The HIF-1/glial TIM-3 axis controls inflammation-associated brain damage under hypoxia.

Inflammation is closely related to the extent of damage following cerebral ischaemia, and the targeting of this inflammation has emerged as a promising therapeutic strategy. Here, we present that hypoxia-induced glial T-cell immunoglobulin and mucin domain protein (TIM)-3 can function as a modulator that links inflammation and subsequent brain damage after ischaemia. We find that TIM-3 is highly expressed in hypoxic brain regions of a mouse cerebral hypoxia-ischaemia (H/I) model. TIM-3 is distinctively upregulated in activated microglia and astrocytes, brain resident immune cells, in a hypoxia-inducible factor (HIF)-1-dependent manner. Notably, blockade of TIM-3 markedly reduces infarct size, neuronal cell death, oedema formation and neutrophil infiltration in H/I mice. Hypoxia-triggered neutrophil migration and infarction are also decreased in HIF-1α-deficient mice. Moreover, functional neurological deficits after H/I are significantly improved in both anti-TIM-3-treated mice and myeloid-specific HIF-1α-deficient mice. Further understanding of these insights could serve as the basis for broadening the therapeutic scope against hypoxia-associated brain diseases

Reproductive and Hormonal Factors Associated with Fatty or Dense Breast Patterns among Korean Women

PURPOSE: Dense breasts have been suggested as a risk factor for breast cancer, but controversy still remains. This study evaluates the association of reproductive and hormonal factors with dense breasts among Korean women. MATERIALS AND METHODS: Using a cross-sectional design, 516 women were recruited and classified for breast density patterns as being either fatty or dense, using the Breast Imaging Reporting and Data System (BI-RADS) of the American College of Radiology. Univariate and multivariate logistic regression models were used for statistical analysis. RESULTS: In univariate logistic regression, older age, higher body mass index, older age at menarche, and oral contraceptive use were associated with more fatty breasts. On the contrary, longer duration of education, alcohol consumption, lower parity, menopause and use of hormone replacement therapy were associated with dense breasts. After adjustment, age and body mass index were inversely associated with breast density (p-value for trend <0.01, respectively), whereas nulliparous and premenopausal status were positively associated. Compared to women who had ≥2 children, nulliparous women had an 11.8-fold increase of dense breasts (p-value for trend <0.01). Compared to postmenopausal women, premenopausal women had 2.4-fold increase of dense breasts (odds ratio, 2.42; 95% confidence interval, 1.36 to 4.32). CONCLUSION: Young age, lower body mass index, lower parity, and premenopausal status were significantly associated with dense breasts in Koreaope

Comparative mapping, genomic structure, and expression analysis of eight pseudo-response regulator genes in Brassica rapa

Circadian clocks regulate plant growth and development in response to environmental factors. In this function, clocks influence the adaptation of species to changes in location or climate. Circadian-clock genes have been subject of intense study in models such as Arabidopsis thaliana but the results may not necessarily reflect clock functions in species with polyploid genomes, such as Brassica species, that include multiple copies of clock-related genes. The triplicate genome of Brassica rapa retains high sequence-level co-linearity with Arabidopsis genomes. In B. rapa we had previously identified five orthologs of the five known Arabidopsis pseudo-response regulator (PRR) genes that are key regulators of the circadian clock in this species. Three of these B. rapa genes, BrPRR1, BrPPR5, and BrPPR7, are present in two copies each in the B. rapa genome, for a total of eight B. rapa PRR (BrPRR) orthologs. We have now determined sequences and expression characteristics of the eight BrPRR genes and mapped their positions in the B. rapa genome. Although both members of each paralogous pair exhibited the same expression pattern, some variation in their gene structures was apparent. The BrPRR genes are tightly linked to several flowering genes. The knowledge about genome location, copy number variation and structural diversity of these B. rapa clock genes will improve our understanding of clock-related functions in this important crop. This will facilitate the development of Brassica crops for optimal growth in new environments and under changing conditions.This work was supported by grants from "Research Program for Agricultural Science & Technology Development (Project No. PJ907049)", National Academy of Agricultural Science and BioGreen 21 Program (project No. PJ008025), the Rural Development Administration, Republic of Korea.OAIID:oai:osos.snu.ac.kr:snu2012-01/102/0000027607/3SEQ:3PERF_CD:SNU2012-01EVAL_ITEM_CD:102USER_ID:0000027607ADJUST_YN:YEMP_ID:A075898DEPT_CD:517CITE_RATE:2.635FILENAME:2012-4-mol genet genomic-배추prr genes김진아.pdfDEPT_NM:식물생산과학부EMAIL:[email protected]_YN:YCONFIRM:

Expressed Sequence Tags Analysis and Design of Simple Sequence Repeats Markers from a Full-Length cDNA Library in Perilla frutescens (L.)

Perilla frutescens is valuable as a medicinal plant as well as a natural medicine and functional food. However, comparative genomics analyses of P. frutescens are limited due to a lack of gene annotations and characterization. A full-length cDNA library from P. frutescens leaves was constructed to identify functional gene clusters and probable EST-SSR markers via analysis of 1,056 expressed sequence tags. Unigene assembly was performed using basic local alignment search tool (BLAST) homology searches and annotated Gene Ontology (GO). A total of 18 simple sequence repeats (SSRs) were designed as primer pairs. This study is the first to report comparative genomics and EST-SSR markers from P. frutescens will help gene discovery and provide an important source for functional genomics and molecular genetic research in this interesting medicinal plant

Clinical Nomograms to Predict Stone-Free Rates after Shock-Wave Lithotripsy: Development and Internal-Validation

<div><p>Purpose</p><p>Shock-wave lithotripsy (SWL) is accepted as the first line treatment modality for uncomplicated upper urinary tract stones; however, validated prediction models with regards to stone-free rates (SFRs) are still needed. We aimed to develop nomograms predicting SFRs after the first and within the third session of SWL. Computed tomography (CT) information was also modeled for constructing nomograms.</p><p>Materials and Methods</p><p>From March 2006 to December 2013, 3028 patients were treated with SWL for ureter and renal stones at our three tertiary institutions. Four cohorts were constructed: Total-development, Total-validation, CT-development, and CT-validation cohorts. The nomograms were developed using multivariate logistic regression models with selected significant variables in a univariate logistic regression model. A C-index was used to assess the discrimination accuracy of nomograms and calibration plots were used to analyze the consistency of prediction.</p><p>Results</p><p>The SFR, after the first and within the third session, was 48.3% and 68.8%, respectively. Significant variables were sex, stone location, stone number, and maximal stone diameter in the Total-development cohort, and mean Hounsfield unit (HU) and grade of hydronephrosis (HN) were additional parameters in the CT-development cohort. The C-indices were 0.712 and 0.723 for after the first and within the third session of SWL in the Total-development cohort, and 0.755 and 0.756, in the CT-development cohort, respectively. The calibration plots showed good correspondences.</p><p>Conclusions</p><p>We constructed and validated nomograms to predict SFR after SWL. To the best of our knowledge, these are the first graphical nomograms to be modeled with CT information. These may be useful for patient counseling and treatment decision-making.</p></div

Baseline characteristics of the total cohort and each development cohort.

<p>Baseline characteristics of the total cohort and each development cohort.</p

Calibration plots for nomograms predicting stone-free rates after the first and within the third session of SWL with and without CT information.

<p>(A) Total-development cohort, (B) CT-development cohort.</p

Study flowchart for patient selection.

<p>Study flowchart for patient selection.</p

Pontin functions as an essential coactivator for Oct4-dependent lincRNA expression in mouse embryonic stem cells

The actions of transcription factors, chromatin modifiers and noncoding RNAs are crucial for the programming of cell states. Although the importance of various epigenetic machineries for controlling pluripotency of embryonic stem (ES) cells has been previously studied, how chromatin modifiers cooperate with specific transcription factors still remains largely elusive. Here, we find that Pontin chromatin remodelling factor plays an essential role as a coactivator for Oct4 for maintenance of pluripotency in mouse ES cells. Genome-wide analyses reveal that Pontin and Oct4 share a substantial set of target genes involved in ES cell maintenance. Intriguingly, we find that the Oct4-dependent coactivator function of Pontin extends to the transcription of large intergenic noncoding RNAs (lincRNAs) and in particular linc1253, a lineage programme repressing lincRNA, is a Pontin-dependent Oct4 target lincRNA. Together, our findings demonstrate that the Oct4-Pontin module plays critical roles in the regulation of genes involved in ES cell fate determination

The concordance index (c-index) yielded by AUC to evaluate the predictive discrimination of the nomograms.

<p>The concordance index (c-index) yielded by AUC to evaluate the predictive discrimination of the nomograms.</p