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1.
Cell ; 178(4): 779-794, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31398336

RESUMO

Metagenomic sequencing is revolutionizing the detection and characterization of microbial species, and a wide variety of software tools are available to perform taxonomic classification of these data. The fast pace of development of these tools and the complexity of metagenomic data make it important that researchers are able to benchmark their performance. Here, we review current approaches for metagenomic analysis and evaluate the performance of 20 metagenomic classifiers using simulated and experimental datasets. We describe the key metrics used to assess performance, offer a framework for the comparison of additional classifiers, and discuss the future of metagenomic data analysis.

2.
Curr Pain Headache Rep ; 23(10): 74, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31388843

RESUMO

PURPOSE OF REVIEW: Trigeminal neuralgia (TN) is characterized by recurrent attacks of lancinating facial pain in the dermatomal distribution of the trigeminal nerve. TN is rare, affecting 4 to 13 people per 100,000. RECENT FINDINGS: Although there remains a debate surrounding the pathogenesis of TN, neurovascular compromise is the most currently accepted theory. Minimal stimulation caused by light touch, talking, or chewing can lead to debilitating pain and incapacitation of the patient. Pain may occur sporadically, though is primarily unilateral in onset. The diagnosis is typically determined clinically. Treatment options include medications, surgery, and complementary approaches. Anti-epileptic and tricyclic antidepressant medications are first-line treatments. Surgical management of patients with TN may be indicated in those who have either failed medical treatment with at least three medications, suffer from intolerable side-effects, or have non-remitting symptoms. Surgical treatment is categorized as either destructive or non-destructive. Deep brain and motor cortex neuro-modulatory stimulation are off label emerging techniques which may offer relief to TN that is otherwise refractory to pharmacological management and surgery. Still, sufficient data has yet to be obtained and more studies are needed.

3.
Biotechniques ; 67(3): 118-122, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31267764

RESUMO

We have previously reported Hi-Plex, a multiplex PCR methodology for building targeted DNA sequencing libraries that offers a low-cost protocol compatible with high-throughput processing. Here, we detail an improved protocol, Hi-Plex2, that more effectively enables the robust construction of small-to-medium panel-size libraries while maintaining low cost, simplicity and accuracy benefits of the Hi-Plex platform. Hi-Plex2 was applied to three panels, comprising 291, 740 and 1193 amplicons, targeting genes associated with risk for breast and/or colon cancer. We show substantial reduction of off-target amplification to enable library construction for small-to-medium-sized design panels not possible using the previous Hi-Plex chemistry.

4.
Nat Biotechnol ; 37(2): 160-168, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30718881

RESUMO

Metagenomic sequencing has the potential to transform microbial detection and characterization, but new tools are needed to improve its sensitivity. Here we present CATCH, a computational method to enhance nucleic acid capture for enrichment of diverse microbial taxa. CATCH designs optimal probe sets, with a specified number of oligonucleotides, that achieve full coverage of, and scale well with, known sequence diversity. We focus on applying CATCH to capture viral genomes in complex metagenomic samples. We design, synthesize, and validate multiple probe sets, including one that targets the whole genomes of the 356 viral species known to infect humans. Capture with these probe sets enriches unique viral content on average 18-fold, allowing us to assemble genomes that could not be recovered without enrichment, and accurately preserves within-sample diversity. We also use these probe sets to recover genomes from the 2018 Lassa fever outbreak in Nigeria and to improve detection of uncharacterized viral infections in human and mosquito samples. The results demonstrate that CATCH enables more sensitive and cost-effective metagenomic sequencing.


Assuntos
Biologia Computacional/métodos , Genoma Viral , Metagenoma , Metagenômica , Animais , Culicidae/virologia , Surtos de Doenças , Biblioteca Gênica , Variação Genética , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Febre Lassa/virologia , Nigéria/epidemiologia , Sondas de Oligonucleotídeos , Oligonucleotídeos/genética , Análise de Sequência de DNA , Viroses
5.
Int J Mol Sci ; 19(10)2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30326623

RESUMO

DNA methylation influences predisposition, development and prognosis for many diseases, including cancer. However, it is not uncommon to encounter samples with incorrect sex labelling or atypical sex chromosome arrangement. Sex is one of the strongest influencers of the genomic distribution of DNA methylation and, therefore, correct assignment of sex and filtering of abnormal samples are essential for the quality control of study data. Differences in sex chromosome copy numbers between sexes and X-chromosome inactivation in females result in distinctive sex-specific patterns in the distribution of DNA methylation levels. In this study, we present a software tool, sEst, which incorporates clustering analysis to infer sex and to detect sex-chromosome abnormalities from DNA methylation microarray data. Testing with two publicly available datasets demonstrated that sEst not only correctly inferred the sex of the test samples, but also identified mislabelled samples and samples with potential sex-chromosome abnormalities, such as Klinefelter syndrome and Turner syndrome, the latter being a feature not offered by existing methods. Considering that sex and the sex-chromosome abnormalities can have large effects on many phenotypes, including diseases, our method can make a significant contribution to DNA methylation studies that are based on microarray platforms.

6.
N Engl J Med ; 379(18): 1745-1753, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30332564

RESUMO

During 2018, an unusual increase in Lassa fever cases occurred in Nigeria, raising concern among national and international public health agencies. We analyzed 220 Lassa virus genomes from infected patients, including 129 from the 2017-2018 transmission season, to understand the viral populations underpinning the increase. A total of 14 initial genomes from 2018 samples were generated at Redeemer's University in Nigeria, and the findings were shared with the Nigerian Center for Disease Control in real time. We found that the increase in cases was not attributable to a particular Lassa virus strain or sustained by human-to-human transmission. Instead, the data were consistent with ongoing cross-species transmission from local rodent populations. Phylogenetic analysis also revealed extensive viral diversity that was structured according to geography, with major rivers appearing to act as barriers to migration of the rodent reservoir.

7.
Anal Chem ; 90(7): 4657-4662, 2018 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-29536737

RESUMO

In blood samples from patients with viral infection, it is often important to separate viral particles from human cells, for example, to minimize background in performing viral whole genome sequencing. Here, we present a microfluidic device that uses spiral inertial microfluidics with continuous circulation to separate host cells from viral particles and free nucleic acid. We demonstrate that this device effectively reduces white blood cells, red blood cells, and platelets from both whole blood and plasma samples with excellent recovery of viral nucleic acid. Furthermore, microfluidic separation leads to greater viral genome coverage and depth, highlighting an important application of this device in processing clinical samples for viral genome sequencing.

8.
BMC Cancer ; 18(1): 165, 2018 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-29422015

RESUMO

BACKGROUND: Breast cancer risk for BRCA1 and BRCA2 pathogenic mutation carriers is modified by risk factors that cluster in families, including genetic modifiers of risk. We considered genetic modifiers of risk for carriers of high-risk mutations in other breast cancer susceptibility genes. METHODS: In a family known to carry the high-risk mutation PALB2:c.3113G>A (p.Trp1038*), whole-exome sequencing was performed on germline DNA from four affected women, three of whom were mutation carriers. RESULTS: RNASEL:p.Glu265* was identified in one of the PALB2 carriers who had two primary invasive breast cancer diagnoses before 50 years. Gene-panel testing of BRCA1, BRCA2, PALB2 and RNASEL in the Australian Breast Cancer Family Registry identified five carriers of RNASEL:p.Glu265* in 591 early onset breast cancer cases. Three of the five women (60%) carrying RNASEL:p.Glu265* also carried a pathogenic mutation in a breast cancer susceptibility gene compared with 30 carriers of pathogenic mutations in the 586 non-carriers of RNASEL:p.Glu265* (5%) (p < 0.002). Taqman genotyping demonstrated that the allele frequency of RNASEL:p.Glu265* was similar in affected and unaffected Australian women, consistent with other populations. CONCLUSION: Our study suggests that RNASEL:p.Glu265* may be a genetic modifier of risk for early-onset breast cancer predisposition in carriers of high-risk mutations. Much larger case-case and case-control studies are warranted to test the association observed in this report.


Assuntos
Neoplasias da Mama/genética , Endorribonucleases/genética , Predisposição Genética para Doença/genética , Adulto , Idade de Início , Austrália , Proteína BRCA1/genética , Proteína BRCA2/genética , Feminino , Heterozigoto , Humanos , Pessoa de Meia-Idade , Mutação , Linhagem , Adulto Jovem
9.
BMC Med Genet ; 19(1): 12, 2018 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-29351780

RESUMO

BACKGROUND: FANCM and RECQL have recently been reported as breast cancer susceptibility genes and it has been suggested that they should be included on gene panel tests for breast cancer predisposition. However, the clinical value of testing for mutations in RECQL and FANCM remains to be determined. In this study, we have characterised the spectrum of FANCM and RECQL mutations in women affected with breast or ovarian cancer from South-West Poland and West Ukraine. METHODS: We applied Hi-Plex, an amplicon-based enrichment method for targeted massively parallel sequencing, to screen the coding exons and proximal intron-exon junctions of FANCM and RECQL in germline DNA from unrelated women affected with breast cancer (n = 338) and ovarian cancer (n = 89) from Poland (n = 304) and Ukraine (n = 123). These women were at high-risk of carrying a genetic predisposition to breast and/or ovarian cancer due to a family history and/or early-onset disease. RESULTS: Among 427 women screened, we identified one carrier of the FANCM:c.1972C > T nonsense mutation (0.23%), and two carriers of the frameshift insertion FANCM:c.1491dup (0.47%). None of the variants we observed in RECQL were predicted to be loss-of-function mutations by standard variant effect prediction tools. CONCLUSIONS: Our study of the Polish and Ukrainian populations has identified a carrier frequency of truncating mutations in FANCM consistent with previous reports. Although initial reports suggesting that mutations in RECQL could be associated with increased breast cancer risk included women from Poland and identified the RECQL:c.1667_1667 + 3delAGTA mutation in 0.23-0.35% of breast cancer cases, we did not observe any carriers in our study cohort. Continued screening, both in research and diagnostic settings, will enable the accumulation of data that is needed to establish the clinical utility of including RECQL and FANCM on gene panel tests.

10.
Methods Mol Biol ; 1712: 53-70, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29224068

RESUMO

Hi-Plex is a suite of methods to enable simple, accurate, and cost-effective highly multiplex PCR-based targeted sequencing (Nguyen-Dumont et al., Biotechniques 58:33-36, 2015). At its core is the principle of using gene-specific primers (GSPs) to "seed" (or target) the reaction and universal primers to "drive" the majority of the reaction. In this manner, effects on amplification efficiencies across the target amplicons can, to a large extent, be restricted to early seeding cycles. Product sizes are defined within a relatively narrow range to enable high-specificity size selection, replication uniformity across target sites (including in the context of fragmented input DNA such as that derived from fixed tumor specimens (Nguyen-Dumont et al., Biotechniques 55:69-74, 2013; Nguyen-Dumont et al., Anal Biochem 470:48-51, 2015), and application of high-specificity genetic variant calling algorithms (Pope et al., Source Code Biol Med 9:3, 2014; Park et al., BMC Bioinformatics 17:165, 2016). Hi-Plex offers a streamlined workflow that is suitable for testing large numbers of specimens without the need for automation.


Assuntos
Primers do DNA/química , DNA/química , Reação em Cadeia da Polimerase Multiplex/métodos , Análise de Sequência de DNA/métodos , Biblioteca Gênica , Variação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Reação em Cadeia da Polimerase Multiplex/economia , Desnaturação de Ácido Nucleico , Hibridização de Ácido Nucleico , Análise de Sequência de DNA/economia , Software
11.
Fam Cancer ; 17(3): 345-349, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29052111

RESUMO

Loss-of-function germline mutations in the PALB2 gene are associated with an increase of breast cancer risk. The purpose of this study was to characterise the spectrum of PALB2 mutations in women affected with breast or ovarian cancer from South-West Poland and West Ukraine. We applied Hi-Plex, an amplicon-based enrichment method for targeted massively parallel sequencing, to screen the coding exons and proximal intron-exon junctions of PALB2 in germline DNA from unrelated women affected with breast cancer (n = 338) and ovarian cancer (n = 89) from Poland (n = 304) and Ukraine (n = 123). These women were at high-risk of carrying a genetic predisposition to breast and/or ovarian cancer due to a family history and/or early-onset disease. Targeted-sequencing identified two frameshift deletions: PALB2:c.509_510del; p.R170Ifs in three women affected with breast cancer and PALB2:c.172_175del;p.Q60Rfs in one woman affected with ovarian cancer. A number of other previously described missense (some predicted to be damaging by PolyPhen-2 and CADD) and synonymous mutations were also identified in this population. This study is consistent with previous reports that PALB2:c.509_510del and PALB2:c.172_175del are recurrent mutations associated with breast cancer predisposition in Polish women with a family history of the disease. Our study contributes to the accumulating evidence indicating that PALB2 should be included in genetic testing for breast cancer susceptibility in these populations to enhance risk assessment and management of women at high-risk of developing breast cancer. This data could also contribute to ongoing work that is assessing the possible association between ovarian cancer risk and PALB2 mutations for which there is currently no evidence.

12.
Artigo em Inglês | MEDLINE | ID: mdl-29276628

RESUMO

In cardiac perfusion imaging, choice of flip angle is an important factor for steady state acquisition. This work focuses on presenting an analytical framework for understanding how non-ideal slice excitation profiles affect contrast in ungated 2D steady state cardiac perfusion studies, and to study a technique for estimating flip angle that maximizes enhanced/unenhanced myocardial contrast-to-noise ratio (CNR) in single slice and multi-slice acquisitions. A numerical simulation of ungated 2D golden ratio radial spoiled gradient echo (SPGR) was created that takes into consideration the actual (Bloch simulated) slice excitation profile. The effect of slice excitation profile on myocardial CNR as a function of flip angle was assessed in phantoms and in-vivo. For fast RF pulses, the flip angle that yields maximum CNR (considering the actual slice excitation profile) was considerably higher than expected, assuming an ideal excitation. The simulation framework presented accurately predicts the flip angle yielding maximum CNR when the actual slice excitation profile is taken into consideration. The prescribed flip angle for optimal contrast in ungated 2D steady-state SPGR cardiac perfusion studies can vary significantly from that calculated when an ideal slice excitation profile is assumed. Consideration of the actual slice excitation can yield a more optimal flip angle estimate in both the single slice and multi-slice cases.

13.
Elife ; 62017 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-28825401

RESUMO

Neural injury triggers swift responses from glia, including glial migration and phagocytic clearance of damaged neurons. The transcriptional programs governing these complex innate glial immune responses are still unclear. Here, we describe a novel injury assay in adult Drosophila that elicits widespread glial responses in the ventral nerve cord (VNC). We profiled injury-induced changes in VNC gene expression by RNA sequencing (RNA-seq) and found that responsive genes fall into diverse signaling classes. One factor, matrix metalloproteinase-1 (MMP-1), is induced in Drosophila ensheathing glia responding to severed axons. Interestingly, glial induction of MMP-1 requires the highly conserved engulfment receptor Draper, as well as AP-1 and STAT92E. In MMP-1 depleted flies, glia do not properly infiltrate neuropil regions after axotomy and, as a consequence, fail to clear degenerating axonal debris. This work identifies Draper-dependent activation of MMP-1 as a novel cascade required for proper glial clearance of severed axons.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila/fisiologia , Metaloproteinase 1 da Matriz/metabolismo , Proteínas de Membrana/metabolismo , Neuroglia/fisiologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Transdução de Sinais , Animais , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Fatores de Transcrição STAT/metabolismo , Análise de Sequência de RNA , Fator de Transcrição AP-1/metabolismo
14.
Nature ; 546(7658): 401-405, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28538723

RESUMO

Zika virus (ZIKV) is causing an unprecedented epidemic linked to severe congenital abnormalities. In July 2016, mosquito-borne ZIKV transmission was reported in the continental United States; since then, hundreds of locally acquired infections have been reported in Florida. To gain insights into the timing, source, and likely route(s) of ZIKV introduction, we tracked the virus from its first detection in Florida by sequencing ZIKV genomes from infected patients and Aedes aegypti mosquitoes. We show that at least 4 introductions, but potentially as many as 40, contributed to the outbreak in Florida and that local transmission is likely to have started in the spring of 2016-several months before its initial detection. By analysing surveillance and genetic data, we show that ZIKV moved among transmission zones in Miami. Our analyses show that most introductions were linked to the Caribbean, a finding corroborated by the high incidence rates and traffic volumes from the region into the Miami area. Our study provides an understanding of how ZIKV initiates transmission in new regions.


Assuntos
Infecção por Zika virus/epidemiologia , Infecção por Zika virus/virologia , Zika virus/genética , Aedes/virologia , Animais , Região do Caribe/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Feminino , Florida/epidemiologia , Genoma Viral/genética , Humanos , Incidência , Epidemiologia Molecular , Mosquitos Vetores/virologia , Zika virus/isolamento & purificação , Infecção por Zika virus/transmissão
15.
Nature ; 546(7658): 411-415, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28538734

RESUMO

Although the recent Zika virus (ZIKV) epidemic in the Americas and its link to birth defects have attracted a great deal of attention, much remains unknown about ZIKV disease epidemiology and ZIKV evolution, in part owing to a lack of genomic data. Here we address this gap in knowledge by using multiple sequencing approaches to generate 110 ZIKV genomes from clinical and mosquito samples from 10 countries and territories, greatly expanding the observed viral genetic diversity from this outbreak. We analysed the timing and patterns of introductions into distinct geographic regions; our phylogenetic evidence suggests rapid expansion of the outbreak in Brazil and multiple introductions of outbreak strains into Puerto Rico, Honduras, Colombia, other Caribbean islands, and the continental United States. We find that ZIKV circulated undetected in multiple regions for many months before the first locally transmitted cases were confirmed, highlighting the importance of surveillance of viral infections. We identify mutations with possible functional implications for ZIKV biology and pathogenesis, as well as those that might be relevant to the effectiveness of diagnostic tests.


Assuntos
Filogenia , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologia , Zika virus/genética , Zika virus/isolamento & purificação , Animais , Brasil/epidemiologia , Colômbia/epidemiologia , Culicidae/virologia , Surtos de Doenças/estatística & dados numéricos , Genoma Viral/genética , Mapeamento Geográfico , Honduras/epidemiologia , Humanos , Metagenoma/genética , Epidemiologia Molecular , Mosquitos Vetores/virologia , Mutação , Vigilância em Saúde Pública , Porto Rico/epidemiologia , Estados Unidos/epidemiologia , Zika virus/classificação , Zika virus/patogenicidade , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologia
16.
Hum Genomics ; 11(1): 10, 2017 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-28511696

RESUMO

BACKGROUND: Genetic variant effect prediction algorithms are used extensively in clinical genomics and research to determine the likely consequences of amino acid substitutions on protein function. It is vital that we better understand their accuracies and limitations because published performance metrics are confounded by serious problems of circularity and error propagation. Here, we derive three independent, functionally determined human mutation datasets, UniFun, BRCA1-DMS and TP53-TA, and employ them, alongside previously described datasets, to assess the pre-eminent variant effect prediction tools. RESULTS: Apparent accuracies of variant effect prediction tools were influenced significantly by the benchmarking dataset. Benchmarking with the assay-determined datasets UniFun and BRCA1-DMS yielded areas under the receiver operating characteristic curves in the modest ranges of 0.52 to 0.63 and 0.54 to 0.75, respectively, considerably lower than observed for other, potentially more conflicted datasets. CONCLUSIONS: These results raise concerns about how such algorithms should be employed, particularly in a clinical setting. Contemporary variant effect prediction tools are unlikely to be as accurate at the general prediction of functional impacts on proteins as reported prior. Use of functional assay-based datasets that avoid prior dependencies promises to be valuable for the ongoing development and accurate benchmarking of such tools.


Assuntos
Algoritmos , Mutação , Software , Bases de Dados Genéticas , Conjuntos de Dados como Assunto , Genes BRCA1 , Genes p53 , Humanos
17.
Nature ; 544(7650): 309-315, 2017 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-28405027

RESUMO

The 2013-2016 West African epidemic caused by the Ebola virus was of unprecedented magnitude, duration and impact. Here we reconstruct the dispersal, proliferation and decline of Ebola virus throughout the region by analysing 1,610 Ebola virus genomes, which represent over 5% of the known cases. We test the association of geography, climate and demography with viral movement among administrative regions, inferring a classic 'gravity' model, with intense dispersal between larger and closer populations. Despite attenuation of international dispersal after border closures, cross-border transmission had already sown the seeds for an international epidemic, rendering these measures ineffective at curbing the epidemic. We address why the epidemic did not spread into neighbouring countries, showing that these countries were susceptible to substantial outbreaks but at lower risk of introductions. Finally, we reveal that this large epidemic was a heterogeneous and spatially dissociated collection of transmission clusters of varying size, duration and connectivity. These insights will help to inform interventions in future epidemics.


Assuntos
Ebolavirus/genética , Ebolavirus/fisiologia , Genoma Viral/genética , Doença pelo Vírus Ebola/transmissão , Doença pelo Vírus Ebola/virologia , Clima , Surtos de Doenças/estatística & dados numéricos , Ebolavirus/isolamento & purificação , Geografia , Doença pelo Vírus Ebola/epidemiologia , Humanos , Internacionalidade , Modelos Lineares , Epidemiologia Molecular , Filogenia , Viagem/legislação & jurisprudência , Viagem/estatística & dados numéricos
18.
Nano Lett ; 17(4): 2313-2318, 2017 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-28358518

RESUMO

DNA-programmable assembly has been used to prepare superlattices composed of octahedral and spherical nanoparticles, respectively. These superlattices have the same body-centered cubic lattice symmetry and macroscopic rhombic dodecahedron crystal habit but tunable lattice parameters by virtue of the DNA length, allowing one to study and determine the effect of nanoscale structure and lattice parameter on the light-matter interactions in the superlattices. Backscattering measurements and finite-difference time-domain simulations have been used to characterize these two classes of superlattices. Superlattices composed of octahedral nanoparticles exhibit polarization-dependent backscattering but via a trend that is opposite to that observed in the polarization dependence for analogous superlattices composed of spherical nanoparticles. Electrodynamics simulations show that this polarization dependence is mainly due to the anisotropy of the nanoparticles and is observed only if the octahedral nanoparticles are well-aligned within the superlattices. Both plasmonic and photonic modes are identified in such structures, both of which can be tuned by controlling the size and shape of the nanoparticle building blocks, the lattice parameters, and the overall size of the three-dimensional superlattices (without changing habit).

19.
Proc Natl Acad Sci U S A ; 114(3): 457-461, 2017 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-28053232

RESUMO

Three-dimensional plasmonic superlattice microcavities, made from programmable atom equivalents comprising gold nanoparticles functionalized with DNA, are used as a testbed to study directional light emission. DNA-guided nanoparticle colloidal crystallization allows for the formation of micrometer-scale single-crystal body-centered cubic gold nanoparticle superlattices, with dye molecules coupled to the DNA strands that link the particles together, in the form of a rhombic dodecahedron. Encapsulation in silica allows one to create robust architectures with the plasmonically active particles and dye molecules fixed in space. At the micrometer scale, the anisotropic rhombic dodecahedron crystal habit couples with photonic modes to give directional light emission. At the nanoscale, the interaction between the dye dipoles and surface plasmons can be finely tuned by coupling the dye molecules to specific sites of the DNA particle-linker strands, thereby modulating dye-nanoparticle distance (three different positions are studied). The ability to control dye position with subnanometer precision allows one to systematically tune plasmon-excition interaction strength and decay lifetime, the results of which have been supported by electrodynamics calculations that span length scales from nanometers to micrometers. The unique ability to control surface plasmon/exciton interactions within such superlattice microcavities will catalyze studies involving quantum optics, plasmon laser physics, strong coupling, and nonlinear phenomena.


Assuntos
DNA/química , Nanopartículas Metálicas/química , Corantes , Simulação por Computador , Cristalização , Ouro/química , Microespectrofotometria , Modelos Moleculares , Nanotecnologia , Fenômenos Ópticos , Dióxido de Silício
20.
Fam Cancer ; 16(3): 411-416, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28063109

RESUMO

An apparently balanced t(2;3)(q37.3;q13.2) translocation that appears to segregate with renal cell carcinoma (RCC) has indicated potential areas to search for the elusive genetic basis of clear cell RCC. We applied Hi-Plex targeted sequencing to analyse germline DNA from 479 individuals affected with clear cell RCC for this breakpoint translocation and genetic variants in neighbouring genes on chromosome 2, ACKR3 and COPS8. While only synonymous variants were found in COPS8, one of the missense variants in ACKR3:c.892C>T, observed in 4/479 individuals screened (0.8%), was predicted likely to damage ACKR3 function. Identification of causal genes for RCC has potential clinical utility, where risk assessment and risk management can offer better outcomes, with surveillance for at-risk relatives and nephron sparing surgery through earlier intervention.


Assuntos
Complexo do Signalossomo COP9/genética , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Proteínas/genética , Receptores CXCR/genética , Adulto , Estudos de Casos e Controles , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença/genética , Humanos , Masculino , Pessoa de Meia-Idade
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