Microcalorimetry and spectroscopic studies on the binding of dye janus green blue to deoxyribonucleic acid

The interaction of the phenazinium dye janus green blue (JGB) with deoxyribonucleic acid was investigated using isothermal titration calorimetry and thermal melting experiments. The calorimetric data were supplemented by spectroscopic studies. Calorimetry results suggested the binding affinity of the dye to DNA to be of the order of 105 M-1. The binding was predominantly entropy driven with a small negative favorable enthalpy contribution to the standard molar Gibbs energy change.The binding became weaker as the temperature and salt concentration was raised. The temperature dependence of the standard molar enthalpy changes yielded negative values of standard molar heat capacity change for the complexation revealing substantial hydrophobic contribution in the DNA binding. An enthalpy–entropy compensation behavior was also observed in the system. The salt dependence of the binding yielded the release of 0.69 number of cations on binding of each dye molecule. The non-polyelectrolytic contribution was found to be the predominant force in the binding interaction. Thermal melting studies revealed that the DNA helix was stabilized against denaturation by the dye. The binding was also characterized by absorbance, resonance light scattering and circular dichroism spectral measurements. The binding constants from the spectral results were close to those obtained from the calorimetric data. The energetic aspects of the interaction of the dye JGB to double stranded DNA are supported by strong binding revealed from the spectral data

A secretome profile indicative of oleate-induced proliferation of HepG2 hepatocellular carcinoma cells

Increased fatty acid (FA) is often observed in highly proliferative tumors. FAs have been shown to modulate the secretion of proteins from tumor cells, contributing to tumor survival. However, the secreted factors affected by FA have not been systematically explored. Here, we found that treatment of oleate, a monounsaturated omega-9 FA, promoted the proliferation of HepG2 cells. To examine the secreted factors associated with oleate-induced cell proliferation, we performed a comprehensive secretome profiling of oleate-treated and untreated HepG2 cells. A comparison of the secretomes identified 349 differentially secreted proteins (DSPs; 145 upregulated and 192 downregulated) in oleate-treated samples, compared to untreated samples. The functional enrichment and network analyses of the DSPs revealed that the 145 upregulated secreted proteins by oleate treatment were mainly associated with cell proliferation-related processes, such as lipid metabolism, inflammatory response, and ER stress. Based on the network models of the DSPs, we selected six DSPs (MIF, THBS1, PDIA3, APOA1, FASN, and EEF2) that can represent such processes related to cell proliferation. Thus, our results provided a secretome profile indicative of an oleate-induced proliferation of HepG2 cell

The abundance and host-seeking behavior of culicine species (Diptera: Culicidae) and Anopheles sinensis in Yongcheng city, people's Republic of China

<p>Abstract</p> <p>Background</p> <p>The knowledge of mosquito species diversity and the level of anthropophily exhibited by each species in a region are of great importance to the integrated vector control. Culicine species are the primary vectors of Japanese encephalitis (JE) virus and filariasis in China. <it>Anopheles sinensis </it>plays a major role in the maintenance of <it>Plasmodium vivax </it>malaria transmission in China. The goal of this study was to compare the abundance and host-seeking behavior of culicine species and <it>An. sinensis </it>in Yongcheng city, a representative region of <it>P. vivax </it>malaria. Specifically, we wished to determine the relative attractiveness of different animal baits versus human bait to culicine species and <it>An. sinensis</it>.</p> <p>Results</p> <p><it>Culex tritaeniorhynchus </it>was the most prevalent mosquito species and <it>An. sinensis </it>was the sole potential vector of <it>P. vivax </it>malaria in Yongcheng city. There were significant differences (P < 0.01) in the abundance of both <it>An. sinensis </it>and <it>Cx. tritaeniorhynchus </it>collected in distinct baited traps. The relative attractiveness of animal versus human bait was similar towards both <it>An. sinensis </it>and <it>Cx. tritaeniorhynchus</it>. The ranking derived from the mean number of mosquitoes per bait indicated that pigs, goats and calves frequently attracted more mosquitoes than the other hosts tested (dogs, humans, and chickens). These trends were similar across all capture nights at three distinct villages. The human blood index (HBI) of female <it>An. sinensis </it>was 2.94% when computed with mixed meals while 3.70% computed with only the single meal. 19:00~21:00 was the primary peak of host-seeking female <it>An. sinensis </it>while 4:00~5:00 was the smaller peak at night. There was significant correlation between the density of female <it>An. sinensis </it>and the average relative humidity (P < 0.05) in Wangshanzhuang village.</p> <p>Conclusions</p> <p>Pigs, goats and calves were more attractive to <it>An. sinensis </it>and <it>Cx. tritaeniorhynchus </it>than dogs, humans, and chickens. Female <it>An. sinensis </it>host-seeking activity mainly occurred from 19:00 to 21:00. Thus, we propose that future vector control against <it>An. sinensis </it>and <it>Cx. tritaeniorhynchus </it>in the areas along the Huang-Huai River of central China should target the interface of human activity with domestic animals and adopt before human hosts go to bed at night.</p

The Cardiac Transcription Network Modulated by Gata4, Mef2a, Nkx2.5, Srf, Histone Modifications, and MicroRNAs

The transcriptome, as the pool of all transcribed elements in a given cell, is regulated by the interaction between different molecular levels, involving epigenetic, transcriptional, and post-transcriptional mechanisms. However, many previous studies investigated each of these levels individually, and little is known about their interdependency. We present a systems biology study integrating mRNA profiles with DNA–binding events of key cardiac transcription factors (Gata4, Mef2a, Nkx2.5, and Srf), activating histone modifications (H3ac, H4ac, H3K4me2, and H3K4me3), and microRNA profiles obtained in wild-type and RNAi–mediated knockdown. Finally, we confirmed conclusions primarily obtained in cardiomyocyte cell culture in a time-course of cardiac maturation in mouse around birth. We provide insights into the combinatorial regulation by cardiac transcription factors and show that they can partially compensate each other's function. Genes regulated by multiple transcription factors are less likely differentially expressed in RNAi knockdown of one respective factor. In addition to the analysis of the individual transcription factors, we found that histone 3 acetylation correlates with Srf- and Gata4-dependent gene expression and is complementarily reduced in cardiac Srf knockdown. Further, we found that altered microRNA expression in Srf knockdown potentially explains up to 45% of indirect mRNA targets. Considering all three levels of regulation, we present an Srf-centered transcription network providing on a single-gene level insights into the regulatory circuits establishing respective mRNA profiles. In summary, we show the combinatorial contribution of four DNA–binding transcription factors in regulating the cardiac transcriptome and provide evidence that histone modifications and microRNAs modulate their functional consequence. This opens a new perspective to understand heart development and the complexity cardiovascular disorders

SOCS2 is dispensable for BCR/ABL1-induced chronic myeloid leukemia-like disease and for normal hematopoietic stem cell function

Suppressor of cytokine signaling 2 (SOCS2) is known as a feedback inhibitor of cytokine signaling and is highly expressed in primary bone marrow (BM) cells from patients with chronic myeloid leukemia (CML). However, it has not been established whether SOCS2 is involved in CML, caused by the BCR/ABL1 fusion gene, or important for normal hematopoietic stem cell (HSC) function. In this study, we demonstrate that although Socs2 was found to be preferentially expressed in long-term HSCs, Socs2-deficient HSCs were indistinguishable from wild-type HSCs when challenged in competitive BM transplantation experiments. Furthermore, by using a retroviral BCR/ABL1-induced mouse model of CML, we demonstrate that SOCS2 is dispensable for the induction and propagation of the disease, suggesting that the SOCS2-mediated feedback regulation of the JAK/STAT pathway is deficient in BCR/ABL1-induced CML.N Hansen, H Ågerstam, M Wahlestedt, N Landberg, M Askmyr, M Ehinger, M Rissler, H Lilljebjörn, P Johnels, J Ishiko, J V Melo, W S Alexander, D Bryder, M Järås, and T Fioreto

Beauty, Symmetry, and Magnetocaloric Effect-Four-Shell Keplerates with 104 Lanthanide Atoms

通讯作者地址: Kong, XJThe hydrolysis of Ln(ClO4)(3) in the presence of acetate leads to the assembly of the three largest known lanthanide-exclusive cluster complexes, [Nd-104(ClO4)(6)(CH3COO)(60)(mu(3)-OH)(168)(mu(4)-O)(30)(H2O)(112)].(ClO4)(18).(CH3CH2OH)(8).xH(2)O (1, x approximate to 158) and [Ln(104)(ClO4)(6)(CH3COO)(56)(mu(3)-OH)(168)(mu(4)-O)(30)(H2O)(112)].(ClO4)(22).(CH3CH2OH)(2).xH(2)O (2, Ln = Nd; 3, Ln = Gd; x approximate to 140). The structure of the common 104-lanthanide core, abbreviated as Ln(8)@Ln(48)@Ln(24)@Ln(24), features a four-shell arrangement of the metal atoms contained in an innermost cube (a Platonic solid) and, moving outward, three Archimedean solids: a truncated cuboctahedron, a truncated octahedron, and a rhombicuboctahedron. The magnetic entropy change of Delta Sm = 46.9 J kg(-1) K-1 at 2 K for Delta H = 7 T in the case of the Gd-104 cluster is the largest among previously known lanthanide-exclusive cluster compounds.973 Project from the Ministry of Science and Technology of China 2012CB821704 2014CB845601 National Natural Science Foundation of China 21422106 21371144 21431005 21390391 Foundation for the Author of National Excellent Doctoral Dissertation of China 201219 U.S. NSF APVV-0132-11 3001690 Czech Research Infrastructures LM201102

Prevalence and trend of hepatitis C virus infection among blood donors in Chinese mainland: a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Blood transfusion is one of the most common transmission pathways of hepatitis C virus (HCV). This paper aims to provide a comprehensive and reliable tabulation of available data on the epidemiological characteristics and risk factors for HCV infection among blood donors in Chinese mainland, so as to help make prevention strategies and guide further research.</p> <p>Methods</p> <p>A systematic review was constructed based on the computerized literature database. Infection rates and 95% confidence intervals (95% CI) were calculated using the approximate normal distribution model. Odds ratios and 95% CI were calculated by fixed or random effects models. Data manipulation and statistical analyses were performed using STATA 10.0 and ArcGIS 9.3 was used for map construction.</p> <p>Results</p> <p>Two hundred and sixty-five studies met our inclusion criteria. The pooled prevalence of HCV infection among blood donors in Chinese mainland was 8.68% (95% CI: 8.01%-9.39%), and the epidemic was severer in North and Central China, especially in Henan and Hebei. While a significant lower rate was found in Yunnan. Notably, before 1998 the pooled prevalence of HCV infection was 12.87% (95%CI: 11.25%-14.56%) among blood donors, but decreased to 1.71% (95%CI: 1.43%-1.99%) after 1998. No significant difference was found in HCV infection rates between male and female blood donors, or among different blood type donors. The prevalence of HCV infection was found to increase with age. During 1994-1995, the prevalence rate reached the highest with a percentage of 15.78% (95%CI: 12.21%-19.75%), and showed a decreasing trend in the following years. A significant difference was found among groups with different blood donation types, Plasma donors had a relatively higher prevalence than whole blood donors of HCV infection (33.95% <it>vs </it>7.9%).</p> <p>Conclusions</p> <p>The prevalence of HCV infection has rapidly decreased since 1998 and kept a low level in recent years, but some provinces showed relatively higher prevalence than the general population. It is urgent to make efficient measures to prevent HCV secondary transmission and control chronic progress, and the key to reduce the HCV incidence among blood donors is to encourage true voluntary blood donors, strictly implement blood donation law, and avoid cross-infection.</p

Metalloproteinases and their inhibitors—diagnostic and therapeutic opportunities in orthopedics

Matrix metalloproteinases (MMPs) and related enzymes (ADAMs, ADAMTS) and their inhibitors control matrix turnover and function. Recent advances in our understanding of musculoskeletal conditions such as tendinopathy, arthritis, Dupuytren's disease, degenerative disc disease, and bone and soft tissue healing suggest that MMPs have prominant roles. Importantly, MMPs are amenable to inhibition by cheap, safe, and widely available drugs such as the tetracycline antibiotics and the bisphosphonates. This indicates that these MMP inhibitors, if proven effective for any novel indication, may be quickly brought into clinical practice