power from measurement of their expression in human breast cancer.

Amino Acid Sequence↗

Silent letters and phonological priming.

Many written English words contain silent letters. Omitting them produces nonwords pronounced identically to the original words, for example, SALM for PSALM and COLUM for COLUMN. We report two naming and two lexical decision experiments in which targets of 4-11 letters followed primes exposed for 100 ms in mask-prime-mask-target sequences. Priming in SALM-psalm and COLUM-column pairs exceeded priming in orthographic control pairs such as ASTA-pasta and COUSI-cousin, pairs in which pronounced letters are omitted to form the primes. SALM and COLUM, however, were less effective primes than PSALM and COLUMN. Results were discussed in terms of the phonological coherence hypothesis, the role of orthographic codes in filtering phonologically activated representations, and graphemes as reading units.

Humans↗

Transfer across delayed discriminations: evidence regarding the nature of prospective working memory.

Pigeons were trained successively either on 2 delayed simple discriminations or on a delayed simple discrimination followed by delayed matching-to-sample. During subsequent transfer tests, the initial stimuli from the 1st task were substituted for those in the 2nd. Performances transferred immediately if both sets of initial stimuli had been associated with the presence versus absence of food on their respective retention tests, and the direction of transfer (positive or negative) depended on whether the substitution involved stimuli with identical or different outcome associates. No transfer was found, however, when the initial stimuli were associated with different patterns of responding but food occurred at the end of every trial. These results are consistent with outcome expectancy mediation but are incompatible with response intention and retrospective coding accounts.

Animals↗

The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein.

The antimicrobial defence of Drosophila relies largely on the challenge-induced synthesis of an array of potent antimicrobial peptides by the fat body. The defence against Gram-positive bacteria and natural fungal infections is mediated by the Toll signalling pathway, whereas defence against Gram-negative bacteria is dependent on the Immune deficiency (IMD) pathway. Loss-of-function mutations in either pathway reduce the resistance to corresponding infections. The link between microbial infections and activation of these two pathways has remained elusive. The Toll pathway is activated by Gram-positive bacteria through a circulating Peptidoglycan recognition protein (PGRP-SA). PGRPs appear to be highly conserved from insects to mammals, and the Drosophila genome contains 13 members. Here we report a mutation in a gene coding for a putative transmembrane protein, PGRP-LC, which reduces survival to Gram-negative sepsis but has no effect on the response to Gram-positive bacteria or natural fungal infections. By genetic epistasis, we demonstrate that PGRP-LC acts upstream of the imd gene. The data on PGRP-SA with respect to the response to Gram-positive infections, together with the present report, indicate that the PGRP family has a principal role in sensing microbial infections in Drosophila.

Animals↗

The area code hypothesis revisited: olfactory receptors and other related transmembrane receptors may function as the last digits in a cell surface code for assembling embryos.

Recent evidence emerging from several laboratories, integrated with new data obtained by searching the genome databases, suggests that the area code hypothesis provides a good heuristic model for explaining the remarkable specificity of cell migration and tissue assembly that occurs throughout embryogenesis. The area code hypothesis proposes that cells assemble organisms, including their brains and nervous systems, with the aid of a molecular-addressing code that functions much like the country, area, regional, and local portions of the telephone dialing system. The complexity of the information required to code cells for the construction of entire organisms is so enormous that we assume that the code must make combinatorial use of members of large multigene families. Such a system would reuse the same receptors as molecular digits in various regions of the embryo, thus greatly reducing the total number of genes required. We present the hypothesis that members of the very large families of olfactory receptors and vomeronasal receptors fulfill the criteria proposed for area code molecules and could serve as the last digits in such a code. We discuss our evidence indicating that receptors of these families are expressed in many parts of developing embryos and suggest that they play a key functional role in cell recognition and targeting not only in the olfactory system but also throughout the brain and numerous other organs as they are assembled.

Animals↗

The complete nucleotide sequence of a common cold virus: human rhinovirus 14.

The complete nucleotide sequence of the single-stranded RNA genome of human rhinovirus 14, one of the causative agents of the common cold, has been determined from cDNA cloned in E. coli. The genome is typical of the picornaviridae family, comprising a 5' non-coding region of 624 nucleotides, a long open reading frame of 6537 nucleotides (90.8% of the genome) and a 3' non-coding region of 47 nucleotides. Comparison of the nucleotide sequence and the predicted amino acid sequence with those of the polioviruses reveals a surprising degree of homology which may allow recognition of regions of antigenic importance and prediction of the virus polyprotein cleavage sites. The results presented here imply a closer genetic relationship between the rhinovirus and enterovirus genera than previously suspected.

Amino Acid Sequence↗

mRNA decay in spinach chloroplasts: psbA mRNA degradation is initiated by endonucleolytic cleavages within the coding region.

The expression of chloroplast genes during leaf development in higher plants is regulated on several levels as transcription, RNA processing and stability, protein stability and turnover. Differential mRNA stability is one major component which contributes to the developmentally controlled accumulation of higher plant chloroplast psbA mRNA, which encodes the D1 protein of photosystem II. To understand the molecular mechanisms of specific mRNA degradation an in vitro mRNA decay system based on lysed chloroplasts from spinach leaves was established. Employing this degradation extract the decay of psbA mRNA was analyzed. Half-life of the psbA mRNA in vitro is dependent on the degradation conditions as the presence of Mg2+, which was found to stabilize the mRNA. Addition of tRNA stabilizes the mRNA and allows the accumulation of distinct degradation intermediates. psbA mRNA derived fragments of the same size were detected in degradation experiments in vitro, in organello and in vivo. 5' ends of the degradation intermediates were identified by primer extension and found to be localized in the 5' part of the coding region. The data indicate a degradation mechanism involving initiation of psbA mRNA decay by specific endonucleolytic cleavage and subsequent exonucleolytic degradation of the fragments. Possible models for cleavage site recognition are discussed.

Base Sequence↗

Mapping of tissue tropism determinants in coxsackievirus genomes.

Genomic regions responsible for the different tissue tropisms of coxsackievirus A9 (CAV9) and coxsackievirus B3 (CBV3) in newborn mice were investigated using recombinant viruses. Infectious cDNA clones of CAV9, a virus known to infect striated muscle, and CBV3, affecting the central nervous system, pancreas, liver, brown fat and striated muscle, were used to generate chimeric viruses. In situ hybridization analysis of different tissues from mice infected with the recombinant viruses, constructed by exchanging the 5' non-coding region (5'NCR), structural and non-structural genes, demonstrated that the pancreo- and liver tropism map predominantly to CBV3 sequences within the capsid genes, evidently due to receptor recognition. Although the major neurotropism determinant in the CBV3 genome was in the capsid region, viruses containing the CAV9 capsid were also able to initiate infection in the central nervous system provided they contained the CBV3 5'NCR. The presence of the 5'NCR of CAV9 clearly enhanced muscle tissue tropism.

5' Untranslated Regions↗