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Hemagglutination properties and nucleotide sequence analysis of the fiber gene of adenovirus genome types 11p and 11a.

The fiber has been suggested to serve as the ligand between the adenovirus capsid and the host cell receptor. The two genome types, Ad11p and Ad11a, of adenovirus serotype 11 display different tropisms. The fiber amino acid sequences of the two genome types have been deduced from the 975 nucleotides that encoded a fiber polypeptide of 35,500 Da. The fiber consists of a tail, a shaft, and a knob region. The amino acids 44 to 140 form a typical shaft domain of six 15-residue repetitive motifs. Ten amino acids in the Ad11p fiber shaft were substituted in Ad11a. Five unpolar residues have been replaced by four polar and one unpolar amino acid. In the knob region, a total of 14 amino acid mismatches were noted between Ad11p and Ad11a. The amino acid sequence Asn-Asp-Glu at positions 283 to 285 in Ad11p was changed to Arg-Ala-Asp in Ad11a. The sequence Thr-Leu-Trp-Thr from positions 133 to 136 was conserved in all analyzed human and canine adenoviruses. The polypeptide at positions 235 to 244, Phe-Met-Pro-Ser-Thr-Thr-Ala-Tyr-Pro-Phe, probably contains a subgenus epitope, since it is conserved among subgenus B adenoviruses. Ad11p aggregated rhesus and vervet erythrocytes at 37 degrees, 22 degrees, and at 4 degrees, respectively, whereas Ad11a did not display hemagglutination under the same conditions. The complete fibers of Ad11p and Ad11a share an overall amino acid homology of 92.3%. The homology within the shaft and the knob region was 89.7 and 92.4%, respectively. These variable amino acids should be expected to be responsible for the differences in hemagglutination and tropism examplified by the persistent urinary tract infections caused by Ad11p and the acute respiratory tract infections caused by Ad11a.

Adenovirus E3 Proteins↗

Antagonism of the discriminative effects of ethylketazocine, cyclazocine, and nalorphine in macaques.

dl-Ethylketazocine (EKC, 0.01 mg/kg) and saline were established as discriminative stimuli for food-maintained responding in macaque monkeys. Thirty consecutive presses on a right or left lever were reinforced with food, contingent on whether EKC or saline were administered before the session. For tests of antagonism, naltrexone, or UM 979 [(l)-5,9-alpha-dimethyl-2-(3-furylmethyl)-2'-hydroxy-6,7-benzomorphan] was administered concomitantly with EKC, dl-cyclazocine, or nalorphine. Both antagonists blocked completely the EKC discriminative stimulus. The antagonism of the stimulus and rate-altering effects of EKC was surmountable, with considerable intersubject variability in the magnitude of the EKC dose increase required to overcome the blockade. Cyclazocine and nalorphine, mixed agonist-antagonist opioids that share stimulus properties with EKC, were also susceptible to antagonism. Naltrexone antagonized completely the EKC stimulus effects of nalorphine; naltrexone and UM 979 antagonized completely the EKC stimulus effects of cyclazocine. Naltrexone antagonism of the cyclazocine stimulus was not surmountable, due to a lack of antagonism of the rate-decreasing effects of high cyclazocine doses.

Analgesics, Opioid↗

Impact of litigation on quality of life outcomes in patients with chronic low back pain.

Low back pain progresses to chronic low back pain (CLBP) in 5-10 per cent of patients. A Multi-disciplinary Pain Management Programme was tested in 20 patients (m = 4, f = 16). This regime involved psychological and behaviour modification strategies, combined with intensive exercise. Treatment outcome in terms of impairment was assessed by lumbar flexibility, trunk muscle endurance and pain. The disability assessed was exercise fitness and handicap was assessed using the Sickness Impact Profile (SIP) to define the impact of the condition on the patient's life. Overall the patients showed significant improvement (p < 0.05) in all of the measured variables. Patients with on-going litigation however (n = 11) showed no significant improvement in the SIP quality of life score, although they shared the significant improvements attained by the whole group in the domains of impairment (lumbar flexibility, trunk muscle endurance and pain) and disability (exercise fitness).

Adult↗

Lipomatosis of the sciatic nerve: typical and atypical MRI features.

Lipomatosis of nerve, also known as fibrolipomatous hamartoma, is a rare condition of nerve, usually affecting the median nerve. The MRI appearance is characteristic. We describe two cases of lipomatosis of nerve involving the sciatic nerve, an extremely unusual location for this lesion, in patients with sciatic neuropathy. These cases share the typical features previously described in the literature for other nerves, but also contain atypical features not previously highlighted, relating to the variability in distribution and extent of the fatty deposition. Recognition of the MRI appearance of this entity is important in order to avoid unnecessary attempts at surgical resection of this lesion.

Adult↗

Cloning and characterization of the mouse alpha globin cluster and a new hypervariable marker.

A 95-kb region of the mouse genome spanning the entire alpha-globin gene cluster was isolated as overlapping cosmid clones and characterized. In addition to the embryonic (zeta) and adult (alpha) genes, the cloned contig contains the complete N-methylpurine-DNA glycosylase (MPG) gene, the alpha-globin-positive regulatory element (mHS-26), and a previously unidentified hypervariable region (named the mouse alpha-HVR). In mice, the distance between the MPG gene and mHS-26 is approximately 18 kb; between the mHS-26 and the zeta-gene, approximately 26 kb; from the zeta-gene to the 5' end of the alpha-gene, approximately 16 kb; and the two alpha-genes are separated by approximately 12 kb. In human, the corresponding distances are approximately 27 kb, approximately 40 kb, approximately 19 kb, and approximately 3 kb respectively. The alpha-HVR is located approximately 18 kb upstream of the mouse zeta-globin gene transcription start site and contains a variable copy number tandem repeat (VNTR) array of a 35-bp sequence rich in (G+C) content. The unit sequence of the HVR shares the short core sequence with the HVRs identified in the human alpha-gene cluster. Thus, this HVR may be a valuable evolutionary marker, as well as a useful genetic marker for the mouse.

Animals↗

Behavioral coronary risk indicators and apolipoproteins A-I and B in young Finnish children: cross-sectional and predictive associations.

The association between behavioral and somatic coronary risk indicators was studied in 3-, and 6-, and 9-year-old children (n = 668). The behavioral risk indicators used were the Type A behavior pattern, hyperactivity, social maladjustment, and life dissatisfactions of the mother. The somatic risk indicators adopted were serum concentrations of apolipoproteins B and A-I. The results might indicate that behavioral and somatic coronary risk indicators are not independent, but could share a common basis, or pathways that are related to the pathogenesis of CHD. In addition, a sex-related difference was discovered: variables associated with the high somatic risk level among girls were hyperactivity, social maladjustment, and impatience, and among boys the variables were the mother's dissatisfaction with herself as a mother, leadership, and a tendency for competitiveness-aggression.

Apolipoproteins A↗

Schwannomatosis: multiple schwannomas of the upper limb.

Schwannomas (also known as neurilemmomas) are neoplasms of the peripheral nerve sheaths. They are the most common benign tumour of peripheral nerves, yet they account for only 5% of all soft tissue tumours. Their incidence in the upper limb is variable, as is their clinical presentation. We present an unusual case of multiple schwannomas in the upper limb so that other surgeons can share our experience and suggest the correct diagnosis when confronted with a similar case.

Adult↗

First evidence of transmission of Leishmania (Viannia) lainsoni in a Sub Andean region of Bolivia.

Using ubiquitous primers which amplify the variable parts of kDNA minicircle of all Leishmania spp, we obtained for Leishmania (viannia) lainsoni a major band of 605 bp (band 1) shared with L. V. braziliensis and a minor 524 bp band (band 2) specific of L. V. lainsoni. The specificity of the two bands was examined through Southern blot hybridization of kDNA PCR obtained from reference strains belonging to L. braziliensis, L. mexicana, L. donovani complexes with L. V. lainsoni species. Band 1 was not specific of L. V. lainsoni since it hybridized with some isolates belonging to L. braziliensis complex. In contrast, band 2 was L. V. lainsoni specific. PCR-based detection followed by hybridization with the new L. V. lainsoni probe (Band 2) and L. V. braziliensis probe (564 bp), was assayed using sample from a pool of 25 females of Lutzomiya nuneztovari anglesi, blood, skin and liver samples of 18 mammals, spinal cords of four mammals and blood and cutaneous ulcers aspirates from 95 patents from Sub Andean region of La Paz, Bolivia. We observed a ositive hybridization of four patients lesions and the pool of L. nuneztovari anglesi with the L. V. lainsoni probe. It is the first time that L. V. lainsoni is observed in a cycle of transmission in Bolivia. PCR products of three patients lesions and the pool of L. nuneztovari anglesi were also hybridized with the specific probe of L. V. braziliensis suggesting mixed infection in this focus.

Animals↗

Fibrous histiocytoma of the corneoscleral limbus: The ultrastructure of a distinctive inclusion.

A case of epibulbar fibrous histiocytoma is presented, with emphasis on the electron microscopic aspects due to the paucity of ultrastructural descriptions of this rare tumor. A tan-yellow conjunctival tumor developed at the corneoscleral limbus in a 31-year-old male. The clinical diagnosis was confirmed by routine histopathologic evaluation, which demonstrated a typical matted or storiform cellular pattern. Electron microscopy revealed a mixed cell population, composed primarily of histiocytic and fibroblastic cells. The histiocytic cells contained lysosomes and phagosomes and had interdigitating cell processes. The fibroblastic cells were characterized by prominent rough-surfaced endoplasmic reticulum and variable amounts of lipid within vacuoles, but did not possess lysosomes or phagosomes. Both cells occasionally contained an unusual curvilinear structure, suggesting a shared histogenesis. This distinctive inclusion appeared to be a modification of the rough-surfaced endoplasmic reticulum. The nature and origin of the tumor cells are discussed on the basis of their ultrastructure.

Adult↗

B-50, the growth associated protein-43: modulation of cell morphology and communication in the nervous system.

The growth-associated protein B-50 (GAP-43) is a presynaptic protein. Its expression is largely restricted to the nervous system. B-50 is frequently used as a marker for sprouting, because it is located in growth cones, maximally expressed during nervous system development and re-induced in injured and regenerating neural tissues. The B-50 gene is highly conserved during evolution. The B-50 gene contains two promoters and three exons which specify functional domains of the protein. The first exon encoding the 1-10 sequence, harbors the palmitoylation site for attachment to the axolemma and the minimal domain for interaction with G0 protein. The second exon contains the "GAP module", including the calmodulin binding and the protein kinase C phosphorylation domain which is shared by the family of IQ proteins. Downstream sequences of the second and non-coding sequences in the third exon encode species variability. The third exon also contains a conserved domain for phosphorylation by casein kinase II. Functional interference experiments using antisense oligonucleotides or antibodies, have shown inhibition of neurite outgrowth and neurotransmitter release. Overexpression of B-50 in cells or transgenic mice results in excessive sprouting. The various interactions, specified by the structural domains, are thought to underlie the role of B-50 in synaptic plasticity, participating in membrane extension during neuritogenesis, in neurotransmitter release and long-term potentiation. Apparently, B-50 null-mutant mice do not display gross phenotypic changes of the nervous system, although the B-50 deletion affects neuronal pathfinding and reduces postnatal survival. The experimental evidence suggests that neuronal morphology and communication are critically modulated by, but not absolutely dependent on, (enhanced) B-50 presence.

Animals↗

Management of change in health care organisations and human resource role.

The paper is focused on the analysis of the most relevant factors necessary to manage change in health care organisations. The approach suggested is the Stakeholder one. According to this approach, the hospital's managers seem to be successful if they are able to satisfy people (internal and external stakeholders) that have a stake in the health care institution. The attention of the author is mainly focused on the internal forces that make the health care sector competitive and successful. In order to motivate internal human resources to accept change and to achieve the organisational targets two main methods can be suggested. The former is based on tangible variables and in particular on a fair reward system; the latter is built on intangible elements e.g. communication, negotiation, contracting, and organisational values sharing. Moreover, in order to cope with change it is important to develop the information technology management and to reengineer delivery processes, taking into consideration both the costs and benefits of these kinds of innovations.

Communication↗

Examination of species boundaries in the Acropora cervicornis group (Scleractinia, cnidaria) using nuclear DNA sequence analyses.

Although Acropora is the most species-rich genus of the scleractinian (stony) corals, only three species occur in the Caribbean: A. cervicornis, A. palmata and A. prolifera. Based on overall coral morphology, abundance and distribution patterns, it has been suggested that A. prolifera may be a hybrid between A. cervicornis and A. palmata. The species boundaries among these three morphospecies were examined using DNA sequence analyses of the nuclear Pax-C 46/47 intron and the ribosomal DNA Internal Transcribed Spacer (ITS1 and ITS2) and 5.8S regions. Moderate levels of sequence variability were observed in the ITS and 5.8S sequences (up to 5.2% overall sequence difference), but variability within species was as large as between species and all three species carried similar sequences. Since this is unlikely to represent a shared ancestral polymorphism, the data suggest that introgressive hybridization occurs among the three species. For the Pax-C intron, A. cervicornis and A. palmata had very distinct allele frequencies and A. cervicornis carried a unique allele at a frequency of 0.769 (although sequence differences between alleles were small). All A. prolifera colonies examined were heterozygous for the Pax-C intron, whereas heterozygosity was only 0.286 and 0.333 for A. cervicornis and A. palmata, respectively. These data support the hypothesis that A. prolifera is the product of hybridization between two species that have a different allelic composition for the Pax-C intron, i.e. A. cervicornis and A. palmata. We therefore suggest that A. prolifera is a hybrid between A. cervicornis and A. palmata, which backcrosses with the parental species at low frequency.

Alleles↗

Spawning times, reproductive compatibilities and genetic structuring in the Acropora aspera group: evidence for natural hybridization and semi-permeable species boundaries in corals.

Species boundaries among five sympatric coral species of the Indo-Pacific Acropora aspera group were examined by a combination of in vitro breeding trials, comparisons of spawning times and DNA sequence analysis of ribosomal DNA internal transcribed spacer (rDNA ITS) and 5.8S regions. The breeding trials showed that reproductive compatibility exists between at least some colonies of all the species pairs tested, suggesting a large potential for natural hybridization and introgression. The Acropora ITS regions exhibited extremely high levels of variability (up to approximately 62% for ITS1, approximately 11% for 5.8S and approximately 43% for ITS2), but most of the variation was shared among four of the five species, A. millepora, A. papillare, A. pulchra and A. spathulata, consistent with extensive introgression. Phylogenetic analyses did not resolve these four species as distinct clusters across a wide biogeographic region stretching from the southern Great Barrier Reef to Papua New Guinea. However, most colonies of the fifth species, A. aspera, constituted a distinct clade in phylogenetic analyses. This is consistent with our observations of a semi-permeable temporal barrier involving differences in spawning times between this and the other four species. Although the majority of colonies of all five species generally spawned within 90 min of each other, in two out of four years, gametes were absent prior to mass spawning episodes from at least some A. aspera colonies. Hence, our data suggest that transient reproductive barriers may be the result of year-to-year variation in the date of spawning and that this difference in spawning time contributes to the genetic structure detected among Acropora species in this group. Occasional leakage through the reproductive barrier was confirmed by the observation of A. aspera xA. pulchra F1 hybrids, identified based on additivity of ITS sequences.

Animals↗

Culture as shared cognitive representations.

Culture consists of shared cognitive representations in the minds of individuals. This paper investigates the extent to which English speakers share the "same" semantic structure of English kinship terms. The semantic structure is defined as the arrangement of the terms relative to each other as represented in a metric space in which items judged more similar are placed closer to each other than items judged as less similar. The cognitive representation of the semantic structure, residing in the mind of an individual, is measured by judged similarity tasks involving comparisons among terms. Using six independent measurements, from each of 122 individuals, correspondence analysis represents the data in a common multidimensional spatial representation. Judged by a variety of statistical procedures, the individuals in our sample share virtually identical cognitive representations of the semantic structure of kinship terms. This model of culture accounts for 70-90% of the total variability in these data. We argue that our findings on kinship should generalize to all semantic domains--e.g., animals, emotions, etc. The investigation of semantic domains is important because they may reside in localized functional units in the brain, because they relate to a variety of cognitive processes, and because they have the potential to provide methods for diagnosing individual breakdowns in the structure of cognitive representations typical of such ailments as Alzheimer disease.

Journal Article↗

Private specificities of CD8 T cell responses control patterns of heterologous immunity.

CD8 T cell cross-reactivity between viruses can play roles in protective heterologous immunity and damaging immunopathology. This cross-reactivity is sometimes predictable, such as between lymphocytic choriomeningitis virus (LCMV) and Pichinde virus, where cross-reactive epitopes share six out of eight amino acids. Here, however, we demonstrate more subtle and less predictable cross-reactivity between LCMV and the unrelated vaccinia virus (VV). Epitope-specific T cell receptor usage differed between individual LCMV-infected C57BL/6 mice, even though the mice had similar epitope-specific T cell hierarchies. LCMV-immune mice challenged with VV showed variations, albeit in a distinct hierarchy, in proliferative expansions of and down-regulation of IL-7Ralpha by T cells specific to different LCMV epitopes. T cell responses to a VV-encoded epitope that is cross-reactive with LCMV fluctuated greatly in VV-infected LCMV-immune mice. Adoptive transfers of splenocytes from individual LCMV-immune donors resulted in nearly identical VV-induced responses in each of several recipients, but responses differed depending on the donor. This indicates that the specificities of T cell responses that are not shared between individuals may influence cross-reactivity with other antigens and play roles in heterologous immunity upon encounter with another pathogen. This variability in cross-reactive T cell expansion that is unique to the individual may underlie variation in the pathogenesis of infectious diseases.

Adoptive Transfer↗

The contributions of motor cortex, nigrostriatal dopamine and caudate-putamen to skilled forelimb use in the rat.

Skilled forelimb use was studied in rats with unilateral lesions of the sensorimotor cortex, the caudate-putamen, or the dopaminergic nigrostriatal bundle, in a task involving reaching for food. Limb preference and efficiency were evaluated, as well as the relationship between limb use, spontaneous, and methamphetamine-induced rotation bias, both preoperatively and postoperatively. To induce use of the nonpreferred limb, a bracelet, which prevented reaching but not other movements, was attached to the forearm of the preferred forelimb. Whereas small cortical lesions of the forepaw area of the sensorimotor cortex mildly influenced limb preference and use, larger lesions changed preference. Furthermore, medium-sized sensorimotor cortex lesions impaired contralateral limb use, although surprising recovery occurred on the forced tests with the bracelet. Large cortical lesions abolished effective reaching even on the forced tests. Impairments similar to those following sensorimotor cortex lesions were also obtained following small and large caudate-putamen lesions. By contrast, unilateral dopamine depletions not only blocked use of the limb contralateral to the depletion but also impaired use of the ipsilateral limb. There was recovery in use of the ipsilateral forelimb but not the contralateral forelimb. Correlational analysis showed a weak relation between methamphetamine-induced rotation and limb preference preoperatively but no significant relation between these two variables postoperatively. The similarity in the deficits following sensorimotor cortex lesions and basal ganglia lesions suggests that skilled forelimb use depends upon a shared neural organization within the two systems.

Animals↗

Rapid evolution of the DNA-binding site in LAGLIDADG homing endonucleases.

Sequence analysis of chloroplast and mitochondrial large subunit rRNA genes from over 75 green algae disclosed 28 new group I intron-encoded proteins carrying a single LAGLIDADG motif. These putative homing endonucleases form four subfamilies of homologous enzymes, with the members of each subfamily being encoded by introns sharing the same insertion site. We showed that four divergent endonucleases from the I-CreI subfamily cleave the same DNA substrates. Mapping of the 66 amino acids that are conserved among the members of this subfamily on the 3-dimensional structure of I-CreI bound to its recognition sequence revealed that these residues participate in protein folding, homodimerization, DNA recognition and catalysis. Surprisingly, only seven of the 21 I-CreI amino acids interacting with DNA are conserved, suggesting that I-CreI and its homologs use different subsets of residues to recognize the same DNA sequence. Our sequence comparison of all 45 single-LAGLIDADG proteins identified so far suggests that these proteins share related structures and that there is a weak pressure in each subfamily to maintain identical protein-DNA contacts. The high sequence variability we observed in the DNA-binding site of homologous LAGLIDADG endonucleases provides insight into how these proteins evolve new DNA specificity.

Amino Acid Motifs↗

Covariation of psychosocial characteristics associated with cardiovascular disease: genetic and environmental influences.

OBJECTIVE: Three psychosocial characteristics associated with cardiovascular disease (CVD)-depression, hostility, and social support-tend to correlate with one another. However, the causes of each characteristic and why they tend to co-occur are not completely understood. Therefore, the current study used a twin design to examine the relative contributions of genetic and environmental influences to the variation and covariation of these three psychosocial characteristics. METHODS: The sources of variation and covariation among the Beck Depression Inventory, the Cook-Medley Hostility Scale, and the Interpersonal Support Evaluation List were examined in a young adult community sample of 157 monozygotic and 75 dizygotic twin pairs. RESULTS: Phenotypic confirmatory factor analysis indicated that a single latent factor could account for their moderate intercorrelations. Twin analyses indicated that the Beck Depression Inventory and Interpersonal Support Evaluation List were each influenced by genetic and nonshared environmental factors, whereas the Cook-Medley Hostility Scale was influenced by familial (genetic and/or shared environmental) and nonshared environmental factors. Bivariate associations between these scales were largely determined by common genetic effects and, to a lesser degree, common nonshared environmental effects. Covariation among the three scales could be explained by a single common genetic factor and a common nonshared environmental factor. Environmental factors shared within families did not contribute to covariation among the psychosocial characteristics. CONCLUSIONS: The results challenge the conventional approach of examining these psychosocial variables as independent risk factors for cardiovascular disease and argue for the importance of investigating specific causes for their covariation.

Adult↗