抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Terrestrial net primary production (NPP) quantifies the amount of atmospheric carbon fixed by plants and accumulated as biomass. Previous studies have shown that climate constraints were relaxing with increasing temperature and solar radiation, allowing an upward trend in NPP from 1982 through 1999. The past decade (2000 to 2009) has been the warmest since instrumental measurements began, which could imply continued increases in NPP; however, our estimates suggest a reduction in the global NPP of 0.55 petagrams of carbon. Large-scale droughts have reduced regional NPP, and a drying trend in the Southern Hemisphere has decreased NPP in that area, counteracting the increased NPP over the Northern Hemisphere. A continued decline in NPP would not only weaken the terrestrial carbon sink, but it would also intensify future competition between food demand and proposed biofuel production.

Drought-Induced Reduction in Global Terrestrial Net Primary Production from 2000 Through 2009

The Analysis of Time Series: An Introduction, 4th edn. By C. Chatfield. ISBN 0 412 31820 2. Chapman and Hall, London, 1989. 242 pp. £13.50.

The Analysis of Time Series: An Introduction

Since their discovery in the 1960s, liposomes have been studied in depth, and they continue to constitute a field of intense research. Liposomes are valued for their biological and technological advantages, and are considered to be the most successful drug-carrier system known to date. Notable progress has been made, and several biomedical applications of liposomes are either in clinical trials, are about to be put on the market, or have already been approved for public use. In this review, we briefly analyze how the efficacy of liposomes depends on the nature of their components and their size, surface charge, and lipidic organization. Moreover, we discuss the influence of the physicochemical properties of liposomes on their interaction with cells, half-life, ability to enter tissues, and final fate in vivo. Finally, we describe some strategies developed to overcome limitations of the "first-generation" liposomes, and liposome-based drugs on the market and in clinical trials.

https://www.dovepress.com/getfile.php?fileID=23533

Liposomes as nanomedical devices

Peptide amphiphiles are a class of molecules that combine the structural features of amphiphilic surfactants with the functions of bioactive peptides and are known to assemble into a variety of nanostructures. A specific type of peptide amphiphiles are known to self-assemble into one-dimensional nanostructures under physiological conditions, predominantly nanofibers with a cylindrical geometry. The resultant nanostructures could be highly bioactive and are of great interest in many biomedical applications, including tissue engineering, regenerative medicine, and drug delivery. In this context, we highlight our strategies for using molecular self-assembly as a toolbox to produce peptide amphiphile nanostructures and materials and efforts to translate this technology into applications as therapeutics. We also review our recent progress in using these materials for treating spinal cord injury, inducing angiogenesis, and for hard tissue regeneration and replacement.

/pdf/self-assembly-of-peptide-amphiphiles-from-molecules-to-59uxjckd9x.pdf

Self‐assembly of peptide amphiphiles: From molecules to nanostructures to biomaterials

Peptide-amphiphiles are amphiphilic structures with a hydrophilic peptide headgroup that incorporates a bioactive sequence and has the potential to form distinct structures, and a hydrophobic tail that serves to align the headgroup, drive self-assembly, and induce secondary and tertiary conformations. In this paper we review the different self-assembled structures of peptide-amphiphiles that range from micelles and nanofibers, to patterned membranes. We also describe several examples where peptide-amphiphiles have found applications as soft bioactive materials for model studies of bioadhesion and characterization of different cellular phenomena, as well as scaffolds for tissue engineering, regenerative medicine, and targeted drug delivery.

Self-assembly and applications of biomimetic and bioactive peptide-amphiphiles

Targeting colon cancer cells using PEGylated liposomes modified with a fibronectin-mimetic peptide.

In recent years, there has been considerable effort in designing improved delivery systems by including site-directed surface ligands to further enhance their selective targeting. The goal of this study is to engineer α5β1-targeted stealth liposomes (nanoparticles covered with poly(ethylene glycol) (PEG)) that will bind to α5β1-expressing LNCaP human prostate cancer cells and efficiently release the encapsulated load intracellularly. For this purpose, liposomes (with and without PEG2000) were functionalized with a fibronectin-mimetic peptide (PR_b) and delivered to LNCaPs. The amount of PEG2000 and other liposomal components were characterized by 1H NMR, and the amount of peptide by the bicinchoninic acid protein assay. Fibronectin is the natural ligand for α5β1, and a promising design for a fibronectin-mimetic peptide includes both the primary binding site (RGD) and the synergy site (PHSRN) connected by a linker and extended off a surface by a spacer. We have previously designed a peptide-amphiphile, PR_...

PR_b-targeted PEGylated liposomes for prostate cancer therapy.

pH-sensitive liposomes undergo rapid destabilization under mildly acidic conditions such as those found in endocytotic vesicles. Though this makes them promising drug carriers, their application is limited due to their rapid clearance from circulation by the reticulo-endothelial system. Researchers have therefore used pH-sensitive liposomes that are sterically stabilized by polyethylene glycol (PEG) molecules (stealth liposomes) on the liposome surface. The goal of this study is to bring bio-functionality to pH-sensitive PEGylated liposomes in order to facilitate their potential use as a targeted drug delivery agent. To improve the selectivity of these nanoparticles, we included a targeting moiety, PR_b which specifically recognizes and binds to integrin α(5)β(1) expressing cells. PR_b (KSSPHSRN(SG)(5)RGDSP) is a novel fibronectin-mimetic peptide sequence that mimics the cell adhesion domain of fibronectin. Integrin α(5)β(1) is expressed on several types of cancer cells, including colon cancer, and plays an important role in tumor growth and metastasis. We have thoroughly studied the release of calcein from pH-sensitive PEGylated liposomes by varying the lipid composition of the liposomes in the absence and presence of the targeting peptide, PR_b, and accounting for the first time for the effect of both pH and time (photo-bleaching effect) on the fluorescence signal of calcein. We have demonstrated that we can design PR_b-targeted pH-sensitive PEGylated liposomes, which can undergo destabilization under mildly acidic conditions and have shown that incorporating the PR_b peptide does not significantly affect the pH-sensitivity of the liposomes. PR_b-targeted pH-sensitive PEGylated liposomes bind to CT26.WT colon carcinoma cells that express integrin α(5)β(1), undergo cellular internalization, and release their load intracellularly in a short period of time as compared to other formulations. Our studies demonstrate that PR_b-functionalized pH-sensitive targeted delivery systems have the potential to deliver a payload directly to cancer cells in an efficient and specific manner.

pH-Sensitive PEGylated Liposomes Functionalized With a Fibronectin-Mimetic Peptide Show Enhanced Intracellular Delivery to Colon Cancer Cells

Systems and processes for application integration with a digital assistant are provided. In accordance with one example, a method includes, at an electronic device having one or more processors and memory, receiving a natural-language user input; identifying, with the one or more processors, an intent object of a set of intent objects and a parameter associated with the intent, where the intent object and the parameter are derived from the natural-language user input. The method further includes identifying a software application associated with the intent object of the set of intent objects; and providing the intent object and the parameter to the software application.

Ashish Garg

Papers

Self-assembly and applications of biomimetic and bioactive peptide-amphiphiles

Targeting colon cancer cells using PEGylated liposomes modified with a fibronectin-mimetic peptide.

PR_b-targeted PEGylated liposomes for prostate cancer therapy.

pH-Sensitive PEGylated Liposomes Functionalized With a Fibronectin-Mimetic Peptide Show Enhanced Intracellular Delivery to Colon Cancer Cells

Application integration with a digital assistant