Histoplasma capsulatum (Hc) exists in the soil and is capable of adapting to the shift in environment during infection to ensure survival. Yeast encounter a restrictive host environment low in nutrients such as zinc. In this study we functionally analyzed a putative zinc regulated transporter, HcZrt2, in zinc limiting conditions by complementation of HcZrt2 and gene knockdown through RNA interference (RNAi). Complementation analysis demonstrated HcZrt2's ability to functionally replace the characterized Saccharomyces cerevisiae zinc plasma membrane transporters Zrt1 and Zrt2 in zinc deficient medium. Gene silencing revealed that HcZrt2 is essential for growth in zinc deficient medium and plays a role in zinc accumulation. Fungal burden was reduced in mice infected with HcZrt2 silenced strains compared to a control strain. Sixty-seven percent of mice infected with a lethal dose of HcZrt2-RNAi#1 survived, and 100% of mice infected with HcZrt2-RNAi#2 withstood lethal infection. Our data suggest that HcZrt2 is a vital part of zinc homeostasis and essential for the pathogenesis of histoplasmosis.
The PLA-coated CS-MTX micro-implants were able to deliver therapeutic release of MTX for a period of more than 1 month without detectable toxicity in a rabbit model. The micro-implants can be further investigated as a prospective alternative to current treatment protocols of repeated intravitreal MTX injections in intraocular disorders such as primary intraocular lymphoma, and selected cases of non-microbial intraocular inflammation.
Arsenic is a toxic element to which humans are primarily exposed through food and water; it occurs as a result of human activities and naturally from the earth's crust. An experiment was developed for a senior level analytical laboratory utilizing an Inductively Coupled Plasma−Mass Spectrometer (ICP−MS) for the analysis of arsenic in household sinus wash and tap water. This powerful instrumental technique can be used to elucidate the elemental composition of a complex sample while offering the benefits of high-precision quantitative analysis. The chosen matrices further provided the opportunity to demonstrate two important analytical concepts. First, the sinus wash samples displayed signal suppression, illustrating the necessity for employment of the internal standard calibration technique. Second, the high chloride matrix of the sinus wash led to the formation of the ArCl + polyatomic ion in the argon plasma, which overlapped with arsenic's single isotope at m/z = 75. Analysis was performed in no gas mode and also with the collision cell in helium mode, allowing the students to observe firsthand the false positive results for arsenic by comparing 75 m/z results in the two modes. In addition, in a third objective, students were able to compare the sinus wash and tap water to current federal drinking water regulations. This laboratory exercise provided a novel and engaging application of ICP−MS and allowed the students to use modern instrumentation and analytical techniques to investigate the current and relevant issue of arsenic in our environment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.