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1.
Am Heart J ; 185: 110-122, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28267464

ABSTRACT

Based on prior research finding the 5HTTLPR L allele associated with increased cardiovascular reactivity to laboratory stressors and increased risk of myocardial infarction, we hypothesized that the 5HTTLPR L allele will be associated with increased blood pressure (BP) and increased hypertension prevalence in 2 large nationally representative samples in the United States and Singapore. METHODS: Logistic regression and linear models tested associations between triallelic (L'S', based on rs25531) 5HTTLPR genotypes and hypertension severity and mean systolic and diastolic blood pressure (SBP and DBP) collected during the Wave IV survey of the National Longitudinal Study of Adolescent to Adult Health (Add Health, N=11,815) in 2008-09 and during 2004-07 in 4196 Singaporeans. RESULTS: In US Whites, L' allele carriers had higher SBP (0.9 mm Hg, 95% CI=0.26-1.56) and greater odds (OR=1.23, 95% CI=1.10-1.38) of more severe hypertension than those with S'S' genotypes. In African Americans, L' carriers had lower mean SBP (-1.27mm Hg, 95% CI=-2.53 to -0.01) and lower odds (OR = 0.78, 95% CI=0.65-0.94) of more severe hypertension than those with the S'S' genotype. In African Americans, those with L'L' genotypes had lower DBP (-1.13mm Hg, 95% CI=-2.09 to -0.16) than S' carriers. In Native Americans, L' carriers had lower SBP (-6.05mm Hg, 95% CI=-9.59 to -2.51) and lower odds of hypertension (OR = 0.34, 95% CI=0.13-0.89) than those with the S'S' genotype. In Asian/Pacific Islanders those carrying the L' allele had lower DBP (-1.77mm Hg, 95% CI=-3.16 to -0.38) and lower odds of hypertension (OR = 0.68, 95% CI=0.48-0.96) than those with S'S'. In the Singapore sample S' carriers had higher SBP (3.02mm Hg, 95% CI=0.54-5.51) and DBP (1.90mm Hg, 95% CI=0.49-3.31) than those with the L'L' genotype. CONCLUSIONS: These findings suggest that Whites carrying the L' allele, African Americans and Native Americans with the S'S' genotype, and Asians carrying the S' allele will be found to be at higher risk of developing cardiovascular disease and may benefit from preventive measures.


Subject(s)
Blood Pressure/genetics , Hypertension/genetics , Serotonin Plasma Membrane Transport Proteins/genetics , Adult , Black or African American/genetics , Asian People/genetics , Female , Gene Frequency , Genotype , Humans , Hypertension/epidemiology , Hypertension/ethnology , Indians, North American/genetics , Linear Models , Logistic Models , Male , Middle Aged , Odds Ratio , Singapore/epidemiology , United States/epidemiology , White People/genetics
2.
BMC Oral Health ; 16(1): 113, 2016 Oct 28.
Article in English | MEDLINE | ID: mdl-27793148

ABSTRACT

BACKGROUND: Successful pulp regeneration depends on identification of pulp stem cells capable of differentiation under odontoblastic lineage and producing pulp-dentinal like structure. Recent studies demonstrate that platelet-derived growth factor (PDGF) plays an important role in damage repair and tissue regeneration. The aim of this study was to identify a subpopulation of dental pulp cells responsive to PDGF and with dentin regeneration potential. METHODS: Pulp tissues were isolated from 12 freshly extracted human impacted third molars. Pulp cells were sorted by their expression of PDGFRß and stem cell marker genes via flow cytometry. For the selected cells, proliferation was analyzed by a colorimetric cell proliferation assay, differentiation was assessed by real time PCR detection the expression of odontoblast marker genes, and mineralization was evaluated by Alizarin Red S staining. GFP marked PDGFRß+/c-kit+ pulp cells were transplanted into emptied root canals of nude rat lower left incisors. Pulp-dentinal regeneration was examined by immunohistochemistry. RESULTS: PDGFRß+/c-kit+ pulp cells proliferated significantly faster than whole pulp cells. In mineralization media, PDGFRß+/c-kit+ pulp cells were able to develop under odontoblastic linage as demonstrated by a progressively increased expression of DMP1, DSPP, and osteocalcin. BMP2 seemed to enhance whereas PDGF-BB seemed to inhibit odontoblastic differentiation and mineralization of PDGFRß+/c-kit+ pulp cells. In vivo root canal transplantation study revealed globular dentin and pulp-like tissue formation by PDGFRß+/c-kit+ cells. CONCLUSIONS: PDGFRß+/c-kit+ pulp cells appear to have pulp stem cell potential capable of producing dentinal like structure in vitro and in vivo.


Subject(s)
Cell Proliferation , Odontoblasts/metabolism , Receptor, Platelet-Derived Growth Factor beta/metabolism , Animals , Cell Differentiation , Dental Pulp , Dentin , Extracellular Matrix Proteins , Humans , Phosphoproteins , Rats , Sialoglycoproteins
3.
ACS Nano ; 18(23): 14978-14988, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38805401

ABSTRACT

3D assembly technology is a cutting-edge methodology for constructing high-performance and multifunctional photodetectors since some attractive photodetection features such as light trapping effect, omnidirectional ability, and high spatial resolution can be introduced. However, there has not been any report of 3D-assembled multimode photodetectors owing to the lack of design and fabrication guideline of electrodes serving for 3D heterostructures. In this study, a 3D-assembled dual-mode photodetector (3DdmPD) was realized successfully via the clever electrical contact between the rolled-up tubular graphene/GaAs/InGaAs heterostructure and planar metal electrode. Arbitrary switching of three coplanar electrodes makes the as-fabricated tubular 3D photodetector work at the unbiased photodiode mode, which is suitable for energy conservation high-speed photodetection, or the biased photoconductive mode, which favors extremely weak light photodetection, fully showing the advantages of multifunctional detection. In more detail, the Ilight/Idark ratio reached as high as 2 × 104, and a responsivity of 42.3 mA/W, a detectivity of 1.5 × 1010 Jones, as well as a rising/falling time (τr/τf) of 360/370 µs were achieved under the self-driven photodiode mode. Excitingly, 3DdmPD shows omnidirectional photodetection ability at the same time. When 3DdmPD works at the photoconductive mode with 5 V bias, its responsivity is extremely high as 7.9 × 104 A/W and corresponding detectivity is increased to 1.0 × 1011 Jones. Benefiting from the totally independent coplanar electrodes, 3DdmPD is much more easily integrated as arrays that are expected to offer the function of high-speed omnidirectional image-sensing with ultralow power consumption than the planar counterparts which share communal bottom electrodes. We believe that our work can contribute to the progress of 3D-assembled optoelectronic devices.

4.
Nano Lett ; 12(4): 1851-6, 2012 Apr 11.
Article in English | MEDLINE | ID: mdl-22439825

ABSTRACT

Formation mechanism and optical properties of InAs quantum dots (QDs) on the surface of GaAs nanowires (NWs) were investigated. This NW-QDs hybrid structure was fabricated by Au-catalyzed metal organic chemical vapor deposition. We found that the formation and distribution of QDs were strongly influenced by the deposition time of InAs as well as the diameter of GaAs NWs. A model based on the adatom diffusion mechanism was proposed to describe the evolution process of the QDs. Photoluminescence emission from the InAs QDs with a peak wavelength of 940 nm was observed at room temperature. The structure also exhibits a decoupling feature that QDs act as gain medium, while NW acts as Fabry-Perot cavity. This hybrid structure could serve as an important element in high-performance NW-based optoelectronic devices, such as near-infrared lasers, optical detectors, and solar cells.

5.
Appl Opt ; 51(24): 5767-72, 2012 Aug 20.
Article in English | MEDLINE | ID: mdl-22907001

ABSTRACT

Hybrid integrated photodetectors with flat-top steep-edge spectral responses that consist of an Si-based multicavity Fabry-Perot (F-P) filter and an InP-based p-i-n absorption structure (with a 0.2 µm In(0.53)Ga(0.47)As absorption layer), have been designed and fabricated. The performance of the hybrid integrated photodetectors is theoretically investigated by including key factors such as the thickness of each cavity, the pairs of each reflecting mirror, and the thickness of the benzocyclobutene bonding layer. The device is fabricated by bonding an Si-based multicavity F-P filter with an InP-based p-i-n absorption structure. A hybrid integrated photodetector with a peak quantum efficiency of 55% around 1549.2 nm, the -0.5 dB band of 0.43 nm, the 25 dB band of 1.06 nm, and 3 dB bandwidth more than 16 GHz, is simultaneously obtained. Based on multicavity F-P structure, this device has good flat-top steep-edge spectral response.

6.
Nano Lett ; 11(9): 3941-5, 2011 Sep 14.
Article in English | MEDLINE | ID: mdl-21848312

ABSTRACT

InAs quantum dots (QDs) are grown epitaxially on Au-catalyst-grown GaAs nanowires (NWs) by metal organic chemical vapor deposition (MOCVD). These QDs are about 10-30 nm in diameter and several nanometers high, formed on the {112} side facets of the GaAs NWs. The QDs are very dense at the base of the NW and gradually sparser toward the top until disappearing at a distance of about 2 µm from the base. It can be concluded that these QDs are formed by adatom diffusion from the substrate as well as the sidewalls of the NWs. The critical diameter of the GaAs NW that is enough to form InAs QDs is between 120 and 160 nm according to incomplete statistics. We also find that these QDs exhibit zinc blende (ZB) structure that is consistent with that of the GaAs NW and their edges are faceted along particular surfaces. This hybrid structure may pave the way for the development of future nanowire-based optoelectronic devices.

7.
Spectrochim Acta A Mol Biomol Spectrosc ; 281: 121626, 2022 Nov 15.
Article in English | MEDLINE | ID: mdl-35868055

ABSTRACT

With the rapid development of trace detection, high-performance flexible surface-enhanced Raman scattering (SERS) substrates have enjoyed steady growth of interest. In this paper, a facile method to improve the robustness of the flexible SERS substrate via the synergistic effect of rigid SiO2 nanospheres and flexible tape was demonstrated for the first time. In detail, the spin-coated SiO2 nanosphere monolayer was transferred from the host silicon wafer into the tape by peeling-off process, followed by O2 plasma etching of tape polymer to expose the nanospheres, and final Au coating to form plentiful SERS "hotspots". The as-prepared SERS sample shows a detection limit of Rhodamine 6G (R6G) down to 10-10 M and can afford a 500 times bending-releasing cyclic test. Our research provides a promising strategy to prepare robust SERS substrates which exhibit good potential in practical molecule detection on curved surfaces.


Subject(s)
Metal Nanoparticles , Nanospheres , Gold/chemistry , Metal Nanoparticles/chemistry , Nanospheres/chemistry , Polymers , Silicon Dioxide/chemistry
8.
Nano Lett ; 10(1): 64-8, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20000817

ABSTRACT

Vertical GaAs nanowires on Si (111) substrate were grown by metal organic chemical vapor deposition via Au-catalyst vapor-liquid-solid mechanism. Stacking-faults-free zinc blende nanowires were realized by using AlGaAs/GaAs buffer layers and growing under the optimized conditions, that the alloy droplet act as a catalyst rather than an adatom collector and its size and composition would keep stable during growth. The stable droplet contributes to the growth of stacking-faults-free nanowires. Moreover, by using the buffer layers, epitaxial growth of well-aligned NWs was not limited by the misfit strain induced critical diameter, and the unintentional doping of the GaAs nanowires with Si was reduced.

9.
Singapore Med J ; 62(3): 143-148, 2021 Mar.
Article in English | MEDLINE | ID: mdl-31989181

ABSTRACT

INTRODUCTION: Fragile X syndrome (FXS) is the most prevalent X-linked intellectual disability (ID) and a leading genetic cause of autism, characterised by cognitive and behavioural impairments. The hyperexpansion of a CGG repeat in the fragile X mental retardation 1 (FMR1) gene leads to abnormal hypermethylation, resulting in the lack or absence of its protein. Tools for establishing the diagnosis of FXS have been extensively developed, including assays based on triplet-primed polymerase chain reaction (TP-PCR) for detection and quantification of the CGG trinucleotide repeat expansion, as well as determination of the methylation status of the alleles. This study aimed to utilise a simple, quick and affordable method for high sensitivity and specificity screening and diagnosis of FXS in institutionalised individuals with ID. METHODS: A total of 109 institutionalised individuals at the Center for Social Rehabilitation of Intellectual Disability Kartini, Temanggung, Central Java, Indonesia, were screened in a three-step process using FastFrax™ Identification, Sizing and Methylation Status Kits. RESULTS: Two samples that were classified as indeterminate with respect to the 41-repeat control at the identification step were subsequently determined to be non-expanded by both sizing and methylation status analyses. Two samples classified as expanded at the identification step were determined to carry full mutation expansions > 200 repeats that were fully methylated using sizing and methylation status analyses, respectively, yielding a disease prevalence of 1.83%. CONCLUSION: Repeat expansion and methylation-specific TP-PCR is practical, effective and inexpensive for the diagnosis of FXS, especially in high-risk populations of individuals with ID of undetermined aetiology.


Subject(s)
Fragile X Syndrome , Intellectual Disability , Fragile X Mental Retardation Protein/genetics , Fragile X Syndrome/diagnosis , Fragile X Syndrome/genetics , Humans , Intellectual Disability/diagnosis , Intellectual Disability/genetics , Methylation , Mutation , Polymerase Chain Reaction
10.
Opt Express ; 18(6): 5879-89, 2010 Mar 15.
Article in English | MEDLINE | ID: mdl-20389605

ABSTRACT

An integrated reconfigurable four-channel wavelength-division-multiplexed drop module for use in the long-wavelength was demonstrated using a tunable wavelength-selective photodetector array. The array consists of an InP-based p-i-n absorption structure and a GaAs-based multistep Fabry-Pérot filtering cavity. The high quality GaAs/InP heteroepitaxy was realized by employing a thin low temperature buffer layer. The GaAs-based multistep cavity was fabricated by wet etching and regrowth. The dropped central wavelengths were 1538, 1550, 1559, and 1570nm. The tunable range reached 10nm with a tuning power efficiency of 14.2nm/W. A spectral linewidth less than 0.5nm (FWHM), a 3dB bandwidth of 9.2GHz, and the peak quantum efficiencies from 13% to 20% were simultaneously obtained, in agreement with the theoretical simulation.


Subject(s)
Photometry/instrumentation , Refractometry/instrumentation , Telecommunications/instrumentation , Transducers , Equipment Design , Equipment Failure Analysis , Systems Integration
11.
Nanotechnology ; 21(47): 475602, 2010 Nov 26.
Article in English | MEDLINE | ID: mdl-21030767

ABSTRACT

The dependence of crystal structure on contributions of adatom diffusion (ADD) and precursor direct impingement (DIM) was investigated for vapor-liquid-solid growth of InAs nanowires (NWs). The ADD contributions from the sidewalls and substrate surface can be changed by using GaAs NWs of different length as the basis for growing InAs NWs. We found that pure zinc-blende structure is favored when DIM contributions dominate. Moreover, without changing the NW diameter or growth parameters (such as temperature or V/III ratio), a transition from zinc-blende to wurtzite structure can be realized by increasing the ADD contributions. A nucleation model is proposed in which ADD and DIM contributions play different roles in determining the location and phase of the nucleus.

12.
PLoS One ; 15(9): e0238857, 2020.
Article in English | MEDLINE | ID: mdl-32898195

ABSTRACT

BACKGROUND: Hypoxia-induced oxidative stress is one of the main mechanisms of myocardial injury, which frequently results in cardiomyocyte death and precipitates life-threatening heart failure. Propofol (2,6-diisopropylphenol), which is used to sedate patients during surgery, was shown to strongly affect the regulation of physiological processes, including hypoxia-induced oxidative stress. However, the exact mechanism is still unclear. METHODS: Expression of LRPPRC, SLIRP, and Bcl-2 after propofol treatment was measured by RT-qPCR and western blot analyses. The effects of propofol under hypoxia were determine by assessing mitochondrial homeostasis and mitochondrial function, including the ATP level and mitochondrial mass. Autophagy/mitophagy was measured by detecting the presence of LC3B, and autophagosomes were observed by transmission microscopy. RESULTS: Propofol treatment inhibited cleaved caspase-9 and caspase-3, indicating its inhibitory roles in mitochondrial-related apoptosis. Propofol treatment also transcriptionally activated LRPPRC, a mitochondrial-associated protein that exerts multiple functions by maintaining mitochondrial homeostasis, in a manner dependent on the presence of hypoxia-induced factor (HIF)-1α transcriptional activity in H9C2 and primary rat cardiomyocytes. LRPPRC induced by propofol maintained the mitochondrial membrane potential (MMP) and promoted mitochondrial function, including ATP synthesis and transcriptional activity. Furthermore, LRPPRC induced by propofol contributes, at least partially, to the inhibition of apoptotic cell death induced by hypoxia. CONCLUSION: Taken together, our results indicate that LRPPRC may have a protective antioxidant effect by maintaining mitochondrial homoeostasis induced by propofol and provide new insight into the protective mechanism of propofol against oxidative stress.


Subject(s)
Gene Expression Regulation/drug effects , Hypoxia/physiopathology , Mitochondria/drug effects , Mitochondrial Proteins/metabolism , Myocytes, Cardiac/drug effects , Propofol/pharmacology , Protective Agents/pharmacology , Anesthetics, Intravenous/pharmacology , Animals , Apoptosis , Cells, Cultured , Membrane Potential, Mitochondrial , Mitochondria/genetics , Mitochondria/metabolism , Mitochondrial Proteins/genetics , Myocytes, Cardiac/cytology , Myocytes, Cardiac/metabolism , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Oxidative Stress , Proto-Oncogene Proteins c-bcl-2 , Rats , Reactive Oxygen Species
13.
Sci Rep ; 9(1): 8280, 2019 06 04.
Article in English | MEDLINE | ID: mdl-31164682

ABSTRACT

Myotonic dystrophy type 1 is a multisystem disorder caused by the expansion of a trinucleotide repeat in the DMPK gene. In this study we evaluated the performance of the FastDM1TM DMPK sizing kit in myotonic dystrophy type 1 testing. This commercially available triplet repeat-primed PCR based kit was validated using reference and clinical samples. Based on testing with 19 reference samples, the assay yielded repeat sizes within three repeats from the consensus reference length, demonstrating an accuracy of 100%. Additionally, the assay generated consistent repeat size information with a concentration range of template-DNA, and upon repetition and reproduction (CV 0.36% to 0.41%). Clinical performance was established with 235 archived prenatal and postnatal clinical samples, yielding results of 100% sensitivity (95% CI, 97.29% to 100%) and 100% specificity (95% CI, 96.19% to 100%) in classifying the samples into the respective genotype groups of 5-35 (normal), 36-50 (non-pathogenic pre-expansion), 51-150 (unstable intermediate-sized pathogenic) or >150 (unstable pathogenic) CTG repeats, respectively. Furthermore, the assay identified interrupted repeat expansions in all samples known to have interruptions, and also identified interruptions in a subset of the clinical samples.


Subject(s)
Myotonic Dystrophy/genetics , Myotonin-Protein Kinase/genetics , Trinucleotide Repeat Expansion/genetics , Trinucleotide Repeats/genetics , Genotype , Humans , Myotonic Dystrophy/diagnosis , Myotonic Dystrophy/pathology , Polymerase Chain Reaction
14.
J Oral Sci ; 59(4): 621-627, 2017.
Article in English | MEDLINE | ID: mdl-29279572

ABSTRACT

An ideal pulp-capping agent needs to have good biocompatibility and promote reparative dentinogenesis. Although the effects of capping agents on healthy pulp are known, limited data regarding their effects on bacterial contaminated pulp are available. This study aimed to evaluate the reaction of contaminated pulps to various capping agents to assist clinicians in making informed decisions. Human dental pulp (HDP) cell cultures were developed from extracted human molars. The cells were exposed to a bacterial cocktail comprising Porphyromonas gingivalis, Prevotella intermedia, and Streptococcus gordonii before being cocultured with capping agents such as mineral trioxide aggregate (MTA) Portland cement (PC), and Dycal. HDP cell proliferation was assayed by MTS colorimetric cell proliferation assay, and its differentiation was evaluated by real-time PCR for detecting alkaline phosphatase, dentin sialophosphoprotein, and osteocalcin expressions. MTA and PC had no apparent effect, whereas Dycal inhibited HDP cell proliferation. PC stimulated HDP cell differentiation, particularly when they were exposed to bacteria. MTA and Dycal inhibited differentiation, regardless of bacterial infection. In conclusion, PC was the most favorable agent, followed by MTA, and Dycal was the least favorable agent for supporting the functions of bacterial compromised pulp cells.


Subject(s)
Bacteria/isolation & purification , Dental Pulp/drug effects , Pulp Capping and Pulpectomy Agents/pharmacology , Adolescent , Adult , Aluminum Compounds/administration & dosage , Calcium Compounds/administration & dosage , Colorimetry , Dental Pulp/cytology , Dental Pulp/microbiology , Drug Combinations , Humans , Oxides/administration & dosage , Porphyromonas gingivalis/drug effects , Prevotella intermedia , Silicates/administration & dosage , Streptococcus gordonii/drug effects , Young Adult
15.
J Dermatol Sci ; 40(1): 21-8, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16051466

ABSTRACT

BACKGROUND: Extracellular calcium is an important regulator of keratinocyte differentiation. An increase in intracellular calcium ion concentration is required for activation of calcium-induced keratinocyte differentiation. The signaling elements in this differentiation response include the calcium sensing receptor, phospholipase C, release of calcium ions from intracellular stores, and store-operated calcium channels. Nothing is currently known about the calcium-entry channels activated by the increase in external calcium. However, canonical transient receptor potential (TRPC) channels have been identified as store-operated calcium channels in several tissues. OBJECTIVE: To examine the expression of TRPC channels in human gingival keratinocytes (HGKs) in primary culture under both low calcium (basal) and high calcium (differentiating) conditions, and in gingival tissue. METHODS: TRPC channel expression was evaluated via RT-PCR, Western blots, and immunohistology. RESULTS: TRPC1, TRPC5, TRPC6 and TRPC7 mRNAs were detected in undifferentiated keratinocytes. Their levels initially increased, then decreased during calcium-induced differentiation. TRPC1 and TRPC6 protein expression reflected these changes. CONCLUSION: TRPC channels are present in both proliferating and differentiating keratinocytes in primary culture and in gingival tissue. The above expression patterns suggest that these channels may be involved in calcium-induced differentiation of keratinocytes.


Subject(s)
Calcium Channels/genetics , Calcium/pharmacology , Cation Transport Proteins/genetics , Gingiva/metabolism , Ion Channels/genetics , Keratinocytes/metabolism , Membrane Proteins/genetics , Cell Differentiation , Cells, Cultured , Gingiva/cytology , Humans , Keratinocytes/cytology , Protein Precursors/genetics , RNA, Messenger/analysis , TRPC Cation Channels , TRPC6 Cation Channel , TRPM Cation Channels
16.
Front Behav Neurosci ; 9: 94, 2015.
Article in English | MEDLINE | ID: mdl-25964750

ABSTRACT

Dysregulations in the brain serotonergic system and exposure to environmental stressors have been implicated in the development of major depressive disorder. Here, we investigate the interactions between the stress and serotonergic systems by characterizing the behavioral and biochemical effects of chronic stress applied during early-life or adulthood in wild type (WT) mice and mice with deficient tryptophan hydroxylase 2 (TPH2) function. We showed that chronic mild stress applied in adulthood did not affect the behaviors and serotonin levels of WT and TPH2 knock-in (KI) mice. Whereas, maternal separation (MS) stress increased anxiety- and depressive-like behaviors of WT mice, with no detectable behavioral changes in TPH2 KI mice. Biochemically, we found that MS WT mice had reduced brain serotonin levels, which was attributed to increased expression of monoamine oxidase A (MAO A). The increased MAO A expression was detected in MS WT mice at 4 weeks old and adulthood. No change in TPH2 expression was detected. To determine whether a pharmacological stressor, dexamethasone (Dex), will result in similar biochemical results obtained from MS, we used an in vitro system, SH-SY5Y cells, and found that Dex treatment resulted in increased MAO A expression levels. We then treated WT mice with Dex for 5 days, either during postnatal days 7-11 or adulthood. Both groups of Dex treated WT mice had reduced basal corticosterone and glucocorticoid receptors expression levels. However, only Dex treatment during PND7-11 resulted in reduced serotonin levels and increased MAO A expression. Just as with MS WT mice, TPH2 expression in PND7-11 Dex-treated WT mice was unaffected. Taken together, our findings suggest that both environmental and pharmacological stressors affect the expression of MAO A, and not TPH2, when applied during the critical postnatal period. This leads to long-lasting perturbations in the serotonergic system, and results in anxiety- and depressive-like behaviors.

17.
Sleep ; 37(1): 27-39, 2014 Jan 01.
Article in English | MEDLINE | ID: mdl-24470693

ABSTRACT

STUDY OBJECTIVES: To identify baseline behavioral and physiologic markers that associate with individual differences in sustained attention during sleep deprivation. DESIGN: In a retrospective study, ocular, electrocardiogram, and electroencephalogram (EEG) measures were compared in subjects who were characterized as resilient (n = 15) or vulnerable (n = 15) to the effects of total sleep deprivation on sustained attention. SETTING: Chronobiology and Sleep Laboratory, Duke-NUS Graduate Medical School Singapore. PARTICIPANTS: Healthy volunteers aged 22-32 years from the general population. INTERVENTIONS: Subjects were kept awake for at least 26 hours under constant environmental conditions. Every 2 hours, sustained attention was assessed using a 10-minute psychomotor vigilance task (PVT). MEASUREMENTS AND RESULTS: During baseline sleep and recovery sleep, EEG slow wave activity was similar in resilient versus vulnerable subjects, suggesting that individual differences in vulnerability to sleep loss were not related to differences in homeostatic sleep regulation. Rather, irrespective of time elapsed since wake, subjects who were vulnerable to sleep deprivation exhibited slower and more variable PVT response times, lower and more variable heart rate, and higher and more variable EEG spectral power in the theta frequency band (6.0-7.5 Hz). CONCLUSIONS: Performance decrements in sustained attention during sleep deprivation associate with instability in behavioral and physiologic measures at baseline. Small individual differences in sustained attention that are present at baseline are amplified during prolonged wakefulness, thus contributing to large between-subjects differences in performance and sleepiness.


Subject(s)
Attention/physiology , Psychomotor Performance/physiology , Sleep Deprivation/physiopathology , Sleep Stages/physiology , Adult , Arousal/physiology , Asian People , Circadian Rhythm/physiology , Electrocardiography , Electroencephalography , Female , Heart Rate , Homeostasis , Humans , Individuality , Male , Reaction Time/physiology , Reproducibility of Results , Sleep Deprivation/diagnosis , Theta Rhythm/physiology , Wakefulness/physiology , Young Adult
18.
Pflugers Arch ; 452(1): 43-52, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16283206

ABSTRACT

External calcium ion concentration is a major regulator of epidermal keratinocyte differentiation in vitro and probably also in vivo. Regulation of calcium-induced differentiation changes is proposed to occur via an external calcium-sensing, signaling pathway that utilizes increases in intracellular calcium ion concentration to activate differentiation-related gene expression. Calcium ion release from intracellular stores and calcium ion influx via store-operated calcium-permeable channels are key elements in this proposed signaling pathway; however, the channels involved have not yet been identified. The present report shows that human gingival keratinocytes (HGKs) also undergo calcium-induced differentiation in vitro as indicated by involucrin expression and morphological changes. Moreover, TRPC1, which functions as a store-operated calcium channel in a number of cell types, including epidermal keratinocytes, is expressed in both proliferating and differentiating HGKs. Transfection of HGKs with TRPC1 siRNA disrupted expression of TRPC1 mRNA and protein compared with transfection with scrambled TRPC1 siRNA. Cells with disrupted TRPC1 expression showed decreased calcium-induced differentiation as measured by involucrin expression or morphological changes, as well as decreased thapsigargin-induced calcium ion influx, and a decreased rate of store calcium release. These results indicate that TRPC1 is involved in calcium-induced differentiation of HGKs likely by supporting a store-operated calcium ion influx.


Subject(s)
Calcium/physiology , Cell Differentiation/physiology , Keratinocytes/cytology , TRPC Cation Channels/physiology , Cell Proliferation , Humans , Keratinocytes/metabolism , Protein Precursors/metabolism , RNA Interference , RNA, Messenger/metabolism , RNA, Small Interfering , TRPC Cation Channels/metabolism
19.
Pflugers Arch ; 448(1): 93-104, 2004 Apr.
Article in English | MEDLINE | ID: mdl-14770313

ABSTRACT

Calcium-sensing receptor (CaSR) expression and function were studied in proliferating and differentiating cultured human gingival keratinocytes (HGKs). CaSR mRNA and protein were present in proliferating HGKs cultured in 0.03 mM [Ca(2+)] and decreased in cells induced to differentiate by culturing in 1.2 mM [Ca(2+)] for 2 days. CaSR protein was also detected in gingival tissue. Exposure to 10 mM extracellular [Ca(2+)] activated two sequential whole-cell currents. The first was a small, transient calcium release activated calcium current I(CRAC)-like current with an inwardly rectifying I-V curve. The second current was larger with a linear I-V curve. Both currents were significantly decreased in differentiating cells. Neither neomycin nor gadolinium induced changes in whole cell currents nor in intracellular [Ca(2+)], but neomycin inhibited the late large current. Extracellular Ca(2+) increased intracellular [Ca(2+)] of proliferating HGKs in a dose-dependent fashion. Comparison of the time-courses of the whole-cell currents and the intracellular [Ca(2+)] responses indicated both induced currents supported a Ca(2+) influx. Extracellular [Mg(2+)] changes did not affect intracellular [Ca(2+)]. La(3+) and 2-APB inhibited the whole cell current and intracellular [Ca(2+)] changes. The results indicate that the CaSR signaling response likely plays a major role in initiating Ca(2+) induced differentiation responses in HGKs.


Subject(s)
Cell Differentiation/physiology , Fura-2/analogs & derivatives , Keratinocytes/cytology , Keratinocytes/metabolism , Receptors, Calcium-Sensing/metabolism , Blotting, Western , Calcium Signaling/physiology , Cells, Cultured , Gadolinium/pharmacology , Gingiva/cytology , Humans , Immunohistochemistry , Membrane Proteins/physiology , Microscopy, Fluorescence , Neomycin/agonists , Patch-Clamp Techniques , Protein Synthesis Inhibitors/agonists , RNA/isolation & purification , Reverse Transcriptase Polymerase Chain Reaction
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