Biomedical subjects

Eric P Hoffman

Publications and source records attributed to Eric P Hoffman.

At least 19 recordsLinked to original sources

PubMed2018

Muscle miRNAome shows suppression of chronic inflammatory miRNAs with both prednisone and vamorolone.

Corticosteroids are highly prescribed and effective anti-inflammatory drugs but the burden of side effects with chronic use significantly detracts from patient quality of life, particularly in children. Developing safer steroids amenable to long-term use is an important goal for treatment of chronic inflammatory diseases such as Duchenne muscular dystrophy (DMD). We have developed vamorolone (VBP15), a first-in-class dissociative glucocorticoid receptor (GR) ligand that shows the anti-inflammatory efficacy of corticosteroids without key steroid side effects in animal models. miRNAs are increasingly recognized as key regulators of inflammatory responses. To define effects of prednisolone and vamorolone on the muscle miRNAome, we performed a preclinical discovery study in the mdx mouse model of DMD. miRNAs associated with inflammation were highly elevated in mdx muscle. Both vamorolone and prednisolone returned these toward wild-type levels (miR-142-5p, miR-142-3p, miR-146a, miR-301a, miR-324-3p, miR-455-5p, miR-455-3p, miR-497, miR-652). Effects of vamorolone were largely limited to reduction of proinflammatory miRNAs. In contrast, prednisolone activated a separate group of miRNAs associated with steroid side effects and a noncoding RNA cluster homologous to human chromosome 14q32. Effects were validated for inflammatory miRNAs in a second, independent preclinical study. For the anti-inflammatory miRNA signature, bioinformatic analyses showed all of these miRNAs are directly regulated by, or in turn activate, the inflammatory transcription factor NF-κB. Moving forward miR-146a and miR-142 are of particular interest as biomarkers or novel drug targets. These data validate NF-κB signaling as a target of dissociative GR-ligand efficacy in vivo and provide new insight into miRNA signaling in chronic inflammation.

Animals↗

PubMed2007

X-linked infantile spinal muscular atrophy: clinical definition and molecular mapping.

PURPOSE: X-linked infantile spinal-muscular atrophy (XL-SMA) is a rare disorder, which presents with the clinical characteristics of hypotonia, areflexia, and multiple congenital contractures (arthrogryposis) associated with loss of anterior horn cells and death in infancy. We have previously reported a single family with XL-SMA that mapped to Xp11.3-q11.2. Here we report further clinical description of XL-SMA plus an additional seven unrelated (XL-SMA) families from North America and Europe that show linkage data consistent with the same region. METHODS: We first investigated linkage to the candidate disease gene region using microsatellite repeat markers. We further saturated the candidate disease gene region using polymorphic microsatellite repeat markers and single nucleotide polymorphisms in an effort to narrow the critical region. Two-point and multipoint linkage analysis was performed using the Allegro software package. RESULTS: Linkage analysis of all XL-SMA families displayed linkage consistent with the original XL-SMA region. CONCLUSION: The addition of new families and new markers has narrowed the disease gene interval for a XL-SMA locus between SNP FLJ22843 near marker DXS 8080 and SNP ARHGEF9 which is near DXS7132 (Xp11.3-Xq11.1).

Chromosome Mapping↗

PubMed2007

Proteomics and systems biology in exercise and sport sciences research.

A systems biology approach toward biological research seeks to model all concurrent processes in a cell, tissue, or organism by global measurements. In this review, we describe recent advances in mass spectrometry-based proteomics and their application toward interpreting the physiological adaptations of skeletal muscle with exercise and obesity.

Biomedical Research↗

PubMed2006

Probe set algorithms: is there a rational best bet?

Affymetrix microarrays have become a standard experimental platform for studies of mRNA expression profiling. Their success is due, in part, to the multiple oligonucleotide features (probes) against each transcript (probe set). This multiple testing allows for more robust background assessments and gene expression measures, and has permitted the development of many computational methods to translate image data into a single normalized "signal" for mRNA transcript abundance. There are now many probe set algorithms that have been developed, with a gradual movement away from chip-by-chip methods (MAS5), to project-based model-fitting methods (dCHIP, RMA, others). Data interpretation is often profoundly changed by choice of algorithm, with disoriented biologists questioning what the "accurate" interpretation of their experiment is. Here, we summarize the debate concerning probe set algorithms. We provide examples of how changes in mismatch weight, normalizations, and construction of expression ratios each dramatically change data interpretation. All interpretations can be considered as computationally appropriate, but with varying biological credibility. We also illustrate the performance of two new hybrid algorithms (PLIER, GC-RMA) relative to more traditional algorithms (dCHIP, MAS5, Probe Profiler PCA, RMA) using an interactive power analysis tool. PLIER appears superior to other algorithms in avoiding false positives with poorly performing probe sets. Based on our interpretation of the literature, and examples presented here, we suggest that the variability in performance of probe set algorithms is more dependent upon assumptions regarding "background", than on calculations of "signal". We argue that "background" is an enormously complex variable that can only be vaguely quantified, and thus the "best" probe set algorithm will vary from project to project.

Algorithms↗

PubMed2006

GRB14, GPD1, and GDF8 as potential network collaborators in weight loss-induced improvements in insulin action in human skeletal muscle.

Obesity is associated with insulin resistance in skeletal muscle; accordingly, weight loss dramatically improves insulin action. We sought to identify molecular remodeling of muscle commensurate with weight loss that could explain improvements in insulin action. Muscle from morbidly obese women was studied before and after gastric bypass surgery. Gastric bypass surgery significantly reduced body mass by approximately 45% and improved insulin action. We then assessed mRNA profiles using a stringent statistical analysis (statistical concordance with three probe set algorithms), with validation in a cross-sectional study of lean (n = 8) vs. morbidly obese (n = 8) muscle. Growth factor receptor-bound protein 14 (GRB14), glycerol-3-phosphate dehydrogenase 1 (GPD1), and growth differentiation factor 8 (GDF8; myostatin) significantly decreased approximately 2.4-, 2.2-, and 2.4-fold, respectively, after weight loss (gastric bypass). Increased expression of these transcripts was associated with increased obesity in the cross-sectional group (lean vs. morbidly obese muscle). Each transcript was validated by real-time quantitative RT-PCR assays in both study groups. Using Ingenuity Pathway Analysis, we show that all three transcripts are involved in the same regulatory network including AKT1, IGF1, TNF, PPARG, and INS. These results suggest that GRB14, GPD1, and GDF8 are weight loss-responsive genes in skeletal muscle and that the observed transcriptional modulation of these would be expected to improve insulin signaling, decrease triglyceride synthesis, and increase muscle mass, respectively, with weight loss. Thus our data provide a possible regulatory pathway involved in the development of insulin resistance in the morbidly obese state, and improvement of insulin resistance with weight loss.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Immunopathogenic pathways in canine inflammatory myopathies resemble human myositis.

Progress in the treatment of inflammatory myopathies is impeded by the lack of suitable animal models. Inflammatory myopathies occur spontaneously in the dog, are a heterogeneous group of disorders, and are more common than in humans. Clinical signs of weakness and muscle atrophy are reliably present, and there are histological and immunohistological similarities to forms of human myositis. In this study, microarray technology followed by quantitative real-time PCR and immunohistochemistry on muscle biopsy sections was used to investigate gene expression in cases of canine inflammatory myopathies. Several genes involved with innate and adaptive immunity were highly upregulated including those that participate in macrophage and dendritic cell activation and migration, and antigen processing and presentation. Other genes including those that participate in B cell growth, development, migration and activation, immunoglobulin genes, genes in pro-inflammatory and anti-inflammatory pathways, and genes involved with tissue remodeling were upregulated. In previous reports utilizing microarray technology in human myositis, there was activation of similar pathways involved in the immune response. This study strengthens the argument that forms of canine myositis may be important animal models of human myositis and suggests useful biomarkers for therapeutic response using the dog in pre-clinical trials.

Animals↗

PubMed2006

NKG2A and CD56 are coexpressed on activated TH2 but not TH1 lymphocytes.

NKG2A is commonly expressed on cytotoxic cells but has been found on activated T helper (TH) cells. In identifying novel markers differentiating between TH1 and TH2 lymphocytes, we focused on NKG2A expression. TH1 and TH2 cells were negatively isolated from healthy volunteers for microarray analysis and reverse transcription polymerase chain reaction (RT-PCR). Flow cytometry of quiescent and activated TH1 and TH2 cells was performed. Isolates were >95% pure CD3+CD4+ cells (TH1=90.3% and TH2=84.1%). Microarrays revealed differential expression of NKG2A and NKG2C isoforms between TH1 and TH2 cells. RT-PCR indicated greater expression of NKG2A in TH2 cells (4-fold) and NKG2C in TH1 cells (3-fold). Flow studies revealed tripling of TH2 NKG2A with activation to 10.76+/-4.01% (p=0.05), a 23-fold increase in CD56 to 35+/-14.54% (p=0.03), and an increase in NKG2A+CD56+ double-positive cells to 3.04+/-1.38% (p=0.04). TH1 lymphocytes did not differ with activation. We identified co-induction of NKG2A and CD56 on activation of TH2 cells. These cells would likely bind more HLA-E and exhibit increased effector inhibition. Given that certain viruses are known to decrease MHC class I and thus HLA-E production by antigen-presenting cells, activated TH2 cells would bind less HLA-E in this scenario. This would likely result in less effector inhibition and a relatively robust TH2 response.

Adolescent↗

PubMed2006

Sexual dimorphism in immune response genes as a function of puberty.

BACKGROUND: Autoimmune diseases are more prevalent in females than in males, whereas males have higher mortality associated with infectious diseases. To increase our understanding of this sexual dimorphism in the immune system, we sought to identify and characterize inherent differences in immune response programs in the spleens of male and female mice before, during and after puberty. RESULTS: After the onset of puberty, female mice showed a higher expression of adaptive immune response genes, while males had a higher expression of innate immune genes. This result suggested a requirement for sex hormones. Using in vivo and in vitro assays in normal and mutant mouse strains, we found that reverse signaling through FasL was directly influenced by estrogen, with downstream consequences of increased CD8+ T cell-derived B cell help (via cytokines) and enhanced immunoglobulin production. CONCLUSION: These results demonstrate that sexual dimorphism in innate and adaptive immune genes is dependent on puberty. This study also revealed that estrogen influences immunoglobulin levels in post-pubertal female mice via the Fas-FasL pathway.

Animals↗

PubMed2006

Musculin isoforms and repression of MyoD in muscle regeneration.

We studied possible negative regulators of MyoD using a 27 time point muscle regeneration series in vivo and identified Musculin as a key candidate for transcriptional repression of MyoD. Characterization of Musculin proteins showed two isoforms: the previously characterized 201 aa protein (1a) and a novel 180 aa isoform (1b). We show that the Musculin 1b isoform is equally effective at blocking MyoD-induced transcription as the 1a isoform. Our data narrow the likely repressor domain to between position 158 and 173 in the Musculin protein sequence, and suggest that the induction of Musculin is responsible for the rapid down-regulation of MyoD at 4-5 days during staged regeneration.

Amino Acid Sequence↗

PubMed2006

Nuclear envelope dystrophies show a transcriptional fingerprint suggesting disruption of Rb-MyoD pathways in muscle regeneration.

Mutations of lamin A/C (LMNA) cause a wide range of human disorders, including progeria, lipodystrophy, neuropathies and autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD). EDMD is also caused by X-linked recessive loss-of-function mutations of emerin, another component of the inner nuclear lamina that directly interacts with LMNA. One model for disease pathogenesis of LMNA and emerin mutations is cell-specific perturbations of the mRNA transcriptome in terminally differentiated cells. To test this model, we studied 125 human muscle biopsies from 13 diagnostic groups (125 U133A, 125 U133B microarrays), including EDMD patients with LMNA and emerin mutations. A Visual and Statistical Data Analyzer (VISDA) algorithm was used to statistically model cluster hierarchy, resulting in a tree of phenotypic classifications. Validations of the diagnostic tree included permutations of U133A and U133B arrays, and use of two probe set algorithms (MAS5.0 and MBEI). This showed that the two nuclear envelope defects (EDMD LMNA, EDMD emerin) were highly related disorders and were also related to fascioscapulohumeral muscular dystrophy (FSHD). FSHD has recently been hypothesized to involve abnormal interactions of chromatin with the nuclear envelope. To identify disease-specific transcripts for EDMD, we applied a leave-one-out (LOO) cross-validation approach using LMNA patient muscle as a test data set, with reverse transcription-polymerase chain reaction (RT-PCR) validations in both LMNA and emerin patient muscle. A high proportion of top-ranked and validated transcripts were components of the same transcriptional regulatory pathway involving Rb1 and MyoD during muscle regeneration (CRI-1, CREBBP, Nap1L1, ECREBBP/p300), where each was specifically upregulated in EDMD. Using a muscle regeneration time series (27 time points) we develop a transcriptional model for downstream consequences of LMNA and emerin mutations. We propose that key interactions between the nuclear envelope and Rb and MyoD fail in EDMD at the point of myoblast exit from the cell cycle, leading to poorly coordinated phosphorylation and acetylation steps. Our data is consistent with mutations of nuclear lamina components leading to destabilization of the transcriptome in differentiated cells.

Biopsy↗

PubMed2006

An interactive power analysis tool for microarray hypothesis testing and generation.

MOTIVATION: Human clinical projects typically require a priori statistical power analyses. Towards this end, we sought to build a flexible and interactive power analysis tool for microarray studies integrated into our public domain HCE 3.5 software package. We then sought to determine if probe set algorithms or organism type strongly influenced power analysis results. RESULTS: The HCE 3.5 power analysis tool was designed to import any pre-existing Affymetrix microarray project, and interactively test the effects of user-defined definitions of alpha (significance), beta (1-power), sample size and effect size. The tool generates a filter for all probe sets or more focused ontology-based subsets, with or without noise filters that can be used to limit analyses of a future project to appropriately powered probe sets. We studied projects from three organisms (Arabidopsis, rat, human), and three probe set algorithms (MAS5.0, RMA, dChip PM/MM). We found large differences in power results based on probe set algorithm selection and noise filters. RMA provided high sensitivity for low numbers of arrays, but this came at a cost of high false positive results (24% false positive in the human project studied). Our data suggest that a priori power calculations are important for both experimental design in hypothesis testing and hypothesis generation, as well as for the selection of optimized data analysis parameters. AVAILABILITY: The Hierarchical Clustering Explorer 3.5 with the interactive power analysis functions is available at www.cs.umd.edu/hcil/hce or www.cnmcresearch.org/bioinformatics. CONTACT: jseo@cnmcresearch.org

Algorithms↗

PubMed2006

Optimized multilayer perceptrons for molecular classification and diagnosis using genomic data.

MOTIVATION: Multilayer perceptrons (MLP) represent one of the widely used and effective machine learning methods currently applied to diagnostic classification based on high-dimensional genomic data. Since the dimensionalities of the existing genomic data often exceed the available sample sizes by orders of magnitude, the MLP performance may degrade owing to the curse of dimensionality and over-fitting, and may not provide acceptable prediction accuracy. RESULTS: Based on Fisher linear discriminant analysis, we designed and implemented an MLP optimization scheme for a two-layer MLP that effectively optimizes the initialization of MLP parameters and MLP architecture. The optimized MLP consistently demonstrated its ability in easing the curse of dimensionality in large microarray datasets. In comparison with a conventional MLP using random initialization, we obtained significant improvements in major performance measures including Bayes classification accuracy, convergence properties and area under the receiver operating characteristic curve (A(z)). SUPPLEMENTARY INFORMATION: The Supplementary information is available on http://www.cbil.ece.vt.edu/publications.htm

Biomarkers, Tumor↗

PubMed2006

Loss of emerin at the nuclear envelope disrupts the Rb1/E2F and MyoD pathways during muscle regeneration.

Emery-Dreifuss muscular dystrophy (EDMD1) is caused by mutations in either the X-linked gene emerin (EMD) or the autosomal lamin A/C (LMNA) gene. Here, we describe the derivation of mice lacking emerin in an attempt to derive a mouse model for EDMD1. Although mice lacking emerin show no overt pathology, muscle regeneration in these mice revealed defects. A bioinformatic array analysis of regenerating Emd null muscle revealed abnormalities in cell-cycle parameters and delayed myogenic differentiation, which were associated with perturbations to transcriptional pathways regulated by the retinoblastoma (Rb1) and MyoD genes. Temporal activation of MyoD transcriptional targets was significantly delayed, whereas targets of the Rb1/E2F transcriptional repressor complex remained inappropriately active. The inappropriate modulation of Rb1/MyoD transcriptional targets was associated with up-regulation of Rb1, MyoD and their co-activators/repressors transcripts, suggesting a compensatory effort to overcome a molecular block to differentiation at the myoblast/myotube transition during regeneration. This compensation appeared to be effective for MyoD transcriptional targets, although was less effective for Rb1 targets. Analysis of Rb1 phosphorylation states showed prolonged hyper-phosphorylation at key developmental stages in Emd null myogenic cells, both in vivo and in vitro. We also analyzed the same pathways in Lmna null muscle, which shows extensive dystrophy. Surprisingly, Lmna null muscle did not show the same perturbations to Rb- and MyoD-dependent pathways. We did observe increased transcriptional expression of Lap2alpha and delayed expression of Rb1, which may regulate alternative transcriptional pathways in the Lmna null myoblasts. We suggest that the dominant LMNA mutations seen in many clinically disparate laminopathies may similarly alter Rb function, with regard to either the timing of exit from the cell cycle or terminal differentiation programs or both.

Animals↗

PubMed2006

Automated sequence screening of the entire dystrophin cDNA in Duchenne dystrophy: point mutation detection.

This is the first report of direct sequencing of the complete 11 kb coding sequence of the dystrophin gene affording high sensitivity for all types of mutations of both coding sequence and splicing. Direct automated capillary gel sequence analysis of dystrophin reverse-transcribed polymerase chain reaction (RT-PCR) products was carried out in 15 Duchenne muscular dystrophy (DMD) patient muscle biopsies (170,000 bp sequenced). We identified mutations in 67% of patients tested (10/15); including premature stop codons (n = 5) and small deletions/duplications (n = 5). Mutation-negative patients (n = 5) were also negative for promoter mutations. All were tested for the possibility of transcription abnormalities using quantitative multiplex fluorescence polymerase chain studies (QMF-PCR), however, equal ratios of mRNA transcripts were identified at the 5'and 3' regions, with mild reduction in overall quantity, suggesting that transcription abnormalities were less likely. We suggested that such patients might have a problem with the 3.5 kb 3' UTR, polyA site or undetected stop codons. It is also possible that splicing defects could result in addition of intron sequence which could lead to preferential amplification of low level residual normal transcript skipping.

Base Sequence↗

PubMed2006

Expression of two temporally distinct microglia-related gene clusters after spinal cord injury.

The dual role of microglia in cytotoxicity and neuroprotection is believed to depend on the specific, temporal expression of microglial-related genes. To better clarify this issue, we used high-density oligonucleotide microarrays to examine microglial gene expression after spinal cord injury (SCI) in rats. We compared expression changes at the lesion site, as well as in rostral and caudal regions after mild, moderate, or severe SCI. Using microglial-associated anchor genes, we identified two clusters with different temporal profiles. The first, induced by 4 h postinjury to peak between 4 and 24 h, included interleukin-1beta, interleukin-6, osteopontin, and calgranulin, among others. The second was induced 24 h after SCI, and peaked between 72 h and 7 days; it included C1qB, Galectin-3, and p22(phox). These two clusters showed similar expression profiles regardless of injury severity, albeit with slight decreases in expression in mild or severe injury vs. moderate injury. Expression was also decreased rostral and caudal to the lesion site. We validated the expression of selected cluster members at the mRNA and protein levels. In addition, we demonstrated that stimulation of purified microglia in culture induces expression of C1qB, Galectin-3, and p22(phox). Finally, inhibition of p22(phox) activity within microglial cultures significantly suppressed proliferation in response to stimulation, confirming that this gene is involved in microglial activation. Because microglial-related factors have been implicated both in secondary injury and recovery, identification of temporally distinct clusters of genes related to microglial activation may suggest distinct roles for these groups of factors.

Acetophenones↗

PubMed2006

The RNA helicases p68/p72 and the noncoding RNA SRA are coregulators of MyoD and skeletal muscle differentiation.

MyoD regulates skeletal myogenesis. Since proteins associated with MyoD exert regulatory functions, their identification is expected to contribute important insights into the mechanisms governing gene expression in skeletal muscle. We have found that the RNA helicases p68/p72 are MyoD-associated proteins and that the noncoding RNA SRA also immunoprecipitates with MyoD. In vitro and in vivo experiments indicated that both p68/p72 and SRA are coactivators of MyoD. RNA interference toward either p68/p72 or SRA prevented proper activation of muscle gene expression and cell differentiation. Unexpectedly, reducing the levels of p68/p72 proteins impaired recruitment of the TATA binding protein TBP; RNA polymerase II; and the catalytic subunit of the ATPase SWI/SNF complex, Brg-1, and hindered chromatin remodeling. These findings reveal that p68/p72 play a critical role in promoting the assembly of proteins required for the formation of the transcription initiation complex and chromatin remodeling.

Amino Acid Sequence↗

PubMed2006

Secreted proteome profiling in human RPE cell cultures derived from donors with age related macular degeneration and age matched healthy donors.

Age-related macular degeneration (AMD) is characterized by progressive loss of central vision, which is attributed to abnormal accumulation of macular deposits called "drusen" at the interface between the basal surface of the retinal pigment epithelium (RPE) and Bruch's membrane. In the most severe cases, drusen deposits are accompanied by the growth of new blood vessels that breach the RPE layer and invade photoreceptors. In this study, we hypothesized that RPE secreted proteins are responsible for drusen formation and choroidal neovascularization. We used stable isotope labeling by amino acids in cell culture (SILAC) in combination with LC-MS/MS analysis and ZoomQuant quantification to assess differential protein secretion by RPE cell cultures prepared from human autopsy eyes of AMD donors (diagnosed by histological examinations of the macula and genotyped for the Y402H-complement factor H variant) and age-matched healthy control donors. In general, RPE cells were found to secrete a variety of extracellular matrix proteins, complement factors, and protease inhibitors that have been reported to be major constituents of drusen (hallmark deposits in AMD). Interestingly, RPE cells from AMD donors secreted 2 to 3-fold more galectin 3 binding protein, fibronectin, clusterin, matrix metalloproteinase-2 and pigment epithelium derived factor than RPE cells from age-matched healthy donors. Conversely, secreted protein acidic and rich in cysteine (SPARC) was found to be down regulated by 2-fold in AMD RPE cells versus healthy RPE cells. Ingenuity pathway analysis grouped these differentially secreted proteins into two groups; those involved in tissue development and angiogenesis and those involved in complement regulation and protein aggregation such as clusterin. Overall, these data strongly suggest that RPE cells are involved in the biogenesis of drusen and the pathology of AMD.

Aged↗

PubMed2006

ACE ID genotype and the muscle strength and size response to unilateral resistance training.

PURPOSE: To examine associations among the angiotensin I-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism and the response to a 12-wk (2 d.wk) unilateral, upper-arm resistance training (RT) program in the trained (T, nondominant) and untrained (UT, dominant) arms. METHODS: Subjects were 631 (mean+/-SEM, 24.2+/-0.2 yr) white (80%) men (42%) and women (58%). The ACE ID genotype was in Hardy-Weinberg equilibrium with frequencies of 23.1, 46.1, and 30.8% for ACE II, ID, and DD, respectively (chi=1.688, P=0.430). Maximum voluntary contraction (MVC) and one-repetition maximum (1RM) assessed peak elbow flexor muscle strength. Magnetic resonance imaging measured biceps muscle cross-sectional area (CSA). Multiple variable and repeated-measures ANCOVA tested whether muscle strength and size differed at baseline and pre- to post-RT among T and UT and ACE ID genotype. RESULTS: Baseline muscle strength and size were greater in UT than T (P<0.001) and did not differ among ACE ID genotype in either arm (P >or= 0.05). In T, MVC increases were greater for ACE II/ID (22%) than DD (17%) (P<0.05), whereas 1RM (51%) and CSA (19%) gains were not different among ACE ID genotype pre- to post-RT (P >or= 0.05). In UT, MVC increased among ACE II/ID (7%) (P<0.001) but was similar among ACE DD (2%) pre- to post-RT (P >or= 0.05). In UT, 1RM (11%) and CSA (2%) increases were greater for ACE DD/ID than ACE II (1RM, 7%; CSA, -0.1%) (P<0.05). ACE ID genotype explained approximately 1% of the MVC response to RT in T and approximately 2% of MVC, 2% of 1RM, and 4% of CSA response in UT (P<0.05). CONCLUSION: ACE ID genotype is associated with the contralateral effects of unilateral RT, perhaps more so than with the muscle strength and size adaptations that result from RT.

Adult↗