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Find video protocols related to scientific articles indexed in Pubmed.
Rickettsia parkeri and Rickettsia montanensis, Kentucky and Tennessee, USA.
Emerging Infect. Dis.
PUBLISHED: 10-02-2014
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We found that 14.3% (15/105) of Amblyomma maculatum and 3.3% (10/299) of Dermacentor variabilis ticks collected at 3 high-use military training sites in west-central Kentucky and northern Tennessee, USA, were infected with Rickettsia parkeri and Rickettsia montanensis, respectively. These findings warrant regional increased public health awareness for rickettsial pathogens and disease.
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Pharmacogenetics of addiction therapy.
Methods Mol. Biol.
PUBLISHED: 08-25-2014
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Drug addiction is a serious relapsing disease that has high costs to society and to the individual addicts. Treatment of these addictions is still in its nascency, with only a few examples of successful therapies. Therapeutic response depends upon genetic, biological, social, and environmental components. A role for genetic makeup in the response to treatment has been shown for several addiction pharmacotherapies. For several addiction pharmacotherapies, response to treatment varies based on individual genetic makeup. In this chapter, we discuss the role of genetics in pharmacotherapies, specifically for cocaine, alcohol, and opioid dependences. The elucidation of the role of genetics should aid in the development of new treatments and increase the efficacy of existing treatments.
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Rational and combinatorial approaches to engineering styrene production by Saccharomyces cerevisiae.
Microb. Cell Fact.
PUBLISHED: 08-21-2014
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Styrene is an important building-block petrochemical and monomer used to produce numerous plastics. Whereas styrene bioproduction by Escherichia coli was previously reported, the long-term potential of this approach will ultimately rely on the use of hosts with improved industrial phenotypes, such as the yeast Saccharomyces cerevisiae.
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Biopsy-proven case of childhood primary angiitis of the central nervous system presenting with bilateral panuveitis and anisocoria.
Pediatr Radiol
PUBLISHED: 06-09-2014
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Childhood primary angiitis of the central nervous system (cPACNS) is a rare and poorly understood immune-mediated vasculitis that preferentially affects blood vessels of the central nervous system (CNS). It must be distinguished from other disorders to initiate prompt treatment and improve the patient's prognosis. The presentation of cPACNS is highly variable, making a clinical diagnosis challenging. However, MRI may be helpful in showing typical findings including perivascular space inflammation and enhancement. Identification of these imaging features allows the radiologist to specifically suggest this rare diagnosis. The purpose of this manuscript is to present a biopsy-confirmed case of cPACNS in a 9-year-old girl who presented uniquely with panuveitis and anisocoria, and emphasize the MRI features that should prompt the radiologist to suggest this rare diagnosis.
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The influence of dopamine ?-hydroxylase gene polymorphism rs1611115 on levodopa/carbidopa treatment for cocaine dependence: a preliminary study.
Pharmacogenet. Genomics
PUBLISHED: 05-10-2014
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Recent studies have suggested that heterogeneity in the level of dopamine activity and function might be useful for identifying a subgroup of cocaine-dependent patients responding better to dopamine-enhancement pharmacotherapy. Here we hypothesized that response to levodopa/carbidopa treatment would be greater in patients with genetically determined low levels of the dopamine metabolizing enzyme dopamine ?-hydroxylase (D?H). Seventy-one cocaine-dependent patients who participated in a 12-week randomized double-blind placebo-controlled trial of levodopa/carbidopa were genotyped for the D?H gene (DBH) polymorphism rs1611115. Our results showed that for patients with the low D?H activity genotypes (CT/TT) who received levodopa, the odds of having cocaine-positive urine decreased significantly over treatment compared with placebo-treated patients with the CT/TT genotypes (P=0.004). Individuals with the normal D?H activity genotype (CC) showed no differential response to levodopa. These preliminary results need to be confirmed in a larger sample focusing on the DBH polymorphism.
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Comparing in situ removal strategies for improving styrene bioproduction.
Bioprocess Biosyst Eng
PUBLISHED: 04-24-2014
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As an important conventional monomer compound, the biological production of styrene carries significant promise with respect to creating novel sustainable materials. Since end-product toxicity presently limits styrene production by previously engineered Escherichia coli, in situ product removal by both solvent extraction and gas stripping were explored as process-based strategies for circumventing its inhibitory effects. In solvent extraction, the addition of bis(2-ethylhexyl)phthalate offered the greatest productivity enhancement, allowing net volumetric production of 836 ± 64 mg/L to be reached, representing a 320 % improvement over single-phase cultures. Gas stripping rates, meanwhile, were controlled by rates of bioreactor agitation and, to a greater extent, aeration. A periodic gas stripping protocol ultimately enabled up to 561 ± 15 mg/L styrene to be attained. Lastly, by relieving the effects of styrene toxicity, new insight was gained regarding subsequent factors limiting its biosynthesis in E. coli and strategies for future strain improvement are discussed.
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Epigenetic variation in the mu-opioid receptor gene in infants with neonatal abstinence syndrome.
J. Pediatr.
PUBLISHED: 03-19-2014
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Neonatal abstinence syndrome (NAS) from in utero opioid exposure is highly variable with genetic factors appearing to play an important role. Epigenetic changes in cytosine:guanine (CpG) dinucleotide methylation can occur after drug exposure and may help to explain NAS variability. We correlated DNA methylation levels in the mu-opioid receptor (OPRM1) promoter in opioid-exposed infants with NAS outcomes.
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Technoeconomic evaluation of bio-based styrene production by engineered Escherichia coli.
J. Ind. Microbiol. Biotechnol.
PUBLISHED: 02-16-2014
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Styrene is an important commodity chemical used in polymers and resins, and is typically produced from the petrochemical feedstocks benzene and ethylene. Styrene has recently been produced biosynthetically for the first time using engineered Escherichia coli, and this bio-based route may represent a lower energy and renewable alternative to petroleum-derived styrene. However, the economics of such an approach has not yet been investigated. Using an early-stage technoeconomic evaluation tool, a preliminary economic analysis of bio-based styrene from C(6)-sugar feedstock has been conducted. Owing to styrene's limited water solubility, it was assumed that the resulting fermentation broth would spontaneously form two immiscible liquid phases that could subsequently be decanted. Assuming current C(6) sugar prices and industrially achievable biokinetic parameter values (e.g., product yield, specific growth rate), commercial-scale bio-based styrene has a minimum estimated selling price (MESP) of 1.90 USD kg(-1) which is in the range of current styrene prices. A Monte Carlo analysis revealed a potentially large (0.45 USD kg(-1)) standard deviation in the MESP, while a sensitivity analysis showed feedstock price and overall yield as primary drivers of MESP.
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In situ butanol recovery from Clostridium acetobutylicum fermentations by expanded bed adsorption.
Biotechnol. Prog.
PUBLISHED: 02-08-2014
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Although butanol is a promising biofuel, its fermentative production suffers from inhibition caused by end product toxicity. The in situ removal of butanol from cultures via expanded bed adsorption offers an effective strategy for mitigating the effects of product toxicity while eliminating the need to clarify cultures via microfiltration. The hydrophobic polymer resin Dowex Optipore L-493 was found to be both an effective butanol adsorbent and suitable for use in expanded bed adsorption. Recirculation rates through the adsorption column were strongly correlated with and ultimately controlled rates of butanol uptake from the media which, reaching as high as 41.1 g/L h, easily exceed those of its production in a typical fermentation. Vacuum application with vapor collection was found to be an effective means of adsorbent regeneration, with an average of 81% butanol recovery possible, with butanol concentrations in the cold trap reaching as high as 85.8 g/L. Integration of expanded bed adsorption with a fed-batch Clostridium acetobutylicum ATCC 824 fermentation and its continuous operation for 38.5 h enabled the net production (i.e., in solution and adsorbed) of butanol and total solvent products at up to 27.2 and 40.7 g/L of culture, respectively, representing 2.2- and 2.3-fold improvements over conventional batch culture. While adsorbent biofouling was found to be minimal, further investigation of biofouling in longer-term studies will provide useful and further insight regarding the robustness of the process strategy.
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Candidate gene associations with mood disorder, cognitive vulnerability, and fronto-limbic volumes.
Brain Behav
PUBLISHED: 02-03-2014
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FOUR OF THE MOST CONSISTENTLY REPLICATED VARIANTS ASSOCIATED WITH MOOD DISORDER OCCUR IN GENES IMPORTANT FOR SYNAPTIC FUNCTION: ANK3 (rs10994336), BDNF (rs6265), CACNA1C (rs1006737), and DGKH (rs1170191).
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'Hybrid' processing strategies for expanding and improving the synthesis of renewable bioproducts.
Curr. Opin. Biotechnol.
PUBLISHED: 01-30-2014
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The versatile functionality of microbial biocatalysts offers a promising solution to the growing need to replace conventional, petroleum-derived fuels, chemicals, and materials with sustainable alternatives from renewable biomass. Whereas metabolic pathway engineering and strain optimization have greatly expanded the range of attainable bioproducts, it is by coupling microbial biosynthesis with traditional chemical conversions that the diversity of products that can ultimately be derived from biomass is truly beginning to reach its full potential. As will be the focus of this short review, such 'hybrid' strategies are now facilitating the generation of new and useful value-added bioproducts from renewable sources, the likes of which have previously been unattainable via biological routes alone.
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Litter and sex effects on maternal behavior and DNA methylation of the Nr3c1 exon 17 promoter gene in hippocampus and cerebellum.
Int. J. Dev. Neurosci.
PUBLISHED: 01-08-2014
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Early life events can alter gene expression through DNA methylation. The methylation status of the exon 17 promoter of the glucocorticoid receptor (Nr3c1 gene) in hippocampus associates with frequency of pup licking. Much of this work was conducted with male rats. Because dams more frequently lick male pups, this may contribute to sex differences in phenotypes through DNA methylation. Modifying litter gender composition (LGC), in which offspring of single-sex litters are compared to mixed-sex litters, alters maternal behavior. Previously, we demonstrated that LGC and sex affected pup licking times as well as anxiety and hippocampal DNA methylation of the Nr3c1 exon 17 promoter gene in adolescence. Now, we expand upon this work by examining effects in cerebellum and measuring mRNA levels. We also re-assessed DNA methylation in hippocampus using pyrosequencing and re-analyzed pup licking with the more commonly used frequency measure. Litters, culled to 8 pups on postnatal day 1 (PN1), were assigned to one of three conditions: all male (n = 10), all female (n = 12), or half of each sex (n = 20). Licking was rated on PN4, 7, and 10. On PN35, hippocampal and cerebellar samples were obtained. Single-sex males were licked the least and mixed-sex males, the most. Hippocampal Nr3c1 mRNA levels were lowest in mixed females with no LGC or Sex effects in DNA methylation. Cerebellar DNA methylation levels were lowest in mixed males with no effect on mRNA levels. Maternal pup licking associated with DNA methylation of the Nr3c1 exon 17 promoter gene in cerebellum and with hippocampal mRNA.
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Tandem isomerization/telomerization of long chain dienes.
Front Chem
PUBLISHED: 01-01-2014
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The first example of a tandem reaction involving double-bond migration in combination with telomerization is reported. Homogeneous and heterogeneous Ru catalysts were employed as isomerization catalysts, and telomerization was realized using a homogeneous Pd(0) precursor complex with a N-heterocyclic carbene (IMes) ligand. Overall conversions approaching 60% were achieved with the best selectivity to telomerization products of 91% attained at 11% conversion. Conversion was markedly higher in the presence of longer-chain alcohol (1-butanol) as the nucleophile (telogen).
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The ?-opioid receptor gene as a predictor of response in a cocaine vaccine clinical trial.
Psychiatr. Genet.
PUBLISHED: 09-03-2013
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We examined the pharmacogenetic association between a variant in the ?-opioid receptor (OPRK1) gene and the response to treatment with a cocaine vaccine tested in a recent clinical trial (October 2003 to April 2005). This gene has a protective allele for opioid addiction that may act by the inhibiting dopamine activation associated with reinforcement.
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Home-based treadmill training to improve gait performance in persons with a chronic transfemoral amputation.
Arch Phys Med Rehabil
PUBLISHED: 05-20-2013
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To investigate the effectiveness of a home-based multiple-speed treadmill training program to improve gait performance in persons with a transfemoral amputation (TFA).
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ANKK1 and DRD2 pharmacogenetics of disulfiram treatment for cocaine abuse.
Pharmacogenet. Genomics
PUBLISHED: 05-03-2013
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Disulfiram is a potential cocaine addiction pharmacotherapy. Since dopamine deficiency has been found with cocaine addiction, our objective was to examine whether functional variants in the ankyrin repeat and kinase domain-containing 1 (ANKK1) and/or the dopamine receptor D2 (DRD2) genes interact with response to treatment with disulfiram.
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Microbial production of the aromatic building-blocks (S)-styrene oxide and (R)-1,2-phenylethanediol from renewable resources.
Biotechnol J
PUBLISHED: 04-26-2013
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(S)-Styrene oxide and (R)-1,2-phenylethanediol are chiral aromatic molecular building blocks used commonly as precursors to pharmaceuticals and other specialty chemicals. Two pathways have been engineered in Escherichia coli for their individual biosynthesis directly from glucose. The novel pathways each constitute extensions of the previously engineered styrene pathway, developed by co-expressing either styrene monooxygenase (SMO) or styrene dioxygenase (SDO) to convert styrene to (S)-styrene oxide and (R)-1,2-phenylethanediol, respectively. StyAB from Pseudomonas putida S12 was determined to be the most effective SMO. SDO activity was achieved using NahAaAbAcAd of Pseudomonas sp. NCIB 9816-4, a naphthalene dioxygenase with known broad substrate specificity. Production of phenylalanine, the precursor to both pathways, was systematically enhanced through a number of mutations, most notably via deletion of tyrA and over-expression of tktA. As a result, (R)-1,2-phenylethanediol reached titers as high as 1.23 g/L, and at 1.32 g/L (S)-styrene oxide titers already approach their toxicity limit. As with other aromatics, product toxicity was strongly correlated with a model of membrane accumulation and disruption. This study additionally demonstrates that greater flux through the styrene pathway can be achieved if its toxicity is addressed, as achieved in this case by reacting styrene to less toxic products. See accompanying commentary by Brian F. Pfleger DOI 10.1002/biot.201300251.
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Choosing wisely: our list.
Otolaryngol Head Neck Surg
PUBLISHED: 02-28-2013
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In February 2013, the American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF) released its list of 5 recommendations of diagnostic and therapeutic interventions that physicians and patients should question, as part of the American Board of Internal Medicine (ABIM) Foundations Choosing Wisely campaign. This commentary outlines the impetus for the AAO-HNSF to join the campaign, our list of 5 recommendations, how they were developed, and our future involvement with the campaign. The AAO-HNSFs 5 recommendations are (1) dont order a computed tomography (CT) scan of the head/brain for sudden hearing loss, (2) dont prescribe oral antibiotics for uncomplicated acute tympanostomy tube otorrhea, (3) dont prescribe oral antibiotics for uncomplicated acute external otitis, (4) dont routinely obtain radiographic imaging for patients who meet diagnostic criteria for uncomplicated acute rhinosinusitis, and (5) dont obtain CT or magnetic resonance imaging in patients with a primary complaint of hoarseness prior to examining the larynx.
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DBH gene as predictor of response in a cocaine vaccine clinical trial.
Neurosci. Lett.
PUBLISHED: 02-21-2013
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We examined a pharmacogenetic association of the dopamine ?-hydroxylase (DBH) gene with a response to an anti-cocaine vaccine that was tested in a recent clinical trial. This gene is associated with cocaine-induced paranoia, which has a slower onset than the euphoria from cocaine. The vaccine reduced euphoria by slowing the entry of cocaine into the brain, but it may not reduce aversive symptoms like paranoia. A 16-week Phase IIb randomized double-blind placebo-controlled trial of 114 cocaine and opioid dependent subjects who received five vaccinations over the first 12 weeks was examined. We genotyped 71 subjects for the rs1611115 (-1021C>T) variant of the DBH gene and compared vaccine to placebo subjects on cocaine-free urines. Using repeated measures analysis of variance, corrected for population structure, vaccine pharmacotherapy reduced cocaine positive urines significantly based on DBH genotype. Patients with the low D?H level genotype dropped from 77% to 51% on vaccine (p=0.0001), while those with the normal D?H level genotype dropped from 83% to 72%. Placebo showed no effect on cocaine use overall or by genotype. This study indicates that a patients DBH genotype could be used to identify a subset of individuals for whom vaccine treatment may be an effective pharmacotherapy for cocaine dependence.
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Sex and litter effects on anxiety and DNA methylation levels of stress and neurotrophin genes in adolescent rats.
Dev Psychobiol
PUBLISHED: 02-04-2013
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Maternal care variations associate with DNA methylation of the glucocorticoid receptor gene, Nr3c1, in hippocampus at a nerve-growth factor-inducible protein 1 binding site. Epigenetic regulation of brain-derived neurotrophin factor is affected by early stress. These systems contribute to anxiety and fear. Early stress has sex-dependent effects perhaps reflecting sex differences in maternal care. Altering litter gender composition affects maternal behavior and DNA methylation levels of another gene in hippocampus and nucleus accumbens (NAc). We now test if DNA methylation levels of Nr3c1, Egr1, and Bdnf differ by litter composition or sex. Rats from mixed- or single-sex litters were tested for anxiety and fear on postnatal day 35. Brain tissues were collected and analyzed using direct sequencing methods. Females showed hypermethylation of Nr3c1 of hippocampal DNA and litter composition modified sex effects on methylation of Egr1 in NAc. Few differences were seen for Bdnf. LGC modified some sex differences in behavior. © 2013 Wiley Periodicals, Inc. Dev Psychobiol.
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Serotonin transporter genotype and mild traumatic brain injury independently influence resilience and perception of limitations in Veterans.
J Psychiatr Res
PUBLISHED: 01-22-2013
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Evidence indicates that individuals with the 5-HTTLPR variant short/short genotype have increased sensitivity to both positive and negative perceptions of perceived social support. The aim of this study was to evaluate this association among Veterans in the context of mild traumatic brain injury (TBI). As part of a larger TBI center, we performed a cross-sectional study of 67 OEF/OIF/OND Veterans (41 with TBI and 26 controls without TBI) who completed the questionnaires and consented to genetic testing. The primary measures included the Connor-Davidson Resilience Scale (CDRISC) and the Perceived Limitations in community participation subscale of the Community Reintegration of Service Members Instrument (CRIS-PL). Both 5-HTTLPR genotype and TBI status were independently associated with the CRIS-PL (p = .009 for genotype, p = .001 for TBI) and the CDRISC (p = .015 for genotype, p = .003 for TBI) scores. This study suggests that both the 5-HTTLPR genotype and TBI status independently, in an almost equal but opposite direction, influence resilience and perceived limitations to social participation. Further, resilience appears more sensitive to perceived limitations in Veterans carrying an SS genotype than in L carriers, but only in the context of having sustained a TBI. While having a TBI appeared to increase a Veterans sensitivity to social stress, the Veterans who were L allele carriers with a TBI fared the worst, with lower resilience and more perceived limitations for community participation compared to L carrier Veterans without a TBI or Veterans with the SS genotype regardless of TBI status.
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Engineering Escherichia coli for renewable production of the 5-carbon polyamide building-blocks 5-aminovalerate and glutarate.
Biotechnol. Bioeng.
PUBLISHED: 01-17-2013
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Through metabolic pathway engineering, novel microbial biocatalysts can be engineered to convert renewable resources into useful chemicals, including monomer building-blocks for bioplastics production. Here we describe the systematic engineering of Escherichia coli to produce, as individual products, two 5-carbon polyamide building blocks, namely 5-aminovalerate (AMV) and glutarate. The modular pathways were derived using "parts" from the natural lysine degradation pathway of Pseudomonas putida KT2440. Endogenous over-production of the required precursor, lysine, was first achieved through metabolic deregulation of its biosynthesis pathway by introducing feedback resistant mutants of aspartate kinase III and dihydrodipicolinate synthase. Further disruption of native lysine decarboxylase activity (by deleting cadA and ldcC) limited cadaverine by-product formation, enabling lysine production to 2.25?g/L at a glucose yield of 138?mmol/mol (18% of theoretical). Co-expression of lysine monooxygenase and 5-aminovaleramide amidohydrolase (encoded by davBA) then resulted in the production of 0.86?g/L AMV in 48?h. Finally, the additional co-expression of glutaric semialdehyde dehydrogenase and 5-aminovalerate aminotransferase (encoded by davDT) led to the production of 0.82?g/L glutarate under the same conditions. At this output, yields on glucose were 71 and 68?mmol/mol for AMV and glutarate (9.5 and 9.1% of theoretical), respectively. These findings further expand the number and diversity of polyamide monomers that can be derived directly from renewable resources.
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Engineering cyanobacteria for photosynthetic production of 3-hydroxybutyrate directly from CO2.
Metab. Eng.
PUBLISHED: 01-03-2013
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(S)- and (R)-3-hydroxybutyrate (3HB) are precursors to synthesize the biodegradable plastics polyhydroxyalkanoates (PHAs) and many fine chemicals. To date, however, their production has been restricted to petroleum-based chemical industry and sugar-based microbial fermentation, limiting its sustainability and economical feasibility. With the ability to fix CO2 photosynthetically, cyanobacteria have attracted increasing interest as a biosynthesis platform to produce fuels and chemicals from alternative renewable resources. To this end, synthesis metabolic pathways have been constructed and optimized in cyanobacterium Synechocystis sp. PCC 6803 to photosynthetically produce (S)- and (R)-3HB directly from CO2. Both types of 3HB molecules were produced and readily secreted from Synechocystis cells without over-expression of transporters. Additional inactivation of the competing pathway by deleting slr1829 and slr1830 (encoding PHB polymerase) from the Synechocystis genome further promoted the 3HB production. Up to 533.4mg/L 3HB has been produced after photosynthetic cultivation of the engineered cyanobacterium Synechocystis TABd for 21 days. Further analysis indicated that the phosphate consumption during the photoautrophic growth and the concomitant elevated acetyl-CoA pool acted as a key driving force for 3HB biosynthesis in Synechocystis. For the first time, the study has demonstrated the feasibility of photosynthetic production of (S)- and (R)-3HB directly from sunlight and CO2.
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Interspecific variation in resistance of Asian, European, and North American birches (Betula spp.) to bronze birch borer (Coleoptera: Buprestidae).
Environ. Entomol.
PUBLISHED: 10-14-2011
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Bronze birch borer (Agrilus anxius Gory) is the key pest of birches (Betula spp.) in North America, several of which have been recommended for ornamental landscapes based on anecdotal reports of borer resistance that had not been confirmed experimentally. In a 20-yr common garden experiment initiated in 1979 in Ohio, North American birch species, including paper birch (Betula papyrifera Marshall), Whitespire gray birch (Betula populifolia Marshall), and river birch (Betula nigra L.), were much more resistant to bronze birch borer than species indigenous to Europe and Asia, including European white birch (Betula pendula Roth), downy birch (Betula pubescens Ehrh.), monarch birch (Betula maximowicziana Regel), and Szechuan white birch (Betula szechuanica Jansson). Within 8 yr of planting, every European white, downy, and Szechuan birch had been colonized and killed, although 100% of monarch birch had been colonized and 88% of these plants were killed after nine years. Conversely, 97% of river birch, 76% of paper birch, and 73% Whitespire gray birch were alive 20 yr after planting, and river birch showed no evidence of colonization. This pattern is consistent with biogeographic theory of plant defense: North American birch species that share a coevolutionary history with bronze birch borer were much more resistant than naïve hosts endemic to Europe and Asia, possibly by virtue of evolution of targeted defenses. This information suggests that if bronze birch borer were introduced to Europe or Asia, it could threaten its hosts there on a continental scale. This study also exposed limitations of anecdotal observation as evidence of host plant resistance.
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Clinical and Radiological Mid-Term Outcomes of Lumbar Single-Level Total Disc Replacement.
Spine
PUBLISHED: 09-14-2011
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ABSTRACT: Study Design. Prospective single-center case cohort study.Objective. Evaluation of clinical and radiographic outcomes of a consecutive 122-patient cohort with discogenic back pain, at 2 - to 10-year follow-up periods, treated by a single surgeon, with CHARITÉ® Artificial Disc (DePuy Spine, Raynham, MA, USA).Summary of Background Data. Minimum two-year clinical and radiographic Level 1 data for the first lumbar artificial disc, the CHARITÉ® Artificial Disc, has recently been published, demonstrating sustained clinical benefit of the device for the treatment of degenerative disc disease (DDD).Methods. Patients were assessed preoperatively using clinical outcome measures, including Visual Analogue Score (VAS) back and leg, Oswestry Disability Index (ODI), Short Form - 36 (SF-36), and Roland-Morris Questionnaires (RMDQ), and further assessed postoperatively, 3-months, 6-months, 12-months, and yearly thereafter.Results. Average follow-up was 44.9±23.3 months (n = 122). The median age at surgery was 43.0±9.0 years. Preoperative diagnosis included DDD in 118 (96.7%) and internal disc disruption (IDD) in 4 (3.3%). Surgery was performed at L5-S1 in 96 (77.9%) patients and at L4-5 in 27 (22.1%). Statistically significant clinical improvements from baseline were observed on VAS (back and leg), ODI, SF-36 PCS, SF-36 MCS, and RMDQ from 3 months onwards. Back VAS scores decreased from 78.2±21.3 preoperatively to 21.9±27.8 by final follow-up. ODI scores decreased from 51.1±17.3 to 16.2±17.9 at last follow-up. The RMDQ scores also decreased, from 16.7±4.7 to 4.2±5.8. SF-36 PCS and MCS increased from 25.7±11.0 to 46.4±10.3 for PCS and from 35.5±17.4 to 51.6±10.8 for MCS. Patient satisfaction surveys indicated that 90.56% patients rated their satisfaction with the surgery as "excellent" or "good" at 2 years. Range of motion averaged 8.6°±3.5° (median: 8.0°) at the last follow-up time point.Conclusions. Outcomes verify the clinical efficacy of total disc replacement (TDR) for treatment of discogenic back pain with or without radiculopathy. The outcomes instruments demonstrated statistically significant improvements from 3 months onwards.
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Clinical course of ICU patients with severe pandemic 2009 influenza A (H1N1) pneumonia: single center experience with proning and pressure release ventilation.
J Intensive Care Med
PUBLISHED: 05-18-2011
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A number of different modalities have been employed in addition to conventional ventilation to improve oxygenation in patients with severe 2009 pandemic influenza A (H1N1) pneumonia. Outcomes with ventilatory and rescue therapies for H1N1 influenza-related acute respiratory distress syndrome (ARDS) have been varied. A single intensive care unit (ICU) experience with management of laboratory-confirmed 2009 pandemic influenza A (H1N1) ARDS with a combination of proning and airway pressure release ventilation (APRV) is described.
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Meaningful use of electronic health records in otolaryngology: recommendations from the American Academy of Otolaryngology--Head and Neck Surgery Medical Informatics Committee.
Otolaryngol Head Neck Surg
PUBLISHED: 04-16-2011
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Under the Health Information Technology for Economic and Clinical Health (HITECH) Act, passed as a part of the American Recovery and Reinvestment Act of 2009, the US Congress implemented new regulations to encourage the adoption of electronic health records (EHRs). The federal government will expend up to $27 billion in incentive payments to physicians and hospitals to increase adoption and implement "meaningful use" of EHRs. Otolaryngologists may receive as much as $44,000 under Medicare or $63,750 under Medicaid as part of this law. In July 2010, the US Department of Health and Human Services announced final rules to support "meaningful use." This commentary discusses recommendations from the American Academy of Otolaryngology--Head and Neck Surgery Medical Informatics Committee for implementing "meaningful use" of EHRs to improve safety, quality, and efficiency of patient care and receiving incentive payments as defined by these new regulations.
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Facial soft-tissue fillers conference: assessing the state of the science.
Plast. Reconstr. Surg.
PUBLISHED: 04-15-2011
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: The American Society of Plastic Surgeons and the American Academy of Dermatology, with the support of other sister societies, conducted the Facial Soft-Tissue Fillers: Assessing the State of the Science conference in December of 2009. The American Society of Plastic Surgeons and the American Academy of Dermatology established a panel of leading experts in the field of soft-tissue fillers-from researchers to clinicians-and other stakeholders for the conference to examine and discuss issues of patient safety, efficacy, and effectiveness in relation to the approved and off-label use of soft-tissue fillers, and other factors, including the training and level of experience of individuals administering fillers. This report represents the systematic literature review that examines comprehensively the available evidence and gaps in the evidence related to soft-tissue fillers, to inform and support the work of the state-of-the-science conference panel. This evidence-based medicine review will serve as the foundation for future evidence-based medicine reports in this growing field.
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Comparison of ventilator-associated pneumonia (VAP) rates between different ICUs: Implications of a zero VAP rate.
J Crit Care
PUBLISHED: 04-11-2011
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Ventilator-associated pneumonia (VAP) is associated with significant morbidity and mortality. Measures to reduce the incidence of VAP have resulted in institutions reporting a zero or near-zero VAP rates. The implications of zero VAP rates are unclear. This study was done to compare outcomes between two intensive care units (ICU) with one of them reporting a zero VAP rate.
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Facial Soft-Tissue Fillers conference: Assessing the State of the Science.
J. Am. Acad. Dermatol.
PUBLISHED: 04-05-2011
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The American Academy of Dermatology and the American Society of Plastic Surgeons, with the support of other sister societies, conducted the Facial Soft-Tissue Fillers: Assessing the State of the Science conference in December of 2009. The American Academy of Dermatology and the American Society of Plastic Surgeons established a panel of leading experts in the field of soft-tissue fillers-from researchers to clinicians-and other stakeholders for the conference to examine and discuss issues of patient safety, efficacy, and effectiveness in relation to the approved and off-label use of soft-tissue fillers, and other factors, including the training and level of experience of individuals administering fillers. This report represents the systematic literature review that examines comprehensively the available evidence and gaps in the evidence related to soft-tissue fillers, to inform and support the work of the state-of-the-science conference panel. This evidence-based medicine review will serve as the foundation for future evidence-based medicine reports in this growing field.
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Facial Soft-Tissue Fillers: Assessing the State of the Science conference---Proceedings report.
J. Am. Acad. Dermatol.
PUBLISHED: 04-05-2011
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The American Academy of Dermatology and the American Society of Plastic Surgeons, with the support of other sister societies, conducted the Facial Soft-Tissue Fillers: Assessing the State of the Science conference in December of 2009. The American Academy of Dermatology and the American Society of Plastic Surgeons established a panel of leading experts in the field of soft-tissue fillers-from researchers to clinicians-and other stakeholders for the conference to examine and discuss issues of patient safety, efficacy, and effectiveness in relation to the approved and off-label use of soft-tissue fillers, and other factors, including the training and level of experience of individuals administering fillers. This report summarizes the deliberations and key points made by the panel and presenters to the panel, and includes a summary of the panels near-term and longer term recommendations for next steps to help guide future efforts to address the safety, efficacy, and effectiveness of facial soft-tissue fillers. This report represents the panels assessment of the medical knowledge available on facial soft-tissue fillers at the time of the conference.
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Styrene biosynthesis from glucose by engineered E. coli.
Metab. Eng.
PUBLISHED: 03-18-2011
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Styrene is a large volume, commodity petrochemical with diverse commercial applications, including as a monomer building-block for the synthesis of many useful polymers. Here we demonstrate how, through the de novo design and development of a novel metabolic pathway, styrene can alternatively be synthesized from renewable substrates such as glucose. The conversion of endogenously synthesized l-phenylalanine to styrene was achieved by the co-expression of phenylalanine ammonia lyase and trans-cinnamate decarboxylase. Candidate isoenzymes for each step were screened from bacterial, yeast, and plant genetic sources. Finally, over-expression of PAL2 from Arabidopsis thaliana and FDC1 from Saccharomyces cerevisiae (originally classified as ferulate decarboxylase) in an l-phenylalanine over-producing Escherichia coli host led to the accumulation of up to 260 mg/L in shake flask cultures. Achievable titers already approach the styrene toxicity threshold (determined as ~300 mg/L). To the best of our knowledge, this is the first report of microbial styrene production from sustainable feedstocks.
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Litter gender composition and sex affect maternal behavior and DNA methylation levels of the oprm1 gene in rat offspring.
Front Psychiatry
PUBLISHED: 02-22-2011
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The mu-opioid receptor is encoded by the Oprm1 gene and contributes to mother-infant behaviors. Rodent dams lick male pups more than female pups in the anogenital region. This behavior is linked to stress responsivity in the offspring that may be mediated by epigenetic changes. We hypothesized that maternal behavior may affect DNA methylation levels of the Oprm1 gene and show sex differences. To further explore sex differences in mother-pup behaviors and DNA methylation levels, we altered the litter gender composition (LGC) of rats. Litters were culled to eight all male, all female, or four male/four female pups on postnatal (PN) day 1. On PN4, 7, and 10, a dam was placed in a test cage with a pup for a 10-min period. Latency to pup contact was determined as were times spent licking the anogenital and other body regions of the pup. Frequencies of other behaviors were tabulated. On PN35, samples from various brain regions were obtained. DNA methylation at specific CpG sites in the Oprm1 promoter region were measured by direct sequencing of bisulfite-treated DNA. LGC and sex interacted with day for latency to pup contact. Latencies were longest on PN4 for single-sex males and on PN10 for single-sex females. Dams licked male pups more than female pups in both the anogenital and other body areas. Sex differences were seen in other behaviors. LGC altered DNA methylation at specific CpGs of Oprm1 in hippocampus with higher levels in single-sex rats. In nucleus accumbens, single-sex males showed hypermethylation levels, a trend seen in caudate-putamen. Results confirm and extend sex differences in maternal care with modest LGC effects. That both LGC and sex have enduring effects on DNA methylation of the Oprm1 gene in brain regions associated with addiction, stress regulation, motivation, and cognition may suggest one factor that contributes to gender differences in these behaviors.
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Species composition, seasonal activity, and semiochemical response of native and exotic bark and ambrosia beetles (Coleoptera: Curculionidae: Scolytinae) in northeastern Ohio.
J. Econ. Entomol.
PUBLISHED: 09-23-2010
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In 2007, we surveyed the alien and endemic scolytine (bark and ambrosia beetles) fauna of northeastern Ohio, and for the most abundant species, we characterized their seasonal activity and response to three semiochemical baits. In total ,5,339 scolytine beetles represented by 47 species and 29 genera were caught in Lindgren funnel traps. Three species constituted 57% of the total catch, including Xylosandrus germanus (Blandford), Tomicus piniperda (L.), and Dryocoetes autographus (Ratzeburg). Of the total captured, 32% of the species and approximately 60% of the individuals were exotic, suggesting that exotic species numerically dominate the scolytine fauna in some urban areas. More native and exotic species were caught in traps baited with ethanol alone than in traps baited with other lures. However, significantly more individuals, especially of T. piniperda, D. autographus, Gnathotrichus materiarius (Fitch), and Ips grandicollis (Eichhoff), and species were caught in traps baited with ethanol plus alpha-pinene than in traps baited with ethanol alone or the exotic Ips lure. This suggests that among these baits, the ethanol plus alpha-pinene baits may be useful in maximizing scolytine beetle catches of these species within this region. Species diversity and richness for both native and exotic beetles was greatest in traps baited with ethanol alone. The period of peak trap capture varied depending upon species: X. germanus was most abundant in traps in mid-May and early-August; T. piniperda in mid-May; D. autographus in early June, mid-July, and mid-September; Anisandrus sayi Hopkins and G. materiarius in mid-May, mid-July, and early September; and I. grandicollis in early April, mid-July, and late September.
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Cell-specific effects of variants of the 68-base pair tandem repeat on prodynorphin gene promoter activity.
Addict Biol
PUBLISHED: 08-23-2010
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A polymorphic 68-bp tandem repeat has been identified within the promoter of the human prodynorphin (PDYN) gene. We found that this 68-bp repeat in the PDYN promoter occurs naturally up to five times. We studied the effect of the number of 68-bp repeats, and of a SNP (rs61761346) found within the repeat on PDYN gene promoter activity. Thirteen promoter forms, different naturally occurring combinations of repeats and the internal SNP, were cloned upstream of the luciferase reporter gene, transfected into human SK-N-SH, H69, or HEK293 cells. Cells were then stimulated with TPA or caffeine. We found cell-specific effects of the number of 68-bp repeats on the transcriptional activity of the PDYN promoter. In SK-N-SH and H69 cells, three or four repeats led to lower expression of luciferase than did one or two repeats. The opposite effect was found in HEK293 cells. The SNP also had an effect on PDYN gene expression in both SK-N-SH and H69 cells; promoter forms with the A allele had significantly higher expression than promoter forms with the G allele. These results further our understanding of the complex transcriptional regulation of the PDYN gene promoter.
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A strategic approach for the design and operation of two-phase partitioning bioscrubbers for the treatment of volatile organic compounds.
Biotechnol. Prog.
PUBLISHED: 08-19-2010
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A strategic approach for the design of two-phase partitioning bioscrubbers (TPPBs) has been formulated using, as a basis, a re-evaluation of extensive literature data available for the degradation of benzene by Achromobacter xylosoxidans Y234 in TPPBs with n-hexadecane as the partitioning phase. Using a previously determined maintenance coefficient for benzene, we determined that an inlet benzene loading rate of 100 mg/h requires 5,928 mg cell mass at biological steady state and 243.0 mg O(2) /h. The total oxygen-transfer rates (TOTRs) into the TPPB increased by 83.5% with 33.3% of organic phase compared with a single aqueous phase and were significantly influenced by gas flow rate, whereas agitation has a minor affect. The fraction of organic phase used was suggested to be the primary parameter with which the TOTR into the TPPB may be altered. Although the presence of an organic solvent in the TPPB remarkably increased the TOTR, the total benzene transfer rate into the TPPB remained largely insensitive due to the intrinsic low Henrys law constant (or relatively high solubility) of benzene in water. Finally, we have integrated the elements of this analysis into a set of heuristic criteria that can serve as a guideline for the design of TPPB systems for future volatile organic compound treatment applications.
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Genome-wide association study identifies genes that may contribute to risk for developing heroin addiction.
Psychiatr. Genet.
PUBLISHED: 06-04-2010
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We have used genome-wide association studies to identify variants that are associated with vulnerability to develop heroin addiction.
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Metabolic engineering of acetoin and meso-2, 3-butanediol biosynthesis in E. coli.
Biotechnol J
PUBLISHED: 03-10-2010
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The functional reconstruction of acetoin and meso-2,3-butanediol (meso-2,3-BD) biosynthetic pathways in Escherichia coli have been explored systematically. Pathway construction involved the in vsivo screening of prospective pathway isozymes of yeast and bacterial origin. After substantial engineering of the host background to increase pyruvate availability, E. coli YYC202(DE3) ldhA(() ilvC( expressing ilvBN from E. coli and aldB from L. lactis (encoding acetolactate synthase and acetolactate decarboxylase activities, respectively) was able to produce up to 870 mg/L acetoin, with no coproduction of diacetyl observed. These strains were also found to produce small quantities of meso-2,3-BD, suggesting the existence of endogenous 2,3-BD dehydrogenase activity. Finally, the coexpression of bdh1 from S. cerevisiae, encoding 2,3-BD dehydrogenase, in this strain resulted in the production of up to 1120 mg/L meso-2,3-BD, with glucose a yield of 0.29 g/g. While disruption of the native lactate biosynthesis pathway increased pyruvate precursor availability to this strain, increased availability of NADH for acetoin reduction to meso-2,3-BD was found to be the most important consequence of ldhA deletion.
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Search for genetic markers and functional variants involved in the development of opiate and cocaine addiction and treatment.
Ann. N. Y. Acad. Sci.
PUBLISHED: 03-06-2010
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Addiction to opiates and illicit use of psychostimulants is a chronic, relapsing brain disease that, if left untreated, can cause major medical, social, and economic problems. This article reviews recent progress in studies of association of gene variants with vulnerability to develop opiate and cocaine addictions, focusing primarily on genes of the opioid and monoaminergic systems. In addition, we provide the first evidence of a cis-acting polymorphism and a functional haplotype in the PDYN gene, of significantly higher DNA methylation rate of the OPRM1 gene in the lymphocytes of heroin addicts, and significant differences in genotype frequencies of three single-nucleotide polymorphisms of the P-glycoprotein gene (ABCB1) between "higher" and "lower" methadone doses in methadone-maintained patients. In genomewide and multigene association studies, we found association of several new genes and new variants of known genes with heroin addiction. Finally, we describe the development and application of a novel technique: molecular haplotyping for studies in genetics of drug addiction.
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Ethnic diversity of DNA methylation in the OPRM1 promoter region in lymphocytes of heroin addicts.
Hum. Genet.
PUBLISHED: 02-19-2010
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The mu-opioid receptor is the site of action of many endogenous opioids as well as opiates. We hypothesize that differences in DNA methylation of specific CpG dinucleotides between former severe heroin addicts in methadone maintenance treatment and control subjects will depend, in part, upon ethnicity. DNA methylation analysis of the mu-opioid receptor gene (OPRM1) promoter region was performed on African-Americans (118 cases, 80 controls) and Hispanics (142 cases, 61 controls) and these were compared with a similar Caucasian cohort from our earlier study. In controls, a higher methylation level was found in the African-Americans compared with the Hispanics or Caucasians. Significant experiment-wise differences in methylation levels were found at the -25 and +12 CpG sites in the controls among the three ethnicities. The overall methylation level of the CpG sites were significantly higher in the former heroin addicts when compared with the controls (point-wise P = 0.0457). However, in the African-Americans, the degree of methylation was significantly decreased experiment-wise in the former heroin addicts at the +12 CpG site (P = 0.0032, Bonferroni corrected general estimating equations). In Hispanics, the degree of methylation was increased in the former heroin addicts at the -25 (P < 0.001, experiment-wise), -14 (P = 0.001, experiment-wise), and +27 (P < 0.001, experiment-wise) CpG sites. These changes in methylation of the OPRM1 promoter region may lead to altered expression of the mu-opioid receptor gene in the lymphocytes of former heroin addicts who are stabilized in methadone maintenance treatment.
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Wrong-site sinus surgery in otolaryngology.
Otolaryngol Head Neck Surg
PUBLISHED: 02-09-2010
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To determine the scope of wrong-site sinus surgery.
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The relationship of interacting immunological components in dengue pathogenesis.
Virol. J.
PUBLISHED: 10-27-2009
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The World Health Organization (WHO) estimates that there are over 50 million cases of dengue fever reported annually and approximately 2.5 billion people are at risk. Mild dengue fever presents with headache, fever, rash, myalgia, osteogenic pain, and lethargy. Severe disease can manifest as dengue shock syndrome (DSS) or dengue hemorrhagic fever (DHF). Symptoms of DSS/DHF are leukopenia, low blood volume and pressure encephalitis, cold and sweaty skin, gastrointestinal bleeding, and spontaneous bleeding from gums and nose. Currently, there are no therapeutics available beyond supportive care and untreated complicated dengue fever can have a 50% mortality rate. According to WHO DSS/DHF is the leading cause of childhood mortality in some Asian countries. Dendritic cells are professional antigen presenting cells that are primary targets in a dengue infection. Dengue binds to Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN). DC-SIGN has a high affinity for ICAM3 which is expressed in activating T-cells. Previous studies have demonstrated an altered T-cell phenotype expressed in dengue infected patients that could be potentially mediated by dengue-infected DCs.Dengue is enhanced by three interacting components of the immune system. Dengue begins by infecting dendritic cells which in immature dendritic cells is mediated by DC-SIGN. In mature dendritic cells, antibodies can enhance dengue infection via Fc receptors. Downstream of dendritic cells T-cells become activated and generate the very cytokines implicated in vascular leak and shock in addition to activating effector cells. Both the virus and the antibodies are involved in release of complement and anaphylatoxins which can cause or exacerbate DHF/DSS. These systems are inextricable and strongly associated with dengue pathogenesis.
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Estimating the cellular maintenance coefficient and its use in the design of two-phase partitioning bioscrubbers.
Bioprocess Biosyst Eng
PUBLISHED: 10-21-2009
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One of the key roles of an organic solvent has emerged to be the enhancement of oxygen transfer in two-phase partitioning bioscrubbers (TPPBs). In order to determine an optimum organic fraction for a given VOCs loading, the oxygen demand of the total cell mass must be estimated, which depends upon the magnitude of the cellular maintenance coefficient. We have estimated the dynamics of the maintenance coefficient for benzene degradation by Achromobacter xylosoxidans Y234 in a TPPB and found that the maintenance coefficient generally decreased as cells accumulated in the TPPB but converged to a specific value of 1.750 x 10(-2) h(-1) at biological steady state. Due to its important influence on all of the essential design parameters of the TPPB system, including optimum organic fraction, aeration rate and agitation speed, the maintenance coefficient should be considered as a key biological determinant for microorganism selection, as well as in overall TPPB design.
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In situ product recovery of n-butanol using polymeric resins.
Biotechnol. Bioeng.
PUBLISHED: 08-07-2009
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Polymeric resins with high n-butanol adsorption affinities were identified from a candidate pool of commercially available materials representing a wide array of physical and chemical properties. Resin hydrophobicity, which was dictated by the chemical structure of its constituent monomer units, most greatly influenced the resin-aqueous equilibrium partitioning of n-butanol whereas ionic functionalization appeared to have no effect. In general, those materials derived from poly(styrene-co-divinylbenzene) possessed the greatest n-butanol affinity, while the adsorption potential of these resins was limited by their specific surface area. Resins were tested for their ability to serve as effective in situ product recovery (ISPR) devices in the n-butanol fermentation by Clostridium acetobutylicum ATCC 824. In small-scale batch fermentations, the addition of 0.05 kg/L Dowex Optipore SD-2 facilitated achievement of effective n-butanol titers as high as 2.22% (w/v), well above the inhibitory threshold of C. acetobutylicum ATCC 824, and nearly twice that of traditional, single-phase fermentations. Retrieval of n-butanol from resins via thermal treatment was demonstrated with high efficiency and predicted to be economically favorable. Due to its modular nature, the proposed ISPR design exhibits strong potential for compatibility with future n-butanol fermentation efforts.
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Engineering alternative butanol production platforms in heterologous bacteria.
Metab. Eng.
PUBLISHED: 05-13-2009
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Alternative microbial hosts have been engineered as biocatalysts for butanol biosynthesis. The butanol synthetic pathway of Clostridium acetobutylicum was first re-constructed in Escherichia coli to establish a baseline for comparison to other hosts. Whereas polycistronic expression of the pathway genes resulted in the production of 34 mg/L butanol, individual expression of pathway genes elevated titers to 200 mg/L. Improved titers were achieved by co-expression of Saccharomyces cerevisiae formate dehydrogenase while overexpression of E. coli glyceraldehyde 3-phosphate dehydrogenase to elevate glycolytic flux improved titers to 580 mg/L. Pseudomonas putida and Bacillus subtilis were also explored as alternative production hosts. Polycistronic expression of butanol biosynthetic genes yielded butanol titers of 120 and 24 mg/L from P. putida and B. subtilis, respectively. Production in the obligate aerobe P. putida was dependent upon expression of bcd-etfAB. These results demonstrate the potential of engineering butanol biosynthesis in a variety of heterologous microorganisms, including those cultivated aerobically.
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A functional haplotype implicated in vulnerability to develop cocaine dependence is associated with reduced PDYN expression in human brain.
Neuropsychopharmacology
PUBLISHED: 05-08-2009
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Dynorphin peptides and the kappa-opioid receptor are important in the rewarding properties of cocaine, heroin, and alcohol. We tested polymorphisms of the prodynorphin gene (PDYN) for association with cocaine dependence and cocaine/alcohol codependence. We genotyped six single nucleotide polymorphisms (SNPs), located in the promoter region, exon 4 coding, and 3 untranslated region, in 106 Caucasians and 204 African Americans who were cocaine dependent, cocaine/alcohol codependent, or controls. In Caucasians, we found point-wise significant associations of 3UTR SNPs (rs910080, rs910079, and rs2235749) with cocaine dependence and cocaine/alcohol codependence. These SNPs are in high linkage disequilibrium, comprising a haplotype block. The haplotype CCT was significantly experiment-wise associated with cocaine dependence and with combined cocaine dependence and cocaine/alcohol codependence (false discovery rate, q=0.04 and 0.03, respectively). We investigated allele-specific gene expression of PDYN, using SNP rs910079 as a reporter, in postmortem human brains from eight heterozygous subjects, using SNaPshot assay. There was significantly lower expression for C allele (rs910079), with ratios ranging from 0.48 to 0.78, indicating lower expression of the CCT haplotype of PDYN in both the caudate and nucleus accumbens. Analysis of total PDYN expression in 43 postmortem brains also showed significantly lower levels of preprodynorphin mRNA in subjects having the risk CCT haplotype. This study provides evidence that a 3UTR PDYN haplotype, implicated in vulnerability to develop cocaine addiction and/or cocaine/alcohol codependence, is related to lower mRNA expression of the PDYN gene in human dorsal and ventral striatum.
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Predicting the adsorption of second generation biofuels by polymeric resins with applications for in situ product recovery (ISPR).
Bioresour. Technol.
PUBLISHED: 03-26-2009
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The application of hydrophobic polymeric resins as solid-phase adsorbent materials for the recovery and purification of prospective second generation biofuel compounds, including ethanol, iso-propanol, n-propanol, iso-butanol, n-butanol, 2-methyl-1-butanol, 3-methyl-1-butanol, and n-pentanol, has been investigated. A simple, yet robust correlation has been proposed to model the relative equilibrium partitioning behavior of a series of branched and n-alcohols as a function of their relative hydrophobicity, and has been applied to ultimately predict their adsorption potential. The proposed model adequately predicts the adsorption behavior of the entire series of alcohols studied, as well as with six different adsorbent phases composed of three different polymer matrices. Those resins with a non-polar monomeric structure and high specific surface area provided the highest overall adsorption of each of the studied compounds. Meanwhile, longer chain alcohols were subject to greater adsorption due to their increasingly hydrophobic nature. Among the tested series of alcohols, five-carbon isomers displayed the greatest potential for economical recovery in future, multiphase bioprocess designs. The present study provides the first demonstration of the ability of hydrophobic polymer resins to serve as effective in situ product recovery (ISPR) devices for the production of second generation biofuels.
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Increased OPRM1 DNA methylation in lymphocytes of methadone-maintained former heroin addicts.
Neuropsychopharmacology
PUBLISHED: 03-24-2009
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The mu-opioid receptor is the site of action of opiates and opioids. We examined whether there are differences in cytosine:guanine (CpG) dinucleotide methylation in the OPRM1 promoter between former heroin addicts and controls. We analyzed methylation at 16 CpG dinucleotides in DNA obtained from lymphocytes of 194 Caucasian former severe heroin addicts stabilized in methadone maintenance treatment and 135 Caucasian control subjects. Direct sequencing of bisulfite-treated DNA showed that the percent methylation at two CpG sites was significantly associated with heroin addiction. The level of methylation at the -18 CpG site was 25.4% in the stabilized methadone-maintained former heroin addicts and 21.4% in controls (p=0.0035, generalized estimating equations (GEE); p=0.0077, t-test; false discovery rate (FDR)=0.048), and the level of methylation at the +84 CpG dinucleotide site was 7.4% in cases and 5.6% in controls (p=0.0095, GEE; p=0.0067, t-test; FDR=0.080). Both the -18 and the +84 CpG sites are located in potential Sp1 transcription factor-binding sites. Methylation of these CpG sites may lead to reduced OPRM1 expression in the lymphocytes of these former heroin addicts.
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Metabolic engineering of Escherichia coli for enhanced production of (R)- and (S)-3-hydroxybutyrate.
Appl. Environ. Microbiol.
PUBLISHED: 03-20-2009
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Synthetic metabolic pathways have been constructed for the production of enantiopure (R)- and (S)-3-hydroxybutyrate (3HB) from glucose in recombinant Escherichia coli strains. To promote maximal activity, we profiled three thiolase homologs (BktB, Thl, and PhaA) and two coenzyme A (CoA) removal mechanisms (Ptb-Buk and TesB). Two enantioselective 3HB-CoA dehydrogenases, PhaB, producing the (R)-enantiomer, and Hbd, producing the (S)-enantiomer, were utilized to control the 3HB chirality across two E. coli backgrounds, BL21Star(DE3) and MG1655(DE3), representing E. coli B- and K-12-derived strains, respectively. MG1655(DE3) was found to be superior for the production of each 3HB stereoisomer, although the recombinant enzymes exhibited lower in vitro specific activities than BL21Star(DE3). Hbd in vitro activity was significantly higher than PhaB activity in both strains. The engineered strains achieved titers of enantiopure (R)-3HB and (S)-3HB as high as 2.92 g liter(-1) and 2.08 g liter(-1), respectively, in shake flask cultures within 2 days. The NADPH/NADP+ ratio was found to be two- to three-fold higher than the NADH/NAD+ ratio under the culture conditions examined, presumably affecting in vivo activities of PhaB and Hbd and resulting in greater production of (R)-3HB than (S)-3HB. To the best of our knowledge, this study reports the highest (S)-3HB titer achieved in shake flask E. coli cultures to date.
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Synthetic metabolism: engineering biology at the protein and pathway scales.
Chem. Biol.
PUBLISHED: 01-21-2009
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Biocatalysis has become a powerful tool for the synthesis of high-value compounds, particularly so in the case of highly functionalized and/or stereoactive products. Nature has supplied thousands of enzymes and assembled them into numerous metabolic pathways. Although these native pathways can be use to produce natural bioproducts, there are many valuable and useful compounds that have no known natural biochemical route. Consequently, there is a need for both unnatural metabolic pathways and novel enzymatic activities upon which these pathways can be built. Here, we review the theoretical and experimental strategies for engineering synthetic metabolic pathways at the protein and pathway scales, and highlight the challenges that this subfield of synthetic biology currently faces.
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The MTHFR C677T Variant is Associated with Responsiveness to Disulfiram Treatment for Cocaine Dependency.
Front Psychiatry
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Objective: Disulfiram is a one of the few pharmacotherapies for cocaine addiction that shows promise. Since disulfiram and cocaine both affect levels of global methylation we hypothesized the MTHFR gene, whose product is involved in supplying methyl groups for DNA and protein methylation, may be associated with responsiveness to disulfiram in cocaine-dependent individuals. Methods: Sixty-seven cocaine-dependent patients were stabilized on methadone for 2?weeks and then randomized into disulfiram (250?mg/day, N?=?32) and placebo groups (N?=?35) for 10?weeks. Patients were genotyped for the MTHFR (rs1801133, also known as C677T) polymorphism and the data was evaluated for association with cocaine-free urines in the disulfiram or placebo groups. Data from patients that completed all 10?weeks of the study (N?=?56) were analyzed using repeated measures analysis of variance (ANOVA), corrected for population structure. Results: The CT or TT MTHFR genotype group (N?=?32) dropped from 73 to 52% cocaine-positive urines on disulfiram (p?=?0.0001), while the placebo group showed no treatment effect. The CC MTHFR genotype group (N?=?24) showed a smaller, but still significant, reduction in cocaine-positive urines on disulfiram compared to placebo; 81-69% (p?=?0.007). Conclusion: This study indicates that a patients MTHFR genotype may be used to identify individuals who might show improved response to disulfiram treatment for cocaine dependence. Clinical Trial: Pharmacogenetics of Disulfiram for Cocaine, clinicaltrials.gov/ct2/show/NCT00149630, NIDA-18197-2, NCT00149630.
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The impact of disulfiram treatment on the reinforcing effects of cocaine: a randomized clinical trial.
PLoS ONE
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Clinical trials indicate that disulfiram (250 mg/d) reduces cocaine use, though one study found that treatment with lower doses of disulfiram (62.5 and 125 mg/d) increased cocaine use. We conducted the present study to better understand how disulfiram alters the reinforcing effects of cocaine in cocaine users.
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Engineering microbial chemical factories to produce renewable "biomonomers".
Front Microbiol
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By applying metabolic engineering tools and strategies to engineer synthetic enzyme pathways, the number and diversity of commodity and specialty chemicals that can be derived directly from renewable feedstocks is rapidly and continually expanding. This of course includes a number of monomer building-block chemicals that can be used to produce replacements to many conventional plastic materials. This review aims to highlight numerous recent and important advancements in the microbial production of these so-called "biomonomers." Relative to naturally-occurring renewable bioplastics, biomonomers offer several important advantages, including improved control over the final polymer structure and purity, the ability to synthesize non-natural copolymers, and allowing products to be excreted from cells which ultimately streamlines downstream recovery and purification. To highlight these features, a handful of biomonomers have been selected as illustrative examples of recent works, including polyamide monomers, styrenic vinyls, hydroxyacids, and diols. Where appropriate, examples of their industrial penetration to date and end-product uses are also highlighted. Novel biomonomers such as these are ultimately paving the way toward new classes of renewable bioplastics that possess a broader diversity of properties than ever before possible.
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Epigenetics of drug abuse: predisposition or response.
Pharmacogenomics
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Drug addiction continues to be a serious medical and social problem. Vulnerability to develop an addiction to drugs is dependent on genetic, environmental, social and biological factors. In particular, the interactions of environmental and genetic factors indicate the significance of epigenetic mechanisms, which have been found to occur in response to illicit drug use or as underlying factors in chronic substance abuse and relapse. Epigenetics is defined as the heritable and possibly reversible modifications in gene expression that do not involve alterations in the DNA sequence. This review discusses the various types of epigenetic modifications and their relevance to drug addiction to elucidate whether epigenetics is a predisposing factor, or a response to, developing an addiction to drugs of abuse.
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Pharmacogenetic randomized trial for cocaine abuse: disulfiram and dopamine ?-hydroxylase.
Biol. Psychiatry
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Disulfiram has been an effective cocaine addiction pharmacotherapy, and one of its possible mechanisms of efficacy is through copper chelation and inhibition of an enzyme involved in catecholamine metabolism, dopamine ?-hydroxylase (D?H), which converts dopamine to norepinephrine. A variant in the gene encoding D?H leads to reduced D?H activity, and as such, disulfiram might not be an effective treatment of cocaine dependence for individuals with this variant. This study explored that potential matching.
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Forced Abstinence from Cocaine Self-Administration is Associated with DNA Methylation Changes in Myelin Genes in the Corpus Callosum: a Preliminary Study.
Front Psychiatry
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Background: Human cocaine abuse is associated with alterations in white matter integrity revealed upon brain imaging, an observation that is recapitulated in an animal model of continuous cocaine exposure. The mechanism through which cocaine may affect white matter is unknown and the present study tested the hypothesis that cocaine self-administration results in changes in DNA methylation that could result in altered expression of several myelin genes that could contribute to the effects of cocaine on white matter integrity. Methods: In the present study, we examined the impact of forced abstinence from cocaine self-administration on chromatin associated changes in white matter. To this end, rats were trained to self-administer cocaine (0.75?mg/kg/0.1?mL infusion) for 14?days followed by forced abstinence for 1?day (n?=?6) or 30?days (n?=?6) before sacrifice. Drug-free, sham surgery controls (n?=?7) were paired with the experimental groups. Global DNA methylation and DNA methylation at specific CpG sites in the promoter regions ofmyelin basic protein (Mbp), proteolipid protein-1 (Plp1), and SRY-related HMG-box-10 (Sox10) genes were analyzed in DNA extracted from corpus callosum. Results: Significant differences in the overall methylation patterns of the Sox10 promoter region were observed in the corpus callosum of rats at 30?days of forced abstinence from cocaine self-administration relative to sham controls; the -189, -142, -93, and -62 CpG sites were significantly hypomethylated point-wise at this time point. After correction for multiple comparisons, no differences in global methylation or the methylation patterns of Mbp or Plp1 were found. Conclusion: Forced abstinence from cocaine self-administration was associated with differences in DNA methylation at specific CpG sites in the promoter region of the Sox10 gene in corpus callosum. These changes may be related to reductions in normal age related changes in DNA methylation and could be a factor in white matter alterations seen after withdrawal from repeated cocaine self-administration. Further research is warranted examining the effects of cocaine on DNA methylation in white matter.
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Common and specific liability to addiction: approaches to association studies of opioid addiction.
Drug Alcohol Depend
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Opioid addiction, whether to opiates such as heroin and morphine, and/or to non-medical use of opioids, is a major problem worldwide. Although drug-induced and environmental factors are essential for the liability to develop opioid addiction, the genetic background of an individual is now known also to play a substantial role.
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Approximating distributions in stochastic learning.
Neural Netw
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On-line machine learning algorithms, many biological spike-timing-dependent plasticity (STDP) learning rules, and stochastic neural dynamics evolve by Markov processes. A complete description of such systems gives the probability densities for the variables. The evolution and equilibrium state of these densities are given by a Chapman-Kolmogorov equation in discrete time, or a master equation in continuous time. These formulations are analytically intractable for most cases of interest, and to make progress a nonlinear Fokker-Planck equation (FPE) is often used in their place. The FPE is limited, and some argue that its application to describe jump processes (such as in these problems) is fundamentally flawed. We develop a well-grounded perturbation expansion that provides approximations for both the density and its moments. The approach is based on the system size expansion in statistical physics (which does not give approximations for the density), but our simple development makes the methods accessible and invites application to diverse problems. We apply the method to calculate the equilibrium distributions for two biologically-observed STDP learning rules and for a simple nonlinear machine-learning problem. In all three examples, we show that our perturbation series provides good agreement with Monte-Carlo simulations in regimes where the FPE breaks down.
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Former heroin addicts with or without a history of cocaine dependence are more impulsive than controls.
Drug Alcohol Depend
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Personality traits such as impulsivity and sensation seeking may contribute to the initiation and maintenance of illicit drug use. Since studies have reported higher impulsivity and sensation seeking traits in cocaine dependent subjects, we were interested in determining whether former heroin addicts in methadone pharmacotherapy with comorbid cocaine addiction have greater impulsivity than those without.
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2012 update on meaningful use of electronic health records: recommendations from the AAO-HNS Medical Informatics Committee.
Otolaryngol Head Neck Surg
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In 2011, the US federal government implemented an oversight program to encourage the adoption and meaningful use of electronic health records (EHRs). Otolaryngologists may receive as much as $44,000 under Medicare or $63,750 under Medicaid as part of this law. To receive this full benefit, otolaryngologists must acquire a certified EHR and demonstrate stage 1 meaningful use requirements by the end of 2012. Furthermore, the Office of the National Coordinator for Health IT intends to advance meaningful use requirements to stage 2 (estimated to go in effect in 2014) and stage 3 requirements. This commentary discusses updated recommendations from the Academy of Otolaryngology-Head and Neck Surgery Medical Informatics Committee for implementing meaningful use of EHRs, receiving incentive payments, and preparing for potential stage 2 and stage 3 requirements.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.