Association between childhood adversities and adulthood depressive symptoms in South Korea: Results from a nationally representative longitudinal study

Objective To examine how childhood adversity (ie, parental death, parental divorce, suspension of school education due to financial strain or being raised in a relative\u27s house due to financial strain) is associated with prevalence and incidence of adulthood depressive symptoms and whether this association differs by gender and by age in South Korea. Design Prospective cohort design. Setting Nationally representative longitudinal survey in South Korea. Participants 11 526 participants in South Korea. Outcome measure Prevalence and incidence of adulthood depressive symptoms were assessed as a dichotomous variable using the Centers for Epidemiologic Studies Depression (CES-D) Scale in 2006 and 2007. Results In the prevalence analysis, each of the four childhood adversities was significantly associated with a higher prevalence of adulthood depressive symptoms. The higher incidence of depressive symptoms was associated with suspension of school education (OR 1.55, 95% CI 1.32 to 1.82) and parental divorce (OR 1.65, 95% CI 1.00 to 2.71). In the age-stratified analyses, prevalence of depressive symptoms was associated with all CAs across different adulthoods, except for parental divorce and late adulthood depressive symptoms. After being stratified by gender, the association was significant for parental divorce (OR 3.76, 95% CI 2.34 to 6.03) in the prevalence analysis and for being raised in a relative’s house (OR 1.89, 95% CI 1.21 to 2.94) in the incidence analysis only among women. Conclusions This study suggests that childhood adversity may increase prevalence and incidence of adulthood depressive symptoms, and the impact of parental divorce or being raised in a relative\u27s house due to financial strain on adulthood depressive symptoms may differ by gender

Rapid Dye Regeneration Mechanism of Dye-Sensitized Solar Cells

During the light-harvesting process of dye-sensitized solar cells (DSSCs), the hole localized on the dye after the charge separation yields an oxidized dye, D^+. The fast regeneration of D^+ using the redox pair (typically the I^–/I_(3)^– couple) is critical for the efficient DSSCs. However, the kinetic processes of dye regeneration remain uncertain, still promoting vigorous debates. Here, we use molecular dynamics simulations to determine that the inner-sphere electron-transfer pathway provides a rapid dye regeneration route of ∼4 ps, where penetration of I^− next to D^+ enables an immediate electron transfer, forming a kinetic barrier. This explains the recently reported ultrafast dye regeneration rate of a few picoseconds determined experimentally. We expect that our MD based comprehensive understanding of the dye regeneration mechanism will provide a helpful guideline in designing TiO_2−dye−electrolyte interfacial systems for better performing DSSCs

Clinical Significance of p16 Protein Expression Loss and Aberrant p53 Protein Expression in Pancreatic Cancer

Pancreatic cancer is a disease with poor prognosis mainly due to low resection rates and late diagnosis. To increase resectability and improve survival rates, a better understanding of pancreatic cancer pathogenesis and more effective screening techniques are required. New methods, such as genetic and molecular alterations, may suggest novel approaches for pancreatic cancer diagnosis and treatment. We immunohistochemically investigated 44 formalin-fixed, paraffin-embedded specimens of pancreatic ductal adenocarcinoma using monoclonal anti-p16 antibodies and monoclonal anti-p53 antibodies. The expressions of p16 and p53 proteins were compared using the Chi-square test with SPSS. Disease-free survival was analyzed using the Kaplan-Meier method, verified by the Log-Rank test. Loss of p16 expression was noted in 20 (45.5%) cases and aberrant p53 protein expression was detected in 14 (31.8%) cases. Loss of p16 expression was associated with a higher incidence of lymph node metastasis (p=0.040) and a more advanced stage (p=0.015), although there was no significant correlation between p16 expression and survival. Aberrant p53 protein expression correlated with histologic grade (p=0.038). Disease-free survival rate was significantly lower in the aberrant p53 protein positive group compared to the negative group (p=0.029). From our results, we suggest that p53 is not a prognostic factor; however, p16 and p53 genes do play important roles in the progression of pancreatic ductal adenocarcinoma

Expression of Heterologous OsDHAR Gene Improves Glutathione (GSH)-Dependent Antioxidant System and Maintenance of Cellular Redox Status in Synechococcus elongatus PCC 7942.

An excess of reactive oxygen species (ROS) can cause severe oxidative damage to cellular components in photosynthetic cells. Antioxidant systems, such as the glutathione (GSH) pools, regulate redox status in cells to guard against such damage. Dehydroascorbate reductase (DHAR, EC 1.8.5.1) catalyzes the glutathione-dependent reduction of oxidized ascorbate (dehydroascorbate) and contains a redox active site and glutathione binding-site. The DHAR gene is important in biological and abiotic stress responses involving reduction of the oxidative damage caused by ROS. In this study, transgenic Synechococcus elongatus PCC 7942 (TA) was constructed by cloning the Oryza sativa L. japonica DHAR (OsDHAR) gene controlled by an isopropyl β-D-1-thiogalactopyranoside (IPTG)-inducible promoter (Ptrc) into the cyanobacterium to study the functional activities of OsDHAR under oxidative stress caused by hydrogen peroxide exposure. OsDHAR expression increased the growth of S. elongatus PCC 7942 under oxidative stress by reducing the levels of hydroperoxides and malondialdehyde (MDA) and mitigating the loss of chlorophyll. DHAR and glutathione S-transferase activity were higher than in the wild-type S. elongatus PCC 7942 (WT). Additionally, overexpression of OsDHAR in S. elongatus PCC 7942 greatly increased the glutathione (GSH)/glutathione disulfide (GSSG) ratio in the presence or absence of hydrogen peroxide. These results strongly suggest that DHAR attenuates deleterious oxidative effects via the glutathione (GSH)-dependent antioxidant system in cyanobacterial cells. The expression of heterologous OsDHAR in S. elongatus PCC 7942 protected cells from oxidative damage through a GSH-dependent antioxidant system via GSH-dependent reactions at the redox active site and GSH binding site residues during oxidative stress

Rewiring of PDZ Domain-Ligand Interaction Network Contributed to Eukaryotic Evolution

PDZ domain-mediated interactions have greatly expanded during metazoan evolution, becoming important for controlling signal flow via the assembly of multiple signaling components. The evolutionary history of PDZ domain-mediated interactions has never been explored at the molecular level. It is of great interest to understand how PDZ domain-ligand interactions emerged and how they become rewired during evolution. Here, we constructed the first human PDZ domain-ligand interaction network (PDZNet) together with binding motif sequences and interaction strengths of ligands. PDZNet includes 1,213 interactions between 97 human PDZ proteins and 591 ligands that connect most PDZ protein-mediated interactions (98%) in a large single network via shared ligands. We examined the rewiring of PDZ domain-ligand interactions throughout eukaryotic evolution by tracing changes in the C-terminal binding motif sequences of the PDZ ligands. We found that interaction rewiring by sequence mutation frequently occurred throughout evolution, largely contributing to the growth of PDZNet. The rewiring of PDZ domain-ligand interactions provided an effective means of functional innovations in nervous system development. Our findings provide empirical evidence for a network evolution model that highlights the rewiring of interactions as a mechanism for the development of new protein functions. PDZNet will be a valuable resource to further characterize the organization of the PDZ domain-mediated signaling proteome

FLT4 as a marker for predicting prognostic risk of refractory acute myeloid leukemia

Treating patients with refractory acute myeloid leukemia (AML) remains challenging. Currently there is no effective treatment for refractory AML. Increasing evidence has demonstrated that refractory/relapsed AML is associated with leukemic blasts which can confer resistance to anticancer drugs. We have previously reported that high expression of Fms-related tyrosine kinase 4 (FLT4) is associated with increased cancer activity in AML. However, the functional role of FLT4 in leukemic blasts remains unknown. Here, we explored the significance of FLT4 expression in leukemic blasts of refractory patients and mechanisms involved in the survival of AML blasts. Inhibition or absence of FLT4 in AML blasts suppressed homing to bone marrow of immunocompromised mice and blocked engraftment of AML blasts. Moreover, FLT4 inhibition by MAZ51, an antagonist, effectively reduced the number of leukemic cell-derived colony-forming units and increased apoptosis of blasts derived from refractory patients when it was co-treated with cytosine arabinoside under vascular endothelial growth factor C, its ligand. AML patients who expressed high cytosolic FLT4 were linked to an AML-refractory status by internalization mechanism. In conclusion, FLT4 has a biological function in leukemogenesis and refractoriness. This novel insight will be useful for targeted therapy and prognostic stratification of AML

Big bottlenecks in cardiovascular tissue engineering.

Although tissue engineering using human-induced pluripotent stem cells is a promising approach for treatment of cardiovascular diseases, some limiting factors include the survival, electrical integration, maturity, scalability, and immune response of three-dimensional (3D) engineered tissues. Here we discuss these important roadblocks facing the tissue engineering field and suggest potential approaches to overcome these challenges

Role of host tissues for sustained humoral effects after endothelial progenitor cell transplantation into the ischemic heart

Noncellular differentiation effects have emerged as important mechanisms mediating therapeutic effects of stem or progenitor cell transplantation. Here, we investigated the expression patterns and sources of humoral factors and their regional and systemic biological effects after bone marrow (BM)-derived endothelial progenitor cell (EPC) transplantation into ischemic myocardium. Although most of the transplanted EPCs disappeared within a week, up-regulation of multiple humoral factors was sustained for longer than two weeks, which correlated well with the recovery of cardiac function. To determine the source of the humoral factors, we injected human EPCs into immunodeficient mice. Whereas the expression of human EPC (donor)-derived cytokines rapidly decreased to a nondetectable level within a week, up-regulation of mouse (recipient)-derived cytokines, including factors that could mobilize BM cells, was sustained. Histologically, we observed higher capillary density, a higher proliferation of myocardial cells, a lower cardiomyocyte apoptosis, and reduced infarct size. Furthermore, after EPC transplantation, BM-derived stem or progenitor cells were increased in the peripheral circulation and incorporated into the site of neovascularization and myocardial repair. These data indicate that myocardial EPC transplantation induces humoral effects, which are sustained by host tissues and play a crucial role in repairing myocardial injury