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1.
Nano Lett ; 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38588382

RESUMEN

Nitrogen vacancy (NV) center-based magnetometry has been proven to be a versatile sensor for various classes of magnetic materials in broad temperature and frequency ranges. Here, we use the longitudinal relaxation time T1 of single NV centers to investigate the spin dynamics of nanometer-thin flakes of α-RuCl3 at room temperature. We observe a significant reduction in the T1 in the presence of α-RuCl3 in the proximity of NVs, which we attribute to paramagnetic spin noise confined in the 2D hexagonal planes. Furthermore, the T1 time exhibits a monotonic increase with an applied magnetic field. We associate this trend with the alteration of the spin and charge noise in α-RuCl3 under an external magnetic field. These findings suggest that the influence of the spin dynamics of α-RuCl3 on the T1 of the NV center can be used to gain information about the material itself and the technique to be used on other 2D materials.

2.
Luminescence ; 37(3): 472-478, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35032091

RESUMEN

This article presents the effect of europium (Eu) doping on the thermoluminescence (TL) of ultraviolet (UV-254 nm) and gamma irradiated triclinic Mg2 B2 O5 nanophosphors. The diffuse reflectance predicts slight decrease in band gap from 5.18 to 4.99 eV with increasing Eu (1%, 3%, and 5%) content in Mg2 B2 O5 . The TL glow curves of UV irradiated samples comprised of a main peak around 500 K with weak intensity peak/shoulders in low temperature region. Interestingly Eu (3%) doped Mg2 B2 O5 shows maximum TL intensity with suppression of low temperature shoulder peaks and almost linear UV dose dependent TL response. However, in the case of gamma irradiated Eu (1% and 3% doped) samples, TL glow curve comprises of a main peak around 425-445 K and closely lying peak around 500-515 K with relatively lesser intensity. In case of Eu (5%) doped samples, TL peak around 508 K starts dominating over peak around 425 K. TL of both UV and gamma irradiated samples showed the presence of various deep and shallow defect states within the bandgap of materials having different kinetic parameters, which were determined using TLanal software based on Kiti's general order equation. The present study shows that Eu doped Mg2 B2 O5 nanophosphors can be tuned for UV and gamma dosimetry.


Asunto(s)
Europio , Dosimetría Termoluminiscente , Rayos gamma , Mediciones Luminiscentes
3.
Environ Geochem Health ; 44(6): 1783-1793, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34676512

RESUMEN

This research paper is devoted to measure the activity contents of natural radionuclide, like, radium (226Ra), thorium (232Th) and potassium (40K) in the soil gathered along the Jwalamukhi thrust of Himachal Pradesh, North Western Himalayas, India. NaI(Tl) Scintillator detector was utilized for the estimation of activity content. The activity concentration of 226Ra, 232Th and 40K for some of the soil samples have been observed to be above the global normal mean values. The outcomes acquired for indoor and outdoor effective dosage are well below the normal international and national proposed results. The determined values of external hazard (Hex) for studied locations are less than unity, therefore; samples assembled from these regions are safe from a health hazard point of view and can be utilized as a construction purposes without producing any radio-logical hazard to human beings. The average estimations of radium equivalent activity were found to be within the limits suggested by Organization for Economic Cooperation and Development (OECD). Radon (222Rn) and thoron (220Rn) exhalation rates have also been calculated and discussed.


Asunto(s)
Monitoreo de Radiación , Radio (Elemento) , Radón , Contaminantes Radiactivos del Suelo , Humanos , India , Radioisótopos de Potasio/análisis , Monitoreo de Radiación/métodos , Radioisótopos , Radio (Elemento)/análisis , Radón/análisis , Suelo , Contaminantes Radiactivos del Suelo/análisis
4.
Cell Commun Signal ; 17(1): 170, 2019 12 23.
Artículo en Inglés | MEDLINE | ID: mdl-31870452

RESUMEN

BACKGROUND: Dishevelled (DVL) is an essential component of the Wnt signaling cascades. Function of DVL is controlled by phosphorylation but the molecular details are missing. DVL3 contains 131 serines and threonines whose phosphorylation generates complex barcodes underlying diverse DVL3 functions. In order to dissect the role of DVL phosphorylation we analyzed the phosphorylation of human DVL3 induced by previously reported (CK1ε, NEK2, PLK1, CK2α, RIPK4, PKCδ) and newly identified (TTBK2, Aurora A) DVL kinases. METHODS: Shotgun proteomics including TiO2 enrichment of phosphorylated peptides followed by liquid chromatography tandem mass spectrometry on immunoprecipitates from HEK293T cells was used to identify and quantify phosphorylation of DVL3 protein induced by 8 kinases. Functional characterization was performed by in-cell analysis of phospho-mimicking/non-phosphorylatable DVL3 mutants and supported by FRET assays and NMR spectroscopy. RESULTS: We used quantitative mass spectrometry and calculated site occupancies and quantified phosphorylation of > 80 residues. Functional validation demonstrated the importance of CK1ε-induced phosphorylation of S268 and S311 for Wnt-3a-induced ß-catenin activation. S630-643 cluster phosphorylation by CK1, NEK2 or TTBK2 is essential for even subcellular distribution of DVL3 when induced by CK1 and TTBK2 but not by NEK2. Further investigation showed that NEK2 utilizes a different mechanism to promote even localization of DVL3. NEK2 triggered phosphorylation of PDZ domain at S263 and S280 prevents binding of DVL C-terminus to PDZ and promotes an open conformation of DVL3 that is more prone to even subcellular localization. CONCLUSIONS: We identify unique phosphorylation barcodes associated with DVL function. Our data provide an example of functional synergy between phosphorylation in structured domains and unstructured IDRs that together dictate the biological outcome. Video Abtract.


Asunto(s)
Proteínas Dishevelled/metabolismo , Células Cultivadas , Proteínas Dishevelled/química , Células HEK293 , Humanos , Espectrometría de Masas , Quinasas Relacionadas con NIMA/metabolismo , Fosforilación , Conformación Proteica , Transducción de Señal
5.
Cryobiology ; 84: 33-39, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30098997

RESUMEN

Cryopreservation results in substantial deterioration of heat shock protein 70 (HSP70) and ultra-structural changes in sperm organelles, resulting in a marked reduction in post-thaw semen quality. The present study was aimed to explicate the effect of sericin supplementation on expression profile of HSP70, redox status and post-thaw semen quality in Barbari goat. Five Barbari bucks were used to collect thirty semen ejaculates by using artificial vagina and each ejaculate was divided into three aliquots to which sericin was supplemented at 0% (Control), 0.25% (T1) and 0.50% (T2). Further, extended semen samples were equilibrated followed by their cryopreservation. Post-thaw semen characteristics, redox status of seminal plasma, enzyme leakage and HSP70 gene/protein expression in spermatozoa were assessed in all the groups. Per cent progressive motile spermatozoa, spermatozoa having intact plasma membrane (HOST + ve) and intact acrosomes in post-thaw spermatozoa were significantly (p < 0.01) higher in T1 and T2 as compared to control. A significant (p < 0.01) reduction in abnormal spermatozoa was found in T1 as compared to T2. Sericin supplementation significantly (p < 0.05) improved the antioxidative status (SOD, GST, CAT), reduced lipid peroxidation (MDA) and also prevented enzyme (ALT, LDH) leakage as compared to control samples. qRT-PCR results revealed that HSP70 mRNA expression was significantly (p < 0.01) upregulated in T1 and T2 group as compared to control. The positive effect of sericin on expression of HSP70 was further confirmed by immunoblotting followed by densitometry revealing higher expression in T1 and T2 compared to control. Inclusion of 0.25% w/v sericin in semen extender ameliorated the post-thaw semen quality by improving antioxidative status and minimizing the leakage of intracellular enzymes. Sericin supplementation had a beneficial effect on HSP70/HSP70 mRNA expression either by induction or by protection of HSP70/HSP70 mRNA as evident from the gene expression and immunoblotting studies.


Asunto(s)
Criopreservación/métodos , Crioprotectores/farmacología , Proteínas HSP70 de Choque Térmico/biosíntesis , Preservación de Semen/métodos , Sericinas/farmacología , Animales , Antioxidantes/farmacología , Cabras , Masculino , Semen , Análisis de Semen , Motilidad Espermática , Espermatozoides/metabolismo
6.
Phys Chem Chem Phys ; 18(9): 6569-79, 2016 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-26866898

RESUMEN

The magneto-dielectric spectroscopy of La0.95Ca0.05CoO3 covering the crossover of spin states reveals the strong coupling of its spin and dipolar degrees of freedom. The signature of the spin-state transition at 30 K clearly manifests in the magnetization data at a 1 Tesla optimal field. Our Co L3,2-edge X-ray absorption spectrum on the doped specimen is consistent with its suppressed low-to-intermediate spin-state transition temperature at ∼30 K compared to ∼150 K, documented for pure LaCoO3. The dispersive activation step in the dielectric constant with the associated relaxation peak in imaginary permittivity characterize the allied influence of coexistent spin-states on the dielectric character. Dipolar relaxation in the low-spin regime below the transition temperature is partly segmental (Vogel-Fulcher-Tamman (VFT) kinetics) and features magnetic-field tunability, whereas in the low/intermediate-spin disordered state above ∼30 K, it is uncorrelated (Arrhenic kinetics) and almost impervious to the magnetic field H. Kinetics-switchover defines the dipolar-glass transition temperature Tg(H) (=27 K|0T), below which their magneto-thermally-activated cooperative relaxations freeze out by the VFT temperature T0(H) (=15 K|0T). An applied magnetic field facilitates thermal activation in toggling the low spins up into the intermediate states. Consequently, the downsized dipolar-glass segments in the low-spin state and the independent dipoles in the intermediate state exhibit accelerated dynamics. A critical 5 Tesla field collapses the entire relaxation kinetics into a single Arrhenic behaviour, signaling that the dipolar glass is completely devitrified under all higher fields. The magneto-electricity (ME) spanning sizeable thermo-spectral range registers diverse signatures here in kinetic, spectral, and field behaviors, in contrast to the static/perturbative ME observed close to the spin-ordering in typical multiferroics. Intrinsic magneto-dielectricity (50%) along with vanishing magneto-loss is obtained at (27 K/50 kHz)9T. The sub-linear deviant and field-hysteretic split seen in above 4 Tesla suggests the emergence of robust dipoles organized into nano-clusters, induced by the internally-generated high magneto-electric field. An elaborate ω-T multi-dispersions diagram maps the rich variety of phase/response patterns, revealing highly-interacting magnetic and electric moments in the system.

7.
Cytokine ; 72(2): 178-84, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25647274

RESUMEN

UNLABELLED: The aim of this study is to identify loci associated with circulating levels of Interleukin 8 (IL8). We investigated the associations of 121,445 single nucleotide polymorphisms (SNPs) from the Illumina 200K CardioMetabochip with IL8 levels in 1077 controls from the Stockholm Heart Epidemiology Program (SHEEP) study, using linear regression under an additive model of inheritance. Five SNPs (rs12075A/G, rs13179413C/T, rs6907989T/A, rs9352745A/C, rs1779553T/C) reached the pre-defined threshold of genome-wide significance (p<1.0×10(-5)) and were tested for in silico replication in three independent populations, derived from the PIVUS, MDC-CC and SCARF studies. IL8 was measured in serum (SHEEP, PIVUS) and plasma (MDC-CC, SCARF). The strongest association was found with the SNP rs12075 A/G, Asp42Gly (p=1.6×10(-6)), mapping to the Duffy antigen receptor for chemokines (DARC) gene on chromosome 1. The minor allele G was associated with 15.6% and 10.4% reduction in serum IL8 per copy of the allele in SHEEP and PIVUS studies respectively. No association was observed between rs12075 and plasma IL8. CONCLUSION: rs12075 was associated with serum levels but not with plasma levels of IL8. It is likely that serum IL8 represents the combination of levels of circulating plasma IL8 and additional chemokine liberated from the erythrocyte DARC reservoir due to clotting. These findings highlight the importance of understanding IL8 as a biomarker in cardiometabolic diseases.


Asunto(s)
Sistema del Grupo Sanguíneo Duffy/genética , Interleucina-8/sangre , Polimorfismo de Nucleótido Simple , Receptores de Superficie Celular/genética , Anciano , Estudios de Casos y Controles , Eritrocitos/inmunología , Femenino , Variación Genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Receptores de Antígenos , Factores de Tiempo
8.
Environ Res ; 134: 251-6, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25173059

RESUMEN

BACKGROUND AND OBJECTIVE: Persistent organic pollutants (POPs) are stable organic compounds generated through different industrial activities. Liver is involved in the metabolism of POPs, and hence exposure to POPs may interfere with liver function. Although a few studies have shown adverse effects of POPs on liver function, large-scale studies involving humans are lacking. We performed this large population-based cross-sectional study to assess the associations between different POPs and liver dysfunction biomarkers. METHODS: A total of 992 individuals (all aged 70 years, 50% males) were recruited as part of Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort. The total toxic equivalency (TEQ) value was calculated for seven mono-ortho and two non-ortho substituted polychlorinated biphenyls (PCBs) and octachloro-p-dibenzodioxin (OCDD) to assess their toxicological effects. The association of TEQ values, summary measures of 16 PCBs (sum of PCBs) and three organochlorine pesticides (sum of OC pesticides) with liver dysfunction biomarkers (bilirubin; alkaline phosphatase, ALP; alanine aminotransferase, ALT; and gamma-glutamyltransferase, GGT) was analyzed utilizing linear regression analysis. RESULTS: The mono-ortho PCB TEQ values were found to be significantly positively associated with bilirubin (ß=0.71, P=0.008), while sum of OC pesticide concentrations was negatively associated with ALP (ß=-0.02, P=0.002) after adjusting for various potential confounders. When analyzed individually, a number of different POPs were associated with ALP, ALT and bilirubin. No such association with GGT was observed. CONCLUSION: Various POPs including PCBs, OCDD and pesticides were associated with the liver dysfunction biomarkers bilirubin, ALT and ALP, suggesting adverse effects on liver function from these environmental pollutants.


Asunto(s)
Biomarcadores/sangre , Contaminantes Ambientales/toxicidad , Hígado/efectos de los fármacos , Compuestos Orgánicos/toxicidad , Anciano , Femenino , Humanos , Hígado/fisiopatología , Pruebas de Función Hepática , Masculino , Estudios Prospectivos , Suecia
9.
Indian J Exp Biol ; 52(3): 223-31, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24669665

RESUMEN

Cysteine proteinases are required for a wide range of physiological processes in all living organisms. In parasitic nematodes, they are particularly crucial for the digestion of host tissues and evasion of host immune responses. Therefore, in general, these are identified as primary targets for the control of parasitic nematodes. Herein, cathepsin S-like cysteine proteinase of Heterodera avenae (Hacp-s) has been cloned and analysed for the first time. The predicted protein is 298 amino acids long and showed significant similarity with cathepsin S of Heterodera glycines (Hgcp-s). The sequence of cathepsin S contains a signal peptide of 30 amino acids which suggests its role in extracellular functions. Multiple sequence alignment revealed the presence of ERFNIN motif and conserved catalytic residues. Three dimensional structure (3D) of Hgcp-s was modelled using homology modelling. In order to illustrate the plausible mode of interaction of cathepsin S (Hgcp-s), docking analysis was performed with E-64 cysteine proteinase inhibitor. Docking studies revealed the hydrogen bonding of E-64 with Gln153, His299 and Gly203 as well as close interaction with catalytic residues Cys159 and Asn320 Expression analysis of Hacp-s using qRT-PCR showed high expression of cathepsin S in pre parasitic J2s and female stages suggesting its significant role in both pre-parasitic and parasitic stages of the nematode life cycle.


Asunto(s)
Catepsinas/genética , Señales de Clasificación de Proteína/genética , Tylenchoidea/genética , Secuencia de Aminoácidos/genética , Animales , Catepsinas/química , Catepsinas/metabolismo , Clonación Molecular , Grano Comestible/parasitología , Regulación del Desarrollo de la Expresión Génica , Estadios del Ciclo de Vida , Simulación del Acoplamiento Molecular , Conformación Proteica , Alineación de Secuencia , Tylenchoidea/metabolismo , Tylenchoidea/patogenicidad
10.
Biophys Chem ; 311: 107257, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38781761

RESUMEN

Voltage-gated ion channels play an important role in generating action potential in neurons. These ion channels are found to be in localized cluster form on the axonal membrane surface and behave cooperatively. However, in Hodgkin & Huxley's model of action potential the ion channels are considered to function independently. According to some recent reports, the activity of an ion channel is influenced by the neighboring ion channels' activities. We have modified the Hodgkin-Huxley's model based on our previous studies on cooperativity among ion channels. Computational analysis of the proposed model shows that the initiation of the action potential, amplitude and hyperpolarization are affected significantly by the cooperative interactions among the voltage-gated ion channels present on the axonal membrane surface. These results are qualitatively supported by the existing experimental facts.


Asunto(s)
Potenciales de Acción , Axones , Canales Iónicos , Axones/metabolismo , Canales Iónicos/metabolismo , Canales Iónicos/química , Modelos Neurológicos , Activación del Canal Iónico , Humanos , Animales
11.
Vasc Med ; 18(4): 192-9, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23892448

RESUMEN

OBJECTIVES: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase. The breakdown of ADMA is mainly governed by the activity of dimethylarginine dimethylaminohydrolases (DDAHs). We investigated if genetic variation in the DDAH1 and DDAH2 genes were related to ADMA and l-arginine levels, as well as measures of endothelium-dependent vasodilation. METHODS: In 1016 70-year-old participants of the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (50% women), we measured endothelium-dependent vasodilation (EDV) using the invasive forearm technique with acetylcholine given in the brachial artery and the brachial artery ultrasound technique with measurement of flow-mediated dilatation (FMD). Plasma l-arginine and ADMA levels were measured by high-performance liquid chromatography and 55 single nucleotide polymorphisms (SNPs) in the DDAH1 and DDAH2 genes were genotyped. RESULTS: Several of the genotypes in the DDAH1 gene were highly significantly related to ADMA levels (p = 10(-7) at best), but not to the l-arginine levels. No relationships between the genotypes in the DDAH2 gene and ADMA or l-arginine levels were found. None of the DDAH1 genotypes being closely related to ADMA levels were significantly related to EDV or FMD. Neither were any of the DDAH2 genotypes closely related to any of the measurements of vasoreactivity. CONCLUSION: A close relationship was seen between SNPs in the DDAH1, but not DDAH2, gene and ADMA levels. However, variation in those genes was not related to measures of EDV in this elderly population.


Asunto(s)
Amidohidrolasas/genética , Arginina/análogos & derivados , Arteria Braquial/fisiología , Endotelio Vascular/fisiología , Polimorfismo de Nucleótido Simple , Vasodilatación , Factores de Edad , Anciano , Amidohidrolasas/metabolismo , Arginina/sangre , Arteria Braquial/diagnóstico por imagen , Arteria Braquial/metabolismo , Cromatografía Líquida de Alta Presión , Endotelio Vascular/diagnóstico por imagen , Endotelio Vascular/metabolismo , Femenino , Genotipo , Humanos , Isoenzimas , Masculino , Fenotipo , Estudios Prospectivos , Suecia , Ultrasonografía
12.
Front Pharmacol ; 14: 1136779, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36969868

RESUMEN

Cancer is a severe health issue, and cancer cases are rising yearly. New anticancer drugs have been developed as our understanding of the molecular mechanisms behind diverse solid tumors, and metastatic malignancies have increased. Plant-derived phytochemical compounds target different oncogenes, tumor suppressor genes, protein channels, immune cells, protein channels, and pumps, which have attracted much attention for treating cancer in preclinical studies. Despite the anticancer capabilities of these phytochemical compounds, systemic toxicity, medication resistance, and limited absorption remain more significant obstacles in clinical trials. Therefore, drug combinations of new phytochemical compounds, phytonanomedicine, semi-synthetic, and synthetic analogs should be considered to supplement the existing cancer therapies. It is also crucial to consider different strategies for increased production of phytochemical bioactive substances. The primary goal of this review is to highlight several bioactive anticancer phytochemical compounds found in plants, preclinical research, their synthetic and semi-synthetic analogs, and clinical trials. Additionally, biotechnological and metabolic engineering strategies are explored to enhance the production of bioactive phytochemical compounds. Ligands and their interactions with their putative targets are also explored through molecular docking studies. Therefore, emphasis is given to gathering comprehensive data regarding modern biotechnology, metabolic engineering, molecular biology, and in silico tools.

13.
Curr Pharm Biotechnol ; 24(10): 1297-1306, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37254276

RESUMEN

BACKGROUND: In recent years, the delivery of drugs by nanocomposites has emerged as an exciting field of research for bio-imaging tools and targeted cancer treatment. The large surface area and porous volume of mesoporous silica nanocomposites (MSN's) have gained a lot of interest for their application in the delivery of drugs and the magnetic properties of iron oxide (IO) nanocomposites play a key role in the targeted delivery system. METHODS: In this study, mesoporous silica encapsulated IO nanocomposites loaded with doxorubicin (DOX) were synthesized for the magnetically guided delivery of anticancer drugs. The synthesis of IO nanocomposites was done through the precipitation method, and then silica encapsulation and drug loading were done by the StÖber method. RESULTS: The magnetically driven delivery of the drug is produced by the encapsulation of magnetically active IO in the mesoporous silica shell. The controlled release of DOX is possible because of the MSN's. TEM images show that the nanocomposites have a spherical morphology and average diameter in the range of 120 nm. Power-XRD data confirm the crystalline nature of nanocomposites. The strong absorption peak was observed in UV-Visible spectroscopy at 490 nm and quenching in fluorescence spectra confirms the encapsulation of DOX in the mesoporous silica shell. VSM data showed the magnetic nature of nanocomposites, with large magnetic susceptibility (74.88 emu/g). The use of DOX/IO@Silica nanocomposites as a sustainable drug release and targeted drug delivery vehicle has been reported here. The pH dependent release of DOX was studied and significant release was observed at lower pH. In-vitro cell viability assay and fluorescence imaging assay have demonstrated that these nanocomposites show significant dose-dependent toxicity to cancer cells in the presence of a magnetic field. CONCLUSION: In-vitro studies via the MTT assay showed that these synthesized nanocomposites in culture are non-toxic to healthy cells compared to DOX-induced cytotoxicity due its controlled release and can be further strengthened by magnetic guidance. Therefore, due to its optical properties and potential for guided delivery of drug to the targeted site, these nanocomposites are ideal as an anticancer agent and bio-imaging prob.


Asunto(s)
Antineoplásicos , Nanocompuestos , Nanopartículas , Preparaciones de Acción Retardada , Dióxido de Silicio/química , Sistemas de Liberación de Medicamentos , Doxorrubicina/farmacología , Antineoplásicos/uso terapéutico , Nanocompuestos/química , Hierro , Liberación de Fármacos , Porosidad , Nanopartículas/química
14.
Biomarkers ; 17(2): 119-24, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22188304

RESUMEN

Transcobalamin (TCII) is a key enzyme involved in intracellular transport of vitamin B12. We had earlier shown that vitamin B12 levels are associated with Coronary Artery Disease (CAD). Herein, we evaluated the association of four nonsynonymous single nucleotide polymorphisms (SNPs) of TCII gene with CAD in 1398 individuals (589 CAD cases and 809 controls). Using logistic regression, we found that three SNPs (G1196A, C776G and C1043T) were significantly associated with CAD and one (G1196A) with vitamin B12 levels even after controlling for confounding factors. Thus, polymorphisms in TCII gene may play an important role in the etiology of CAD.


Asunto(s)
Enfermedad de la Arteria Coronaria/genética , Polimorfismo de Nucleótido Simple/genética , Transcobalaminas/genética , Vitamina B 12/sangre , Población Blanca/genética , Adulto , Alelos , Estudios de Casos y Controles , Enfermedad de la Arteria Coronaria/sangre , Femenino , Frecuencia de los Genes , Genotipo , Humanos , India , Masculino , Persona de Mediana Edad , Análisis de Regresión , Transcobalaminas/metabolismo
15.
PLoS Genet ; 5(10): e1000694, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19851442

RESUMEN

The INSIG2 rs7566605 polymorphism was identified for obesity (BMI> or =30 kg/m(2)) in one of the first genome-wide association studies, but replications were inconsistent. We collected statistics from 34 studies (n = 74,345), including general population (GP) studies, population-based studies with subjects selected for conditions related to a better health status ('healthy population', HP), and obesity studies (OB). We tested five hypotheses to explore potential sources of heterogeneity. The meta-analysis of 27 studies on Caucasian adults (n = 66,213) combining the different study designs did not support overall association of the CC-genotype with obesity, yielding an odds ratio (OR) of 1.05 (p-value = 0.27). The I(2) measure of 41% (p-value = 0.015) indicated between-study heterogeneity. Restricting to GP studies resulted in a declined I(2) measure of 11% (p-value = 0.33) and an OR of 1.10 (p-value = 0.015). Regarding the five hypotheses, our data showed (a) some difference between GP and HP studies (p-value = 0.012) and (b) an association in extreme comparisons (BMI> or =32.5, 35.0, 37.5, 40.0 kg/m(2) versus BMI<25 kg/m(2)) yielding ORs of 1.16, 1.18, 1.22, or 1.27 (p-values 0.001 to 0.003), which was also underscored by significantly increased CC-genotype frequencies across BMI categories (10.4% to 12.5%, p-value for trend = 0.0002). We did not find evidence for differential ORs (c) among studies with higher than average obesity prevalence compared to lower, (d) among studies with BMI assessment after the year 2000 compared to those before, or (e) among studies from older populations compared to younger. Analysis of non-Caucasian adults (n = 4889) or children (n = 3243) yielded ORs of 1.01 (p-value = 0.94) or 1.15 (p-value = 0.22), respectively. There was no evidence for overall association of the rs7566605 polymorphism with obesity. Our data suggested an association with extreme degrees of obesity, and consequently heterogeneous effects from different study designs may mask an underlying association when unaccounted for. The importance of study design might be under-recognized in gene discovery and association replication so far.


Asunto(s)
Estudio de Asociación del Genoma Completo/normas , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas de la Membrana/genética , Obesidad/genética , Proyectos de Investigación/normas , Adolescente , Adulto , Femenino , Genética de Población , Humanos , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Polimorfismo Genético , Adulto Joven
17.
ACS Omega ; 7(34): 29840-29849, 2022 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-36061706

RESUMEN

Detection of Sn2+ ions in environmental and biological samples is essential owing to the toxicological risk posed by excess use tin worldwide. Herein, we have designed a nanoprobe involving upconversion nanophosphors linked with a rhodamine-based fluorophore, which is selectively sensitive to the presence of Sn2+ ions. Upon excitation with near-infrared (NIR) light, the green emission of the nanophosphor is reabsorbed by the fluorophore with an efficiency that varies directly with the concentration of the Sn2+ ions. We have explored this NIR-excited fluorescence resonance energy transfer (FRET) process for the quantitative and ratiometric detection of Sn2+ ions in an aqueous phase. We have observed an excellent linear correlation between the ratiometric emission signal variation and the Sn2+ ion concentration in the lower micromolar range. The detection limit of Sn2+ ions observed using our FRET-based nanoprobe is about 10 times lower than that observed using other colorimetric or fluorescence-based techniques. Due to the minimal autofluorescence and great penetration depth of NIR light, this method is ideally suited for the selective and ultrasensitive detection of Sn2+ ions in complex biological or environmental samples.

18.
J Phys Condens Matter ; 34(46)2022 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-36063793

RESUMEN

We have investigated the magnetic, dielectric and thermal properties of theSRu= 1 magnetic dimer Ba3BiRu2O9, which is known to exhibit a spin-gap opening in conjunction with a first-order magneto-elastic phase transition at ∼175 K. Above the spin-gap temperature, the temperature dependence dielectric constant shows a peak like feature with pronounced frequency dependence. The critical slowing down behavior of this frequency dispersion suggests that a ferroelectric relaxor like electrical glassy state exists above the spin-gap opening temperature regime. The extermination of frequency dispersion-right at the magneto-elastic phase transition, is suggestive of a strong coupling between the lattice and charge-spin degrees of freedom in this triple perovskite system.

19.
Ann Maxillofac Surg ; 12(1): 114-116, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36199452

RESUMEN

The Rationale: Condyle fractures are a common type of mandibular fracture that can result in malocclusion. Open reduction and internal fixation (ORIF) in condylar fracture is considered as the most acceptable treatment modality. Patient Concerns: The patient complained of pain and difficulty in the jaw while chewing. Diagnosis: An orthopantomogram and reverse Towne's view can lead to diagnosis of the condylar fracture. Treatment: Open reduction and internal fixation using intraoperative real-time visualisation of subcondylar fracture reduction utilising the C-arm fluoroscopic approach were used to allow for adequate anatomical repositioning and fast restoration of function to meet the patient's concerns. Outcomes: We were able to achieve correct reduction of the fracture fragments with restoration of function and occlusion. Take-away Lessons: When this procedure is used to treat condylar fractures, surgeons can get a better view of the fracture segments while eliminating the need for postoperative intermaxillary fixation and also reduces the complications from inappropriate reduction and fixation.

20.
J Neurosci ; 30(9): 3419-31, 2010 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-20203201

RESUMEN

Rearrangement of the actin cytoskeleton is essential for dynamic cellular processes. Decreased actin turnover and rigidity of cytoskeletal structures have been associated with aging and cell death. Gelsolin is a Ca(2+)-activated actin-severing protein that is widely expressed throughout the adult mammalian brain. Here, we used gelsolin-deficient (Gsn(-/-)) mice as a model system for actin filament stabilization. In Gsn(-/-) mice, emigration of newly generated cells from the subventricular zone into the olfactory bulb was slowed. In vitro, gelsolin deficiency did not affect proliferation or neuronal differentiation of adult neural progenitors cells (NPCs) but resulted in retarded migration. Surprisingly, hippocampal neurogenesis was robustly induced by gelsolin deficiency. The ability of NPCs to intrinsically sense excitatory activity and thereby implement coupling between network activity and neurogenesis has recently been established. Depolarization-induced [Ca(2+)](i) increases and exocytotic neurotransmitter release were enhanced in Gsn(-/-) synaptosomes. Importantly, treatment of Gsn(-/-) synaptosomes with mycotoxin cytochalasin D, which, like gelsolin, produces actin disassembly, decreased enhanced Ca(2+) influx and subsequent exocytotic norepinephrine release to wild-type levels. Similarly, depolarization-induced glutamate release from Gsn(-/-) brain slices was increased. Furthermore, increased hippocampal neurogenesis in Gsn(-/-) mice was associated with a special microenvironment characterized by enhanced density of perfused vessels, increased regional cerebral blood flow, and increased endothelial nitric oxide synthase (NOS-III) expression in hippocampus. Together, reduced filamentous actin turnover in presynaptic terminals causes increased Ca(2+) influx and, subsequently, elevated exocytotic neurotransmitter release acting on neural progenitors. Increased neurogenesis in Gsn(-/-) hippocampus is associated with a special vascular niche for neurogenesis.


Asunto(s)
Citoesqueleto de Actina/metabolismo , Gelsolina/genética , Hipocampo/metabolismo , Neurogénesis/fisiología , Bulbo Olfatorio/metabolismo , Células Madre/metabolismo , Citoesqueleto de Actina/ultraestructura , Animales , Señalización del Calcio/fisiología , Movimiento Celular/fisiología , Circulación Cerebrovascular/fisiología , Citocalasina D/farmacología , Hipocampo/citología , Ventrículos Laterales/citología , Potenciales de la Membrana/fisiología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Neuronas/metabolismo , Neuronas/ultraestructura , Neurotoxinas/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Norepinefrina/metabolismo , Inhibidores de la Síntesis del Ácido Nucleico/farmacología , Bulbo Olfatorio/citología , Técnicas de Cultivo de Órganos , Terminales Presinápticos/metabolismo , Células Madre/ultraestructura , Sinaptosomas/efectos de los fármacos , Sinaptosomas/metabolismo
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