The Drosophila basic helix-loop-helix protein DIMMED directly activates PHM, a gene encoding a neuropeptide-amidating enzyme

The basic helix-loop-helix (bHLH) protein DIMMED (DIMM) supports the differentiation of secretory properties in numerous peptidergic cells of Drosophila melanogaster. DIMM is coexpressed with diverse amidated neuropeptides and with the amidating enzyme peptidylglycine α-hydroxylating monooxygenase (PHM) in approximately 300 cells of the late embryo. Here we confirm that DIMM has transcription factor activity in transfected HEK 293 cells and that the PHM gene is a direct target. The mammalian DIMM orthologue MIST1 also transactivated the PHM gene. DIMM activity was dependent on the basic region of the protein and on the sequences of three E-box sites within PHM's first intron; the sites make different contributions to the total activity. These data suggest a model whereby the three E boxes interact cooperatively and independently to produce high PHM transcriptional activation. This DIMM-controlled PHM regulatory region displayed similar properties in vivo. Spatially, its expression mirrored that of the DIMM protein, and its activity was largely dependent on dimm. Further, in vivo expression was highly dependent on the sequences of the same three E boxes. This study supports the hypothesis that DIMM is a master regulator of a peptidergic cell fate in Drosophila and provides a detailed transcriptional mechanism of DIMM action on a defined target gene

Cooperative Interaction of Transcription Termination Factors with the RNA Polymerase II C-terminal Domain

Phosphorylation of the C-terminal domain of RNA polymerase II controls the co-transcriptional assembly of RNA processing and transcription factors. Recruitment relies on conserved CTDinteracting domains that recognize different CTD phosphoisoforms during the transcription cycle, but the molecular basis for their specificity remains unclear. We show that the CTD-interacting domains of two transcription termination factors, Rtt103 and Pcf11, achieve high affinity and specificity both by specifically recognizing the phosphorylated CTD and by cooperatively binding to neighboring CTD repeats. Single amino acid mutations at the protein-protein interface abolish cooperativity and affect recruitment at the 3′-end processing site in vivo. We suggest that this cooperativity provides a signal-response mechanism to ensure that its action is confined only to proper polyadenylation sites where Serine 2 phosphorylation density is highest

The Effects of Government Support on Corporate Performance Hedging against International Environmental Regulation

Government support systems are crucial for export SMEs (Small to Medium Enterprises) to cope with growing international environmental regulations. However, empirical studies show a limited research area to explore the performance of export SMEs with the help of government support systems to meet international environmental regulations. This study draws implications on the relationship between government support and corporate performance on export SMEs between two countries: Korea and China. Based on 350 samples from Korea and 320 from China, we diagnosed government supports most positively affects corporate performances in the area of eco-innovation. While education, certificate, and tax supports were less pressing areas to support, no significance was found in information support. Furthermore, we found that eco-innovation is the strongest motive to accelerate corporate performance. Finally, the support of Chinese government on firms seems to be more affective when compared to Korean government support

Using Lymphovenous Anastomosis and Lymph Node to Vein Anastomosis for Treatment of Posttraumatic Chylothorax with Increased Thoracic Duct Pressure in 3-Year-Old Child

Chylothorax is a rare disease and massive lymph fluid loss can cause life-threatening condition such as severe malnutrition, weight loss, and impaired immune system. If untreated, mortality rate of chylothorax can be up to 50%. This is a case report of a 3-year-old child with iatrogenic chylothorax. Despite conservative treatment and procedures, like perm catheter insertion, the patient failed to improve the respiratory symptoms over 3 months of period. As an alternative to surgical option, such as pleurodesis and thoracic duct ligation which has high complication rate, the patient underwent lymphovenous anastomosis (LVA) and lymph node to vein anastomosis (LNVA). Follow-up at fourth month showed clear lungs without breathing difficulty despite perm catheter removal. This is the first report to show the effectiveness of LVA and LNVA against iatrogenic chylothorax

Prognostic value of human apurinic/apyrimidinic endonuclease 1 (APE1) expression in breast cancer.

Human apurinic/apyrimidinic endonuclease 1 (APE1) is an essential protein for DNA base excision repair (BER) and redox regulation. The ability of cancer cells to recognize DNA damage and initiate DNA repair is an important mechanism for therapeutic resistance. Several recent studies have suggested that APE1 expression levels and/or subcellular dysregulation may be used to indicate the sensitivity of tumors to radiotherapy or chemotherapy. In this study, we assessed the prognostic significance of APE1 and differences in APE1 expression levels according to breast cancer molecular subtypes. We analyzed formalin-fixed, paraffin-embedded tumor tissue sections from 243 cases diagnosed as invasive breast cancer at Ewha Womans University Medical Center between January 2003 and December 2008. Immunohistochemistry was performed and the nuclear level of APE1 was scored by taking into account the percentage of positive cells. Medical records were reviewed to investigate clinicopathologic characteristics. We found that nuclear APE1 high-level expression (proportion ≥50%) in breast cancer showed a tendency towards unfavorable prognosis regarding disease-free survival (p = 0.093). However, there was no significant difference in overall survival between low and high-level expression groups (p = 0.294). Interestingly, within the Ki-67 low-level expression group, APE1 low-level expression was significantly associated with poor overall survival (p = 0.007). A significant positive correlation was observed between APE1 nuclear expression and estrogen receptor status (75.7% vs. 59.7%, p = 0.022). Also, the luminal A subtype was the most commonly observed breast cancer subtype in the APE1 high-level expression group (61.6% vs. 45.2%, p = 0.000). This study suggests that APE1 expression may be associated with breast cancer prognosis. In particular, its role as a prognostic factor would be significant for breast cancers with a low Ki-67 proliferation index. It is proposed that nuclear APE1 may be a novel target in breast cancer with a low proliferation rate to obtain better outcome