For infrared imaging systems with high sampling width applying to the traditional display device or real-time processing system with 8-bit data width, this paper presents a new high dynamic range compression and detail enhancement (DRCDDE) algorithm for infrared images. First, a bilateral filter is adopted to separate the original image into two parts: the base component that contains large-scale signal variations, and the detail component that contains high-frequency information. Then, the operator model for DRC with local-contrast preservation is established, along with a new proposed nonlinear intensity transfer function (ITF) to implement adaptive DRC of the base component. For the detail component, depending on the local statistical characteristics, we set up suitable intensity level extension criteria to enhance the low-contrast details and suppress noise. Finally, the results of the two components are recombined with a weighted coefficient. Experiment results by real infrared data, and quantitative comparison with other well-established methods, show the better performance of the proposed algorithm. Furthermore, the technique could effectively project a dim target while suppressing noise, which is beneficial to image display and target detection.
We present an investigation of two-dimensional coordination networks formed by 5,10,15,20-tetra(4-pyridyl)porphyrin and iron atoms on a Au(111) surface. The coordination bonds are very robust as evidenced by STM manipulated lateral displacement of an entire network of islands consisting of hundreds of molecules and atoms. We also applied vertical manipulation to detach and attach single Fe atoms at the coordination sites. Moreover, low-temperature tunneling spectroscopy reveals a Kondo resonance at the Fe coordination center. These findings evidence that the network structure is stabilized by a coordination motif in which a pair of vertically aligned Fe atoms is ligated by four equatorial pyridyl groups. Such out-of-plane dinuclear coordination centers provide potential functions, such as catalytic, adsorption, and template for growing three-dimensional framework architectures.
A number of studies have examined the association between interleukin-6 (IL-6) rs1800796 polymorphism and risk of lung cancer but revealed inconsistent results. The aim of this study was to clarify the association between IL-6 rs1800796 polymorphism and risk of lung cancer.
We observed the effect of scalp point cluster-needling treatment on learning and memory function and neurotransmitter levels in rats with vascular dementia (VD). Permanent ligation of the bilateral carotid arteries was used to create the VD rat model. A Morris water maze was used to measure the rats' learning and memory function, and the changes in neurotransmitter levels in the rats' hippocampus were analyzed. The results show that scalp point cluster-needling can increase the VD rat model's learning and memory score. The VD rat model's learning and memory score was significantly different when compared with that of the sham operation group (P < 0.05). Hippocampal acetylcholine (ACh), dopamine (DA), and 5-hydroxytryptamine (5-HT) concentrations significantly decreased in the rat model. Compared with the model group, the scalp point cluster-needling group's ACh concentration markedly increased and DA and 5-HT levels increased as well. In conclusion, scalp point cluster-needling can improve learning and memory function in VD rats, and its function may be related to an increase in neurotransmitter release.
We demonstrate manipulation of photon emission efficiency in a tunneling gap by tuning the rates of elastic and inelastic electron tunneling processes with local electronic states. The artificial local electronic states are created by a scanning tunneling microscope tip on a CuN nanoisland grown on a Cu(100) surface at cryogenic temperature. These local electronic states can either enhance or suppress the excitation of tip-induced surface plasmon modes at specific bias voltages, and thus the induced photon emission rates. A theoretical model quantitatively analyzing inelastic and elastic tunneling processes associated with characteristic electronic states shows good agreement with experiments. We also show that tip-induced photon emission measurement can be used for probing the electronic states in the tunneling gap.
Nanostructured graphene on SiO2 substrates paves the way for enhanced light-matter interactions and explorations of strong plasmon-phonon hybridization in the mid-infrared regime. Unprecedented large-area graphene nanodot and antidot optical arrays are fabricated by nanosphere lithography, with structural control down to the sub-100 nm regime. The interaction between graphene plasmon modes and the substrate phonons is experimentally demonstrated, and structural control is used to map out the hybridization of plasmons and phonons, showing coupling energies of the order 20 meV. Our findings are further supported by theoretical calculations and numerical simulations.
The mechanism for the ring expansion reaction between cyclopropenylidene and azetidine was systematically investigated employing second-order Møller-Plesset perturbation theory (MP2) in order to better understand the reactivity of cyclopropenylidene with the four-membered ring compound azetidine. Geometry optimizations and vibrational analyses were performed for the stationary points on the potential energy surfaces of the system. The results of our calculations show that cyclopropenylidene can insert into azetidine at its C-N or C-C bond. From a kinetic viewpoint, it is easier for cyclopropenylidene to insert into the C-N bond of azetidine than into the C-C bond. During the first insertion step and the second ring-opening step, it forms spiro and carbene intermediates, respectively. In the following two H-transfer steps, the carbene intermediate forms allenes and alkynes, respectively, as products. From a thermodynamic perspective, allenes are the dominant product because the reaction is exothermic by 373.4 kJ/mol?¹.
To investigate the inhibitory effects of microRNA-30d (miR-30d) on renal carcinoma cell proliferation and the underlying molecular mechanisms, miR-30d expression in renal cell carcinoma (RCC) specimens was analyzed by quantitative polymerase chain reaction (qPCR). The inhibition of the proliferation of miR-30d on renal carcinoma cells (ACHN cell line) was analyzed by MTT and colony formation assays. The effects of miR-30d on cyclin E2 expression were detected by the luciferase activity of the reporter gene. In addition, the effects of miR-30d on endogenous cyclin E2 expression at the RNA and protein levels were investigated by qPCR and western blot analysis, respectively. Cell cycles were analyzed by flow cytometry. The results showed the following: i) Expression of miR-30d was significantly downregulated in renal carcinoma tissues compared with paraneoplastic tissues; ii) overexpression of miR-30d inhibited renal carcinoma cell proliferation and colony formation; iii) miR-30d inhibited cyclin E2 3' untranslated region-mediated reporter gene expression; and iv) overexpression of miR-30d downregulated endogenous cyclin E2 expression and blocked the cell cycle at the G1 phase. In conclusion, miR-30d functions as a tumor suppressor gene in RCC and inhibits renal carcinoma cell proliferation. Cell cycle regulatory factor cyclin E2 is a target gene of miR-30d. miR-30d inhibits renal carcinoma cell proliferation via the regulation of cyclin E2 expression at the post-transcriptional level.
In this work, a xanthone derivative was obtained by cationic modification of the free hydroxyl group of xanthone with dimethylamine group of high pKa value. The interactions of xanthones with DNA were investigated by spectroscopic methods, electrophoretic migration assay and polymerase chain reaction test. Results indicate that xanthones can intercalate into the DNA base pairs by the hydrophobic plane and the xanthone with dimethylamine side chain may also bind the DNA phosphate framework by the basic amine alkyl chain, thus showing a better DNA binding ability than the xanthone. Furthermore, inhibition on tumor cells (ECA109, SGC7901, GLC-82) proliferation of xanthones were evaluated by MTT method. Analysis results show that the xanthone with dimethylamine side chain exhibits more effective inhibition activity against three cancer cells than the xanthone. The effects on the inhibition of tumor cells in vitro agree with the studies of DNA binding. It means that the amine alkyl chain would play an important role in its antitumor activity and DNA binding property.
Aneuploidy is one of the major factors that result in low efficiency in human infertility treatment by in vitro fertilization (IVF). The development of DNA microarray technology allows for aneuploidy screening by analyzing all 23 pairs of chromosomes in human embryos. All chromosome screening for aneuploidy is more accurate than partial chromosome screening, as errors can occur in any chromosome. Currently, chromosome screening for aneuploidy is performed in developing embryos, mainly blastocysts. It has not been performed in arrested embryos and/or compared between developing embryos and arrested embryos from the same IVF cycle.
Hepatitis C virus (HCV) is a highly mutable RNA virus and circulates as a heterogeneous population in individual patients. The magnitude of such population heterogeneity has long been proposed to be linked with diverse clinical phenotypes, including antiviral therapy. Yet data accumulated thus far are fairly inconclusive. By the integration of long RT-PCR with 454 sequencing, we have built a pipeline optimized for the quantification of HCV genome-wide mutation load at 1% resolution of mutation frequency, followed by a retrospective study to examine the role of HCV mutation load in peginterferon-alpha2a and ribavirin combination antiviral therapy. Genome-wide HCV mutation load varied widely with a range from 92 to 1639 mutations and presented a Poisson distribution among 56 patients (Kolmogorov-Smirnov statistic ?=?0.078, p?=?0.25). Patients achieving sustained virological response (n?=?26) had significantly lower mutation loads than that in null responders (n?=?30) (mean and standard derivation: 524±279 vs. 805±271, p?=?0.00035). All 36,818 mutations detected in 56 patients displayed a power-law distribution in terms of mutation frequency in viral population. The low-frequency mutation load, but not the high-frequency load, was proportional firmly to the total mutation load. In-depth analyses revealed that intra-patient HCV population structure was shaped by multiple factors, including immune pressure, strain difference and genetic drift. These findings explain previous conflicting reports using low-resolution methods and highlight a dominant role of natural selection in response to therapeutic intervention. By attaining its signatures from complex interaction between host and virus, the high-resolution quantification of HCV mutation load predicts outcomes from interferon-based antiviral therapy and could also be a potential biomarker in other clinical settings.
Testing the pyrazinamide (PZA) susceptibility of Mycobacterium tuberculosis isolates is challenging. In a previous paper, we described the development of a rapid colorimetric test for the PZA susceptibility of M. tuberculosis by a PCR-based in vitro-synthesized-pyrazinamidase (PZase) assay. Here, we present an integrated approach to detect M. tuberculosis and PZA susceptibility directly from sputum specimens. M. tuberculosis was detected first, using a novel long-fragment quantitative real-time PCR (LF-qPCR), which amplified a fragment containing the whole pncA gene. Then, the positive amplicons were sequenced to find mutations in the pncA gene. For new mutations not found in the Tuberculosis Drug Resistance Mutation Database (www.tbdreamdb.com), the in vitro PZase assay was used to test the PZA resistance. This approach could detect M. tuberculosis within 3 h with a detection limit of 7.8 copies/reaction and report the PZA susceptibility within 2 days. In an initial testing of 213 sputum specimens, the LF-qPCR found 53 positive samples with 92% sensitivity and 97% specificity compared to the culture test for M. tuberculosis detection. DNA sequencing of the LF-qPCR amplicons revealed that 49 samples were PZA susceptible and 1 was PZA resistant. In the remaining 3 samples, with new pncA mutations, the in vitro PZase assay found that 1 was PZA susceptible and 2 were PZA resistant. This integrated approach provides a rapid, efficient, and relatively low-cost solution for detecting M. tuberculosis and PZA susceptibility without culture.
China has the highest incidence of hepatitis B virus (HBV) infection worldwide. HBV genotypes have variable impacts on disease pathogenesis and drug tolerance. We have developed a technically simple and accurate method for HBV genotyping that will be applicable to pre-treatment diagnosis and individualized treatment. Multiple sequence alignments of HBV genomes from GenBank were used to design primers and probes for genotyping of HBV A through H. The hybridization was carried out on nitrocellulose (NC) membranes with probes fixed in an array format, which was followed by hybrid amplification by an extension step with DNA polymerase to reinforce the double-stranded DNA hybrids on the NC membrane and subsequent visualization using an avidin-biotin system. Genotyping results were confirmed by DNA sequencing and bioinformatics analysis using the National Center for Biotechnology Information genotyping database, and compared with results from the line probe assay. The data show that multiple sequence alignment defined a 630 bp region in the HBV PreS and S regions that was suitable for genotyping. All genotyping significant single nucleotides in the region were defined. Two-hundred-and-ninety-one HBV-positive serum samples from Northwest Chinese patients were genotyped, and the genotyping rate from the new modified hybridization-extension method was 100% compared with direct sequencing. Compared with line probe assay, the newly developed method is superior, featuring reduced reaction time, lower risk of contamination, and increased accuracy for detecting single nucleotide mutation. In conclusion, a novel hybridization-extension method for HBV genotyping was established, which represents a new tool for accurate and rapid SNP detection that will benefit clinical testing.
A novel molecularly imprinted organic-inorganic hybrid polymer (MI-MAA/APTS) based on a dummy molecular imprinting technique and an organic-inorganic hybrid material technique was synthesised and used as a sorbent in solid-phase extraction for the selective isolation and determination of ofloxacin (OFL), lomefloxacin (LOM), and ciprofloxacin (CIP) in tilapia samples. The MI-MAA/APTS sorbent was prepared from 3-aminopropyltriethoxysilanes (APTS) as an inorganic source and methacrylic acid (MAA) as an organic source and exhibited high mechanical strength and special affinities to the analytes. A comparison of MI-MAA/APTS with other conventional sorbents (C18 and HLB) showed that MI-MAA/APTS displayed good selectivity and affinity for OFL, LOM, and CIP, and the recoveries of the analytes at three spiked levels were in the range of 85.1-101.0%, with the relative standard deviations ?5.1%. The presented MI-MAA/APTS-SPE-HPLC method could be potentially applied to the determination of fluoroquinolones (FQs) in complex fish samples.
High proportions of human embryos produced by in vitro fertilization are aneuploidy and mosaic. DNA microarray is one of the most practical screening methods to select euploid embryos for transfer. However, mosaic pregnancy is still possible due to embryonic mosacism. Here we report a successful pregnancy after transfer of a mosaic blastocyst with euploid inner cell mass.
Novel fluffy Fe@alpha-Fe2O3 core-shell nanowires have been synthesized using the chemical reactionof ferrous sulfate and sodium borohydride, as well as the post-annealing process in air. Thecoercivity of the as-synthesized nanowires is above 684 Oe in the temperature range of 5 to 300 K,which is significantly higher than that of the bulk Fe (approximately 0.9 Oe). Through the annealingprocess in air, the coercivity and the exchange field are evidently improved. Both the coercivity andthe exchange field increase with increasing annealing time (TA) and reach their maximum values of1,042 and 78 Oe, respectively, at TA = 4 h. The magnetic measurements show that the effectiveanisotropy is increased with increasing the thickness of the alpha-Fe2O3 by annealing. The large valuesof coercivity and exchange field, as well as the high surface area to volume ratio, may make thefluffy Fe@alpha-Fe2O3 core-shell nanowire a promising candidate for the applications of the magneticdrug delivery, electrochemical energy storage, gas sensors, photocatalysis, and so forth.
Prostate carcinoma is the most common cancer for men and among the leading cancer-related causes. Many evidences have shown that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) potently induces apoptosis in cancer cells, and thus, is a promising biologic agent for prostate carcinoma therapy. However, TRAIL expression mediated by the current vectors lacks tumor specificity, thereby exerting cytotoxicity to normal cells. To solve this problem, we inserted miRNA response elements (MREs), miR-143 and miR-145, expression levels of which were reduced in prostate carcinoma, as well as that of miR-122, which is specifically expressed in hepatic cells, into adenoviral vectors to control TRAIL expression (Ad-TRAIL-M3). qPCR data confirmed that miR-143, miR-145, and miR-122 levels were all decreased in prostate carcinoma cell lines and prostate cancer samples from patients. Luciferase assays showed that MREs-regulated luciferase expression was potently suppressed in normal cells, but not in prostate cancer cells. Ad-TRAIL-M3, which expresses TRAIL in a MREs-regulated manner, produced high level of TRAIL and suppressed the survival of prostate cancer cells by inducing apoptosis, while Ad-TRAIL-M3 had no TRAIL expression in normal cells and thus exerted no cytotoxicity to them. The studies on PC-3 tumor xenograft in mice further confirmed that Ad-TRAIL-M3 was able to inhibit the growth of tumors and possessed high biosafety. In conclusion, we successfully generated an adenoviral vector that expresses TRAIL in miRNA-regulated mechanism. This miRNA-based gene therapy may be promising for prostate carcinoma treatment.
The sustainable supply of lipids is the bottleneck for current biodiesel production. Here microbial recycling of glycerol, byproduct of biodiesel production to biodiesel in engineered Escherichia coli strains was reported. The KC3 strain with capability of producing fatty acid ethyl esters (FAEEs) from glucose was used as a starting strain to optimize fermentation conditions when using glycerol as sole carbon source. The YL15 strain overexpressing double copies of atfA gene displayed 1.7-fold increase of FAEE productivity compared to the KC3 strain. The titer of FAEE in YL15 strain reached to 813mgL(-1) in minimum medium using glycerol as sole carbon source under optimized fermentation conditions. The titer of glycerol-based FAEE production can be significantly increased by both genetic modifications and fermentation optimization. Microbial recycling of glycerol to biodiesel expands carbon sources for biodiesel production.
Influenza A/H1N1 virus spreads worldwide and has been a threat to human health and the poultry industry. Although H1N1 lateral-flow immunoassay strips are available for the detection of 2009/A/H1N1 antigens, the specificity and sensitivity of these strips are limited. Because of the monodispersity, the strong magnetic signal and the stable brown color of superparamagnetic nanoparticles, which were employed in this study as label instead of commonly used colloidal gold particles. Two different monoclonal anti-HA (hemagglutinin) and anti-HA-tag mAbs were paired for conjugating with paramagnetic beads and immobilizing on the surface of nitrocellulose (NC) membrane as capture antibody respectively. After optimizing the experimental condition, we generated a superparamagnetic bead-based immunochromatographic strip. The strip could detect HA antigen from H1N1 influenza A virus sample sensitively, its detection limit was 100 pg/mL. It had low cross reactivity with H3N2 influenza A virus and did not detect influenza B virus. It had no false positive detection in all of the tested control samples. With the help of magnetic assay reader (MAR), the magnetic intensity on test lines could be recorded and quantified proportionally with the amount of antigens captured. Those properties were indeed superior to the colloidal gold-based strips. More importantly, the strip was affordable and easy to use. Conceivably, superparamagnetic bead-based immunochromatographic strip should be a valuable point-of-care test for the rapid and specific detection of influenza A virus.
Purpose: S100P has been shown to participate in processes of various human malignancies. In this study, we analyzed the tissue expression of S100P in gastric cancer and evaluated its significance.?Methods: We determined the S100P expression in 156 gastric cancer patients by quantitative RT-PCR. Tumor characteristics and overall survival (OS) for each patient were examined. In vitro experiments were conducted to examine whether ectopic expression of S100P modifies the proliferation and drug resistance of gastric cancer cells.?Results: Higher expression of S100P occurred in human gastric cancer tissues in comparison with normal controls. Highly expressed S100P in gastric cancer was correlated with TNM stage and prognosis. The 5-year survival rate was significantly lower in patients with high levels of S100P expression than in patients with low levels of expression. Ectopic expression of S100P was associated with an increase in tumor cell proliferation and drug resistance. ?Conclusion: The expression of S100P in human gastric cancer tissues was upregulated in comparison with normal controls. By establishing an association between S100P expression and shortened OS, increase in proliferation and drug resistance, this study indicates that S100P may be a useful prognostic marker for gastric cancer patients.
Fetal overexposure to glucocorticoids leads to growth restriction. Optimal fetal glucocorticoid level is ensured by the expression of cortisol-inactivating enzyme 11?-hydroxysteroid dehydrogenase type 2 (11?-HSD2) in placental syncytiotrophoblasts. The transcription factor selective promoter factor 1 (Sp1) is known to up-regulate 11?-HSD2 expression in the presence of enhanced histone acetylation in syncytiotrophoblasts, but the mechanisms underlying histone acetylation remain unknown.
BACKGROUND: Long interspersed nuclear element-1 (LINE-1 or L1), the most abundant and only autonomously active family of non-LTR retrotransposons in the human genome, expressed not only in the germ lines but also in somatic tissues. It contributes to genetic instability, aging, and age-related diseases, such as cancer. Our previous study identified in human gastric adenocarcinoma an upregulated transcript GCRG213, which shared 88% homology with human LI sequence and contained a putative conserved apurinic/apyrimidinic endonucleas1 domain. METHODS: Immunohistochemistry was carried out by using a monoclonal mouse anti-human GCRG213 protein (GCRG213p) antibody produced in our laboratory, on tissue microarray constructed with specimens from 175 gastric adenocarcinoma patients. The correlation between GCRG213p expression and patient clinicopathological parameters was evaluated. GCRG213p expression in gastric cancer cell lines were studied using Western blotting analysis. L1 promoter methylation status of gastric cancer cells was tested using methylation-specific PCR. BLASTP was used at the NCBI Blast server to identify GCRG213p sequence to any alignments in the Protein Data Bank databases. RESULTS: Most primary gastric cancer, lymph node metastases and gastric intestinal metaplasia glands showed positive GCRG213p immunoreactivity. High GCRG213p immunostaining score in the primary gastric cancer was positively correlated with tumor differentiation (well differentiated, p = 0.001), Laurens classification (intestinal type, p < 0.05) and a late age onset of gastric adenocarcinoma (>=65 yrs; p < 0.05). GCRG213p expression has no association with other clinicopathological parameters, including survival. Western blotting analysis of GCRG213p expression in gastric cancer cells indicated that GCRG213p level was higher in gastric cancer cell lines than in human normal gastric epithelium immortalized cell line GES-1. Partial methylation of L1 in gastric cancer cells was confirmed by methylation-specific PCR. BLASTP program analysis revealed that GCRG213p peptide shared 83.0% alignment with the C-terminal region of L1 endonuclease (L1-EN). GCRG213p sequence possesses the important residues that compose the conserved features of L1-EN. CONCLUSIONS: GCRG213p could be a variant of L1-EN, a functional member of L1-EN family. Overexpression of GCRG213p is common in both primary gastric cancer and lymph node metastasis. These findings provide evidence of somatic L1 expression in gastric cancer, and its potential consequences in the form of tumor.
Serum is the most common and easily accessible patient specimen in a minimally invasive manner. As a biological resource, RNA in serum has been less explored for its clinical utilization due to prevailing concerns regarding its high degradable nature. In the current study, however, we have documented the use of human serum RNA for viral categorization and discovery through transcriptome sequencing and analysis using well-curated databases and advanced bioinformatic tools. Such an integrated approach may have an immediate application in any clinical situations concerning with viral etiology.
BACKGROUND: The prognostic value of gender and age in the survival of nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT) is unclear. Several studies have suggested a female advantage in the prognosis of solid tumors. We investigated the relationship between gender differences and disease outcome in NPC patients treated with IMRT in South China. METHODS: A total of 299 patients with non-disseminated NPC were analyzed retrospectively. IMRT was delivered with a simultaneous modulated, accelerated radiotherapy boost technique at prescribed doses of 70 Gy/30 fractions/6 weeks to the primary tumor (GTVp) and positive neck nodes (GTVn), 60Gy (2.0 Gy/day) to the clinical target volume (CTV) and upper neck region and 54 Gy (1.8 Gy/day) to the clinically negative low neck. A median boost dose of 9.2 Gy (4--20 Gy) was administered to patients with persistent disease at the primary site. RESULTS: With a median follow-up of 52 months, the male patients had a significantly unfavorable 5-year OS (70.7% compared to 94.1%, P < 0.001), DPFS (71.5% compared to 87.3%, P = 0.029) and DMFS (77.2% compared to 89.7%, P = 0.036) than the female patients. In patients younger than 45, the male patients had a poorer 5-year OS (66.8% compared to 91.2%, P = 0.008), DPFS (59.9% compared to 91.2%, P = 0.005) and DMFS (66.4% compared to 94.0%, P = 0.004) than the female patients. For patients older than 45, only the 5-year OS (72.2% compared to 96.0%, P = 0.001) was significantly different. CONCLUSIONS: Gender and age are strong independent prognostic factors for NPC in this study. We are the first to report that younger male patients were more likely to have distant metastases and exhibited inferior overall survival and disease progression-free survival rates compared to other patients.
Cyanobacteria can utilize solar energy and convert carbon dioxide into biofuel molecules in one single biological system. Synechocystis sp. PCC 6803 is a model cyanobacterium for basic and applied research. Alkanes are the major constituents of gasoline, diesel and jet fuels. A two-step alkane biosynthetic pathway was identified in cyanobacteria recently. It opens a door to achieve photosynthetic production of alka(e)nes with high efficiency by genetically engineering cyanobacteria.
Detailed mechanisms for the formation of hydroxyl or alkoxyl radicals in the reactions between tetrachloro-p-benzoquinone (TCBQ) and organic hydroperoxides are crucial for better understanding the potential carcinogenicity of polyhalogenated quinones. Herein, the mechanism of the reaction between TCBQ and H2O2 has been systematically investigated at the B3LYP/6-311++G** level of theory in the presence of different numbers of water molecules. We report that the whole reaction can easily take place with the assistance of explicit water molecules. Namely, an initial intermediate is formed first. After that, a nucleophilic attack of H2O2 onto TCBQ occurs, which results in the formation of a second intermediate that contains an OOH group. Subsequently, this second intermediate decomposes homolytically through cleavage of the O-O bond to produce a hydroxyl radical. Energy analyses suggest that the nucleophilic attack is the rate-determining step in the whole reaction. The participation of explicit water molecules promotes the reaction significantly, which can be used to explain the experimental phenomena. In addition, the effects of F, Br, and CH3 substituents on this reaction have also been studied.
In the title compound, C14H16N2O3, an analog of the chromophore in green fluorescent protein, the meth-oxy-phenyl substituent and the imidazole N adopt a Z conformation with respect to the C=C bond. Aside from the hy-droxy-ethyl group, the mol-ecule is approximately planar, with the five- and six-membered ring planes forming a dihedral angle of 9.3?(1)°. An intra-molecular C-H?N contact occurs. In the crystal, O-H?N hydrogen bonds link the mol-ecules, forming chains along the b-axis direction. C-H?O hydrogen bonds are also observed.
Summary Fluorescence in situ hybridization (FISH) is a cytogenetic technology used to detect chromosomal abnormalities in preimplantation human embryos. However, its efficiency is not stable due to improper sample preparation. The present study was designed to modify the current sample preparation technique and then to evaluate its efficiency in human preimplantation genetic diagnosis (PGD). Day 3 cleavage embryos as well as day 5 and 6 blastocysts were biopsied by mechanical aspiration method. In the present study, two methods were used for sample preparation of the biopsied cells. Method I was the traditional method, in which each blastomere was placed in a hypotonic solution for 5 min and then fixed on glass slides. The slides were kept at room temperature before the FISH procedures. Method II was a modified method, in which all blastomeres were placed individually in hypotonic solution drops covered by oil for at least 5 min and then fixed on slides with 0.1% Tween/HCl. After fixation, the slides were kept at -20°C for at least 30 min before the FISH procedures. The two methods were compared in terms of time consumption and proportions of blastomeres with FISH signals. In total, 329 blastomeres from day 3 embryos were fixed by Method I with an average fixation time of 8-10 min for each blastomere. By contrast, with Method II, 362 blastomeres were fixed and the average time was 3-4 min for each blastomere. After FISH, more nuclei had signals with Method II (97.2%) than with Method I (86.9%). All cells that were biopsied from blastocysts and prepared with Method II had FISH signals. However, Method I was not suitable for the fixation of multiple cells biopsied from blastocysts as cells were not traceable during the fixation. The present study indicates that proper sample preparation is critical for obtaining FISH signals in cells biopsied from preimplantation human embryos; hence these modifications can increase the efficiency of human PGD.
B7-H1 is a co-inhibitory molecule belonging to the B7 family. The B7-H1 protein is only expressed on macrophage lineage of cells in normal tissues, but is overexpressed in most types of tumor. The aberrant expression of cell surface B7-H1 on cancer cells is generally associated with high-risk prognostic factors. The tumor-associated B7-H1 increases apoptosis of antigen-specific T cells through interaction with its receptor PD-1 on CD8+ T cells and contributes to tumor immune evasion. These features suggest that B7-H1 may be a therapeutic target for the B7-H1-expressing tumors. We developed a therapeutic vaccine by coupling a tetanus toxoid T-helper cell epitope with the N-terminal of B7-H1 IgV-like domain. This vaccine was able to induce high titers of antibodies against B7-H1 in mice which were able to bind to native cell surface B7-H1. We chose the B7-H1-expressing SP2/0 myeloma and its syngeneic host (the BALB/c mouse) as the model to study the antitumor activity of the rhB7-H1M vaccine. Vaccination with this modified B7-H1 protein resulted in almost complete protection from SP2/0 tumor challenge and efficiently eliminated pre-established tumors in mice. In addition, B7-H1 vaccination was able to decrease the percentage of CD4+ Foxp3+ regulatory T cells in tumor-bearing mice and which might improve antitumor immunity. These data demonstrate the potential of B7-H1-based vaccine as a therapeutic agent for the treatment of cancer overexpressing B7-H1.
Vitrification is a novel cryopreservation method for mammalian blastocysts. This study was designed to compare different vitrification methods and slow freezing for their effects on survival rate and DNA integrity in mouse and human blastocysts. In Experiment 1, embryo survival and DNA integrity were compared between mouse blastocysts with collapsed and non-collapsed blastoceles. In Experiment 2, embryo survival and DNA integrity were compared between vitrified and slow-frozen mouse blastocysts. In Experiment 3, embryo survival and DNA integrity were compared between vitrified and slow-frozen human blastocysts. Fresh blastocysts were used as controls in all experiments. Higher (P?0.05) blastocyst survival rates were obtained in mouse blastocysts vitrified with collapsed versus intact blastoceles, although DNA-integrity indices in the surviving blastocysts were the same among vitrified and fresh blastocysts. More mouse blastocysts (P?0.05) survived after vitrification (100%) as compared to slow freezing (82.5%). DNA-integrity indices examined in the surviving blastocysts were also higher (P?0.001) in fresh (93.6%) and vitrified/warmed (93.7%) blastocysts than in slow-frozen/thawed (75.8%) ones. More human blastocysts survived with a higher DNA-integrity index after vitrification/warming than after slow freezing/thawing. These results indicate that higher survival rates can be obtained by vitrification of blastocele-collapsed blastocysts, and that vitrification causes less cell apoptosis in both mouse and human blastocysts compared to slow freezing. Vitrification of blastocysts after blastocele collapse by single laser pulse supports a higher survival rate and less DNA apoptosis, suggesting that laser blastocele collapse is a safe procedure for blastocyst vitrification.
Quasispecies is a remarkable characteristic of hepatitis C virus (HCV) and has profound roles in HCV biology and clinical practice. The understanding of HCV quasispecies behavior, in particular in acute HCV infection, is valuable for vaccine development and therapeutic interference. However, acute HCV infection is seldom encountered in clinic practice due to its silent onset. In the present study, we reported a unique case of de novo HCV infection associated with the transplantation of bone marrow from a HCV-positive donor. HCV quasispecies diversity was determined in both the donor and the recipient over a 4-year follow-up, accompanied with simultaneous measurement of HCV neutralizing antibody. Detailed genetic and phylogenetic analyses revealed a divergent quasispecies evolution, which was not related to dynamic changes of HCV neutralizing antibody. Instead, our data suggested an essential role of the fitness adaptation of founder viral population in driving such an evolutionary pattern.
We studied the supramolecular assembly of a multifunctional ligand, cis-bis-terpyridine tetraphenyl ethylene, on a Cu(111) surface by low-temperature scanning tunneling microscopy (STM). Three distinctive supramolecular structures, metallacycles, propeller-shaped clusters and extended linear chains, are formed under specific assembly conditions owing to different inter-molecular binding modes of Cu-coordination, van der Waals interaction and hydrogen bonding, respectively.
Pyrazinamide (PZA) is an important first-line anti-tuberculosis drug. But PZA susceptibility test is challenging because PZA activity is optimal only in an acid environment that inhibits the growth of M. tuberculosis. For current phenotypic methods, inconsistent results between different labs have been reported. Direct sequencing of pncA gene is being considered as an accurate predictor for PZA susceptibility, but this approach needs expensive sequencers and a mutation database to report the results. An in-vitro synthesized Pyrazinamidase (PZase) assay was developed based on PCR amplification of pncA gene and an in vitro wheat germ system to express the pncA gene into PZase. The activity of the synthesized PZase was used as an indicator for PZA susceptibility. Fifty-one clinical isolates were tested along with pncA sequencing and the BACTEC MGIT 960 methods. The in-vitro synthesized PZase assay was able to detect PZA susceptibility of M. tuberculosis within 24 h through observing the color difference either by a spectrometer or naked eyes. This method showed agreements of 100% (33/33) and 88% (14/16) with the pncA sequencing method, and agreements of 96% (27/28) and 65% (15/23) with the BACTEC MGIT 960 method, for susceptible and resistant strains, respectively. The novel in-vitro synthesized PZase assay has significant advantages over current methods, such as its fast speed, simplicity, no need for expensive equipment, and the potentials of being a direct test, predicting resistance level and easy reading results by naked eyes. After confirmation by more clinical tests, this method may provide a radical change to the current PZA susceptibility assays.
We have studied the organometallic intermediate of a surface-supported Ullmann coupling reaction from 4, 4?-dibromo-p-terphenyl to poly(para-phenylene) by scanning tunneling microscopy/spectroscopy and density functional theory calculations. Our study reveals at a single-molecular level that the intermediate consists of biradical terphenyl (ph)(3) units that are connected by single Cu atoms through C-Cu-C bridges. Upon further increasing the temperature, the neighboring biradical (ph)(3) units are coupled by C-C bonds forming poly(para-phenylene) oligomers while the Cu atoms are released.
Nasopharyngeal cancer (NPC) is a relatively uncommon malignant epithelial cancer seen worldwide. The treatment of NPC has evolved toward combined modality treatment with radiation therapy and chemotherapy. However, chemotherapeutic agents currently have a secondary role, due to their lack of efficacy as curative agents. Recent identification of a novel property of statin drugs raises a promising hope that concurrent use of statins may enhance the efficacy of single-drug chemotherapy in NPC. However, the effects of statins have not been studied before in NPC. In this in vitro study, we demonstrate a unique property of statins that can enhance the efficacy of cisplatin in NPC.
To determine if statins induce anti-inflammatory effects in upper airway inflammation. Mediators of innate and adaptive immunity regulate airway inflammation. Release of these mediators involves enzymatic conversion of polyunsaturated fatty acids into biologically active mediators, which can be blocked by statins. Although upper airway inflammation and chronic sinusitis occur in millions of patients with asthma worldwide, the anti-inflammatory effects of statins in upper airway inflammation have not been previously studied.
We study single conjugated polyphenylene oligomers consisting of 3n (2 ? n ? 12) phenyl units by means of cryogenic scanning tunneling microscopy and spectroscopy. The spatially resolved local densities of states reveal a progressive development of a continuous conduction band out of discrete molecular orbitals as the length of the oligomers increases. The experimental results are satisfactorily described by tight-binding calculations which gave a conduction band bandwidth of 4.5 ± 0.2 eV and a band gap of 3.1 ± 0.2 eV for an infinitely long polymer. We observed two types of defects, known as conformational torsional angle misfit and metasite kink. Tight-binding as well as density-functional theory model calculations confirm that both types of defects effectively destroy the delocalization.
Transcription factor forkhead box protein 3 (FOXP3) is a specific marker of naturally occurring regulatory T cells (Tregs). Recently, various reports have suggested that FOXP3 may represent a tumor escape mechanism in cancer cells apart from its roles in Tregs. In the present study, the clinical and biological characteristics of FOXP3 were evaluated in human gastric cancer. The expression and localization of FOXP3 in gastric cancer cell lines was analyzed to evaluate its cellular biological features. Sections of human gastric cancer specimens were stained using immunohistochemistry (IHC) to assess the relationship between FOXP3 expression and tumor differentiation, in order to identify its clinical characteristics in gastric cancer. Expression of FOXP3 mRNA and protein was found in four gastric cancer cell lines (AGS, SGC-7901, MKN-28 and MKN-45). IHC of the gastric cancer sections revealed that more than 56% of gastric cancers displayed nuclear or cytoplasmic FOXP3 staining. Furthermore, a linear relationship between the differentiation of the gastric cancer tissues and FOXP3 expression intensity was shown. IHC and confocal analysis showed that the expression of FOXP3 was mainly present in the nucleus of tumor cells in the tissues and cell lines. Thus, FOXP3 nuclear staining may be associated with the risk of poor tumor differentiation. Apart from the lymphocytes, no FOXP3 staining was noted in the normal gastric tissues and para-tumor tissues. The high frequency of FOXP3 expression in gastric cancer tissue is a significant finding in the investigation of tumor differentiation and immune escape. This mechanism provides a further understanding of gastric cancer and a novel therapeutic strategy is presented.
To better understand the potential role of sulfuric acid aerosols in the atmosphere, the electron capture properties of the H(2)SO(4)...HOO? complex have been systematically investigated by employing the MP2 and B3LYP methods in combination with the atoms in molecules (AIM) theory, energy decomposition analysis (EDA), and ab initio molecular dynamics. It was found that the electron capture process is a favorable reaction thermodynamically and kinetically. The excess electron can be captured by the HOO? fragment initially, and then the proton of the H(2)SO(4) fragment associated with the intermolecular H-bonds is transferred to the HOO? fragment without any activation barriers, resulting in the formation of the HOOH species directly. Therefore, the electron capture process of the H(2)SO(4)...HOO? complex provides an alternative source of HOOH in the atmosphere. The nature of the coupling interactions in the electron capture products are clarified, and the most stable anionic complex is also determined. Additionally, the influences of the adjacent water molecules on the electron capture properties are investigated, as well as the distinct IR features of the most stable electron capture product.
The production of high value biochemicals and high energy biofuels from sustainable resources through the use of microbial based, green conversion technologies could reduce the dependence on petrochemical resources. However, a sustainable source of carbon and a clean, cost effective method for its conversion to high quality biofuel products are obstacles that must be overcome. Here we describe the biosynthesis of fatty alcohols in a genetically engineered cyanobacterial system through heterologously expressing fatty acyl-CoA reductase and the effect of environmental stresses on the production of fatty alcohols in the mutant strains. Hydrocarbon production in three representative types of native cyanobacterial model strains and the mutant strain overexpressing acetyl-CoA carboxylase was evaluated. The results of this investigation demonstrate the potential for direct production of high value chemicals and high energy fuels in a single biological system that utilizes solar energy as the energy source and carbon dioxide as the carbon source.
Peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonists have been shown to be involved in the regulation of allergic inflammatory responses. The molecular mechanisms by which PPAR-gamma activation inhibits the inflammatory process have not been well understood.
A detailed knowledge of coupling interactions among sulfuric acid (H(2)SO(4)), the hydroperoxyl radical (HOO?), and water molecules (H(2)O) is crucial for the better understanding of the uptake of HOO? radicals by sulfuric acid aerosols at different atmospheric humidities. In the present study, the equilibrium structures, binding energies, equilibrium distributions, and the nature of the coupling interactions in H(2)SO(4)···HOO?···(H(2)O)(n) (n = 0-2) clusters have been systematically investigated at the B3LYP/6-311++G(3df,3pd) level of theory in combination with the atoms in molecules (AIM) theory, natural bond orbital (NBO) method, energy decomposition analyses, and ab initio molecular dynamics. Two binary, five ternary, and twelve tetramer clusters possessing multiple intermolecular H-bonds have been located on their potential energy surfaces. Two different modes for water molecules have been observed to influence the coupling interactions between H(2)SO(4) and HOO? through the formations of intermolecular H-bonds with or without breaking the original intermolecular H-bonds in the binary H(2)SO(4)···HOO? cluster. It was found that the introduction of one or two water molecules can efficiently enhance the interactions between H(2)SO(4) and HOO?, implying the positive role of water molecules in the uptake of the HOO? radical by sulfuric acid aerosols. Additionally, the coupling interaction modes of the most stable clusters under study have been verified by the ab initio molecular dynamics.
A molecular rotor which includes a central rotator group was investigated by scanning tunneling microscopy at 4.9 K as it was grafted on a Cu(111) surface via its two terminal groups. Topographs with submolecular resolution revealed several distinct molecular conformations which we attribute to different angular orientations of the rotator and which are locally stable states according to density functional theory calculations. Time-resolved tunneling current spectra showed that the rotator undergoes a torsional motion around the molecular long axis as stimulated by tunneling electrons in a one-electron process with an excitation energy threshold of 355 meV. Calculations identified an intrinsic axial vibration mode of the rotator group at 370 meV as adsorbed on the surface, which we propose to be the channel for effectively converting the tunneling electron energy into the mechanical energy of the intramolecular torsion.
Superexchange coupling in poly-p-phenylene molecular wires was probed using scanning tunneling microscopy/spectroscopy at cryogenic temperatures. The coupling strength was characterized by measuring the energy splitting between the molecular states constructed by symmetric and antisymmetric dimerization of molecular fragments orbitals. The results confirm the theoretically predicted exponential decay behavior of the superexchange coupling on a single-molecule level. A decay constant of 0.10 +/- 0.02 A(-1) was obtained. Owing to the high spatial resolution of scanning tunneling microscopy, the molecules internal states (e.g., molecular conformation) as well as external states (e.g., interaction with foreign atoms or molecules) were elucidated with atomic precision at the mean time of characterizing the superexchange coupling. This method provides a new approach to quantify how intramolecular charge transfer is influenced by molecular conformation and interaction with the surroundings.
We have fabricated atom-molecule contacts by attachment of single Cu atoms to terpyridine side groups of bis-terpyridine tetra-phenyl ethylene molecules on a Cu(111) surface. By means of scanning tunneling microscopy, spectroscopy, and density functional calculations, we have found that, due to the localization characteristics of molecular orbitals, the Cu-atom contact modifies the state localized at the terpyridine side group which is in contact with the Cu atom but does not affect the states localized at other parts of the molecule. These results illustrate the contact effects at individual orbitals and offer possibilities to manipulate orbital alignments within molecules.
Controversies exists with regard to target volumes as far as thoracic radiotherapy (TRT) is concerned in the multimodality treatment for limited-stage small cell lung cancer (LSCLC). The aim of this study is to prospectively compare the local control rate, toxicity profiles, and overall survival (OS) between patients received different target volumes irradiation after induction chemotherapy.
The preparation process and photoluminescent properties of one-dimensional BaF2:Eu3+ nanorods (NRs) and microrods (MRs) were investigated. The results indicate that the samples were NRs with uniform diameters in the range of 30-50 nm, and lengths in the range of 1.2-3 microm when cooled to room temperature naturally. However, the samples were MRs with length of 1.5-3.0 microm and outer diameters of 200-250 nm when cooled to room temperature immediately. Furthermore, the relative intensity of 5D0 --> 7F2 depended on the two structures obtained under different temperatures. This work demonstrates that a MRs may be more favorable than NRs for photoluminescence.
To gain a better understanding of the antioxidation behaviors of vitamin C, the reactions between vitamin C (monoanionic form, AAH(-)) and two radicals, (·)H and (·)OH, have been investigated employing the B3LYP and BHandHLYP methods in combination with the atoms in molecules (AIM) theory and energy decomposition analyses (EDA). Both the radical additions to the five-membered ring of AAH(-) and H-abstraction reactions are explored. The reaction profiles of various reactions have been obtained. The most favorable active site to be attacked by radical addition has been confirmed to be the C2 site of AAH(-), which is different from that of the C3 site in the neutral vitamin C. The (·)OH addition reactions are essentially diffusion-controlled processes, which is in contrast to the previous reports. A new source for the formation of the principal anion free radical (AFR) of AAH(-) has been observed in the (·)OH attack process, i.e., AFR can be formed mainly from the H13 abstraction reaction involving two types of concerted proton-electron transfer (CPET) mechanisms. Moreover, the binding characters and formation mechanisms of the stable reaction complex formed during the formation of AFR have been systematically investigated.
Mg-Zn-Ca bulk metallic glass with different compositions (Mg66Zn30Ca4 and Mg70Zn25Ca5) have been prepared for this study and their feasibility as biodegradable metallic materials have been evaluated by the microstructural, surface analysis, mechanical testing, corrosion and cytotoxicity tests. It was found that the Mg66Zn30Ca4 sample presents a more uniform corrosion morphology than as-rolled pure Mg and Mg70Zn25Ca5 samples, with much smaller micro-scale uniformly distributed pores beneath the corrosion product layer. The corrosion products were identified to be Mg(OH)(2) and Zn(OH)(2), and a uniform corrosion mechanism is proposed. Both indirect cytotoxicity and direct cell culture experiments were carried out using L929 and MG63 cell lines. The results show higher cell viabilities for Mg-Zn-Ca extracts than that for as-rolled pure Mg. In addition, L929 and MG63 cells were found to adhere and proliferate on the surface of Mg66Zn30Ca4 sample.
We study the propagation of plane electromagnetic waves through different systems consisting of arrays of split rings of different orientations. Many extraordinary EM phenomena were discovered in such systems, contributed by the off-diagonal magnetoelectric susceptibilities. We find a mode such that the electric field becomes elliptically polarized with a component in the longitudinal direction (i.e. parallel to the wavevector). Even though the group velocity [Formula: see text] and the wavevector k are parallel, in the presence of damping, the Poynting vector does not just get broadened, but can possess a component perpendicular to the wavevector. The speed of light can be real even when the product ?? is negative. Other novel properties are explored.
APMCF1 is a novel human gene first cloned from apoptotic MCF-7 cells. Our previous study found ectogenic APMCF1 could induce G1 arrest in hepatocarcinoma cell line HHCC. In order to search its broad expression profile for further understanding of its mechanism in tumor, we investigated a subcellular location of APMCF1 and performed an immunohistochemistry study including various tumor and normal tissues. Discovery from the expression characterization of AMPCF1 may have applicability in the analysis of its biological function in tumor.
Poor quality embryos discarded from in vitro fertilization (IVF) laboratories are good sources for deriving human embryonic stem cell (hESC) lines. In this study, 166 poor quality embryos donated from IVF centers on day 3 were cultured in a blastocyst medium for 2 days, and 32 early blastocysts were further cultured in a blastocyst optimum culture medium for additional 2 days so that the inner cell masses (ICMs) could be identified and isolated easily. The ICMs of 17 blastocysts were isolated by a mechanical method, while those of the other 15 blastocysts were isolated by immunosurgery. All isolated ICMs were inoculated onto a feeder layer for subcultivation. The rates of ICM attachment, primary ICM colony formation and the efficiency of hESC derivation were similar between the ICMs isolated by the two methods (P>0.05). As a result, four new hESC lines were established. Three cell lines had normal karyotypes and one had an unbalanced Robertsonian translocation. All cell lines showed normal hESC characteristics and had the differentiation ability. In conclusion, we established a stable and effective method for hESC isolation and culture, and it was confirmed that the mechanical isolation was an effective method to isolate ICMs from poor embryos. These results further indicate that hESC lines can be derived from poor quality embryos discarded by IVF laboratories.
Two-component systems (TCSs), typically consisting of a histidine kinase (HK) and a cognate response regulator (RR), are the most common signaling systems in bacteria. Besides paired genes encoding TCSs, there also exists unpaired HKs and orphan RRs. In Streptomyces coelicolor, 13 orphan RRs have been annotated. Because of lack of cognate HKs, little is known as yet about the regulation of orphan RRs. Bioinformatic analysis revealed that several orphan RRs had high amino acid sequence identities with RRs from typical TCSs in S. coelicolor. Among them, the orphan RR SCO3818 and RR SCO0204, which paired with HK SCO0203, showed the highest identity (65%), suggesting that the two RRs might both be under the regulation of SCO0203. Following studies showed that SCO0203 could phosphorylate not only SCO0204 but also SCO3818. Deletion of either sco0203 or sco3818 led to enhanced production of blue-pigmented antibiotic actinorhodin, which indicated a functional correlation between SCO0203 and SCO3818. These results suggested that SCO3818 might be regulated by SCO0203. This is the first report describing the regulation of an orphan RR by an HK. Moreover, this is also the first identification of cross-talk between different TCS components in S. coelicolor.
Adjuvants are necessary to elicit high titers of antibodies in vaccine-immunization procedures. We previously developed a mouse tumor necrosis factor-alpha (TNF-alpha) autovaccine (mTNF-PADRE) capable of inducing anti-TNF-alpha antibodies. In this study, we investigated the therapeutic effect of adjuvant-free administration of the autovaccine on collagen-type-II-induced rheumatoid arthritis (CIA) in mice. Our results showed that the vaccine could ameliorate the symptoms of CIA in mice. In addition, this study suggests that it is possible to control the antibody levels in mice immunized with mTNF-PADRE without adjuvant.
Two-component system AfsQ1-Q2 of Streptomyces coelicolor was identified previously for its ability to stimulate actinorhodin (ACT) and undecylprodigiosin (RED) production in Streptomyces lividans. However, disruption of either afsQ1 or afsQ2 in S. coelicolor led to no detectable changes in secondary metabolite formation or morphogenesis. In this study, we reported that, when cultivated on defined minimal medium (MM) with glutamate as the sole nitrogen source, the afsQ mutant exhibited significantly decreased ACT, RED, and calcium-dependent antibiotic (CDA) production and rapid growth of aerial mycelium. In addition, we also found that deletion of sigQ, which is located upstream of afsQ1-Q2 and encodes a putative sigma factor, led to the precocious hyperproduction of these antibiotics and delayed formation of sporulating aerial mycelium in the same glutamate-based defined MM. Reverse-transcription polymerase chain reaction and egfp fusion analyses showed that the expression of sigQ was under control by afsQ. In addition, deletion of both afsQ-sigQ resulted in the phenotype identical to that of afsQ mutant. The results suggested that afsQ1-Q2 and sigQ worked together in the regulation of both antibiotic biosynthesis and morphological development, and sigQ might be responsible for antagonizing the function of AfsQ1-Q2 in S. coelicolor, however, in a medium-dependent manner. Moreover, the study showed that the medium-dependent regulation of antibiotic biosynthesis by AfsQ1-Q2-SigQ was through pathway-specific activator genes actII-ORF4, redD, and cdaR. The study provides new insights on regulation of antibiotic biosynthesis and morphological development in S. coelicolor.
Controversial roles of FOXP3 in different cancers have been reported previously, while its role in gastric cancer is largely unknown. Here we found that FOXP3 is unexpectedly upregulated in some gastric cancer cells. To test whether increased FOXP3 remains the tumor suppressor role in gastric cancer as seen in other cancers, we test its function in cell proliferation both at basal and TNF? mimicked inflammatory condition. Compared with the proliferation inhibitory role observed in basal condition, FOXP3 is insufficient to inhibit the cell proliferation under TNF? treatment. Molecularly, we found that TNF? induced an interaction between FOXP3 and p65, which in turn drive the FOXP3 away from the promoter of the well known target p21. Our data here suggest that although FOXP3 is upregulated in gastric cancer, its tumor suppressor role has been dampened due to the inflammation environment.
Trophectoderm (TE) biopsy and DNA microarray have become the new technologies for preimplantation genetic diagnosis in humans. In this study, we comprehensively examined aneuploid formation in human blastocysts produced in vitro with microarray and investigated the clinical outcome after transfer of euploid embryos. Biopsied cells from either TE or inner cell mass (ICM) were processed for microarray to examine the errors in 23 pairs of chromosomes and the consistency between TE and ICM. It was found that 56.6% of blastocysts were aneuploid. Further analysis indicated that 62.3% of aneuploid blastocysts had single and 37.7% had multiple chromosomal abnormalities. Chromosome errors could occur in any chromosome, but errors in chromosome 21 accounted for the most (11.3%) among the 23 pairs of chromosomes. Transfer of array-screened blastocysts produced high pregnancy (70.2%) and implantation (63.5%) rates. Microarray of TE and ICM cells in the same blastocysts revealed that high proportions of aneuploid blastocysts (69.2%) were mosaic, including aneuploid TE and euploid ICM, inconsistent anomalies between ICM and TE, or euploid TE cells and aneuploid ICM in the same blastocyst. These results indicate that high proportions of human blastocysts produced in vitro from women of advanced maternal age are aneuploid and mosaic. Errors can occur in any of the 23 pairs of chromosomes in human blastocysts. Biopsy from TE in blastocysts does not exactly predict the chromosomal information in ICM if the embryos are aneuploid. Some mosaic blastocysts have euploid ICM, which may indicate important differentiate mechanism(s) of human preimplantation embryos.
Human fetal membranes express 11?-hydroxysteroid dehydrogenase type 1 (11?-HSD1), which reduces biologically inert cortisone to active cortisol and may provide an extraadrenal source of cortisol mediating fetal development and parturition. The reductase activity of 11?-HSD1 depends on the availability of the cofactor reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) derived from the enzymatic activity of hexose-6-phosphodehydrogenase (H6PD). Based on the feed-forward induction of 11?-HSD1 by glucocorticoids in human fetal membranes, we hypothesize that glucocorticoids simultaneously induce H6PD in the fetal membranes. We found a parallel distribution of H6PD and 11?-HSD1 in the amnion, chorion, and decidua. In cultured human amnion fibroblasts, small interfering RNA-mediated knockdown of H6PD expression significantly attenuated the conversion of cortisone to cortisol. Cortisol (0.01-1 ?m) induced H6PD expression in a concentration-dependent manner, which was attenuated by glucocorticoid receptor (GR) antagonist RU486. Cortisol induced the expression of p300, a histone acetyltransferase, whereas C646, an inhibitor of p300, attenuated the induction of H6PD by cortisol. Coimmunoprecipitation revealed GR and p300 in the same nuclear protein complex upon cortisol stimulation. Chromatin immunoprecipitation showed that cortisol increased the binding of p300 and GR to H6PD promoter and the acetylation of histone 3 lysine 9 on the promoters. In conclusion, the induction of H6PD by cortisol requires the participation of GR and p300 as well as the acetylation of H3K9 by p300. This may be a prerequisite for the parallel induction of reductase activity of 11?-HSD1 in human amnion fibroblasts in a feed-forward loop that may influence fetal development and the onset of parturition.
A simple semiclassical drude-like conductivity of graphene is employed to describe plasmon excitations of graphene in the ring structures. A quasi-static self-consistent integral equation approach is performed, allowing the calculation of all the plasmon modes with different angular momentum l. Among them only the dipole modes (l = 1) will couple out to the radiation modes, which in turn can be excited optically by the plane waves, and the excitation energies as a function of the ratio of the radius of the inner hole to that of the outer ring have also been investigated. It is demonstrated that the energy of symmetric modes will monotonically decrease as the ratio rises, and the energy of antisymmetric modes does not exhibit a monotonically increasing behavior as in a three-dimensional metallic ring, but first reduces and then increases. These predictions are tested by full-wave simulations using the optical conductivity of graphene that was obtained from the random phase approximation (RPA).
Alzheimers disease (AD) is characterized by ?-amyloid (A?) plaques consisted primarily of aggregated A? proteins and neurofibrillary tangles formed by hyperphosphorylated tau protein. Both A? and hyperphosphorylated tau are toxic both in vivo and in vitro. Immunotherapy targeting A? seems to provide a promising approach to reduce the toxic species in the brain. However, there is little evidence from clinical trials so far indicating the efficacy of A? immunotherapy in cognitive improvement. Immunization with tau peptides or anti-tau antibodies could remove the tau aggregates and improve the cognitive function in preclinical study, which provides a novel strategy of AD therapy. In this article, we will summarize the immunotherapeutic strategies targeting either A? or tau.
It has been a long-term desire to fabricate hybrid silicon-molecular devices by taking advantages of organic molecules and the existing silicon-based technology. However, one of the challenging tasks is to design applicable functions on the basis of the intrinsic properties of the molecules, as well as the silicon substrates. Here we demonstrate a silicon-molecular system that produces negative differential resistance (NDR) by making use of the well-defined intrinsic surface-states of the Si (111)-?3 × ?3-Ag (R3-Ag/Si) surface and the molecular orbital of cobalt(II)-phthalocyanine (CoPc) molecules. From our experimental results obtained using scanning tunneling microscopy/spectroscopy, we find that NDR robustly appears at the Co(2+) ion centers of the CoPc molecules, independent of the adsorption configuration of the CoPc molecules and irrespective of doping type and doping concentration of the silicon substrates. Joint with first principle calculations, we conclude that NDR is originated from the resonance between the intrinsic surface-state band S(1) of the R3-Ag/Si surface and the localized unoccupied Co(2+)d(z(2)) orbital of the adsorbed CoPc molecules. We expect that such a mechanism can be generally used in other silicon-molecular systems.
Direct conversion of solar energy and carbon dioxide to drop in fuel molecules in a single biological system can be achieved from fatty acid-based biofuels such as fatty alcohols and alkanes. These molecules have similar properties to fossil fuels but can be produced by photosynthetic cyanobacteria.
Nonlinear excitations associated with dopant states play fundamental roles for charge transport in conjugated polymers. Here we report on real-space visualization of individual dopant states in single conjugated oligomers of poly-para-phenylene using cryogenic scanning tunneling microscopy and spectroscopy. We have found that these states exhibit a typical spatial extension of 4 nm along the oligomers. In particular, these states create a shallow level inside the band gap of the parent oligomers. The origin of these states is traced to a novel doping mechanism of dehydrogenation of the phenylene moiety. Furthermore, we use a scanning tunneling microscope tip to charge/discharge the dopant states and measure their lifetimes. The present results demonstrate a strategy to characterize and manipulate individual dopant states in conjugated polymers with subnanometer resolution.
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