In vivo evidence for homeostatic regulation of ribosomal protein levels in Drosophila.

The ribosome is a molecular machine essential for protein synthesis, which is composed of approximately 80 different ribosomal proteins (Rps). Studies in yeast and cell culture systems have revealed that the intracellular level of Rps is finely regulated by negative feedback mechanisms or ubiquitin-proteasome system, which prevents over- or under-abundance of Rps in the cell. However, in vivo evidence for the homeostatic regulation of intracellular Rp levels has been poor. Here, using Drosophila genetics, we show that intracellular Rp levels are regulated by proteasomal degradation of excess Rps that are not incorporated into the ribosome. By establishing an EGFP-fused Rp gene system that can monitor endogenously expressed Rp levels, we found that endogenously expressed EGFP-RpS20 or -RpL5 is eliminated from the cell when RpS20 or RpL5 is exogenously expressed. Notably, the level of endogenously expressed Hsp83, a housekeeping gene, was not affected by exogenous expression of Hsp83, suggesting that the strict negative regulation of excess protein is specific for intracellular Rps. Further analyses revealed that the maintenance of cellular Rp levels is not regulated at the transcriptional level but by proteasomal degradation of excess free Rps as a protein quality control mechanism. Our observations provide not only the in vivo evidence for the homeostatic regulation of Rp levels but also a novel genetic strategy to study in vivo regulation of intracellular Rp levels and its role in tissue homeostasis via cell competition.Key words: ribosomal protein, proteasomal degradation, Drosophila.

Concentration of fifty-six elements in excreta of penguins from the Antarctic Peninsula area.

Seabird feces as indicators of the exposure to environmental contaminants have been studied worldwide. Penguins are indicator species for marine pollution, but their role as biovectors of rare earth elements (REEs) to ecosystems have been little studied. The present study quantified the concentration of REEs and trace elements (TEs) in feces of gentoo penguin (Pygoscelis papua). Adult penguin excreta from Fildes Bay (King George Island) and Yelcho Base (Palmer Archipelago) were collected and then analyzed by ICP-MS. Among REEs, levels ranged from 0.0038 to 1.02 µg g-1 d.w. for Lu and Ce, respectively. For TEs, the levels varied widely through the sample set, with Al, Fe, Sr, Zn and Ti as the highest mean levels, particularly at Fildes Bay. The data show that gentoo penguins act as a biovector organism by transporting TEs and REEs from the sea to land via excreta, reaffirming that this species acts as an important biovector organism in Antarctic ecosystems. The potential impacts of this process on Antarctic ecosystems needs further research.

The early neutrophil-committed progenitors aberrantly differentiate into immunoregulatory monocytes during emergency myelopoiesis.

Inflammatory stimuli cause a state of emergency myelopoiesis leading to neutrophil-like monocyte expansion. However, their function, the committed precursors, or growth factors remain elusive. In this study we find that Ym1+Ly6Chi monocytes, an immunoregulatory entity of neutrophil-like monocytes, arise from progenitors of neutrophil 1 (proNeu1). Granulocyte-colony stimulating factor (G-CSF) favors the production of neutrophil-like monocytes through previously unknown CD81+CX3CR1lo monocyte precursors. GFI1 promotes the differentiation of proNeu2 from proNeu1 at the cost of producing neutrophil-like monocytes. The human counterpart of neutrophil-like monocytes that also expands in response to G-CSF is found in CD14+CD16- monocyte fraction. The human neutrophil-like monocytes are discriminated from CD14+CD16- classical monocytes by CXCR1 expression and the capacity to suppress T cell proliferation. Collectively, our findings suggest that the aberrant expansion of neutrophil-like monocytes under inflammatory conditions is a process conserved between mouse and human, which may be beneficial for the resolution of inflammation.

Occurrence of rare earth elements (REEs) and trace elements (TEs) in feathers of adult and young Gentoo penguins from King George Island, Antarctica.

Penguins are sentinel species for marine pollution, but their role as potential biovectors of REEs or TEs to ecosystems has been poorly studied. The present study analyzed (ICP-MS) feathers of young and adult Gentoo penguins from Fildes Bay, for 63 elements (including 15 REEs). Most of the REEs were present at very low levels, ranging from 0.002 (Lu) to 0.452 (Sm) µg g-1 d.w., several orders of magnitude lower than TEs. The content of TEs varied widely, with Al, Fe, Zn, Sr, Ba, Ti and Mn as the seven having the highest concentrations in the feathers of both age groups. The results show that P. papua deposits REEs and TEs through the feathers on the penguin rockery, whose potential actual impacts and long-term fate in remote regions need deeper research. This work presents essential baseline data that will be useful for further studies on Antarctic penguins.

Trace and rare earth elements in excreta of two species of marine mammals from South Shetland Islands, Antarctica.

Pinnipeds are sentinel species for marine pollution, but their role as vectors of trace elements (TEs) or rare earth elements (REEs) to ecosystems has been poorly studied. The present study tested pinniped feces for 61 elements, including REEs. Feces of adult seals (Mirounga leonina, Hydrurga leptonyx) from Fildes Bay, King George Island, Antarctica, were analyzed by ICP-MS. TEs varied by several orders of magnitude across the suite examined herein, with Fe, Al, Zn, Mn, HgII and Sr as the top six in both species. Of the REEs, Ce, Dy, Er, Eu, Gd, Ho, La, Lu, Nd, Pr, Sc, Sm, Tb, Y and Yb were found consistently in all samples and ranged from 0.935 to 0.006 µg g-1 d.w. The results show that both species act as biovector organisms of TEs and REEs through feces in remote environments, whose actual impacts and long-term fate need further exploration.

Extracellular vesicles from human bone marrow mesenchymal stem cells repair organ damage caused by cadmium poisoning in a medaka model.

Treatment modalities for kidney disease caused by long-term exposure to heavy metals, such as cadmium (Cd), are limited. Often, chronic, long-term environmental exposure to heavy metal is not recognized in the early stages; therefore, chelation therapy is not an effective option. Extracellular vesicles (EVs) derived from stem cells have been demonstrated to reduce disease pathology in both acute and chronic kidney disease models. To test the ability of EVs derived from human bone marrow mesenchymal stem cells (hBM-MSCs) to treat Cd damage, we generated a Cd-exposed medaka model. This model develops heavy metal-induced cell damage in various organs and tissues, and shows decreased overall survival. Intravenous injection of highly purified EVs from hBM-MSCs repaired the damage to apical and basolateral membranes and mitochondria of kidney proximal tubules, glomerular podocytes, bone deformation, and improved survival. Our system also serves as a model with which to study age- and sex-dependent cell injuries of organs caused by various agents and diseases. The beneficial effects of EVs on the tissue repair process, as shown in our novel Cd-exposed medaka model, may open new broad avenues for interventional strategies.

Cytotoxic and genotoxic effects of arsenic on erythrocytes of Oryzias latipes: Bioremediation using Spirulina platensis.

BACKGROUND: Exposure to the environmental pollutants poses a serious threat to aquatic organism. The arsenic exposure in fish increases the risk of developing serious alterations from embryo to adult. OBJECTIVES: The present investigation was done to study the toxic effects of heavy metal arsenic [As(III)] on medaka (Oryzias latipes). Morphological alterations, apoptosis, nuclear abnormalities, and genotoxic biomarkers in erythrocytes were used to determine the stress caused by arsenic (As) exposure. METHODS: Medaka was exposed to As for 15 days at two toxic sublethal concentrations (7 ppm and 10 ppm) in combination with Spirulina platensis (SP) treatment as antioxidant algae at 200 mg/L. RESULTS: Results were consistent with a previous study results on tilapia. Exposure of medaka to As resulted in a dose-dependent increase in most the biomarkers used in the current study. Fish exposed to10 ppm As showed highest level of DNA damage. For the first time to our knowledge, using SP to counter the As toxicity in medaka, DNA damage restored to control levels. CONCLUSION: Accordingly, those results suggests that SP can protect medaka in aquaculture against As-induced damage by its ability as reactive oxygen species (ROS) reducer, antioxidant role, and DNA damage scavenger.