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

Irrespective of the morphological features of end-stage cell death (that may be apoptotic, necrotic, autophagic, or mitotic), mitochondrial membrane permeabilization (MMP) is frequently the decisive event that delimits the frontier between survival and death. Thus mitochondrial membranes constitute the battleground on which opposing signals combat to seal the cell's fate. Local players that determine the propensity to MMP include the pro- and antiapoptotic members of the Bcl-2 family, proteins from the mitochondrialpermeability transition pore complex, as well as a plethora of interacting partners including mitochondrial lipids. Intermediate metabolites, redox processes, sphingolipids, ion gradients, transcription factors, as well as kinases and phosphatases link lethal and vital signals emanating from distinct subcellular compartments to mitochondria. Thus mitochondria integrate a variety of proapoptotic signals. Once MMP has been induced, it causes the release of catabolic hydrolases and activators of such enzymes (including those of caspases) from mitochondria. These catabolic enzymes as well as the cessation of the bioenergetic and redox functions of mitochondria finally lead to cell death, meaning that mitochondria coordinate the late stage of cellular demise. Pathological cell death induced by ischemia/reperfusion, intoxication with xenobiotics, neurodegenerative diseases, or viral infection also relies on MMP as a critical event. The inhibition of MMP constitutes an important strategy for the pharmaceutical prevention of unwarranted cell death. Conversely, induction of MMP in tumor cells constitutes the goal of anticancer chemotherapy.

Mitochondrial Membrane Permeabilization in Cell Death

Reported values in the literature on the number of cells in the body differ by orders of magnitude and are very seldom supported by any measurements or calculations. Here, we integrate the most up-to-date information on the number of human and bacterial cells in the body. We estimate the total number of bacteria in the 70 kg "reference man" to be 3.8·1013. For human cells, we identify the dominant role of the hematopoietic lineage to the total count (≈90%) and revise past estimates to 3.0·1013 human cells. Our analysis also updates the widely-cited 10:1 ratio, showing that the number of bacteria in the body is actually of the same order as the number of human cells, and their total mass is about 0.2 kg.

/pdf/revised-estimates-for-the-number-of-human-and-bacteria-cells-4fb3y5elnx.pdf

Revised Estimates for the Number of Human and Bacteria Cells in the Body.

https://www.cell.com/molecular-cell/pdf/S1097-2765(08)00292-X.pdf

Oxygen Sensing by Metazoans: The Central Role of the HIF Hydroxylase Pathway

http://basicmed.med.ncku.edu.tw/admin/up_img/1007-2.pdf

Oncometabolite 2-Hydroxyglutarate Is a Competitive Inhibitor of α-Ketoglutarate-Dependent Dioxygenases

Cell-cell adhesion molecules

Epidermolysis bullosa pruriginosa (EBP) is a rare subtype of EB which is characterized by intense pruritus with blistering and nodular or lichenoid lesions most prominent on the lower extremities. It is caused by variants in COL7A1 which encodes for type VII collagen. There is wide phenotypic and genotypic variability between affected individuals. We report 2 potentially pathogenic variants in COL7A1 occurring on the same allele in a family with EBP and autosomal dominant inheritance. Late-onset EBP and incomplete penetrance may lead to delayed presentation in affected family members with the same variants. The broad phenotypic variability seen in EBP suggests that further genotypic and environmental factors may influence presentation. Genetic and histopathological diagnosis is essential, given the considerable overlap with clinically similar presentations such as hypertrophic lichen planus.

Coinheritance of 2 New Potentially Damaging Heterozygous COL7A1 Variants in a Family With Autosomal Dominant Epidermolysis Bullosa Pruriginosa.

Molecular evidence that Hay-Wells and Rapp-Hodgkin ectodermal dysplasia syndromes are genetically indistinct.

283 Genome-wide association study in frontal fibrosing alopecia identifies 4 genomic loci and implicates auto-immunity and xenobiotic exposure in aetiopathogenesis

References 1 Weyant GW, Chung CG, Helm KF. Halo nevus: review of the literature and clinicopathologic findings. Int J Dermatol 2015; 54: e433–e435. 2 Kluger N, Seit e S, Taieb C. The prevalence of tattooing and motivations in five major countries over the world. J Eur Acad Dermatol Venereol 2019. https://doi.org/10.1111/jdv.15808. 3 Kluger N, Catala D, Thibaut I. Naevus and tattooing: a matter of concern. J Eur Acad Dermatol Venereol 2008; 22: 767–768. 4 Dodgen T, Crowe D. Tattoo pigment removal by halo nevus phenomenon. JAAD Case Rep 2019; 5: 317–318. 5 Baranska A, Shawket A, Jouve M, et al. Unveiling skin macrophage dynamics explains both tattoo persistence and strenuous removal. J Exp Med 2018; 215: 1115–1133. 6 Pan H, Song W, Xu A. A case of vitiligo induced by tattooing eyebrow. Int J Dermatol 2011; 50: 607–608. 7 Kluger N, Trouche F. Vitiligo on a tattoo. Ann Dermatol Venereol 2011; 138: 549–550.

John A. McGrath

Papers

Cell-cell adhesion molecules

Coinheritance of 2 New Potentially Damaging Heterozygous COL7A1 Variants in a Family With Autosomal Dominant Epidermolysis Bullosa Pruriginosa.

Molecular evidence that Hay-Wells and Rapp-Hodgkin ectodermal dysplasia syndromes are genetically indistinct.

283 Genome-wide association study in frontal fibrosing alopecia identifies 4 genomic loci and implicates auto-immunity and xenobiotic exposure in aetiopathogenesis

Griscelli syndrome type 3 in Ethiopian sisters resulting from a homozygous missense mutation in MLPH.