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Biomedical subjects

David A Ross

Publications and source records attributed to David A Ross.

33 records · Page 2Linked to original sources
PubMed2004

A nonmusical paradigm for identifying absolute pitch possessors.

The ability to identify and reproduce sounds of specific frequencies is remarkable and uncommon. The etiology and defining characteristics of this skill, absolute pitch (AP), have been very controversial. One theory suggests that AP requires a specific type of early musical training and that the ability to encode and remember tones depends on these learned musical associations. An alternate theory argues that AP may be strongly dependent on hereditary factors and relatively independent of musical experience. To date, it has been difficult to test these hypotheses because all previous paradigms for identifying AP have required subjects to employ knowledge of musical nomenclature. As such, these tests are insensitive to the possibility of discovering AP in either nonmusicians or musicians of non-Western training. Based on previous literature in pitch memory, a paradigm is presented that is intended to distinguish between AP possessors and nonpossessors independent of the subjects' musical experience. The efficacy of this method is then tested with 20 classically defined AP possessors and 22 nonpossessors. Data from these groups strongly support the validity of the paradigm. The use of a nonmusical paradigm to identify AP may facilitate research into many aspects of this phenomenon.

Adult↗
PubMed2004

Dual roles for the Notch target gene Hes-1 in the differentiation of 3T3-L1 preadipocytes.

The process of adipogenesis involves a complex program of gene expression that includes down-regulation of the gene encoding Hes-1, a target of the Notch signaling pathway. To determine if Notch signaling affects adipogenesis, we exposed 3T3-L1 preadipocytes to the Notch ligand Jagged1 and found that differentiation was significantly reduced. This effect could be mimicked by constitutive expression of Hes-1. The block was associated with a complete loss of C/EBPalpha and peroxisome proliferator-activated receptor gamma (PPARgamma) induction and could be overcome by retroviral expression of either C/EBPalpha or PPARgamma2. Surprisingly, small interfering RNA (siRNA)-mediated reduction of Hes-1 mRNA in 3T3-L1 cells also inhibited differentiation, suggesting an additional, obligatory role for Hes-1 in adipogenesis. This role may be related to our observation that both Notch signaling and Hes-1 down-regulate transcription of the gene encoding DLK/Pref-1, a protein known to inhibit differentiation of 3T3-L1 cells. The results presented in this study establish a new target downstream of the Notch-Hes-1 pathway and suggest a dual role for Hes-1 in adipocyte development.

3T3 Cells↗
PubMed2004

Selecting tagging SNPs for association studies using power calculations from genotype data.

Recent studies have indicated that linkage disequilibrium (LD) between single nucleotide polymorphism (SNP) markers can be used to derive a reduced set of tagging SNPs (tSNPs) for genetic association studies. Previous strategies for identifying tSNPs have focused on LD measures or haplotype diversity, but the statistical power to detect disease-associated variants using tSNPs in genetic studies has not been fully characterized. We propose a new approach of selecting tSNPs based on determining the set of SNPs with the highest power to detect association. Two-locus genotype frequencies are used in the power calculations. To show utility, we applied this power method to a large number of SNPs that had been genotyped in Caucasian samples. We demonstrate that a significant reduction in genotyping efforts can be achieved although the reduction depends on genotypic relative risk, inheritance mode and the prevalence of disease in the human population. The tSNP sets identified by our method are remarkably robust to changes in the disease model when small relative risk and additive mode of inheritance are employed. We have also evaluated the ability of the method to detect unidentified SNPs. Our findings have important implications in applying tSNPs from different data sources in association studies.

Algorithms↗
PubMed2004

All Kids Count 1991-2004: developing information systems to improve child health and the delivery of immunizations and preventive services.

The All Kids Count program began in late 1991 with funding from The Robert Wood Johnson Foundation. The purpose was to improve child health and the delivery of immunizations and preventive services through the development of health information systems. All Kids Count concluded in mid-2004 having worked directly with 38 state and local health agencies through its grant and Connections program. The lessons learned from the 13-year program are applicable to other public health and medical care initiatives. Health information systems projects should: (1) involve stakeholders from the beginning, (2) recognize the complexity of establishing a population-based information system, (3) develop the policy/business/value case for information systems, (4) define the requirements of the system to support users' needs, (5) develop information systems according to current standards, (6) address common problems collaboratively, (7) plan for change, (8) plan boldly but build incrementally, (9) develop a good communications strategy, and (10) use the information (even if not perfect). Opportunities exist for public health agencies to share their experiences from developing immunization registries and integrated child health information systems and to develop collaborative approaches to improving the nation's health information infrastructure.

Child↗
PubMed2004

A vision for child health information systems: developing child health information systems to meet medical care and public health needs.

In both the medical care and public health arenas, a variety of information systems have been developed to serve providers and program managers. In general, these systems have not been designed to share information with other information systems and provide comprehensive information about a child's health status to the information user. A number of initiatives are underway to develop integrated information systems. In December 2003, All Kids Count hosted an invitational conference "Developing Child Health Information Systems to Meet Medical Care and Public Health Needs." Through a series of plenary presentations and breakout discussion groups, participants developed a series of recommendations about governance, economic issues, information infrastructure, and uses of information from integrated child health information systems (CHIS). Common threads in the recommendations were: (1) development of a national coalition of stakeholders to promote integration of separate child health information systems within the context of ongoing national initiatives such as the National Health Information Infrastructure and the Public Health Information Network, (2) the need to develop the business and policy cases for integrated CHIS, (3) the need to develop agreement on standards for collecting and transferring information, and (4) the need to get the word out about the importance of integrating separate CHIS to improve health and health services.

Child↗
PubMed2003

Cortical plasticity in an early blind musician: an fMRl study.

Many studies have examined tactile perception and simple auditory perception in the blind, but none have previously investigated the neural basis of musical ability in this group. This topic is of particular interest because it has been suggested that early blind individuals may possess advanced musical skills (such as absolute pitch). Presumably, these skills could be the result of neural plasticity. It has been hard to empirically assess this claim because of the difficulty in recruiting an adequate number of subjects for use in a conventional paradigm. In the present paper, we report data from a congenitally blind musician, subject ML. Behavioral tests show that she possessed absolute pitch abilities that were similar to those of a reference group of AP musicians with normal vision. To examine the neural basis of her abilities we then tested subject ML and five control subjects using an fMRI paradigm. A regions-of-interest analysis found that similar areas (the right secondary auditory cortex, left IFG, left SMG) were activated in ML and the control subjects, to a similar degree, in response to music processing. However, ML showed additional activations in left parietal association cortices and extrastriate regions of the occipital lobe. Subject ML's data are consistent with a vast body of literature on blindness-induced plasticity. They extend these findings by demonstrating that cortical plasticity may underlie special musical skills as well. These data illustrate the potential value of case studies to investigate particularly rare phenotypes.

Adolescent↗
PubMed2003

Absolute pitch does not depend on early musical training.

The etiology and defining characteristics of absolute pitch (AP) have been controversial. To test the importance of musical training in the development of this skill, we developed a new paradigm for identifying AP that is independent of a subject's musical experience. We confirm the efficacy of the paradigm using classically defined AP and non-AP musicians. We then present data from a nonmusician who nevertheless appears to possess AP. We conclude that musical training is not necessary for the development of AP.

Adult↗
PubMed2002

Oct2 transcription factor of a teleost fish: activation domains and function from an enhancer.

Oct2 transcription factors of the catfish (Ictalurus punctatus) are expressed as alternatively spliced alpha and beta isoforms. Functional analysis revealed an N-terminal glutamine (Q)-rich transactivation domain common to both isoforms of catfish Oct2. A C-terminal proline, serine, threonine (PST)-rich activation domain was identified exclusively in the beta isoform. Activation domains of fish and mammalian Oct2 showed cell type- and species-specific activity correlated with their biochemical composition (Q-rich vs PST-rich). In contrast the activation domains of the aryl hydrocarbon receptor and aryl hydrocarbon receptor nuclear translocator of fish and mammals showed no correlation of activity with biochemical composition or species of origin. Although isolated catfish Oct2 activation domains were unable to drive transcription from a site 1.9kb distal to the promoter, Oct2beta activated transcription from both an IgH enhancer and an array of octamer motifs at this distal position. The properties of catfish Oct2 activation domains differ depending on whether they are studied in isolation or as components of the intact transcription factor.

Alternative Splicing↗
PubMed2002

Genetic, physical, and comparative map of the subtelomeric region of mouse Chromosome 4.

The subtelomeric region of mouse chromosome (Chr) 4 harbors loci with effects on behavior, development, and disease susceptibility. Regions near the telomeres are more difficult to map and characterize than other areas because of the unique features of subtelomeric DNA. As a result of these problems, the available mapping information for this part of mouse Chr 4 was insufficient to pursue candidate gene evaluation. Therefore, we sought to characterize the area in greater detail by creating a comprehensive genetic, physical, and comparative map. We constructed a genetic map that contained 30 markers and covered 13.3 cM; then we created a 1.2-Mb sequence-ready BAC contig, representing a 5.1-cM area, and sequenced a 246-kb mouse BAC from this contig. The resulting sequence, as well as approximately 40 kb of previously deposited genomic sequence, yielded a total of 284 kb of sequence, which contained over 20 putative genes. These putative genes were confirmed by matching ESTs or cDNA in the public databases to the genomic sequence and/or by direct sequencing of cDNA. Comparative genome sequence analysis demonstrated conserved synteny between the mouse and the human genomes (1p36.3). DNA from two strains of mice (C57BL/6ByJ and 129P3/J) was sequenced to detect single nucleotide polymorphisms (SNPs). The frequency of SNPs in this region was more than threefold higher than the genome-wide average for comparable mouse strains (129/Sv and C57BL/6J). The resulting SNP map, in conjunction with the sequence annotation and with physical and genetic maps, provides a detailed description of this gene-rich region. These data will facilitate genetic and comparative mapping studies and identification of a large number of novel candidate genes for the trait loci mapped to this region.

Animals↗
PubMed2002

Recommendations for vitamin A supplementation.

In all populations where vitamin A deficiency is an important public health problem, prophylactic vitamin A supplements should be given to all infants and young children (0-59 mo), pregnant women and postpartum women within 6 wk after delivery. The efficacy of vitamin A supplementation of young children is one of the best-proven, safest and most cost-effective interventions in international public health. The International Vitamin A Consultative Group (IVACG) also recommends that three 50,000-international unit (IU) doses of vitamin A should be given at the same time as infant vaccines during the first 6 mo of life. Recent kinetic studies have indicated that this regimen will be safe and is necessary to maintain the infant's vitamin A stores, even when the mother is also given 400,000 IU within the first 6 wk after delivery. IVACG will make a decision on whether to recommend prophylactic supplementation of all women of childbearing age when the results of two large trials in Ghana and Bangladesh are available. Active corneal xerophthalmia is always a medical emergency that should be treated with immediate high-dose vitamin A. High-dose vitamin A treatment is also recommended for infants and young children with xerophthalmia, severe malnutrition or measles. Low-dose vitamin A treatment is recommended for women with night blindness and/or Bitot's spots. Given the evidence of the cost-effectiveness of vitamin A supplementation, it is essential that effective vitamin A supplementation programs are made universally available to all populations where vitamin A deficiency is an important public health problem.

Adolescent↗
PubMed2001

Positional cloning of the combined hyperlipidemia gene Hyplip1.

Familial combined hyperlipidemia (FCHL, MIM-144250) is a common, multifactorial and heterogeneous dyslipidemia predisposing to premature coronary artery disease and characterized by elevated plasma triglycerides, cholesterol, or both. We identified a mutant mouse strain, HcB-19/Dem (HcB-19), that shares features with FCHL, including hypertriglyceridemia, hypercholesterolemia, elevated plasma apolipoprotein B and increased secretion of triglyceride-rich lipoproteins. The hyperlipidemia results from spontaneous mutation at a locus, Hyplip1, on distal mouse chromosome 3 in a region syntenic with a 1q21-q23 FCHL locus identified in Finnish, German, Chinese and US families. We fine-mapped Hyplip1 to roughly 160 kb, constructed a BAC contig and sequenced overlapping BACs to identify 13 candidate genes. We found substantially decreased mRNA expression for thioredoxin interacting protein (Txnip). Sequencing of the critical region revealed a Txnip nonsense mutation in HcB-19 that is absent in its normolipidemic parental strains. Txnip encodes a cytoplasmic protein that binds and inhibits thioredoxin, a major regulator of cellular redox state. The mutant mice have decreased CO2 production but increased ketone body synthesis, suggesting that altered redox status down-regulates the citric-acid cycle, sparing fatty acids for triglyceride and ketone body production. These results reveal a new pathway of potential clinical significance that contributes to plasma lipid metabolism.

Animals↗
PubMedDate not supplied

'She was bewitched and caught an illness similar to AIDS': AIDS and sexually transmitted infection causation beliefs in rural northern Tanzania.

HIV/AIDS programmes and interventions are more likely to succeed if they engage with local people's beliefs about AIDS causation. This study examined beliefs about general illness, sexually-transmitted infection (STI) and AIDS aetiology in rural Mwanza, Tanzania. From 1999-2002, participant observation was carried out in nine villages for a total of 158 person-weeks. Beliefs about general illness causation included God's will, chance, natural/biological, ancestral spirits, and witchcraft. STIs were generally attributed to natural causes, but beliefs about AIDS causation were more complex. Few villagers had heard of HIV, but most had heard of AIDS and understood that AIDS could be contracted through sex. A small proportion of villagers knew that such an infected person might appear healthy, but they generally believed the asymptomatic period to last only a few months after exposure; if healthy beyond that, the person was not believed to have been infected. Many people in all villages reported belief in both a 'real' (natural) AIDS, which leads to certain death, and a similar illness caused by witchcraft, which can be cured using traditional medicine. Punishment of accused witches occurs officially and informally, and this may increase with increasing AIDS deaths. There is an urgent need for culturally appropriate interventions to address HIV/AIDS causation beliefs in the region.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Predicting oxygen uptake in older adults using lower-limb accelerometer measures.

Assessing physical activity in older adults has proven to be difficult but important, because regular participation has a protective and rehabilitative effect against disability and morbidity. Commercially available physical activity monitors measure waist movements and have not been validated for older adults. This study developed a model for establishing prediction equations to estimate older adults physical activity levels based on lower-limb accelerometer measures. Oxygen uptake and lower-limb accelerometer data were simultaneously recorded from treadmill and stair-climbing exercises. The best stepwise regression equations were obtained when accelerometer and weight measures were regressed on oxygen uptake when subjects walked 1, 2, and 3 miles per hour (R = 0.69 with accelerometer on back of the heel) and for accelerometer measures and gender when subjects climbed stairs (R = 0.77 with accelerometer on mid-ankle). These findings illustrate that physical activity can be effectively predicted in older adults from lower-limb accelerometer measurements.

Aged↗