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In JoVE (1)
Other Publications (7)
Articles by Justin Lam in JoVE
Synthesis of an In vivo MRI-detectable Apoptosis Probe
Justin Lam1, Paul C. Simpson2,3, Phillip C. Yang1, Rajesh Dash1
1Division of Cardiovascular Medicine, Department of Medicine, Stanford University Medical Center, 2Division of Cardiology, Department of Medicine, University of California, San Francisco, 3San Francisco VAMC
Early detection of apoptosis may identify at-risk cell populations in a variety of diseases. Here we demonstrate a method to link an early apoptosis-detection protein (Annexin V) to a MRI-detectable iron oxide nanoparticle (SPIO). This method may be extended to other proteins of interest to generate MRI-detectable molecular imaging probes.
Other articles by Justin Lam on PubMed
Analytica Chimica Acta. Sep, 2012 | Pubmed ID: 22840711
Because of their unique characteristics, DNAs have been widely studied for uses in biosensors. In this work, we utilize single-stranded homopolymeric deoxyadenosines (abbreviated as poly (dA)) as recognition elements and gold nanoparticles (abbreviated as AuNPs) as reporter parts for the construction of pH alarms, which are able to produce sharp colorimetric responses upon specific pH thresholds within the range from pH 2 to 4. These biosensors are convenient to prepare and easy to operate. Their pH thresholds for colorimetric response can be easily tuned by changes of DNA strand length, concentration and DNA sequence. With an increase in the number of nucleotide bases per DNA chain while keeping the overall number of nucleotide base in the system constant, the pH threshold can be raised. Increasing the concentration of the single-stranded poly (dA) DNA lowers the pH response threshold. Moreover, as they can sense a range as narrow as a 0.4 pH unit which equals to 2.5 fold [H(+)] change, they can be used as a potential pH alarm for specific pH range.
RDR1 and SGS3, Components of RNA-mediated Gene Silencing, Are Required for the Regulation of Cuticular Wax Biosynthesis in Developing Inflorescence Stems of Arabidopsis
Plant Physiology. Jun, 2012 | Pubmed ID: 22689894
The cuticle is a protective layer that coats the primary aerial surfaces of land plants and mediates plant interactions with the environment. It is synthesized by epidermal cells and is composed of a cutin polyester matrix that is embedded and covered with cuticular waxes. Recently, we have discovered a novel regulatory mechanism of cuticular wax biosynthesis that involves the ECERIFERUM7 (CER7) ribonuclease, a core subunit of the exosome. We hypothesized that at the onset of wax production, the CER7 ribonuclease degrades an mRNA specifying a repressor of CER3, a wax biosynthetic gene whose protein product is required for wax formation via the decarbonylation pathway. In the absence of this repressor, CER3 is expressed, leading to wax production. To identify the putative repressor of CER3 and to unravel the mechanism of CER7-mediated regulation of wax production, we performed a screen for suppressors of the cer7 mutant. Our screen resulted in the isolation of components of the RNA-silencing machinery, RNA-DEPENDENT RNA POLYMERASE1 and SUPPRESSOR OF GENE SILENCING3, implicating RNA silencing in the control of cuticular wax deposition during inflorescence stem development in Arabidopsis (Arabidopsis thaliana).
Inertia on Hypoglycemia: Highlight from a Taiwan Subgroup Analysis of Real-Life Effectiveness and Care Patterns of Diabetes Management (RECAP-DM) Study
Diabetes Research and Clinical Practice. Jun, 2012 | Pubmed ID: 22704126
Type 2 diabetes mellitus is a global health issue. Patients with poor glycemic control often suffer from cardiovascular, cerebrovascular, neuropathic, and nephropathic complications as well as other chronic conditions. Therapeutic guidelines recommend that diabetic patients should maintain their HbA(1c) level below a certain target in order to minimize the risk of developing complications. However, hypoglycemia is recognized as a major impediment to the adequate control of type 2 diabetes. Hypoglycemia can manifest symptoms of varying degrees of severity. Moreover, an association between hypoglycemia and cardiovascular morbidity and mortality has been reported. Here, we present a post hoc Taiwan subgroup analysis of these data collected in the RECAP-DM study to indicate probably more emphasis and concern on hypoglycemia in type 2 diabetic patients in Taiwan. In this analysis, we found no significant difference was observed in treatment-related satisfaction between Taiwanese patients with or without hypoglycemia. Another finding of our study further shows that varying order of hypoglycemic symptoms or severity has no effect on patients' assessment of health-related quality of life scores. We need to pay more attention to this issue because of its enduring impact on compliance and concerns about hypoglycemia in type 2 diabetic patients. Nevertheless, socio-demographic characteristics are also important factors influencing glycemic control and patients' health-related quality of life. Future interventions and therapeutic algorithms should emphasize the probable patients' unawareness or neglect on hypoglycemia in diabetic patients.
Journal of Alzheimer's Disease : JAD. Jul, 2012 | Pubmed ID: 22785396
Mitochondrial dysfunction is a prominent hallmark of Alzheimer's disease (AD). Mitochondrial DNA (mtDNA) damage may be a major cause of abnormal reactive oxidative species production in AD or increase neuronal susceptibility to oxidative injury during aging. The purpose of this study was to assess the influence of mtDNA sequence variation on clinically significant cognitive impairment and dementia risk in the population-based Health, Aging, and Body Composition (Health ABC) Study. We first investigated the role of common mtDNA haplogroups and individual variants on dementia risk and 8-year change on the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) among 1,631 participants of European genetic ancestry. Participants were free of dementia at baseline and incidence was determined in 273 cases from hospital and medication records over 10-12 follow-up years. Participants from haplogroup T had a statistically significant increased risk of developing dementia (OR = 1.86, 95% CI = 1.23, 2.82, p = 0.0008) and haplogroup J participants experienced a statistically significant 8-year decline in 3MS (β = -0.14, 95% CI = -0.27, -0.03, p = 0.0006), both compared with common haplogroup H. The m.15244A>G, p.G166G, CytB variant was associated with a significant decline in DSST score (β = -0.58, 95% CI -0.89, -0.28, p = 0.00019) and the m.14178T>C, p.I166V, ND6 variant was associated with a significant decline in 3MS score (β = -0.87, 95% CI -1.31, -3.86, p = 0.00012). Finally, we sequenced the complete ∼16.5 kb mtDNA from 135 Health ABC participants and identified several highly conserved and potentially functional nonsynonymous variants unique to 22 dementia cases and aggregate sequence variation across the hypervariable 2-3 regions that influences 3MS and DSST scores.
Nature Biotechnology. Jul, 2012 | Pubmed ID: 22797562
We describe genome mapping on nanochannel arrays. In this approach, specific sequence motifs in single DNA molecules are fluorescently labeled, and the DNA molecules are uniformly stretched in thousands of silicon channels on a nanofluidic device. Fluorescence imaging allows the construction of maps of the physical distances between occurrences of the sequence motifs. We demonstrate the analysis, individually and as mixtures, of 95 bacterial artificial chromosome (BAC) clones that cover the 4.7-Mb human major histocompatibility complex region. We obtain accurate, haplotype-resolved, sequence motif maps hundreds of kilobases in length, resulting in a median coverage of 114× for the BACs. The final sequence motif map assembly contains three contigs. With an average distance of 9 kb between labels, we detect 22 haplotype differences. We also use the sequence motif maps to provide scaffolds for de novo assembly of sequencing data. Nanochannel genome mapping should facilitate de novo assembly of sequencing reads from complex regions in diploid organisms, haplotype and structural variation analysis and comparative genomics.
Archives of Neurology. Jul, 2012 | Pubmed ID: 22801742
OBJECTIVE To identify plasma biomarkers for the diagnosis of Alzheimer disease (AD). DESIGN Baseline plasma screening of 151 multiplexed analytes combined with targeted biomarker and clinical pathology data. SETTING General community-based, prospective, longitudinal study of aging. PARTICIPANTS A total of 754 healthy individuals serving as controls and 207 participants with AD from the Australian Imaging Biomarker and Lifestyle study (AIBL) cohort with identified biomarkers that were validated in 58 healthy controls and 112 individuals with AD from the Alzheimer Disease Neuroimaging Initiative (ADNI) cohort. RESULTS A biomarker panel was identified that included markers significantly increased (cortisol, pancreatic polypeptide, insulinlike growth factor binding protein 2, β2 microglobulin, vascular cell adhesion molecule 1, carcinoembryonic antigen, matrix metalloprotein 2, CD40, macrophage inflammatory protein 1α, superoxide dismutase, and homocysteine) and decreased (apolipoprotein E, epidermal growth factor receptor, hemoglobin, calcium, zinc, interleukin 17, and albumin) in AD. Cross-validated accuracy measures from the AIBL cohort reached a mean (SD) of 85% (3.0%) for sensitivity and specificity and 93% (3.0) for the area under the receiver operating characteristic curve. A second validation using the ADNI cohort attained accuracy measures of 80% (3.0%) for sensitivity and specificity and 85% (3.0) for area under the receiver operating characteristic curve. CONCLUSIONS This study identified a panel of plasma biomarkers that distinguish individuals with AD from cognitively healthy control subjects with high sensitivity and specificity. Cross-validation within the AIBL cohort and further validation within the ADNI cohort provides strong evidence that the identified biomarkers are important for AD diagnosis.
A Randomized, Double-blind Placebo Controlled Trial of Balapiravir, a Polymerase Inhibitor, in Adult Dengue Patients
The Journal of Infectious Diseases. Jul, 2012 | Pubmed ID: 22807519
Background. Dengue is the most common arboviral infection of humans. There are currently no specific treatments for dengue. Balapiravir is a prodrug of a nucleoside analogue (called R1479) and an inhibitor of Hepatitis C virus replication in vivo.Methods. We conducted in vitro experiments to determine the potency of balapiravir against dengue viruses and then an exploratory, dose-escalating, randomized placebo-controlled trial in adult male dengue patients with less than 48hrs of fever.Results. The clinical and laboratory adverse event profile in patients receiving balapiravir at doses of 1500mg (n=10) or 3000mg (n=22) orally for 5 days was similar to patients receiving placebo (n=32), indicating balapiravir was well tolerated. However, twice daily assessment of viremia and daily assessment of NS1 antigenemia indicated balapiravir did not measurably alter the kinetics of these virological markers, nor did it reduce the fever clearance time. The kinetics of plasma cytokine concentrations and the whole blood transcriptional profile were also not attenuated by balapiravir treatment.Conclusions. Although this trial, the first of its kind in dengue, does not support balapiravir as a candidate drug, it does establish a framework for anti-viral treatment trials in dengue and provides the field with a clinically evaluated benchmark molecule.