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PubMed1991

The changing scene of neurotrophic factors.

The purification of brain-derived neurotrophic factor (BDNF), the elucidation of its primary structure, and the subsequent identification of neurotrophin-3 (NT-3) ended the monopoly of NGF as the only well-characterized, target-derived neurotrophic molecule. NGF, BDNF and NT-3 are members of a gene family called neurotrophins. They have strictly conserved domains that determine their basic structure. However, they also have distinctly variable domains that determine their different neuronal specificity mediated by different high affinity receptors, and that share a common low affinity subunit. These similarities and dissimilarities between the members of the neurotrophin gene family are also reflected by their regional distribution, cellular localization and developmental regulation. In this article the neurotrophins are compared with ciliary neurotrophic factor (CNTF), which is a representative of the category of neurotrophic molecules that, according to their regional distribution, developmental expression and cellular localization, do not fulfil the criteria of a target-derived neurotrophic molecule. The physiological and pathophysiological functions of neurotrophins and CNTF are discussed in the context of their potential use for the treatment of traumatic and degenerative diseases of the peripheral and central nervous systems.

Animals↗

PubMed1996

Variation in diagnoses: influence of specialists' training on selecting and ranking relevant information in geriatric case vignettes.

Variation in aspects of medical practice such as diagnosis, has been studied at different levels of aggregation. At the inter-practitioner aggregation level, attention is increasingly being paid to factors explaining medical variation which are attributed to 'professional uncertainty'. The concept of 'professional uncertainty' refers to variability that is considered to be inherent to the nature and structure of medical knowledge which depend on the epistemological characteristics of medical science. In this study the relationship between specialty training and variation in diagnostic practice was examined at the inter-practitioner aggregation level. Determination of a direct relationship would support the thesis that specialization is a structuring factor in the inherent variability of medical practice. Three groups of medical specialists participated in the study: geriatricians, geriatric-psychiatrists and internists. Four case scenarios were submitted to the specialists. The cases used involved elderly patients presenting with problems in domains common to all the participating specialists. For each case the specialists were requested to select those facts they considered important for reaching diagnoses and to rank these facts in order of perceived salience. Subsequently they were asked to provide (tentative) diagnoses, ranked in order of perceived significance. The occurrence of variability in diagnostic practice due to 'professional uncertainty' and the influence of specialist specific factors and shared knowledge, respectively, are demonstrated. The results clearly show that these three groups of specialists focused on different elements of information, and formulated different diagnoses in the same case, but expressed similar ranking patterns.

Aged↗

PubMed2004

A study for minisatellitic markers of Conidiobolus coronatus' pathogenicity to Galleria mellonella larvae.

A selected panel of 13 colonies of entomopathogenic fungus Conidiobolus coronatus representing 6 variants of pathogenicity to Galleria mellonella larvae (ranged from 100 to 10% of efficiency), derived from single spores, were tested for the presence of hypervariable loci in their genomes by hybridization with Jeffreys' human minisatellite probe 33.6. The probe produced informative fingerprints and revealed slight differences among colonies analyzed. Up to 20 variable bands per colony were recognized in the size range of 2-20 kb. The band sharing within groups with the same pathogenicity ranged from 0.966 to 0.800. The genetic distance between different variants ranged from 0.026 to 0.282. A few characteristic bands for high and low pathogenicity to the larvae were found.

Animals↗

PubMed1996

Porcine reproductive and respiratory syndrome (PRRS): a review, with emphasis on pathological, virological and diagnostic aspects.

Despite early attempts to control the spread of the disease, porcine reproductive and respiratory syndrome (PRRS) has now become endemic in many countries including Britain. The occurrence of subclinical herd infections, the prolonged circulation of virus within herds and probable aerogenic virus spread all mitigated against the success of control measures. The origin of the disease is unknown but the causative agent has been shown to be an arterivirus with shared features to lactate dehydrogenase virus of mice. There is evidence of extreme genetic and antigenic variability between American and European isolates. PRRS virus has a predilection for alveolar macrophages and does not grow in most cell lines. In infected pigs, viraemia can persist for many weeks in the face of circulating antibodies and little is known about the mechanisms by which immunity to infection develops. A wide spectrum of disease has been reported from the field, accompanied in some cases by heavy economic losses. Reproductive and perinatal losses were most prominent when the disease first appeared. In the endemic phase, PRRS may be more significant as a contributory factor to a post-weaning respiratory syndrome of young pigs of 3-8 weeks. On-farm techniques have been developed to reduce the recycling of PRRS virus from older infected nursery pigs to the younger newly weaned pig. Vaccines are now marketed for the control of PRRS, but are not licensed for use in Britain. Improvements in knowledge of virion composition and antigenic stability and in the nature of the immune response of the pig should result in genetically engineered subunit vaccines becoming available. Diagnosis of PRRS is still difficult as many animals do not show clinical signs and may only be detected by serology and often only when other respiratory diseases are being investigated. Now that the infection is widespread, serological testing must be properly targeted and interpreted to give meaningful results about virus circulation. An increasing arsenal of diagnostic methods are becoming available to detect virus in both fresh and fixed specimens. The pathogenic mechanisms of PRRS remain poorly defined and more work is needed to reveal the nature of the interaction between PRRS virus and other factors in disease.

Animals↗

PubMed2001

Molecular cloning of cDNA encoding thyroid stimulating hormone beta subunit of bighead carp Aristichthys nobilis and regulation of its gene expression.

The complementary DNA (cDNA) encoding pituitary thyroid stimulating hormone beta subunit (TSH-beta) of bighead carp was cloned and regulation of its gene expression was investigated for understanding phylogenetic divergence and evolution of TSH molecule. The cDNA was obtained from bighead carp pituitary total RNA by reverse transcription and polymerase chain reaction. Oligonucleotide primers were designed from the sequence of common carp. The full length sequence was then obtained by 3' and 5' rapid amplification of cDNA ends (RACE). The full-length sequence consisting of 3' and 5' untranslated regions was 585 bp long. The predicted amino acid sequence consisted of a signal peptide of 19 amino acid residues and a mature TSH beta subunit protein of 131 residues. The coding sequences of the cDNAs showed variable percentage homologies with those of other teleosts and vertebrate species. The predicted amino acid sequence shared 71% identity with rainbow trout and salmon, 90% with goldfish, 50% with eel and 94% with common carp in the mature protein region. The percentages of identity in the same region in comparison with bovine, porcine, rat, mouse, human and chicken were only 39, 42, 41, 40, 45 and 46%, respectively. TSH beta mRNA expression was found only in the pituitary tissue out of other tissues tested as testis, muscle, brain and heart. For the first time, thyrotropin releasing hormone (TRH) and thyroxine (T4) effects on pituitary TSH mRNA expression were tested in teleosts under in vitro conditions. TRH treatment on pituitary cells increased TSH beta mRNA level, while T4 treatment decreased TSH beta mRNA level. The present study provides a direct evidence, for the first time that TRH directly upregulates TSH beta gene expression in teleosts.

Amino Acid Sequence↗

PubMed2002

Polymerase chain reaction amplification of DNA from aged blood stains: quantitative evaluation of the "suitability for purpose" of four filter papers as archival media.

In collaboration with the Armed Forces Institute of Pathology's Department of Defense DNA Registry, the National Institute of Standards and Technology recently evaluated the performance of a short tandem repeat multiplex with dried whole blood stains on four different commercially available identification card matrixes. DNA from 70 stains that had been stored for 19 months at ambient temperature was extracted or directly amplified and then processed using routine methods. All four storage media provided fully typeable (qualitatively identical) samples. After standardization, the average among-locus fluorescence intensity (electropherographic peak height or area) provided a suitable metric for quantitative analysis of the relative amounts of amplifiable DNA in an archived sample. The amounts of DNA in Chelex extracts from stains on two untreated high-purity cotton linter pulp papers and a paper treated with a DNA-binding coating were essentially identical. Average intensities for the aqueous extracts from a paper treated with a DNA-releasing coating were somewhat lower but also somewhat less variable than for the Chelex extracts. Average intensities of directly amplified punches of the DNA-binding paper were much larger but somewhat more variable than the Chelex extracts. Approximately 25% of the observed variation among the intensity measurements is shared among the four media and thus can be attributed to intrinsic variation in white blood count among the donors. All of the evaluated media adequately "bank" forensically useful DNA in well-dried whole blood stains for at least 19 months at ambient temperature.

Blood Stains↗

PubMed2006

Low self-esteem during adolescence predicts poor health, criminal behavior, and limited economic prospects during adulthood.

Using prospective data from the Dunedin Multidisciplinary Health and Development Study birth cohort, the authors found that adolescents with low self-esteem had poorer mental and physical health, worse economic prospects, and higher levels of criminal behavior during adulthood, compared with adolescents with high self-esteem. The long-term consequences of self-esteem could not be explained by adolescent depression, gender, or socioeconomic status. Moreover, the findings held when the outcome variables were assessed using objective measures and informant reports; therefore, the findings cannot be explained by shared method variance in self-report data. The findings suggest that low self-esteem during adolescence predicts negative real-world consequences during adulthood.

Adolescent↗

PubMed2003

Cross-sectional and longitudinal patterns of dedifferentiation in late-life cognitive and sensory function: the effects of age, ability, attrition, and occasion of measurement.

The dedifferentiation hypothesis is examined with respect to age-group differences, ability-group differences, attrition-group differences, and time. Cognitive and sensory data were analyzed from individuals (n = 1,823) who completed a clinical assessment on at least 1 of 3 occasions of measurement in the Australian Longitudinal Study of Ageing. Inconsistent dedifferentiation effects were associated with low ability and early attrition from the study, but age-related dedifferentiation was not found. Longitudinal analyses confirmed the cross-sectional analyses. Even though instances of dedifferentiation were identified between pairs of sensory and cognitive variables, consistent patterns of dedifferentiation were not found. These results do not support the view that shared biological factors become increasingly important for explaining within-individual change in cognitive and sensory function in later life.

Age Factors↗

PubMed2003

Pure class III agents for prevention of sudden cardiac death.

The results of clinical trials in postmyocardial infarction patients using type I antiarrhythmic drugs have been disappointing. There was optimism that IKr blockers might result in a reduction in sudden cardiac death in postinfarct population. Four trials are reviewed here, and the results are variable. The four drugs reviewed--d,l-sotalol, d-sotalol, dofetilide, and azimilide--all share IKr-blocking properties. In addition, d,l-sotalol is a beta-blocker and azimilide is an IKs blocker. The primary uses of d,l-sotalol, dofetilide, and, if approved, azimilide are currently for treatment of atrial fibrillation. Thus, the mortality trials reviewed here are primarily used as support of safety in high-risk patients, because none has achieved a mortality reduction in postinfarction patients. These trials play pivotal roles for regulatory approval of these drugs for use in atrial fibrillation.

Adolescent↗

PubMedDate not supplied

Genetic and environmental influences on intraindividual variability in reaction time.

Reaction time (RT) data from the Minnesota Twin Study of Adult Development and Aging were used to investigate genetic and environmental influences on intraindividual variability in RT. The sample was 738 individuals (aged 27 to 95 years), including 185 monozygotic (MZ) and 131 dizygotic (DZ) twin pairs. Two RT factors were created: decision time and movement time. Age-corrected heritability estimates were 40% for mean RT; 21% for intraindividual variability in movement time; and 0% for intraindividual variability in decision time. Multivariate analysis indicated that all genetic variance in the RT measures was shared among measures; environmental variance was specific to each RT measure.

Adult↗

PubMed2004

dChipSNP: significance curve and clustering of SNP-array-based loss-of-heterozygosity data.

MOTIVATION: Oligonucleotide microarrays allow genotyping of thousands of single-nucleotide polymorphisms (SNPs) in parallel. Recently, this technology has been applied to loss-of-heterozygosity (LOH) analysis of paired normal and tumor samples. However, methods and software for analyzing such data are not fully developed. RESULT: Here, we report automated methods for pooling SNP array replicates to make LOH calls, visualizing SNP and LOH data along chromosomes in the context of genes and cytobands, making statistical inference to identify shared LOH regions, clustering samples based on LOH profiles and correlating the clustering results to clinical variables. Application of these methods to prostate and breast cancer datasets generates biologically important results. AVAILABILITY: The software module dChipSNP implementing these methods is available at http://biosun1.harvard.edu/complab/dchip/snp/ SUPPLEMENTARY INFORMATION: The breast cancer data are provided by Andrea L. Richardson, Zhigang C. Wang and James D. Iglehart.

Algorithms↗

PubMed1997

A multinational study of the factorial structure and other characteristics of the Dartmouth COOP Functional Health Assessment Charts/WONCA.

BACKGROUND: The 'Dartmouth COOP Functional Health Assessment Charts/WONCA' constitute a relatively new derived instrument for assessing health status that is specifically intended for use in primary care on a world-wide basis. It needs further validation in its special area of use. OBJECTIVES: Over a range of countries, social backgrounds and case mixes, our aim was (i) to examine the factorial structure of the instrument; (ii) to explore how well it was understood; (iii) to check its acceptability; and (iv) to assess the value of the pictures on the charts. METHODS: The charts themselves, accompanied by a short questionnaire about the charts, were administered to 1719 patients at eight varied types of treatment centre in Canada, Japan, Nepal and Spain. The responses to the instrument were subjected to standard factor analysis and a special Q-type principal components analysis. The responses to direct questions about the charts were compared with the answers to open-ended questions. RESULTS: Factor analysis suggested a shared factorial pattern for all sites, with the first two factors accounting for 88.5% of the variability in correlations between the charts across the sites. The individual questions were understood by most patients, but a substantial minority did not appear to grasp the underlying purpose of the instrument. The instrument was well accepted. The pictures were considered to be helpful by most respondents, especially those at the Nepal sites. The variability in the scores for the individual charts across sites was less than expected and not always in the expected direction. CONCLUSIONS: The COOP/WONCA system continues to show promise, but needs more validation.

Canada↗

PubMed1985

Molecular epidemiology of plasmid-mediated ampicillin resistance in Haemophilus influenzae type b isolates from Alaska.

Native Alaskans have a high incidence of disease caused by invasive Haemophilus influenzae type b and represent an isolated population for epidemiological study. We used plasmid DNA analysis and subtyping of outer membrane proteins as markers to characterize 29 ampicillin-resistant, invasive strains and seven ampicillin-resistant, noninvasive strains of this organism from distinct geographic regions. All 36 strains produced beta-lactamase; 34 strains transferred resistance by conjugation. Seven of the 36 strains harbored detectable plasmid DNA: four had a molecular mass of 40 MDa, and three had a molecular mass of 3 MDa. Furthermore, 20 transconjugants had a similar large plasmid, and four had a similar small plasmid. Ten of 12 transconjugants with either the large, small, or undetectable plasmid DNA were able to retransfer resistance. Transformation of resistance was successful with two large plasmids. DNA-DNA hybridization studies revealed that 33 of 36 strains had DNA homology. Restriction endonuclease digestion of 10 large plasmids revealed five patterns; identity was evident within a geographic region, and similarity existed between regions. Seven restricted plasmids demonstrated an identical pattern with a small beta-lactamase probe. Ampicillin resistance in these isolates from Alaska is primarily due to a common, 40-MDa conjugative plasmid that mediates beta-lactamase production, a finding which differs from that for ampicillin-resistant plasmids isolated elsewhere in the United States. Despite variable outer membrane protein profiles of the distinct strains of H. influenzae type b, the plasmids shared significant DNA homology. It appears that a common genetic element was responsible for the dissemination of this phenotype for resistance in Alaska.

Alaska↗

PubMedDate not supplied

Evaluation of genetic variation within and between different chicken lines by DNA fingerprinting.

A DNA fingerprinting technique was used to assess the extent of genetic variation within and between 12 lines of chickens of different origin. DNA fingerprints were obtained with the restriction endonucleases AluI and HinfI and with the oligonucleotide probes (CA)8, (CAC)5, (GGAT)4, and (GACA)4. Different methods that are based on band sharing and band frequency were tested to estimate genetic variation within and between populations. The genetic variability was significantly different within the populations. It was highest in a commercial broiler line and lowest in a White Leghorn inbred line. All three measures of genetic variation within populations provided results that were highly correlated (r = 0.89-0.97). A lower degree of correspondence was observed for the estimation of genetic variation between populations by three different methods. This is shown by differences of the phylogenetic trees and by coefficients of correlation between these measures ranging from r = 0.51-0.96.

Animals↗

PubMed1989

Predictive motifs derived from cytosine methyltransferases.

Thirteen bacterial DNA methyltransferases that catalyze the formation of 5-methylcytosine within specific DNA sequences possess related structures. Similar building blocks (motifs), containing invariant positions, can be found in the same order in all thirteen sequences. Five of these blocks are highly conserved while a further five contain weaker similarities. One block, which has the most invariant residues, contains the proline-cysteine dipeptide of the proposed catalytic site. A region in the second half of each sequence is unusually variable both in length and sequence composition. Those methyltransferases that exhibit significant homology in this region share common specificity in DNA recognition. The five highly conserved motifs can be used to discriminate the known 5-methylcytosine forming methyltransferases from all other methyltransferases of known sequence, and from all other identified proteins in the PIR, GenBank and EMBL databases. These five motifs occur in a mammalian methyltransferase responsible for the formation of 5-methylcytosine within CG dinucleotides. By searching the unidentified open reading frames present in the GenBank and EMBL databases, two potential 5-methylcytosine forming methyltransferases have been found.

Amino Acid Sequence↗

PubMed1996

Molecular phylogeny of symbiotic dinoflagellates from planktonic foraminifera and radiolaria.

Recent analyses of the small subunit ribosomal DNA (srDNA) from dinoflagellate symbionts of cnidaria have confirmed historical descriptions of a diverse but well-defined clade, Symbiodinium, as well as several other independent symbiont lineages (Rowan 1991; Rowan and Powers 1992; Sadler et al. 1992; McNally et al 1994). Dinoflagellates also occur as intracellular symbionts in a number of pelagic protistan taxa, but the srDNA of these symbionts has not been examined. We analyzed the srDNA sequences of the symbiotic dinoflagellates from four planktonic foraminiferal species and six radiolarian species. The symbionts from these sarcodines formed two distinct lineages within the dinoflagellates. Within each lineage, symbionts obtained from different host species showed few, if any, srDNA sequence differences. The planktonic foraminiferal symbionts were most closely related to Gymnodinium simplex and the Symbiodinium clade, whereas the radiolarian symbionts were most closely related to the dinoflagellate symbiont from the oceanic chondrophore, Velella velella. Therefore, although the dinoflagellate symbionts of foraminifera appear to be a sister taxon of the symbionts from benthic foraminifera and invertebrates, the symbionts of radiolaria are distinct and arose from an independent lineage of dinoflagellate symbionts that shares common ancestry with the symbiont of at least one pelagic metazoan. The lack of srDNA variability within the sarcodine symbiont lineages suggests that coevolution of host and symbiont has not occurred.

Animals↗

PubMed1997

The ability to form intrastrand tetraplexes is an evolutionarily conserved feature of the 3' end of L1 retrotransposons.

Mammalian genomes contain many thousands of members of a family of retrotransponsons known as L1 (or LINE-1) elements. These elements lack long terminal repeats (LTRs), and are thought to use a retroposition mechanism than differs from that of retroviruses and other LTR-containing retroelements. In order to define those regions of the L1 element that may be important for L1 retroposition, we examined the 3' untranslated regions (UTRs) of L1 elements from a diverse group of mammals. We show that while the 3' UTRs of L1 elements from different species share little if any sequence homology, they all contain a G-rich polypurine tract of variable length and sequence which can form one or more intrastrand tetraplexes. This conservation over the 100 Myr since the mammalian radiation suggests that either the G-rich motif itself or a conserved structure such as the tetraplex that can be formed by this motif is a significant structural feature of L1 elements and may play a role in their propagation.

Animals↗

PubMed2000

Beticolins, nonpeptidic, polycyclic molecules produced by the phytopathogenic fungus Cercospora beticola, as a new family of ion channel-forming toxins.

Beticolins are toxins produced by Cercospora beticola, a phytopathogenic fungus responsible for the leaf spot disease of sugar beet. They form a family of 20 nonpeptidic compounds (named B0 to B19) that share the same polycyclic skeleton but differ by isomeric configuration (ortho- or para-) and by a variable residue R (bridging two carbons in one of the six cycles). It has been previously shown that B0 assembles itself into a multimeric structure and forms ion channels into planar lipid bilayers (C. Goudet, A.-A. Very, M.-L. Milat, M. Ildefonse, J.-B. Thibaud, H. Sentenac, and J.-P. Blein, Plant J. 14:359-364, 1998). In the present work, we investigate pore formation by three ortho-beticolins, B0, B2, and B4, and their related (i.e., same R) para-isomers, B13, B1, and B3, respectively, using planar lipid bilayers. All beticolins were able to form ion channels with multiple conductance states, although the type of cyclization (ortho- or para-) and residue (R) result in variations of channel conductance and ionic permeability, respectively. Channel formation by beticolins is likely to be involved in the biological activity of these toxins.

Ascomycota↗