Adaptive reuse of cultural heritage can be a valid strategy to recover heritage buildings in a state of abandonment or underuse, as well as to implement the circular economy model in cities and ...regions, contributing to the achievement of climate objectives, to social cohesion, wellbeing and quality of life, making cities more attractive, safe, sustainable and resilient. The aim of this paper is to develop and test an ex-ante evaluation methodology to support participatory decision-making processes for the adaptive reuse of cultural heritage according to the circular economy perspective. A multidimensional and multicriteria evaluation framework was experimented in the city of Salerno, Italy, to assess alternative solutions for the adaptive reuse of four large historic buildings in abandonment, and identify a satisfying solution based on interactions with local stakeholders. The TOPSIS (Technique for Order Preference by Similarity to Ideal Solution) multi-criteria evaluation method was used to compare adaptive reuse project alternatives including stakeholder objectives and preferences. Starting from 14 adaptive reuse proposals, the participative evaluation methodology supported stakeholders in the identification of 4 preferable solutions further developed and co-designed, as well as in the search of a final satisfying solution engaging diverse stakeholders groups. Moreover, operational circularity criteria for the adaptive reuse of cultural heritage were identified. The results of the study show the potential of Multi-Criteria Decision Analysis (MCDA) mixed with participative methods for co-design and co-evaluation to support inclusive decision-making processes for circular adaptive reuse of cultural heritage.
A Wee1 checkpoint inhibits anaphase onset Lianga, Noel; Williams, Elizabeth C; Kennedy, Erin K ...
The Journal of cell biology,
06/2013, Letnik:
201, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Cdk1 drives both mitotic entry and the metaphase-to-anaphase transition. Past work has shown that Wee1 inhibition of Cdk1 blocks mitotic entry. Here we show that the budding yeast Wee1 kinase, Swe1, ...also restrains the metaphase-to-anaphase transition by preventing Cdk1 phosphorylation and activation of the mitotic form of the anaphase-promoting complex/cyclosome (APC(Cdc20)). Deletion of SWE1 or its opposing phosphatase MIH1 (the budding yeast cdc25(+)) altered the timing of anaphase onset, and activation of the Swe1-dependent morphogenesis checkpoint or overexpression of Swe1 blocked cells in metaphase with reduced APC activity in vivo and in vitro. The morphogenesis checkpoint also depended on Cdc55, a regulatory subunit of protein phosphatase 2A (PP2A). cdc55Δ checkpoint defects were rescued by mutating 12 Cdk1 phosphorylation sites on the APC, demonstrating that the APC is a target of this checkpoint. These data suggest a model in which stepwise activation of Cdk1 and inhibition of PP2A(Cdc55) triggers anaphase onset.
Essential tremor (ET) is a common neurodegenerative disorder that is characterized by a postural or motion tremor. Despite a strong genetic basis, a gene with rare pathogenic mutations that cause ET ...has not yet been reported. We used exome sequencing to implement a simple approach to control for misdiagnosis of ET, as well as phenocopies involving sporadic and senile ET cases. We studied a large ET-affected family and identified a FUS p.Gln290∗ mutation as the cause of ET in this family. Further screening of 270 ET cases identified two additional rare missense FUS variants. Functional considerations suggest that the pathogenic effects of ET-specific FUS mutations are different from the effects observed when FUS is mutated in amyotrophic lateral sclerosis cases; we have shown that the ET FUS nonsense mutation is degraded by the nonsense-mediated-decay pathway, whereas amyotrophic lateral sclerosis FUS mutant transcripts are not.
The present experiment was undertaken to determine the effects of dietary supplements of folic acid and vitamin B12 given from 3 wk before to 8 wk after calving on lactational performance and ...metabolism of 24 multiparous Holstein cows assigned to 6 blocks of 4 cows each according to their previous milk production. Supplementary folic acid at 0 or 2.6 g/d and vitamin B12 at 0 or 0.5 g/d were used in a 2 x 2 factorial arrangement. Supplementary folic acid increased milk production from 38.0 +/- 0.9 to 41.4 +/- 1.0 kg/d and milk crude protein yield from 1.17 +/- 0.02 to 1.25 +/- 0.03 kg/d. It also increased plasma Gly, Ser, Thr, and total sulfur AA, decreased Asp, and tended to increase plasma Met. Supplementary B12 decreased milk urea N, plasma Ile, and Leu and tended to decrease Val but increased homocysteine, Cys, and total sulfur AA. Liver concentration of phospholipids was higher in cows fed supplementary B12. Plasma and liver concentrations of folates and B12 were increased by their respective supplements, but the increase in plasma folates and plasma and liver B12 was smaller for cows fed the 2 vitamins together. In cows fed folic acid supplements, supplementary B12 increased plasma glucose and alanine, tended to decrease plasma biotin, and decreased Km of the methylmalonyl-coenzyme A mutase in hepatic tissues following addition of deoxyadenosylcobalamin, whereas it had no effect when cows were not fed folic acid supplements. There was no treatment effect on plasma nonesterified fatty acids as well as specific activity and gene expression of Met synthase and methylmalonyl-coenzyme A mutase in the liver. Ingestion of folic acid supplements by cows fed no supplementary B12 increased total lipid and triacylglycerols in liver, whereas these supplements had no effect in cows supplemented with B12. The increases in milk and milk protein yields due to folic acid supplements did not seem to be dependent on the vitamin B12 supply. However, when vitamin B12 was given in combination with folic acid, utilization of the 2 vitamins seems to be increased, probably more so in extrahepatic tissues. Metabolic efficiency seems also to be improved as suggested by similar lactational performance and dry matter intake for cows fed supplementary folic acid but increased plasma glucose and decreased hepatic lipids in cows fed folic acid and vitamin B12 together.
Childhood-onset schizophrenia (COS), defined by the onset of illness before age 13 years, is a rare severe neurodevelopmental disorder of unknown etiology. Recently, sequencing studies have ...identified rare, potentially causative de novo variants in sporadic cases of adult-onset schizophrenia and autism. In this study, we performed exome sequencing of 17 COS trios in order to test whether de novo variants could contribute to this disease. We identified 20 de novo variants in 17 COS probands, which is consistent with the de novo mutation rate reported in the adult form of the disease. Interestingly, the missense de novo variants in COS have a high likelihood for pathogenicity and were enriched for genes that are less tolerant to variants. Among the genes found disrupted in our study, SEZ6, RYR2, GPR153, GTF2IRD1, TTBK1 and ITGA6 have been previously linked to neuronal function or to psychiatric disorders, and thus may be considered as COS candidate genes.
Lung cancer is a leading cause of cancer death, where the amplification of oncogenes contributes to tumorigenesis. Genomic profiling of 128 lung cancer cell lines and tumors revealed frequent focal ...DNA amplification at cytoband 14q13.3, a locus not amplified in other tumor types. The smallest region of recurrent amplification spanned the homeobox transcription factor TITF1 (thyroid transcription factor 1; also called NKX2-1), previously linked to normal lung development and function. When amplified, TITF1 exhibited increased expression at both the RNA and protein levels. Small interfering RNA (siRNA)-mediated knockdown of TITF1 in lung cancer cell lines with amplification led to reduced cell proliferation, manifested by both decreased cell-cycle progression and increased apoptosis. Our findings indicate that TITF1 amplification and overexpression contribute to lung cancer cell proliferation rates and survival and implicate TITF1 as a lineage-specific oncogene in lung cancer.
It is well established that the plasma metabolite profile changes during metabolic dysfunction, such as elevated non-esterified fatty acid (NEFA) release when body reserve mobilization is excessive ...in early lactation cows. Relationships between changes in plasma concentrations of metabolites caused by a metabolic impairment and the status of vitamins, such as folates and vitamin B12, have barely been studied in cattle. This study was undertaken to assess relationships between peripartum plasma concentrations of folates, vitamin B12, NEFA, and beta-hydroxybutyrate (BHB). Longitudinal data of 48 multiparous Holstein cows from 5 studies were taken from days −14 to 21 relative to calving. Blood samples were taken weekly before calving and either twice or thrice per week postpartum, and plasma was analyzed for folate, vitamin B12, NEFA, and BHB concentrations. Postpartum plasma NEFA and BHB concentrations were negatively related to plasma folate concentration at days −14 and −7 relative to parturition, whereas the opposite relationship was noted for the plasma vitamin B12:folate ratio. The plasma folate and NEFA areas under the curve from the whole studied period were negatively associated, and the opposite was observed with the association between the plasma vitamin B12:folate ratio and NEFA as well as the BHB areas under the curve. The results suggest that there is an increased use of folate for metabolic functions during elevated concentrations of plasma NEFA and BHB. Future research should focus on finding an optimal plasma vitamin B12:folate ratio to favor cow health during the challenging period of parturition.
▸ Autistics display enhanced mental imagery abilities. ▸ Mental rotation skills aggregate with IQ and visuospatial skills in autistics only. ▸ Autistics with a Block Design peak show the best ...performance in mental rotation.
The formation and manipulation of mental images represents a key ability for successfully solving visuospatial tasks like Wechsler's Block Design or visual reasoning problems, tasks where autistics perform at higher levels than predicted by their Wechsler IQ. Visual imagery can be used to compare two mental images, allowing judgment of their relative properties. To examine higher visual processes in autism, and their possible role in explaining autistic visuospatial peaks, we carried out two mental imagery experiments in 23 autistic and 14 age and IQ matched, non-autistic adolescents and adults. Among autistics, 11 had significantly higher Block Design scores than predicted by their IQ. Experiment 1 involved imagining a letter inside a circle, followed by a decision concerning which of two highlighted portions of the circle would contain the greater proportion of the letter. Experiment 2 involved four classic mental rotation tasks utilizing two- and three-dimensional geometric figures, hands and letters. Autistics were more accurate in the formation and comparison of mental images than non-autistics. Autistics with a Block Design peak outperformed other participants in both speed and accuracy of mental rotation. Also, Performance IQ and Block Design scores were better predictors of mental rotation accuracy in autistic compared to non-autistic participants. The ability to form, access and manipulate visual mental representations may be more developed in autistics. We propose two complementary mechanisms to explain these processing advantages: (1) a global advantage in perceptual processing, discussed in the framework of the enhanced perceptual functioning model, and (2) particular strengths in veridical mapping, the ability to efficiently detect isomorphisms among entities and then to use these mappings to process stimulus characteristics, thereby facilitating judgments about their differences.
•Polyphenols reduced lipid oxidation in pea and soy protein solutions.•Polymeric polyphenols more effectively reduced lipid oxidation than monomeric.•Crude extracts and purified polyphenols were ...equally effective.•Lipid oxidation is likely reduced via polyphenol-protein interactions.•Reduced lipid oxidation could increase consumer acceptability of plant proteins.
Significant lipid-derived off-flavors hinder broader acceptance and applicability of plant protein ingredients. Polyphenols are strong antioxidants and can react with protein and carbonyl compounds to reduce oxidative off-flavor development. The effects of polyphenols (catechin, tannic acid (TA), grape seed extract (GSE), and green tea extract (GTE)) on lipid oxidation in pea and soy protein solutions were investigated. All polyphenols reduced lipid oxidation products and volatile compound concentration versus their respective controls. TA, GSE, and GTE reduced the secondary products in pea and soy proteins by an average of 75 % and 50 %, respectively, versus controls, compared to catechin’s 61 % and 13 %, respectively. The chemical structures of TA, GSE, and GTE likely allowed them to interact more effectively than catechin with proteins, especially lipoxygenase. However, no significant differences between the polyphenols’ antioxidant capacities were observed. Thus, polyphenols predominantly reduced lipid oxidation via interactions with proteins, rather than electron transfer or radical quenching.
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