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2.
Brain Res Bull ; 157: 1-9, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31982453

RESUMO

Contrast sensitivity (CS) is one of the primary fundamental factors determining how well we can see, and it directly influences object recognition. Whether bisphenol-A (BPA, an environmental xenoestrogen) can perturb contrast detection in the visual system has yet to be elucidated. In the present study, we analyzed CS of single neurons in the primary visual cortex (area 17, A17) of cats before and after BPA exposure using a multiple-channel recording technique. The results showed that CS of A17 neurons was markedly depressed with an increased contrast threshold after two hour of intravenous BPA administration, which had a positive correlation with decreased firing rates of A17 neurons. Additionally, responses of these neurons presented an overt increase in the trial-to-trail response variability (a kind of neuronal noise), which could disturb the information-filtering function of single neurons. We also found that neuronal CS in the visual relay station was not disturbed after BPA administration, which rules out the contribution of CS alteration in the optical pathway. Importantly, acute BPA treatment obviously increased the inhibitory innervation to the visual pyramidal neurons. This implies that alteration of intracortical inhibitory regulation contributes to the compromised contrast detection in the visual system after BPA treatment.

3.
Int J Pharm ; 574: 118921, 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31812796

RESUMO

DNA delivery through cell membrane is a fundamental step for efficiency gene therapy. As a potential DNA carrier, carbon nanotubes (CNTs) have been extensively studied due to its unique properties. However, the mechanism of DNA translocation with CNTs through cell membrane is still not well understood. In this study, the DNA translocation process through POPC (1-palmitoyl-2-oleoylphosphatidylcholine) membrane with the assistance of CNTs was explored by molecular dynamics (MD) simulation. Our simulation results demonstrated that the CNTs could insert steadily into the POPC membrane, and DNA molecules tends to insert into the inner space of CNTs. With the assistance of CNTs, the free energy of nucleotides passing through the POPC membrane decreases. Moreover, the free energy of nucleotides (DA (deoxyadenosine), DT (deoxythymidine), DC (deoxycytidine), and DG (deoxyguanosine)) passing through POPC membrane follows the order: DA (deoxyadenosine) > DG (deoxyguanosine) > DC (deoxycytidine) > DT (deoxythymidine). These results may promote the design and application of CNT-based gene delivery system.

4.
Nanotechnology ; 31(14): 145504, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-31860900

RESUMO

Numerous investigations have been devoted to visualizing latent fingerprints (LFPs) for personal identification in forensic investigation and age estimation. While simultaneous detection of chemicals in fingerprint residues has yet to be explored. Herein, fluorescent NaYF4:Yb/Tm up-conversion nanoparticles (UCNPs), which can emit blue fluorescence upon 980 nm near-infrared irradiation, have been employed in the imaging of LFPs with high contrast and high sensitivity. The furrows and ridges which provide detailed information of LFP have been displayed clearly by Tm-doped UCNPs. Meanwhile, the quantitation of nicotine residue in LFPs has been achieved based on the blue fluorescence absorbed by I2-nicotine complex, and the data was analyzed by MATLAB with modified OPTA algorithm. It was proved that the established strategy was specific, sensitive, reliable and practical toward nicotine residue in LFPs with a detection limit of 0.05 µg.

5.
J Mol Med (Berl) ; 97(11): 1575-1588, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31673738

RESUMO

Glioblastoma is one of the most aggressive types of brain tumor. Epidermal growth factor receptors (EGFRs) are overexpressed in glioma, and EGFR amplifications and mutations lead to rapid proliferation and invasion. EGFR-targeted therapy might be an effective treatment for glioma. Gefitinib (Ge) is an EGFR tyrosine kinase inhibitor (TKI), and Golgi phosphoprotein 3 (GOLPH3) expression is associated with worse glioma prognosis. Downregulation of GOLPH3 could promote EGFR degradation. Here, an angiopep-2 (A2)-modified cationic lipid-poly (lactic-co-glycolic acid) (PLGA) nanoparticle (A2-N) was developed that can release Ge and GOLPH3 siRNA (siGOLPH3) upon entering glioma cells and therefore acts as a combinatorial anti-tumor therapy. The in vitro and in vivo studies proved that A2-N/Ge/siGOLPH3 successfully crossed the blood-brain barrier (BBB) and targeted glioma. Released siGOLPH3 effectively silenced GOLPH3 mRNA expression and further promoted EGFR and p-EGFR degradation. Released Ge also markedly inhibited EGFR signaling. This combined EGFR-targeted action achieved remarkable anti-glioma effects and could be a safe and effective treatment for glioma. KEY MESSAGES: Angiopep-2-modified cationic lipid polymer can penetrate the BBB. Gefitinib can inhibit EGFR signaling and block the autophosphorylation of critical tyrosine residues on EGFR. GOLPH3 siRNA can be transfected into glioma and downregulate GLOPH3 expression. A2-N/Ge/siGOLPH3 can inhibit glioma growth.

6.
Zootaxa ; 4614(2): zootaxa.4614.2.2, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31716378

RESUMO

A catalogue for the eight Goniaceritae genera that occur in New Zealand is presented, treating a total of 62 species. Seventeen holotypes are confirmed, 38 lectotypes and 99 paralectotypes are designated herein for all valid species but Eupines acceptus Broun, for which type material was not located. One synonymy is proposed: Anabaxis electrica (King, 1863) (= Rybaxis brevis Oke, 1928). Four species of Eupines known only by females are valid species, but without subgeneric assignment. Images of primary type specimens and their original labels are provided.


Assuntos
Besouros , Distribuição Animal , Animais , Feminino , Nova Zelândia
7.
BMC Psychiatry ; 19(1): 293, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533672

RESUMO

BACKGROUND: Schizophrenia is a severe mental disease with high morbidity and heritability. The SLC39A8 gene is located in 4q24 and encodes a protein that transports many metal ions. Multiple previous studies found that one of the most pleiotropic single nucleotide polymorphisms (SNPs) in SLC39A8, rs13107325, is associated with schizophrenia in the European population. However, the polymorphism of this locus is rare in other populations. In China, the Han Chinese and the Uygur Chinese are two ethnic populations that originate from different races. METHODS: A case-control study was conducted with 983 schizophrenia cases and 1230 healthy controls of the Chinese Uygur population. To validate the most promising SNP, meta-analyses were conducted with the Han Chinese and the European PGC2 data sets reported previously. RESULTS: A susceptible locus, rs10014145 (pallele = 0.014, pallele = 0.098 after correction; pgenotype = 0.004, pgenotype = 0.032 after correction) was identified in case-control study of the Chinese Uygur population. Further, the association between rs10014145 and schizophrenia was supported by a meta-analysis of Han and Uygur Chinese samples (pooled OR [95% CI] =1.10 [1.03-1.17], Z = 2.73, p = 0.006). The association between rs10014145 and schizophrenia was not significant in a meta-analysis of combined Chinese and European samples (pooled OR [95% CI] =1.07 [1.00-1.14], Z = 1.88, and p = 0.06). In addition, the "CCAC" haplotype of rs4698844-rs233814-rs13114343-rs151394 was significantly associated with schizophrenia in Uygur Chinese (P = 0.003, corrected p = 0.012). CONCLUSIONS: The results of this study support that SLC39A8 is a susceptible gene for schizophrenia in the populations of Han Chinese and Uygur Chinese in China, further studies are suggested to validate the association.

8.
Hereditas ; 156: 15, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31148953

RESUMO

Background: Athletic performances are complex traits with heritability of ~66%. Dynamic balance is one of the most important athletic performances, and there has been little studies for it in sports genomics. The candidate PPARD gene was reported to be able to affect muscle development for balance predisposition and influence the athletic performance including skiing triumph in the Caucasian population. This study aims to investigate whether the PPARD gene is a susceptibility gene for dynamic balance performance in Han Chinese children. Results: A total 2244 children were recruited and their balance beam performances were measured. Five polymorphisms in the PPARD gene were genotyped through the MassARRAY Sequenom platform. Rs2016520 exerted significant association with dynamic balance performance (minor allele C, P = 0.015, Pcorrected < 0.05) and was affirmed in a meta-analysis by combining previously reported Caucasian cohorts (OR = 1.57, 95% CI = [1.30, 1.91], P < 10 -5) . Another polymorphism, rs2267668, was also significantly associated with dynamic balance performance (minor allele G, P = 0.015, Pcorrected < 0.05). In the dichotomous study, 321 cases (61% boys and 39% girls) and 370 controls (49% boys and 51% girls) in our samples were selected as representatives, and the thresholds were the mean velocity (0.737 m/s) ± standard deviation (0.264 m/s), in which rs2016520-C and rs2267668-G still remained significant (CI =1.41 [1.11~1.79], P = 0.004, Pcorrected < 0.016; CI =1.45 [1.14~1.86], P = 0.002, Pcorrected < 0.016). In different genders, consistent OR direction was observed for each variant. Conclusions: Our results suggested that the PPARD gene is associated with dynamic balance performance of human being, and further studies to reveal its etiology is strongly suggested.


Assuntos
Genótipo , PPAR delta/genética , Polimorfismo de Nucleotídeo Único , Equilíbrio Postural/genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Criança , China , Feminino , Frequência do Gene , Estudos de Associação Genética , Ligação Genética , Predisposição Genética para Doença , Humanos , Desequilíbrio de Ligação , Masculino , Razão de Chances , Locos de Características Quantitativas
9.
Intensive Care Med ; 45(7): 928-938, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31089761

RESUMO

PURPOSE: New-onset atrial fibrillation (NOAF) is common and associated with increased morbidity and mortality. However, its clinical importance and management in critically ill patients are not well described. The aim of this scoping review is to assess the epidemiology and management strategies of NOAF during critical illness. METHOD: The review was conducted in accordance with the PRISMA extension for scoping reviews. We searched PubMed, EMBASE and the Cochrane Library for studies assessing the incidence, outcome and management strategies of NOAF in adult critically ill patients. The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: A total of 99 studies were included, of which 79 were observational and 20 were interventional. The incidence of NOAF varied from 1.7% to 43.9% with considerable inter-population variation (very low quality of evidence). Commonly identified risk factors for NOAF included higher age, cardiovascular comorbidities and sepsis. The occurrence of NOAF was associated with adverse outcomes, including stroke, prolonged length of stay and mortality (very low quality of evidence). We found limited data on the optimal management strategy with no evidence for firm benefit or harm for any intervention (very low/low quality of evidence). CONCLUSIONS: The definition and incidence of NOAF in critically ill patients varied considerably and many risk factors were identified. NOAF seemed to be associated with adverse outcomes, but data were very limited and current management strategies are not evidence-based.

10.
J Craniofac Surg ; 30(6): 1767-1771, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30950953

RESUMO

Cleidocranial dysplasia is a rare autosomal-dominant condition that affects ossification. The main symptoms of this cleidocranial dysplasia patient include craniofacial abnormalities, hypoplasia of clavicles, narrow thorax, retarded exfoliation of deciduous teeth, retarded eruption of permanent teeth, and multiple impacted supernumerary teeth. The aim of this treatment was to correct the craniofacial abnormalities and provide an adequate functional reconstruction of the occlusion. The patient was treated with a multidisciplinary therapeutic protocol including removal of supernumerary teeth, surgical exposure of impacted teeth, orthodontic, and orthognathic surgery. After 6 years' follow-up, the treatment objectives of acceptable occlusion, normal function, and acceptable profile were achieved.

11.
Biomed Chromatogr ; 33(7): e4535, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30883816

RESUMO

Celosin A (CA), a natural compound isolated from Celosia argentea L., has been shown significant hepatoprotective effect on AHNP-induced liver injury. This study described a rapid and sensitive ultra-high-pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) assay for determination of CA in rat plasma. Methanol-mediated precipitation was used for sample pretreatment. Chromatographic separation was achieved on a T3 column with gradient elution using water and acetonitrile as mobile phase. Determination was obtained using an electrospray ionization source in negative selected reaction monitoring mode at the transitions of m/z 793.3 → m/z 661.2 and m/z 955.6 → m/z 793.2 for CA and IS, respectively. The assay was linear over the concentration range 0.25-2500 ng/mL (r > 0.995) with a lowest limit of quantification (LLOQ) of 0.25 ng/mL. The intra- and inter-day precisions (RSD) were 1.65-9.84 and 2.46-13.49%, respectively, while accuracy (RR) ranged from 96.21 to 99.45%, respectively. The recovery ranged from 95.09 to 102.22% and the matrix effect from 98.29 to 100.13%. The analyte was stable under the tested storage conditions. The method has been successfully applied to a preclinical pharmacokinetic study in rats after a single intravenous (2 mg/kg) or oral (50 mg/kg) administration. The oral bioavailability of CA was ~1.94%; in addition, there was no difference between male and female rats. This is the first time of the use of an UHPLC-MS/MS method for determination of CA concentration in rat plasma and for evaluation of its pharmacokinetic behavior.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Ácido Oleanólico/análogos & derivados , Saponinas/sangue , Espectrometria de Massas em Tandem/métodos , Animais , Estabilidade de Medicamentos , Feminino , Limite de Detecção , Modelos Lineares , Masculino , Ácido Oleanólico/sangue , Ácido Oleanólico/química , Ácido Oleanólico/farmacocinética , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Saponinas/química , Saponinas/farmacocinética
12.
Aesthetic Plast Surg ; 43(3): 826-835, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30843098

RESUMO

BACKGROUND: Nowadays, the use of cryopreserved fat tissue for soft tissue augmentation is common, except for its unpredictable fat graft absorption, and the toxicity of the cryoprotective agent remains a limitation. In this study, the effects of freezing stored fat tissue without a cryoprotector, and the addition of the stromal vascular fraction (SVF) on the survival of cryopreserved transplants was studied. METHODS: Lipoaspirates from six donors were processed and cryopreserved at - 20 °C, - 80 °C and - 196 °C, respectively. The authors evaluated the lipoaspirates in vitro, on the basis of fat tissue and SVF viability after cryopreservation. In vivo fat grafting was performed in nude mice. Six trenches were injected on the backs of mice. Cryopreserved tissues (- 20 °C, - 80 °C and - 196 °C) were injected on the right side, and the other side received the SVF combination. At 4 and 8 weeks after transplantation, the authors examined the weight, volume and morphology of the tissue and analyzed histochemical staining and immunohistochemistry (i.e., DIL, CD31 and VWF) to evaluate the survival of the fat grafts. RESULTS: After cryopreservation without the cryoprotective agent, adipose tissue maintained its morphology better in - 80 °C than - 20 °C and - 196 °C. SVF cells can retain their adhesive and proliferative properties after cryopreservation. Although cryopreservation caused damage to fat tissue, all explants showed intact adipocytes and vascular ingrowth. Most of all, the - 80 °C group had less graft resorption and fibrosis than the other temperature groups. There was increased survival of fat grafts in the SVF group compared with the control group. CONCLUSION: In this study, the authors demonstrated that the storage temperature of - 80 °C was promising for 3 months of adipose tissue cryopreservation without a cryoprotective agent, and SVF could increase the survival rate of cryopreserved fat tissue. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

13.
Nanoscale ; 11(10): 4503-4514, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30806416

RESUMO

Graphene quantum dots (GQDs) are increasingly being recognized as anti-cancer drug carriers, e.g., doxorubicin delivery, in many experiments. In this work, the structure, thermodynamics and dynamic properties of model drugs (doxorubicin and deoxyadenosine) translocating into a POPC lipid membrane with the assistance of GQDs were investigated via MD simulation and free energy calculation. The simulation results imply that GQD19 can facilitate the permeation of model drugs into the lipid membrane on the nanosecond timescale with less deformation of the cell membrane structure. More importantly, free energy calculations further revealed that the translocation free energy of doxorubicin or deoxyadenosine permeating into the lipid bilayer could be significantly reduced with the assistance of GQD19. Our results suggest that GQDs with appropriate size may assist in the drug delivery process by reducing the translocation free energy permeating into the biomembrane. These results may promote the molecular design and application of GQD-based drug delivery systems.


Assuntos
Doxorrubicina , Portadores de Fármacos , Grafite , Membranas Artificiais , Fosfatidilcolinas/química , Pontos Quânticos/química , Doxorrubicina/química , Doxorrubicina/farmacocinética , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Grafite/química , Grafite/farmacocinética
14.
Mol Pharm ; 16(3): 987-994, 2019 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-30624945

RESUMO

A combination of different chemotherapy approaches can obtain the best response for many cancers. However, the greatest challenge is the development of a nanoparticle formulation that can encapsulate different chemotherapeutic agents to achieve the proper synergetic chemotherapy for the tumor. Here, amphiphilic ferrocenium-tetradecyl (Fe-C14) was constructed to form cationic micelles in an aqueous solution via self-assembly. Then, it was coated by hyaluronic acid (HA) through electrostatic interactions to generate HA-Fe-C14 micelles. The HA-Fe-C14 micelles were used to deliver doxorubicin (DOX), and it showed that the DOX could be released rapidly under a high-GSH tumor environment. The HA-Fe-C14/DOX micelles were able to accumulate efficiently in tumor and showed significant anticancer effect both in vitro and in vivo. These results suggest that HA-Fe-C14/DOX micelles are a useful drug delivery system that enhances synergic antitumor treatment effects.


Assuntos
Doxorrubicina/química , Doxorrubicina/uso terapêutico , Sistemas de Liberação de Medicamentos , Compostos Ferrosos/química , Glutationa/química , Ácido Hialurônico/química , Metalocenos/química , Micelas , Neoplasias/terapia , Alcanos/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada , Liberação Controlada de Fármacos , Compostos Ferrosos/síntese química , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias/patologia , Células PC-3 , Solubilidade , Resultado do Tratamento , Carga Tumoral
15.
Colloids Surf B Biointerfaces ; 174: 575-581, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30502669

RESUMO

Due to the unique structural and mechanical properties, graphene quantum dots (GQDs) are considered as potential candidates in the field of biosensors, bioimaging, and drug delivery etc. In this work, the adsorption of protein villin headpiece (HP35) on GQDs with different sizes was investigated by molecular dynamics simulations. The simulation results identified the key role of the π-π stacking interactions between the aromatic residues of HP35 and GQDs as the binding site. More importantly, with the increase of GQD size, the amount and binding strength of adsorbed residues increase, and sequentially enhance the structure change of adsorbed protein, verified by various analysis of protein structures etc. These findings may improve the understanding of the cytotoxicity and biosafety of GQDs, and hence promote the design and application of GQDs-based biomedical devices.


Assuntos
Técnicas Biossensoriais , Grafite/química , Proteínas de Neurofilamentos/metabolismo , Fragmentos de Peptídeos/metabolismo , Pontos Quânticos , Humanos , Proteínas de Neurofilamentos/química , Fragmentos de Peptídeos/química
16.
Cancer Biol Ther ; 20(1): 52-64, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30183476

RESUMO

Small cell lung cancer (SCLC) is a malignant neuroendocrine tumor with very high mortality. Effective new therapy for advanced SCLC patients is urgently needed. By screening a FDA-approved drug library, we identified a cardiac glycoside (CG), namely digoxin (an inhibitor of cellular Na+/K+ ATPase pump), which was highly effective in inhibiting SCLC cell growth. Intriguing findings showed that NaCl supplement markedly enhanced the anti-tumor activities of digoxin in both in vitro and in vivo models of SCLC. Subsequent analysis revealed that this novel combination of digoxin/NaCl caused an up-regulation of intracellular Na+ and Ca2+ levels with an induction of higher resting membrane potential of SCLC cells. We also found that this combination lead to morphological shrinking of SCLC cells, together with high levels of cytochrome C release. Lastly, our data revealed that NaCl supplement was able to induce the expression of ATP1A1 (a Na+/K+ ATPase subunit), in which contributes directly to the increased sensitivity of SCLC cells to digoxin. Thus, this is the first demonstration that NaCl is a potent supplement necessitating superior anti-cancer effects of digoxin for SCLC. Further, our study suggests that digoxin treatment could need to be combined with NaCl supplement in future clinical trial of SCLC, particularly where low Na+ is often present in SCLC patients.

17.
Mol Genet Genomics ; 294(1): 47-56, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30167790

RESUMO

The ACTN3 gene locates on 11q13-q14 and encodes the α-actinin-3 protein, which is only expressed in human skeletal muscle and influenced muscle function and metabolism. The previous studies reported that SNP rs1815739 is associated with elite power athletes' performance. In this study, we investigated the association between five SNPs within the ACTN3 gene and Chinese children physical fitness. We recruited 2244 Han Chinese children participants, and measured their 25-m run, stand broad jump, 10-m shuttle run, handgrip, BMI (calculated by weight and height) data. SNPs rs1671064, rs2275998, rs2290463, rs10791881, and rs1815739 of ACTN3 gene were genotyped and analyzed in five physical fitness data. QTL analysis on genotype and physical fitness data was carried out in all samples. Furthermore, a dichotomous division of samples into an overweight group (543) and a normal group (1701) was used for an association study of overweight. In the QTL analysis, we found rs2290463 was significantly associated with stand broad jump (corrected P value = 0.009, beta = 2.692). After added age and gender as covariates in the regression test, the association became more significant (P value = 5.80 × 10- 5, corrected P value = 4.06 × 10- 4); when we used BMI as a covariate, the association still existed (P value = 4.65 × 10- 4, corrected P value = 0.001). In the association study of overweight, rs2275998 was found to be significant (OR, 95% CI = 0.733 [0.6-0.895]; Pallele = 0.011, Pgenotype = 0.024) after the Bonferroni correction, and the association did not change much after a further correction for gender, age, and stand broad jump performance. Our results showed that common variants in ACTN3 are significantly associated with both stand broad jump performance and overweight in Han Chinese children.


Assuntos
Actinina/genética , Grupo com Ancestrais do Continente Asiático/etnologia , Sobrepeso/genética , Aptidão Física , Polimorfismo de Nucleotídeo Único , Grupo com Ancestrais do Continente Asiático/genética , Criança , Pré-Escolar , Feminino , Estudos de Associação Genética , Genótipo , Força da Mão , Humanos , Masculino , Locos de Características Quantitativas
18.
Phys Chem Chem Phys ; 20(45): 28886-28893, 2018 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-30420980

RESUMO

Nanopore-based DNA sequencing is considered to be a low-cost, high resolution and superfast method. Solid state nanopores, especially MoS2 nanopores, have been considered to be a promising choice for DNA sequencing. However, researchers still have a very limited understanding of the effects of multiple factors on MoS2-based DNA sequencing. In this study, the effects of the applied voltage and the diameter of the MoS2 nanopore on the resolution of DNA sequencing were investigated. Our results demonstrate that the translocation time of DNA can increase with a decrease in the applied voltage. DNA can be stretched significantly to translocate a 2 nm nanopore under a high applied voltage (>400 mV nm-1). To achieve a 1 base per µs translocation speed (1 GHz bandwidth), we suggest that three methods could be applied, including a decrease in the applied voltage, a decrease in the diameter of the MoS2 nanopore or modification of the MoS2 nanopore. In addition, the size of the nanopore can severely affect the possibility of DNA entering the nanopore, and the translocation time of DNA could be significantly increased with a smaller MoS2 nanopore. These findings may help to design MoS2 nanopores with higher resolution for use in DNA sequencing.


Assuntos
DNA/química , Dissulfetos/química , Molibdênio/química , Nanoporos , Sequência de Bases , Técnicas Eletroquímicas/métodos , Simulação de Dinâmica Molecular , Análise de Sequência de DNA/métodos
19.
Nat Commun ; 9(1): 3171, 2018 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-30093687

RESUMO

Cushing's disease results from corticotroph adenomas of the pituitary that hypersecrete adrenocorticotropin (ACTH), leading to excess glucocorticoid and hypercortisolism. Mutations of the deubiquitinase gene USP8 occur in 35-62% of corticotroph adenomas. However, the major driver mutations in USP8 wild-type tumors remain elusive. Here, we report recurrent mutations in the deubiquitinase gene USP48 (predominantly encoding p.M415I or p.M415V; 21/91 subjects) and BRAF (encoding p.V600E; 15/91 subjects) in corticotroph adenomas with wild-type USP8. Similar to USP8 mutants, both USP48 and BRAF mutants enhance the promoter activity and transcription of the gene encoding proopiomelanocortin (POMC), which is the precursor of ACTH, providing a potential mechanism for ACTH overproduction in corticotroph adenomas. Moreover, primary corticotroph tumor cells harboring BRAF V600E are sensitive to the BRAF inhibitor vemurafenib. Our study thus contributes to the understanding of the molecular mechanism of the pathogenesis of corticotroph adenoma and informs therapeutic targets for this disease.


Assuntos
Mutação , Hipersecreção Hipofisária de ACTH/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteases Específicas de Ubiquitina/genética , Adenoma/genética , Adulto , Sítios de Ligação , Ilhas de CpG , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Pró-Opiomelanocortina/genética , Análise de Sequência de DNA
20.
Zootaxa ; 4382(3): 531-552, 2018 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-29689931

RESUMO

The New Zealand members of the genus Anabaxis Raffray are revised to accommodate three species, including one new species: Anabaxis chathamensis sp. nov. A key and an illustrated catalogue to the described species from New Zealand and Australia are included. Lectotypes are designated for A. brevis Oke, A. electrica King, A. foveolata Broun, A. inusitata Blackburn, A. lunatica King, A. quinquefoveolata Raffray, and A. vagus Oke. The widespread New Zealand species A. foveolata exhibits an unusual form of clinal variation in sex-linked characters of the male legs. The length of the tibial spine increased with increasing latitude and the length of the mesotrochanteral spine decreased with increasing latitude.


Assuntos
Besouros , Distribuição Animal , Animais , Austrália , Masculino , Nova Zelândia
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