Search for Boosted Dark Matter in COSINE-100.

We search for energetic electron recoil signals induced by boosted dark matter (BDM) from the galactic center using the COSINE-100 array of NaI(Tl) crystal detectors at the Yangyang Underground Laboratory. The signal would be an excess of events with energies above 4 MeV over the well-understood background. Because no excess of events are observed in a 97.7 kg·yr exposure, we set limits on BDM interactions under a variety of hypotheses. Notably, we explored the dark photon parameter space, leading to competitive limits compared to direct dark photon search experiments, particularly for dark photon masses below 4 MeV and considering the invisible decay mode. Furthermore, by comparing our results with a previous BDM search conducted by the Super-Kamionkande experiment, we found that the COSINE-100 detector has advantages in searching for low-mass dark matter. This analysis demonstrates the potential of the COSINE-100 detector to search for MeV electron recoil signals produced by the dark sector particle interactions.

Genetic origin, admixture and population history of aurochs (Bos primigenius) and primitive European cattle.

This corrects the article DOI: 10.1038/hdy.2016.79.

Genetic origin, admixture and population history of aurochs (Bos primigenius) and primitive European cattle.

The domestication of taurine cattle initiated ~10 000 years ago in the Near East from a wild aurochs (Bos primigenius) population followed by their dispersal through migration of agriculturalists to Europe. Although gene flow from wild aurochs still present at the time of this early dispersion is still debated, some of the extant primitive cattle populations are believed to possess the aurochs-like primitive features. In this study, we use genome-wide single nucleotide polymorphisms to assess relationship, admixture patterns and demographic history of an ancient aurochs sample and European cattle populations, several of which have primitive features and are suitable for extensive management. The principal component analysis, the model-based clustering and a distance-based network analysis support previous works suggesting different histories for north-western and southern European cattle. Population admixture analysis indicates a zebu gene flow in the Balkan and Italian Podolic cattle populations. Our analysis supports the previous report of gene flow between British and Irish primitive cattle populations and local aurochs. In addition, we show evidence of aurochs gene flow in the Iberian cattle populations indicating wide geographical distribution of the aurochs. Runs of homozygosity (ROH) reveal that demographic processes like genetic isolation and breed formation have contributed to genomic variations of European cattle populations. The ROH also indicate recent inbreeding in southern European cattle populations. We conclude that in addition to factors such as ancient human migrations, isolation by distance and cross-breeding, gene flow between domestic and wild-cattle populations also has shaped genomic composition of European cattle populations.

Performance of PCR-REBA assay for screening and identifying pathogens directly in whole blood of patients with suspected sepsis.

AIMS: Rapid and accurate identification of a broad range of bacterial and fungal pathogens is the key to successful management of patients with bloodstream infections (BSIs). The aim of this study was to evaluate the diagnostic performance of PCR-REBA Sepsis-ID test for the detection of BSIs pathogens. METHODS AND RESULTS: EDTA anticoagulated blood for REBA Sepsis-ID assay and blood culture samples from 882 patients with suspected sepsis were simultaneously collected from January 2014 to December 2014. Of 115 patients with positive blood culture, 64 (55·7%) were Gram-positive bacteria, 35 (30·4%) were Gram-negative bacteria, 1 (0·9%) was Candida albicans and 15 (13·0%) were polymicrobial infections. The concordance rate of blood culture system and PCR-REBA Sepsis ID test was 83·0% (95% confidence interval (CI), 79·8-84·8, P < 0·0001). Compared to blood culture, the diagnosis of bacterial proven pathogens by PCR-REBA revealed 81·0% (95% CI, 73·4-86·8, P < 0·0001) sensitivity, 83·4% (95% CI, 80·0-85·4, P < 0·0001) specificity, 80·9% positive and 95·8% negative predictive values respectively. In 10 cases with PCR-REBA positive but blood culture negative, the levels of C-reactive protein were significantly elevated 18·5 mg dl(-1) (SD ± 13·7, 95% CI 1·8-41·9) and six cases has been proven to have pathogen by bacterial 16S rRNA sequencing. Although the sensitivity for pathogen identification was not significantly different between PCR-REBA and blood culture (P = 0·5), the combination of the two methods resulted in a significantly increased rate of pathogen detection (P = 0·002). The results of this study suggested that PCR-REBA may be helpful when added to blood culture in the diagnosis and management of sepsis. CONCLUSIONS: PCR-REBA Sepsis-ID test is a useful tool for the rapid identification of pathogenic isolates in whole blood to ensure adequate treatment for the causative agents of BSIs. SIGNIFICANCE AND IMPACT OF THE STUDY: Although the cost of molecular diagnostic assays is higher than the cost of conventional methods, clinical and economic cost-benefit analysis is still needed. PCR-REBA may provide essential information for accelerating therapeutic decisions to ensure effective treatment with antibiotics in the acute phase of pathogen infection.

Comparative effect of topical silicone gel and topical tretinoin cream for the prevention of hypertrophic scar and keloid formation and the improvement of scars.

BACKGROUND: Numerous modalities have been used to treat keloids and hypertrophic scars; however, optimal treatment has not yet been established. Therefore, prevention is the mainstay. Recently, silicone gel and tretinoin cream have been shown to be useful for the prevention of hypertrophic scars and keloids. However, there has been no comparative study of the two topical agents thus far. OBJECTIVE: To determine and compare the effectiveness of silicone gel and tretinoin cream for the prevention of hypertrophic scars and keloids resulting from postoperative wounds and for scar improvement. METHOD: This study included 26 patients with 44 different wounds. The postoperative wounds were divided into two treatment groups and one control group. The patients in the first and second treatment group applied silicone gel and tretinoin cream, respectively, twice a day on their wounds after their stitches were removed. In contrast, the control group patients did not apply anything. We used the Modified Vancouver Scar Scale to quantitatively examine the effectiveness of silicone gel and tretinoin cream just after stitches removal, and at 4, 8, 12 and 24 weeks after removal of the stitches. RESULTS: The silicone gel and tretinoin cream effectively prevented hypertrophic scars and keloids and improved scar effects in the two treatment groups compared with those in the control group. However, no significant difference was noted between the two treatment groups. CONCLUSION: To prevent hypertrophic scars and keloids and improve scars after surgery, application of a silicone gel or a tretinoin cream to the wounds is needed.

Clinical characteristics and risk of melanoma development from giant congenital melanocytic naevi in Korea: a nationwide retrospective study.

BACKGROUND: Giant congenital melanocytic naevi (GCMN) are known risk factors for the development of melanoma. However, melanoma risk among Asians is rarely evaluated. OBJECTIVES: To evaluate the clinical characteristics and risk of melanoma development from GCMN in Koreans, we performed a nationwide retrospective cohort study in Korea. GCMN were defined as those comprising ≥5% body surface area in children or measuring ≥20cm in adults. METHODS: In total, 131 patients with GCMN were enrolled, with a mean age of 10·3years (range: birth-70years). RESULTS: The posterior trunk was the most common site (67, 51·1%), followed by lateral trunk, anterior trunk, legs, both anterior and posterior trunk, buttocks, and arms. Satellite naevi were present in 69 cases (52·7%), and axial areas were more commonly involved in patients with satellite naevi than in those without satellite lesions. Atypical features such as rete ridge elongation and bridges were seen, and, among these, pagetoid spread and ballooning cell changes were more common in patients <4years old. Proliferative nodules were found in three cases. Melanomas had developed in three of 131 patients (2·3%; a 6-year-old girl, a 14-year-old girl and a 70-year-old man), and the incidence rate was 990 per 100000 person-years. Melanomas in these three patients consisted of two cutaneous melanomas and one extracutaneous meningeal melanoma. CONCLUSIONS: We should be aware of melanoma development from GCMN, and lifelong follow-up is required due to the risk of melanoma arising in GCMN.

Association of sequence variants in CKM (creatine kinase, muscle) and COX4I2 (cytochrome c oxidase, subunit 4, isoform 2) genes with racing performance in Thoroughbred horses.

REASONS FOR PERFORMING STUDY: The wild progenitors of the domestic horse were subject to natural selection for speed and stamina for millennia. Uniquely, this process has been augmented in Thoroughbreds, which have undergone at least 3 centuries of intense artificial selection for athletic phenotypes. While the phenotypic adaptations to exercise are well described, only a small number of the underlying genetic variants contributing to these phenotypes have been reported. OBJECTIVES: A panel of candidate performance-related genes was examined for DNA sequence variation in Thoroughbreds and the association with racecourse performance investigated. MATERIALS AND METHODS: Eighteen candidate genes were chosen for their putative roles in exercise. Re-sequencing in Thoroughbred samples was successful for primer sets in 13 of these genes. SNPs identified in this study and from the EquCab2.0 SNP database were genotyped in 2 sets of Thoroughbred samples (n = 150 and 148) and a series of population-based case-control investigations were performed by separating the samples into discrete cohorts on the basis of retrospective racecourse performance. RESULTS: Twenty novel SNPs were detected in 3 genes: ACTN3, CKM and COX4I2. Genotype frequency distributions for 3 SNPs in CKM and COX4I2 were significantly (P < 0.05) different between elite Thoroughbreds and racehorses that had never won a race. These associations were not validated when an additional (n = 130) independent set of samples was genotyped, but when analyses included all samples (n = 278) the significance of association at COX4I2 g.22684390C > T was confirmed (P < 0.02). CONCLUSIONS: While molecular genetic information has the potential to become a powerful tool to make improved decisions in horse industries, it is vital that rigour is applied to studies generating these data and that adequate and appropriate sample sets, particularly for independent replication, are used.

Technical note: High fidelity of whole-genome amplified sheep (Ovis aries) deoxyribonucleic acid using a high-density single nucleotide polymorphism array-based genotyping platform.

Advances in high-throughput genotyping technologies have afforded researchers the opportunity to study ever-increasing numbers of SNP in animal genomes. However, many studies encounter difficulties in obtaining sufficient quantities of high-quality DNA for such analyses, particularly when the source biological material is limited or degraded. The recent development of in vitro whole-genome amplification approaches has permitted researchers to circumvent these challenges by increasing the amount of usable DNA in normally small-quantity samples. Here, we assess the performance of whole-genome amplification products generated from ovine genomic DNA using a high-throughput SNP genotyping platform, the newly developed Illumina ovineSNP50 BeadChip. Our results demonstrate a high genotype call rate for conventional genomic DNA and whole-genome amplified genomic DNA. The data also reveal an exceptionally high concordance rate ( > or = 99%) between the genotypes generated from whole-genome amplified products and their conventional genomic DNA counterparts. This study supports the use of whole-genome amplification as a viable solution for the analysis of high-density SNP genotypic data using compromised or limited starting material.

A catalogue of validated single nucleotide polymorphisms in bovine orthologs of mammalian imprinted genes and associations with beef production traits.

Genetic (or 'genomic') imprinting, a feature of approximately 100 mammalian genes, results in monoallelic expression from one of the two parentally inherited chromosomes. To date, most studies have been directed on imprinted genes in murine or human models; however, there is burgeoning interest in the effects of imprinted genes in domestic livestock species. In particular, attention has focused on imprinted genes that influence foetal growth and development and that are associated with several economically important production traits in cattle, sheep and pigs. We have re-sequenced regions in 20 candidate bovine imprinted genes in order to validate single nucleotide polymorphisms (SNPs) that may influence important production traits in cattle. Putative SNPs detected via re-sequencing were subsequently re-formatted for high-throughput SNP genotyping in 185 cattle samples comprising 138 performance-tested European Bos taurus (all Limousin bulls), 29 African B. taurus and 18 Indian B. indicus samples. Analysis of the resulting genotypic data identified 117 validated SNPs. Preliminary genotype-phenotype association analyses using 83 SNPs that were polymorphic in the Limousin samples with minor allele frequencies ⩾0.05 revealed significant associations between two candidate bovine imprinted genes and a range of important beef production traits: average daily gain, average feed intake, live weight, feed conversion ratio, residual feed intake and residual gain. These genes were the Ras protein-specific guanine nucleotide releasing factor gene (RASGRF1) and the zinc finger, imprinted 2 gene (ZIM2). Despite the relatively small sample size used in these analyses, the observed associations with production traits are supported by the purported biological function of the RASGRF1 and ZIM2 gene products. These results support the hypothesis that imprinted genes contribute significantly to important complex production traits in cattle. Furthermore, these SNPs may be usefully incorporated into future marker-assisted and genomic selection breeding schemes.

Gene expression profiling of the host response to Mycobacterium bovis infection in cattle.

Bovine tuberculosis (BTB), caused by Mycobacterium bovis, continues to pose a threat to livestock worldwide and, as a zoonotic infection, also has serious implications for human health. The implementation of comprehensive surveillance programmes to detect BTB has been successful in reducing the incidence of infection in many countries, yet BTB has remained recalcitrant to eradication in several EU states, particularly in Ireland and the UK. There are well-recognized limitations in the use of the current diagnostics to detect all infected animals and this has led to renewed efforts to uncover novel diagnostic biomarkers that may serve to enhance the performance of the tests. Studies of single immunological parameters have so far been unable to unlock the complexities of the immune response to mycobacterial infection. However, the development of high-throughput methods including pan-genomic gene expression technologies such as DNA microarrays has facilitated the simultaneous identification and analysis of thousands of genes and their interactions during the immune response. In addition, the application of these new genomic technologies to BTB has identified pathogen-associated immune response signatures of host infection. The objective of these investigations is to understand the changing profile of immune responses throughout the course of infection and to identify biomarkers for sensitive diagnosis, particularly during the early stages of infection. Transcriptional profiling via microarray and more recently via next-generation sequencing technologies may lead to the development of specific and sensitive diagnostics for M. bovis infection and will enhance the prospect of eradication of tuberculosis from cattle populations.

The measurement of 129I for the cement and the paraffin solidified low and intermediate level wastes (LILWs), spent resin or evaporated bottom from the pressurized water reactor (PWR) nuclear power plants.

In this paper a relatively simple and low cost analysis procedure to apply to a routine analysis of (129)I in low and intermediate level radioactive wastes (LILWs), cement and paraffin solidified evaporated bottom and spent resin, which are produced from nuclear power plants (NPPs), pressurized water reactors (PWR), is presented. The (129)I is separated from other nuclides in LILWs using an anion exchange adsorption and solvent extraction by controlling the oxidation and reduction state and is then precipitated as silver iodide for counting the beta activity with a low background gas proportional counter (GPC). The counting efficiency of GPC was varied from 4% to 8% and it was reversely proportional to the weight of AgI by a self absorption of the beta activity. Compared to a higher pH, the chemical recovery of iodide as AgI was lowered at pH 4. It was found that the chemical recovery of iodide for the cement powder showed a lower trend by increasing the cement powder weight, but it was not affected for the paraffin sample. In this experiment, the overall chemical recovery yield of the cement and paraffin solidified LILW samples and the average weight of them were 67+/-3% and 5.43+/-0.53 g, 70+/-7% and 10.40+/-1.60 g, respectively. And the minimum detectable activity (MDA) of (129)I for the cement and paraffin solidified LILW samples was calculated as 0.070 and 0.036 Bq/g, respectively. Among the analyzed cement solidified LILW samples, (129)I activity concentration of four samples was slightly higher than the MDA and their ranges were 0.076-0.114 Bq/g. Also of the analyzed paraffin solidified LILW samples, five samples contained a little higher (129)I activity concentration than the MDA and their ranges were 0.036-0.107 Bq/g.

Mitochondrial DNA sequence diversity in extant Irish horse populations and in ancient horses.

Equine mitochondrial DNA sequence variation was investigated in three indigenous Irish horse populations (Irish Draught Horse, Kerry Bog Pony and Connemara Pony) and, for context, in 69 other horse populations. There was no evidence of Irish Draught Horse or Connemara Pony sequence clustering, although the majority of Irish Draught Horse sequences (47%) were assigned to haplogroup D. Conversely, 31% of the Kerry Bog Pony sequences were assigned to the rare haplogroup E. In addition to the extant population analyses, ancient DNA sequences were generated from three out of four Irish archaeological specimens, all of which were assigned to haplogroup A.

Comparative RNA expression analyses from small-scale, single-donor platelet samples.

BACKGROUND: Comparisons of platelet RNAs could provide crucial information on platelet function, thrombopoiesis and the etiology of megakaryocyte (MK) or platelet disorders. OBJECTIVES: We developed a method for stringent purification of platelets from small blood samples from single donors. Purity of the platelet preparations was verified by an RT-PCR assay. We tested three methods to identify the differences in RNA between platelet sources. METHODS: Differential hybridization to cDNA macro-arrays and suppressive-subtractive hybridization PCR (SSH-PCR) were used to compare RNAs from normal platelets to those from a Bernard-Soulier syndrome (BSS) patient. Affymetrix GeneChip U133 plus 2.0 arrays were used to compare male and female platelet RNAs. RESULTS: Macroarrays identified approximately 7500 platelet transcripts, but failed to identify differentially expressed transcripts with confidence. SSH-PCR produced libraries almost exclusively of mitochondrial-derived transcripts, but included nuclear-encoded genes that could not be confirmed by immunoblotting of normal and BSS platelet lysates. The Affymetrix platform gave reproducible profiles from our small-scale purified platelet preparations, whereas a partially purified platelet preparation produced a drastically skewed transcript profile. The microarray analysis identified the heparanase precursor transcript as overexpressed in female platelets, and we observed variable yet consistently higher levels of heparanase protein in female platelets compared with male platelets in four independent donor pairs. CONCLUSIONS: This demonstrates for the first time that differential platelet transcript levels can identify changes in expression level of platelet proteins. Combined with our small-scale platelet preparation method, this establishes a system to compare platelets from the limited clinical sources to help elucidate molecular bases for platelet or megakaryocyte pathologies.

Management of Meloidogyne incognita on tomato by root-dip treatment in culture filtrate of the blue-green alga, Microcoleus vaginatus.

The nematicidal potential of culture filtrates of the blue-green alga, Microcoleus vaginatus (Cyanobacterium) was tested against Meloidogyne incognita on tomato in pots under greenhouse conditions. Prior to the transplantation of tomato seedling, roots were dipped in different concentrations (0.2%, 0.5%, 1%, 2%, 10%, 50% and 100%) of culture filtrate of M. vaginatus for 30 min. Root-dip treatment reduced the root galling and final population of M. incognita and increased vegetative growth of plants and root-mass production compared with the control. The beneficial effect of root-dip treatment increased with the increase in the concentration of culture filtrate. Root galling and final nematode populations were reduced by 65.9% and 97.5%, respectively when treated at the highest concentration.

Integration of proteomics and genomics in platelets: a profile of platelet proteins and platelet-specific genes.

Platelets, while anucleate, contain RNA, some of which is translated into protein upon activation. Hypothesising that the platelet proteome is reflected in the transcriptome, we identified 82 proteins secreted from activated platelets and compared these, as well as published proteomic data, to the transcriptional profile. We also compared the transcriptome of platelets to other tissues to identify platelet-specific genes and used ontology to determine gene categories over-represented in platelets. RNA was isolated from highly pure platelet preparations for hybridization to Affymetrix oligonucleotide arrays. We identified 2,928 distinct messages as being present in platelets. The platelet transcriptome was compared with the proteome by relating both to UniGene clusters. Platelet proteomic data correlated well with the transcriptome, with 69% of secreted proteins detectable at the mRNA level, and similar concordance was obtained using two published datasets. While many of the most abundant mRNAs are for known platelet proteins, messages were detected for proteins not previously reported in platelets. Some of these may represent residual megakaryocyte messages; however, proteomic analysis confirmed the expression of many previously unreported genes in platelets. Transcripts for well-described platelet proteins are among the most platelet-specific messages. Ontological categories related to signal transduction, receptors, ion channels, and membranes are over-represented in platelets, while categories involved in protein synthesis are depleted. Despite the absence of gene transcription, the platelet proteome is mirrored in the transcriptome. Conversely, transcriptional analysis predicts the presence of novel proteins in the platelet. Transcriptional analysis is relevant to platelet biology, providing insights into platelet function and the mechanisms of platelet disorders.

Feasibility and utility of microsatellite markers in archaeological cattle remains from a Viking Age settlement in Dublin.

Nineteen cattle bones from the Viking 10th and early 11th century levels in Dublin were assessed for presence of reliable genotypes from three autosomal markers. Due to the good preservational condition of the samples, it was possible to amplify and type at least two out of three of the microsatellite markers (CSRM60, HEL1 and ILSTS001) in 11 specimens. Full three-loci genotypes were obtained from a subset of seven of these samples. A comparative analysis was performed using data from the same three markers in 11 extant British, Irish and Nordic cattle breeds. Although the medieval remains displayed lower levels of diversity than the modern European breeds, the results fit within the ranges obtained from the extant populations. The results indicate a probable origin for the ancient Irish cattle as the remains group significantly more closely with breeds from the British Isles than with those from Scandinavia. The data collected indicate that microsatellites may be useful for the further study of ancient cattle.

Srg3, a mouse homolog of yeast SWI3, is essential for early embryogenesis and involved in brain development.

Srg3 (SWI3-related gene product) is a mouse homolog of yeast SWI3, Drosophila melanogaster MOIRA (also named MOR/BAP155), and human BAF155 and is known as a core subunit of SWI/SNF complex. This complex is involved in the chromatin remodeling required for the regulation of transcriptional processes associated with development, cellular differentiation, and proliferation. We generated mice with a null mutation in the Srg3 locus to examine its function in vivo. Homozygous mutants develop in the early implantation stage but undergo rapid degeneration thereafter. An in vitro outgrowth study revealed that mutant blastocysts hatch, adhere, and form a layer of trophoblast giant cells, but the inner cell mass degenerates after prolonged culture. Interestingly, about 20% of heterozygous mutant embryos display defects in brain development with abnormal organization of the brain, a condition known as exencephaly. Histological examination suggests that exencephaly is caused by the failure in neural fold elevation, resulting in severe brain malformation. Our findings demonstrate that Srg3 is essential for early embryogenesis and plays an important role in the brain development of mice.

Epidemiologic and clinical survey of Behcet's disease in Korea: the first multicenter study.

The prevalence of Behcet's disease is the highest in the East Asian and the Mediterranean countries. Behcet's disease is also distributed in the Asian countries, but the nationwide survey has not been performed in Korea yet. The Korean Study Group for Behcet's Disease, founded in 1999, conducted a multicenter, retrospective survey on epidemiologic and clinical features of the patients with Behcet's disease from 20 hospitals around the nation from 1997 to 1999. Of 3,497 patients, 1,527 were classified into complete or incomplete type of Behcet's disease according to the revised Shimizu's classification. The sex ratio was 1:1.75 with the female predominance. Geographical distribution showed the highest frequency in Seoul (38.5%). Clinically, 98.8% had oral ulcers, 83.2% had genital ulcers, 84.3% had skin lesions and 50.9% had ocular lesions. As for the minor clinical manifestations, articular symptoms were the most frequent. The pathergy test showed positive in 15.4% of patients and revealed a higher positive rate in males (20.2%) than in females (12.7%). In conclusion, we performed the first multicenter study on Behcet's disease in Korea and revealed the female predominance, higher frequency of ocular lesions, and lower positivity of pathergy test in the patients.

Progesterone together with estrogen attenuates homologous upregulation of gonadotropin-releasing hormone receptor mRNA in primary cultured rat pituitary cells.

In a previous study, we clearly demonstrated that an application of gonadotropin-releasing hormone (GnRH) to cultured rat pituitary cells increased the expression of GnRH receptor (GnRH-R) mRNA through transcriptional activation of GnRH-R gene rather than suppression of the turnover rate of GnRH-R mRNA. Along with GnRH, gonadal steroids seem to be an important regulator for GnRH-R expression in the pituitary gland. Recent in vivo studies reported that an application of gonadal steroids to gonadectomized animals modulated GnRH-R mRNA expression in the pituitary gland. However, it has not been clearly understood whether steroids may act directly at the pituitary or indirectly via modulation of hypothalamic GnRH release. Therefore, we assessed the effects of estrogen and progesterone on GnRH-R mRNA expression in primary cultured female rat pituitary cells. Neither estradiol nor progesterone modulates the basal expression of GnRH-R mRNA in primary cultured pituitary cells. When cultured pituitary cells were exposed to different doses of estradiol in combination with GnRH (0.2 nM), the GnRH-stimulated increment of GnRH-R mRNA expression was not significantly changed by estradiol at any given doses. However, when different doses of progesterone were added to primary cultured pituitary cells in combination with GnRH (0.2 nM), GnRH-induced increases in GnRH-R mRNA levels were reduced in a dose-related manner, showing a significant reduction at 100 nM progesterone. Furthermore, the addition of estradiol reinforced the suppressive effect of progesterone on the homologous upregulation of GnRH-R mRNA expression. Collectively, our results clearly demonstrated that progesterone directly attenuates the homologous upregulation of GnRH-R mRNA expression at the pituitary level, and that estradiol potentiates the effect of progesterone.

Notch1 confers a resistance to glucocorticoid-induced apoptosis on developing thymocytes by down-regulating SRG3 expression.

We previously have reported that SRG3 is required for glucocorticoid (GC)-induced apoptosis in the S49.1 thymoma cell line. Activation of Notch1 was shown to induce GC resistance in thymocytes. However, the specific downstream target of Notch1 that confers GC resistance on thymocytes is currently unknown. We found that the expression level of SRG3 was critical in determining GC sensitivity in developing thymocytes. The expression of SRG3 also was down-regulated by the activated form of Notch1 (NotchIC). The promoter activity of the SRG3 gene also was down-regulated by NotchIC. Expression of transgenic SRG3 resulted in the restoration of GC sensitivity in thymocytes expressing transgenic Notch1. These results suggest that SRG3 is the downstream target of Notch1 in regulating GC sensitivity of thymocytes.