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

Excitotoxicity: bridge to various triggers in neurodegenerative disorders.

Progress in Nuclear Magnetic Resonance Spectroscopy Vol. 2. Edited by J. W. Emsley, J. Feeney and L. H. Sutcliffe. Pp. vii + 269. (Oxford, London and New York: Pergamon Press, Ltd, 1967.) 90s. net. Advances in Magnetic Resonance Vol. 2. By John S. Waugh. Pp. xii + 269. (New York: Academic Press, Inc.; London: Academic Press, Inc. (London), Ltd, 1966.) $12.00. Guide to the NMR Empirical Method A Workbook. By Roy H. Bible jun.. Pp. xi + 305. (New York: Plenum Press, 1967.) $9.50.

/pdf/nuclear-magnetic-resonance-m75j2z9fc0.pdf

Nuclear Magnetic Resonance

The plasma membrane of eukaryotic cells contains several types of lipids displaying high biochemical variability in both their apolar moiety (e.g. the acyl chain of glycerolipids) and their polar head (e.g. the sugar structure of glycosphingolipids). Among these lipids, cholesterol is unique because its biochemical variability is almost exclusively restricted to the oxidation of its polar -OH group. Although generally considered the most rigid membrane lipid, cholesterol can adopt a broad range of conformations due to the flexibility of its isooctyl chain linked to the polycyclic sterane backbone. Moreover, cholesterol is an asymmetric molecule displaying a planar face and a rough  face. Overall, these structural features open up a number of possible interactions between cholesterol and membrane lipids and proteins, consistent with the prominent regulatory functions that this unique lipid exerts on membrane components. The aim of this review is to describe how cholesterol interacts with membrane lipids and proteins at the molecular/atomic scale, with special emphasis on transmembrane domains of proteins containing either the consensus cholesterol-binding motifs CRAC and CARC or a tilted peptide. Despite their broad structural diversity, all these domains bind cholesterol through common molecular mechanisms, leading to the identification of a subset of amino acid residues that are overrepresented in both linear and three-dimensional membrane cholesterol-binding sites.

/pdf/how-cholesterol-interacts-with-membrane-proteins-an-4fbhlpho06.pdf

How cholesterol interacts with membrane proteins: an exploration of cholesterol-binding sites including CRAC, CARC, and tilted domains

Antioxidant, antimicrobial and cytotoxic activities of selected medicinal plants from Yemen

C99 is the transmembrane carboxyl-terminal domain of the amyloid precursor protein that is cleaved by γ-secretase to release the amyloid-β polypeptides, which are associated with Alzheimer’s disease. Nuclear magnetic resonance and electron paramagnetic resonance spectroscopy show that the extracellular amino terminus of C99 includes a surface-embedded “N-helix” followed by a short “N-loop” connecting to the transmembrane domain (TMD). The TMD is a flexibly curved α helix, making it well suited for processive cleavage by γ-secretase. Titration of C99 reveals a binding site for cholesterol, providing mechanistic insight into how cholesterol promotes amyloidogenesis. Membrane-buried GXXXG motifs (G, Gly; X, any amino acid), which have an established role in oligomerization, were also shown to play a key role in cholesterol binding. The structure and cholesterol binding properties of C99 may aid in the design of Alzheimer’s therapeutics.

/pdf/the-amyloid-precursor-protein-has-a-flexible-transmembrane-39epowqlle.pdf

The Amyloid Precursor Protein Has a Flexible Transmembrane Domain and Binds Cholesterol

As of mid 2013 a Medline search on "cholesterol" yielded over 200,000 hits, reflecting the prominence of this lipid in numerous aspects of animal cell biology and physiology under conditions of health and disease. Aberrations in cholesterol homeostasis underlie both a number of rare genetic disorders and contribute to common sporadic and complex disorders including heart disease, stroke, type II diabetes, and Alzheimer's disease. The corresponding author of this review and his lab stumbled only recently into the sprawling area of cholesterol research when they discovered that the amyloid precursor protein (APP) binds cholesterol, a topic covered by the Hans Neurath Award lecture at the 2013 Protein Society Meeting. Here, we first provide a brief overview of cholesterol-protein interactions and then offer our perspective on how and why binding of cholesterol to APP and its C99 domain (β-CTF) promotes the amyloidogenic pathway, which is closely related to the etiology of Alzheimer's disease.

/pdf/cholesterol-as-a-co-solvent-and-a-ligand-for-membrane-11aeek4xxc.pdf

Cholesterol as a co-solvent and a ligand for membrane proteins

Isolation, structure elucidation, antioxidative and immunomodulatory properties of two novel dihydrocoumarins from Aloe vera.

The 99-residue transmembrane C-terminal domain (C99, also known as β-CTF) of the amyloid precursor protein (APP) is the product of the β-secretase cleavage of the full-length APP and is the substrate for γ-secretase cleavage. The latter cleavage releases the amyloid-β polypeptides that are closely associated with Alzheimer’s disease. C99 is thought to form homodimers; however, the free energy in favor of dimerization has not previously been quantitated. It was also recently documented that cholesterol forms a 1:1 complex with monomeric C99 in bicelles. Here, the affinities for both homodimerization and cholesterol binding to C99 were measured in bilayered lipid vesicles using both electron paramagnetic resonance (EPR) and Forster resonance energy transfer (FRET) methods. Homodimerization and cholesterol binding were seen to be competitive processes that center on the transmembrane G700XXXG704XXXG708 glycine-zipper motif and adjacent Gly709. On one hand, the observed Kd for cholesterol binding (Kd = 2.7 ± ...

/pdf/competition-between-homodimerization-and-cholesterol-binding-5avdtb7mwj.pdf

Competition Between Homodimerization and Cholesterol Binding to the C99 Domain of the Amyloid Precursor Protein

Real-time monitoring of bioprocesses by the integration of analytics at critical unit operations is one of the paramount necessities for quality by design manufacturing and real-time release (RTR) of biopharmaceuticals. A well-defined process analytical technology (PAT) roadmap enables the monitoring of critical process parameters and quality attributes at appropriate unit operations to develop an analytical paradigm that is capable of providing real-time data. We believe a comprehensive PAT roadmap should entail not only integration of analytical tools into the bioprocess but also should address automated-data piping, analysis, aggregation, visualization, and smart utility of data for advanced-data analytics such as machine and deep learning for holistic process understanding. In this review, we discuss a broad spectrum of PAT technologies spanning from vibrational spectroscopy, multivariate data analysis, multiattribute chromatography, mass spectrometry, sensors, and automated-sampling technologies. We also provide insights, based on our experience in clinical and commercial manufacturing, into data automation, data visualization, and smart utility of data for advanced-analytics in PAT. This review is catered for a broad audience, including those new to the field to those well versed in applying these technologies. The article is also intended to give some insight into the strategies we have undertaken to implement PAT tools in biologics process development with the vision of realizing RTR testing in biomanufacturing and to meet regulatory expectations.

Yuanli Song

Papers

The Amyloid Precursor Protein Has a Flexible Transmembrane Domain and Binds Cholesterol

Cholesterol as a co-solvent and a ligand for membrane proteins

Isolation, structure elucidation, antioxidative and immunomodulatory properties of two novel dihydrocoumarins from Aloe vera.

Competition Between Homodimerization and Cholesterol Binding to the C99 Domain of the Amyloid Precursor Protein

Technology outlook for real-time quality attribute and process parameter monitoring in biopharmaceutical development-A review.