The Circular Economy (CE) has received considerable attention as an approach that promises to reconcile ecological systems and economic growth. In spite of its increased popularity, little is known ...about the implementation struggles of incumbent firms across industrial sectors. Furthermore, although the notion of circular production systems is at the intersection of different research areas such as sustainable product design, sustainable supply chains, and reverse logistics, knowledge on how these concepts combine to ease or impede firms' transition towards circularity is scarce. To shed light on these gaps, I used multiple case studies from Cradle to Cradle certified companies in the textile industry in Europe. By employing qualitative research, I identified a set of factors along the textile value chain, from product design to take-back and reprocessing, that are crucial in expediting or delaying a firm's aspirations to develop a circular product. The main contribution of this paper is the dynamic understanding of how certain collaborative supplier-buyer innovation factors (i.e., supply chain position, power balance, and a shared vision) coupled with complex aspects in product design, namely in basic materials, architecture, and functionality, combine to determine the output speed and quantity of circular products to be sold, taken back, and ultimately regenerated.
By means of a system dynamics computer simulation model, this paper analyzes the systemic effects of combining multiple product design and business model strategies for slowing and closing resource ...loops in a circular economy. In the model, green (i.e., recycled) and brown (i.e., traditional linear) products, as well as products under a PSS model, flow in a closed-loop supply chain. The model structure covers issues related to product design, product use and replacement, second-hand use, product discard, and finally, collection and processing for product recycling. Results from this research provide insights into the relationship between design considerations at the beginning of a product's life and their implications for the product's take-back stage when a new manufacturing cycle begins. The main contributions of this paper are the considerations of time delays and reinforcing feedback loops in the design of an effective closed-loop supply chain.
Antimicrobial peptides (AMPs), or host defense peptides, are small cationic or amphipathic molecules produced by prokaryotic and eukaryotic organisms that play a key role in the innate immune defense ...against viruses, bacteria and fungi. AMPs have either antimicrobial or anticancer activities. Indeed, cationic AMPs are able to disrupt microbial cell membranes by interacting with negatively charged phospholipids. Moreover, several peptides are capable to trigger cytotoxicity of human cancer cells by binding to negatively charged phosphatidylserine moieties which are selectively exposed on the outer surface of cancer cell plasma membranes. In addition, some AMPs, such as LTX-315, have shown to induce release of tumor antigens and potent damage associated molecular patterns by causing alterations in the intracellular organelles of cancer cells. Given the recognized medical need of novel anticancer drugs, AMPs could represent a potential source of effective therapeutic agents, either alone or in combination with other small molecules, in oncology. In this review we summarize and describe the properties and the mode of action of AMPs as well as the strategies to increase their selectivity toward specific cancer cells.
The transcription factor nuclear factor erythroid 2‐related factor 2 (NRF2) is considered the master regulator of the phase II antioxidant response. It controls a plethora of cytoprotective genes ...related to oxidative stress, inflammation, and protein homeostasis, among other processes. Activation of these pathways has been described in numerous pathologies including cancer, cardiovascular, respiratory, renal, digestive, metabolic, autoimmune, and neurodegenerative diseases. Considering the increasing interest of discovering novel NRF2 activators due to its clinical application, initial efforts were devoted to the development of electrophilic drugs able to induce NRF2 nuclear accumulation by targeting its natural repressor protein Kelch‐like ECH‐associated protein 1 (KEAP1) through covalent modifications on cysteine residues. However, off‐target effects of these drugs prompted the development of an innovative strategy, the search of KEAP1‐NRF2 protein–protein interaction (PPI) inhibitors. These innovative activators are proposed to target NRF2 in a more selective way, leading to potentially improved drugs with the application for a variety of diseases that are currently under investigation. In this review, we summarize known KEAP1‐NRF2 PPI inhibitors to date and the bases of their design highlighting the most important features of their respective interactions. We also discuss the preclinical pharmacological properties described for the most promising compounds.
Reactive nitrogen species in cellular signaling Adams, Levi; Franco, Maria C; Estevez, Alvaro G
Experimental biology and medicine (Maywood, N.J.),
06/2015, Letnik:
240, Številka:
6
Journal Article
Recenzirano
Odprti dostop
The transduction of cellular signals occurs through the modification of target molecules. Most of these modifications are transitory, thus the signal transduction pathways can be tightly regulated. ...Reactive nitrogen species are a group of compounds with different properties and reactivity. Some reactive nitrogen species are highly reactive and their interaction with macromolecules can lead to permanent modifications, which suggested they were lacking the specificity needed to participate in cell signaling events. However, the perception of reactive nitrogen species as oxidizers of macromolecules leading to general oxidative damage has recently evolved. The concept of redox signaling is now well established for a number of reactive oxygen and nitrogen species. In this context, the post-translational modifications introduced by reactive nitrogen species can be very specific and are active participants in signal transduction pathways. This review addresses the role of these oxidative modifications in the regulation of cell signaling events.
Human brucellosis Franco, María Pía, MD; Mulder, Maximilian, MD; Gilman, Robert H, Prof ...
The Lancet infectious diseases,
12/2007, Letnik:
7, Številka:
12
Journal Article
Recenzirano
Summary Human brucellosis still presents scientists and clinicians with several challenges, such as the understanding of pathogenic mechanisms of Brucella spp, the identification of markers for ...disease severity, progression, and treatment response, and the development of improved treatment regimens. Molecular studies have shed new light on the pathogenesis of Brucella spp, and new technologies have permitted the development of diagnostic tools that will be useful in developing countries, where brucellosis is still a very common but often neglected disease. However, further studies are needed to establish optimum treatment regimens and local and international control programmes. This Review summarises current knowledge of the pathogenic mechanisms, new diagnostic advances, therapeutic options, and the situation of developing countries in regard to human brucellosis.
By using fragments endowed with interesting and complementary properties for the treatment of Alzheimer’s disease (AD), a new family of tacrine–4-oxo-4H-chromene hybrids has been designed, ...synthesized, and evaluated biologically. The tacrine fragment was selected for its inhibition of cholinesterases, and the flavonoid scaffold derived from 4-oxo-4H -chromene was chosen for its radical capture and β-secretase 1 (BACE-1) inhibitory activities. At nano- and picomolar concentrations, the new tacrine–4-oxo-4H-chromene hybrids inhibit human acetyl- and butyrylcholinesterase (h-AChE and h-BuChE), being more potent than the parent inhibitor, tacrine. They are also potent inhibitors of human BACE-1, better than the parent flavonoid, apigenin. They show interesting antioxidant properties and could be able to penetrate into the CNS according to the in vitro PAMPA-BBB assay. Among the hybrids investigated, 6-hydroxy-4-oxo- N-{10-(1,2,3,4-tetrahydroacridin-9-yl)aminodecyl}-4 H-chromene-2-carboxamide (19) shows potent combined inhibition of human BACE-1 and ChEs, as well as good antioxidant and CNS-permeable properties.
To investigate food insecurity (FI) prevalence in two favelas in Brazil in the early weeks of the social distancing policy, from 27 March 2020 to 1 June 2020.
A cross-sectional study using an online ...questionnaire to elicit information on socio-economic and demographic characteristics, the types of stores visited to buy food, and FI screening. The FI experience was evaluated according to the Brazilian Food Insecurity Scale. Factors associated with moderate or severe FI were investigated using the logistic regression model.
São Paulo city, Brazil.
Totally, 909 householders.
Eighty-eight per cent of the households included young women working as cleaners or kitchen assistants and in sales services. One-fifth of the participants were involved in the federal cash transfer programme, called Bolsa Família. There were 92 % households with children. The most frequent experience reported was uncertainty about food acquisition or receiving more (89 %), eating less than one should (64 %), not being able to eat healthy and nutritious food (46 %), and skipping a meal (39 %). Forty-seven per cent of the participants experienced moderate or severe FI. Factors associated with moderate and severe FI were low income, being a Bolsa Família recipient, having a low level of education and living in a household without children.
Half of the participants experienced moderate or severe FI, and almost 10 % experienced hunger. Our data suggest that families with children were at a lower risk of moderate to severe FI. It is possible that nationally established social programmes such as Bolsa Família were protecting those families.
Climate change constitutes a rising challenge to the agricultural base of developing countries. Most of the literature has focused on the impact of changes in the means of weather variables on mean ...changes in production and has found very little impact of weather upon agricultural production. Instead, we focus on the relationship between extreme events in weather and extreme losses in crop production. Indeed, extreme events are of the greatest interest for scholars and policy makers only when they carry extraordinary negative effects. We build on this idea and for the first time, we adopt a conditional dependence model for multivariate extreme values to understand the impact of extreme weather on agricultural production. Specifically, we look at the probability that an extreme event drastically reduces the harvest of any of the major crops. This analysis, which is run on data for six different crops and four different weather variables in a vast array of countries in Africa, Asia and Latin America, shows that extremes in weather and yield losses of major staples are associated events. We find a high heterogeneity across both countries and crops and we are able to predict per country and per crop the risk of a yield reduction above 90% when extreme events occur. As policy implication, we can thus assess which major crop in each country is less resilient to climate shocks.
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