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Robert Friedman

Publications and source records attributed to Robert Friedman.

52 records · Page 3Linked to original sources
PubMed2003

The temporal distribution of gene duplication events in a set of highly conserved human gene families.

Using a data set of protein translations associated with map positions in the human genome, we identified 1520 mapped highly conserved gene families. By comparing sharing of families between genomic windows, we identified 92 potentially duplicated blocks in the human genome containing 422 duplicated members of these families. Using branching order in the phylogenetic trees, we timed gene duplication events in these families relative to the primate-rodent divergence, the amniote-amphibian divergence, and the deuterostome-protostome divergence. The results showed similar patterns of gene duplication times within duplicated blocks and outside duplicated blocks. Both within and outside duplicated blocks, numerous duplications were timed prior to the deuterostome-protostome divergence, whereas others occurred after the amniote-amphibian divergence. Thus, neither gene duplication in general nor duplication of genomic blocks could be attributed entirely to polyploidization early in vertebrate history. The strongest signal in the data was a tendency for intrachromosomal duplications to be more recent than interchromosomal duplications, consistent with a model whereby tandem duplication-whether of single genes or of genomic blocks-may be followed by eventual separation of duplicates due to chromosomal rearrangements. The rate of separation of tandemly duplicated gene pairs onto separated chromosomes in the human lineage was estimated at 1.7 x 10(-9) per gene-pair per year.

Animals↗
PubMed2003

Parallel evolution by gene duplication in the genomes of two unicellular fungi.

Phylogenetic analysis of conserved gene families in fission yeast Schizosaccharomyces pombe and brewer's yeast Saccharomyces cerevisiae showed that gene duplications have occurred independently in the same families in each of these two lineages to a far greater extent than expected by chance. These species represent distinct lineages of the phylum Ascomycota that independently evolved a "yeast" life cycle with a unicellular thallus that reproduces by budding, and many of the genes that have duplicated independently in the two lineages are known to be involved in crucial aspects of this life cycle. Parallel gene duplication thus appears to have played a role in the independent origin of similar adaptations in the two species. The results indicate that using phylogenetic analysis to test for parallel gene duplication in different species may help in identifying genes responsible for similar but independently evolved adaptations.

Evolution, Molecular↗
PubMed2003

Hypertension management in patients with diabetes: the need for more aggressive therapy.

OBJECTIVE: Clinical trials have demonstrated the importance of tight blood pressure control among patients with diabetes. However, little is known regarding the management of hypertension in patients with coexisting diabetes. To examine this issue, we addressed 1) whether hypertensive patients with coexisting diabetes are achieving lower levels of blood pressure than patients without diabetes, 2) whether there are differences in the intensity of antihypertensive medication therapy provided to patients with and without diabetes, and 3) whether diabetes management affects decisions to increase antihypertensive medication therapy. RESEARCH DESIGN AND METHODS: We abstracted medical records to collect detailed information on 2 years of care provided for 800 male veterans with hypertension. We compared patients with and without diabetes on intensity of therapy and blood pressure control. Intensity of therapy was described using a previously validated measure that captures the likelihood of an increase in antihypertensive medications. We also determined whether increases in antihypertensive medications were less likely at those visits in which the diabetes medications were being adjusted. RESULTS: Of the 274 hypertensive patients with diabetes, 73% had a blood pressure > or =140/90 mmHg, compared with 66% in the 526 patients without diabetes (P = 0.04). Diabetic patients also received significantly (P = 0.05) less intensive antihypertensive medication therapy than patients without diabetes. Less intensive therapy in diabetic patients could not be explained by clinicians being distracted by the treatment for diabetes. CONCLUSIONS: There is an urgent need to improve hypertension care and blood pressure control in patients with diabetes. Additional information is required to understand why clinicians are not more aggressive in managing blood pressure when patients also have diabetes.

Aged↗
PubMed2003

2R or not 2R: testing hypotheses of genome duplication in early vertebrates.

The widely popular hypothesis that there were two rounds of genome duplication by polyploidization early in vertebrate history (the 2R hypothesis) has been difficult to test until recently. Among the lines of evidence adduced in support of this hypothesis are relative genome size, relative gene number, and the existence of genomic regions putatively duplicated during polyploidization. The availability of sequence for a substantial portion of the human genome makes possible the first rigorous tests of this hypothesis. Comparison of gene family size in the human genome and in invertebrate genomes shows no evidence of a 4:1 ratio between vertebrates and invertebrates. Furthermore, explicit phylogenetic tests for the topology expected from two rounds of polyploidization have revealed alternative topologies in a substantial majority of human gene families. Likewise, phylogenetic analyses have shown that putatively duplicated genomic regions often include genes duplicated at widely different times over the evolution of life. The 2R hypothesis thus can be decisively rejected. Rather, current evidence favors a model of genome evolution in which tandem duplication, whether of genomic segments or of individual genes, predominates.

Animals↗
PubMed2003

Parallel evolution by gene duplication in the genomes of two unicellular fungi.

Phylogenetic analysis of conserved gene families in fission yeast Schizosaccharomyces pombe and brewer's yeast Saccharomyces cerevisiae showed that gene duplications have occurred independently in the same families in each of these two lineages to a far greater extent than expected by chance. These species represent distinct lineages of the phylum Ascomycota that independently evolved a "yeast" life cycle with a unicellular thallus that reproduces by budding, and many of the genes that have duplicated independently in the two lineages are known to be involved in crucial aspects of this life cycle. Parallel gene duplication thus appears to have played a role in the independent origin of similar adaptations in the two species. The results indicate that using phylogenetic analysis to test for parallel gene duplication in different species may help in identifying genes responsible for similar but independently evolved adaptations

Evolution, Molecular↗
PubMed2002

Molecular evolution of the NF-kappaB signaling system.

The mechanisms of innate immunity in vertebrates show certain overall resemblances to immune mechanisms of insects. Two hypotheses have been proposed to explain these resemblances. (1) According to the evolutionary continuity hypothesis, innate immune mechanisms evolved in the common ancestor of vertebrates and insects and have been conserved since that time. (2) In the independent-evolution hypothesis, the mechanisms of innate immunity in vertebrates evolved independently from invertebrate immune mechanisms. Phylogenetic analysis of five gene families (Pelle, Rel, IkappaB, Toll, and TRAF) whose members are involved in NF-kappaB signaling in vertebrates and insects were used to decide between these hypotheses. The phylogenies of the Rel and TRAF families strongly supported independent evolution of immune functions in vertebrates and invertebrates, and, except for a possible case in the Pelle family, orthologous molecules having immune functions in both vertebrates and invertebrates were not found. The results suggest that NF-kappaB represents an ancient, generalized signaling system that has been co-opted for immune system roles independently in vertebrate and insect lineages.

Amino Acid Sequence↗
PubMed2002

Effects of a computer-based, telephone-counseling system on physical activity.

BACKGROUND: There is increasing interest in developing interventions to promote physical activity (PA) that do not involve face-to-face contact with health professionals. We developed a fully automated PA counseling system (telephone-linked communication, TLC-PA) that was delivered via telephone. DESIGN: A randomized, controlled trial with 298 adult, sedentary members (mean age, 45.9 years; 72% women; 45% white; and 45% African American) of a multi-site medical practice. The comparison group (TLC-Eat) received an automated intervention promoting healthy eating, which was also delivered via telephone. INTERVENTION: The TLC-PA promoted moderate-intensity PA (MI-PA) based on the transtheoretical model of behavior change and social cognitive theory. The system was available to participants for 6 months. MAIN OUTCOMES: Energy expenditure in MI-PA, proportion of participants who met recommendations for MI-PA, and motivational readiness for PA. MEASURES: Self-reports of PA behavior and motivational readiness at baseline, 3 months, and 6 months. RESULTS: At 3 months, intention-to-treat analyses showed that the TLC-PA group was more likely to meet recommendations for MI- or vigorous-intensity PA (VI-PA) compared to the TLC-Eat group (TLC-PA=26% vs TLC-Eat=19.6%, p=0.04). Among study completers, TLC-PA subjects reported significantly higher daily kilocalorie energy expenditure in MI-PA (2.3 kcal/kg/d vs 2.0 kcal/kg/d, p=0.02); a larger proportion met recommendations for MI- or VI-PA (31.2% vs 21.3%, p=0.02) and were in more advanced stages of motivational readiness than TLC-Eat subjects (TLC-PA=52.5% vs TLC-Eat=42.2%, p=0.04). Results were not maintained at 6 months. The proportion of TLC-PA users decreased significantly over the intervention period. CONCLUSIONS: A fully automated counseling system had positive short-term effects on PA among sedentary adults. Lack of maintenance of effects may be due to a decrease in the number of participants who continued to use the system.

Chi-Square Distribution↗
PubMed2002

Organization of six functional mouse alcohol dehydrogenase genes on two overlapping bacterial artificial chromosomes.

Mammalian alcohol dehydrogenases (ADH) form a complex enzyme system based on amino-acid sequence, functional properties, and gene expression pattern. At least four mouse Adh genes are known to encode different enzyme classes that share less than 60% amino-acid sequence identity. Two ADH-containing and overlapping C57BL/6 bacterial artificial chromosome clones, RP23-393J8 and -463H24, were identified in a library screen, physically mapped, and sequenced. The gene order in the complex and two new mouse genes, Adh5a and Adh5b, and a pseudogene, Adh5ps, were obtained from the physical map and sequence. The mouse genes are all in the same transcriptional orientation in the order Adh4-Adh1-Adh5a-Adh5b-Adh5ps-Adh2-Adh3. A phylogenetic tree analysis shows that adjacent genes are most closely related suggesting a series of duplication events resulted in the gene complex. Although mouse and human ADH gene clusters contain at least one gene for ADH classes I-V, the human cluster contains 3 class I genes while the mouse cluster has two class V genes plus a class V pseudogene.

Alcohol Dehydrogenase↗
PubMed2002

Harnessing motivational forces in the promotion of physical activity: the Community Health Advice by Telephone (CHAT) project.

Physical inactivity among middle- and older-aged adults is pervasive, and is linked with numerous chronic conditions that diminish health and functioning. Counselor-directed physical activity programs may enhance extrinsic motivation (reflected in social influence theories, such as self-presentation theory) and, in turn, physical activity adherence, while the counselor is in charge of program delivery. However, external influences can undermine intrinsic motivation, making it more difficult to maintain physical activity once counselor-initiated contact ends. In contrast, programs that diminish the socially evaluative and controlling aspects of the counseling interchange may promote intrinsic motivation (described in cognitive evaluation theory), and, thus, physical activity maintenance, even when counselor-initiated contact ceases. The objective of the Community Health Advice by Telephone (CHAT) project is to compare these two theories by conducting a randomized controlled trial evaluating the effects of a telephone-administered counseling program delivered by a person (social influence enhancement) or computer (cognitive evaluation enhancement) on physical activity adoption and maintenance over 18 months. Healthy, sedentary adults (n = 225) aged 55 years and older are randomized to one of these programs or to a control arm. This study will contribute to advancing motivational theory as well as provide information on the sustained effectiveness of interventions with substantial public health applicability.

Aged↗
PubMed2002

The extent of nucleotide polymorphism is highly variable across a 3-kb region on Plasmodium falciparum chromosome 2.

Genomic nucleotide polymorphism in the virulent human malarial parasite Plasmodium falciparum was surveyed by sequencing a 3-kb region of chromosome 2 from 21 isolates, including the MSP4 and MSP5 genes. Extensive sequence polymorphism was observed in the coding regions of these genes and in the region downstream to MSP5, and the average pairwise divergence time of haplotypes in this region was estimated to be at least about 200,000 years. But nucleotide polymorphism was not found in the introns and was much reduced in the intergenic region. Over the entire region, nucleotide diversity was negatively correlated with a nucleotide content skewed toward thymine. Together with the previous evidence of limited nucleotide polymorphism in introns of P. falciparum, these data suggest the existence of a mechanism suppressing single-nucleotide polymorphism in regions of the P. falciparum genome with highly skewed nucleotide content.

Amino Acid Sequence↗
PubMed2002

Genomewide pattern of synonymous nucleotide substitution in two complete genomes of Mycobacterium tuberculosis.

Comparison of the pattern of synonymous nucleotide substitution between two complete genomes of Mycobacterium tuberculosis at 3298 putatively orthologous loci showed a mean percent difference per synonymous site of 0.000328 0.000022. Although 80.5% of loci showed no synonymous or nonsynonymous nucleotide differences, the level of polymorphism observed at other loci was greater than suggested by previous studies of a small number of loci. This level of nucleotide difference leads to the conservative estimate that the common ancestor of these two genotypes occurred approximately 35000 ago, which is twice as high as some recent estimates of the time of origin of this species. Our results suggest that a large number of loci should be examined for an accurate assessment of the level of nucleotide diversity in natural populations of pathogenic microorganisms.

Base Sequence↗
PubMedDate not supplied

Foraminal injection of a painful sacral nerve root using an epidural catheter: case report.

BACKGROUND AND OBJECTIVES: Nerve root pain has been treated with steroid injections since the 1970s. We will describe a novel method for nerve root injection using a directed epidural catheter. CASE REPORT: A case is described where catheter placement accurately reproduced symptoms which were then relieved with local anesthetic and steroid. CONCLUSION: This is a novel approach to treatment of painful nerve roots with a catheter.

Catheterization↗
PubMedDate not supplied

Loss of ancestral genes in the genomic evolution of Ciona intestinalis.

Comparison of the predicted protein sets encoded by the complete genomes of two vertebrates (human and pufferfish), the urochordate Ciona intestinalis, three nonchordate animals, and two fungi were used to reconstruct a set of gene families present in the common ancestor of chordates. These ancestral families were much more likely to be lost in Ciona than in either vertebrate. In addition, of 256 duplicate gene pairs that arose by duplication prior to the most recent common ancestor of vertebrates and insects, one of the duplicate genes was four times as likely to be lost in Ciona as in the vertebrates. These results show that the genome of Ciona is not representative of the ancestral chordate genome with respect to gene content but rather shows derived features that may reflect adaptation of the specific ecological niche of urochordates.

Animals↗