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Lymphoproliferative diseases (LPDs) of the ocular adnexa encompass the majority of orbital diseases and include reactive follicular hyperplasia (RFH), atypical lymphoid hyperplasia (ALH), and mucosa-associated lymphoid tissue lymphoma (MALToma). Lymphoid follicles (LFs) are usually observed during the histological examination of LPDs. Currently, because there is a lack of specific clinical signs and diagnostic immunohistochemical biomarkers, it is difficult for pathologists to distinguish MALToma from ocular RFH and ALH, which makes the clinical management of these conditions difficult. Here, we analyzed the clinical features of patients with ocular adnexal LPDs (n = 125) and investigated the structure of LFs in paraffin-embedded tissue samples using anti-CD23 and anti-IgD immunochemistry. We found that some clinical features including age, sex, and laterality were different among RFH, LFH, and MALToma. Additionally, immunohistochemistry revealed that the expression of IgD and CD23 was higher in RFH patients and decreased in patients with ALH and MALToma. Moreover, LFs in RFH were intact, whereas the structures of most LFs were disrupted in ALH. In MALToma specimens, few intact LFs were observed. In a further investigation, we combined the results for CD23/IgD immunohistochemistry and the structure of LFs to establish a scoring method for the differential diagnosis of LPDs. According to the BIOMED-2 protocol, we further detected IgH gene monoclonal rearrangement in 73 cases (35 RFH, 17 ALH, and 21 MALToma cases). The sensitivity of our scoring method, based on a comparison with the results of IgH gene monoclonal rearrangement detection, was 85.7% (18/21) for MALToma and 35.3% (6/17) for ALH. Our study provides a method that may be useful for the differential diagnosis of RFH, ALH, and MALToma. [ABSTRACT FROM AUTHOR]

Recent emerging data indicate that the increase in the expression and activity of the transforming growth factor beta 1 (Tgf-β1) signaling may have detrimental effect to mature articular cartilage of knee joints. However, there is no information about whether or not this is the case in condylar cartilages. The objective of this study is to investigate the protein expression and activity of Tgf-β1 signaling in degenerative condylar cartilages. We also investigate biological effects of the conditional deletion of transforming growth factor receptor type II (Tgfbr2) in condylar cartilage of adult mice after a partial discectomy. Two mouse models of osteoarthritis (OA) were used to examine protein expressions of Tgf-β1 and p-Smad2/3 in condylar cartilages at early degenerative stages. In addition, cartilage specific Tgfbr2-deficient adult mice were subjected to a partial discectomy. The morphological condition of condylar cartilages was evaluated in mice at 4 and 12 weeks after the surgery. We found that protein levels of Tgf-β1 and p-Smad2/3 were increased in the degenerative condylar cartilage of the mouse models. The conditional removal of Tgfbr2 in mature condylar cartilage significantly delayed the progressive progression of the cartilage degeneration induced by a partial discectomy. We conclude that the increase in the expression and activity of Tgf-β1 signaling may have detrimental effect to mature condylar cartilages. Therefore, inhibition of Tgf-β1 signaling may be able to protect condylar cartilages from being degraded in mature temporomandibular joints. [ABSTRACT FROM AUTHOR]

Browning of white adipose tissue (WAT) has been highlighted as a new possible therapeutic target for obesity, diabetes and lipid metabolic disorders, because WAT browning could increase energy expenditure and reduce adiposity. The new clusters of adipocytes that emerge with WAT browning have been named ‘beige’ or ‘brite’ adipocytes. Recent reports have indicated that the renin-angiotensin system (RAS) plays a role in various aspects of adipose tissue physiology and dysfunction. The biological effects of angiotensin II, a major component of RAS, are mediated by two receptor subtypes, angiotensin II type 1 receptor (AT1R) and type 2 receptor (AT2R). However, the functional roles of angiotensin II receptor subtypes in WAT browning have not been defined. Therefore, we examined whether deletion of angiotensin II receptor subtypes (AT1aR and AT2R) may affect white-to-beige fat conversion in vivo. AT1a receptor knockout (AT1aKO) mice exhibited increased appearance of multilocular lipid droplets and upregulation of thermogenic gene expression in inguinal white adipose tissue (iWAT) compared to wild-type (WT) mice. AT2 receptor-deleted mice did not show miniaturization of lipid droplets or alteration of thermogenic gene expression levels in iWAT. An in vitro experiment using adipose tissue-derived stem cells showed that deletion of the AT1a receptor resulted in suppression of adipocyte differentiation, with reduction in expression of thermogenic genes. These results indicate that deletion of the AT1a receptor might have some effects on the process of browning of WAT and that blockade of the AT1 receptor could be a therapeutic target for the treatment of metabolic disorders. [ABSTRACT FROM AUTHOR]

The article outlines ten simple rules regarding how to effectively run a statistical analysis. It suggests that statistical methods should enable data to answer scientific questions. It mentions that signals always come with noise wherein it makes statistical interferences possible. It notes that statistical models help link data to goals by shifting attention to theoretical quantities of interest.

C3 and TC-1 are the two model cell lines most commonly used in studies of vaccines and drugs against human papillomavirus (HPV) infection. Because C3 cells contain both the HPV16 E and L genes, but TC-1 cells contain only the HPV16 E genes, C3 cells are usually used as the model cell line in studies targeting the HPV16 L protein. However, expression of the L1 protein is difficult to detect in C3 cells using common methods. In our study, Short tandem repeat analysis (STR) was used to demonstrate that C3 cells are indeed derived from mice, PCR results show that HPV16 L1, E6 and E7 genes were detected in C3 genomic DNA, and RT-PCR results demonstrated that L1 transcription had occurred in C3 cells. However, the expression of C3 protein was not found in the results of western blot and immunohistochemistry (IHC). Growth and proliferation of C3 were inhibited by mice spleen lymphocytes that had been immunized with a vaccine against HPV16L1. The luciferase gene was integrated into C3 cells, and it was confirmed that addition of the exogenous gene had no effect on C3 cells by comparing cell growth and tumor formation with untransformed cells. Cells stably expressing luciferase (C3-luc) were screened and subcutaneously injected into the mice. Tumors became established and were observed using a Spectrum Pre-clinical in Vivo Imaging System. Tumor size of mice in the different groups at various time points was calculated by counting photons. The sensitivity of the animals to the vaccine was quantified by statistical comparison. Ten or 30 days following injection of the C3-luc cells, tumor size differed significantly between the PBS and vaccine groups, indicating that C3 cells were susceptible to vaccination even after tumors were formed in vivo. [ABSTRACT FROM AUTHOR]

In pharmaceutical sciences, a crucial step of the drug discovery process is the identification of drug-target interactions. However, only a small portion of the drug-target interactions have been experimentally validated, as the experimental validation is laborious and costly. To improve the drug discovery efficiency, there is a great need for the development of accurate computational approaches that can predict potential drug-target interactions to direct the experimental verification. In this paper, we propose a novel drug-target interaction prediction algorithm, namely neighborhood regularized logistic matrix factorization (NRLMF). Specifically, the proposed NRLMF method focuses on modeling the probability that a drug would interact with a target by logistic matrix factorization, where the properties of drugs and targets are represented by drug-specific and target-specific latent vectors, respectively. Moreover, NRLMF assigns higher importance levels to positive observations (i.e., the observed interacting drug-target pairs) than negative observations (i.e., the unknown pairs). Because the positive observations are already experimentally verified, they are usually more trustworthy. Furthermore, the local structure of the drug-target interaction data has also been exploited via neighborhood regularization to achieve better prediction accuracy. We conducted extensive experiments over four benchmark datasets, and NRLMF demonstrated its effectiveness compared with five state-of-the-art approaches. [ABSTRACT FROM AUTHOR]

Vav1, a guanine nucleotide exchange factor (GEF) for Rho family GTPases, is a hematopoietic protein involved in a variety of cellular events. In recent years, aberrant expression of Vav1 has been reported in non-hematopoietic cancers including human breast cancer. It remains to be answered how Vav1 is expressed and what Vav1 does in its non-resident tissues. In this study, we aimed to explore the mechanism for Vav1 expression in breast cancer cells in correlation with estrogen-ER pathway. We not only verified the ectopic expression of Vav1 in human breast cancer cell lines, but also observed that Vav1 expression was induced by 17β-estradiol (E2), a typical estrogen receptor (ER) ligand, in ER-positive cell lines. On the other hand, Tamoxifen, a selective estrogen receptor modulator (SERM), and ICI 182,780, an ER antagonist, suppressed the expression of Vav1. The estrogen receptor modulating Vav1 expression was identified to be α form, not β. Furthermore, treatment of E2 increased the transcription of vav1 gene by enhancing the promoter activity, though there was no recognizable estrogen response element (ERE). Nevertheless, two regions at the vav1 gene promoter were defined to be responsible for E2-induced activation of vav1 promoter. Chromatin immunoprecipitation (ChIP) and co-immunoprecipitation (Co-IP) analyses suggested that ERα might access to the vav1 promoter via interacting with transcription factors, c-Myb and ELF-1. Consequently, the enhanced expression of Vav1 led to the elevation of Cyclin D1 and the progression of cell cycle. The present study implies that estrogen-ER modulates the transcription and expression of Vav1, which may contribute to the proliferation of cancerous cells. [ABSTRACT FROM AUTHOR]

The microRNA319 (miR319) family is conserved among diverse plant species. In rice (Oryza sativa L.), the miR319 gene family is comprised of two members, Osa-miR319a and Osa-miR319b. We found that overexpressing Osa-miR319b in rice resulted in wider leaf blades and delayed development. Here, we focused on the biological function and potential molecular mechanism of the Osa-miR319b gene in response to cold stress in rice. The expression of Osa-miR319b was down-regulated by cold stress, and the overexpression of Osa-miR319b led to an enhanced tolerance to cold stress, as evidenced by higher survival rates and proline content. Also, the expression of a handful of cold stress responsive genes, such as DREB1A/B/C, DREB2A, TPP1/2, was increased in Osa-miR319b transgenic lines. Furthermore, we demonstrated the nuclear localization of the transcription factors, OsPCF6 and OsTCP21, which may be Osa-miR319b-targeted genes. We also showed that OsPCF6 and OsTCP21 expression was largely induced by cold stress, and the degree of induction was obviously repressed in plants overexpressing Osa-miR319b. As expected, the down-regulation of OsPCF6 and OsTCP21 resulted in enhanced tolerance to cold stress, partially by modifying active oxygen scavenging. Taken together, our findings suggest that Osa-miR319b plays an important role in plant response to cold stress, maybe by targeting OsPCF6 and OsTCP21. [ABSTRACT FROM AUTHOR]