Contrast-enhanced ultrasound features as a potential biomarker for the prediction of breast cancer recurrence.

PURPOSE: To investigate the associations between contrast-enhanced ultrasound imaging features and disease recurrence among patients with locally advanced breast cancer treated with neoadjuvant chemotherapy. MATERIALS AND METHODS: In the study, pre- and post-neoadjuvant chemotherapy contrast-enhanced ultrasound images of 43 patients with breast cancer were retrospectively analysed. Post-acquisition image processing involved the placement of freehand-drawn regions of interest, followed by the generation of blood flow kinetics representing blood volume and velocity for these regions of interest. Qualitative and quantitative contrast-enhanced ultrasound parameters were compared to predict recurrence, and receiver operating characteristic analysis was used to evaluate predictive ability. RESULTS: Among the 43 patients, 10 (23%) exhibited disease recurrence (median [range]: 27 [4-68] months). Post-neoadjuvant chemotherapy peak enhancement, wash-in area under the curve, wash-out area under the curve, and wash-in and wash-out area under the curve (p=0.003, p=0.004, p=0.026, and p=0.014, respectively) differed between the no-recurrence and recurrence groups. The area under the receiver operating characteristic curve (0.88; 95% confidence interval: 0.75-1.00) for post-neoadjuvant chemotherapy peak enhancement was the highest among the contrast-enhanced ultrasound parameters, with a cut-off of 13.33 arbitrary units. CONCLUSION: Higher peak enhancement on post-neoadjuvant chemotherapy contrast-enhanced ultrasound images was associated with recurrence in women with locally advanced breast cancer and is a potential biomarker of tumor recurrence.

Regulation of stomatal development by stomatal lineage miRNAs.

Stomata in the plant epidermis play a critical role in growth and survival by controlling gas exchange, transpiration, and immunity to pathogens. Plants modulate stomatal cell fate and patterning through key transcriptional factors and signaling pathways. MicroRNAs (miRNAs) are known to contribute to developmental plasticity in multicellular organisms; however, no miRNAs appear to target the known regulators of stomatal development. It remains unclear as to whether miRNAs are involved in stomatal development. Here, we report highly dynamic, developmentally stage-specific miRNA expression profiles from stomatal lineage cells. We demonstrate that stomatal lineage miRNAs positively and negatively regulate stomatal formation and patterning to avoid clustered stomata. Target prediction of stomatal lineage miRNAs implicates potential cellular processes in stomatal development. We show that miR399-mediated PHO2 regulation, involved in phosphate homeostasis, contributes to the control of stomatal development. Our study demonstrates that miRNAs constitute a critical component in the regulatory mechanisms controlling stomatal development.

The Spectrum of Hepatic Involvement in Patients With Telomere Disease.

Loss-of-function mutations in genes that encode for components of the telomere repair complex cause accelerated telomere shortening. Hepatic involvement has been recognized as a cause of morbidity in telomere diseases, but very few studies have characterized the nature and extent of liver involvement in affected patients. We report the prevalence and characteristics of liver involvement in a large cohort of patients with telomere disease evaluated serially at the National Institutes of Health. One hundred twenty-one patients with known or suspected telomere disease were screened; 40 patients with liver involvement were included in the current study. Median follow-up was 2.4 years. Data were collected regarding their demographic information, laboratory analysis, imaging, and histopathology. Forty patients (40% of the cohort) with a median age of 42 years were found to have liver involvement. Liver enzyme elevation was cholestatic in pattern; 8 (21%) had drug-related enzyme elevations. The most common imaging finding was increased hepatic echogenicity on ultrasound in 39% (9) of patients, followed by hepatomegaly in 26% (6). Biopsies were infrequent because of risk associated with thrombocytopenia, but in 6 patients, there were varying findings: nodular regenerative hyperplasia, steatohepatitis, hemosiderosis, cholestasis, and cirrhosis with hepatic steatosis. Almost half the cohort had pulmonary diffusion abnormalities, and 25% died during the follow-up period. Conclusion: In patients with telomere disease, hepatic involvement is common and can present in diverse ways, including elevated liver enzymes as well as histopathologic and imaging abnormalities. Liver disease has important implications for morbidity and mortality in patients with telomere disease.

Danazol Treatment for Telomere Diseases.

BACKGROUND: Genetic defects in telomere maintenance and repair cause bone marrow failure, liver cirrhosis, and pulmonary fibrosis, and they increase susceptibility to cancer. Historically, androgens have been useful as treatment for marrow failure syndromes. In tissue culture and animal models, sex hormones regulate expression of the telomerase gene. METHODS: In a phase 1-2 prospective study involving patients with telomere diseases, we administered the synthetic sex hormone danazol orally at a dose of 800 mg per day for a total of 24 months. The goal of treatment was the attenuation of accelerated telomere attrition, and the primary efficacy end point was a 20% reduction in the annual rate of telomere attrition measured at 24 months. The occurrence of toxic effects of treatment was the primary safety end point. Hematologic response to treatment at various time points was the secondary efficacy end point. RESULTS: After 27 patients were enrolled, the study was halted early, because telomere attrition was reduced in all 12 patients who could be evaluated for the primary end point; in the intention-to-treat analysis, 12 of 27 patients (44%; 95% confidence interval [CI], 26 to 64) met the primary efficacy end point. Unexpectedly, almost all the patients (11 of 12, 92%) had a gain in telomere length at 24 months as compared with baseline (mean increase, 386 bp [95% CI, 178 to 593]); in exploratory analyses, similar increases were observed at 6 months (16 of 21 patients; mean increase, 175 bp [95% CI, 79 to 271]) and 12 months (16 of 18 patients; mean increase, 360 bp [95% CI, 209 to 512]). Hematologic responses occurred in 19 of 24 patients (79%) who could be evaluated at 3 months and in 10 of 12 patients (83%) who could be evaluated at 24 months. Known adverse effects of danazol--elevated liver-enzyme levels and muscle cramps--of grade 2 or less occurred in 41% and 33% of the patients, respectively. CONCLUSIONS: In our study, treatment with danazol led to telomere elongation in patients with telomere diseases. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01441037.).

POWERDRESS and HDA9 interact and promote histone H3 deacetylation at specific genomic sites in Arabidopsis.

Histone acetylation is a major epigenetic control mechanism that is tightly linked to the promotion of gene expression. Histone acetylation levels are balanced through the opposing activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). Arabidopsis HDAC genes (AtHDACs) compose a large gene family, and distinct phenotypes among AtHDAC mutants reflect the functional specificity of individual AtHDACs However, the mechanisms underlying this functional diversity are largely unknown. Here, we show that POWERDRESS (PWR), a SANT (SWI3/DAD2/N-CoR/TFIII-B) domain protein, interacts with HDA9 and promotes histone H3 deacetylation, possibly by facilitating HDA9 function at target regions. The developmental phenotypes of pwr and hda9 mutants were highly similar. Three lysine residues (K9, K14, and K27) of H3 retained hyperacetylation status in both pwr and hda9 mutants. Genome-wide H3K9 and H3K14 acetylation profiling revealed elevated acetylation at largely overlapping sets of target genes in the two mutants. Highly similar gene-expression profiles in the two mutants correlated with the histone H3 acetylation status in the pwr and hda9 mutants. In addition, PWR and HDA9 modulated flowering time by repressing AGAMOUS-LIKE 19 expression through histone H3 deacetylation in the same genetic pathway. Finally, PWR was shown to physically interact with HDA9, and its SANT2 domain, which is homologous to that of subunits in animal HDAC complexes, showed specific binding affinity to acetylated histone H3. We therefore propose that PWR acts as a subunit in a complex with HDA9 to result in lysine deacetylation of histone H3 at specific genomic targets.

Contrast-Enhanced Ultrasound for Early Prediction of Response of Breast Cancer to Neoadjuvant Chemotherapy.

PURPOSE: To evaluate the time-intensity curve (TIC) parameters on contrast-enhanced ultrasound (CEUS) for early prediction of the response of breast cancer to neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: This prospective study included 41 patients with breast cancer. CEUS was performed before and after the first cycle of NAC. TIC parameters were analyzed for different regions of interest (ROIs). ROI 1 targeted the hotspot area of greatest enhancement, ROI 2 delineated the area of hyperenhancement, ROI 3 included the entire tumor on grayscale ultrasound, and ROI 4 encircled the normal parenchyma. The TIC perfusion values for ROI 1, 2, and 3 were divided by the ROI 4 value. RESULTS: 11 (26.8 %) of the 41 patients showed a good response (Miller-Payne score 4 or 5) and 30 (73.2 %) showed a minor response (Miller-Payne score 1, 2, or 3). There were significant differences in the wash-out area under the curve, the wash-in and wash-out areas under the curve on ROI 1/4 after the first cycle of NAC, pre-NAC mean transit time local (mTTl) on ROI 2/4, and pre-NAC mTTl on ROI 3/4 between good and minor responders (area under the receiver-operating characteristic curve > 0.70, p < 0.05). CONCLUSION: Some TIC parameters obtained by CEUS may allow prediction of the response of breast cancer to NAC at a very early time point.

Traffic into silence: endomembranes and post-transcriptional RNA silencing.

microRNAs (miRNAs) and small interfering RNAs (siRNAs) are small RNAs that repress gene expression at the post-transcriptional level in plants and animals. Small RNAs guide Argonaute-containing RNA-induced silencing complexes to target RNAs in a sequence-specific manner, resulting in mRNA deadenylation followed by exonucleolytic decay, mRNA endonucleolytic cleavage, or translational inhibition. Although our knowledge of small RNA biogenesis, turnover, and mechanisms of action has dramatically expanded in the past decade, the subcellular location of small RNA-mediated RNA silencing still needs to be defined. In contrast to the prevalent presumption that RNA silencing occurs in the cytosol, emerging evidence reveals connections between the endomembrane system and small RNA activities in plants and animals. Here, we summarize the work that uncovered this link between small RNAs and endomembrane compartments and present an overview of the involvement of the endomembrane system in various aspects of RNA silencing. We propose that the endomembrane system is an integral component of RNA silencing that has been long overlooked and predict that a marriage between cell biology and RNA biology holds the key to a full understanding of post-transcriptional gene regulation by small RNAs.

Prognostic impact of skeletal muscle volume derived from cross-sectional computed tomography images in breast cancer.

PURPOSE: This study aimed to determine whether the prognosis of breast cancer is affected by muscle or fat volume as measured from computed tomography (CT) images. METHODS: We identified 1460 patients with chest CT who were diagnosed as having breast cancer at the National Cancer Center, Korea, between January 2001 and December 2009. Using CT images of 10-mm slices, we measured the cross-sectional areas of skeletal muscle and adipose tissue at the 3rd lumbar vertebrae, and derived their volumes. The skeletal muscle volume, fat volume, and muscle-to-fat ratio were evaluated for association with overall survival (OS) and recurrence-free survival (RFS). RESULTS: The median skeletal muscle and fat volumes among the patients were 93.3 cc (range 39.6-236.9) and 420.1 cc (range 19.5-1392.3), respectively. Patients with higher muscle volume had better prognosis than those with lower muscle volume [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.34-0.92, P = 0.022 for OS; HR 0.72, 95% CI 0.52-0.99, P = 0.046 for RFS]. However, body mass index (BMI) and fat volume were not associated with prognosis. In addition, muscle volume was a significant prognosticator for OS, regardless of BMI (HR 0.55, 95% CI 0.32-0.93, P = 0.034 in BMI < 25.0; HR 0.44, 95% CI 0.21-0.91, P = 0.026 in BMI ≥ 25.0). Among older patients (≥ 50), those with higher muscle volume showed better OS and RFS (HR 0.44, 95% CI 0.23-0.85, P = 0.015; HR 0.55, 95% CI 0.34-0.90, P = 0.017, respectively). CONCLUSION: This study demonstrated that breast cancer patients with higher skeletal muscle volume showed more favorable prognosis.

Beyond the genetic code in leaf senescence.

Leaf senescence is not only genetically programmed but also induced by exogenous stress to ensure completion of the plant life cycle, successful reproduction and environmental adaptability. Genetic reprogramming is a major aspect of leaf senescence, and the senescence signaling that follows is controlled by a complex regulatory network. Recent studies suggest that the activity of transcription factors together with epigenetic mechanisms ensures the robustness of this network, with the latter including chromatin remodeling, DNA modification, and RNA-mediated control of transcription factors and other senescence-associated genes. In this review, we provide an overview of the relevant epigenetic mechanisms and summarize recent findings of epigenetic regulators of plant leaf senescence involved in DNA methylation and histone modification along with the functions of small RNAs in this process.

SUVH1, a Su(var)3-9 family member, promotes the expression of genes targeted by DNA methylation.

Transposable elements are found throughout the genomes of all organisms. Repressive marks such as DNA methylation and histone H3 lysine 9 (H3K9) methylation silence these elements and maintain genome integrity. However, how silencing mechanisms are themselves regulated to avoid the silencing of genes remains unclear. Here, an anti-silencing factor was identified using a forward genetic screen on a reporter line that harbors a LUCIFERASE (LUC) gene driven by a promoter that undergoes DNA methylation. SUVH1, a Su(var)3-9 homolog, was identified as a factor promoting the expression of the LUC gene. Treatment with a cytosine methylation inhibitor completely suppressed the LUC expression defects of suvh1, indicating that SUVH1 is dispensable for LUC expression in the absence of DNA methylation. SUVH1 also promotes the expression of several endogenous genes with promoter DNA methylation. However, the suvh1 mutation did not alter DNA methylation levels at the LUC transgene or on a genome-wide scale; thus, SUVH1 functions downstream of DNA methylation. Histone H3 lysine 4 (H3K4) trimethylation was reduced in suvh1; in contrast, H3K9 methylation levels remained unchanged. This work has uncovered a novel, anti-silencing function for a member of the Su(var)3-9 family that has previously been associated with silencing through H3K9 methylation.

Successful Interferon-Free Therapy of Chronic Hepatitis C Virus Infection Normalizes Natural Killer Cell Function.

BACKGROUND & AIMS: Chronic hepatitis C virus infection activates an intrahepatic immune response, leading to increased expression of interferon (IFN)-stimulated genes and activation of natural killer (NK) cells-the most prevalent innate immune cell in the liver. We investigated whether the elimination of hepatitis C virus with direct-acting antiviral normalizes expression of IFN-stimulated genes and NK cell function. METHODS: We used multicolor flow cytometry to analyze NK cells from the liver and blood of 13 HCV-infected patients who did not respond to treatment with pegylated interferon and ribavirin. Samples were collected before and during IFN-free treatment with daclatasvir and asunaprevir and compared with samples from the blood of 13 healthy individuals (controls). Serum levels of chemokine C-X-C motif ligand (CXCL) 10 or CXCL11 were measured by enzyme-linked immunosorbent assay. RESULTS: Before treatment, all patients had increased levels of CXCL10 or CXCL11 and a different NK cell phenotype from controls, characterized by increased expression of HLA-DR, NKp46, NKG2A, CD85j, signal transducer and activator of transcription 1 (STAT1), phosphorylated STAT1, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). NK cells from patients also had increased degranulation and decreased production of IFNγ and tumor necrosis factor α compared with NK cells from controls. Nine patients had an end-of-treatment response (undetectable virus) and 4 had virologic breakthrough between weeks 4 and 12 of therapy. A rapid decrease in viremia and level of inflammatory cytokines in all patients was associated with decreased activation of intrahepatic and blood NK cells; it was followed by restoration of a normal NK cell phenotype and function by week 8 in patients with undetectable viremia. This normalized NK cell phenotype was maintained until week 24 (end of treatment). CONCLUSIONS: Direct-acting antiviral-mediated clearance of HCV is associated with loss of intrahepatic immune activation by IFNα, which is indicated by decreased levels of CXCL10 and CXCL11 and normalization of NK cell phenotype and function.

POWERDRESS and diversified expression of the MIR172 gene family bolster the floral stem cell network.

Termination of the stem cells in the floral meristem (also known as floral determinacy) is critical for the reproductive success of plants, and the molecular activities regulating floral determinacy are precisely orchestrated during the course of floral development. In Arabidopsis thaliana, regulators of floral determinacy include several transcription factor genes, such as APETALA2 (AP2), AGAMOUS (AG), SUPERMAN (SUP), and CRABSCLAW (CRC), as well as a microRNA (miRNA), miR172, which targets AP2. How the transcription factor and miRNA genes are coordinately regulated to achieve floral determinacy is unknown. A mutation in POWERDRESS (PWR), a previously uncharacterized gene encoding a SANT-domain-containing protein, was isolated in this study as an enhancer of the weakly indeterminate ag-10 allele. PWR was found to promote the transcription of CRC, MIR172a, b, and c and/or enhance Pol II occupancy at their promoters, without affecting MIR172d or e. A mutation in mature miR172d was additionally found to enhance the determinacy defects of ag-10 in an AP2-dependent manner, providing direct evidence that miR172d is functional in repressing AP2 and thereby contributes to floral determinacy. Thus, while PWR promotes floral determinacy by enhancing the expression of three of the five MIR172 members as well as CRC, MIR172d, whose expression is PWR-independent, also functions in floral stem cell termination. Taken together, these findings demonstrate how transcriptional diversification and functional redundancy of a miRNA family along with PWR-mediated co-regulation of miRNA and transcription factor genes contribute to the robustness of the floral determinacy network.

The role of Mediator in small and long noncoding RNA production in Arabidopsis thaliana.

Mediator is a conserved multi-subunit complex known to promote the transcription of protein-coding genes by RNA polymerase II (Pol II) in eukaryotes. It has been increasingly realized that Pol II transcribes a large number of intergenic loci to generate noncoding RNAs, but the role of Mediator in Pol II-mediated noncoding RNA production has been largely unexplored. The role of Mediator in noncoding RNA production in plants is particularly intriguing given that plants have evolved from Pol II two additional polymerases, Pol IV and Pol V, to specialize in noncoding RNA production and transcriptional gene silencing at heterochromatic loci. Here, we show that Mediator is required for microRNA (miRNA) biogenesis by recruiting Pol II to promoters of miRNA genes. We also show that several well-characterized heterochromatic loci are de-repressed in Mediator mutants and that Mediator promotes Pol II-mediated production of long noncoding scaffold RNAs, which serve to recruit Pol V to these loci. This study expands the function of Mediator to include Pol II-mediated intergenic transcription and implicates a role of Mediator in genome stability.

Histogram analysis of apparent diffusion coefficient at 3.0t: Correlation with prognostic factors and subtypes of invasive ductal carcinoma.

PURPOSE: To evaluate apparent diffusion coefficient (ADC) histogram parameters that show correlations with prognostic factors and subtypes of breast cancer. MATERIALS AND METHODS: At 3.0T, various ADC histogram parameters were calculated including the entire tumor volume in 173 invasive ductal carcinomas: the minimum, 10th percentile, mean, median, 90th percentile, and maximum. ADC parameters were correlated with prognostic factors and subtype. RESULTS: The mean ADCmedian value was significantly higher in the group with lymph node metastasis, HER2 positivity, and a Ki-67 value <14% than in the group with negativity for lymph node metastasis, HER2 negativity, and a Ki-67 value ≥14% (0.907, 0.978, and 0.941 vs. 0.735, 0.778, and 0.761 × 10(-3) mm(2) /s, respectively) (P < 0.01). There was no significant correlation between ADCmedian and tumor size, histologic grade, estrogen receptor expression, and progesterone receptor expression (P = 0.272, 0.113, 0.261, and 0.181, respectively). For most ADC parameters except for ADCmin , the mean of variable ADC parameters of HER2-positive, luminal A, luminal B-HER2(+), triple-negative, and luminal B-HER2(-) diseases were arranged in descending order (1.175, 0.936, 0.863, 0.811, and 0.665 × 10(-3) mm(2) /s in ADCmedian , respectively) with statistical significant difference (P < 0.001). In multivariate analysis, histologic grade, the Ki-67 index, and HER2 expression were statistically significant explanatory prognostic factors for ADCmedian and the Ki-67 index had the most robust effects on ADC parameters (standardized coefficient = -0.317). CONCLUSION: Various ADC parameters were correlated with prognostic factors and subtype, except for ADCmin . HER2 positivity showed high ADC values and high Ki-67 index revealed low ADC values.

Gel pad application for automated breast sonography.

The purpose of this study was to describe the technical aspects of gel pad application for automated breast sonography and to show its effects on pain relief, scan coverage, and image quality. Twenty patients underwent 2 sets of automated breast sonography with and without gel pad application and were then asked to provide feedback on the examination-related pain. Scan coverage and image quality were compared quantitatively and qualitatively. The degree of pain was significantly decreased after gel pad application (P < .0001). The scan coverage was expanded particularly at the mid-portion of the breast. Image quality was satisfactory without significant differences between the sets. Gel pad application for automated breast sonography is easy and provides significant pain relief. The scan coverage was expanded, while the image quality was maintained.

AGAMOUS terminates floral stem cell maintenance in Arabidopsis by directly repressing WUSCHEL through recruitment of Polycomb Group proteins.

Floral stem cells produce a defined number of floral organs before ceasing to be maintained as stem cells. Therefore, floral stem cells offer an ideal model to study the temporal control of stem cell maintenance within a developmental context. AGAMOUS (AG), a MADS domain transcription factor essential for the termination of floral stem cell fate, has long been thought to repress the stem cell maintenance gene WUSCHEL (WUS) indirectly. Here, we uncover a role of Polycomb Group (PcG) genes in the temporally precise repression of WUS expression and termination of floral stem cell fate. We show that AG directly represses WUS expression by binding to the WUS locus and recruiting, directly or indirectly, PcG that methylates histone H3 Lys-27 at WUS. We also show that PcG acts downstream of AG and probably in parallel with the known AG target KNUCKLES to terminate floral stem cell fate. Our studies identify core components of the network governing the temporal program of floral stem cells.

Invasive ductal carcinoma of the breast in a 14-year-old girl.

Breast cancer is rare in children and adolescents. In particular, there are very few cases of invasive ductal carcinoma in childhood. We report a case of invasive ductal carcinoma of the breast in a 14-year-old girl presenting as a palpable mass. While the tumor demonstrated a relatively benign appearance on ultrasound, magnetic resonance imaging revealed typical malignant features. Several polymorphisms of single nucleotide variation were observed on gene analysis. The patient underwent breast conserving surgery and received subsequent concurrent chemo-radiation therapy. An awareness that ductal carcinoma of the breast rarely occurs in children is important to detect early stage breast cancer.

ARGONAUTE10 and ARGONAUTE1 regulate the termination of floral stem cells through two microRNAs in Arabidopsis.

Stem cells are crucial in morphogenesis in plants and animals. Much is known about the mechanisms that maintain stem cell fates or trigger their terminal differentiation. However, little is known about how developmental time impacts stem cell fates. Using Arabidopsis floral stem cells as a model, we show that stem cells can undergo precise temporal regulation governed by mechanisms that are distinct from, but integrated with, those that specify cell fates. We show that two microRNAs, miR172 and miR165/166, through targeting APETALA2 and type III homeodomain-leucine zipper (HD-Zip) genes, respectively, regulate the temporal program of floral stem cells. In particular, we reveal a role of the type III HD-Zip genes, previously known to specify lateral organ polarity, in stem cell termination. Both reduction in HD-Zip expression by over-expression of miR165/166 and mis-expression of HD-Zip genes by rendering them resistant to miR165/166 lead to prolonged floral stem cell activity, indicating that the expression of HD-Zip genes needs to be precisely controlled to achieve floral stem cell termination. We also show that both the ubiquitously expressed ARGONAUTE1 (AGO1) gene and its homolog AGO10, which exhibits highly restricted spatial expression patterns, are required to maintain the correct temporal program of floral stem cells. We provide evidence that AGO10, like AGO1, associates with miR172 and miR165/166 in vivo and exhibits "slicer" activity in vitro. Despite the common biological functions and similar biochemical activities, AGO1 and AGO10 exert different effects on miR165/166 in vivo. This work establishes a network of microRNAs and transcription factors governing the temporal program of floral stem cells and sheds light on the relationships among different AGO genes, which tend to exist in gene families in multicellular organisms.

Molecular epidemiological analysis of five outbreaks associated with Salmonella enterica serovar Enteritidis between 2008 and 2010 on Jeju Island, Republic of Korea.

With the increasing incidence of Salmonella enterica serovar Enteritidis (SE) infections, five SE foodborne outbreaks were identified between 2008 and 2010 on Jeju Island, Republic of Korea. In this study, the genetic relatedness of isolates recovered from the five outbreaks was investigated to identify the source of foodborne SE infections. In total, 57 SE isolates from five outbreaks (17 isolates, 5 isolates, 18 isolates, 8 isolates, and 9 isolates, respectively) were used for antimicrobial susceptibility testing, pulsed-field gel electrophoresis (PFGE), and multiple-locus variable-number tandem repeat analysis (MLVA). SE isolates from 2008 and 2009 were resistant to nalidixic acid, whereas SE isolates from 2010 were resistant to five antibiotics. Of the five outbreaks, outbreaks A, B, and D had identical PFGE-XbaI and PFGE-BlnI patterns, SEGX01.003 and SEGA26.001, respectively. Outbreak C had patterns SEGX01.011 and SEGA26.005, and outbreak E had patterns SEGX01.007 and SEGA26.007. However, MLVA profiles further distinguished the SE isolates from each outbreak into patterns SEGM.014 (outbreak A), SEGM.012 (outbreak B), SEGM.008 (outbreak C), SEGM.016 (outbreak D), and SEGM.015 (outbreak E). Among these five outbreaks, three outbreaks were presumed to be caused by the clonal SE isolates depending on PFGE pattern, but the MLVA results elucidated that these were caused by different SE isolates from the different origins. Therefore, for the epidemiological investigation or surveillance of SE foodborne diseases, both PFGE and MLVA should be used together.

Crosstalk between RNA silencing and RNA quality control in plants.

RNAs are pivotal molecules acting as messengers of genetic information and regulatory molecules for cellular development and survival. From birth to death, RNAs face constant cellular decision for the precise control of cellular function and activity. Most eukaryotic cells employ conserved machineries for RNA decay including RNA silencing and RNA quality control (RQC). In plants, RQC monitors endogenous RNAs and degrades aberrant and dysfunctional species, whereas RNA silencing promotes RNA degradation to repress the expression of selected endogenous RNAs or exogenous RNA derived from transgenes and virus. Interestingly, emerging evidences have indicated that RQC and RNA silencing interact with each by sharing target RNAs and regulatory components. Such interaction should be tightly organized for proper cellular survival. However, it is still elusive that how each machinery specifically recognizes target RNAs. In this review, we summarize recent advances on RNA silencing and RQC pathway and discuss potential mechanisms underlying the interaction between the two machineries. [BMB Reports 2023; 56(6): 321-325].