We report a charge sensitive optical detection technique for label-free study of molecular interactions. Traditional label-free optical detection techniques largely rely on the detection of the mass of a molecule, which are insensitive to small molecules. In contrast, the present technique detects the charge of a molecule, where the signal does not diminish with the size of the molecule, thus capable for studying small molecules. In addition, the technique is compatible with the standard microplate platform, making it suitable for high-throughput screening of drug candidates. Using the technique, we have detected 0.2 nM anti-BSA and 15 ?M anti-cancer drug (imatinib) with an enzyme modified surface. The achieved effective charge detection limit is ~0.25 electron charge/?m(2), corresponding to ~0.3 fg/mm(2) for imatinib, which is orders of magnitude better than traditional label-free optical detection methods.
A series of solution processible greenish-blue-emitting Ir dendrimers with polyether dendrons that consist of N-phenylcarbazole (NPC) are developed via a convenient post-dendronization method. It involves two steps: (i) the successful preparation of a reactive Ir core, namely m-HO-dfppyIr, only when the hydroxyl group is located at the meta position relative to the N atom in the C^N ligand so as to eliminate the possible resonance structure between enol and keto; and (ii) the subsequent functionalization with NPC-based polyether dendrons to afford the first, second and third generation Ir dendrimers (Ir-G1B, Ir-G2B and Ir-G3B) with ease and high yields over 60%. All these dendritic complexes possess good thermal stability with decomposition temperatures higher than 380 °C and glass transition temperatures higher than 200 °C. In addition, with the growing generation number, the intermolecular interactions between emissive Ir cores are expected to be effectively inhibited to avoid the luminescence quenching, which is confirmed from the blue-shifted emission peak and the enhanced lifetime of Ir-G3B in the solid state. As a result, on going from Ir-G1B to Ir-G3B, the maximum luminous efficiency rises upward from 4.7 to 9.2 cd A(-1) for nondoped electrophosphorescent devices. Further optimization by doping them into a dendritic H2 host leads to the improved luminous efficiencies as high as 20.0-25.2 cd A(-1).
Conventional evaluation methods of chemotherapeutic efficacy such as tissue biopsy and anatomical measurement are either invasive with potential complications or dilatory to capture the rapid pathological changes. Here, a sensitive and resolution-scalable photoacoustic microscopy (PAM) with theranostic nanoformulation was developed to noninvasively monitor the therapy response in a timely manner. Ultrasmall graphene oxide (GO) nanosheets were designed as both drug loading vehicle and photoacoustic signal amplifier to the tumor. With the signal enhancement by the injected contrast agents, the subtle microvascular changes of the chemotherapy response in tumor were advantagely revealed by our PAM system, which was much earlier than the morphological measurement by standard imaging techniques. High tumor uptake of the enhanced nanodrug with Cy5.5 labeling was validated by fluorescence imaging. At different observation scales, PAM offered unprecedented sensitivity of optical absorption and high spatial resolution over optical imaging. Our studies demonstrate the PAM system with synergistic theranostic strategy to be multiplexing platforms for tumor diagnosis, drug delivery, and chemotherapy response monitoring in a very early stage and effective way.
A smart pH-responsive photodynamic therapy system based on upconversion nanoparticle loaded PEG coated polymeric lipid vesicles (RB-UPPLVs) was designed and prepared. These RB-UPPLVs which are promising agents for deep cancer photodynamic therapy applications can achieve enhanced tumor cellular internalization and near-infrared light-triggered photodynamic therapy.
New N-substituted sophoridinic acid/ester and sophoridinol derivatives were synthesized and evaluated for their cytotoxic activity in human HepG2 hepatoma cells from the lead sophoridine (1). Among the newly synthesized compounds, sophoridinol 7i displayed a potential antiproliferative activity with an IC50 of 3.1 ?M. Importantly, it exerted an almost equipotent effect against both wild MCF-7 and adriamycin (AMD)-resistant MCF-7 (MCF-7/AMD) breast carcinoma cell lines. Its mode of action was to arrest the cell cycle at the G0/G1 phase, consistent with that of the parent 1. In addition, compound 7i also showed a reasonable ClogP value and favorable pharmacokinetic property with an area under the concentration-time curve (AUC) of 10.3 ?M·h in rats, indicating an ideal druggable characteristic. We consider sophoridinol derivatives to be a novel family of promising antitumor agents with an advantage of inhibiting drug-resistant cancer cells.
Sequence-related amplified polymorphism (SRAP), amplified fragment length polymorphism (AFLP), and inter-simple sequence repeat (ISSR) markers were used to estimate the genetic diversity and relationships among Eucommia ulmoides cultivars in China. A total of 240, 192, and 150 DNA fragments were detected by 10 SRAP primer combinations, 10 AFLP primer combinations, and 10 ISSR primers, among which 89.2, 65.1, and 88.0% of the fragments were polymorphic, respectively. Cluster analysis revealed that Qinzhong No. 3, Xiaoyeci, Qinzhong No. 1, and Qinzhong No. 2 formed independent clusters. The other 15 cultivars exhibited two clusters. The results of this study will help in the selection of parents for both genome mapping and crossbreeding purposes.
A new type of pH-responsive hydrogel surface with varying nanoparticle adsorptivities was fabricated to form a micro-patterned film. To increase its responsivity to environmental pH changes, we incorporated graphene oxide (GO) into a poly(methacrylic acid)-polyethylene glycol copolymer. Incorporating GO in the pH-responsive hydrogel significantly increased the adsorption-desorption responsivity of Ag nanoparticles on the gel surface. A pH oscillator in a closed reaction system composed of BrO3(-)-Fe(CN)6(4-)-SO3(2-) facilitated the self-oscillating adsorption-desorption of Ag nanoparticles on the GO-incorporated gel surface. The reversible adsorption-desorption of Ag nanoparticles on the patterned hydrogel surface in response to pH oscillations was determined using UV-visible spectroscopy in aqueous solution. The observed heterogeneous oscillations indicated that the adsorptivity of the gel surface can be reversibly changed on the patterned pH-responsive gel. This phenomenon is similar to various natural biological systems.
A series of surfaces that can either be fully wetted or non-wetted by three kinds of ionic liquids (ILs) are successfully designed by rationally controlling surface chemistries and structures. Meanwhile, the adhesion forces between these surfaces and the ILs can also be effectively modulated in a wide range. This fundamental research will greatly promote the development of IL-based materials in practical applications.
Electrostatic gating field and light illumination are two widely used stimuli for semiconductor devices. Via capacitive effect, a gate field modifies the carrier density of the devices, while illumination generates extra carriers by exciting trapped electrons. Here we report an unusual illumination-enhanced gating effect in a two-dimensional electron gas at the LaAlO3/SrTiO3 interface, which has been the focus of emergent phenomena exploration. We find that light illumination decreases, rather than increases, the carrier density of the gas when the interface is negatively gated through the SrTiO3 layer, and the density drop can be 20 times as large as that caused by the conventional capacitive effect. This effect is further found to stem from an illumination-accelerated interface polarization, an originally extremely slow process. This unusual effect provides a promising controlling of the correlated oxide electronics in which a much larger gating capacity is demanding due to their intrinsic larger carrier density.
Numerous studies have revealed that regular consumption of certain fruits and vegetables can reduce the risk of many diseases. The rhizome of Zingiber officinale (ginger) is consumed worldwide as a spice and herbal medicine. It contains pungent phenolic substances collectively known as gingerols. 6-Gingerol is the major pharmacologically-active component of ginger. It is known to exhibit a variety of biological activities including anticancer, anti-inflammation, and anti-oxidation. 6-Gingerol has been found to possess anticancer activities via its effect on a variety of biological pathways involved in apoptosis, cell cycle regulation, cytotoxic activity, and inhibition of angiogenesis. Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, 6-gingerol has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various diseases. Taken together, this review summarizes the various in vitro and in vivo pharmacological aspects of 6-gingerol and the underlying mechanisms.
We report on a quantitative study of small molecule binding kinetics on protein microarrays with plasmonic-based electrochemical impedance microscopy (P-EIM). P-EIM measures electrical impedance optically with high spatial resolution by converting a surface charge change to a surface plasmon resonance (SPR) image intensity change, and the signal is not scaled to the mass of the analyte. Using P-EIM, we measured binding kinetics and affinity between small molecule drugs (imatinib and SB202190) and their target proteins (kinases Abl1 and p38-?). The measured affinity values are consistent with reported values measured by an indirect competitive binding assay. We also found that SB202190 has weak bindings to ABL1 with KD > 10 ?M, which is not reported in the literature. Furthermore, we found that P-EIM is less prone to nonspecific binding, a long-standing issue in SPR. Our results show that P-EIM is a novel method for high-throughput measurement of small molecule binding kinetics and affinity, which is critical to the understanding of small molecules in biological systems and discovery of small molecule drugs.
Surface plasmon resonance (SPR) has become an indispensable tool for label-free detection and quantification of molecular binding. Traditionally, the principle of SPR biosensors is described with a stratified medium model, in which discrete molecules are approximated with a uniform thin film. With the recent technical advances, SPR can now detect extremely low coverage of molecules, which raises the question of the validity of the traditional model. Here, we present combined theoretical, numerical and experimental analysis of SPR detection principle by considering the discrete nature of the molecules (particles). Our results show that the stratified medium model can provide reasonable description of SPR biosensors for relatively high coverage and weakly scattering samples. However, interference between the SPR images of individual particles needs to be considered for high spatial resolution images and for strong scattering samples at certain incident angles of light.
This study assessed conflict monitoring during presentation of risky decision alternatives, as indexed by the Nogo-N2, Nogo-P3, N2d and P3d event-related potentials (ERP). Decision-makers were tested on a Go/Nogo gambling task in which gain/loss outcomes as well as stimulus type (Go/Nogo) were equiprobable. Frontal-central Nogo-N2 and Nogo-P3 did not significantly differ across risky decision alternatives, whereas N2d and P3d amplitudes were more sensitive to the nature of risky decision alternatives. Frontal-central N2d was moderated by the magnitude of alternatives, with N2d amplitude greater for large than small alternatives, a result that suggests a greater degree of conflict monitoring for the former. Central P3d was associated with alternative valence, such that P3d amplitude was greater for loss than gain valences, again suggestive of more conflict monitoring for the former. The N2d and P3d potentials in risky decision alternatives are discussed in terms of the functional significance of the N2/P3 complex.
Progeny performances, variations and combining abilities for growth traits were evaluated in a factorial mating design of Eucommia ulmoides. Three marker systems, sequence-related amplified polymorphism, amplified fragment length polymorphism, and inter-simple sequence repeat, were used to determine genetic distances between parents. Correlations of genetic distances with progeny performances, within-family coefficients of variation and specific-combining abilities were established for height and basal diameter traits. Significant positive correlations were found between progeny performances of growth traits and genetic distances of parents based on sequence-related amplified polymorphism markers or a combination of all 3 marker systems. This revealed that crosses between genetically distant parents produced progenies with excellent growth performances. The lack of correlations between parental genetic distances and within-family coefficients of variation or specific-combining abilities suggested that these characteristics were unpredictable. The results of this study represent a potential criterion to predict progeny performances and choose parents in the breeding program.
The regulatory elements for nosiheptide biosynthesis were identified by a novel host-vector system with an endogenous gene within the biosynthetic gene cluster as a reporter gene. The present study offers a rapid and reliable method for the identification of regulatory elements in the biosynthesis of various bioactive natural products.
Abstract 1. The Krüppel-like factor (KLF) family of zinc-finger transcription factors plays a critical role in cell differentiation, phenotypic modulation and physiologic function. KLF15 has been proposed to regulate adipogenesis and gluconeogenesis. The objective of this study was to establish the association between KLF15 gene polymorphism and chicken growth and carcass traits. 2. An F2resource population of Gushi chickens crossed with Anka broilers was used to investigate the genetic effects of the chicken KLF15 gene. A 2-bp indel mutation (G13781_13782del/insAG) within intron 2 was detected, and a polymerase chain reaction-restriction fragment length polymorphism method was developed to genotype the F2 individuals. 3. Association analysis showed that the Single Nucleotide Polymorphisms (SNP) was significantly associated with chicken growth and carcass traits. The chickens with the insAG/insAG genotype generally had a significantly higher body weight and size than other genotypes. Gene expression for each genotype showed that birds carrying insAG/insAG had a higher expression level than the other genotypes. 4. The results suggested that this polymorphic site may serve as a useful target for marker assisted selection of chicken growth and carcass traits.
Detection of a single or small amount of charges and molecules in biologically relevant aqueous solutions is a long-standing goal in analytical science and detection technology. Here we report on self-assembled nano-oscillators for charge and molecular binding detections in aqueous solutions. Each nano-oscillator consists of a nanoparticle linked to a solid surface via a molecular tether. By applying an oscillating electric field normal to the surface, the nanoparticles oscillate, which is detected individually with ?0.1 nm accuracy by a plasmonic imaging technique. From the oscillation amplitude and phase, the charge of the nanoparticles is determined with a detection limit of ?0.18 electron charges along with the charge polarity. We further demonstrate the detection of molecular binding with the self-assembled nano-oscillators.
Harmonic motion imaging for focused ultrasound (HMIFU) utilizes an amplitude-modulated HIFU beam to induce a localized focal oscillatory motion simultaneously estimated. The objective of this study is to develop and show the feasibility of a novel fast beamforming algorithm for image reconstruction using GPU-based sparse-matrix operation with real-time feedback. In this study, the algorithm was implemented onto a fully integrated, clinically relevant HMIFU system. A single divergent transmit beam was used while fast beamforming was implemented using a GPU-based delay-and-sum method and a sparse-matrix operation. Axial HMI displacements were then estimated from the RF signals using a 1-D normalized cross-correlation method and streamed to a graphic user interface with frame rates up to 15 Hz, a 100-fold increase compared to conventional CPU-based processing. The real-time feedback rate does not require interrupting the HIFU treatment. Results in phantom experiments showed reproducible HMI images and monitoring of 22 in vitro HIFU treatments using the new 2-D system demonstrated reproducible displacement imaging, and monitoring of 22 in vitro HIFU treatments using the new 2-D system showed a consistent average focal displacement decrease of 46.7 ±14.6% during lesion formation. Complementary focal temperature monitoring also indicated an average rate of displacement increase and decrease with focal temperature at 0.84±1.15%/(°)C, and 2.03±0.93%/(°)C , respectively. These results reinforce the HMIFU capability of estimating and monitoring stiffness related changes in real time. Current ongoing studies include clinical translation of the presented system for monitoring of HIFU treatment for breast and pancreatic tumor applications.
Activated tumor-associated fibroblasts (TAFs) with abundant fibroblast activation protein (FAP) expression attract tremendous attention in tumor progression studies. In this work, we report a rapid 24 h FAP activation method for fibroblasts using silicon nanowires (SiNWs) as culture substrates instead of growth factors or chemokines. In contrast with cells cultured on flat silicon which rarely express FAP, SiNW cultivated cells exhibit FAP levels similar to those found in cancerous tissue. We demonstrated that activated cells grown on SiNWs maintain their viability and proliferation in a time-dependent manner. Moreover, environmental scanning electron microscopy (ESEM) and focused ion beam and scanning electron microscopy (FIB-SEM) analysis clearly revealed that activated cells on SiNWs adapt to the structure of their substrates by filling inter-wire cavities via filopodia in contrast to cells cultured on flat silicon which spread freely. We further illustrated that the expression of FAP was rarely detected in activated cells after being re-cultured in Petri dishes, suggesting that the unique structure of SiNWs may have a certain influence on FAP activation.
Mutations of presenilin 1 (PSEN1) gene are the most frequent cause for familial Alzheimers disease (AD). This study was set to explore potential mutation of PSEN1 gene in a Chinese family featuring early-onset Alzheimers disease (FAD).
Inspired by the interactions between platelets and tumor cells, multiscaled cytophilic interfaces are fabricated by assembling platelet-mimicking microspheres via oxidative polymerization of polyaniline nanohairs through transverse nanochannels in the shells of hollow polystyrene microspheres, and modifying specific recognition molecules. This interface realizes efficient tumor-cell recognition and isolation from artificial blood, suggesting a new platform for metastasis diagnosis and cancer treatment.
We examined mRNA expression levels of ERCC1, BRCA1, RRM1, and human ?-tubulin-III (TUBB3) in non-small-cell lung carcinoma (NSCLC) patients and investigated the association between expression of these genes and the clinical outcome of NSCLC treatment. A total of 366 patients who underwent surgery for NSCLC were included in this study. All patients received third-generation platinum-based chemotherapy as first-line treatment. The relative cDNA quantification for ERCC1, RRM1, BRCA1, and TUBB3 was determined using a fluorescence-based, real-time detection method. We found that low expression of ERCC1 and BRCA1 was associated with a good response to platinum-based chemotherapy, with an odds ratio [95% confidence interval (CI)] of 2.09 (1.33-3.27) and 2.92 (1.85-4.62), respectively. Multivariate Cox regression analysis indicated that patients with low expression of ERCC1 and BRCA1 attained a longer overall survival time than those with high expression, with a hazard ratio (95%CI) of 0.42 (0.23-0.77) and 0.39 (0.21-0.71), respectively. However, RMM1 and TUBB2 expressions were not correlated with clinical outcome of NSCLC. In conclusion, we found that low expression of ERCC1 and BRCA1 can be useful for selecting NSCLC patients who would benefit from chemotherapy and warrants further investigation in prospective studies.
Multifunctional "smart" particles with magnetic, topographic, cell-targeting, and stimulus-responsive properties are obtained using a "live template" strategy. These particles exhibit improved efficiency in capture of target cancer cells by introducing synergistic topographic interaction, and enable the release of captured cells with high viability via reduction of disulfide bonds. Diverse multifunctional particles could be designed using the "live template" strategy.
Mucoadhesives have been perceived as an effective approach for targeting the mucosa-associated diseases, which relied on the adhesive molecules to enhance the specificity. Here, topographical binding is proposed based on the fabrication of surface pore size tunable pollen-mimetic microspheres with phase separation and electrospray technology. We proved that microspheres with large-pores (pore size of 1005±448 nm) were the excellent potential candidate for the mucoadhesives, as they not only possessed better adhesion ability, but also could topographically bind cervical cancer cells. Our methods of topographical binding offered a new way of designing the mucoadhesives for treating the mucosa-associated diseases.
Many drugs are effective in the early stage of treatment, but patients develop drug resistance after a certain period of treatment, causing failure of the therapy. An important example is Herceptin, a popular monoclonal antibody drug for breast cancer by specifically targeting human epidermal growth factor receptor 2 (Her2). Here we demonstrate a quantitative binding kinetics analysis of drug-target interactions to investigate the molecular scale origin of drug resistance. Using a surface plasmon resonance imaging, we measured the in situ Herceptin-Her2 binding kinetics in single intact cancer cells for the first time, and observed significantly weakened Herceptin-Her2 interactions in Herceptin-resistant cells, compared to those in Herceptin-sensitive cells. We further showed that the steric hindrance of Mucin-4, a membrane protein, was responsible for the altered drug-receptor binding. This effect of a third molecule on drug-receptor interactions cannot be studied using traditional purified protein methods, demonstrating the importance of the present intact cell-based binding kinetics analysis.
Quantifying the interactions of bacteria with external ligands is fundamental to the understanding of pathogenesis, antibiotic resistance, immune evasion, and mechanism of antimicrobial action. Due to inherent cell-to-cell heterogeneity in a microbial population, each bacterium interacts differently with its environment. This large variability is washed out in bulk assays, and there is a need of techniques that can quantify interactions of bacteria with ligands at the single bacterium level. In this work, we present a label-free and real-time plasmonic imaging technique to measure the binding kinetics of ligand interactions with single bacteria, and perform statistical analysis of the heterogeneity. Using the technique, we have studied interactions of antibodies with single Escherichia coli O157:H7 cells and demonstrated a capability of determining the binding kinetic constants of single live bacteria with ligands, and quantify heterogeneity in a microbial population.
In order to gain an understanding of the nature of the interactions among thiophene (TS), thiophene sulfone (TSO2), dibenzothiophene (DBT), dibenzothiophene sulfone (DBTO2) and the ionic liquid N-butylpyridinium hydrogen sulfate ([BPY][HSO4]), a systematic investigation has been carried out using ab initio methods. The most stable structures indicate that both [BPY](+) and [HSO4](-) play crucial roles in the interactions between TS, TSO2, DBT, DBTO2 and [BPY][HSO4]. Analyses of the most stable optimized structures suggest the occurrence of steric effects, ?-? stacking effects, hydrogen bonds, and dihydrogen bonds. The ?-? stacking effect in [BPY][HSO4]-TSO2/[BPY][HSO4]-DBTO2 is less significant than that in [BPY][HSO4]-TS/[BPY][HSO4]-DBT, as TSO2 and DBTO2 are more nucleophilic than TS and DBT, resulting in stronger interactions between [BPY][HSO4] and TSO2/DBTO2 than between [BPY][HSO4] and TS/DBT. Thermodynamical data also demonstrate that TSO2/DBTO2 are more prone to interact with [BPY][HSO4] compared with TS/DBT.
This study provided insight into the characterization of secondary effluent from a wastewater treatment plant located in northeastern China. The secondary effluent was separated into three fractions, the dissolved, the near-colloidal and the suspended, to study their individual characteristics. It revealed that most of the organics in the secondary effluent existed in the dissolved form, accounting for 78.1-86.5% of the total chemical oxygen demand and 82.6-86.6% of the total organic carbon. Results from the molecular weight distribution study further indicated that organics with MW < 1k Da constituted 56.3-62.7% of total organics. Moreover, the particle size distribution study suggested that particles between 2.0 and 6.8 ?m in diameter made up 80.0% of the total suspended solids. Both biological oxygen demand/chemical oxygen demand and biological dissolved organic carbon/dissolved organic carbon were measured ranging from 0.2 to 0.3, suggesting the most secondary effluent organics were biologically refractory. This conclusion was further strengthened by the functional groups information obtained from the GC/MS (gas chromatography/mass spectrometry) analysis. The characteristics information revealed from this study will help the design and selection of water quality-specific tertiary treatment technologies for secondary effluent water purification and reuse.
Phenylalanine ammonia-lyase (PAL; E.C.18.104.22.168) is a key enzyme of the phenylpropanoid pathway in plant development, and it catalyses the deamination of phenylalanine to trans-cinnamic acid, leading to the production of secondary metabolites. This enzyme has been identified in many organisms, ranging from prokaryotes to higher plants. Because Nelumbo nucifera is a basal dicot rich in many secondary metabolites, it is a suitable candidate for research on the phenylpropanoid pathway.
Fractal structures in nature offer a unique "fractal contact mode" that guarantees the efficient working of an organism with an optimized style. Fractal nanostructured biointerfaces have shown great potential for the ultrasensitive detection of disease-relevant biomarkers from small biomolecules on the nanoscale to cancer cells on the microscale. This review will present the advantages of fractal nanostructures, the basic concept of designing fractal nanostructured biointerfaces, and their biomedical applications for the ultrasensitive detection of various disease-relevant biomarkers, such microRNA, cancer antigen 125, and breast cancer cells, from unpurified cell lysates and the blood of patients.
Neurotransmission at different synapses is highly variable, and cell-adhesion molecules like ?-neurexins (?-Nrxn) and their extracellular binding partners determine synapse function. Although ?-Nrxn affect transmission at excitatory and inhibitory synapses, the contribution of neurexophilin-1 (Nxph1), an ?-Nrxn ligand with restricted expression in subpopulations of inhibitory neurons, is unclear. To reveal its role, we investigated mice that either lack or overexpress Nxph1. We found that genetic deletion of Nxph1 impaired GABAB receptor (GABA(B)R)-dependent short-term depression of inhibitory synapses in the nucleus reticularis thalami, a region where Nxph1 is normally expressed at high levels. To test the conclusion that Nxph1 supports presynaptic GABA(B)R, we expressed Nxph1 ectopically at excitatory terminals in the neocortex, which normally do not contain this molecule but can be modulated by GABA(B)R. We generated Nxph1-GFP transgenic mice under control of the Thy1.2 promoter and observed a reduced short-term facilitation at these excitatory synapses, representing an inverse phenotype to the knockout. Consistently, the diminished facilitation could be reversed by pharmacologically blocking GABA(B)R with CGP-55845. Moreover, a complete rescue was achieved by additional blocking of postsynaptic GABA(A)R with intracellular picrotoxin or gabazine, suggesting that Nxph1 is able to recruit or stabilize both presynaptic GABA(B)R and postsynaptic GABA(A)R. In support, immunoelectron microscopy validated the localization of ectopic Nxph1 at the synaptic cleft of excitatory synapses in transgenic mice and revealed an enrichment of GABA(A)R and GABA(B)R subunits compared with wild-type animals. Thus, our data propose that Nxph1 plays an instructive role in synaptic short-term plasticity and the configuration with GABA receptors.
BackgroundThe chloroplast genome is important for plant development and plant evolution. Nelumbo nucifera is one member of relict plants surviving from the late Cretaceous. Recently, a new sequencing platform PacBio RS II, known as `SMRT (Single Molecule, Real-Time) sequencing¿, has been developed. Using the SMRT sequencing to investigate the chloroplast genome of N. nucifera will help to elucidate the plastid evolution of basal eudicots.ResultsThe sizes of the de novo assembled complete chloroplast genome of N. nucifera were 163,307 bp, 163,747 bp and 163,600 bp with average depths of coverage of 7×, 712× and 105× sequenced by Sanger, Illumina MiSeq and PacBio RS II, respectively. The precise chloroplast genome of N. nucifera was obtained from PacBio RS II data proofread by Illumina MiSeq reads, with a quadripartite structure containing a large single copy region (91,846 bp) and a small single copy region (19,626 bp) separated by two inverted repeat regions (26,064 bp). The genome contains 113 different genes, including four distinct rRNAs, 30 distinct tRNAs and 79 distinct peptide-coding genes. A phylogenetic analysis of 133 taxa from 56 orders indicated that Nelumbo with an age of 177 million years is a sister clade to Platanus, which belongs to the basal eudicots. Basal eudicots began to emerge during the early Jurassic with estimated divergence times at 197 million years using MCMCTree. IR expansions/contractions within the basal eudicots seem to have occurred independently.ConclusionsBecause of long reads and lack of bias in coverage of AT-rich regions, PacBio RS II showed a great promise for highly accurate `finished¿ genomes, especially for a de novo assembly of genomes. N. nucifera is one member of basal eudicots, however, evolutionary analyses of IR structural variations of N. nucifera and other basal eudicots suggested that IR expansions/contractions occurred independently in these basal eudicots or were caused by independent insertions and deletions. The precise chloroplast genome of N. nucifera will present new information for structural variation of chloroplast genomes and provide new insight into the evolution of basal eudicots at the primary sequence and structural level.
Biointerfaces with the controlled adhesion of bacteria are highly important, owing to their wide applications, which range from decreasing the probability of infection to promoting higher efficiency and sensitivity in biocatalysts and biosensors. In this Focus Review, we summarize the recent progress in chemically and physically designed biointerfaces with controlled bacterial adhesion. On one hand, several smart-responsive biointerfaces that can be switched between bacteria-adhesive states and bacteria-resistant states by applying an external stimulus have been rationally designed and developed for adhering and detaching bacteria, whilst, on the other hand, the adhesive behavior of bacteria can be controlled by regulating the topography of the biointerface. In addition, new technologies (i.e., biosensors) and materials (i.e., graphene) provide promising approaches for efficiently controlling the adhesion of bacteria for practical applications.
Periodic micro-grooved organogel surfaces can easily realize the anisotropic sliding of water droplets attributing to the formed slippery water/oil/solid interface. Different from the existing anisotropic surfaces, this novel surface provides a versatile candidate for the anisotropic sliding of water droplets and might present a promising way for the easy manipulation of liquid droplets for water collection, liquid-directional transportation, and microfluidics.
The capability of imaging and detecting single DNA molecules is critical in the study, analysis, and applications of DNA. Fluorescence imaging is a widely used method, but it suffers from blinking and photobleaching, and fluorescence tags may block or affect binding sites on DNA. We report on label-free imaging of single DNA molecules with a differential plasmonic imaging technique. The technique produces high contrast images due to the scattering of surface plasmonic waves by the molecules and the removal of background noises and interference patterns, allowing for quantitative analysis of individual DNA molecules. Simulation of the images based on a scattering model shows good agreement with the experiment. We further demonstrate optical mapping of single DNA molecules.
A blue-emitting iridium dendrimer, namely B-G2, has been successfully designed and synthesized with a secondgeneration oligocarbazole as the dendron, which is covalently attached to the emissive tris[2-(2,4-difluorophenyl)-pyridyl]iridium(III) core through a nonconjugated link to form an efficient self-host system in one dendrimer. Unlike small molecular phosphors and other phosphorescent dendrimers, B-G2 shows a continuous enhancement in the device efficiency with increasing doping concentration. When using neat B-G2 as the emitting layer, the nondoped device is achieved without loss in efficiency, thus giving a state-of-art EQE as high as 15.3% (31.3 cdA1, 28.9 lmW1) along with CIE coordinates of (0.16, 0.29).
The past two decades have seen great progress in understanding the mechanisms of ecosystem stability in local ecological systems. There is, however, an urgent need to extend existing knowledge to larger spatial scales to match the scale of management and conservation. Here, we develop a general theoretical framework to study the stability and variability of ecosystems at multiple scales. Analogously to the partitioning of biodiversity, we propose the concepts of alpha, beta and gamma variability. Gamma variability at regional (metacommunity) scale can be partitioned into local alpha variability and spatial beta variability, either multiplicatively or additively. On average, variability decreases from local to regional scales, which creates a negative variability-area relationship. Our partitioning framework suggests that mechanisms of regional ecosystem stability can be understood by investigating the influence of ecological factors on alpha and beta variability. Diversity can provide insurance effects at the various levels of variability, thus generating alpha, beta and gamma diversity-stability relationships. As a consequence, the loss of biodiversity and habitat impairs ecosystem stability at the regional scale. Overall, our framework enables a synthetic understanding of ecosystem stability at multiple scales and has practical implications for landscape management.
Harmonic motion imaging for focused ultrasound (HMIFU) is a recently developed high-intensity focused ultrasound (HIFU) treatment monitoring method with feasibilities demonstrated in vitro and in vivo. Here, a multi-parametric study is performed to investigate both elastic and acoustics-independent viscoelastic tissue changes using the Harmonic Motion Imaging (HMI) displacement, axial compressive strain and change in relative phase shift during high energy HIFU treatment with tissue boiling. Forty three (n = 43) thermal lesions were formed in ex vivo canine liver specimens (n = 28). Two-dimensional (2D) transverse HMI displacement maps were also obtained before and after lesion formation. The same method was repeated in 10 s, 20 s and 30 s HIFU durations at three different acoustic powers of 8, 10, and 11 W, which were selected and verified as treatment parameters capable of inducing boiling using both thermocouple and passive cavitation detection (PCD) measurements. Although a steady decrease in the displacement, compressive strain, and relative change in the focal phase shift (??) were obtained in numerous cases, indicating an overall increase in relative stiffness, the study outcomes also showed that during boiling, a reverse lesion-to-background displacement contrast was detected, indicating potential change in tissue absorption, geometrical change and/or, mechanical gelatification or pulverization. Following treatment, corresponding 2D HMI displacement images of the thermal lesions also mapped consistent discrepancy in the lesion-to-background displacement contrast. Despite the expectedly chaotic changes in acoustic properties with boiling, the relative change in phase shift showed a consistent decrease, indicating its robustness to monitor biomechanical properties independent of the acoustic property changes throughout the HIFU treatment. In addition, the 2D HMI displacement images confirmed and indicated the increase in the thermal lesion size with treatment duration, which was validated against pathology. In conclusion, multi-parametric HMIFU was shown capable of monitoring and mapping tissue viscoelastic response changes during and after HIFU boiling, some of which were independent of the acoustic parameter changes.
Idiopathic hypereosinophilic syndrome is an uncommon leukoproliferative systemic disorder characterized by the sustained eosinophilia and target organ damage. We report the case of a 56-year-old man presenting with multiple cerebral embolism, Löffler endocarditis, and hypereosinophilia. This patient also had pleural, bone marrow, and skin involvement. The unique feature was multifocal embolisms in the brain.
This protocol describes an isothermal amplification approach for ultrasensitive detection of specific microRNAs (miRNAs). It achieves this level of sensitivity through quadratic amplification of the target oligonucleotide by using a Bst DNA polymerase-induced strand-displacement reaction and a lambda exonuclease-aided recycling reaction. First, the target miRNA binds to a specifically designed molecular beacon, causing it to become a fluorescence emitter. A primer then binds to the activated beacon, and Bst polymerase initiates the synthesis of a double-stranded DNA segment templated on the molecular beacon. This causes the concomitant release of the target miRNA from the beacon--the first round of 'recycling'. Second, the duplex beacon thus produced is a suitable substrate for a nicking enzyme present in solution. After the duplex beacon is nicked, the lambda exonuclease digests the beacon and releases the DNA single strand just synthesized, which is complementary to the molecular beacon, inducing the second round of recycling. The miRNA detection limit of this protocol is 10 fmol at 37 °C and 1 amol at 4 °C. This approach also affords high selectivity when applied to miRNA extracted from MCF-7 and PC3 cell lines and even from breast cancer tissue samples. Upon isolation of miRNA, the detection process can be completed in ?2 h.
The control of cell gradients is critical for understanding many biological systems and realizing the unique functionality of biomimetic implants. Herein, we report a nanotopographic gradient strategy that can rapidly generate cell gradients on a nanodendritic silica substrate without any chemical modification. We can achieve controllable cell gradients within only half an hour of cell incubation solely induced by the topographic effect of the gradient nanodendrites. We also demonstrate that cell gradients can be modulated by the combination of nanotopographic and chemical gradients. The results reveal that the enhanced topographic interactions between the nanodentritic structure and nanoscaled filopodia of the cells mainly contribute to the generation of cell gradients.
A novel poly(amic acid) with pendant aniline tetramer and sulfonic acid groups (ESPAA) was synthesized by ternary polymerization and characterized by Fourier-transform infrared spectra, ((1))H NMR and gel permeation chromatography. The polymer showed good thermal stability and excellent solubility in the common organic solvents. The electrochemical properties were investigated carefully on a CHI 660A Electrochemical Workstation. The polymer displayed good electroactivity in acid, neutral and even in alkaline solutions (pH=1-10) due to the self-doping effect between aniline tetramer and sulfonic/carboxylic acid groups. It also exhibited satisfactory electrochromic performance with high contrast value, acceptable coloration efficiency and fast switching time in the range of pH=1-9.
Three-dimensional nano-biointerface has been emerging as an important topic for chemistry, nanotechnology, and life sciences in recent years. Understanding the exchanges of materials, signals, and energy at biological interfaces has inspired and helped the serial design of three-dimensional nano-biointerfaces. The intimate interactions between cells and nanostructures bring many novel properties, making three-dimensional nano-biointerfaces a powerful platform to guide cell fate in a controllable and accurate way. These advantages and capabilities endow three-dimensional nano-biointerfaces with an indispensable role in developing advanced biological science and technology. This tutorial review is mainly focused on the recent progress of three-dimensional nano-biointerfaces and highlights the new explorations and unique phenomena of three-dimensional nano-biointerfaces for cell-related fundamental studies and biomedical applications. Some basic bio-inspired principles for the design and creation of three-dimensional nano-biointerfaces are also delivered in this review. Current and further challenges of three-dimensional nano-biointerfaces are finally addressed and proposed.
We report a facile colloidal synthesis of tin-germanium (Sn-Ge) heterostructures in the form of nanorods with a small aspect ratio of 1.5-3 and a length smaller than 50 nm. In the two-step synthesis, presynthesized Sn nanoparticles act as a low-melting-point catalyst for decomposing the Ge precursor, bis[bis(trimethylsilyl)amido]Ge(II), and for crystallization of Ge via solution-liquid-solid growth mechanism. Creation of such Sn-Ge nanoheterodimers can serve as a well-controlled method of mixing these nearly immiscible chemical elements for the purpose of obtaining Sn-Ge nanocomposite electrodes for high-energy density Li-ion batteries. Comparable mass content of Sn and Ge leads to synergistic effects in electrochemical performance: high charge storage capacity above 1000 mAh g(-1) at a relatively high current density of 1 A g(-1) is due to high theoretical capacity of Ge, while high rate capability is presumably caused by the enhancement of electronic transport by metallic Sn. At a current density of 4 A g(-1), Sn-Ge nanocomposite electrodes retain up to 80% of the capacity obtained at a lower current density of 0.2 A g(-1). Temporally separated lithiation of both elements, Sn and Ge, at different electrochemical potentials is proposed as a main factor for the overall improvement of the cycling stability.
Cytoplasmic male sterility (CMS) is a widely observed phenomenon, which is especially useful in hybrid seed production. Meixiang A (MxA) is a new rice CMS line derived from a pollen-free sterile line named Yunnan ZidaoA (ZD-CMS). In this study, a homologous WA352 gene with variation in two nucleotides was identified in MxA. Cytological analysis revealed that MxA was aborted in the early uninucleate stage. The protein expression profiles of MxA and its maintainer line MeixiangB (MxB) were systematically compared using iTRAQ-based quantitative proteomics technology using young florets at the early uninucleate stage. A total of 688 proteins were quantified in both rice lines, and 45 of these proteins were found to be differentially expressed. Bioinformatics analysis indicated a large number of the proteins involved in carbohydrate metabolism or the stress response were downregulated in MxA, suggesting that these metabolic processes had been hindered during pollen development in MxA. The ROS (reactive oxygen species) level was increased in the mitochondrion of MxA, and further ultrastructural analysis showed the mitochondria with disrupted cristae in the rice CMS line MxA. These findings substantially contribute to our knowledge of pollen developmental defects in ZD-CMS rice line.
Rice blast caused by Magnaporthe grisea is one of the three major diseases that seriously affect the rice production. Alpha-momorcharin (?-MC), a ribosome-inactivating protein (RIP) isolated from Momordica charantia seeds, has antifungal effects in vitro. In this study, the ?-MC gene was constitutively expressed under the control of the 2×35S promoter in transgenic rice (Oryza sativa L.) using an Agrobacterium tumefaciens-mediated method. The nine transgenic plants were obtained and confirmed by PCR and RT-PCR, and the four (B2, B4, B7 and B9) of them whose copy numbers were 1, 2, 3 and 3, respectively, were shown to express the ?-MC protein by Western blot. The molecular weight of ?-MC in transgenic plants was approximately 38 kDa larger than the purified ?-MC protein (28 kDa) in vitro. When the confirmed T1 generations were inoculated with a suspension of M. grisea spores for ten days, the lesions on leaves of transgenic plants were much lesser than those found on wild type (WT). According to the criteria of International Rice Research Institute standard, the mean values for morbidity and disease index numbers were 29.8% and 14.9%, respectively, which were lower than for WT. It is unclear whether RIPs could impact plant fitness and however our results suggest that the ?-MC protein is an effective antifungal protein preventing rice blast in transgenic rice.
By mimicking certain biochemical and physical attributes of biological cells, bio-inspired particles have attracted great attention for potential biomedical applications based on cell-like biological functions. Inspired by leukocytes, hierarchical biointerfaces are designed and prepared based on specific molecules-modified leukocyte-inspired particles. These biointerfaces can efficiently recognize cancer cells from whole blood samples through the synergistic effect of molecular recognition and topographical interaction. Compared to flat, mono-micro or nano-biointerfaces, these micro/nano hierarchical biointerfaces are better able to promote specific recognition interactions, resulting in an enhanced cell-capture efficiency. It is anticipated that this study may provide promising guidance to develop new bio-inspired hierarchical biointerfaces for biomedical applications.
The aim of the present study was to construct tissue-engineered bone using a bioreactor and platelet-rich plasma (PRP). Bone marrow mesenchymal stem cells (BMSCs) and ?-tricalcium phosphate (?-TCP) were cultured in a perfusion bioreactor with PRP-containing medium for 21 days to form a BMSC-TCP composite. Rabbits were then implanted with the BMSC-TCP composite. The morphology of the implanted BMSC-TCP composite was observed three months after surgery by scanning electron microscopy and hematoxylin and eosin (H&E) staining. In addition, the expression of cluster of differentiation (CD)31 and von Willebrand factor (WF) in the implanted BMSC-TCP composite was detected using immunohistochemistry. Bone formation was determined by comprehensive testing Following culture in a perfusion bioreactor and PRP, the BMSCs adhered to the ?-TCP scaffold and the secretion of extracellular matrix was observed. The spreading and proliferation of cells was found to be enhanced on the scaffold. Furthermore, the vascular endothelial cell markers CD31 and VEF, were positively expressed. Therefore, these results suggest that tissue-engineered bone may be constructed using a bioreactor and PRP. PRP, which contains multiple growth factors, may promote vascularization of tissue-engineered bone.
The delivery of drugs to specific neural targets faces two fundamental problems: (1) most drugs do not cross the blood-brain barrier, and (2) those that do, spread to the entire brain. To date, there exists only one non-invasive methodology with the potential to solve these problems: selective blood-brain barrier (BBB) opening using micro-bubble enhanced focused ultrasound. We have recently developed a single-element 500-kHz spherical transducer ultrasound setup for targeted BBB opening in the non-human primate that does not require simultaneous MRI monitoring. So far, however, the targeting accuracy that can be achieved with this system has not been quantified systematically. In this paper, the accuracy of this system was tested by targeting caudate nucleus and putamen of the basal ganglia in two macaque monkeys. The average lateral targeting error of the system was ?2.5 mm while the axial targeting error, i.e., along the ultrasound path, was ?1.5 mm. We have also developed a real-time treatment monitoring technique based on cavitation spectral analysis. This technique also allowed for delineation of a safe and reliable acoustic parameter window for BBB opening. In summary, the targeting accuracy of the system was deemed to be suitable to reliably open the BBB in specific sub-structures of the basal ganglia even in the absence of MRI-based verification of opening volume and position. This establishes the method and the system as a potentially highly useful tool for brain drug delivery.
A simple device for high-speed microfluidic delivery of liquid samples to a surface plasmon resonance sensor surface is presented. The delivery platform is comprised of a four-port microfluidic cell, two ports serve as inlets for buffer and sample solutions, respectively, and a high-speed selector valve to control the alternate opening and closing of the two outlet ports. The time scale of buffer/sample switching (or sample injection rise and fall time) is on the order of milliseconds, thereby minimizing the opportunity for sample plug dispersion. The high rates of mass transport to and from the central microfluidic sensing region allow for SPR-based kinetic analysis of binding events with dissociation rate constants (k(d)) up to 130 s(-1). The required sample volume is only 1 ?L, allowing for minimal sample consumption during high-speed kinetic binding measurement.
Activated thrombin-activatable fibrinolysis inhibitor is a coagulation factor in some thrombotic diseases. However, available data on whether thrombin-activatable fibrinolysis inhibitor is activated in islet transplant are limited. In this study, changes of plasma-activated thrombin-activatable fibrinolysis inhibitor levels in instant blood-mediated inflammatory reaction after islet transplant were assessed.
The hierarchical assembly of gold nanoparticles (GNPs) allows the localized surface plasmon resonance peaks to be engineered to the near-infrared (NIR) region for enhanced photothermal therapy (PTT). Herein we report a novel theranostic platform based on biodegradable plasmonic gold nanovesicles for photoacoustic (PA) imaging and PTT. The disulfide bond at the terminus of a PEG-b-PCL block-copolymer graft enables dense packing of GNPs during the assembly process and induces ultrastrong plasmonic coupling between adjacent GNPs. The strong NIR absorption induced by plasmon coupling and very high photothermal conversion efficiency (?=37?%) enable simultaneous thermal/PA imaging and enhanced PTT efficacy with improved clearance of the dissociated particles after the completion of PTT. The assembly of various nanocrystals with tailored optical, magnetic, and electronic properties into vesicle architectures opens new possibilities for the construction of multifunctional biodegradable platforms for biomedical applications.
Harmonic Motion Imaging (HMI) for Focused Ultrasound (HMIFU) is a recently developed high-intensity focused ultrasound (HIFU) treatment monitoring method with feasibilities demonstrated in silica, in vitro and in vivo. Its principle is based on emission of an Amplitude-modulated therapeutic ultrasound beam utilizing a therapeutic transducer to induce an oscillatory radiation force while tracking the focal tissue mechanical response during the HIFU treatment using a confocally-aligned diagnostic transducer. In order to translate towards the clinical implementation of HMIFU, a complete assessment study is required in order to investigate the optimal radiation force threshold for reliable monitoring the local tissue mechanical property changes, i.e., the estimation HMIFU displacement under thermal, acoustical, and mechanical effects within focal medium (i.e., boiling, cavitation, and nonlinearity) using biological specimen. In this study, HMIFU technique is applied on HIFU treatment monitoring on freshly excised ex vivo canine liver specimens. In order to perform the multi-characteristic assessment, the diagnostic transducer was operated as either a pulse-echo imager or Passive Cavitation Detector (PCD) to assess the acoustic and mechanical response, while a bare-wire thermocouple was used to monitor the focal temperature change. As the acoustic power of HIFU treatment was ranged from 2.3 to 11.4 W, robust HMI displacement was observed across the entire range. Moreover, an optimized range for high quality displacement monitoring was found to be between 3.6 to 5.2W, where displacement showed an increase followed by significant decrease, indicating a stiffening of focal medium due to thermal lesion formation, while the correlation coefficient was maintained above 0.95.
Neutral models of species diversity predict patterns of abundance for communities in which all individuals are ecologically equivalent. These models were originally developed for Panamanian trees and successfully reproduce observed distributions of abundance. Neutral models also make macroevolutionary predictions that have rarely been evaluated or tested. Here we show that neutral models predict a humped or flat relationship between species age and population size. In contrast, ages and abundances of tree species in the Panamanian Canal watershed are found to be positively correlated, which falsifies the models. Speciation rates vary among phylogenetic lineages and are partially heritable from mother to daughter species. Variable speciation rates in an otherwise neutral model lead to a demographic advantage for species with low speciation rate. This demographic advantage results in a positive correlation between species age and abundance, as found in the Panamanian tropical forest community.
Focused ultrasound, in the presence of microbubbles, has been used non-invasively to induce reversible blood-brain barrier (BBB) opening in both rodents and non-human primates. This study was aimed at identifying the dependence of BBB opening properties on polydisperse microbubble (all clinically approved microbubbles are polydisperse) type and distribution by using a clinically approved ultrasound contrast agent (Definity microbubbles) and in-house prepared polydisperse (IHP) microbubbles in mice. A total of 18 C57 BL/6 mice (n = 3) were used in this study, and each mouse was injected with either Definity or IHP microbubbles via the tail vein. The concentration and size distribution of activated Definity and IHP microbubbles were measured, and the microbubbles were diluted to 6 × 10(8)/mL before injection. Immediately after microbubble administration, mice were subjected to focused ultrasound with the following parameters: frequency = 1.5 MHz, pulse repetition frequency = 10 Hz, 1000 cycles, in situ peak rarefactional acoustic pressures = 0.3, 0.45 and 0.6 MPa for a sonication duration of 60 s. Contrast-enhanced magnetic resonance imaging was used to confirm BBB opening and allowed for image-based analysis. Permeability of the treated region and volume of BBB opening did not significantly differ between the two types of microbubbles (p > 0.05) at peak rarefractional acoustic pressures of 0.45 and 0.6 MPa, whereas IHP microbubbles had significantly higher permeability and opening volume (p < 0.05) at the relatively lower pressure of 0.3 MPa. The results from this study indicate that microbubble type and distribution could have significant effects on focused ultrasound-induced BBB opening at lower pressures, but less important effects at higher pressures, possibly because of the stable cavitation that governs the former. This difference may have become less significant at higher pressures, where inertial cavitation typically occurs.
Photoacoustic (PA) imaging promises deeper tissue penetration while maintaining rich optical contrast as compared to other high resolution optical imaging techniques. In this report, a near-infrared pulse laser serves as the excitation source, and 128 ultrasonic transducers are spirally distributed on a hemispherical surface to receive PA signals for three-dimensional (3D) image reconstruction. With these attributes, the unique modality produces an isotropic and homogeneous spatial resolution (?200 ?m) with penetration depth of centimeters. Cyclic Arg-Gly-Asp (RGD) peptides conjugated plasmonic gold nanostars (RGD-GNS) are designed to specifically target over-expressed integrin ?v ?3 on tumor neovasculature, enabling highly sensitive angiography and photothermal therapy (PTT). After the administration of RGD-GNS, tumor angiogenesis is clearly imaged with enhanced contrast, and the growth of tumor is effectively inhibited by PTT after laser irradiation. This study suggest that the PA angiography with plasmonic RGD-GNS can be applied as a triple functional platform for tumor diagnosis, PTT, and treatment monitoring. This PA technique offers deeper imaging depth with homogeneous resolution over existing optical imaging techniques for early diagnosis of tumor angiogenesis as well as on-the-spot nanotherapeutic evaluation.
Large-area dual-scaled porous nitrocellulose (p-NC) membranes are fabricated by a facile, inexpensive and scalable perforating approach. These p-NC membranes show stable superhydrophilicity in air and underwater superoleophobicity. The p-NC membranes with intrinsic nanopores and array of microscale perforated pores could selectively and efficiently separate water from various oil/water mixtures with high efficiency (> 99%) rapidly.
Successful heterochromatin formation is critical for genome stability in eukaryotes, both to maintain structures needed for mitosis and meiosis and to silence potentially harmful transposable elements. Conversely, inappropriate heterochromatin assembly can lead to inappropriate silencing and other deleterious effects. Hence targeting heterochromatin assembly to appropriate regions of the genome is of utmost importance. Here we focus on heterochromatin assembly in Drosophila melanogaster, the model organism in which variegation, or cell-to-cell variable gene expression resulting from heterochromatin formation, was first described. In particular, we review the potential role of transposable elements as genetic determinants of the chromatin state and examine how small RNA pathways may participate in the process of targeted heterochromatin formation.
Iridescent colloidal crystal coatings with variable structural colors were fabricated by incorporating carbon black nanoparticles (CB-NPs) into the voids of polystyrene (PS) colloidal crystals. The structural color of the colloid crystal coatings was not only greatly enhanced after the composition but also varied with observation angles. By changing the diameter of monodisperse PS colloids in the composites, colloidal crystal coatings with three primary colors for additive or subtractive combination were obtained. After incorporation of the PS/CB-NPs hybrid coatings into polydimethylsiloxane (PDMS) matrix, manmade opal jewelry with variable iridescent colors was made facilely.
Inspired by selective wettability and hierarchical structure of papillae on lotus seeds, papilla-like magnetic particles were fabricated by thermal treatment of Fe microparticles. The papilla-like magnetic particles modified by lauric acid exhibited superhydrophobicity, superoleophilicity and great oil removing capability from water.
A well-documented pattern in the fossil record is a long-term decline in the origination rate of new taxa after diversity rebounds from a mass extinction. The mechanisms for this pattern remain elusive. In this article, we investigate the macroevolutionary predictions of an individual-based birth-death model (BDI model) where speciation and extinction rates emerge from population dynamics. We start with the simplest neutral model in which every individual has the same per capita rates of birth, death, and speciation. Although the prediction of the simplest neutral model agrees qualitatively with the fossil pattern, the predicted decline in per-species speciation rates is too fast to explain the long-term trend in fossil data. We thus consider models with variation among species in per capita rates of speciation and a suite of alternative assumptions about the heritability of speciation rate. The results show that interspecific variation in per capita speciation rate can induce differences among species in their ability to resist extinction because a low speciation rate confers a small but important demographic advantage. As a consequence, the model predicts an appropriately slow temporal decline in speciation rates, which provides a mechanistic explanation for the fossil pattern.
Charge-based detection of small molecules is demonstrated by plasmonic-based electrochemical impedance microscopy (P-EIM). The dependence of surface plasmon resonance (SPR) on surface charge density is used to detect small molecules (60-120 Da) printed on a dextran-modified sensor surface. Local variations in charge density on an electrode surface are manifest in an optical SPR signal. The SPR response to an applied ac potential measures the sensor surface impedance which is a function of the surface charge density. This optical signal is comprised of a dc and an ac component, and is measured with high spatial resolution. The dc element of the SPR signal represents conventional SPR imaging information. The amplitude and phase of local surface impedance is provided by the ac component. The phase signal of the small molecules is a function of their charge status, which is manipulated by the pH of a solution. Small molecules with positive, neutral, and negative charge are detected by P-EIM. This technique is used to detect and distinguish small molecules based on their charge status, thereby circumventing the mass limitation (~100 Da) of conventional SPR measurement.
With the advent of high-throughput sequencing technologies, much progress has been made in the identification of somatic structural rearrangements in cancer genomes. However, characterization of the complex alterations and their associated mechanisms remains inadequate. Here, we report a comprehensive analysis of whole-genome sequencing and DNA copy number data sets from The Cancer Genome Atlas to relate chromosomal alterations to imbalances in DNA dosage and describe the landscape of intragenic breakpoints in glioblastoma multiforme (GBM). Gene length, guanine-cytosine (GC) content, and local presence of a copy number alteration were closely associated with breakpoint susceptibility. A dense pattern of repeated focal amplifications involving the murine double minute 2 (MDM2)/cyclin-dependent kinase 4 (CDK4) oncogenes and associated with poor survival was identified in 5% of GBMs. Gene fusions and rearrangements were detected concomitant within the breakpoint-enriched region. At the gene level, we noted recurrent breakpoints in genes such as apoptosis regulator FAF1. Structural alterations of the FAF1 gene disrupted expression and led to protein depletion. Restoration of the FAF1 protein in glioma cell lines significantly increased the FAS-mediated apoptosis response. Our study uncovered a previously underappreciated genomic mechanism of gene deregulation that can confer growth advantages on tumor cells and may generate cancer-specific vulnerabilities in subsets of GBM.
Underwater-transparent nanodendritic coatings are easily fabricated by a three-step template process. After modification with anti-EpCAM, the coatings exhibit the capability for efficiently capturing rare number of cancer cells from whole blood. On the other hand, the unique underwater transparency enables the coatings to directly monitor captured cancer cells by optical imaging.
A novel polymer featuring oligoaniline pendants that exhibits reversible electroactivity and good electrochromic properties with high contrast value, acceptable switching times, and excellent coloration efficiency is presented. This polymer can undergo reversible changes in fluorescence in response to reductive and oxidative chemical stimulus, pH, and electrical potential. The fluorescence switching operation shows reasonable reversibility and reproducibility when subjected to multiple stimuli. In this elegant fluorescence switching system, the oligoaniline pendants are used as fluorophore and regulatory units simultaneously.
Increased attention has been paid to the transportation and removal efficiencies of nanoparticles during water treatment. Here, C?? was selected as nano-pollutant to investigate its removal efficiency in the process of coagulation by Al(3+) in regard to different ions. Negatively charged C?? tends to adsorb hydrated Al(3+) to form positively charged C??-Al(OH)(n)((m-?)+) particles, leading to the restabilization of C??. Multivalent anions, i.e., CO?(2-), SO?(2-), HPO?(2-),and humic acid (HA), were shown to bridge the C??-Al (OH)(n)((m-?)+) particles together and induce the formation of flocs, resulting in enhanced C?? removal (>80%). Monovalent anions, such as OH(-), NO?(-) and the surfactant SDS, were not able to bridge the C??-Al (OH)(n)((m-?)+) particles together; hence, they had no effect on the C?? removal. The addition of Na(+) and Ca(2+) increased the ionic strength of the aqueous solution, which compressed the electric double layer and induced the C??-Al(OH)(n)((m-?)+) particles to aggregate. However, they are not the essential factors for flocs formation. This is the first study to report the bridging phenomena between multivalent anions and C??-Al(OH)(n)((m-?)+) in water treatments, and it highlights that the presence of multivalent anions and cations in raw water are important for the effective removal of C??.
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