34 research outputs found
Membrane-Anchoring, Comb-Like Pseudopeptides for Efficient, pH-Mediated Membrane Destabilization and Intracellular Delivery
Endosomal
release has been identified as a rate-limiting step for intracellular
delivery of therapeutic agents, in particular macromolecular drugs.
Herein, we report a series of synthetic pH-responsive, membrane-anchoring
polymers exhibiting dramatic endosomolytic activity for efficient
intracellular delivery. The comb-like pseudopeptidic polymers were
synthesized by grafting different amounts of decylamine (NDA), which
act as hydrophobic membrane anchors, onto the pendant carboxylic acid
groups of a pseudopeptide, polyÂ(l-lysine iso-phthalamide).
The effects of the hydrophobic relatively long alkyl side chains on
aqueous solution properties, cell membrane destabilization activity,
and in-vitro cytotoxicity were investigated. The optimal polymer containing
18 mol % NDA exhibited limited hemolysis at pH 7.4 but induced nearly
complete membrane destabilization at endosomal pH within only 20 min.
The mechanistic investigation of membrane destabilization suggests
the polymer-mediated pore formation. It has been demonstrated that
the polymer with hydrophobic side chains displayed a considerable
endosomolytic ability to release endocytosed materials into the cytoplasm
of various cell lines, which is of critical importance for intracellular
drug delivery applications
Figure 2 in A Late Cretaceous diversification of Asian oviraptorid dinosaurs: evidence from a new species
Figure 2. The whole skeleton of the holotype Tongtianlong limosus gen. et sp. nov. in dorsal view (a) and lateral view (b). Scale bar = 10 cm
Figure 4 in A Late Cretaceous diversification of Asian oviraptorid dinosaurs: evidence from a new species
Figure 4. The photograph (a) and line drawing (b) of the skull: Tongtianlong limosus gen. et sp. nov. in right lateral view. Abbreviations: aof, antorbital fenestra; bc, braincase; d, dentary; emf, external mandibular fenestra; eo, exoccipital; f, frontal; j, jugal; l, lacrimal; ltf: lower temporal fenestra; m, maxilla; n, nasal; nar, narial opening; npc, nasopharyngeal canal; o, orbit; p, parietal; pm, premaxilla; pno, pneumatic opening; po, postorbital; q, quadrate; qj, quadratojugal; sa, surangular; sq, squamosal; stf, supratemporal fenestra. Scale bar = 5 cm
Figure 1 in A Late Cretaceous diversification of Asian oviraptorid dinosaurs: evidence from a new species
Figure 1. Map of the fossil locality near Ganzhou, Iiangxi Province, southern China. The solid five-pointed star represents the fossil site. Modified from LĂĽ et al. 29
Figure 5 in A Late Cretaceous diversification of Asian oviraptorid dinosaurs: evidence from a new species
Figure 5. An artistic reconstruction, showing the last-ditch struggle of Tongtianlong limosus as it was mired in mud, one possible, but highly speculative, interpretation for how the specimen was killed and buried (Drawn by Zhao Chuang)
Molecular characterization, expression pattern and function analysis of the <i>OsHSP90</i> family in rice
<p>The HSP90 is an abundant chaperone protein that is conserved in all eukaryotes. The main function of HSP90 is to assist other proteins to fold properly. In this study, we uncovered and analysed nine OsHSP90 (OsHSP90-1--OsHSP90-9) family members in rice <i>Nipponbare</i>, in which three distinct motifs were identified. All the HSP90 proteins were classified into three major groups (I, II, III) by phylogenetic analysis. The expression of <i>OsHSP90</i> family in 10 tissues was examined by real-time polymerase chain reaction (PCR). <i>OsHSP90-4</i>, <i>OsHSP90-6</i> and <i>OsHSP90-7</i> had high expression, while <i>OsHSP90-5</i> and <i>OsHSP90-8</i> had very low expression across almost all 10 samples. The gene that encodes <i>OsHSP90-1</i> was preferentially expressed in embryo at 14Â days after flowering. It has been reported that some heat shock proteins were up-regulated in response to heat or other stresses. However, in our study the expression pattern of <i>OsHSP90</i> genes is heterogeneous under a range of stress conditions. The expression of <i>OsHSP90-2</i> and <i>OsHSP90-4</i> was up-regulated under drought, salt, cold and heat conditions, while the expression of <i>OsHSP90-3</i> and <i>OsHSP90-5</i> was down-regulated under salt and drought conditions. <i>OsHSP90-7</i> and <i>OsHSP90-9</i> were down-regulated only under drought conditions. <i>OsHSP90-6</i> did not change its expression across all conditions compared to control. Overexpression of <i>OsHSP90-2</i> in <i>E. coli</i> could enhance cell viability and significantly improved resistance to heat, high salinity and drought stress conditions. The results presented here may provide new insights into the function of <i>OsHSP90</i> family in rice.</p
Potentiating the Immune Responses of HBsAg-VLP Vaccine Using a Polyphosphoester-Based Cationic Polymer Adjuvant
Virus-like particle (VLP)-based vaccines are required
to be associated
with a suitable adjuvant to potentiate their immune responses. Herein,
we report a novel, biodegradable, and biocompatible polyphosphoester-based
amphiphilic cationic polymer, poly(ethylene glycol)-b-poly(aminoethyl ethylene phosphate) (PEG–PAEEP), as a Hepatitis
B surface antigen (HBsAg)-VLP vaccine adjuvant. The polymer adjuvant
effectively bound with HBsAg-VLP through electrostatic interactions
to form a stable vaccine nanoformulation with a net positive surface
charge. The nanoformulations exhibited enhanced cellular uptake by
macrophages. HBsAg-VLP/PEG–PAEEP induced a significantly higher
HBsAg-specific IgG titer in mice than HBsAg-VLP alone after second
immunization, indicative of the antigen-dose sparing advantage of
PEG–PAEEP. Furthermore, the nanoformulations exhibited a favorable
biocompatibility and in vivo tolerability. This work
presents the PEG–PAEEP copolymer as a promising vaccine adjuvant
and as a potentially effective alternative to aluminum adjuvants
Molecular characterization and function analysis of the rice <i>OsDUF946</i> family
<p>The domain of unknown function DUF946 family consists of plant proteins with an average length of around 239 residues that have no characterized function. The gene family needs deeper characterization and functional analysis of its members. In this study, we report five <i>OsDUF</i><i>946</i> (<i>OsDUF946.1</i>–<i>OsDUF946.5</i>) family members in rice <i>Nipponbare</i> with three distinct motifs. All the OsDUF946 proteins were classified into three major groups (I, II, III) by phylogenetic analysis. Real-time polymerase chain reaction showed that the expression patterns of the five <i>OsDUF946</i> family members were different in 15 different rice tissues as well as under various stress conditions and abscisic acid treatment. The expression of <i>OsDUF946.1</i> was significantly downregulated under salt, cold and heat stress, while the expression of <i>OsDUF946.4</i> and <i>OsDUF946.5</i> was significantly upregulated under drought and salt conditions. Overexpression of <i>OsDUF946.4</i> in <i>E</i><i>scherichia</i> <i>coli</i> significantly improved the resistance to salt and drought, while overexpression of <i>OsDUF946.5</i> in <i>E. coli</i> did not have such an effect. The obtained results provide a starting point for further research into the function of the <i>OsDUF946</i> family in rice.</p
Molecular characterization, expression pattern and function analysis of the rice <i>OsDUF866</i> family
<p>Domain-of-unknown function (DUF) proteins represent a number of gene families with no functional annotation in the Pfam database. So far, the <i>DUF866</i> family has not been characterized, and no member has been functionally studied. In this study, we uncovered and analysed four OsDUF866 (OsDUF866.1–OsDUF866.4) family members in rice <i>Nipponbare</i>, in which three distinct motifs were identified. The expression of <i>OsDUF866</i> family in nine tissues was examined by real-time polymerase chain reaction (PCR), and the highest expression of four genes members was found in embryos at 14 days after flowering. We performed real-time PCR to examine the expression of <i>OsDUF866</i> family under abiotic stress and abscisic acid (ABA) treatment conditions. The expression level of <i>OsDUF866.1</i> displayed significant decrease under drought and salt conditions, while significant increase under heat conditions. The expression level of <i>OsDUF866.2</i> displayed significant decrease under drought conditions. The expression level of <i>OsDUF866.3</i> was significantly elevated under drought and cold, while lowered under heat conditions. The expression level of <i>OsDUF866.4</i> was increased under cold and heat conditions, while decreased under drought conditions. Interestingly, the expression level of <i>OsDUF866</i> members was approximately constant under ABA treatment conditions. Overexpression of <i>OsDUF866.1</i> in <i>Escherichia coli</i> could enhance cell viability and significantly improve the resistance to heat stress conditions. The results may provide new insights into the function of <i>OsDUF866</i> family in rice.</p
Highly Luminescent and Nontoxic Amine-Capped Nanoparticles from Porous Silicon: Synthesis and Their Use in Biomedical Imaging
Stable and brightly luminescent amine-terminated Si nanoparticles
(SiNPs) have been synthesized from electrochemically etched porous
silicon (PSi). The surface amine termination was confirmed by FTIR,
NMR, and XPS studies. The mean diameter of the crystal core of 4.6
nm was measured by transmission electron microscopy (TEM), which is
in a good agreement with the size obtained by dynamic light scattering
(DLS). The dry, amine-terminated product can be obtained from bulk
silicon wafers in less than 4 h. This represents a significant improvement
over similar routines using PSi where times of >10 h are common.
The
emission quantum yield was found to be about 22% and the nanoparticles
exhibited an exceptional stability over a wide pH range (4–14).
They are resistant to aging over several weeks. The amine-terminated
SiNPs showed no significant cytotoxic effects toward HepG2 cells,
as assessed with MTT assays