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  • 1
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    Peroxisome Proliferator-Activated Receptor {gamma} Level Contributes to Structural Integrity and Component Production of Elastic Fibers in the Aorta [PPAR[gamma ] and Aortic Aneurysm] (2016)
    American Heart Association (AHA)
    Details
    Publication Date: 2016-05-12
    Description: Loss of integrity and massive disruption of elastic fibers are key features of abdominal aortic aneurysm (AAA). Peroxisome proliferator–activated receptor (PPAR) has been shown to attenuate AAA through inhibition of inflammation and proteolytic degradation. However, its involvement in elastogenesis during AAA remains unclear. PPAR was highly expressed in human AAA within all vascular cells, including inflammatory cells and fibroblasts. In the aortas of transgenic mice expressing PPAR at 25% normal levels ( Pparg C /– mice), we observed the fragmentation of elastic fibers and reduced expression of vital elastic fiber components of elastin and fibulin-5. These were not observed in mice with 50% normal PPAR expression ( Pparg +/– mice). Infusion of a moderate dose of angiotensin II (500 ng/kg per minute) did not induce AAA but Pparg +/– aorta developed flattened elastic lamellae, whereas Pparg C/– aorta showed severe destruction of elastic fibers. After infusion of angiotensin II at 1000 ng/kg per minute, 73% of Pparg C/– mice developed atypical suprarenal aortic aneurysms: superior mesenteric arteries were dilated with extensive collagen deposition in adventitia and infiltrations of inflammatory cells. Although matrix metalloproteinase inhibition by doxycycline somewhat attenuated the dilation of aneurysm, it did not reduce the incidence nor elastic lamella deterioration in angiotensin II–infused Pparg C/– mice. Furthermore, PPAR antagonism downregulated elastin and fibulin-5 in fibroblasts, but not in vascular smooth muscle cells. Chromatin immunoprecipitation assay demonstrated PPAR binding in the genomic sequence of fibulin-5 in fibroblasts. Our results underscore the importance of PPAR in AAA development though orchestrating proper elastogenesis and preserving elastic fiber integrity.
    Keywords: Animal Models of Human Disease, Remodeling, Aneurysm, Vascular Disease
    Print ISSN: 0194-911X
    Topics: Medicine
    Published by American Heart Association (AHA)
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  • 2
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    Increased Aortic Stiffness and Attenuated Lysyl Oxidase Activity in Obesity [Translational Science] (2013)
    American Heart Association (AHA)
    Details
    Publication Date: 2013-03-14
    Description: Objective— One potential mechanism through which obesity exerts adverse effects on the vascular system is by increasing aortic stiffness, a change known to be predictive of increased cardiovascular mortality. The aim of this study was to investigate the pathophysiology that links obesity to aortic stiffening. Approach and Results— Obese ( ob/ob ) mice were used to examine physical, morphological, and molecular changes in the aorta in response to obesity. ob/ob mice had increased aortic pulse wave velocity and tissue rigidity. ob/ob aorta exhibited decreases of lysyl oxidase (LOX) activity and cross-linked elastin, and increases of elastin fragmentation and elastolytic activity. The aortas of ob/ob mice were surrounded by a significant amount of proinflammatory and pro-oxidative perivascular adipose tissue. In vitro studies revealed that the conditioned medium from differentiated adipocytes or the perivascular adipose tissue of ob/ob mice attenuated LOX activity. Furthermore, inhibition of LOX in wild-type lean mice caused elastin fragmentation and induced a significant increase in pulse wave velocity. Finally, we found that obese humans had stiffer arteries and lower serum LOX levels than do normal-weight humans. Conclusion— Our results demonstrated that obesity resulted in aortic stiffening in both humans and mice, and established a causal relationship between LOX downregulation and aortic stiffening in obesity.
    Keywords: Animal models of human disease, Cell biology/structural biology, Other arteriosclerosis, Other Vascular biology
    Print ISSN: 1079-5642
    Electronic ISSN: 1524-4636
    Topics: Medicine
    Published by American Heart Association (AHA)
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  • 3
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    Correlation of impulsivity with self-harm and suicidal attempt: a community study of adolescents in Taiwan (2017)
    BMJ Publishing
    In: BMJ Open
    Details
    Publication Date: 2017-12-08
    Description: Objectives The aim of this study was to investigate differences and similarities in risk factors for deliberate self-harm (DSH) and suicidal attempt (SA), and the role of impulsivity among a group of community adolescents. Setting This is a cross-sectional study conducted at high schools in Northern Taiwan. Data and participants We recruited grade 1 students from 14 high schools. A total of 5879 participants (mean age 16.02 years, female adolescents: 57.7%) completed the online assessment. Outcome measures Participants completed online questionnaires about sociodemographic data, suicidality, history of DSH and SA, depressed mood, self-esteem, social support, family discord, impulsivity (Barratt Impulsiveness Scale Version 11 (BIS-11)) and the use of alcohol, tobacco and illicit drugs. A subsample was interviewed about lifetime SA, and the results were compared with those from the online questionnaires. Results In our sample, 25% of the students had lifetime DSH and 3.5% had lifetime SA. Two hundred and seventy-two students received face-to-face interviews. The concordance between the online questionnaires and interviews in terms of ascertaining cases of SA was moderate (concordance rate 82.76%; kappa value 0.59). Similar risk factors for DSH/SA among the whole sample included female gender, lower academic performance, depression, substance use (tobacco and alcohol) and low self-esteem. The BIS-11 score was correlated with DSH. Factor 3 score of the BIS-11 (novelty seeking) was correlated with DSH in both boys and girls, whereas factor 2 score (lack of self-control) was correlated with SA in boys. Social support was a protective factor against SA among the female adolescents. Gender modulated the association of impulsivity and DSH/SA. Associations between impulsivity and DSH and SA were particularly strong among boys. Conclusions Risk factors for DSH and SA were similar, but not identical. Early identification of those at risk and appropriate interventions may be helpful.
    Keywords: Open access, Mental health
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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  • 4
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    Elucidating challenges that electronic cigarettes pose to tobacco control in Asia: a population-based national survey in Taiwan (2017)
    BMJ Publishing
    In: BMJ Open
    Details
    Publication Date: 2017-03-28
    Description: Objectives This study investigated the prevalence and correlates of electronic cigarettes (e-cigarettes) use in Taiwan. Design and setting We studied a nationally representative random sample in the 2015 Taiwan Adult Smoking Behavior Survey. Participants This study included 26 021 participants aged 15 years or older (51% women, 79% non-smokers, 16% aged 15–24 years), after excluding 31 persons (0.1%) who had missing information on e-cigarette use. Primary outcome measures The prevalence of ever having used e-cigarettes was calculated in the overall sample and by smoking status (current, former and never) or age (15–24, 25–44 and ≥45 years). We performed multivariable log-binomial regression to assess correlates of ever having used e-cigarettes among all participants and separately for subgroups by smoking status and age. Results Approximately 3% of all participants had ever used e-cigarettes. The prevalence of ever having used e-cigarettes was high in current smokers (14%) and people aged 18–24 years (7%). E-cigarette use was particularly common in people aged 15–24 years who were current (49–52%) or former (22–39%) smokers. Ever having used e-cigarettes was positively associated with tobacco smoking (adjusted prevalence ratio (aPR): 21.5, 95% CI 15.4 to 29.8, current smokers; aPR: 8.3, 95% CI 15.2 to 13.1, former smokers), younger age and high socioeconomic status. Age remained a significant factor of ever having used e-cigarettes across smoking status groups. Among non-smokers, men had a 2.4-fold (95% CI 1.5 to 3.8) greater prevalence of e-cigarette use than women. Conclusions E-cigarette use was uncommon in the general population in Taiwan, but prevalence was high among smokers and young people. This study highlights challenges that e-cigarettes pose to tobacco control, which warrant high priority action by policymakers and public health professionals. E-cigarette regulations should focus on young people.
    Keywords: Open access, Health policy, Public health, Smoking and tobacco
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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  • 5
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    GLK-IKK{beta} signaling induces dimerization and translocation of the AhR-ROR{gamma}t complex in IL-17A induction and autoimmune disease (2018)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2018-09-13
    Description: Retinoic-acid-receptor-related orphan nuclear receptor t (RORt) controls the transcription of interleukin-17A (IL-17A), which plays critical roles in the pathogenesis of autoimmune diseases. Severity of several human autoimmune diseases is correlated with frequencies of germinal center kinase–like kinase (GLK) (also known as MAP4K3)–overexpressing T cells; however, the mechanism of GLK overexpression–induced autoimmunity remains unclear. We report the signal transduction converging on aryl hydrocarbon receptor (AhR)–RORt interaction to activate transcription of the IL-17A gene in T cells. T cell–specific GLK transgenic mice spontaneously developed autoimmune diseases with selective induction of IL-17A in T cells. In GLK transgenic T cells, protein kinase C (PKC) phosphorylated AhR at Ser 36 and induced AhR nuclear translocation. AhR also interacted with RORt and transported RORt into the nucleus. IKKβ (inhibitor of nuclear factor B kinase β)–mediated RORt Ser 489 phosphorylation induced the AhR-RORt interaction. T cell receptor (TCR) signaling also induced the novel RORt phosphorylation and subsequent AhR-RORt interaction. Collectively, TCR signaling or GLK overexpression induces IL-17A transcription through the IKKβ-mediated RORt phosphorylation and the AhR-RORt interaction in T cells. Our findings suggest that inhibitors of GLK or the AhR-RORt complex could be used as IL-17A–blocking agents for IL-17A–mediated autoimmune diseases.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 6
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    Dopamine neurons modulate neural encoding and expression of depression-related behaviour (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-12-14
    Description: Major depression is characterized by diverse debilitating symptoms that include hopelessness and anhedonia. Dopamine neurons involved in reward and motivation are among many neural populations that have been hypothesized to be relevant, and certain antidepressant treatments, including medications and brain stimulation therapies, can influence the complex dopamine system. Until now it has not been possible to test this hypothesis directly, even in animal models, as existing therapeutic interventions are unable to specifically target dopamine neurons. Here we investigated directly the causal contributions of defined dopamine neurons to multidimensional depression-like phenotypes induced by chronic mild stress, by integrating behavioural, pharmacological, optogenetic and electrophysiological methods in freely moving rodents. We found that bidirectional control (inhibition or excitation) of specified midbrain dopamine neurons immediately and bidirectionally modulates (induces or relieves) multiple independent depression symptoms caused by chronic stress. By probing the circuit implementation of these effects, we observed that optogenetic recruitment of these dopamine neurons potently alters the neural encoding of depression-related behaviours in the downstream nucleus accumbens of freely moving rodents, suggesting that processes affecting depression symptoms may involve alterations in the neural encoding of action in limbic circuitry.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4160519/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4160519/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tye, Kay M -- Mirzabekov, Julie J -- Warden, Melissa R -- Ferenczi, Emily A -- Tsai, Hsing-Chen -- Finkelstein, Joel -- Kim, Sung-Yon -- Adhikari, Avishek -- Thompson, Kimberly R -- Andalman, Aaron S -- Gunaydin, Lisa A -- Witten, Ilana B -- Deisseroth, Karl -- DP2 DA035149/DA/NIDA NIH HHS/ -- F32 MH880102/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Jan 24;493(7433):537-41. doi: 10.1038/nature11740. Epub 2012 Dec 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Picower Institute for Learning and Memory, Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. kaytye@mit.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23235822" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Depression/chemically induced/*physiopathology ; Dopamine/metabolism ; Dopaminergic Neurons/drug effects/*metabolism/radiation effects ; Female ; Male ; Mice ; Models, Neurological ; Nucleus Accumbens/metabolism ; Optogenetics ; Phenotype ; Rats ; Rats, Long-Evans ; Stress, Psychological/physiopathology ; Time Factors ; Ventral Tegmental Area/cytology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 7
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    Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-12-14
    Description: Ventral tegmental area (VTA) dopamine neurons in the brain's reward circuit have a crucial role in mediating stress responses, including determining susceptibility versus resilience to social-stress-induced behavioural abnormalities. VTA dopamine neurons show two in vivo patterns of firing: low frequency tonic firing and high frequency phasic firing. Phasic firing of the neurons, which is well known to encode reward signals, is upregulated by repeated social-defeat stress, a highly validated mouse model of depression. Surprisingly, this pathophysiological effect is seen in susceptible mice only, with no apparent change in firing rate in resilient individuals. However, direct evidence--in real time--linking dopamine neuron phasic firing in promoting the susceptible (depression-like) phenotype is lacking. Here we took advantage of the temporal precision and cell-type and projection-pathway specificity of optogenetics to show that enhanced phasic firing of these neurons mediates susceptibility to social-defeat stress in freely behaving mice. We show that optogenetic induction of phasic, but not tonic, firing in VTA dopamine neurons of mice undergoing a subthreshold social-defeat paradigm rapidly induced a susceptible phenotype as measured by social avoidance and decreased sucrose preference. Optogenetic phasic stimulation of these neurons also quickly induced a susceptible phenotype in previously resilient mice that had been subjected to repeated social-defeat stress. Furthermore, we show differences in projection-pathway specificity in promoting stress susceptibility: phasic activation of VTA neurons projecting to the nucleus accumbens (NAc), but not to the medial prefrontal cortex (mPFC), induced susceptibility to social-defeat stress. Conversely, optogenetic inhibition of the VTA-NAc projection induced resilience, whereas inhibition of the VTA-mPFC projection promoted susceptibility. Overall, these studies reveal novel firing-pattern- and neural-circuit-specific mechanisms of depression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554860/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554860/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chaudhury, Dipesh -- Walsh, Jessica J -- Friedman, Allyson K -- Juarez, Barbara -- Ku, Stacy M -- Koo, Ja Wook -- Ferguson, Deveroux -- Tsai, Hsing-Chen -- Pomeranz, Lisa -- Christoffel, Daniel J -- Nectow, Alexander R -- Ekstrand, Mats -- Domingos, Ana -- Mazei-Robison, Michelle S -- Mouzon, Ezekiell -- Lobo, Mary Kay -- Neve, Rachael L -- Friedman, Jeffrey M -- Russo, Scott J -- Deisseroth, Karl -- Nestler, Eric J -- Han, Ming-Hu -- F31 MH095425/MH/NIMH NIH HHS/ -- F32 MH096464/MH/NIMH NIH HHS/ -- K99 MH094405/MH/NIMH NIH HHS/ -- R01 MH092306/MH/NIMH NIH HHS/ -- R25 GM064118/GM/NIGMS NIH HHS/ -- T32 MH020016/MH/NIMH NIH HHS/ -- T32 MH087004/MH/NIMH NIH HHS/ -- T32 MH096678/MH/NIMH NIH HHS/ -- England -- Nature. 2013 Jan 24;493(7433):532-6. doi: 10.1038/nature11713. Epub 2012 Dec 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology and Systems Therapeutics, Friedman Brain Institute, Mount Sinai School of Medicine, New York, New York 10029, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23235832" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Depression/etiology/*physiopathology ; Dopaminergic Neurons/*metabolism ; Food Preferences ; Male ; Mesencephalon/*cytology ; Mice ; Neural Pathways ; Nucleus Accumbens/physiology ; Optogenetics ; Phenotype ; Prefrontal Cortex/physiology ; *Social Behavior ; Stress, Psychological/complications/*physiopathology ; Sucrose/administration & dosage ; Time Factors ; Ventral Tegmental Area/physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 8
    Electronic Resource
    Electronic Resource
    Insertion reactions of aryl nitrenes
    Amsterdam : Elsevier
    Tetrahedron Letters 6 (1965), S. 2211-2216 
    Details
    ISSN: 0040-4039
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/S0040-4039(00)90181-3
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  • 9
    Electronic Resource
    Electronic Resource
    Materials considerations related to sodium-based rechargeable cells for use above room temperature
    Amsterdam : Elsevier
    Solid State Ionics 42 (1990), S. 109-115 
    Details
    ISSN: 0167-2738
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0167-2738(90)90266-T
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  • 10
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    Chemokine co-receptor usage in HIV-1-infected treatment-naive voluntary counselling and testing clients in Southern Taiwan (2015)
    BMJ Publishing
    In: BMJ Open
    Details
    Publication Date: 2015-05-01
    Description: Objective The goal of this present study was to determine the proportion of CCR5-tropic and CXCR4-tropic viruses and impact of tropism test on clinical presentation, CD4 cell counts, viral load and genotypic drug resistance from drug-naïve, voluntary counselling and testing (VCT) clients in southern Taiwan. Design This was a cross-sectional study. Plasma samples were collected from HIV-1-infected patients from January 2013 to December 2013; subjects were recruited from free VCT centres in southern Taiwan. Setting Taiwan. Participants Plasma samples from 108 HIV-1-infected, treatment-naïve, VCT clients were analysed. HIV-1 strains were sequenced, genotype resistance was determined by a commercial kit (Viro-seq) and co-receptor tropism (CRT) was predicted by an internet tool geno2pheno [coreceptor] , with a 10% false-positive rate as the cut-off. Differences in progression markers, patient characteristics, VCT questionnaires and HIV subtype distribution were evaluated statistically. Results All the 108 VCT clients were male with 90% between the ages of 20 and 40 years. Eighty-eight per cent of the patients were men who have sex with men (MSM). The median (IQR) CD4 cell count was 342 cells/µL (221–454) and the viral load was 4.6 log (4.0–5.0). HIV-transmitted drug resistance was found in 9.3% (10/108) of the patients. CRT predictions indicated that 74% of the patients had only R5-tropic strains. CRT was not associated with CD4 cell counts, patient characteristics, VCT questionnaire and transmitted drug resistance. There was a significant difference with regard to viral load at the time of presentation, showing that patients with R5 more often had a higher viral load as compared with those with X4/DM strains (4.6±0.6 log vs 4.33±0.7 log, p=0.036). Conclusions We found that 74% of the VCT clients were infected with R5-tropic virus strains. HIV-transmitted drug resistance was not associated with CRT predictions. Higher viral load at presentation was predictive of R5 co-receptor usage.
    Keywords: Open access, Infectious diseases, HIV AIDS
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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