Human TTRV30M localization within podocytes in a transgenic mouse model of transthyretin related amyloidosis: does the environment play a role?

Transthyretin related amyloidosis is a nosological entity that leads to disability, diminished quality of life, all stages of chronic kidney disease and eventually death. Podocytes are polarized, highly differentiated epithelial cells important for proper nephron function. In the present study we investigated whether deposited TTRVal30Met (TTRV30M) molecules could be localized within podocytes in situ under the effect of different housing conditions (i.e. specific pathogen free [SPF] vs. non-SPF). Murine renal glomeruli from human TTRV30M (hTTRV30M) transgenic mice were examined via direct and indirect immunofluorescence techniques for the presence of hTTRV30M, murine serum amyloid P, activated caspase-3 and NPHS1. Association strength and amount of colocalization for NPHS1?ChTTRV30M, NPHS1-activated caspase-3, hTTRV30M-murine serum amyloid P were estimated. Localization of hTTRV30M in podocytes was demonstrated by immuno-electron microscopy. Renal hTTRV30M gene and NPHS1 gene expression levels were estimated. Non-SPF transgenic mice showed increased glomerular hTTRV30M deposition compared to their SPF counterparts. Furthermore increased podocytic localization of hTTRV30M was noticed in non-SPF mice. Glomerular caspase-3 activation was increased only in the non SPF housing conditions. Podocytic caspase-3 activation was increased in SPF and in non-SPF transgenic mice when compared to non transgenic controls. Environmental conditions influence glomerular deposition and podocytic localization of hTTRV30M. In this context increased caspase-3 activation occurred.     

A Framework to Assess Biogeochemical Response to Ecosystem Disturbance Using Nutrient Partitioning Ratios

Disturbances affect almost all terrestrial ecosystems, but it has been difficult to identify general principles regarding these influences. To improve our understanding of the long-term consequences of disturbance on terrestrial ecosystems, we present a conceptual framework that analyzes disturbances by their biogeochemical impacts. We posit that the ratio of soil and plant nutrient stocks in mature ecosystems represents a characteristic site property. Focusing on nitrogen (N), we hypothesize that this partitioning ratio (soil N: plant N) will undergo a predictable trajectory after disturbance. We investigate the nature of this partitioning ratio with three approaches: (1) nutrient stock data from forested ecosystems in North America, (2) a process-based ecosystem model, and (3) conceptual shifts in site nutrient availability with altered disturbance frequency. Partitioning ratios could be applied to a variety of ecosystems and successional states, allowing for improved temporal scaling of disturbance events. The generally short-term empirical evidence for recovery trajectories of nutrient stocks and partitioning ratios suggests two areas for future research. First, we need to recognize and quantify how disturbance effects can be accreting or depleting, depending on whether their net effect is to increase or decrease ecosystem nutrient stocks. Second, we need to test how altered disturbance frequencies from the present state may be constructive or destructive in their effects on biogeochemical cycling and nutrient availability. Long-term studies, with repeated sampling of soils and vegetation, will be essential in further developing this framework of biogeochemical response to disturbance.     

Imprint of oaks on nitrogen availability and δ<Superscript>15</Superscript>N in California grassland-savanna: a case of enhanced N inputs?

Woody vegetation is distributed patchily in many arid and semi-arid ecosystems, where it is often associated with elevated nitrogen (N) pools and availability in islands of fertility. We measured N availability and δ¹⁵N in paired blue-oak versus annual grass dominated patches to characterize the causes and consequences of spatial variation in N dynamics of grassland-savanna in Sequoia-Kings Canyon National Park. We found significantly greater surface soil N pools (0–20 cm) in oak patches compared to adjacent grass areas across a 700 m elevation gradient from foothills to the savanna-forest boundary. N accumulation under oaks was associated with a 0.6‰ depletion in soil δ¹⁵N relative to grass patches. Results from a simple δ¹⁵N mass balance simulation model, constrained by surface soil N and δ¹⁵N measured in the field, suggest that the development of islands of N fertility under oaks can be traced primarily to enhanced N inputs. Net N mineralization and percent nitrification in laboratory incubations were consistently higher under oaks across a range of experimental soil moisture regimes, suggesting a scenario whereby greater N inputs to oak patches result in net N accumulation and enhanced N cycling, with a potential for greater nitrate loss as well. N concentrations of three common herbaceous annual plants were nearly 50% greater under oak than in adjacent grass patches, with community composition shifted towards more N-demanding species under oaks. We find that oaks imprint distinct N-rich islands of fertility that foster local feedback between soil N cycling, plant N uptake, and herbaceous community composition. Such patch-scale differences in N inputs and plant–soil interactions increase biogeochemical heterogeneity in grassland-savanna ecosystems and may shape watershed-level responses to chronic N deposition.     

Ecosystem N Distribution and δ<Superscript>15</Superscript>N during a Century of Forest Regrowth after Agricultural Abandonment

Abstract Stable isotope ratios of terrestrial ecosystem nitrogen (N) pools reflect internal processes and input–output balances. Disturbance generally increases N cycling and loss, yet few studies have examined ecosystem δ¹⁵N over a disturbance-recovery sequence. We used a chronosequence approach to examine N distribution and δ¹⁵N during forest regrowth after agricultural abandonment. Site ages ranged from 10 to 115 years, with similar soils, climate, land-use history, and overstory vegetation (white pine Pinus strobus). Foliar N and δ¹⁵N decreased as stands aged, consistent with a progressive tightening of the N cycle during forest regrowth on agricultural lands. Over time, foliar δ¹⁵N became more negative, indicating increased fractionation along the mineralization–mycorrhizal–plant uptake pathway. Total ecosystem N was constant across the chronosequence, but substantial internal N redistribution occurred from the mineral soil to plants and litter over 115 years (>25% of ecosystem N or 1,610 kg ha⁻¹). Temporal trends in soil δ¹⁵N generally reflected a redistribution of depleted N from the mineral soil to the developing O horizon. Although plants and soil δ¹⁵N are coupled over millennial time scales of ecosystem development, our observed divergence between plants and soil suggests that they can be uncoupled during the disturbance-regrowth sequence. The approximate 2‰ decrease in ecosystem δ¹⁵N over the century scale suggests significant incorporation of atmospheric N, which was not detected by traditional ecosystem N accounting. Consideration of temporal trends and disturbance legacies can improve our understanding of the influence of broader factors such as climate or N deposition on ecosystem N balances and δ¹⁵N. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

MicroRNA expression characterizes oligometastasis(es)

Background

Cancer staging and treatment presumes a division into localized or metastatic disease. We proposed an intermediate state defined by ≤5 cumulative metastasis(es), termed oligometastases. In contrast to widespread polymetastases, oligometastatic patients may benefit from metastasis-directed local treatments. However, many patients who initially present with oligometastases progress to polymetastases. Predictors of progression could improve patient selection for metastasis-directed therapy.

Methods

Here, we identified patterns of microRNA expression of tumor samples from oligometastatic patients treated with high-dose radiotherapy.

Results

Patients who failed to develop polymetastases are characterized by unique prioritized features of a microRNA classifier that includes the microRNA-200 family. We created an oligometastatic-polymetastatic xenograft model in which the patient-derived microRNAs discriminated between the two metastatic outcomes. MicroRNA-200c enhancement in an oligometastatic cell line resulted in polymetastatic progression.

Conclusions

These results demonstrate a biological basis for oligometastases and a potential for using microRNA expression to identify patients most likely to remain oligometastatic after metastasis-directed treatment.     

Metal accumulation in two contiguous eutrophic peri-urban lakes,Chivero and Manyame,Zimbabwe

Concentrations of aluminium, cadmium, chromium, cobalt, copper, iron, lead, nickel and zinc were determined in surface water, benthic sediments, and the gills, liver and stomach muscle tissues of Oreochromis niloticus and Clarias gariepinus in peri-urban lakes Chivero and Manyame, Zimbabwe. Five sites were sampled in each lake once per month in November 2015, February, May, August and November 2016. Pollution load index detected no metal contamination, whereas the geo-accumulation index reflected heavy to extreme sediment pollution, with Fe, Cd, Zn, Cr, Ni and Cu present in both lakes. Significant spatial temporal variations were detected for Al, Cr, Cu and Pb across sites within and between the two lakes. High Fe, Al and Cr concentrations in water and sediments in lakes Chivero and Manyame derive from geogenic background sources in addition to anthropogenic loads and intensity. Elevated concentrations of Al, Pb, Cu, Cd, Fe and Zn detected in gills, liver and stomach tissue of catfish corroborate concentrations in water and sediments, and pose the highest ecological and health risk for hydrobionts in lakes Chivero and Manyame. Contiguity of peri-urban lakes exposes them to similar threats, necessitating creative water management strategies, which ensure ecological continuity.