Supply Chain Finance techniques and risks

Supply Chain Finance is as a portfolio of financing and risk mitigation practices and techniques to optimize the management of the working capital and liquidity invested in supply chain processes and transactions. SCF techniques existing on the market can be divided into three categories: receivable purchase, advanced payable, and loans. These financing solutions are significantly ‘eventdriven’, since they aim at satisfying the financial requirements of buyers and sellers, that are triggered by purchase orders, invoices, receivables, other claims, and related pre-shipment and post-shipment processes along the increasingly complex supply chains in which they are involved. Along the way from raw material procurement to production, sales and end-users, several source of risks can threaten the possibility of completing the transactions and the regular functioning of supply chain finance. Digitization can help in managing these risks, facilitating the control of the factors underlying them

Haplotype affinities resolve a major component of goat (<i>Capra hircus</i>) MtDNA D-loop diversity and reveal specific features of the Sardinian stock

Goat mtDNA haplogroup A is a poorly resolved lineage absorbing most of the overall diversity and is found in locations as distant as Eastern Asia and Southern Africa. Its phylogenetic dissection would cast light on an important portion of the spread of goat breeding. The aims of this work were 1) to provide an operational definition of meaningful mtDNA units within haplogroup A, 2) to investigate the mechanisms underlying the maintenance of diversity by considering the modes of selection operated by breeders and 3) to identify the peculiarities of Sardinian mtDNA types. We sequenced the mtDNA D-loop in a large sample of animals (1,591) which represents a non-trivial quota of the entire goat population of Sardinia. We found that Sardinia mirrors a large quota of mtDNA diversity of Western Eurasia in the number of variable sites, their mutational pattern and allele frequency. By using Bayesian analysis, a distance-based tree and a network analysis, we recognized demographically coherent groups of sequences identified by particular subsets of the variable positions. The results showed that this assignment system could be reproduced in other studies, capturing the greatest part of haplotype diversity. We identified haplotype groups overrepresented in Sardinian goats as a result of founder effects. We found that breeders maintain diversity of matrilines most likely through equalization of the reproductive potential. Moreover, the relevant amount of inter-farm mtDNA diversity found does not increase proportionally with distance. Our results illustrate the effects of breeding practices on the composition of maternal gene pool and identify mtDNA types that may be considered in projects aimed at retrieving the maternal component of the oldest breeds of Sardinia.</br

13C detected experiments illuminate the vicinity of the metal center

Funding Information: The support of the CERM/CIRMMP center of Instruct-ERIC is gratefully acknowledged. This work was supported in part by the project “Potentiating the Italian Capacity for Structural Biology Services in Instruct-ERIC" (ITACA.SB, Project no. IR0000009) within the call MUR 3264/2021 PNRR M4/C2/L3.1.1, funded by the European Union—Next Generation EU. LQ is a PhD student under the Tuscany Health Ecosystem-ECS_00000017 (CUP B83C22003920001), spoke 7, funded by the European Union—Next Generation EU. This work was funded by national funds through FCT–Fundação para a Ciência e a Tecnologia, I.P. (FCT), Project MOSTMICRO-ITQB with refs UIDB/04612/2020 and UIDP/04612/2020, and LS4FUTURE Associated Laboratory (LA/P/0087/2020). Funding Information: Open access funding provided by Università degli Studi di Firenze within the CRUI-CARE Agreement. Publisher Copyright: © 2023, The Author(s).The robustness of NMR coherence transfer in proximity of a paramagnetic center depends on the relaxation properties of the nuclei involved. In the case of Iron-Sulfur Proteins, different pulse schemes or different parameter sets often provide complementary results. Tailored versions of HCACO and CACO experiments significantly increase the number of observed Cα/C’ connectivities in highly paramagnetic systems, by recovering many resonances that were lost due to paramagnetic relaxation. Optimized 13C direct detected experiments can significantly extend the available assignments, improving the overall knowledge of these systems. The different relaxation properties of Cα and C’ nuclei are exploited in CACO vs COCA experiments and the complementarity of the two experiments is used to obtain structural information. The two [Fe2S2]+ clusters containing NEET protein CISD3 and the one [Fe4S4]2+ cluster containing HiPIP protein PioC have been taken as model systems. We show that tailored experiments contribute to decrease the blind sphere around the cluster, to extend resonance assignment of cluster bound cysteine residues and to retrieve details on the topology of the iron-bound ligand residues.publishersversionpublishe

Molecular bases of cluster release and destabilizing effects of nitric oxide

Funding Information: Cindy Vallières was supported by Marie Skłodowska-Curie Actions MSCA-IF-2020 (FungiFeS/ID 101030584 ). Deborah Grifagni was supported by European Molecular Biology Organization (EMBO) through Grant Application Number 9373 and by PHC Galileo PROJECT N° 48929TH. L. B., F. C. and M. P. acknowledges the support by the Italian Ministry for University and Research (FOE funding) to the CERM/CIRMMP Italian Centre of Instruct-ERIC, a ESFRI Landmark. OA Fees have been covered with the support of the European Cooperation in Science and Technology ( COST ) Action CA21115. Funding Information: This article is based on work from COST Action FeSImmChemNet (CA21115) supported by COST (European Cooperation in Science and Technology). We acknowledge the financial support from the Agence Nationale de la Recherche (ANR-21-CE44-0016) and from the European Union - NextGenerationEU-National Recovery and Resilience Plan, Mission 4 Component 2-Investment 1.5-THE-Tuscany Health Ecosystem-ECS00000017-CUP B83C22003920001. This work was funded also by national funds through FCT–Fundação para a Ciência e a Tecnologia , I.P. (FCT), Project MOSTMICRO-ITQB with refs UIDB/04612/2020 and UIDP/04612/2020 , and LS4FUTURE Associated Laboratory ( LA/P/0087/2020 ). The authors are grateful to Inês B. Trindade for helpful discussions on the electrochemical data. Publisher Copyright: © 2024 The AuthorsThe NEET proteins, an important family of iron-sulfur (Fe-S) proteins, have generated a strong interest due to their involvement in diverse diseases such as cancer, diabetes, and neurodegenerative disorders. Among the human NEET proteins, CISD3 has been the least studied, and its functional role is still largely unknown. We have investigated the biochemical features of CISD3 at the atomic and in cellulo levels upon challenge with different stress conditions i.e., iron deficiency, exposure to hydrogen peroxide, and nitric oxide. The redox and cellular stability properties of the protein agree on a predominance of reduced form of CISD3 in the cells. Upon the addition of iron chelators, CISD3 loses its Fe-S clusters and becomes unstructured, and its cellular level drastically decreases. Chemical shift perturbation measurements suggest that, upon cluster oxidation, the protein undergoes a conformational change at the C-terminal CDGSH domain, which determines the instability of the oxidized state. This redox-associated conformational change may be the source of cooperative electron transfer via the two [Fe2S2] clusters in CISD3, which displays a single sharp voltammetric signal at −31 mV versus SHE. Oxidized CISD3 is particularly sensitive to the presence of hydrogen peroxide in vitro, whereas only the reduced form is able to bind nitric oxide. Paramagnetic NMR provides clear evidence that, upon NO binding, the cluster is disassembled but iron ions are still bound to the protein. Accordingly, in cellulo CISD3 is unaffected by oxidative stress induced by hydrogen peroxide but it becomes highly unstable in response to nitric oxide treatment.publishersversionpublishe

Possible implications for SARS-CoV-2 impact on brain development

Funding Information: The authors would like to thank Dr. Marc Peschanski (I-Stem, Évry, France) for providing IMR90-hiPSCs, and Dr. Anna Navarro Cuenca for providing the license for the use of BioRender.com. Publisher Copyright: © 2022The possible neurodevelopmental consequences of SARS-CoV-2 infection are presently unknown. In utero exposure to SARS-CoV-2 has been hypothesized to affect the developing brain, possibly disrupting neurodevelopment of children. Spike protein interactors, such as ACE2, have been found expressed in the fetal brain, and could play a role in potential SARS-CoV-2 fetal brain pathogenesis. Apart from the possible direct involvement of SARS-CoV-2 or its specific viral components in the occurrence of neurological and neurodevelopmental manifestations, we recently reported the presence of toxin-like peptides in plasma, urine and fecal samples specifically from COVID-19 patients. In this study, we investigated the possible neurotoxic effects elicited upon 72-hour exposure to human relevant levels of recombinant spike protein, toxin-like peptides found in COVID-19 patients, as well as a combination of both in 3D human iPSC-derived neural stem cells differentiated for either 2 weeks (short-term) or 8 weeks (long-term, 2 weeks in suspension + 6 weeks on MEA) towards neurons/glia. Whole transcriptome and qPCR analysis revealed that spike protein and toxin-like peptides at non-cytotoxic concentrations differentially perturb the expression of SPHK1, ELN, GASK1B, HEY1, UTS2, ACE2 and some neuronal-, glia- and NSC-related genes critical during brain development. Additionally, exposure to spike protein caused a decrease of spontaneous electrical activity after two days in long-term differentiated cultures. The perturbations of these neurodevelopmental endpoints are discussed in the context of recent knowledge about the key events described in Adverse Outcome Pathways relevant to COVID-19, gathered in the context of the CIAO project (https://www.ciao-covid.net/).publishersversionpublishe

Decoding Depression: Exploring the Environome Across Life Course

Depression is a central marker in mental health issues due to its widespread prevalence, significant disability burden, and extensive social and economic impacts. The COVID-19 pandemic, ongoing conflicts, natural disasters, and the climate crisis have exacerbated mental health challenges across populations, necessitating robust and adaptive policy responses, particularly affecting youth and individuals with pre-existing conditions linked to e.g., genetic, biological, medical, psychological, social and environmental factors. These global events highlight the need for comprehensive mental health strategies that can withstand and mitigate such polycrises. The European Commission has recognised this urgency through its political guidelines for 2024-2029, with a renewed commitment to mental health as a key component of its preventive health strategies and social policies. It issued a Comprehensive Approach on Mental Healthe on June 7th, 2023, to address the urgent need for action on mental health and depression. In line with President Ursula von der Leyen's strategic priorities, the Commission's approach integrates mental health into broader socio-economic initiatives, including anti-poverty, social rights, affordable housing, and health plans aimed at fostering resilience and inclusivity. This report draws on scientific knowledge and insights from transdisciplinary healthcare professionals alongside lived experience experts, gathered during the scientific workshop “Crowdsourcing Knowledge on Depression Mechanisms: From Risk Factors to Treatment” held at the European Commission’s Joint Research Centre in April 2023, and further refined in a co-editing workshop in June 2024, “Decoding Depression: A Life Course Exploration of Vulnerabilities through Transdisciplinary Inquiry”. It emphasises the complex, environome-driven nature of depression, where personal, social, natural, and built environments converge to shape mental health outcomes. Central to our approach is embracing the advancements from various disciplines, including life sciences, environmental studies, education, and technological innovation. The report champions a One Health Governance and transdisciplinary collaboration to address the multifaceted challenges of depression, integrating insights from a broad spectrum of scientific and societal perspectives. It identifies seven key areas essential to tackling depression: healthcare and social inclusion, education, arts with an emphasis on cultural sensitivity and equity, technology and digital tools, labor market and economics, humanitarian considerations alongside local and global welfare, urban planning and environmental health. These categories, underpinned by the Commission's framework, are integral to formulating comprehensive policies that apply the multifaceted evidence-based scientific nature of depression. An evolving Interactive Depression Dashboard (InDepDash) has been created as a dynamic, centralised information hub, offering a comprehensive navigation and synthesis of the extensive and evolving scientific literature on depression. It supports the strategic vision of the European Commission by providing an evidence-based digital platform for policy-makers, helping to guide decision-making processes and fostering a culture of Open Science. We focus on identifying essential policy interventions that span prevention, the spectrum of supportive resources —both conventional and alternative— and recovery processes.JRC.F.7 - Digital Healt

Decoding Depression and Environmental Influences: Vulnerabilities and Policy Insights

The Dissemination Brochure and the Introductory and Demo videos provide a comprehensive overview of the Joint Research Centre's (JRC) science for policy work on depression, framed within the European Commission's Comprehensive Approach to Mental Health initiative. The material aims to bridge the gap between complex scientific research and public communication, making the findings accessible to a broad audience, including policymakers and stakeholders, during the critical 2024-2029 European Commission period. Highlighting the outcomes from pivotal workshops, the Brochure and videos show the synthesis of evidence and policy recommendations emerging from the scientific workshop “Crowdsourcing Knowledge on Depression Mechanisms: From Risk Factors to Treatment” and the subsequent co-editing workshop “Decoding Depression: A Life Course Exploration of Vulnerabilities through Transdisciplinary Inquiry.” These events, hosted by the EC JRC, united healthcare professionals, scientists, and individuals with lived experience to explore the mechanisms of depression through a collaborative, transdisciplinary approach. Furthermore, both videos showcases innovative digital health tools developed by the EC JRC, such as the SciWalker and the MAATrica digital metric, with a particular focus on the 'InDepDash' platform. InDepDash, an interactive dashboard, provides policymakers with a panoramic view of global data on depression, enabling informed, evidence-based decisions and promoting mental health resilience within society. Through this communication videos and the Brochure, we aim to elucidate the EC JRC's dedicated efforts in advancing mental health policy and practice through state-of-the-art science and technology.JRC.F.7 - Digital Healt

Haplotype Affinities Resolve a Major Component of Goat (Capra hircus) MtDNA D-Loop Diversity and Reveal Specific Features of the Sardinian Stock

Goat mtDNA haplogroup A is a poorly resolved lineage absorbing most of the overall diversity and is found in locations as distant as Eastern Asia and Southern Africa. Its phylogenetic dissection would cast light on an important portion of the spread of goat breeding. The aims of this work were 1) to provide an operational definition of meaningful mtDNA units within haplogroup A, 2) to investigate the mechanisms underlying the maintenance of diversity by considering the modes of selection operated by breeders and 3) to identify the peculiarities of Sardinian mtDNA types. We sequenced the mtDNA D-loop in a large sample of animals (1,591) which represents a non-trivial quota of the entire goat population of Sardinia. We found that Sardinia mirrors a large quota of mtDNA diversity of Western Eurasia in the number of variable sites, their mutational pattern and allele frequency. By using Bayesian analysis, a distance-based tree and a network analysis, we recognized demographically coherent groups of sequences identified by particular subsets of the variable positions. The results showed that this assignment system could be reproduced in other studies, capturing the greatest part of haplotype diversity