Molecular approaches to child psychopathology

Basic research into the genetics of childhood psychiatric disorders has substantially increased during the last two decades. Specific genetic mutations have been characterized in some developmental disorders (e.g., fragile X syndrome and Prader-Willi syndrome), but thus far identification of etiological gene mutations in psychiatric illnesses has been unsuccessful. Several psychiatric disorders serve as examples of the current state of molecular approaches in child psychopathology. Investigations to date of Gilles de la Tourette's syndrome (GTS) have not resulted in the discovery of a gene of major effect. Some studies have implicated the D2 and D4 dopamine receptors as having a direct role in the etiology of GTS, but other studies have disputed those findings. However, the dopamine D2 receptor may modulate the severity of GTS. Obsessive-compulsive disorder has a reported association with a low-activity allele of the enzyme catechol-O-methyltransferase; however, the low-activity genotype is also seen in a significant proportion of unaffected individuals. For reading disability two distinct phenotypes (phonological awareness and single-word reading) have been linked to separate loci on chromosomes 6 and 15. Attention deficit hyperactivity disorder (ADHD) has a reported association with the dopamine transporter. Findings of a genetic locus for the personality trait of novelty seeking remain controversial.     

Molecular approaches to cancer immunotherapy

The use of cytokines and costimulatory molecule gene-engineered tumor cells to enhance tumor immunogenicity and elicit curative responses against established tumors and tumor recurrences has become an attractive prospect. The immunotherapy data obtained in many experimental tumor systems using these engineered cells are reviewed here to provide a realistic assessment of the potential and limits of this technique.     

Molecular approaches to the diagnosis of male infertility

We investigated the effects of aging and/or swimming training on the antioxidant enzyme system in diaphragm of mice. Young (2 months old) and old (26 months old) male mice were swimming-trained for 6 weeks (1 h/day, 5 days/week). Cu,Zn-Superoxide dismutase (Cu,Zn-SOD) activity was significantly upregulated with aging, and swimming training definitely enhanced the activity only in young mice. Neither aging nor swimming training had overt effect on Mn-SOD activity. Glutathione peroxidase activity in young mice was significantly increased after training, but not in old mice. Both of immunoreactive Cu,Zn-SOD and Mn-SOD were significantly increased with aging but were unaffected by swimming training. Consequently, physical training significantly enhanced the specific activity of Cu,Zn-SOD in young mice, but not in old mice. Meanwhile, swimming training significantly increased xanthine oxidase activity in both age groups, the extent of the increase being greater in old mice than in young mice. We concluded that the antioxidant enzyme system in mouse diaphragm trends to be upregulated with aging, but that swimming training improved the system only in young mouse diaphragm.     

Molecular biology of Mycoplasma

Mycoplasmas are the smallest free living microorganisms with the smallest genome. The G+C content is in general low (25-33%) and the coding capacity is about 600 proteins. Mycoplasma species are phylogenetically related, they use the genetic codon UGA for tryptophan, and show rapid evolution, with a high rate of divergence. The genomes of Mycoplasma genitalium and Mycoplasma pneumoniae have been fully sequenced. Striking features of the M. genitalium sequencing project are the presence of a high number of membrane proteins with no resemblance to previously sequenced genes and the presence of repeated fragments of the gene encoding the tip-localized 140 kDa adhesin (MgPa). Many Mycoplasma species display a high frequency of antigenic variation, both as phase and size variation of individual antigens. Mycoplasma hominis isolates are known to be antigenic heterogeneous, as reflected in the reactivity with monoclonal antibodies (MAbs). The genetics of the antigenic variation has been studied for three different surface exposed antigens: P120, Lmp, and P50/Vaa. The gene encoding P120 had a hyper-variable region in the N-terminal region. In addition, a second gene with homology to p120 was identified. The gene encoding Lmp, a 135 kDa protein is repeated and both genes are translated and both contain internal repeated sequences. Deletion mutants in the lmp gene were obtained by cultivation of M. hominis PG21 with MAb 552 specific for the repeated part of Lmp. One of the lmp genes had deletions of from four to eight repeats. The other gene was left unaltered. The genes encoding P50/Vaa show a different form of variability where domains of the genes seem to be exchangeable. The genomic maps of five M. hominis strains showed that even though the size of the genomes varied the position of the different genes were in general conserved.     

Forward and reverse genetic approaches to synaptogenesis

The growing need for information about managed care and for the use of managed care organization (MCO) members in clinical and health services research requires research capability within MCOs. To learn the extent to which such capability exists, we conducted a survey of readily identifiable MCO research programs. Responses were obtained from twenty of twenty-three eligible organizations. Although there is great variability in size, these organizations have a collective budget of $93 million, more than 158 career researchers, and extensive research infrastructure and applied research activities.     

Molecular genetic study in congenital myotonic dystrophy

Congenital myotonic dystrophy (CMD) is the neonatal form of Steinert's myotonia. However, the symptoms and neuro-physiological findings are different from the classical adult form, there is a high mortality and early diagnosis of the condition is difficult. CMD occurs as a result of abnormal expansion of CTG triplets on chromosome 19. There is dominant autosomal transmission of this multi-systemic disorder, although when it occurs in children, it is the mother who is always the affected parent. Molecular genetic techniques enable unequivocal diagnosis of the condition, evaluation of anticipation and the possibility of offering genetic counselling to the families involved.     

Molecular approaches to renal physiology and therapeutics

The relationship of long-term and heavy exposure of nonnarcotic analgesics to the risk of chronic renal disease (CRD) has been the object of intensive clinical, pharmacologic, toxicologic, and epidemiologic research for 4 decades. The clinical evidence of an increased risk has been suggestive but inconclusive. The experimental evidence in animal models has been inconsistent, and in any case it cannot be generalized to humans. The epidemiologic evidence has been unsatisfactory for the most part: most of the early studies had severe methodologic limitations; moreover, they related mainly to phenacetin-containing drugs and did not have useful information on other analgesics. Since 1980, 9 analytical epidemiologic studies have attempted to confirm that a causal relationship exists between phenacetin or other analgesics and CRD. In the aggregate, despite methodologic flaws, this work suggests that excessive use of phenacetin-containing analgesics probably causes renal papillary necrosis and interstitial nephritis. In contrast, there is no convincing epidemiologic evidence that nonphenacetin-containing analgesics (including acetaminophen, aspirin, and mixtures of these two compounds) or that nonsteroidal antiinflammatory drugs cause CRD. Moreover, the nature of dose-response relationships, the types of renal disease possibly caused by analgesics, and the cofactors that might be related both to analgesic use and to the development of CRD in humans are still uncertain, and the pathologic mechanisms of analgesic-induced CRD in humans remain unclear. It may take many years before all the outstanding issues are settled. Until they are, as a matter of good clinical judgment it would be prudent to consider all analgesics as potentially nephrotoxic and, as much as possible, to avoid excessive, protracted use.     

Molecular approaches to measuring microbial marine pollution

BACKGROUND: Selection for body weight provides important animal models for studying mechanisms of growth regulation. This study evaluated growth responses of the gastrointestinal tract (GIT) to long-term selection of mice for high (H line) or low (L line) 8-week body weight as compared with random-bred controls (C line). METHODS: Weights and dimensions of the various parts of the GIT were recorded from 8-month-old mice. For light microscopic stereological analyses, samples were taken from eight equidistant locations covering the whole jejunum/ileum. Vertical sections were used for estimation of fractional volumes of mucosa, submucosa, and muscularis and of villous surface area density and for measurement of villus length. RESULTS: Differences between groups in weights and dimensions of the various parts of the GIT were more pronounced in the proximal than in the distal segments, with greatest values in H, followed by C and L mice. Relative to body weight, intestinal growth was similar in the three lines, except for significantly (P < 0.001) increased relative weights of jejunum/ ileum, caecum, and colon in L mice. The fractional volume of mucosa and villus length decreased, whereas the fractional volumes of submucosa and muscularis increased from the proximal to the distal locations. The absolute volume of mucosa was greatest in H mice, followed by C and L mice. Relative to body weight, the volume of mucosa was significantly (P < 0.01) greater in L mice than in the two other lines. The mean total villous surface area of jejunum/ileum was significantly (P < 0.01) different among the three lines (L line: 144 cm2; C line: 227 cm2; H line: 304 cm2) but proportionate to differences in metabolic body weight. CONCLUSIONS: Selection for body weight affected various parts of the GIT to a different extent. The parameters investigated changed markedly along the small intestine, demonstrating the need for systematic sampling. Vertical section stereology provides unbiased estimates of total villous surface area, which is a parameter of major biological significance.     

Forward and reverse genetic approaches to behavior in the mouse

Modern molecular genetic and genomic approaches are revolutionizing the study of behavior in the mouse. "Reverse genetics" (from gene to phenotype) with targeted gene transfer provides a powerful tool to dissect behavior and has been used successfully to study the effects of null mutations in genes implicated in the regulation of long-term potentiation and spatial learning in mice. In addition, "forward genetics" (from phenotype to gene) with high-efficiency mutagenesis in the mouse can uncover unknown genes and has been used to isolate a behavioral mutant of the circadian system. With the recent availability of high-density genetic maps and physical mapping resources, positional cloning of virtually any mutation is now feasible in the mouse. Together, these approaches permit a molecular analysis of both known and previously unknown genes regulating behavior.     

Biorobotic approaches to the study of motor systems

Biorobotics is a promising new area of research at the interface between biology and robotics. Robots can either be used as physical models of biological systems or be directly inspired by biological studies. A great deal of progress has recently been made in biorobotic studies of locomotion, orientation, and vertebrate arm control.     

Epidemiologic and genetic approaches in the study of gene-environment interaction: an overview of available methods

The purpose of this study was to assess what impacts on organized mosquito control the implementation of an Endangered Species Protection Program for the Houston toad might have in Chambers and Harris counties, Texas. The study was also intended to demonstrate the value of using geographic information system (GIS) techniques and methodologies in making such assessments to those in mosquito control who are unfamiliar with GIS and its applications. Using the GIS, Geographical Analysis Support System (GRASS), databases were developed on the habitats and patterns of mosquito control insecticide usage occurring in Chambers and Harris counties. These databases were then employed by means of various utilities associated with GRASS and computer-supported, rule-based reasoning processes to create maps depicting the amount and locations of toad habitat and the areas treated annually with insecticides by districts in Chambers and Harris counties. This map information was then used via other GRASS utilities to identify and depict zones of overlap or coincidence between toad habitat and areas treated with insecticides for mosquito control in the 2 counties. As compared to existing maps for toad habitat, our resulting GIS-generated maps gave more precise, easy-to-use information that could be used to make decisions as to how to protect the toad in the zones of coincidence in each county without causing undue disruption to mosquito control activities in these zones.     

The study of persistence.

An analysis of basic approaches to the study of persistence indicates that trait oriented studies have difficulty in accounting for variation among situations. Conceptualizations of persistence as resistance to extinction have difficulty in accounting for individual differences. A more fruitful approach is to consider persistence as a motivational phenomenon, "where the theory of motivation considers interaction of both personality characteristics and situationally determined influences." (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Molecular study of persistence of Nocardia asteroides and Nocardia otitidiscaviarum strains in patients with long-term nocardiosis

Three Nocardia asteroides and five Nocardia otitidiscaviarum isolates recovered from three patients with long-term nocardiosis were compared by random amplification of polymorphic DNA fingerprinting, antibiotic susceptibility testing, and enzymatic characterization. Results obtained with primer DKU49 (P. Palittapongarnpim, S. Chomyc, A. Fanning, and D. Kunimoto, J. Infect. Dis. 167:975-978, 1993) provide evidence that patient A was infected by two N. asteroides strains during a single episode of nocardiosis and that patients B and C remained infected by the same strain, respectively. Resistance to minocycline that was present in the first isolate recovered from patient B reverted to intermediate resistance in the second isolate and reverted to susceptibility in the third isolate. Resistance to penicillin G and beta-lactams was acquired by the second isolate obtained from patient C.