Apoptotic Cell Death and Inhibition of Wnt/β-Catenin Signaling Pathway in Human Colon Cancer Cells by an Active Fraction (HS7) from Taiwanofungus camphoratus

Aberrant activation of Wnt/β-catenin signaling plays an important role in the development of colon cancer. HS7 is an active fraction extracted from Taiwanofungus camphoratus, which had been widely used as complementary medicine for Taiwan cancer patients in the past decades. In this study, we demonstrated the effects of HS7 on the growth inhibition, apoptosis induction, and Wnt/β-catenin signaling suppression in human colon cancer cells. HS7 significantly inhibited proliferation of HT29, HCT116, and SW480 colon cancer cells in a dose- and time-dependent manner. The apoptosis induction was evidenced by DNA fragmentation and subG1 accumulation, which was associated with increased Bax/Bcl-2 ratio, activation of caspase-3 and cleavage of PARP. By using Tcf-dependent luciferase activity assay, HS7 was found to inhibit the β-catenin/Tcf transcriptional activities. In addition, HS7 strongly suppressed the binding of Tcf complexes to its DNA-binding site shown in electrophoretic mobility shift assay. This inhibition was further confirmed by the decreased protein levels of Tcf-4 and β-catenin. The β-catenin/Tcf downstream target genes, such as survivin, c-myc, cyclin D1, MMP7, and MT1-MMP involved in apoptosis, invasion, and angiogenesis were also diminished as well. These results indicate that Taiwanofungus camphoratus may provide a benefit as integrative medicine for the treatment of colon cancer

Proteomics reveals the significance of vacuole Pi transporter in the adaptability of Brassica napus to Pi deprivation

Vacuolar Pi transporters (VPTs) have recently been identified as important regulators of cellular Pi status in Arabidopsis thaliana and Oryza sativa. In the oil crop Brassica napus, BnA09PHT5;1a and BnC09PHT5;1a are two homologs of AtPHT5;1, the vacuolar Pi influx transporter in Arabidopsis. Here, we show that Pi deficiency induces the transcription of both homologs of PHT5;1a genes in B. napus leaves. Brassica PHT5;1a double mutants (DM) had smaller shoots and higher cellular Pi concentrations than wild-type (WT, Westar 10), suggesting the potential role of BnPHT5;1a in modulating cellular Pi status in B. napus. A proteomic analysis was performed to estimate the role of BnPHT5;1a in Pi fluctuation. Results show that Pi deprivation disturbs the abundance of proteins in the physiological processes involved in carbohydrate metabolism, response to stimulus and stress in B. napus, while disruption of BnPHT5;1a genes may exacerbate these processes. Besides, the processes of cell redox homeostasis, lipid metabolic and proton transmembrane transport are supposed to be unbalanced in BnPHT5;1a DM under the -Pi condition. Noteworthy, disruption of BnPHT5;1a genes severely alters the abundance of proteins related to ATP biosynthesis, and proton/inorganic cation transmembrane under normal Pi condition, which might contribute to B. napus growth limitations. Additionally, seven new protein markers of Pi homeostasis are identified in B. napus. Taken together, this study characterizes the important regulatory role of BnPHT5;1a genes as vacuolar Pi influx transporters in Pi homeostasis in B. napus

Nitrogen-Functionalized Graphene Nanoflakes (GNFs:N): Tunable Photoluminescence and Electronic Structures

This study investigates the strong photoluminescence (PL) and X-ray excited optical luminescence observed in nitrogen-functionalized 2D graphene nanoflakes (GNFs:N), which arise from the significantly enhanced density of states in the region of {\pi} states and the gap between {\pi} and {\pi}* states. The increase in the number of the sp2 clusters in the form of pyridine-like N-C, graphite-N-like, and the C=O bonding and the resonant energy transfer from the N and O atoms to the sp2 clusters were found to be responsible for the blue shift and the enhancement of the main PL emission feature. The enhanced PL is strongly related to the induced changes of the electronic structures and bonding properties, which were revealed by the X-ray absorption near-edge structure, X-ray emission spectroscopy, and resonance inelastic X-ray scattering. The study demonstrates that PL emission can be tailored through appropriate tuning of the nitrogen and oxygen contents in GNFs and pave the way for new optoelectronic devices.Comment: 8 pages, 6 figures (including toc figure

Proteomics reveals the significance of vacuole Pi transporter in the adaptability of Brassica napus to Pi deprivation

Vacuolar Pi transporters (VPTs) have recently been identified as important regulators of cellular Pi status in Arabidopsis thaliana and Oryza sativa. In the oil crop Brassica napus, BnA09PHT5;1a and BnC09PHT5;1a are two homologs of AtPHT5;1, the vacuolar Pi influx transporter in Arabidopsis. Here, we show that Pi deficiency induces the transcription of both homologs of PHT5;1a genes in B. napus leaves. Brassica PHT5;1a double mutants (DM) had smaller shoots and higher cellular Pi concentrations than wild-type (WT, Westar 10), suggesting the potential role of BnPHT5;1a in modulating cellular Pi status in B. napus. A proteomic analysis was performed to estimate the role of BnPHT5;1a in Pi fluctuation. Results show that Pi deprivation disturbs the abundance of proteins in the physiological processes involved in carbohydrate metabolism, response to stimulus and stress in B. napus, while disruption of BnPHT5;1a genes may exacerbate these processes. Besides, the processes of cell redox homeostasis, lipid metabolic and proton transmembrane transport are supposed to be unbalanced in BnPHT5;1a DM under the -Pi condition. Noteworthy, disruption of BnPHT5;1a genes severely alters the abundance of proteins related to ATP biosynthesis, and proton/inorganic cation transmembrane under normal Pi condition, which might contribute to B. napus growth limitations. Additionally, seven new protein markers of Pi homeostasis are identified in B. napus. Taken together, this study characterizes the important regulatory role of BnPHT5;1a genes as vacuolar Pi influx transporters in Pi homeostasis in B. napus

Enumeration of condition-dependent dense modules in protein interaction networks

Motivation: Modern systems biology aims at understanding how the different molecular components of a biological cell interact. Often, cellular functions are performed by complexes consisting of many different proteins. The composition of these complexes may change according to the cellular environment, and one protein may be involved in several different processes. The automatic discovery of functional complexes from protein interaction data is challenging. While previous approaches use approximations to extract dense modules, our approach exactly solves the problem of dense module enumeration. Furthermore, constraints from additional information sources such as gene expression and phenotype data can be integrated, so we can systematically mine for dense modules with interesting profiles

From harmful Microcystis blooms to multi-functional core-double-shell microsphere bio-hydrochar materials

Harmful algal blooms (HABs) induced by eutrophication is becoming a serious global environmental problem affecting public health and aquatic ecological sustainability. A novel strategy for the utilization of biomass from HABs was developed by converting the algae cells into hollow mesoporous biohydrochar microspheres via hydrothermal carbonization method. The hollow microspheres were used as microreactors and carriers for constructing CaO2 core-mesoporous shell-CaO2 shell microspheres (OCRMs). The CaO2 shells could quickly increase dissolved oxygen to extremely anaerobic water in the initial 40 min until the CaO2 shells were consumed. The mesoporous shells continued to act as regulators restricting the release of oxygen from CaO2 cores. The oxygen-release time using OCRMs was 7 times longer than when directly using CaO2. More interestingly, OCRMs presented a high phosphate removal efficiency (95.6%) and prevented the pH of the solution from rising to high levels in comparison with directly adding CaO2 due to the OH− controlled-release effect of OCRMs. The distinct core-doubleshell micro/nanostructure endowed the OCRMs with triple functions for oxygen controlled-release, phosphorus removal and less impact on water pH. The study is to explore the possibility to prepare smarter bio-hydrochar materials by utilizing algal blooms

Claudin 1 Mediates TNFα-Induced Gene Expression and Cell Migration in Human Lung Carcinoma Cells

Epithelial-mesenchymal transition (EMT) is an important mechanism in carcinogenesis. To determine the mechanisms that are involved in the regulation of EMT, it is crucial to develop new biomarkers and therapeutic targets towards cancers. In this study, when TGFβ1 and TNFα were used to induce EMT in human lung carcinoma A549 cells, we found an increase in an epithelial cell tight junction marker, Claudin 1. We further identified that it was the TNFα and not the TGFβ1 that induced the fibroblast-like morphology changes. TNFα also caused the increase in Claudin-1 gene expression and protein levels in Triton X-100 soluble cytoplasm fraction. Down-regulation of Claudin-1, using small interfering RNA (siRNA), inhibited 75% of TNFα-induced gene expression changes. Claudin-1 siRNA effectively blocked TNFα-induced molecular functional networks related to inflammation and cell movement. Claudin-1 siRNA was able to significantly reduce TNF-enhanced cell migration and fibroblast-like morphology. Furthermore, over expression of Claudin 1 with a Claudin 1-pcDNA3.1/V5-His vector enhanced cell migration. In conclusion, these observations indicate that Claudin 1 acts as a critical signal mediator in TNFα-induced gene expression and cell migration in human lung cancer cells. Further analyses of these cellular processes may be helpful in developing novel therapeutic strategies

X-ray emission from the Sombrero galaxy: discrete sources

We present a study of discrete X-ray sources in and around the bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival Chandra observations with a total exposure of ~200 ks. With a detection limit of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30 kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray binaries (LMXBs). We quantify the differential luminosity functions (LFs) for both the detected GC and field LMXBs, whose power-low indices (~1.1 for the GC-LF and ~1.6 for field-LF) are consistent with previous studies for elliptical galaxies. With precise sky positions of the GCs without a detected X-ray source, we further quantify, through a fluctuation analysis, the GC LF at fainter luminosities down to 1E35 erg/s. The derived index rules out a faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent findings in several elliptical galaxies and the bulge of M31. On the other hand, the 2-6 keV unresolved emission places a tight constraint on the field LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101 sources in the halo of Sombrero. The presence of these sources cannot be interpreted as galactic LMXBs whose spatial distribution empirically follows the starlight. Their number is also higher than the expected number of cosmic AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray surveys. We suggest that either the cosmic X-ray background is unusually high in the direction of Sombrero, or a distinct population of X-ray sources is present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres

Kinase and phosphatase engagement is dissociated between memory formation and extinction

Associative long-term memories (LTMs) support long-lasting behavioural changes resulting from sensory experiences. Retrieval of a stable LTM by means of a large number of conditioned stimulus (CS) alone presentations produces inhibition of the original memory through extinction. Currently, there are two opposing hypotheses to account for the neural mechanisms supporting extinction. The unlearning hypothesis posits that extinction affects the original memory trace by reverting the synaptic changes supporting LTM. On the contrary, the new learning hypothesis proposes that extinction is simply the formation of a new associative memory that inhibits the expression of the original one. We propose that detailed analysis of extinction-associated molecular mechanisms could help distinguish between these hypotheses. Here we will review experimental evidence regarding the role of protein kinases and phosphatases on LTM formation and extinction. Even though kinases and phosphatases regulate both memory processes, their participation appears to be dissociated. LTM formation recruits kinases, but is constrained by phosphatases. Memory extinction presents a more diverse molecular landscape, requiring phosphatases and some kinases, but also being constrained by kinase activity. Based on the available evidence, we propose a new theoretical model for memory extinction: a neuronal segregation of kinases and phosphatases supports a combination of time-dependent reversible inhibition of the original memory (CS-US), with establishment of a new associative memory trace (CS-noUS)