Iron trafficking as an antimicrobial target

Iron is essential for the survival of most organisms. Microbial iron acquisition depends on multiple, sometimes complex steps, many of which are not shared by higher eukaryotes. Depriving pathogenic microbes of iron is therefore a potential antimicrobial strategy. The following minireview briefly describes general elements in microbial iron uptake pathways and summarizes some of the current work aiming at their medicinal inhibition.     

SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD,RBD, and S2

1. Download : Download high-res image (157KB)
2. Download : Download full-size image

     

Identifying Amsterdam's nutrient hotspots: A new method to map human excreta at building and neighborhood scale

Recovering nutrients from human excreta and wastewater has been receiving increasing attention as a means to supplement or replace synthetic fertilizer production. Apart from technologies for nutrient recovery at centralized wastewater treatment plants, numerous decentralized, source‐separated sanitation systems, also known as new sanitation systems, have been developed to facilitate recovery. Decision‐making for the planning and implementation of new sanitation systems would benefit from a spatially explicit inventory of nutrient hotspots in urban areas. To provide visual representations of nutrient loads, we developed a methodology that combines spatial‐temporal modeling with geographic information system analysis, and used it for the city of Amsterdam. The methodology is new in the field of nutrient mapping, especially at the smallest geographical scale: building. Nitrogen, phosphorus, and potassium loads and hotspots are mapped at both building and neighborhood scale, drawing attention to the need for multiple scale analyses in decision‐making. This study concludes with a discussion on the potential to further develop the method proposed to include more detailed and verified data and to identify nutrient hotspots that are promising as nutrient recovery sites with new sanitation systems.     

Knockdown of acyl-CoA:diacylglycerol acyltransferase 2 with antisense oligonucleotide reduces VLDL TG and ApoB secretion in mice

Acyl-CoA:diacylglycerol acyltransferases (DGATs) are enzymes that catalyze the formation of triglyceride (TG) from acyl-CoA and diacylglycerol. Two DGATs have been identified which belong to two distinct gene families and both are ubiquitously expressed. DGAT2 knockout mice are lipopenic and die shortly after birth. In the current study, wild type mice were treated with increasing doses (25-60 mg/kg twice weekly) of a DGAT2 gene-specific antisense oligonucleotide (ASO). Treatment resulted in a dose dependent decrease in hepatic DGAT2 gene expression (up to 80%) which was associated with a 40% decrease in hepatic DGAT2 activity and a 45% decrease in hepatic TG. Decreased levels of DGAT2 resulted in a significant dose dependent decrease in VLDL TG secretion (up to 52%) and reduced plasma TG, total cholesterol, and ApoB. Similar results were obtained when DGAT1 KO mice were treated with the DGAT2 ASO. Treatment of ob/ob mice with the DGAT2 ASO resulted in significant decreases in weight gain (10%), adipose weight (25%) and hepatic TG content (80%). Our findings indicate that the majority of TG destined for secretion by liver is synthesized by DGAT2 and suggests that DGAT2 may be a therapeutic target for treatment of hypertriglyceridemia, hepatic steatosis and obesity.     

Oral or nasal antigen induces regulatory T cells that suppress arthritis and proliferation of arthritogenic T cells in joint draining lymph nodes

The propagation of mucosal tolerance as a therapeutic approach in autoimmune diseases remains a difficult goal to achieve, and therefore further mechanistic studies are necessary to develop potential clinical protocols to induce mucosal regulatory T cells (Tr cells). In this study we addressed whether oral or nasal proteoglycan induced functional Tr cells in the cartilage proteoglycan-induced chronic arthritis model. Both nasal and oral application of human proteoglycan before induction of disease suppressed arthritis severity and incidence. Tolerized mice showed enhanced numbers of IL-10 producing CD4(+) cells in the paw-draining lymph nodes. Furthermore, CD4(+) spleen cells displayed enhanced expression of molecules associated with Tr cells, such as IL-10, Foxp3, and TGF-beta. Transfer of CD4(+) spleen cells from mucosally tolerized donors into proteoglycan-immunized mice abolished arthritis and reduced humoral responses, indicative of Tr cells with the capacity to inhibit already induced immune responses. Tr cells were activated upon transfer, because enhanced proliferation was observed in the joint draining lymph nodes compared with activated T cells from nontolerized donors. Upon cotransfer with naive proteoglycan-specific T cells, mucosally induced Tr cells inhibited proliferation of these arthritogenic T cells in vivo. Herein we show that both oral and nasal Ag application induced Tr cells, which had a direct inhibitory effect on already established pathogenic B and T cell responses.     

Response of regional tree-line forests to climate change: evidence from the northeastern Tibetan Plateau

Tree-ring width and age structure of Juniperus przewalskii (Qilian juniper) forests were analyzed for four tree-line sites in Qilian and Anyemaqen Mountains, northeastern Tibetan Plateau, to investigate their relationships to climate change. Tree-line growth on Qilian Mountain was mainly limited by temperature at the low-frequency band. However, tree-line growth in the Anyemaqen Mountain was highly correlated with the current growing season temperature at the high-frequency band, and with the previous growing season precipitation at the low-frequency band. A temperature-stressed growth pattern at colder western sites and a moisture-stressed growth pattern at the warm, drier eastern tree-line sites were detected. The number of surviving trees in the tree-line ecotone was not clearly correlated with temperature before the 1900s. An unprecedented rise in the number of trees coincided well with the rapid global warming after the 1900s.     

Calicivirus Inactivation by Nonionizing (253.7-Nanometer-Wavelength [UV]) and Ionizing (Gamma) Radiation

Noroviruses (previously Norwalk-like viruses) are the most common viral agents associated with food- and waterborne outbreaks of gastroenteritis. In the absence of culture methods for noroviruses, animal caliciviruses were used as model viruses to study inactivation by nonionizing (253.7-nm-wavelength [UV]) and ionizing (gamma) radiation. Here, we studied the respiratory feline calicivirus (FeCV) and the presumed enteric canine calicivirus (CaCV) and compared them with the well-studied bacteriophage MS2. When UV irradiation was used, a 3-log₁₀ reduction was observed at a fluence of 120 J/m² in the FeCV suspension and at a fluence of 200 J/m² for CaCV; for the more resistant phage MS2 there was a 3-log₁₀ reduction at a fluence of 650 J/m². Few or no differences were observed between levels of UV inactivation in high- and low-protein-content virus stocks. In contrast, ionizing radiation could readily inactivate MS2 in water, and there was a 3-log₁₀ reduction at a dose of 100 Gy, although this did not occur when the phage was diluted in high-protein-content stocks of CaCV or FeCV. The low-protein-content stocks showed 3-log₁₀ reductions at a dose of 500 Gy for FeCV and at a dose of 300 for CaCV. The inactivation rates for both caliciviruses with ionizing and nonionizing radiation were comparable but different from the inactivation rates for MS2. Although most FeCV and CaCV characteristics, such as overall particle and genome size and structure, are similar, the capsid sequences differ significantly, making it difficult to predict human norovirus inactivation. Adequate management of UV and gamma radiation processes for virus inactivation should limit public health risks.     

Quantum dot-based cell motility assay

Motility and migration are measurable characteristics of cells that are classically associated with the invasive potential of cancer cells, but in vitro assays of invasiveness have been less than perfect. We previously developed an assay to monitor cell motility and migration using water-soluble CdSe/ZnS nanocrystals; cells engulf the fluorescent nanocrystals as they crawl across them and leave behind a fluorescent-free trail. We show here that semiconductor nanocrystals can also be used as a sensitive two-dimensional in vitro invasion assay. We used this assay to compare the behavior of seven different adherent human cell lines, including breast epithelial MCF 10A, breast tumor MDA-MB-231, MDA-MB-435S, MCF 7, colon tumor SW480, lung tumor NCI H1299, and bone tumor Saos-2, and observed two distinct behaviors of cancer cells that can be used to further categorize these cells. Some cancer cell lines demonstrate fibroblastic behaviors and leave long fluorescent-free trails as they migrate across the dish, whereas other cancer cells leave clear zones of varying sizes around their periphery. This assay uses fluorescence detection, requires no processing, and can be used in live cell studies. These features contribute to the increased sensitivity of this assay and make it a powerful new tool for discriminating between non-invasive and invasive cancer cell lines.