Biliverdin reductase--a protein levels and activity in the brains of subjects with Alzheimer disease and mild cognitive impairment

Biliverdin reductase-A is a pleiotropic enzyme involved not only in the reduction of biliverdin-IX-alpha into bilirubin-IX-alpha, but also in the regulation of glucose metabolism and cell growth secondary to its serine/threonine/tyrosine kinase activity. Together with heme oxygenase, whose metabolic role is to degrade heme into biliverdin-IX-alpha, it forms a powerful system involved in the cell stress response during neurodegenerative disorders. In this paper, an up-regulation of the biliverdin reductase-A protein levels was found in the hippocampus of the subjects with Alzheimer disease and arguably its earliest form, mild cognitive impairment. Moreover a significant reduction in the phosphorylation of serine, threonine and tyrosine residues of biliverdin reductase-A was found, and this was paralleled by a marked reduction in its reductase activity. Interestingly, the levels of both total and phosphorylated biliverdin reductase-A were unchanged as well as its enzymatic activity in the cerebella. These results demonstrated a dichotomy between biliverdin reductase-A protein levels and activity in the hippocampus of subjects affected by Alzheimer disease and mild cognitive impairment, and this effect likely is attributable to a reduction in the phosphorylation of serine, threonine and tyrosine residues of biliverdin reductase-A. Consequently, not just the increased levels of biliverdin reductase-A, but also its changed activity and phosphorylation state, should be taken into account when considering potential biomarkers for Alzheimer disease and mild cognitive impairment.     

Dispersal in microbes: fungi in indoor air are dominated by outdoor air and show dispersal limitation at short distances

The indoor microbiome is a complex system that is thought to depend on dispersal from the outdoor biome and the occupants'' microbiome combined with selective pressures imposed by the occupants'' behaviors and the building itself. We set out to determine the pattern of fungal diversity and composition in indoor air on a local scale and to identify processes behind that pattern. We surveyed airborne fungal assemblages within 1-month time periods at two seasons, with high replication, indoors and outdoors, within and across standardized residences at a university housing facility. Fungal assemblages indoors were diverse and strongly determined by dispersal from outdoors, and no fungal taxa were found as indicators of indoor air. There was a seasonal effect on the fungi found in both indoor and outdoor air, and quantitatively more fungal biomass was detected outdoors than indoors. A strong signal of isolation by distance existed in both outdoor and indoor airborne fungal assemblages, despite the small geographic scale in which this study was undertaken (<500 m). Moreover, room and occupant behavior had no detectable effect on the fungi found in indoor air. These results show that at the local level, outdoor air fungi dominate the patterning of indoor air. More broadly, they provide additional support for the growing evidence that dispersal limitation, even on small geographic scales, is a key process in structuring the often-observed distance–decay biogeographic pattern in microbial communities.     

Study of the synthesis, antiproliferative properties, and interaction with DNA and polynucleotides of cisplatin-like Pt(II) complexes containing carcinogenic polyaromatic amines

The chemical and biological features of two newly synthesized [PtCl₂(L)(2-aminonaphthalene)] complexes (L is NH₃ or 2-aminonaphthalene) were compared with those of two already reported enantiomeric complexes of formula [PtCl₂(DABN)] [DABN is (R)-1,1′-binaphthyl-2,2′-diamine or (S)-1,1′-binaphthyl-2,2′-diamine]. Solution behavior, lipophilicity, cytotoxicity with regard to one colorectal (HCT116) and two ovarian (A2780 and A2780Cp8) human carcinoma cell lines, and in vitro DNA- and G-quadruplex-binding properties were evaluated. In particular, the cytotoxicity of [PtCl₂(NH₃)(2-aminonaphthalene)] was better than that of cisplatin for all cell lines, and rather resembled that of oxaliplatin. The solution behavior of the whole series of complexes and the absence of an evident relationship between lipophilicity and cytotoxicity seem to suggest that all these experimental parameters are probably smoothed out during the 3-day cytotoxicity experiments and do not strongly affect the half-maximal inhibitory concentrations. The results of electrophoretic studies indicate that different kinds of interaction with DNA can be involved in the mode of action of these complexes, with intercalation in double-stranded DNA and stacking on G-quadruplex DNA being strongly implicated in particular for [PtCl₂(NH₃)(2-aminonaphthalene)].     

Impairment of proteostasis network in Down syndrome prior to the development of Alzheimer's disease neuropathology: Redox proteomics analysis of human brain

DS is the most frequent genetic cause of intellectual disability characterized by the anomalous presence of three copies of chromosome 21. One of the peculiar features of DS is the onset of Alzheimer's disease neuropathology after the age of 40 years characterized by deposition of senile plaques and neurofibrillary tangles. Growing studies demonstrated that increased oxidative damage, accumulation of unfolded/damaged protein aggregates and dysfunction of intracellular degradative system are key players in neurodegenerative processes. In this study, redox proteomics approach was used to analyze the frontal cortex from DS subjects under the age of 40 compared with age-matched controls, and proteins found to be increasingly carbonylated were identified. Interestingly, our results showed that oxidative damage targets specifically different components of the intracellular quality control system such as GRP78, UCH-L1, V0-ATPase, cathepsin D and GFAP that couples with decreased activity of the proteasome and autophagosome formation observed. We also reported a slight but consistent increase of Aβ 1–42 SDS- and PBS-soluble form and tau phosphorylation in DS versus CTR. We suggest that disturbance in the proteostasis network could contribute to the accumulation of protein aggregates, such as amyloid deposits and NFTs, which occur very early in DS. It is likely that a sub-optimal functioning of degradative systems occur in DS neurons, which in turn provide the basis for further accumulation of toxic protein aggregates. The results of this study suggest that oxidation of protein members of the proteostatis network is an early event in DS and might contribute to neurodegenerative phenomena.     

Costructal law,exergy analysis and life cycle energy sustainability assessment: an expanded framework applied to a boiler

The International Journal of Life Cycle Assessment - Life cycle sustainability assessment (LCSA) is one of the most relevant tools delving in sustainability science, based currently on the triple...     

Towards social life cycle assessment of mobility services: systematic literature review and the way forward

Purpose

The main purpose of this review is to describe the state of the art of social impact assessment with a focus on mobility services. Whereas the use phase plays an important role for the assessment of services in general, the evaluation of the use phase has been underrepresented in previous social life cycle assessment studies. For that reason, particular attention has been paid to indicators, which allow the assessment of social impacts during the use phase of mobility services.

Methods

Continuous efforts to mitigate climate change and to improve quality of life in cities result in new mobility solutions based on collective use. This will have a huge impact on our society transforming the use of vehicles. In order to better understand the implications for cities, society and the automotive industry, it is essential to evaluate the social impact generated along a product life cycle with particular attention to the use phase. To reach the goal, a systematic literature review was carried out with a focus on social indicators that allow assessing use phase impacts of mobility services. The indicators were analysed and allocated to stakeholder groups. Based on the analysis, a core set of indicators is proposed under consideration of data availability.

Results and discussion

Based on the selected search strings, 51 publications were selected for the literature review, including 579 social indicators. The analysis revealed a wide variety and diversity of indicators that are trying to measure the same aspect. The allocation to the respective stakeholder groups showed that most of the indicators (36%) evaluate impacts regarding the stakeholder group local community. The majority of analysed indicators are of quantitative nature (63%). Nevertheless, a clear assessment method was often missing in the respective publications. Therefore, for the core set of indicators, an assessment method is proposed for every indicator.

Conclusions

The results from this study can help practitioners as well as researchers in the field of urban mobility assessment as it systematically analyses social sustainability aspects. The presented data gives an overview of various indicators that are suggested in other publications, and the proposed core set of indicators can be used to evaluate different mobility services in further research.

     

Unveiling asexual reproductive traits in black corals: polyp bail-out in Antipathella subpinnata

Cnidarians are known to undergo reverse development as a survival mechanism against adverse environmental conditions. Polyp bail-out consists in the polyps’ detachment from the mother colony due to stressful conditions, followed by a complete tissue and cells rearrangement and in some cases in a regression into a simple, ciliated form. Here we describe a massive polyp bail-out event occurred in the mesophotic black coral Antipathella subpinnata in reared conditions. This is the first report of a bail-out event in this species providing new insights into the life cycle and ecology of black corals.

     

Fusicoccin-induced catalase inhibitor is produced independently of H+-ATPase activation and behaves as an organic acid

The phytotoxin fusicoccin (FC) was found to induce an increase in apoplastic H₂O₂ content in Arabidopsis thaliana cells, apparently linked to the presence of an as yet unidentified catalase inhibitor detectable even in the external medium of FC‐treated cells. This study, aimed to further characterize the inhibitor's features, shows that (1) FC‐induced H₂O₂ accumulation increases as a function of FC concentration and correlates to the amount of inhibitor released at apoplastic level. The pattern of H⁺ efflux, conversely, does not fit with that of these two parameters, suggesting that neither the production nor the release of the catalase inhibitor is linked to the main role of FC in activating the plasma membrane (PM) H⁺‐ATPase; (2) treatment with 10 µM erythrosin B (EB) early and totally inhibits net H⁺ and K⁺ fluxes across the PM, indicative of the H⁺ pump activity; nevertheless, also in these conditions a huge FC‐induced H₂O₂ accumulation occurs, confirming that this effect is not related to the FC‐induced PM H⁺‐ATPase activation; (3) the inhibitor's release increases with time in all conditions tested and is markedly affected by extracellular pH (a higher pH value being associated to a larger efflux), in agreement with a weak acid release; and (4) the inhibitor can be almost completely recovered in a CH₂Cl₂‐soluble fraction extracted from the incubation medium by sequential acid–base partitioning which contains nearly all of the organic acids released. These final results strongly suggest that the metabolite responsible for the FC‐induced catalase inhibition belongs to the organic acid class.