Tandem ChoRE and CCAAT Motifs and Associated Factors Regulate Txnip Expression in Response to Glucose or Adenosine-Containing Molecules

Background: Thioredoxin interacting protein (Txnip) is a multifunctional protein involved in regulation of cell cycle events and cellular metabolism. The expression of Txnip is known to be induced by glucose, adenosine-containing molecules, and other physiological cues; however, the underlying regulatory mechanisms remain elusive. Methodology/Principal Findings: In this study, using promoter reporter, electrophoresis mobility shift (EMSA), and chromatin immuno-precipitation (ChIP) assays, we have identified an additional carbohydrate response element (ChoRE) on the promoter of Txnip gene, which functions cooperatively with the earlier identified ChoRE to mediate optimal Txnip expression. However, these two ChoREs are not sufficient to mediate the induction of Txnip expression by glucose or adenosine-containing molecules; and two CCAAT boxes, both of which can recruit nuclear factor Y (NF-Y) to the Txnip promoter, are also required for the induction. Accordingly, we have found that the function of ChoREs and associated factors is contingent on tandem CCAAT boxes, in that occupancy of the Txnip promoter by NF-Y is a prerequisite for efficacious recruitment of Mondo/MLX to ChoREs under glucose stimulation. Conclusions/Significance: Our findings suggest a synergy between the tandem CCAAT and ChoRE motifs and associated NF-Y and Mondo/MLX transcription factors in enhancing transcription from the Txnip promoter. This piece of information will be helpful for future dissection of molecular mechanisms governing the transcriptional regulation of Txnip, a glucos

INCREMENTAL CONTOUR FUSION BASED ON LINE/LINE TOPOLOGICAL RELATIONS

Incremental contour fusion plays a very important role in updating topographic database. The most popular fusion methods in current use depend on manual work basically, in which it results in large workload, low efficiency and it can’t ensure the quality of the spatial data. Therefore, the automatization of contour fusion should be developed exactly. Topological relation between unchanged contour and changed one is an important topic for contour fusion. In this paper, a new approach based on whole object is pursued to compute the binary topological relationship between them, in which “FL Points ” are introduced, intersection and difference operators are selected from set operators to distinguish the topological relations between neighboring spatial line objects; three types of topological invariants are used for the computational results of set operations: contents, dimension and connectivity-number. Then 14 fusion rules are concluded and a prototype system for automated fusion is implemented. The proposed approach is examined to be reasonable and practicable by real and simulated experimental data. 1

Neuroprotective effects of bis(7)-tacrine against glutamate-induced retinal ganglion cells damage

<p>Abstract</p> <p>Background</p> <p>Glutamate-mediated excitotoxicity, primarily through N-methyl-D-aspartate (NMDA) receptors, may be an important cause of retinal ganglion cells (RGCs) death in glaucoma and several other retinal diseases. Bis(7)-tacrine is a noncompetitive NMDA receptors antagonist that can prevent glutamate-induced hippocampal neurons damage. We tested the effects of bis(7)-tacrine against glutamate-induced rat RGCs damage in vitro and in vivo.</p> <p>Results</p> <p>In cultured neonatal rats RGCs, the MTT assay showed that glutamate induced a concentration- and time-dependent toxicity. Bis(7)-tacrine and memantine prevented glutamate-induced cell death in a concentration-dependent manner with IC50 values of 0.028 μM and 0.834 μM, respectively. The anti-apoptosis effects of bis(7)-tacrine were confirmed by annexin V-FITC/PI staining. In vivo, TUNEL analysis and retrograde labeling analysis found that pretreatment with bis(7)-tacrine(0.2 mg/kg) induced a significant neuroprotective effect against glutamate-induced RGCs damage.</p> <p>Conclusions</p> <p>Our results showed that bis(7)-tacrine had neuroprotective effects against glutamate-induced RGCs damage in vitro and in vivo, possibly through the drug's anti-NMDA receptor effects. These findings make bis(7)-tacrine potentially useful for treating a variety of ischemic or traumatic retinopathies inclusive of glaucoma.</p

Acetoacetate extract of Pleione bulbocodioides (Franch.) rolfe induces apoptosis of human leukemia thp-1cells through a mitochondria-regulated intrinsic apoptotic pathway

The tubers of three orchidaceous plants, including Pleione bulbocodioides (Franch.) Rolfe, have been used as ‘Shan-Ci-Gu’ in traditional Chinese medicine for the treatment of bacterial infections and cancers for thousands of years. In this study, the effects of an acetoacetate (EtOAc) extract of P. bulbocodioides on the cell viability and apoptosis of THP-1 (human acute monocytic leukemia cell line) cells and its interaction with possible apoptotic pathways were investigated. THP-1 cells were treated with the EtOAc extract of P. bulbocodioides at different concentrations. The results showed that THP-1 cell viability was significantly inhibited by the EtOAc extract of P. bulbocodioides with an IC50 of 51.37±2.68 µg/ mL at 24 h. The examination of cytotoxic effects on healthy cells showed that the EtOAc extract of P. bulbocodioides did not show any effect on healthy Vero cells. Selectivity indexes were greater than 15.57, suggesting that the EtOAc extract of P. bulbocodioides had selective toxicity against THP-1 cells. The results of annexin V-FITC/PI and DAPI staining showed that the EtOAc extract of P. bulbocodioides induced cell apoptosis in a dose-dependent manner. The apoptotic rate was increased in the treatment groups compared with that in the control group (P<0.05). The distribution of cells in the G2 phase of the cell cycle increased along with typical cell apoptosis-induced morphological changes. The levels of the pro-apoptotic proteins Bax, cleaved PARP and cleaved caspase-3 increased with increasing concentration of acetoacetate extract of P. bulbocodioides, while the anti-apoptosis protein Bcl-2 was downregulated. Cyt c and AIF, which are characteristic proteins of the mitochondria-regulated intrinsic apoptosis pathway, also increased in the cytosol with increasing concentrations of the EtOAc extract of P. bulbocodioides. These results showed that the EtOAc extract of P. bulbocodioides significantly inhibits cell viability and induces cell apoptosis in the human leukemia cell line THP-1 through a mitochondria-regulated intrinsic apoptotic pathway

MAP4K family kinases act in parallel to MST1/2 to activate LATS1/2 in the Hippo pathway.

The Hippo pathway plays a central role in tissue homoeostasis, and its dysregulation contributes to tumorigenesis. Core components of the Hippo pathway include a kinase cascade of MST1/2 and LATS1/2 and the transcription co-activators YAP/TAZ. In response to stimulation, LATS1/2 phosphorylate and inhibit YAP/TAZ, the main effectors of the Hippo pathway. Accumulating evidence suggests that MST1/2 are not required for the regulation of YAP/TAZ. Here we show that deletion of LATS1/2 but not MST1/2 abolishes YAP/TAZ phosphorylation. We have identified MAP4K family members--Drosophila Happyhour homologues MAP4K1/2/3 and Misshapen homologues MAP4K4/6/7-as direct LATS1/2-activating kinases. Combined deletion of MAP4Ks and MST1/2, but neither alone, suppresses phosphorylation of LATS1/2 and YAP/TAZ in response to a wide range of signals. Our results demonstrate that MAP4Ks act in parallel to and are partially redundant with MST1/2 in the regulation of LATS1/2 and YAP/TAZ, and establish MAP4Ks as components of the expanded Hippo pathway

Global Proteomic Analysis of Lysine Malonylation in Toxoplasma gondii

Lysine malonylation (Kmal) is a new post-translational modification (PTM), which has been reported in several prokaryotic and eukaryotic species. Although Kmal can regulate many and diverse biological processes in various organisms, knowledge about this important PTM in the apicomplexan parasite Toxoplasma gondii is limited. In this study, we performed the first global profiling of malonylated proteins in T. gondii tachyzoites using affinity enrichment and Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Three experiments performed in tandem revealed 294, 345, 352 Kmal sites on 203, 236, 230 malonylated proteins, respectively. Computational analysis showed the identified malonylated proteins to be localized in various subcellular compartments and involved in many cellular functions, particularly mitochondrial function. Additionally, one conserved Kmal motif with a strong bias for cysteine was detected. Taken together, these findings provide the first report of Kmal profile in T. gondii and should be an important resource for studying the physiological roles of Kmal in this parasite

Seroprevalence of Toxoplasma gondii infection in pet dogs in Kunming, Southwest China

BACKGROUND: Toxoplasmosis is a zoonotic parasitic disease caused by the protozoan Toxoplasma gondii, which infects almost all warm-blooded animals, including humans, with a worldwide distribution. However, little is known of T. gondii seroprevalence in pet dogs in Kunming, the capital of Yunnan Province, southwest China. The objective of this investigation was to estimate the seroprevalence of T. gondii infection in pet dogs in this area. METHODS: A total of 611 serum samples were collected from 7 pet hospitals in Kunming, and assayed for T. gondii antibodies by the indirect haemagglutination (IHA) using a commercially-marked kit. RESULTS: 132 (21.6%) pet dogs were positive for T. gondii antibodies, and the seroprevalence ranged from 17.3% to 34.7% among different sampling regions, the difference was statistically significant (P < 0.05). The T. gondii seroprevalence in female and male dogs were 20.8% and 22.4%, respectively, the difference was not statistically significant (P > 0.05). The seroprevalence ranged from 17.5% to 23.6% among different age groups, but the difference was not statistically significant (P > 0.05), and there were no interactions in statistics (P > 0.05) between gender and age of pet dogs in the region. CONCLUSIONS: The findings of the present survey indicate high T. gondii seroprevalance in pet dogs in Kunming, southwest China, posing significant public health concern. It is necessary to enhance integrated strategies and measures to prevent and control T. gondii infection in pet dogs in this area

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The Global Search for Liquid Water on Mars from Orbit: Current and Future Perspectives

Due to its significance in astrobiology, assessing the amount and state of liquid water present on Mars today has become one of the drivers of its exploration. Subglacial water was identified by the Mars Advanced Radar for Subsurface and Ionosphere Sounding (MARSIS) aboard the European Space Agency spacecraft Mars Express through the analysis of echoes, coming from a depth of about 1.5 km, which were stronger than surface echoes. The cause of this anomalous characteristic is the high relative permittivity of water-bearing materials, resulting in a high reflection coefficient. A determining factor in the occurrence of such strong echoes is the low attenuation of the MARSIS radar pulse in cold water ice, the main constituent of the Martian polar caps. The present analysis clarifies that the conditions causing exceptionally strong subsurface echoes occur solely in the Martian polar caps, and that the detection of subsurface water under a predominantly rocky surface layer using radar sounding will require thorough electromagnetic modeling, complicated by the lack of knowledge of many subsurface physical parameters. Higher-frequency radar sounders such as SHARAD cannot penetrate deep enough to detect basal echoes over the thickest part of the polar caps. Alternative methods such as rover-borne Ground Penetrating Radar and time-domain electromagnetic sounding are not capable of providing global coverage. MARSIS observations over the Martian polar caps have been limited by the need to downlink data before on-board processing, but their number will increase in coming years. The Chinese mission to Mars that is to be launched in 2020, Tianwen-1, will carry a subsurface sounding radar operating at frequencies that are close to those of MARSIS, and the expected signal-to-noise ratio of subsurface detection will likely be sufficient for identifying anomalously bright subsurface reflectors. The search for subsurface water through radar sounding is thus far from being concluded