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

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems provide bacteria and archaea with adaptive immunity against viruses and plasmids by using CRISPR RNAs (crRNAs) to guide the silencing of invading nucleic acids. We show here that in a subset of these systems, the mature crRNA that is base-paired to trans-activating crRNA (tracrRNA) forms a two-RNA structure that directs the CRISPR-associated protein Cas9 to introduce double-stranded (ds) breaks in target DNA. At sites complementary to the crRNA-guide sequence, the Cas9 HNH nuclease domain cleaves the complementary strand, whereas the Cas9 RuvC-like domain cleaves the noncomplementary strand. The dual-tracrRNA:crRNA, when engineered as a single RNA chimera, also directs sequence-specific Cas9 dsDNA cleavage. Our study reveals a family of endonucleases that use dual-RNAs for site-specific DNA cleavage and highlights the potential to exploit the system for RNA-programmable genome editing.

https://zenodo.org/record/1230922/files/article.pdf

A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity.

The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

SPAdes, a new genome assembly algorithm and its applications to single-cell sequencing ( 7th Annual SFAF Meeting, 2012)

1. Introduction 20642. Synthesis of Magnetic Nanoparticles 20662.1. Classical Synthesis by Coprecipitation 20662.2. Reactions in Constrained Environments 20682.3. Hydrothermal and High-TemperatureReactions20692.4. Sol-Gel Reactions 20702.5. Polyol Methods 20712.6. Flow Injection Syntheses 20712.7. Electrochemical Methods 20712.8. Aerosol/Vapor Methods 20712.9. Sonolysis 20723. Stabilization of Magnetic Particles 20723.1. Monomeric Stabilizers 20723.1.1. Carboxylates 20733.1.2. Phosphates 20733.2. Inorganic Materials 20733.2.1. Silica 20733.2.2. Gold 20743.3. Polymer Stabilizers 20743.3.1. Dextran 20743.3.2. Polyethylene Glycol (PEG) 20753.3.3. Polyvinyl Alcohol (PVA) 20753.3.4. Alginate 20753.3.5. Chitosan 20753.3.6. Other Polymers 20753.4. Other Strategies for Stabilization 20764. Methods of Vectorization of the Particles 20765. Structural and Physicochemical Characterization 20785.1. Size, Polydispersity, Shape, and SurfaceCharacterization20795.2. Structure of Ferro- or FerrimagneticNanoparticles20805.2.1. Ferro- and Ferrimagnetic Nanoparticles 20805.3. Use of Nanoparticles as Contrast Agents forMRI20825.3.1. High Anisotropy Model 20845.3.2. Small Crystal and Low Anisotropy EnergyLimit20855.3.3. Practical Interests of Magnetic NuclearRelaxation for the Characterization ofSuperparamagnetic Colloid20855.3.4. Relaxation of Agglomerated Systems 20856. Applications 20866.1. MRI: Cellular Labeling, Molecular Imaging(Inﬂammation, Apoptose, etc.)20866.2.

Magnetic Iron Oxide Nanoparticles: Synthesis, Stabilization, Vectorization, Physicochemical Characterizations, and Biological Applications

The development of novel materials is a fundamental focal point of chemical research; and this interest is mandated by advancements in all areas of industry and technology. A good example of the synergism between scientific discovery and technological development is the electronics industry, where discoveries of new semiconducting materials resulted in the evolution from vacuum tubes to diodes and transistors, and eventually to miniature chips. The progression of this technology led to the development * To whom correspondence should be addressed. B.L.C.: (504) 2801385 (phone); (504) 280-3185 (fax); bcushing@uno.edu (e-mail). C.J.O.: (504)280-6846(phone);(504)280-3185(fax);coconnor@uno.edu (e-mail). 3893 Chem. Rev. 2004, 104, 3893−3946

http://depa.fquim.unam.mx/amyd//archivero/FidelmarLechugaSanabria_4940.pdf

Recent advances in the liquid-phase syntheses of inorganic nanoparticles.

Self-assembled cage structures of nanometre dimensions can be used as constrained environments for the preparation of nanostructured materials1,2 and the encapsulation of guest molecules3, with potential applications in drug delivery4 and catalysis5. In synthetic systems the number of subunits contributing to cage structures is typically rather small3,6. But the protein coats of viruses (virions) commonly comprise hundreds of subunits that self-assemble into a cage for transporting viral nucleic acids. Many virions, moreover, can undergo reversible structural changes that open or close gated pores to allow switchable access to their interior7. Here we show that such a virion — that of the cowpea chlorotic mottle virus — can be used as a host for the synthesis of materials. We report the mineralization of two polyoxometalate species (paratungstate and decavanadate) and the encapsulation of an anionic polymer inside this virion, controlled by pH-dependent gating of the virion's pores. The diversity in size and shape of such virus particles make this a versatile strategy for materials synthesis and molecular entrapment.

Host–guest encapsulation of materials by assembled virus protein cages

The use of biological molecules, assemblies and systems in the development of inorganic materials synthesis continues to offer new and exciting alternatives to conventional synthetic strategies. Biological templates, such as protein cages, viroid capsules, bacterial rhapidosomes, S-layers, multicellular superstructures, biolipid cylinders, and DNA, have been utilized to direct the deposition, assembly, and patterning of inorganic nanoparticles and microstructures. In this paper, we report a new approach to the template-directed synthesis of inorganic±organic nanotubes using tobacco mosaic virus (TMV). TMV is a remarkably stable virion, remaining intact at temperatures up to 60 C and at pH values between 2 and 10. Each viral particle consists of 2130 identical protein subunits arranged in a helical motif around a single strand of RNA to produce a hollow protein tube, 300 18 nm in size, with a 4 nm-wide central channel. The internal and external surfaces of the protein consist of repeated patterns of charged amino acid residues, such as glutamate, aspartate, arginine, and lysine. In principle, these functionalities should offer a wide variety of nucleation sites for surface-controlled inorganic deposition, which, in association with the high thermal and pH stability, could be exploited in the synthesis of unusual materials such as high-aspect-ratio composites and protein-confined inorganic nanowires. Here we show that TMV is a suitable template for reactions such as co-crystallization (CdS and PbS), oxidative hydrolysis (iron oxides), and sol-gel condensation (SiO2) (Fig. 1).

Inorganic–Organic Nanotube Composites from Template Mineralization of Tobacco Mosaic Virus

The study of viruses has traditionally focused on their roles as infectious agents and as tools for understanding cell biology. Viruses are now finding a new expanded role as nanoplatforms with applications in materials science and medicine. Viruses form highly symmetrical monodisperse architectures and are ideal templates for engineering multifunctionality, including multivalent display of surface ligands and encapsulation of inorganic and organic materials. These developments assure that viruses will find applications as versatile nanoscale materials.

/pdf/viruses-making-friends-with-old-foes-3xnr4nupdv.pdf

Viruses: Making Friends with Old Foes

Materials scientists increasingly draw inspiration from the study of how biological systems fabricate materials under mild synthetic conditions by using self-assembled macromolecular templates. Containerlike protein architectures such as viral capsids and ferritin are examples of such biological templates. These protein cages have three distinct interfaces that can be synthetically exploited: the interior, the exterior, and the interface between subunits. The subunits that comprise the building blocks of these structures can be modified both chemically and genetically in order to impart designed functionality to different surfaces of the cage. Therefore, the cages possess a great deal of synthetic flexibility, which allows for the introduction of multifunctionality in a single cage. In addition, hierarchical assembly of the functionalized cages paves the way for development of a new class of materials with a wide range of applications from electronics to biomedicine.

Biological Containers: Protein Cages as Multifunctional Nanoplatforms

The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of humans, we analyzed a deep DNA sequence dataset of active bacteriophages and available metagenomic datasets of the gut bacteriophage community from healthy individuals. We found 23 shared bacteriophages in more than one-half of 64 healthy individuals from around the world. These shared bacteriophages were found in a significantly smaller percentage of individuals with gastrointestinal/irritable bowel disease. A network analysis identified 44 bacteriophage groups of which 9 (20%) were shared in more than one-half of all 64 individuals. These results provide strong evidence of a healthy gut phageome (HGP) in humans. The bacteriophage community in the human gut is a mixture of three classes: a set of core bacteriophages shared among more than one-half of all people, a common set of bacteriophages found in 20-50% of individuals, and a set of bacteriophages that are either rarely shared or unique to a person. We propose that the core and common bacteriophage communities are globally distributed and comprise the HGP, which plays an important role in maintaining gut microbiome structure/function and thereby contributes significantly to human health.

https://www.pnas.org/content/pnas/113/37/10400.full.pdf

Mark J. Young

Papers

Host–guest encapsulation of materials by assembled virus protein cages

Inorganic–Organic Nanotube Composites from Template Mineralization of Tobacco Mosaic Virus

Viruses: Making Friends with Old Foes

Biological Containers: Protein Cages as Multifunctional Nanoplatforms

Healthy human gut phageome