JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Activity-dependent FUS dysregulation disrupts synaptic homeostasis.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 10-16-2014
Show Abstract
Hide Abstract
The RNA-binding protein fused-in-sarcoma (FUS) has been associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), two neurodegenerative disorders that share similar clinical and pathological features. Both missense mutations and overexpression of wild-type FUS protein can be pathogenic in human patients. To study the molecular and cellular basis by which FUS mutations and overexpression cause disease, we generated novel transgenic mice globally expressing low levels of human wild-type protein (FUS(WT)) and a pathological mutation (FUS(R521G)). FUS(WT) and FUS(R521G) mice that develop severe motor deficits also show neuroinflammation, denervated neuromuscular junctions, and premature death, phenocopying the human diseases. A portion of FUS(R521G) mice escape early lethality; these escapers have modest motor impairments and altered sociability, which correspond with a reduction of dendritic arbors and mature spines. Remarkably, only FUS(R521G) mice show dendritic defects; FUS(WT) mice do not. Activation of metabotropic glutamate receptors 1/5 in neocortical slices and isolated synaptoneurosomes increases endogenous mouse FUS and FUS(WT) protein levels but decreases the FUS(R521G) protein, providing a potential biochemical basis for the dendritic spine differences between FUS(WT) and FUS(R521G) mice.
Related JoVE Video
Circadian genomics reveals a role for post-transcriptional regulation in mammals.
Biochemistry
PUBLISHED: 10-11-2014
Show Abstract
Hide Abstract
In order to maintain daily cycles, the circadian clock must tightly regulate the rhythms of thousands of mRNAs and proteins with the correct period, phase, and amplitude to ultimately drive the wide range of rhythmic biological processes. Recent genomic approaches have revolutionized our view of circadian gene expression and highlighted the importance of post-transcriptional regulation in driving mRNA rhythmicity. Even after transcripts are made from DNA, subsequent processing and regulatory steps determine when, where, and how much protein will be generated. These post-transcriptional regulatory mechanisms can add flexibility to overall gene expression and alter protein levels rapidly without requiring transcript synthesis, and are therefore beneficial for cells; however, the extent to which circadian post-transcriptional mechanisms contribute to rhythmic profiles throughout the genome and the mechanisms involved have not been fully elucidated. In this review, we will summarize how circadian genomics have revealed new insights into rhythmic post-transcriptional regulation in mammals, and discuss potential implications of such regulation in controlling many circadian-driven physiologies.
Related JoVE Video
The STRIDE Weight Loss and Lifestyle Intervention for Individuals Taking Antipsychotic Medications: A Randomized Trial.
Am J Psychiatry
PUBLISHED: 09-16-2014
Show Abstract
Hide Abstract
The STRIDE study assessed whether a lifestyle intervention, tailored for individuals with serious mental illnesses, reduced weight and diabetes risk. The authors hypothesized that the STRIDE intervention would be more effective than usual care in reducing weight and improving glucose metabolism.
Related JoVE Video
Molecular assembly of the period-cryptochrome circadian transcriptional repressor complex.
Elife
PUBLISHED: 08-15-2014
Show Abstract
Hide Abstract
The mammalian circadian clock is driven by a transcriptional-translational feedback loop, which produces robust 24-hr rhythms. Proper oscillation of the clock depends on the complex formation and periodic turnover of the Period and Cryptochrome proteins, which together inhibit their own transcriptional activator complex, CLOCK-BMAL1. We determined the crystal structure of the CRY-binding domain (CBD) of PER2 in complex with CRY2 at 2.8 Å resolution. PER2-CBD adopts a highly extended conformation, embracing CRY2 with a sinuous binding mode. Its N-terminal end tucks into CRY adjacent to a large pocket critical for CLOCK-BMAL1 binding, while its C-terminal half flanks the CRY2 C-terminal helix and sterically hinders the recognition of CRY2 by the FBXL3 ubiquitin ligase. Unexpectedly, a strictly conserved intermolecular zinc finger, whose integrity is important for clock rhythmicity, further stabilizes the complex. Our structure-guided analyses show that these interspersed CRY-interacting regions represent multiple functional modules of PERs at the CRY-binding interface.
Related JoVE Video
Costs of care for persons with opioid dependence in commercial integrated health systems.
Addict Sci Clin Pract
PUBLISHED: 08-14-2014
Show Abstract
Hide Abstract
When used in general medical practices, buprenorphine is an effective treatment for opioid dependence, yet little is known about how use of buprenorphine affects the utilization and cost of health care in commercial health systems.
Related JoVE Video
Approaches to Mixed Methods Dissemination and Implementation Research: Methods, Strengths, Caveats, and Opportunities.
Adm Policy Ment Health
PUBLISHED: 04-12-2014
Show Abstract
Hide Abstract
Limited translation of research into practice has prompted study of diffusion and implementation, and development of effective methods of encouraging adoption, dissemination and implementation. Mixed methods techniques offer approaches for assessing and addressing processes affecting implementation of evidence-based interventions. We describe common mixed methods approaches used in dissemination and implementation research, discuss strengths and limitations of mixed methods approaches to data collection, and suggest promising methods not yet widely used in implementation research. We review qualitative, quantitative, and hybrid approaches to mixed methods dissemination and implementation studies, and describe methods for integrating multiple methods to increase depth of understanding while improving reliability and validity of findings.
Related JoVE Video
A 12-week weight reduction intervention for overweight individuals taking antipsychotic medications.
Community Ment Health J
PUBLISHED: 02-16-2014
Show Abstract
Hide Abstract
People taking antipsychotic medications are at increased risk for obesity, diabetes, and early mortality. Few weight loss interventions have targeted this population. Thirty-six individuals were randomized to an evidence-based 12-week weight loss intervention (PREMIER with DASH diet, n = 18) or to usual care (n = 18) in this feasibility trial. Average attendance was 8.6 of 12 sessions. Intent-to-treat analyses of covariance, adjusted for baseline weight, showed significant changes in weight: Mean weight in intervention participants declined from 213.3 to 206.6 pounds, while control participants' weight was unchanged. It is possible to recruit, assess, intervene with, and retain participants taking antipsychotic medications in a dietary and exercise lifestyle change trial. Participants reported high levels of satisfaction with the intervention.
Related JoVE Video
TH17 cell differentiation is regulated by the circadian clock.
Science
PUBLISHED: 11-09-2013
Show Abstract
Hide Abstract
Circadian clocks regulate numerous physiological processes that vary across the day-night (diurnal) cycle, but if and how the circadian clock regulates the adaptive immune system is mostly unclear. Interleukin-17-producing CD4(+) T helper (T(H)17) cells are proinflammatory immune cells that protect against bacterial and fungal infections at mucosal surfaces. Their lineage specification is regulated by the orphan nuclear receptor ROR?t. We show that the transcription factor NFIL3 suppresses T(H)17 cell development by directly binding and repressing the Ror?t promoter. NFIL3 links T(H)17 cell development to the circadian clock network through the transcription factor REV-ERB?. Accordingly, TH17 lineage specification varies diurnally and is altered in Rev-erb?(-/-) mice. Light-cycle disruption elevated intestinal T(H)17 cell frequencies and increased susceptibility to inflammatory disease. Thus, lineage specification of a key immune cell is under direct circadian control.
Related JoVE Video
Purposeful Sampling for Qualitative Data Collection and Analysis in Mixed Method Implementation Research.
Adm Policy Ment Health
PUBLISHED: 11-07-2013
Show Abstract
Hide Abstract
Purposeful sampling is widely used in qualitative research for the identification and selection of information-rich cases related to the phenomenon of interest. Although there are several different purposeful sampling strategies, criterion sampling appears to be used most commonly in implementation research. However, combining sampling strategies may be more appropriate to the aims of implementation research and more consistent with recent developments in quantitative methods. This paper reviews the principles and practice of purposeful sampling in implementation research, summarizes types and categories of purposeful sampling strategies and provides a set of recommendations for use of single strategy or multistage strategy designs, particularly for state implementation research.
Related JoVE Video
Phosphorylation of the Cryptochrome 1 C-terminal Tail Regulates Circadian Period Length.
J. Biol. Chem.
PUBLISHED: 10-24-2013
Show Abstract
Hide Abstract
The Cryptochrome (CRY) proteins are critical components of the mammalian circadian clock and act to rhythmically repress the activity of the transcriptional activators CLOCK and BMAL1 at the heart of the clock mechanism. The CRY proteins are part of a large repressive complex, the components of which are not completely known. Using mass spectroscopy, we identified the catalytic subunit of DNA-dependent protein kinase as a CRY-interacting protein and found that loss or inhibition of this kinase results in circadian rhythms with abnormally long periods. We then identified serine 588 in the C-terminal tail of mouse CRY1 as a potential DNA-PK phosphorylation site but surprisingly found that the phosphomimetic mutation S588D also results in long period rhythms, similar to the loss of DNA-PK. Consistent with this, we found that phosphorylation of this site is increased in cells lacking DNA-PK, suggesting that DNA-PK negatively regulates the phosphorylation of this site most likely through indirect means. Furthermore, we found that phosphorylation of this site increases the stability of the CRY1 protein and prevents FBXL3-mediated degradation. The phosphorylation of this site is robustly rhythmic in mouse liver nuclei, peaking in the middle of the circadian day at a time when CRY1 levels are declining. Therefore, these data suggest a new role for the C-terminal tail of CRY1 in which phosphorylation rhythmically regulates CRY1 stability and contributes to the proper circadian period length.
Related JoVE Video
STRIDE: a randomized trial of a lifestyle intervention to promote weight loss among individuals taking antipsychotic medications.
BMC Psychiatry
PUBLISHED: 09-11-2013
Show Abstract
Hide Abstract
Individuals diagnosed with serious mental illnesses are at increased risk of obesity- and cardiovascular-related morbidity and early mortality. Lifestyle interventions aimed at weight loss, even those adapted to suit the needs of this particular subgroup, have rarely produced clinically meaningful reductions in weight.
Related JoVE Video
The recovery group project: development of an intervention led jointly by peer and professional counselors.
Psychiatr Serv
PUBLISHED: 09-04-2013
Show Abstract
Hide Abstract
OBJECTIVE The objective of this study was to develop and evaluate a low-cost, strengths-based group intervention led jointly by peer counselors and professional counselors to foster recovery among adults with serious mental illnesses. METHODS Cohort 1 included development of materials and a feasibility pilot, with participants recruited from community mental health centers (CMHCs). Cohorts 2 and 3 included a small randomized controlled trial with participants recruited from members of a not-for-profit, integrated health plan. Cohorts 4 and 5 involved evaluation of the most appropriate length for the intervention with a pre-post design that allowed intervention length to vary between 12 and 18 sessions; participants and peer leaders were recruited from two CMHCs (N=82). RESULTS Participants were very satisfied with the recovery-focused group intervention, preferred a greater number of weekly sessions (17 or 18 sessions), and reported improved outcomes across multiple domains. CONCLUSIONS Using peer-developed materials and a combination of peer and professional counselors as group leaders is feasible to offer and valuable to participants. Outcomes measures suggest that the intervention has potential to facilitate recovery in multiple domains.
Related JoVE Video
Recovery from serious mental illness: trajectories, characteristics, and the role of mental health care.
Psychiatr Serv
PUBLISHED: 09-04-2013
Show Abstract
Hide Abstract
OBJECTIVE The objective was to identify trajectories of recovery from serious mental illnesses. METHODS A total of 177 members (92 women; 85 men) of a not-for-profit integrated health plan participated in a two-year mixed-methods study of recovery (STARS, the Study of Transitions and Recovery Strategies). Diagnoses included schizophrenia, schizoaffective disorder, bipolar disorder, and affective psychosis. Data sources included self-reported standardized measures, interviewer ratings, qualitative interviews, and health plan data. Recovery was conceptualized as a latent construct, and factor analyses and factor scores were used to calculate recovery trajectories. Individuals with similar trajectories were identified through cluster analyses. RESULTS Four trajectories were identified-two stable (high and low levels of recovery) and two fluctuating (higher and lower). Few demographic or diagnostic factors differentiated clusters at baseline. Discriminant analyses for trajectories found differences in psychiatric symptoms, physical health, satisfaction with mental health clinicians, resources and strains, satisfaction with medications, and mental health service use. Those with higher scores on recovery factors had fewer psychiatric symptoms, better physical health, greater satisfaction with mental health clinicians, fewer strains and greater resources, less service use, better quality of care, and greater satisfaction with medication. Consistent predictors of trajectories included psychiatric symptoms, physical health, resources and strains, and use of psychiatric medications. CONCLUSIONS Having access to good-quality mental health care-defined as including satisfying relationships with clinicians, responsiveness to needs, satisfaction with psychiatric medications, receipt of services at needed levels, support in managing deficits in resources and strains, and care for general medical conditions-may facilitate recovery. Providing such care may improve recovery trajectories.
Related JoVE Video
Seeking, Delaying, and Avoiding Routine Health Care Services: Patient Perspectives.
Am J Health Promot
PUBLISHED: 08-23-2013
Show Abstract
Hide Abstract
Abstract Purpose . To explore/identify patient perspectives regarding seeking, delaying, and avoiding health care services, particularly barriers and facilitators. Design . Face-to-face interviews with health plan survey respondents. Setting . An integrated health plan providing comprehensive care to 480,000 people in Oregon and Washington. Participants . Willing respondents randomly selected to maximize heterogeneity within the following strata: gender, health care utilization, and self-reported alcohol consumption (indicator of health practices). Participants were 75 men and 75 women (150 total), 21 to 64 years old, with ?12 months of health plan membership. Method . Participants were recruited by letter (52.5% agreed). Data collection stopped when planned interviews were completed; saturation (the point at which additional interviews were not producing novel information) was achieved for key study questions. Semi-structured interviews were recorded, transcribed, and coded. Reviews of codes related to care seeking and feelings/attitudes about providers produced common themes. Results . Facilitators of care seeking included welcoming staff, collaborative relationships with providers, and education about the value of preventive care. Barriers included costs, time needed for appointments, and cumbersome processes. Some participants delayed procedures, some avoided care until absolutely necessary, others framed care as routinely necessary. Conclusion . Increasing comfort, improving appointment and visit-related processes, having positive patient-physician relationships, and enhancing communication and clinician-provided education may facilitate appropriate use of preventive services. Further research is needed with larger, representative samples to evaluate findings.
Related JoVE Video
"The chief of the service is very enthusiastic about it": A qualitative study of the adoption of buprenorphine for opioid addiction treatment.
J Subst Abuse Treat
PUBLISHED: 08-13-2013
Show Abstract
Hide Abstract
Qualified physicians may prescribe buprenorphine to treat opioid dependence, but medication use remains controversial. We examined adoption of buprenorphine in two not-for-profit integrated health plans, over time, completing 101 semi-structured interviews with clinicians and clinician-administrators from primary and specialty care. Transcripts were reviewed, coded, and analyzed. A strong leader championing the new treatment was critical for adoption in both health plans. Once clinicians began using buprenorphine, patients and other clinicians experiences affected decisions more than did the champion. With experience, protocols developed to manage unsuccessful patients and changed to support maintenance rather than detoxification. Diffusion outside addiction and mental health settings was nonexistent; primary care clinicians cited scope-of-practice issues and referred patients to specialty care. With greater diffusion came questions about long-term use and safety. Recognizing how implementation processes develop may suggest where, when, and how to best expend resources to increase adoption of such treatments.
Related JoVE Video
Molecular architecture of the mammalian circadian clock.
Trends Cell Biol.
PUBLISHED: 04-30-2013
Show Abstract
Hide Abstract
Circadian clocks coordinate physiology and behavior with the 24h solar day to provide temporal homeostasis with the external environment. The molecular clocks that drive these intrinsic rhythmic changes are based on interlocked transcription/translation feedback loops that integrate with diverse environmental and metabolic stimuli to generate internal 24h timing. In this review we highlight recent advances in our understanding of the core molecular clock and how it utilizes diverse transcriptional and post-transcriptional mechanisms to impart temporal control onto mammalian physiology. Understanding the way in which biological rhythms are generated throughout the body may provide avenues for temporally directed therapeutics to improve health and prevent disease.
Related JoVE Video
Competing E3 ubiquitin ligases govern circadian periodicity by degradation of CRY in nucleus and cytoplasm.
Cell
PUBLISHED: 01-30-2013
Show Abstract
Hide Abstract
Period determination in the mammalian circadian clock involves the turnover rate of the repressors CRY and PER. We show that CRY ubiquitination engages two competing E3 ligase complexes that either lengthen or shorten circadian period in mice. Cloning of a short-period circadian mutant, Past-time, revealed a glycine to glutamate missense mutation in Fbxl21, an F-box protein gene that is a paralog of Fbxl3 that targets the CRY proteins for degradation. While loss of function of FBXL3 leads to period lengthening, mutation of Fbxl21 causes period shortening. FBXL21 forms an SCF E3 ligase complex that slowly degrades CRY in the cytoplasm but antagonizes the stronger E3 ligase activity of FBXL3 in the nucleus. FBXL21 plays a dual role: protecting CRY from FBXL3 degradation in the nucleus and promoting CRY degradation within the cytoplasm. Thus, the balance and cellular compartmentalization of competing E3 ligases for CRY determine circadian period of the clock in mammals.
Related JoVE Video
An essential role for the circadian-regulated gene nocturnin in osteogenesis: the importance of local timekeeping in skeletal homeostasis.
Ann. N. Y. Acad. Sci.
PUBLISHED: 11-16-2011
Show Abstract
Hide Abstract
The role of circadian proteins in regulating whole-body metabolism and bone turnover has been studied in detail and has led to the discovery of an elemental system for timekeeping involving the core genes Clock, Bmal1, Per, and Cry. Nocturnin?(Noc; Ccrn4l), a peripheral circadian-regulated gene has been shown to play a very important role in regulating adipogenesis by deadenylation of key mRNAs and intracytoplasmic transport of PPAR?. The role that it plays in osteogenesis has previously not been studied in detail. In this report we examined in vitro and in vivo osteogenesis in the presence and absence of Noc and show that loss of Noc enhances bone formation and can rescue rosiglitazone-induced bone loss in mice. The circadian rhythm of Noc is likely to be an essential element of marrow stromal cell fate.
Related JoVE Video
Methodological reporting in qualitative, quantitative, and mixed methods health services research articles.
Health Serv Res
PUBLISHED: 11-08-2011
Show Abstract
Hide Abstract
Methodologically sound mixed methods research can improve our understanding of health services by providing a more comprehensive picture of health services than either method can alone. This study describes the frequency of mixed methods in published health services research and compares the presence of methodological components indicative of rigorous approaches across mixed methods, qualitative, and quantitative articles.
Related JoVE Video
An exploration of site effects in a multisite trial of OROS-methylphenidate for smokers with attention deficit/hyperactivity disorder.
Am J Drug Alcohol Abuse
PUBLISHED: 08-23-2011
Show Abstract
Hide Abstract
Multisite trials, the gold standard for conducting studies in community-based settings, can mask variability across sites resulting in misrepresentation of effects in specific sites. In a placebo-controlled trial of osmotic-release oral system methylphenidate (OROS-MPH) as augmentation treatment for smokers with attention deficit hyperactivity/impulsivity disorder (ADHD), three types of sites were selected according to their clinical research specialty (ADHD, smoking cessation, and general mental health).
Related JoVE Video
Gender research in the National Institute on Drug Abuse National Treatment Clinical Trials Network: a summary of findings.
Am J Drug Alcohol Abuse
PUBLISHED: 08-23-2011
Show Abstract
Hide Abstract
The National Institute of Drug Abuses National Drug Abuse Treatment Clinical Trials Network (CTN) was established to foster translation of research into practice in substance abuse treatment settings. The CTN provides a unique opportunity to examine in multi-site, translational clinical trials, the outcomes of treatment interventions targeting vulnerable subgroups of women; the comparative effectiveness of gender-specific protocols to reduce risk behaviors; and gender differences in clinical outcomes.
Related JoVE Video
Delivering a lifestyle and weight loss intervention to individuals in real-world mental health settings: Lessons and opportunities.
Transl Behav Med
PUBLISHED: 08-04-2011
Show Abstract
Hide Abstract
BACKGROUND: Most weight loss interventions for obesity-related risks exclude people with serious mental health conditions. PURPOSE: To adapt a successful lifestyle/weight loss intervention for this population, deliver it in an HMO and two public mental health clinics, and concurrently measure implementation factors. METHODS: Developmental and implementation-focused formative evaluations guided adaptations and identified barriers/facilitators to successful program deployment. RESULTS: Adaptations included content specific to the populations needs, consciousness-raising among clinicians and patients, additional case-management, and greater program flexibility. Barriers included instability in both settings from different sources. Facilitators included familiarity with groups, manual integrity, and appreciation of the program. It was delivered consistently across settings with maximum exposure and fairly good fidelity to the protocol (mean rating=1.7, 2.0=complete fidelity). CONCLUSIONS: This mixed-method implementation evaluation demonstrated that lifestyle/weight loss interventions in mental health settings are complex, but feasible, and valued by participants. Main program outcomes will be reported at the trials conclusion.
Related JoVE Video
The circadian deadenylase Nocturnin is necessary for stabilization of the iNOS mRNA in mice.
PLoS ONE
PUBLISHED: 07-06-2011
Show Abstract
Hide Abstract
Nocturnin is a member of the CCR4 deadenylase family, and its expression is under circadian control with peak levels at night. Because it can remove poly(A) tails from mRNAs, it is presumed to play a role in post-transcriptional control of circadian gene expression, but its target mRNAs are not known. Here we demonstrate that Nocturnin expression is acutely induced by the endotoxin lipopolysaccharide (LPS). Mouse embryo fibroblasts (MEFs) lacking Nocturnin exhibit normal patterns of acute induction of TNF? and iNOS mRNAs during the first three hours following LPS treatment, but by 24 hours, while TNF? mRNA levels are indistinguishable from WT cells, iNOS message is significantly reduced 20-fold. Accordingly, analysis of the stability of the mRNAs showed that loss of Nocturnin causes a significant decrease in the half-life of the iNOS mRNA (t(1/2) = 3.3 hours in Nocturnin knockout MEFs vs. 12.4 hours in wild type MEFs), while having no effect on the TNF? message. Furthermore, mice lacking Nocturnin lose the normal nighttime peak of hepatic iNOS mRNA, and have improved survival following LPS injection. These data suggest that Nocturnin has a novel stabilizing activity that plays an important role in the circadian response to inflammatory signals.
Related JoVE Video
Nocturnin regulates circadian trafficking of dietary lipid in intestinal enterocytes.
Curr. Biol.
PUBLISHED: 05-09-2011
Show Abstract
Hide Abstract
Efficient metabolic function in mammals depends on the circadian clock, which drives temporal regulation of metabolic processes. Nocturnin is a clock-regulated deadenylase that controls its target mRNA expression posttranscriptionally through poly(A) tail removal. Mice lacking nocturnin (Noc(-/-) mice) are resistant to diet-induced obesity and hepatic steatosis yet are not hyperactive or hypophagic.
Related JoVE Video
Post-transcriptional control of circadian rhythms.
J. Cell. Sci.
PUBLISHED: 01-19-2011
Show Abstract
Hide Abstract
Circadian rhythms exist in most living organisms. The general molecular mechanisms that are used to generate 24-hour rhythms are conserved among organisms, although the details vary. These core clocks consist of multiple regulatory feedback loops, and must be coordinated and orchestrated appropriately for the fine-tuning of the 24-hour period. Many levels of regulation are important for the proper functioning of the circadian clock, including transcriptional, post-transcriptional and post-translational mechanisms. In recent years, new information about post-transcriptional regulation in the circadian system has been discovered. Such regulation has been shown to alter the phase and amplitude of rhythmic mRNA and protein expression in many organisms. Therefore, this Commentary will provide an overview of current knowledge of post-transcriptional regulation of the clock genes and clock-controlled genes in dinoflagellates, plants, fungi and animals. This article will also highlight how circadian gene expression is modulated by post-transcriptional mechanisms and how this is crucial for robust circadian rhythmicity.
Related JoVE Video
Nocturnin expression is induced by fasting in the white adipose tissue of restricted fed mice.
PLoS ONE
PUBLISHED: 01-13-2011
Show Abstract
Hide Abstract
The relationship between circadian clocks and metabolism is intimate and complex and a number of recent studies have begun to reveal previously unknown effects of food and its temporal availability on the clock and the rhythmic transcriptome of peripheral tissues. Nocturnin, a circadian deadenylase, is expressed rhythmically in a wide variety of tissues, but we report here that Nocturnin expression is arrhythmic in epididymal white adipose tissue (eWAT) of mice housed in 12:12 LD with ad libitum access to food. However, Nocturnin expression becomes rhythmic in eWAT of mice placed on restricted feeding. We show here that Nocturnins rhythmic expression pattern is not dependent upon feeding, nor is it acutely induced by feeding in the liver or eWAT of ad libitum fed mice. However, Nocturnin is acutely induced by the absence of the expected meal in eWAT of restricted fed mice. A rise in cAMP levels also induces Nocturnin expression, suggesting that Nocturnins induction in eWAT by fasting is likely mediated through the same pathways that activate lipolysis. Therefore, this suggests that Nocturnin plays a role in linking nutrient sensing by the circadian clock to lipid mobilization in the adipocytes.
Related JoVE Video
Differential contribution of rod and cone circadian clocks in driving retinal melatonin rhythms in Xenopus.
PLoS ONE
PUBLISHED: 08-28-2010
Show Abstract
Hide Abstract
Although an endogenous circadian clock located in the retinal photoreceptor layer governs various physiological events including melatonin rhythms in Xenopus laevis, it remains unknown which of the photoreceptors, rod and/or cone, is responsible for the circadian regulation of melatonin release.
Related JoVE Video
Nocturnin suppresses igf1 expression in bone by targeting the 3 untranslated region of igf1 mRNA.
Endocrinology
PUBLISHED: 08-04-2010
Show Abstract
Hide Abstract
IGF-I is an anabolic factor that mediates GH and PTH actions in bone. Expression of skeletal Igf1 differs for inbred strains of mice, and Igf expression levels correlate directly with bone mass. Previously we reported that peroxisome proliferator-activated receptor-?2 activation in bone marrow suppressed Igf1 expression and that peroxisome proliferator-activated receptor-?2 activation-induced Nocturnin (Noc) expression, a circadian gene with peak expression at light offset, which functions as a deadenylase. In 24-h studies we found that Igf1 mRNA exhibited a circadian rhythm in femur with the lowest Igf1 transcript levels at night when Noc transcripts were highest. Immunoprecipitation/RT-PCR analysis revealed a physical interaction between Noc protein and Igf1 transcripts. To clarify which portions of the Igf1 3 untranslated region (UTR) were necessary for regulation by Noc, we generated luciferase constructs containing various lengths of the Igf1 3UTR. Noc did not affect the 170-bp short-form 3UTR, but suppressed luciferase activity in constructs bearing the longer-form 3UTR, which contains a number of potential regulatory motifs involved in mRNA degradation. C57BL/6J mice have low skeletal Igf1 mRNA compared with C3H/HeJ mice, and the Igf1 3 UTR is polymorphic between these strains. Interestingly, the activity of luciferase constructs bearing the long-form 3UTR from C57BL/6J mice were repressed by Noc overexpression, whereas those bearing the corresponding region from C3H/HeJ were not. In summary, Noc interacts with Igf1 in a strain- and tissue-specific manner and reduces Igf1 expression by targeting the longer form of the Igf1 3UTR. Posttranscriptional regulation of Igf1 may be critically important during skeletal acquisition and maintenance.
Related JoVE Video
Drinking Patterns, Gender and Health II: Predictors of Preventive Service Use.
Addict Res Theory
PUBLISHED: 07-01-2010
Show Abstract
Hide Abstract
Chronic diseases and injuries are elevated among people with substance use problems/dependence, yet heavier drinkers use fewer routine and preventive health services than non-drinkers and moderate drinkers, while former drinkers and abstainers use more than moderate drinkers. Researchers hypothesize that drinking clusters with attitudes and practices that produce better health among moderate drinkers and that heavy drinkers avoid doctors until becoming ill, subsequently quitting and using more services. Gender differences in alcohol consumption, health-related attitudes, practices, and prevention-services use may affect these relationships.
Related JoVE Video
A circadian-regulated gene, Nocturnin, promotes adipogenesis by stimulating PPAR-gamma nuclear translocation.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 05-24-2010
Show Abstract
Hide Abstract
Nocturnin (NOC) is a circadian-regulated protein related to the yeast family of transcription factors involved in the cellular response to nutrient status. In mammals, NOC functions as a deadenylase but lacks a transcriptional activation domain. It is highly expressed in bone-marrow stromal cells (BMSCs), hepatocytes, and adipocytes. In BMSCs exposed to the PPAR-gamma (peroxisome proliferator-activated receptor-gamma) agonist rosiglitazone, Noc expression was enhanced 30-fold. Previously, we reported that Noc(-/-) mice had low body temperature, were protected from diet-induced obesity, and most importantly exhibited absence of Pparg circadian rhythmicity on a high-fat diet. Consistent with its role in influencing BMSCs allocation, Noc(-/-) mice have reduced bone marrow adiposity and high bone mass. In that same vein, NOC overexpression enhances adipogenesis in 3T3-L1 cells but negatively regulates osteogenesis in MC3T3-E1 cells. NOC and a mutated form, which lacks deadenylase activity, bind to PPAR-gamma and markedly enhance PPAR-gamma transcriptional activity. Both WT and mutant NOC facilitate nuclear translocation of PPAR-gamma. Importantly, NOC-mediated nuclear translocation of PPAR-gamma is blocked by a short peptide fragment of NOC that inhibits its physical interaction with PPAR-gamma. The inhibitory effect of this NOC-peptide was partially reversed by rosiglitazone, suggesting that effect of NOC on PPAR-gamma nuclear translocation may be independent of ligand-mediated PPAR-gamma activation. In sum, Noc plays a unique role in the regulation of mesenchymal stem-cell lineage allocation by modulating PPAR-gamma activity through nuclear translocation. These data illustrate a unique mechanism whereby a nutrient-responsive gene influences BMSCs differentiation, adipogenesis, and ultimately body composition.
Related JoVE Video
Impact of attention-deficit/hyperactivity disorder (ADHD) treatment on smoking cessation intervention in ADHD smokers: a randomized, double-blind, placebo-controlled trial.
J Clin Psychiatry
PUBLISHED: 05-18-2010
Show Abstract
Hide Abstract
High smoking rates in adults with attention-deficit/hyperactivity disorder (ADHD) and nicotines amelioration of ADHD suggest that effective ADHD treatment might facilitate abstinence in smokers with ADHD. The present study evaluated if using osmotic-release oral system methylphenidate (OROS-MPH) to treat ADHD enhances response to smoking cessation treatment in smokers with ADHD.
Related JoVE Video
Genetic suppression of the circadian Clock mutation by the melatonin biosynthesis pathway.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 04-19-2010
Show Abstract
Hide Abstract
Most laboratory mouse strains including C57BL/6J do not produce detectable levels of pineal melatonin owing to deficits in enzymatic activity of arylalkylamine N-acetyltransferase (AANAT) and N-acetylserotonin O-methyl transferase (ASMT), two enzymes necessary for melatonin biosynthesis. Here we report that alleles segregating at these two loci in C3H/HeJ mice, an inbred strain producing melatonin, suppress the circadian period-lengthening effect of the Clock mutation. Through a functional mapping approach, we localize mouse Asmt to chromosome X and show that it, and the Aanat locus on chromosome 11, are significantly associated with pineal melatonin levels. Treatment of suprachiasmatic nucleus (SCN) explant cultures from Period2(Luciferase) (Per2(Luc)) Clock/+ reporter mice with melatonin, or the melatonin agonist, ramelteon, phenocopies the genetic suppression of the Clock mutant phenotype observed in living animals. These results demonstrate that melatonin suppresses the Clock/+ mutant phenotype and interacts with Clock to affect the mammalian circadian system.
Related JoVE Video
Nocturnin: a circadian target of Pparg-induced adipogenesis.
Ann. N. Y. Acad. Sci.
PUBLISHED: 04-16-2010
Show Abstract
Hide Abstract
Nuclear receptors (NRs) control cell fate and regulate tissue function. Some of the NRs are expressed in a circadian and tissue-specific manner. Clock genes are part of the circadian network and fine-tune gene expression in adipose and skeletal tissues. Pparg, a master transcription factor that determines adipogenesis, exhibits a circadian expression pattern in white adipose tissue and liver. Here we report the finding that the message and protein for a peripheral clock gene, nocturnin, is markedly upregulated with Pparg activation in adipocytes and bone marrow stromal cells. Nocturnin is also expressed in relatively high amounts in other tissues that may have physiologic relevance for bone, including the brain and hypothalamus. Of importance, we found polymorphic strain differences in bone marrow nocturnin expression that relate to phenotypic determinants of skeletal acquisition. Defining the function of nocturnin in peripheral tissues should provide new insights into lineage allocation and the intimate relationship between nuclear receptors and physiologic timekeeping.
Related JoVE Video
Drinking Patterns, Gender and Health I: Attitudes and Health Practices.
Addict Res Theory
PUBLISHED: 04-01-2010
Show Abstract
Hide Abstract
Despite considerable research, relationships among gender, alcohol consumption, and health remain controversial, due to potential confounding by health-related attitudes and practices associated with drinking, measurement challenges, and marked gender differences in drinking. We examined gender/alcohol consumption differences in health-related attitudes and practices, and evaluated how these factors affected relationships among gender, alcohol consumption, and health status.
Related JoVE Video
MicroRNA-122 modulates the rhythmic expression profile of the circadian deadenylase Nocturnin in mouse liver.
PLoS ONE
PUBLISHED: 03-26-2010
Show Abstract
Hide Abstract
Nocturnin is a circadian clock-regulated deadenylase thought to control mRNA expression post-transcriptionally through poly(A) tail removal. The expression of Nocturnin is robustly rhythmic in liver at both the mRNA and protein levels, and mice lacking Nocturnin are resistant to diet-induced obesity and hepatic steatosis. Here we report that Nocturnin expression is regulated by microRNA-122 (miR-122), a liver specific miRNA. We found that the 3-untranslated region (3-UTR) of Nocturnin mRNA harbors one putative recognition site for miR-122, and this site is conserved among mammals. Using a luciferase reporter construct with wild-type or mutant Nocturnin 3-UTR sequence, we demonstrated that overexpression of miR-122 can down-regulate luciferase activity levels and that this effect is dependent on the presence of the putative miR-122 recognition site. Additionally, the use of an antisense oligonucleotide to knock down miR-122 in vivo resulted in significant up-regulation of both Nocturnin mRNA and protein expression in mouse liver during the night, resulting in Nocturnin rhythms with increased amplitude. Together, these data demonstrate that the normal rhythmic profile of Nocturnin expression in liver is shaped in part by miR-122. Previous studies have implicated Nocturnin and miR-122 as important post-transcriptional regulators of both lipid metabolism and circadian clock controlled gene expression in the liver. Therefore, the demonstration that miR-122 plays a role in regulating Nocturnin expression suggests that this may be an important intersection between hepatic metabolic and circadian control.
Related JoVE Video
Methadone maintenance and the cost and utilization of health care among individuals dependent on opioids in a commercial health plan.
Drug Alcohol Depend
PUBLISHED: 02-12-2010
Show Abstract
Hide Abstract
Few health plans provide maintenance medication for opioid dependence. This study assessed the cost of treating opioid-dependent members in a commercial health plan and the impacts of methadone maintenance on costs of care.
Related JoVE Video
Another breed of "service" animals: STARS study findings about pet ownership and recovery from serious mental illness.
Am J Orthopsychiatry
PUBLISHED: 10-21-2009
Show Abstract
Hide Abstract
This study elucidates the role of pets in recovery processes among adults with serious mental illness. Data derive from interviews with 177 HMO members with serious mental illness (52.2% women, average age 48.8 years) in the Study of Transitions and Recovery Strategies (STARS). Interviews and questionnaires addressed factors affecting recovery processes and included questions about pet ownership. Data were analyzed using a modified grounded theory method to identify the roles pets play in the recovery process. Primary themes indicate pets assist individuals in recovery from serious mental illness by (a) providing empathy and "therapy"; (b) providing connections that can assist in redeveloping social avenues; (c) serving as "family" in the absence of or in addition to human family members; and (d) supporting self-efficacy and strengthening a sense of empowerment. Pets appear to provide more benefits than merely companionship. Participants reports of pet-related contributions to their well-being provide impetus to conduct more formal research on the mechanisms by which pets contribute to recovery and to develop pet-based interventions.
Related JoVE Video
Social support, activities, and recovery from serious mental illness: STARS study findings.
J Behav Health Serv Res
PUBLISHED: 09-05-2009
Show Abstract
Hide Abstract
Research on the role of social support in recovery from severe mental illness is limited and even more limited is research on the potential effects of participating in various activities. This study explores these relationships by analyzing baseline data from a 153-participant subsample in the Study of Transitions and Recovery Strategies. Higher scores on the recovery assessment scale were related to both social support/network size and engagement in more activities. The particular nature of the activities (more/less social, more/less physically active, inside/outside the home) was not important, rather, activities of any type were related to recovery. Furthermore, engagement in activities was more important as levels of social support declined. The results suggest that both social support and activities may promote recovery, and that for persons with poor social support, engagement in a variety of individualized activities may be particularly beneficial.
Related JoVE Video
Generation of a novel allelic series of cryptochrome mutants via mutagenesis reveals residues involved in protein-protein interaction and CRY2-specific repression.
Mol. Cell. Biol.
PUBLISHED: 08-17-2009
Show Abstract
Hide Abstract
CRYPTOCHOME proteins are necessary for mammalian circadian rhythms and have many well-established biochemical roles within the molecular clock. While studies examining the effect of null Cry alleles have been informative, they have failed to dissect out the relative importance of, and the molecular mechanisms behind, the many roles of the CRY1 and CRY2 proteins. To address this, we created an allelic series of Cry mutants through random mutagenesis, followed by a cell-based screen to isolate mutants with aberrant repression of CLOCK-BMAL1. We identified 22 mutants with mutations resulting in single amino acid substitutions which cause a variety of deficiencies in different CRY functions. To illustrate the breadth and value of these new tools, we present an in-depth analysis of two of these mutants, CRY2G354D and CRY2G351D; the former shows deficiency in clock protein binding and is required for repression by both CRYs, while in contrast, the latter displays normal binding function but exhibits a CRY2-specific repression phenotype. Further, while overexpression of CRY2 in NIH 3T3 cells caused a dose-dependent decrease in rhythm amplitude, overexpression of CRY2G351D abolished rhythmicity. In summary, characterization of these unique alleles provides new opportunities for more-sophisticated insight into the multifaceted functions of the CRY proteins in circadian rhythms.
Related JoVE Video
Development of the Patient Activation Measure for mental health.
Adm Policy Ment Health
PUBLISHED: 03-16-2009
Show Abstract
Hide Abstract
Our objective was to adapt the physical health Patient Activation Measure (PAM) for use among people with mental health conditions (PAM-MH). Data came from three studies among people with chronic mental health conditions and were combined in Rasch analyses. The PAM-MHs psychometric properties equal those of the original 13-item PAM. Test-retest reliability and concurrent validity were good, and the PAM-MH showed sensitivity to change. The PAM-MH appears to be a reliable and valid measure of patient activation among individuals with mental health problems. It appears to have potential for use in assessing change in activation.
Related JoVE Video
A primary care-based interdisciplinary team approach to the treatment of chronic pain utilizing a pragmatic clinical trials framework.
Transl Behav Med
Show Abstract
Hide Abstract
Chronic pain affects at least 116 million adults in the USA and exacts a tremendous cost in suffering and lost productivity. While health systems offer specialized pain services, the primary care setting is where most patients seek and receive care for pain. Primary care-based treatment of chronic pain by interdisciplinary teams (including behavioral specialists, nurse case managers, physical therapists, and pharmacists) is one of the most effective approaches for improving outcomes and managing costs. To ensure robust integration of such services into sustainable health-care programs, evaluations must be conducted by researchers well versed in the methodologies of clinical trials, mixed methods and implementation research, bioinformatics, health services, and cost-effectiveness. Recent national health policy changes, in addition to the increasing recognition of the high prevalence and cost of chronic pain conditions, present a unique opportunity to shift the care paradigm for patients with chronic pain.
Related JoVE Video
Kiss your tail goodbye: the role of PARN, Nocturnin, and Angel deadenylases in mRNA biology.
Biochim. Biophys. Acta
Show Abstract
Hide Abstract
PARN, Nocturnin and Angel are three of the multiple deadenylases that have been described in eukaryotic cells. While each of these enzymes appear to target poly(A) tails for shortening and influence RNA gene expression levels and quality control, the enzymes differ in terms of enzymatic mechanisms, regulation and biological impact. The goal of this review is to provide an in depth biochemical and biological perspective of the PARN, Nocturnin and Angel deadenylases. Understanding the shared and unique roles of these enzymes in cell biology will provide important insights into numerous aspects of the post-transcriptional control of gene expression. This article is part of a Special Issue entitled: RNA Decay mechanisms.
Related JoVE Video
Circadian control of mRNA polyadenylation dynamics regulates rhythmic protein expression.
Genes Dev.
Show Abstract
Hide Abstract
Poly(A) tails are 3 modifications of eukaryotic mRNAs that are important in the control of translation and mRNA stability. We identified hundreds of mouse liver mRNAs that exhibit robust circadian rhythms in the length of their poly(A) tails. Approximately 80% of these are primarily the result of nuclear adenylation coupled with rhythmic transcription. However, unique decay kinetics distinguish these mRNAs from other mRNAs that are transcribed rhythmically but do not exhibit poly(A) tail rhythms. The remaining 20% are uncoupled from transcription and exhibit poly(A) tail rhythms even though the steady-state mRNA levels are not rhythmic. These are under the control of rhythmic cytoplasmic polyadenylation, regulated at least in some cases by cytoplasmic polyadenylation element-binding proteins (CPEBs). Importantly, we found that the rhythmicity in poly(A) tail length is closely correlated with rhythmic protein expression, with a several-hour delay between the time of longest tail and the time of highest protein level. Our study demonstrates that the circadian clock regulates the dynamic polyadenylation status of mRNAs, which can result in rhythmic protein expression independent of the steady-state levels of the message.
Related JoVE Video
Engaging youths with serious mental illnesses in treatment: STARS study consumer recommendations.
Psychiatr Rehabil J
Show Abstract
Hide Abstract
The purpose of this study was to identify better methods of engaging youths in mental health services by asking experienced mental health consumers for suggestions for clinicians.
Related JoVE Video
Crystal structure of the heterodimeric CLOCK:BMAL1 transcriptional activator complex.
Science
Show Abstract
Hide Abstract
The circadian clock in mammals is driven by an autoregulatory transcriptional feedback mechanism that takes approximately 24 hours to complete. A key component of this mechanism is a heterodimeric transcriptional activator consisting of two basic helix-loop-helix PER-ARNT-SIM (bHLH-PAS) domain protein subunits, CLOCK and BMAL1. Here, we report the crystal structure of a complex containing the mouse CLOCK:BMAL1 bHLH-PAS domains at 2.3 Å resolution. The structure reveals an unusual asymmetric heterodimer with the three domains in each of the two subunits--bHLH, PAS-A, and PAS-B--tightly intertwined and involved in dimerization interactions, resulting in three distinct protein interfaces. Mutations that perturb the observed heterodimer interfaces affect the stability and activity of the CLOCK:BMAL1 complex as well as the periodicity of the circadian oscillator. The structure of the CLOCK:BMAL1 complex is a starting point for understanding at an atomic level the mechanism driving the mammalian circadian clock.
Related JoVE Video
Nocturnin: at the crossroads of clocks and metabolism.
Trends Endocrinol. Metab.
Show Abstract
Hide Abstract
Many aspects of metabolism exhibit daily rhythmicity under the control of endogenous circadian clocks, and disruptions in circadian timing result in dysfunctions associated with the metabolic syndrome. Nocturnin (Noc) is a robustly rhythmic gene that encodes a deadenylase thought to be involved in the removal of polyA tails from mRNAs. Mice lacking the Noc gene display resistance to diet-induced obesity and hepatic steatosis, due in part to reduced lipid trafficking in the small intestine. In addition, Noc appears to play important roles in other tissues and has been implicated in lipid metabolism, adipogenesis, glucose homeostasis, inflammation and osteogenesis. Therefore, Noc is a potential key post-transcriptional mediator in the circadian control of many metabolic processes.
Related JoVE Video
Central and peripheral circadian clocks in mammals.
Annu. Rev. Neurosci.
Show Abstract
Hide Abstract
The circadian system of mammals is composed of a hierarchy of oscillators that function at the cellular, tissue, and systems levels. A common molecular mechanism underlies the cell-autonomous circadian oscillator throughout the body, yet this clock system is adapted to different functional contexts. In the central suprachiasmatic nucleus (SCN) of the hypothalamus, a coupled population of neuronal circadian oscillators acts as a master pacemaker for the organism to drive rhythms in activity and rest, feeding, body temperature, and hormones. Coupling within the SCN network confers robustness to the SCN pacemaker, which in turn provides stability to the overall temporal architecture of the organism. Throughout the majority of the cells in the body, cell-autonomous circadian clocks are intimately enmeshed within metabolic pathways. Thus, an emerging view for the adaptive significance of circadian clocks is their fundamental role in orchestrating metabolism.
Related JoVE Video
Improving quality of care in substance abuse treatment using five key process improvement principles.
J Behav Health Serv Res
Show Abstract
Hide Abstract
Process and quality improvement techniques have been successfully applied in health care arenas, but efforts to institute these strategies in alcohol and drug treatment are underdeveloped. The Network for the Improvement of Addiction Treatment (NIATx) teaches participating substance abuse treatment agencies to use process improvement strategies to increase client access to, and retention in, treatment. NIATx recommends five principles to promote organizational change: (1) understand and involve the customer, (2) fix key problems, (3) pick a powerful change leader, (4) get ideas from outside the organization, and (5) use rapid cycle testing. Using case studies, supplemented with cross-agency analyses of interview data, this paper profiles participating NIATx treatment agencies that illustrate successful applications of each principle. Results suggest that organizations can successfully integrate and apply the five principles as they develop and test change strategies, improving access and retention in treatment, and agencies financial status. Upcoming changes requiring increased provision of behavioral health care will result in greater demand for services. Treatment organizations, already struggling to meet demand and client needs, will need strategies that improve the quality of care they provide without significantly increasing costs. The five NIATx principles have potential for helping agencies achieve these goals.
Related JoVE Video

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.