Environmental performance of chocolate produced in ghana using life cycle assessment

Ghana is an important cocoa producer and exporter and this production is of high economic importance. Increasing interest in the sustainable productions of cocoa/chocolate necessitated the need to assess the environmental impacts associated with the production of different chocolate variants (extra dark (EDC), dark (DC), milk (MC) and flavoured milk (FMC) in Ghana, including the identification of environmental hotspots for improvement. The life cycle assessment tool was used following the CML_IA and CED impact assessment methods. EDC had the lowest scores for most of the impact categories while FMC was most impactful. For Global Warming Potential (GWP), EDC and FMC were estimated to be 1.61 kg CO2 eq. and 4.21 kg CO2 eq., respectively. CED ranged from 1.44 × 102 to 1.50 × 102 MJ-eq. Chocolate manufacturing phase was generally more impactful than cocoa cultivation due to high emissions from milk and sugar production. The impact scores for 100 g packaged chocolate bar were the lowest in comparison to 300 g chocolate pouches and 12.5 g packaged chocolate strips. GWP for 100 g and 12.5 g were 0.20 kg CO2 eq. and 0.39 kg CO2 eq., respectively. Comparing different destination points for the manufactured chocolate, impact scores for the international destination were similar to those recorded for local destinations. Improvement options are suggested for all phases to ensure more sustainable chocolate production and distribu-tion

Roles of sorcin in drug resistance in cancer: one protein, many mechanisms, for a novel potential anticancer drug target

The development of drug resistance is one of the main causes of failure in anti-cancer treatments. Tumor cells adopt many strategies to counteract the action of chemotherapeutic agents, e.g., enhanced DNA damage repair, inactivation of apoptotic pathways, alteration of drug targets, drug inactivation, and overexpression of ABC (Adenosine triphosphate-binding cassette, or ATP-binding cassette) transporters. These are broad substrate-specificity ATP-dependent efflux pumps able to export toxins or drugs out of cells; for instance, ABCB1 (MDR1, or P-glycoprotein 1), overexpressed in most cancer cells, confers them multidrug resistance (MDR). The gene coding for sorcin (SOluble Resistance-related Calcium-binding proteIN) is highly conserved among mammals and is located in the same chromosomal locus and amplicon as the ABC transporters ABCB1 and ABCB4, both in human and rodent genomes (two variants of ABCB1, i.e., ABCB1a and ABCB1b, are in rodent amplicon). Sorcin was initially characterized as a soluble protein overexpressed in multidrug (MD) resistant cells and named “resistance-related” because of its co-amplification with ABCB1. Although for years sorcin overexpression was thought to be only a by-product of the co-amplification with ABC transporter genes, many papers have recently demonstrated that sorcin plays an important part in MDR, indicating a possible role of sorcin as an oncoprotein. The present review illustrates sorcin roles in the generation of MDR via many mechanisms and points to sorcin as a novel potential target of different anticancer molecules

Life cycle assessment of protected strawberry productions in central Italy

Agricultural activities in Europe cover half of the total area of the continent and are simultaneously a cause of environmental impact and victims of the same impact. Horticultural or fruit crops are considered highly intensive and often employ many crop inputs such as fertilizers, pesticides, and various materials. Strawberry falls into this group, and it has grown in acreage and production more than others globally. The aim of this study is to compare the environmental impact of two strawberry cultivation systems in central Italy, a mulched soil tunnel and a soilless tunnel system. The method used to assess the impact is LCA, widely applied in agriculture and supported by international standards. The data used are mainly primary, related to 2018, and representative of the cultivation systems of central Italy. For impact assessment, the method selected was the CML_IA baseline version. From the results obtained, the two systems show a similar impact per kg of strawberries produced (e.g., for global warming: 0.785 kg CO2 eq for soilless, 0.778 kg CO2 eq for mulched soil tunnel). Reduced differences can be observed for the use of crop inputs (greater for the tunnel) and the use of materials and technology (greater for soilless). The mitigation measures considered concern the replacement of the packaging (excluding plastic) and the growing medium of the soilless using perlite and compost from insect breeding

Doxorubicin and other anthracyclines in cancers: activity, chemoresistance and its overcoming

Anthracyclines have been important and effective treatments against a number of cancers since their discovery. However, their use in therapy has been complicated by severe side effects and toxicity that occur during or after treatment, including cardiotoxicity. The mode of action of anthracyclines is complex, with several mechanisms proposed. It is possible that their high toxicity is due to the large set of processes involved in anthracycline action. The development of resistance is a major barrier to successful treatment when using anthracyclines. This resistance is based on a series of mechanisms that have been studied and addressed in recent years. This work provides an overview of the anthracyclines used in cancer therapy. It discusses their mechanisms of activity, toxicity, and chemoresistance, as well as the approaches used to improve their activity, decrease their toxicity, and overcome resistance

Innovative approach for a classic target: fragment screening on trypanothione reductase reveals new opportunities for drug design

Trypanothione reductase (TR) is a key factor in the redox homeostasis of trypanosomatid parasites, critical for survival in the hostile oxidative environment generated by the host to fight infection. TR is considered an attractive target for the development of new trypanocidal agents as it is essential for parasite survival but has no close homolog in humans. However, the high efficiency and turnover of TR challenging targets since only potent inhibitors, with nanomolar IC50, can significantly affect parasite redox state and viability. To aid the design of effective compounds targeting TR, we performed a fragment-based crystal screening at the Diamond Light Source XChem facility using a library optimized for follow-up synthesis steps. The experiment, allowing for testing over 300 compounds, resulted in the identification of 12 new ligands binding five different sites. Interestingly, the screening revealed the existence of an allosteric pocket close to the NADPH binding site, named the "doorstop pocket" since ligands binding at this site interfere with TR activity by hampering the "opening movement" needed to allow cofactor binding. The second remarkable site, known as the Z-site, identified by the screening, is located within the large trypanothione cavity but corresponds to a region not yet exploited for inhibition. The fragments binding to this site are close to each other and have some remarkable features making them ideal for follow-up optimization as a piperazine moiety in three out of five fragments

Targeted Protein Degradation for Infectious Diseases: from Basic Biology to Drug Discovery

Targeted protein degradation (TPD) is emerging as one of the most innovative strategies to tackle infectious diseases. Particularly, proteolysis-targeting chimera (PROTAC)-mediated protein degradation may offer several benefits over classical anti-infective small-molecule drugs. Because of their peculiar and catalytic mechanism of action, anti-infective PROTACs might be advantageous in terms of efficacy, toxicity, and selectivity. Importantly, PROTACs may also overcome the emergence of antimicrobial resistance. Furthermore, anti-infective PROTACs might have the potential to (i) modulate "undruggable"targets, (ii) "recycle"inhibitors from classical drug discovery approaches, and (iii) open new scenarios for combination therapies. Here, we try to address these points by discussing selected case studies of antiviral PROTACs and the first-in-class antibacterial PROTACs. Finally, we discuss how the field of PROTAC-mediated TPD might be exploited in parasitic diseases. Since no antiparasitic PROTAC has been reported yet, we also describe the parasite proteasome system. While in its infancy and with many challenges ahead, we hope that PROTAC-mediated protein degradation for infectious diseases may lead to the development of next-generation anti-infective drugs

Structure and metal-binding properties of PA4063, a novel player in periplasmic zinc trafficking by Pseudomonas aeruginosa

The capability to obtain essential nutrients in hostile environments is a critical skill for pathogens. Under zinc-deficient conditions, Pseudomonas aeruginosa expresses a pool of metal homeostasis control systems that is complex compared with other Gram-negative bacteria and has only been partially characterized. Here, the structure and zinc-binding properties of the protein PA4063, the first component of the PA4063-PA4066 operon, are described. PA4063 has no homologs in other organisms and is characterized by the presence of two histidine-rich sequences. ITC titration detected two zinc-binding sites with micromolar affinity. Crystallographic characterization, performed both with and without zinc, revealed an α/β-sandwich structure that can be classified as a noncanonical ferredoxin-like fold since it differs in size and topology. The histidine-rich stretches located at the N-terminus and between β3 and β4 are disordered in the apo structure, but a few residues become structured in the presence of zinc, contributing to coordination in one of the two sites. The ability to bind two zinc ions at relatively low affinity, the absence of catalytic cavities and the presence of two histidine-rich loops are properties and structural features which suggest that PA4063 might play a role as a periplasmic zinc chaperone or as a concentration sensor useful for optimizing the response of the pathogen to zinc deficiency

Musical Activities, Prosocial Behaviors, and Executive Function Skills of Kindergarten Children

Prosocial behaviors and executive function are staples of child development. Engagement in music has been associated with enhanced prosocial behaviors and executive function skills in children and youth. Yet, research concerning the role of formal music programs in the development of these important behaviors and skills remains elusive. The aim of this exploratory study was to investigate the role of a 5-week music program on prosocial behaviors (instrumental helping and sharing) and executive function skills (cognitive flexibility and working memory/inhibition control) of 103 kindergarten children from two public schools in a large urban center in the United States, serving predominantly Latinx children from underserved communities. Our data suggested that the short music program positively influenced children's cognitive flexibility, but not working memory, nor prosocial skills (sharing and helping). Findings are discussed in light of earlier studies, methodological issues, and limitations, and in relation to developmental and cultural issues surrounding child participants. Implications for future research and practice are outlined