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

Fish bioaccumulation and biomarkers in environmental risk assessment: a review

The fish gill is a multipurpose organ that, in addition to providing for aquatic gas exchange, plays dominant roles in osmotic and ionic regulation, acid-base regulation, and excretion of nitrogenous wastes Thus, despite the fact that all fish groups have functional kidneys, the gill epithelium is the site of many processes that are mediated by renal epithelia in terrestrial vertebrates Indeed, many of the pathways that mediate these processes in mammalian renal epithelial are expressed in the gill, and many of the extrinsic and intrinsic modulators of these processes are also found in fish endocrine tissues and the gill itself The basic patterns of gill physiology were outlined over a half century ago, but modern immunological and molecular techniques are bringing new insights into this complicated system Nevertheless, substantial questions about the evolution of these mechanisms and control remain

https://people.clas.ufl.edu/devans/files/PRVGill.pdf

The Multifunctional Fish Gill: Dominant Site of Gas Exchange, Osmoregulation, Acid-Base Regulation, and Excretion of Nitrogenous Waste

Nature And Properties Of Soils

Silver nanoparticles are nanoparticles of silver which are in the range of 1 and 100 nm in size. Silver nanoparticles have unique properties which help in molecular diagnostics, in therapies, as well as in devices that are used in several medical procedures. The major methods used for silver nanoparticle synthesis are the physical and chemical methods. The problem with the chemical and physical methods is that the synthesis is expensive and can also have toxic substances absorbed onto them. To overcome this, the biological method provides a feasible alternative. The major biological systems involved in this are bacteria, fungi, and plant extracts. The major applications of silver nanoparticles in the medical field include diagnostic applications and therapeutic applications. In most of the therapeutic applications, it is the antimicrobial property that is being majorly explored, though the anti-inflammatory property has its fair share of applications. Though silver nanoparticles are rampantly used in many medical procedures and devices as well as in various biological fields, they have their drawbacks due to nanotoxicity. This review provides a comprehensive view on the mechanism of action, production, applications in the medical field, and the health and environmental concerns that are allegedly caused due to these nanoparticles. The focus is on effective and efficient synthesis of silver nanoparticles while exploring their various prospective applications besides trying to understand the current scenario in the debates on the toxicity concerns these nanoparticles pose.

/pdf/silver-nanoparticles-mechanism-of-antimicrobial-action-3x1asgjbb2.pdf

Silver nanoparticles: mechanism of antimicrobial action, synthesis, medical applications, and toxicity effects

Protein tyrosine phosphatases (PTPs) are key enzymes in cellular regulation. The 107 human PTPs are regulated by redox signalling, phosphorylation, dimerisation, and proteolysis. Recent findings of very strong inhibition of some PTPs by zinc ions at concentrations relevant in a cellular environment suggest yet another mechanism of regulation. One of the most extensively investigated PTPs is PTP1B (PTPN1). It regulates the insulin and leptin signalling pathway and is implicated in cancer and obesity/diabetes. The development of novel assay conditions to investigate zinc inhibition of PTP1B provides estimates of about 5.6 nM affinity for inhibitory zinc(II) ions. Analysis of three PTP1B 3D structures (PDB id: 2CM2, 3I80 and 1A5Y) identified putative zinc binding sites and supports the kinetic studies in suggesting an inhibitory zinc only in the closed and cysteinyl–phosphate intermediate forms of the enzyme. These observations gain significance with regard to recent findings of regulatory roles of zinc ions released from the endoplasmic reticulum.

/pdf/zinc-ions-modulate-protein-tyrosine-phosphatase-1b-activity-2uo0mflhhn.pdf

Zinc ions modulate protein tyrosine phosphatase 1B activity.

Renal Cu and Na excretion and hepatic Cu metabolism in both Cu acclimated and non acclimated rainbow trout (Oncorhynchus mykiss)

SUMMARY Knowledge of the uptake mechanisms and metabolism of metals is essential for understanding the factors governing metal toxicity, discerning means by which acclimation and homeostasis may be achieved and characterising interactions between the metal of interest and other environmental moieties. Zinc is both an important aquatic contaminant and a vital micronutrient. The physiological characterisation of dietary zinc absorption in fish has, therefore, important implications for environmental protection and aquaculture. The present study aimed to elucidate the mechanism of intestinal zinc uptake in freshwater rainbow trout ( Oncorhynchus mykiss ), using an in vivo cannulation technique. Only a saturable component of zinc uptake, with a concentration giving half-maximal rate of accumulation ( K 0.5 ) of 309 μmol l –1 , and a maximal rate of accumulation ( J max ) of 933 nmol kg –1  h –1 , was described. This characterised the intestine as a low-affinity, high-capacity zinc absorption pathway. Physiological mechanisms appear to regulate zinc uptake. Intestinal mucus was one important regulatory locus, promoting zinc uptake at low concentrations yet buffering the animal against high luminal zinc loads. Regulatory mechanisms also seemed to limit subepithelial zinc accumulation. Experiments using ethylene glycol tetraacetic acid (EGTA) to wash the intestinal lumen following zinc perfusion exhibited a higher proportion of loosely associated zinc at higher perfused concentrations. This was attributed to saturation of the uptake process or efflux from the subepithelium. Two distinct pathways for passage of zinc across the epithelium were discerned, with post-intestinal transfer possibly mediated by sulphydryl groups, as illustrated by N -ethylmaleimide perfusion experiments. Putative roles of zinc transporters and/or intracellular-binding proteins are discussed.

In vivo characterisation of intestinal zinc uptake in freshwater rainbow trout

Resolving the mechanisms underlying the temporal and spatial profile of zinc transporter expression in response to zinc availability is key to understanding zinc homeostasis. The mRNA expression of seven zinc transporters was studied in zebrafish gills when treated with zinc deficiency/excess over a 14-day period. Of these, ZnT1, ZnT5, ZIP3, and ZIP10 were differentially expressed in response to changed zinc status. The mRNA level of zinc exporter, ZnT1, was upregulated in fish subjected to excess zinc and downregulated by zinc deprivation. This response was similar to that of metallothionein-2 (MT2). Zinc deficiency caused an increased abundance of mRNA for zinc importers ZnT5, ZIP3, and ZIP10. Expression of ZnT5 and ZIP10, but not ZIP3, was inhibited by excess zinc. Zinc influx function of ZIP10 was demonstrated by 65Zn transport assays in Xenopus oocyte expression experiments, suggesting that the inverse relationship between zinc availability and ZIP10 expression serves to maintain zinc homeostasis. Two distinct transcription start sites (TSS) for ZIP10 were found in gill and kidney. Luciferase assays and mutation/deletion analysis of DNA fragments proximal to the respective TSS revealed that ZIP10 has two alternative promoters (P1 and P2) displaying opposite regulatory control in response to zinc status. Positive as well as negative regulation by zinc involves MRE clusters in the respective promoters. These results provide experimental evidence for MREs functioning as repressor elements, implicating MTF1 involvement in the negative regulation of ZIP10. This is in contrast to the well-established positive regulation by MTF1 of other genes, such as MT2 and ZnT1.

https://www.physiology.org/doi/pdf/10.1152/physiolgenomics.90206.2008

Regulation of ZIP and ZnT zinc transporters in zebrafish gill: zinc repression of ZIP10 transcription by an intronic MRE cluster

High-carbohydrate diets (HCD) can induce the occurrence of nonalcoholic fatty liver disease (NAFLD), characterized by dramatic accumulation of hepatic lipid droplets (LDs). However, the potential molecular mechanisms are still largely unknown. In this study, we investigated the role of autophagy in the process of HCD-induced changes of hepatic lipid metabolism, and to examine the process of underlying mechanisms during these molecular contexts. We found that HCD significantly increased hepatic lipid accumulation and activated autophagy. Using primary hepatocytes, we found that HG increased lipid accumulation and stimulated the release of NEFA by autophagy-mediated lipophagy, and that lipophagy significantly alleviated high glucose (HG)-induced lipid accumulation. Oxidative and endoplasmic reticulum (ER) stress pathways played crucial regulatory roles in HG-induced lipophagy activation and HG-induced changes of lipid metabolism. Further investigation found that HG-activated lipophagy and HG-induced changes of lipid metabolism were via enhancing carbohydrate response element-binding protein (ChREBP) DNA binding capacity at PPARγ promoter region, which in turn induced transcriptional activation of the key genes related to lipogenesis and autophagy. The present study, for the first time, revealed the novel mechanism for lipophagy mediating HCD-induced changes of lipid metabolism by oxidative stress and ER stress, and ChREBP/PPARγ pathways. Our study provided innovative evidence for the direct relationship between carbohydrate and lipid metabolism via ChREBP/PPARγ pathway.

/pdf/lipophagy-mediated-carbohydrate-induced-changes-of-lipid-4ej0k76286.pdf

Christer Hogstrand

Papers

Zinc ions modulate protein tyrosine phosphatase 1B activity.

Renal Cu and Na excretion and hepatic Cu metabolism in both Cu acclimated and non acclimated rainbow trout (Oncorhynchus mykiss)

In vivo characterisation of intestinal zinc uptake in freshwater rainbow trout

Regulation of ZIP and ZnT zinc transporters in zebrafish gill: zinc repression of ZIP10 transcription by an intronic MRE cluster

Lipophagy mediated carbohydrate-induced changes of lipid metabolism via oxidative stress, endoplasmic reticulum (ER) stress and ChREBP/PPARγ pathways