A Case of Successful TEVAR for Acute Stanford Type A Aortic Dissection with a Thrombosed False Lumen / 日本心臓血管外科学会雑誌

In acute Stanford type A aortic dissection, except for some thrombosed false-lumen types, graft replacement is a standard treatment. On the other hand, thoracic endovascular aortic repair (TEVAR) might be considered for high-risk patients with retrograde type A aortic dissection when entry is in the descending aorta, although its efficacy in a case of an extensive thrombosed false lumen without obvious entry is unknown. We report a case of successful zone 3 TEVAR using RelayPro NBS for Stanford type A aortic dissection with a localized CT-enhanced false lumen in the proximal descending aorta. An 83-year-old woman was admitted for acute Stanford type A aortic dissection with a thrombosed false lumen of the ascending thoracic aorta. She was initially treated conservatively because of being a high-risk patient for open surgery. One week after hospitalization, the ascending aorta diameter increased and the false lumen in the proximal descending aorta grew sporadically in a CT image. We suspected that the ascending aorta was enlarged due to a partially patent false lumen of the descending thoracic aorta, and performed zone 3 TEVAR using RelayPro NBS to close a possible entry in the proximal descending aorta even though there was no obvious entry. The patient had a good postoperative course and was discharged 15 days after TEVAR. Shrinkage of the false lumen in the ascending aorta was observed in CT images two months after TEVAR.

MRN complex is an essential effector of DNA damage repair / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Genome stability can be threatened by both endogenous and exogenous agents. Organisms have evolved numerous mechanisms to repair DNA damage, including homologous recombination (HR) and non-homologous end joining (NHEJ). Among the factors associated with DNA repair, the MRE11-RAD50-NBS1 (MRN) complex (MRE11-RAD50-XRS2 in

The utility of NBS-profiling for characterization of yellow rust resistance in an F6 durum wheat population

Seedling and adult plant (field) resistance to yellow rust in the durum wheat (Triticum turgidum ssp. durum) cross Kunduru-1149 x Cham-1 was characterized using a functionally-targeted DNA marker system, NBS-profiling. Chi-squared analysis indicated a four gene model conferring seedling yellow rust resistance against Puccinia striiformis f. sp. tritici isolate WYR85/22 (virulent on Yr2, Yr6, Yr7 and Yr9). Interval mapping located two QTL for yellow rust resistance on the long arm of chromosome 1B, while Kruskal–Wallis single marker regression identified a number of additional marker loci associated with seedling and/or adult plant, field resistance to yellow rust. These results suggested that much of the yellow rust resistance seen in the field may be due to seedling expressed resistance (R) genes. Characterization of the DNA sequence of three NBS marker loci indicated that all showed significant homology to functionally-characterized R-genes and resistance gene analogues (RGAs), with the greatest homology being NBS-LRR-type R-genes and RGAs from cereal species.

Genome wide identification of nucleotide-binding site leucine-rich repeat (NBS-LRR) gene encoding regions in Solanum lycopersicum resistant to environmental pathogens by computational methods

Aim: The nucleotide binding site leucine rich repeat (NBS-LRR) genes are responsive to pathogen strike in plants. This study focused on identifying the loci specific NBS-LRR gene encoding regions in tomato at whole genome level. Methodology: Major computational challenges in analyzing large genomic data using existing analytical tools were limited by the amount of memory used for reading large data. In this study, a specific algorithm was developed to identify a signature pattern associated with stress tolerant coding regions using stream readers for reading whole tomato genome, chromosome wise, to locate NBS-LRR coding sequences. Results: The computer program reads chromosome wise data and extracts the potential stress tolerant coding regions. It was found that more than 300 disease resistance protein coding regions were found across all chromosome, specifically in chromosome 12 more NBS-LRR concentration were found and their respective locus were identified. Interpretation: The identified disease resistance protein coding regions, specifically the NBS-LRR coding regions and their loci can be useful for plant breeders to select parental lines for developing plants tolerant to disease and pest invasion

Inherited NBN Mutations and Prostate Cancer Risk and Survival / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to establish the contribution of four founder alleles of NBN to prostate cancer risk and cancer survival. MATERIALS AND METHODS: Five thousand one hundred eighty-nine men with prostate cancer and 6,152 controls were genotyped for four recurrent variants of NBN (657del5, R215W, I171V, and E185Q). RESULTS: The NBN 657del5 mutation was detected in 74 of 5,189 unselected cases and in 35 of 6,152 controls (odds ratio [OR], 2.5; p < 0.001). In carriers of 657del5 deletion, the cancer risk was restricted to men with the GG genotype of the E185Q variant of the same gene. Among men with the GG genotype, the OR associated with 657del5 was 4.4 (95% confidence interval [CI], 2.4 to 8.0). Among men with other E185Q genotypes, the OR associated with 657del5 was 1.4 (95% CI, 0.8 to 2.4) and the interaction was significant (homogeneity p=0.006). After a median follow-up of 109 months, mortality was worse for 657del5 mutation carriers than for non-carriers (hazard ratio [HR], 1.6; p=0.001). The adverse effect of 657del5 on survival was only seen on the background of the GG genotype of E185Q (HR, 1.9; p=0.0004). CONCLUSION: The NBN 657del5 mutation predisposes to poor prognosis prostate cancer. The pathogenicity of this mutation, with regards to both prostate cancer risk and survival, is modified by a missense variant of the same gene (E185Q).

Implementation of a Targeted Next-Generation Sequencing Panel for Constitutional Newborn Screening in High-Risk Neonates

PURPOSE: Newborn screening (NBS) programs are important for appropriate management of susceptible neonates to prevent serious clinical problems. Neonates admitted to neonatal intensive care units (NICU) are at a potentially high risk of false-positive results, and repetitive NBS after total parenteral nutrition is completely off results in delayed diagnosis. Here, we present the usefulness of a targeted next-generation sequencing (TNGS) panel to complement NBS for early diagnosis in high-risk neonates. MATERIALS AND METHODS: The TNGS panel covered 198 genes associated with actionable genetic and metabolic diseases that are typically included in NBS programs in Korea using tandem mass spectrometry. The panel was applied to 48 infants admitted to the NICU of Severance Children's Hospital between May 2017 and September 2017. The infants were not selected for suspected metabolic disorders. RESULTS: A total of 13 variants classified as likely pathogenic or pathogenic were detected in 11 (22.9%) neonates, including six genes (DHCR7, PCBD1, GAA, ALDOB, ATP7B, and GBA) associated with metabolic diseases not covered in NBS. One of the 48 infants was diagnosed with an isobutyl-CoA dehydrogenase deficiency, and false positive results of tandem mass screening were confirmed in two infants using the TNGS panel. CONCLUSION: The implementation of TNGS in conjunction with conventional NBS can allow for better management of and earlier diagnosis in susceptible infants, thus preventing the development of critical conditions in these sick infants.

Expression Analysis of Pyrenophora teres f. maculata-Responsive Loci in Hordeum vulgare

Abstract Pyrenophora teres f. maculata is the causal agent of barley spot form net blotch (SFNB), a major stubble-borne disease in many barley-growing areas worldwide. In plants, the Nucleotide-Binding Site-Leucine-Rich Repeat (NBS-LRR) gene family functions in immunity against a variety of pathogens and pests. From a pre-established set of NBS-type resistance gene candidates, we have selected three candidate genes, HvNBS10, HvNBS72 and HvNBS85, to analyze their possible involvement in P. teres f. maculata resistance. The studied genes were mapped on chromosomes 5H and 7H. Expression profiles using qRT-PCR, 48 hours after infection by P. teres. f. maculata, revealed that the transcription of all genes acted in the same direction (down-regulation) in both resistant and susceptible cultivars, although they showed a variation in transcript dosage. This result suggests that coordinated transcriptional responses of multiple barley NBS genes would be required to an efficient response against P. teres f. maculata. Moreover, the phylogenetic analysis revealed that the studied barley candidate R genes were characterized by a high homology with the barley Nbs2-Rdg2a gene conferring resistance to the fungus Pyrenophora graminea, suggesting a common origin of P. graminea and P. teres resistance genes in barley, following pathogens evolution. The genes characterized in the present study hold potential in elucidating the molecular pathways and developing novel markers associated with SFNB resistance in barley.

Perspectives on Next-Generation Newborn Screening

Newborn screening (NBS) has been effective for detecting asymptomatic newborns with inherited metabolic diseases and has facilitated early clinical intervention, which has resulted in significant decreases in the rates of morbidity and mortality caused by these diseases. The outcome of the NBS program heavily depends on technological advances. Since Dr. Robert Guthrie developed a bacterial inhibition assay to screen for metabolic diseases in the early 1960s, use of the NBS program has spread to many countries. Tandem mass spectrometry (TMS) was a second major technological breakthrough that has allowed screening to be extended to disorders of fatty acid and organic acid metabolism as well as to those of amino acid metabolism, and recently screening has also been expanded to include lysosomal storage diseases. TMS can detect multiple analytes rapidly and simultaneously and is currently applied to nearly 80% of the newborn population in Korea. Next-generation sequencing (NGS) technology could be another major breakthrough to improve the current NBS program. To integrate NGS into the NBS program, various considerations about its analytical validity, clinical validity, clinical utility, and ethical, legal, and social implications should be addressed on the basis of population screening. Here, the authors review population screening criteria, the current status of NBS, and recent advances in NGS. In addition, we discuss the practical and ethical issues, opportunities, and challenges regarding the implementation of NGS in NBS.

Expression of NBS1 in the salivary gland of radiation-injured rats / 中华放射医学与防护杂志

Objective To investigate the expressions of NBS1 mRNA and protein in the salivary gland of irradiated rats and explore the role of NBS1 in the repair of radiation injury of salivary gland epithelial cells.Methods Eighty rats were randomly divided into two groups for radiation and control (n =40 each).The rats were fractionally exposed to 3 Gy of 60Co γ-rays once in two days,leading to an accumulation dose of 3,6,9,12,15 Gy.The sham-irradiated controls were anesthetized in parallel but without irradiation.After 2-4 h of irradiation,the rats were sacrificed,IHC and RT-PCR were used to detect the expressions of NBS1 protein and mRNA in parotid and submandibular glands,and the ultra-structural changes in the glands were observed by a transmission electron microscopy.Results After irradiation,the salivary glands became atrophy and the parotid gland cells were damaged more serious than the submandibular gland cells.Compared with the controls,with the groups of dose,at 9,12,15 Gy in parotid gland (t =7.10,17.93,20.86,P ＜ 0.05),at 12,15 Gy in the submandibular gland (t =3.13,7.53,P ＜0.05),the expression of NBS1 mRNA was reduced.With the groups of dose at 9,12,15 Gy in paretid gland (t =4.29,17.91,91.29,P ＜ 0.05 ),the dose at 12,15 Gy in submandibular gland ( t =4.61,11.84,P＜0.05),the expression of NBS1 protein in serous cells,and the dose at 12,15 Gy in parotid gland ductal epithelial cell ( t =3.09,5.62,P ＜ 0.05) were reduced.But in the ductal epithelial cells as well as muoass cells in the submandibualr gland were steadily.Conclusions After irradiation,NBS1 at both protein and mRNA levels was dropped in the salivary gland of rats,which might contribute to the repair of radiation injury of salivary gland.

Papel da proteína Mx1 na resposta a interferons e no processo neoplásico / Role of Mx1 protein in the response to interferons and neoplastic process

A proteína Mx1 é codificada por um gene induzido por interferon e compartilha a organização de seus domínios, a capacidade de homo-oligomerização e associação com membranas com as grandes dinaminas GTPases. A proteína Mx1 está envolvida na resposta contra um grande número de vírus de RNA, como aqueles pertencentes à família Buniavírus e o vírus influenza. Curiosamente, o gene MX1 foi encontrado como silenciado por metilação em diversos processos neoplásicos, incluindo carcinomas de cabeça e pescoço de células escamosas. Neste cenário, o silenciamento gênico de MX1 está associado à imortalização de uma série de linhagens celulares neoplásicas. Assim, Mx1 se destaca como uma das principais proteínas envolvidas nas respostas imunes induzidas por interferon e também desempenha um importante papel no controle do ciclo celular. Aqui discutimos os aspectos funcionais da proteína Mx1 abordando sua atividade antiviral, organização estrutural, envolvimento com neoplasias e, principalmente, os aspectos funcionais obtidos pela determinação de seus parceiros celulares.

The Mx1 protein is encoded by an interferon-induced gene and shares domain organization, homo-oligomerization capacity and membrane association with the large dynamin-like GTPases. The Mx1 protein is involved in the response to a large number of RNA viruses, such as the bunyavirus family and the influenza virus. Interestingly, it has also been found as a methylation-silenced gene in several types of neoplasm, including head and neck squamous cell carcinoma. In this scenario, MX1 gene silencing is associated with immortalization in several neoplastic cell lines. Thus, Mx1 stands out as one of the key proteins involved in interferon-induced immune response and also plays an important role in cell cycle control. Here we discuss some of the functions of the Mx1 protein, including its antiviral activity, protein folding and involvement in neoplasia, as well as those revealed by investigating its cellular partners.

Cloning and analysis of a NBS-LRR disease resistance gene candidate PnAG1 from peanut (Arachis hypogaea L. )

Background: Based on the conserved sequences of a known NBS resistance gene, a pair of degenerate primers was designed to amplify the NBS-LRR resistance gene from peanut using PCR and RACE methods. Results: Analyzing the amino acid sequence by BLAST on NCBI, which was deduced from the 1088bp-long gene named PnAG1-2, showed that it had a certain homology with some resistance proteins, among which Arachis cardenasii resistance protein gene had the highest homology (66 percent). Relative quantification PCR analysis indicated that PnAG1-2 gene expresses more in J11 (an A. flavus-resistant variety) than in JH1012 (an A. flavus-susceptible variety) when the harvest time was coming. Conclusions: In this study, the NBS-LRR resistance sequence was successfully cloned from peanut and prokaryotic expression was done on the gene, which provided a foundation for cultivating anti-A. flavus peanut varieties.

Study on the association between DNA double-strand break repair gene NBS1 polymorphisms and susceptibility on lung cancer / 中华流行病学杂志

Objective To study the association between DNA double-strand break repair gene NBS1(nijmegen breakage syndrome gene)polymorphisms and the susceptibility to lung cancer.Methods A case-control study design was applied.PCR-RFLP was used to identify NBS1 polymorphisms among 575 lung cancer cases and 575 controls.Results The frequencies of C/C,C/G and G/G genotypes at NBS1 rs 1805794 site were 25.9%,51.8%,22.3% among controls compared to 20.5%,52.3%,27.1% among cases.There was significant difference between controls and cases(χ~2=6.38,P=0.04).Individuals carrying C/G + G/G genotypes had an increased risk for lung cancer (OR=1.46,95%CI:1.09-1.97)compared to the C/C genotype.The frequencies of G/G,G/C and C/C genotypes at NBS1 rs2735383 site were 37.9%,47.0%,15.1% among controls compared to 35.5%,48.5%,16.0% among cases,with no significant difference between the two groups(χ~2=0.75,P=0.69).Individuals earning Hap4-GC haplotype(OR=1.70,95%CI:1.24-2.31)and Hap4/Hap2 dihaplotype(OR=1.75,95%CI:1.11-2.76)had an increased risk on lung cancer.Joint associations of smoking and the NBS1 polymorphism with the risk of lung cancer were observed(P＜0.05).Conclusion The G/G genotype at NBS1 rs1805794 site and the Hap4-GC haplotype and Hap4/Hap2 dihaplotype from rs1805794 and rs2735383 were both associated with lung cancer.

Construction and Identification of NBS1-targeting microRNA Expressing Eukaryotic Vector / 中国生物工程杂志

Objective:To construct NBS1 microRNA expressing eukaryotic recombinants,and identify biological activity of recombinants in Hela cell after transfection.Methods:According to sequence of NBS1mRNA,the NBS1 pre-microRNA was designed and synthesized,then cloned into the GFP reporter pcDNA6.2-GW/EmGFP-miR vector and transfected into Hela cell line.To detect integrity of inset fragment through colony PCR and sequencing analysis.The biological activity of recombinants through identify interference efficiency of NBS1 microRNA recombinants by way of Real-Time PCR and Western blot were determined.Results:Sequences of inset fragment in four microRNA expressing recombinants were correct.NBS1 mRNA and protein expression of four microRNA recombinants were decrease,which is the lowest in the NBS1mi-2 group.Conclusion:Four NBS1-targeting microRNA expressing recombinants all have biological activity in Hela cell line,and NBS1mi-2 recombinant has the most interference efficiency.The microRNA expressing plasmid which were successfully constructed and lay foundation for the studies on the tumor gene therapy of microrna targeting NBS1.

Estudo químico das sementes e casca da madeira de guarea trichilioides (meliaceae)

In this paper we related the identification and isolation of stearic, linolenic and palmitic acids and the isolation and structural determination of the 7-desacetoxy-7-hidroxyazadirone present in the hexan extract of the fruits of Guarea trichilioides. From the chloroform extrat of steam bark were isolated and identificated the antraquinones: chrysophanol and physcion.

Da casca da madeira de Guarea trichilioides foram isoladas e identificadas através de métodos espectrométricos as antraquinonas crisofanol e fisciona e das sementes o limonóide 7-desacetoxi-7-hidroxiazadirona. Da fração lipofílica das sementes foram ainda identificados por co-injeçao de padrões, através de cromatografia gasosa os ácidos esteárico, palmítico e linolênico.