Effects of Tolvaptan on Oxidative Stress in ADPKD: A Molecular Biological Approach

Autosomal dominant polycystic disease (ADPKD) is the most frequent monogenic kidney disease. It causes progressive renal failure, endothelial dysfunction, and hypertension, all of which are strictly linked to oxidative stress (OxSt). Treatment with tolvaptan is known to slow the renal deterioration rate, but not all the molecular mechanisms involved in this effect are well-established. We evaluated the OxSt state in untreated ADPKD patients compared to that in tolvaptan-treated ADPKD patients and healthy subjects. OxSt was assessed in nine patients for each group in terms of mononuclear cell p22phox protein expression, NADPH oxidase key subunit, MYPT-1 phosphorylation state, marker of Rho kinase activity (Western blot) and heme oxygenase (HO)-1, induced and protective against OxSt (ELISA). p22phox protein expression was higher in untreated ADPKD patients compared to treated patients and controls: 1.42 ± 0.11 vs. 0.86 ± 0.15 d.u., p = 0.015, vs. 0.53 ± 0.11 d.u., p < 0.001, respectively. The same was observed for phosphorylated MYPT-1: 0.96 ± 0.28 vs. 0.68 ± 0.09 d.u., p = 0.013 and vs. 0.47 ± 0.13 d.u., p < 0.001, respectively, while the HO-1 expression of untreated patients was significantly lower compared to that of treated patients and controls: 5.33 ± 3.34 vs. 2.08 ± 0.79 ng/mL, p = 0.012, vs. 1.97 ± 1.22 ng/mL, p = 0.012, respectively. Tolvaptan-treated ADPKD patients have reduced OxSt levels compared to untreated patients. This effect may contribute to the slowing of renal function loss observed with tolvaptan treatment.

Plant trans-golgi network/early endosome pH regulation requires cation chloride cotransporter (CCC1)

Plant cells maintain a low luminal pH in the Trans-Golgi-Network/Early Endosome (TGN/EE), the organelle in which the secretory and endocytic pathways intersect. Impaired TGN/EE pH regulation translates into severe plant growth defects. The identity of the proton pump and proton/ion antiporters that regulate TGN/EE pH have been determined, but an essential component required to complete the TGN/EE membrane transport circuit remains unidentified - a pathway for cation and anion efflux. Here, we have used complementation, genetically encoded fluorescent sensors, and pharmacological treatments to demonstrate that Arabidopsis Cation Chloride Cotransporter (CCC1) is this missing component necessary for regulating TGN/EE pH and function. Loss of CCC1 function leads to alterations in TGN/EE-mediated processes including endocytic trafficking, exocytosis and response to abiotic stress, consistent with the multitude of phenotypic defects observed in ccc1 knockout plants. This discovery places CCC1 as a central component of plant cellular function.

Circular RNA CREBBP Suppresses Hepatic Fibrosis Via Targeting the hsa-miR-1291/LEFTY2 Axis

CircRNAs (circRNAs) are commonly dysregulated in a variety of human diseases and are involved in the development and progression of cancer. However, the role of circRNAs in hepatic fibrosis (HF) is still unclear. Our previous high throughput screen revealed changes in many circRNAs in mice with carbon tetrachloride (CCl4)-induced HF. For example, circCREBBP was significantly down-regulated in primary hepatic stellate cells (HSCs) and liver tissue of HF mice induced by CCl4 compared to those in the vehicle group. Overexpression of circCREBBP with AAV8-circCREBBP in vivo prevented CCl4-induced HF worsening by reducing serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) contents, liver hydroxyproline levels, collagen deposition, and levels of pro-fibrosis genes and pro-inflammatory cytokines. Furthermore, in vitro function loss and function gain analysis showed that circCREBBP inhibited HSCs activation and proliferation. Mechanically, circCREBBP acts as a sponge for hsa-miR-1291 and subsequently promotes LEFTY2 expression. In conclusion, our current results reveal a novel mechanism by which circCREBBP alleviates liver fibrosis by targeting the hsa-miR-1291/LEFTY2 axis, and also suggest that circCREBBP may be a potential biomarker for heart failure.

Biodiversity offsets under the Resource Management Act 1991: A New Environmental Bottom-Line?

<p>Biodiversity offsets, a form of environmental compensation, are increasingly being offered by developers and taken into account as part of the process for determining planning permissions in New Zealand. This paper outlines the concept of biodiversity offsets and, with reference to a case study, the role it currently plays under New Zealand's primary planning legislation – the Resource Management Act 1991 (RMA). The paper argues that while the current approach to offsets under the RMA is sub-optimal, recent developments of the law pertaining to national policy statements provide an opportunity to use biodiversity offsets as part of implementing an environmental bottom line for biodiversity and ecosystem function loss.</p>

Biodiversity offsets under the Resource Management Act 1991: A New Environmental Bottom-Line?

<p>Biodiversity offsets, a form of environmental compensation, are increasingly being offered by developers and taken into account as part of the process for determining planning permissions in New Zealand. This paper outlines the concept of biodiversity offsets and, with reference to a case study, the role it currently plays under New Zealand's primary planning legislation – the Resource Management Act 1991 (RMA). The paper argues that while the current approach to offsets under the RMA is sub-optimal, recent developments of the law pertaining to national policy statements provide an opportunity to use biodiversity offsets as part of implementing an environmental bottom line for biodiversity and ecosystem function loss.</p>

Selecting species for restoration in foundational assemblages

Humans have long sought to restore species but little attention has been directed at how best to do so for rich assemblages of foundation species that support ecosystems, like rainforests and coral reefs that are increasingly threatened by environmental change. We developed a two-part triage process for selecting optimized sets of species for restoration. We demonstrated this process using phenotypic traits and ecological characteristics for reef building corals found along the east coast of Australia. Without clear linkages between phenotypic traits and ecosystem functions, the first part of the triage hedges against function loss by ensuring an even spread of life history traits. The second part hedges against future species losses by weighting species based on characteristics that are known to increase their ecological persistence to current environmental pressures--abundance, species range and thermal bleaching tolerance--as well as their amenability to restoration methods. We identified sets of ecologically persistent and restorable species most likely to protect against functional loss by examining marginal returns in occupancy of phenotypic trait space per restored species. We also compared sets of species with those from the southern-most accretional reef as well as a coral restoration program to demonstrate how trait space occupancy is likely to protect against local loss of ecosystem function. Synthesis and applications. A quantitative approach to selecting sets of foundational species for restoration can inform decisions about ecosystem protection to guide and optimize future restoration efforts. The approach addresses the need to insure against unpredictable losses of ecosystem functions by investing in a wide range of phenotypes. Furthermore, the flexibility of the approach enables the functional goals of restoration to vary depending on environmental context, stakeholder values, and the spatial and temporal scales at which meaningful impacts can be achieved.

Effects of Low Temperature on Shrimp and Crab Physiology, Behavior, and Growth: A Review

As important aquaculture species worldwide, shrimps and crabs are thermophilic animals with a feeble thermoregulation ability. Changes in environmental factors are the main reason for the decrease in the immunity and disease resistance ability of cultured organisms. Water temperature is one of the most common abiotic stress factors for aquatic ectotherms. It influences nearly all biochemical and physiological processes in crustaceans, resulting in an imbalance in ion and water homeostasis, neuromuscular function loss, cellular dehydration, and altered metabolic pathways. The present review summarizes the current knowledge on the effects of low temperature on the physiological response, and the behavior, development, and growth of shrimp and crab. We suggest a deeper research to understand the physiological processes involved in thermoregulation; this knowledge could be used to reduce the adverse effects in the shrimps and crabs during the culture.