The significance of peroxisomes in secondary metabolite biosynthesis in filamentous fungi

Peroxisomes are ubiquitous organelles characterized by a protein-rich matrix surrounded by a single membrane. In filamentous fungi, peroxisomes are crucial for the primary metabolism of several unusual carbon sources used for growth (e.g. fatty acids), but increasing evidence is presented that emphasize the crucial role of these organelles in the formation of a variety of secondary metabolites. In filamentous fungi, peroxisomes also play a role in development and differentiation whereas specialized peroxisomes, the Woronin bodies, play a structural role in plugging septal pores. The biogenesis of peroxisomes in filamentous fungi involves the function of conserved PEX genes, as well as genes that are unique for these organisms. Peroxisomes are also subject to autophagic degradation, a process that involves ATG genes. The interplay between organelle biogenesis and degradation may serve a quality control function, thereby allowing a continuous rejuvenation of the organelle population in the cells

Microbial shifts in the aging mouse gut

YesBackground: The changes that occur in the microbiome of aging individuals are unclear, especially in light of the imperfect correlation of frailty with age. Studies in older human subjects have reported subtle effects, but these results may be confounded by other variables that often change with age such as diet and place of residence. To test these associations in a more controlled model system, we examined the relationship between age, frailty, and the gut microbiome of female C57BL/6 J mice. Results: The frailty index, which is based on the evaluation of 31 clinical signs of deterioration in mice, showed a near-perfect correlation with age. We observed a statistically significant relationship between age and the taxonomic composition of the corresponding microbiome. Consistent with previous human studies, the Rikenellaceae family, which includes the Alistipes genus, was the most significantly overrepresented taxon within middle-aged and older mice. The functional profile of the mouse gut microbiome also varied with host age and frailty. Bacterial-encoded functions that were underrepresented in older mice included cobalamin (B12) and biotin (B7) biosynthesis, and bacterial SOS genes associated with DNA repair. Conversely, creatine degradation, associated with muscle wasting, was overrepresented within the gut microbiomes of the older mice, as were bacterial-encoded β-glucuronidases, which can influence drug-induced epithelial cell toxicity. Older mice also showed an overabundance of monosaccharide utilization genes relative to di-, oligo-, and polysaccharide utilization genes, which may have a substantial impact on gut homeostasis. Conclusion: We have identified taxonomic and functional patterns that correlate with age and frailty in the mouse microbiome. Differences in functions related to host nutrition and drug pharmacology vary in an age-dependent manner, suggesting that the availability and timing of essential functions may differ significantly with age and frailty. Future work with larger cohorts of mice will aim to separate the effects of age and frailty, and other factors.This work was supported by the Canadian Institutes of Health Research (CIHR) through an Emerging Team Grant to RGB, CIHR Operating Grants to Langille et al. Microbiome 2014, 2:50 Page 10 of 12 http://www.microbiomejournal.com/content/2/1/50 SEH (MOP 126018) and RAR (MOP 93718), and a CIHR Fellowship to MGIL. Infrastructure was supported by the Canada Foundation for Innovation through a grant to RGB. RGB also acknowledges the support of the Canada Research Chairs program

Copper and zinc concentrations in plant and animal raw materials collected in the vicinity of the Zelazny most waste treatment tailings pond

The study was carried out on the Cu and Zn content of plant material (wheat grain, hay and potato tubers) and animal food products (cow’s milk, hen’s eggs and chicken meat) collected in the vicinity of the Żelazny Most waste treatment tailings pond (Lower Silesia, Poland). The samples for the study accomplished in 2016-2018 were collected from the places located in the nearest vicinity of the tailings pond (6 farms within a distance shorter than 4 km – zone I) and those located further away (6 farms within a distance from 4 to 10 km from the tailings pond – zone II). Copper and Zn concentrations were measured on a Varian Spectra AA220 Fast Sequential atomic absorption spectrophotmeter. The mean values of Cu noted in wheat grain harvested in the years under investigation ranged from 3.87 to 5.27 mg kg-1 DM, while the maximum value was 6.97 mg kg-1 DM. The highest accumulation of Cu and Zn was in hay (max. 10.10 and 99.04 mg kg-1 DM, respectively), while the lowest values were noted in milk and eggs. The zinc content of cow’s milk was found within the range from 2.64 to 4.01 mg kg-1 FM and the highest amount was 6.32 mg kg-1 FM. It was also found the mean Cu concentrations in poultry meat varied from 0.53 to 1.55 mg kg-1 FM and the maximum value was 3.50 mg kg-1 FM. No significant differences between zones I and II were observed (p≤0.05). The current results are comparable with those obtained in 2007 and 2013. With only a few exceptions, the biomonitoring studies did not show that the levels of the two metals in the biological material tested exceeded data reported in the Polish and international literature. Nowadays, there is no reason to consider the Żelazny Most tailings pond to be an toxicological threat to the natural and agricultural environment regarding Cu and Zn, but its periodic biomonitoring is necessary due to the chemical properties of these two elements and their potential effect on some environmental factors

Synthesis and Antitumor Efficacy of a β-Glucuronidase-Responsive Albumin-Binding Prodrug of Doxorubicin.

International audienceIn this paper we describe the synthesis and biological evaluation of the first β-glucuronidase-responsive albumin-binding prodrug designed for the selective delivery of doxorubicin at the tumor site. This prodrug leads to superior antitumor efficacy in mice compared to HMR 1826, a well-known glucuronide prodrug of doxorubicin that cannot bind covalently to circulating albumin. Furthermore, this compound inhibits tumor growth in a manner similar to that of doxorubicin while avoiding side effects induced by the free drug