Supporting the Transformation of Livelihoods: Village Development Funds Managed by Self-Help Groups

This primer is used to train, monitor, and coach communities implementing the Biodiversity Conservation Corridors Project (BCCP) in Cambodia on Village Development Funds, which aims to help villages effectively achieve better livelihoods and infrastructures in their communities

Electrical characterization of MXenes and their applications on photovoltaic cells

Ti3C2Tx is a particular type of MXene whose electrical properties have been studied. Specifically, its performance as a hole transport layer (HTL) in an n-type Si photovoltaic cell has been evaluated and compared to a cell without MXene. Additionally, a layer of a dipolar material, PAMAM, has been implemented alongside with MXene to improve the overall behaviour of the cell. J-V and EQE characteristics have been measured for the di↵erent cells and figures of merit have been computed to determine the e↵ect of adding layers of MXene and PAMAM. The measurements have been done at room temperature and after a 1002021/202

Biomarker of food intake for assessing the consumption of dairy and egg products

Foods of animal origin constitute one of the predominant food groups consumed in Western diets. They play an essential role in human nutrition as they represent an excellent source of high quality proteins, vitamins, minerals and fats. Foods of animal origin are highly diverse (e.g. meat, fish, dairy products and eggs) and their associations with a range of nutritional and health outcomes are therefore heterogeneous. Such associations are also often weak or debated due to the difficulty in establishing correct assessments of dietary intake. Therefore, in order to better characterize associations between the consumption of specific foods of animal origin and health outcomes, it is important to identify reliable biomarkers of food intake (BFIs). BFIs provide a more accurate measure of intake and are independent of the memory and sincerity of the subjects as well as of their knowledge about the consumed foods. To date, only a very limited number of compounds have been proposed as biomarkers of the intake of foods of animal origin and further studies are necessary to validate them and to discover new candidate BFIs. We have, therefore, conducted a systematic search of the scientific literature to evaluate the current status of potential BFIs for each category of foods of animal origin commonly consumed in Europe. This review reports on candidate biomarkers for dairy products and eggs intake, while biomarkers for fish and meat intake will be published separately. Remarkably, validated BFIs for dairy products and eggs are not available. A series of challenges hinders their identification and validation, in particular the heterogeneous composition of each food within a product category and the lack of specificity of the markers identified so far. Untargeted metabolomic strategies may allow the identification of novel food biomarkers, that, when taken separately or in combination, could be used to assess the intake of dairy products and eggs

Information resources for action researchers/practitioners in Climate Resilient Agriculture

Most of the resources featured here were generated from actual climate-smart agriculture/climate resilient agriculture (CSA/CRA) programs implemented. Some of them reflect the action research nature of the CSA/CRA work of the International Institute of Rural Reconstruction in Asia, specifically in the Philippines, Cambodia, and Myanmar. This compilation includes publications generated from projects supported by the CGIAR Research Program on Climate Change, Agriculture and Food Security, Asian Development Bank, the International Development Research Station, the Latter Day Saints Charities, the Department of Agriculture in the Philippines and the Forest Foundation of the Philippines, among others. Some of these resources represent five years of field-derived experiences, now made available in their current form for those at the frontlines as part of efforts to address climate risks that affect smallholder farmers and family farms. Other references were drawn from desk researches

Non-pegylated liposomal doxorubicin in older adjuvant early breast cancer patients: cardiac safety analysis and final results of the COLTONE study

Aims: To explore the cardiac safety of adjuvant Non-Pegylated Liposomal Doxorubicin (NPL-DOX) plus Cyclophosphamide (CTX) followed by weekly Paclitaxel, in elderly women (≥ 65 years) with high-risk breast cancer. Previously, we described no symptomatic cardiac events within the first 12 months from starting treatment. We now reported the updated results after a median follow-up 76 months. Methods: The cardiac activity was evaluated with left ventricular ejection fraction (LVEF) echocardiograms assessments, before starting chemotherapy and every 6 months, until 30 months from baseline, then yearly for at least 5 years. Results: Forty-seven women were recruited by two Units of Medical Oncology (Ethics Committee authorization CESM-AOUP, 3203/2011; EudraCT identification number: 2010-024067-41, for Pisa and Pontedera Hospitals). An episode of grade 3 CHF (NCI-CTCAE, version 3.0) occurred after 18 months the beginning of chemotherapy. The echocardiograms assessments were performed comparing the LVEF values of each patient evaluated at fixed period of time, compared to baseline. We observed a slight changed in terms of mean values at 48, 60, 72 and 84 months. At these time points, a statistically significant reduction of - 3.2%, - 4.6%, - 6.4% and - 7.1%, respectively, was observed. However, LVEF remained above 50% without translation in any relevant clinical signs. No other cardiac significant episodes were reported. To this analysis, in 13 patients (28%) occurred disease relapse and,  of them, 11 (23%) died due to metastatic disease. Eight patients died of cancer-unrelated causes. Conclusions: The combination including NPL-DOX in elderly patients revealed low rate of cardiac toxic effects. Comparative trials are encouraged

Absence of system xc⁻ on immune cells invading the central nervous system alleviates experimental autoimmune encephalitis

Background: Multiple sclerosis (MS) is an autoimmune demyelinating disease that affects the central nervous system (CNS), leading to neurodegeneration and chronic disability. Accumulating evidence points to a key role for neuroinflammation, oxidative stress, and excitotoxicity in this degenerative process. System x(c)- or the cystine/glutamate antiporter could tie these pathological mechanisms together: its activity is enhanced by reactive oxygen species and inflammatory stimuli, and its enhancement might lead to the release of toxic amounts of glutamate, thereby triggering excitotoxicity and neurodegeneration. Methods: Semi-quantitative Western blotting served to study protein expression of xCT, the specific subunit of system x(c)-, as well as of regulators of xCT transcription, in the normal appearing white matter (NAWM) of MS patients and in the CNS and spleen of mice exposed to experimental autoimmune encephalomyelitis (EAE), an accepted mouse model of MS. We next compared the clinical course of the EAE disease, the extent of demyelination, the infiltration of immune cells and microglial activation in xCT-knockout (xCT(-/-)) mice and irradiated mice reconstituted in xCT(-/-) bone marrow (BM), to their proper wild type (xCT(+/+)) controls. Results: xCT protein expression levels were upregulated in the NAWM of MS patients and in the brain, spinal cord, and spleen of EAE mice. The pathways involved in this upregulation in NAWM of MS patients remain unresolved. Compared to xCT(+/+) mice, xCT(-/-) mice were equally susceptible to EAE, whereas mice transplanted with xCT(-/-) BM, and as such only exhibiting loss of xCT in their immune cells, were less susceptible to EAE. In none of the above-described conditions, demyelination, microglial activation, or infiltration of immune cells were affected. Conclusions: Our findings demonstrate enhancement of xCT protein expression in MS pathology and suggest that system x(c)- on immune cells invading the CNS participates to EAE. Since a total loss of system x(c)- had no net beneficial effects, these results have important implications for targeting system x(c)- for treatment of MS

C. elegans expressing D76N β 2 -microglobulin: a model for in vivo screening of drug candidates targeting amyloidosis

Funder: Ministero dell'Istruzione, dell'Università e della Ricerca Dipartimenti di Eccellenza 2018-2022 grant to the Molecular Medicine Department (University of Pavia)Abstract: The availability of a genetic model organism with which to study key molecular events underlying amyloidogenesis is crucial for elucidating the mechanism of the disease and the exploration of new therapeutic avenues. The natural human variant of β2-microglobulin (D76N β2-m) is associated with a fatal familial form of systemic amyloidosis. Hitherto, no animal model has been available for studying in vivo the pathogenicity of this protein. We have established a transgenic C. elegans line, expressing the human D76N β2-m variant. Using the INVertebrate Automated Phenotyping Platform (INVAPP) and the algorithm Paragon, we were able to detect growth and motility impairment in D76N β2-m expressing worms. We also demonstrated the specificity of the β2-m variant in determining the pathological phenotype by rescuing the wild type phenotype when β2-m expression was inhibited by RNA interference (RNAi). Using this model, we have confirmed the efficacy of doxycycline, an inhibitor of the aggregation of amyloidogenic proteins, in rescuing the phenotype. In future, this C. elegans model, in conjunction with the INVAPP/Paragon system, offers the prospect of high-throughput chemical screening in the search for new drug candidates

CD4+ T Cell Depletion, Immune Activation and Increased Production of Regulatory T Cells in the Thymus of HIV-Infected Individuals

Mechanisms by which HIV affects the thymus are multiple and only partially known, and the role of thymic dysfunction in HIV/AIDS immunopathogenesis remains poorly understood. To evaluate the effects of HIV infection on intra-thymic precursors of T cells in HIV-infected adults, we conducted a detailed immunophenotypic study of thymic tissue isolated from 7 HIV-infected and 10 HIV-negative adults who were to undergo heart surgery. We found that thymuses of HIV-infected individuals were characterized by a relative depletion of CD4+ single positive T cells and a corresponding enrichment of CD8+ single positive T cells. In addition, thymocytes derived from HIV-infected subjects showed increased levels of activated and proliferating cells. Our analysis also revealed a decreased expression of interleukin-7 receptor in early thymocytes from HIV-infected individuals, along with an increase in this same expression in mature double- and single-positive cells. Frequency of regulatory T cells (CD25+FoxP3+) was significantly increased in HIV-infected thymuses, particularly in priorly-committed CD4 single positive cells. Our data suggest that HIV infection is associated with a complex set of changes in the immunophenotype of thymocytes, including a reduction of intrathymic CD4+ T cell precursors, increased expression of activation markers, changes in the expression pattern of IL-7R and enrichment of T regulatory cells generation

Progettazione e sintesi di molecole multitarget a struttura chinazolinica per il trattamento del tumore della pelle non-melanoma

Il tumore della pelle non-melanoma (NMSC) è il più diffuso cancro della pelle, ha origine nei cheratinociti a differenza del melanoma che coinvolge i melanociti. Con il termine NMSC ci si riferisce soprattutto al carcinoma delle cellule basali (BCC) e al carcinoma delle cellule squamose SCC. Circa il 75%-80% dei casi totali di cancro della pelle è rappresentato da BCC. Questo tipo di cancro ha origine nelle cellule basali, tende ad accrescersi molto lentamente ed ha scarsa tendenza a metastatizzare. Quando non viene trattato può però diventare deturpante ed evolvere in forme maligne. SCC, che rappresenta circa il 20% dei casi di tumori della pelle, si sviluppa nelle cellule squamose, lo strato più esterno dell’epidermide. Rispetto al BCC, è caratterizzato da un più rapido accrescimento, da una maggior tendenza a diffondere nei tessuti circostanti e a metastatizzare. Il fattore di rischio principale per lo sviluppo di NMSC è l’esposizione prolungata ai raggi UV, sia solari che derivanti da dispositivi abbronzanti. Si ritiene che le radiazioni UV sono agenti mutageni in grado di indurre danno cellulare responsabile poi della trasformazione dei cheratinociti. Le radiazioni UV vanno, infatti, ad alterare meccanismi importanti come l’apoptosi, la proliferazione, il metabolismo, l’infiammazione e il meccanismo di riparo dei danni al DNA del tessuto epiteliale. Inoltre sia gli UVA che gli UVB sono potenti soppressori del sistema immunitario, contribuendo quindi a stimolare la carcinogenesi cutanea. I raggi UVB causano un danno diretto al DNA instaurando un legame covalente tra pirimidine adiacenti e creando così dei prodotti mutageni. I raggi UVA invece inducono la produzione di specie reattive dell’ossigeno (ROS), e quindi di stress ossidativo. Perciò l’utilizzo di molecole ad azione antiossidante potrebbe risultare utile nel ridurre il danno ossidativo mediato dalle radiazioni UV. Una delle vie coinvolte nel meccanismo di tumorigenesi è quella indotta dall’attivazione del recettore del fattore di crescita epiteliale (EGFR), che svolge un ruolo importante nella crescita e nella sopravvivenza di molti tumori e anche dei tumori della pelle. In particolare è stato riportato che, in coltura di cheratinociti e nella pelle, l'irradiazione UV attiva l'EGFR, portando alla proliferazione dei cheratinociti, alla soppressione dell'apoptosi e dell'iperplasia epidermica. Inoltre, studi condotti su modelli animali di carcinogenesi cutanea hanno dimostrato che l'EGFR e un suo ligando, il fattore di crescita trasformante α (TGF), sono coinvolti nella proliferazione dei cheratinociti e nella crescita del cancro della pelle, attraverso la stimolazione di Akt, di trasduttori del segnale e attivatori della trascrizione.[7] In circa il 35%-100% degli SCC è stata rilevata una sovraespressione di EGFR e TGF, associata ad un alto rischio di progressione del cancro. Tuttavia, ci sono studi limitati sugli inibitori di EGFR nel SCC. Recentemente è stato condotto uno studio clinico di fase II con l'inibitore della tirosin chinasi di EGFR gefitinib, in pazienti con SCC recidivante e/o metastatico incurabile, dimostrando una modesta attività di questo inibitore e sottolineando quindi un ruolo terapeutico importante degli inibitori delle tirosin-chinasi EGFR in NMSC. La stimolazione di EGFR da parte dei suoi ligandi porta all'attivazione di geni di trascrizione responsabili degli effetti biologici di EGFR, tra cui la ciclossigenasi-2 (COX-2). che è responsabile della produzione di prostaglandina E2 (PGE2), che va a fosforilare (o transattiva) rapidamente EGFR, per innescare la via di segnalazione MAPK. Quindi, una sovraespressione di COX-2 dovuta alla stimolazione di EGFR può stabilire un circolo vizioso (figura 1) che porta all’ aumento della proliferazione cellulare ed a una differenziazione cellulare incompleta. L’azione combinata di inibitori di EGFR e di COX-2, come riportato in letteratura si è dimostrata efficace nel trattamento di SCC della testa e del collo.[10] In uno studio condotto da Jalili e collaboratori, è stato descritto il trattamento SCC in un anziano paziente con una combinazione di cetuximab (anticorpo monoclonale contro EGFR) e celecoxib (inibitore COX-2 selettivo). Questo tipo di trattamento si è dimostrato efficace, ben tollerato e ha mostrato scarsi effetti collaterali a livello cutaneo. Tuttavia, come ampiamente documentato, la combinazione di farmaci può presentare degli svantaggi dovuti alla somministrazione contemporanea di diversi farmaci con diversi profili di biodisponibilità, farmacocinetica e metabolismo. Al contrario l’approccio multi-target, che consiste nella progettazione di una singola molecola in grado di agire simultaneamente su più target, sembra possedere un maggiore potenziale terapeutico. Sulla base di queste considerazioni, in questa tesi di laurea è stata progettata la sintesi di molecole ibride 1-12 che potenzialmente potrebbero inibire EGFR e contemporaneamente avere attività antiinfiammatoria o antiossidante. Il nucleo chinazolinico opportunamente sostituito è stato scelto in quanto caratteristico di molecole già dimostrate attive nell’inibire EGFR come i derivati A e B, sintetizzati da Tsou et al. e che sono risultati efficaci inibitori della crescita tumorale in modelli di carcinoma epidermoide umano (A431), e il Gefitinib, noto inibitore di EGFR, utilizzato in terapia per il carcinoma polmonare non a piccole cellule e in fase sperimentale per altri tipi di tumore come quello cutaneo. Entrambi i nuclei chinazolinici sono stati coniugati attraverso legame ammidico con molecole ad attività antiinfiammatoria come il diclofenac e il ketoprofene, ottenendo i composti 1-4. I composti 5-12 derivano, invece, dalla coniugazione dei nuclei chinazolinici con molecole naturali ad azione antiossidante e antiproliferativa come l’acido gallico, caffeico, ferulico e cumarico

Myanmar local food systems in a changing climate: Insights from multiple stakeholders

Understanding the impacts of climate on food systems is vital to identifying the most effective food system interventions to support climate-smart agriculture. The study examines how climate change is affecting food systems and what can be done to mitigate its effects. Two methodological approaches were combined in the study. The first was an Asia-wide regional consultation and forum to explore a range of initiatives that transform food systems among stakeholders working in Myanmar. The second method was an in-depth food systems study employing qualitative methods in Htee Pu Village in the Myanmar Central Dry Zone, a research site of IIRR since 2017. Key informant interviews (KII) and focus group discussions (FGD) were conducted to capture insights and data. Food systems consist of components, drivers, actors, and elements that interact with one another and other systems such as social, health, and transportation. The Myanmar food system is complex. Making it sustainable and transformative requires a mix of different approaches implemented at various scales from local to national. It also requires actions that engage various actors in the system from producers to consumers. The study of the local food system of Htee Pu Village indicates that the village has a rural and traditional food system and that climate change is one of its key food system drivers. Climate change negatively impacted farming and agricultural practices and disrupted the input supply of the local food systems. The role of intermediaries such as traders and consolidators is critical in the supply and distribution of food in the Central Dry Zone. Improved and more connected roads are essential for the supply and distribution of food for the village. The informal market outlets serve as the primary food source or sale points for households. Household diets are inadequate in quantity as the population remains highly dependent on their crops for their diets due to relatively low income. Climate adaptation must be embedded in the local level management to mitigate the effect of climate change in food production in the longer term