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

Autophagy, or cellular self-digestion, is a cellular pathway involved in protein and organelle degradation, with an astonishing number of connections to human disease and physiology. For example, autophagic dysfunction is associated with cancer, neurodegeneration, microbial infection and ageing. Paradoxically, although autophagy is primarily a protective process for the cell, it can also play a role in cell death. Understanding autophagy may ultimately allow scientists and clinicians to harness this process for the purpose of improving human health.

/pdf/autophagy-fights-disease-through-cellular-self-digestion-5i6zc9bv8a.pdf

Autophagy fights disease through cellular self-digestion

Autophagy is an intracellular degradation system that delivers cytoplasmic constituents to the lysosome. Despite its simplicity, recent progress has demonstrated that autophagy plays a wide variety of physiological and pathophysiological roles, which are sometimes complex. Autophagy consists of several sequential steps--sequestration, transport to lysosomes, degradation, and utilization of degradation products--and each step may exert different function. In this review, the process of autophagy is summarized, and the role of autophagy is discussed in a process-based manner.

http://genesdev.cshlp.org/content/21/22/2861.full.pdf

Autophagy: process and function

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.

https://biblio.ugent.be/publication/8555786/file/8555788.pdf

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

▪ Abstract DNA topoisomerases solve the topological problems associated with DNA replication, transcription, recombination, and chromatin remodeling by introducing temporary single- or double-strand breaks in the DNA. In addition, these enzymes fine-tune the steady-state level of DNA supercoiling both to facilitate protein interactions with the DNA and to prevent excessive supercoiling that is deleterious. In recent years, the crystal structures of a number of topoisomerase fragments, representing nearly all the known classes of enzymes, have been solved. These structures provide remarkable insights into the mechanisms of these enzymes and complement previous conclusions based on biochemical analyses. Surprisingly, despite little or no sequence homology, both type IA and type IIA topoisomerases from prokaryotes and the type IIA enzymes from eukaryotes share structural folds that appear to reflect functional motifs within critical regions of the enzymes. The type IB enzymes are structurally distinct from a...

DNA topoisomerases: structure, function, and mechanism.

Publisher Summary This chapter discusses the methods of transcription, transfection, and checking yield and quality of ribonucleic acid (RNA). RNA transfection is useful for starting an infection in cell lines that lack a specific virus receptor, studying replicating sub-viral RNAs, studying the translation of RNAs, and allowing viral proteins to be expressed. Many methods have been developed to transfect DNA into mammalian cells. The chapter presents three methods that have optimized for RNA. Lipofectin transfection and electroporation are useful when only a small quantity of RNA is available. Electroporation is particularly convenient for cells in suspension culture. Several methods are available to quantify specific RNAs in a mixed RNA population such as polymerase chain reaction on reverse-transcribed RNA, RNase protection, northern blots, and dot or slot blots. The RNA is purified by phenol extraction and ethanol precipitation. Two-cycle RNase protection is used to quantify any RNA in the presence of a greater amount of its complement.

RNA: Transcription, transfection and quantitation

The invention features recombinant viral vectors that take advantage of the activity of picornaviral protein 3A in modulating cytokine secretion and antigen presentation on MHC Class I (MHC I), which in turn provides for modulation of a Th1-mediated immune response to the transfected host cell Specifically, a recombinant viral vector comprising a sequence encoding picornaviral protein 3A provides for decreased antigen presentation on MHC I and a decreased incidence of Th1-mediated immune response, while a recombinant picornaviral vector that is deficient in protein 3A production provides for increased cytokine secretion, increased antigen presentation on MHC I and increased Th1-mediated immune response towards the transfected host cell The invention also features methods of inducing humoral or cellular immunity using the vectors

Viral vectors useful in induction of humoral or cellular immunity

http://web.stanford.edu/group/kirkegaard/pdf/Cooper_JBiotechnology_1994.pdf

The photocatalytic production of organic-free water for molecular biological and pharmaceutical applications.

Compositions and methods of modulating an immune response by controlling levels of interferon-gamma (IFN-γ) production by leukocytes are disclosed. Adjustment of IFN-γ levels is achieved by increasing or decreasing the activity of NeST (nettoie Salmonella pas Theiler's [cleanup Salmonella not Theiler's]), a long non-coding RNA that induces expression of IFN-γ. In particular, the invention relates to the use of NeST and inhibitors of NeST to modulate levels of IFN-γ for treatment of inflammatory conditions, autoimmune diseases, infectious diseases, immunodeficiency, and cancer.

Karla Kirkegaard

Papers

RNA: Transcription, transfection and quantitation

Viral vectors useful in induction of humoral or cellular immunity

The photocatalytic production of organic-free water for molecular biological and pharmaceutical applications.

IMMUNOMODULATION BY CONTROLLING INTERFERON-GAMMA LEVELS WITH THE LONG NON-CODING RNA NeST

The molecular basis of viral replication