Germ cell-specific gene 1 targets testis-specific poly(A) polymerase to the endoplasmic reticulum through protein–protein interactions

AbstractTestis-specific poly(A) polymerase (TPAP) is a cytoplasmic poly(A) polymerase that is highly expressed in round spermatids. We identified germ cell-specific gene 1 (GSG1) as a TPAP interaction partner protein using yeast two-hybrid and coimmunoprecipitation assays. Subcellular fractionation analysis showed that GSG1 is exclusively localized in the endoplasmic reticulum (ER) of mouse testis where TPAP is also present. In NIH3T3 cells cotransfected with TPAP and GSG1, both proteins colocalize in the ER. Moreover, expression of GSG1 stimulates TPAP targeting to the ER, suggesting that interactions between the two proteins lead to the redistribution of TPAP from the cytosol to the ER.Structured summaryMINT-6168263:Gsg1 (uniprotkb:Q8R1W2), TPAP (uniprotkb:Q9WVP6) and Calmegin (uniprotkb:P52194) colocalize (MI:0403) by cosedimentation (MI:0027)MINT-6168204, MINT-6168178:Gsg1 (uniprotkb:Q8R1W2) and TPAP (uniprotkb:Q9WVP6) colocalize (MI:0403) by fluorescence microscopy (MI:0416)MINT-6167930:Gsg1 (uniprotkb:Q8R1W2) physically interacts (MI:0218) with TPAP (uniprotkb:Q9WVP6) by two-hybrid (MI:0018)MINT-6168112, MINT-6168011, MINT-6168054:Gsg1 (uniprotkb:Q8R1W2) physically interacts (MI:0218) with TPAP (uniprotkb:Q9WVP6) by coimmunoprecipitation (MI:0019)MINT-61668069, MINT-6168101:Gsg1 (uniprotkb:Q8R1W2) physically interacts (MI:0218) with TPAP (uniprotkb:Q9WVP6) by pull-down (MI:0096)MINT-6168218:Gsg1 (uniprotkb:Q8R1W2) and GRP78 (uniprotkb:P20029) colocalize (MI:0403) by fluorescence microscopy (MI:0416)MINT-6168381:TPAP (uniprotkb:Q9WVP6) and GRP78 (uniprotkb:P20029) colocalize (MI:0403) by fluorescence microscopy (MI:0416

Factors affecting advance directives completion among older adults in Korea

ObjectiveAdvance directives (ADs) provide an opportunity for patients to enhance the quality of their end-of-life care and prepare for a dignified death by deciding treatment plans. The purpose of this study was to explore the multiple factors that influence the advance directives completion among older adults in South Korea.MethodsThis was a secondary analysis of a cross-sectional study of 9,920 older adults. The differences in ADs based on subjects’ sociodemographic characteristics, health-related characteristics, and attitude toward death were tested using the chi-squared and t-test. A multinomial logistic regression model was used to identify the influencing factor of ADs.ResultsThe number of chronic diseases, number of prescribed medications, depression, insomnia, suicide intention, and hearing, vision, or chewing discomfort were higher in the ADs group compared to the non-ADs group. The influencing factors of the signing of ADs included men sex, higher education level, exercise, death preparation education, lower awareness of dying-well, and experience of fracture.ConclusionInformation dissemination regarding ADs should be promoted and relevant authorities should consider multiple options to improve the physical and psychological health of older adults, as well as their attitude toward death to increase the ADs completion rate

Factors Affecting the Perception of Importance and Practice of Patient Safety Management among Hospital Employees in Korea

SummaryPurposeThe study was undertaken to identify factors affecting perception of the importance and practice of patient safety management (PSM) among hospital employees in Korea.MethodsThis study was conducted using a descriptive design and a self-report questionnaire. Two hundred and eighty employees were recruited from three hospitals using a convenience sampling method. Measures were perception of the importance, practice, and characteristics of PSM. Data were analyzed using descriptive statistics including t test, one-way analysis of variance, Pearson's correlation analysis, and multiple regression.ResultsFactors affecting perception of the importance of PSM were whether hospital employees were in contact with patients while on duty, weekly working hours, education on PSM, and perceived adequacy of PSM system construction. Factors affecting the practice of PSM were perceived adequacy of work load, perceived adequacy of PSM system construction and perception of its importance.ConclusionThe findings of this study indicate a need for developing strategies to improve perception of the importance and practice of PSM among all hospital employees, and provide a reference for future experimental studies

ERK is a novel regulatory kinase for poly(A) polymerase

Poly(A) polymerase (PAP), which adds poly(A) tails to the 3′ end of mRNA, can be phosphorylated at several sites in the C-terminal domain. Phosphorylation often mediates regulation by extracellular stimuli, suggesting PAP may be regulated by such stimuli. In this study, we found that phosphorylation of PAP was increased upon growth stimulation and that the mitogen-activated protein kinase ERK was responsible for the increase in phosphorylation. We identified serine 537 of PAP as a unique phosphorylation site by ERK. PAP phosphorylation of serine 537 by ERK increased its nonspecific polyadenylation activity in vitro. This PAP activity was also activated by stimulation of ERK with phorbol-12-myristate-13-acetate in vivo. These data suggest that ERK is a novel regulatory kinase for PAP and further, that PAP activity could be regulated by extracellular stimuli through an ERK-dependent signaling pathway(s)

Timarete posteria, a new cirratulid species from Korea (Annelida, Polychaeta, Cirratulidae)

A new cirratulid species, Timarete posteria sp. n., is described from the intertidal habitats of the eastern coast of South Korea. The new species is closely related to Timarete luxuriosa (Moore, 1904) from southern California based on morphological similarity of the branchial and tentacular finalents and the noto- and neuropodial spines. However, T. posteria sp. n. differs from the latter based on the following characteristics: 1) evenly divided peristomium into three annulations; 2) 2–4 neuropodial spines originating in the posterior chaetigers alternated by a few capillaries; and 3) complete shift in branchial finalents located about one-third between the notopodium and the dorsal midline. The new species has a methyl green staining pattern (MGSP) distinct from other Timarete species. Detailed description and illustrations of the new species are provided with molecular information based on the partial sequences of the mitochondrial cytochrome c oxidase subunit I (COI) and 16S ribosomal RNA (16S). This study also includes a key and discussion of known Timarete species from East Asia

Dysfunction of 67-kDa Laminin Receptor Disrupts BBB Integrity via Impaired Dystrophin/AQP4 Complex and p38 MAPK/VEGF Activation Following Status Epilepticus

Status epilepticus (SE, a prolonged seizure activity) impairs brain-blood barrier (BBB) integrity, which results in secondary complications following SE. The non-integrin 67-kDa laminin receptor (67-kDa LR) plays a role in cell adherence to laminin (a major glycoprotein component in basement membrane), and participates laminin-mediated signaling pathways including p38 mitogen-activated protein kinase (p38 MAPK). Thus, we investigated the role of 67-kDa LR in SE-induced vasogenic edema formation in the rat piriform cortex (PC). SE diminished 67-kDa LR expression, but increased laminin expression, in endothelial cells accompanied by the reduced SMI-71 (a rat BBB barrier marker) expression. Astroglial 67-kDa LR expression was also reduced in the PC due to massive astroglial loss. 67-kDa LR neutralization led to serum extravasation in the PC concomitant with the reduced SMI-71 expression. 67-kDa LR neutralization also decreased expressions of dystrophin and aquaporin-4 (AQP4). In addition, it increased p38 MAPK phosphorylation and expressions of vascular endothelial growth factor (VEGF), laminin and endothelial nitric oxide synthase (eNOS), which were abrogated by SB202190, a p38 MAPK inhibitor. Therefore, our findings indicate that 67-kDa LR dysfunction may disrupt dystrophin-AQP4 complex, which would evoke vasogenic edema formation and subsequent laminin over-expression via activating p38 MAPK/VEGF axis

CD4+ T cells from MHC II-dependent thymocyte–thymocyte interaction provide efficient help for B cells

Recently, a novel CD4+ T-cell developmental pathway was reported that generates thymocyte–thymocyte (T–T) CD4+ T cells. We established a mouse system (CIITAtgCIITApIV−/−) where thymic positive selection occurred only by major histocompatibility complex (MHC) class II+ thymocytes. T–T CD4+ T cells selected via MHC class II-dependent T–T interaction are comprised of PLZF-negative and innate PLZF-positive populations. Until recently, the functional role of the PLZF-negative population was unclear. In this study, we demonstrate that naïve T–T CD4+ T cells provide B-cell help to a level comparable with that of naïve conventional CD4+ T cells. Considering the absence of PLZF expression in naïve T–T CD4+ T cells, these results suggest that PLZF-negative naïve T–T CD4+ T cells are functionally equivalent to conventional naïve CD4+ T cells in terms of B-cell help

Clinicopathological Characteristics in Combined Hepatocellular-Cholangiocarcinoma: A Single Center Study in Korea

PURPOSE: Combined hepatocellular-cholangiocarcinoma (CHCC) is an uncommon form of cancer, and its clinicopathological features have rarely been reported in detail. This study was undertaken to evaluate the clinicopathological characteristics and prognostic factors of CHCC. MATERIALS AND METHODS: The clinicopathological features of patients diagnosed with CHCC at Severance Hospital between January 1996 and December 2007 were retrospectively studied by comparing them with the features of patients with hepatocellular carcinoma (HCC) or cholangiocarcinoma (CC) who had undergone a hepatic resection during the same period. RESULTS: Forty-three patients diagnosed with CHCC were included in this study (M : F=35 : 8, median age, 55 years). According to the parameters of the American Joint Committee on Cancer staging, there were 6 (14.0%), 9 (20.9%), 25 (58.1%), and 3 (7.0%) patients with stages I, II, III, and IV cancer, respectively. Thirty-two of the 43 patients underwent resection with curative intent. After resection, 27 patients (84.4%) had tumor recurrence during the follow-up period of 18 months (range: 6-106 months), and the median time to recurrence was 13 months. Overall median survival periods after hepatic resection of CHCC, HCC and CC were 34, 103 and 38.9 months, respectively (p<0.001). The median overall survival for all patients with CHCC was 21 months, and the 5-year survival rate was 18.1%. The presence of portal vein thrombosis and distant metastasis were independent prognostic factors of poor survival. CONCLUSION: Even after curative hepatic resection, the presence of a cholangiocellular component appeared to be a poor prognostic indicator in patients with primary liver cancer.ope

Ameliorating effects of Mango (Mangifera indica L.) fruit on plasma ethanol level in a mouse model assessed with 1H-NMR based metabolic profiling

The ameliorating effects of Mango (Mangifera indica L.) flesh and peel samples on plasma ethanol level were investigated using a mouse model. Mango fruit samples remarkably decreased mouse plasma ethanol levels and increased the activities of alcohol dehydrogenase and acetaldehyde dehydrogenase. The 1H-NMR-based metabolomic technique was employed to investigate the differences in metabolic profiles of mango fruits, and mouse plasma samples fed with mango fruit samples. The partial least squares-discriminate analysis of 1H-NMR spectral data of mouse plasma demonstrated that there were clear separations among plasma samples from mice fed with buffer, mango flesh and peel. A loading plot demonstrated that metabolites from mango fruit, such as fructose and aspartate, might stimulate alcohol degradation enzymes. This study suggests that mango flesh and peel could be used as resources for functional foods intended to decrease plasma ethanol level after ethanol uptake