Influence of non-allergenic fining agents on white wine phenolic and volatile composition

White wine fining is important to stabilize wine colour by removing phenolic compounds. The choice of oenological products is important since consumers are concerned regarding food safety. Due to allergic reaction problems by some consumers, together with the restriction of EU legislation [1], non-allergenic fining agents are being developed in detriment of traditionally used. However, the impact these fining agents on wine phenolic and volatile compounds are not well known. This work aims to evaluate the impact of six fining agents (one traditionally used potassium caseinate and five non-allergens) on wine phenolic and volatile compounds as well as on the sensory profile of a white wine from the Douro Region. All non-allergenic fining agents tested prevent the browning capacity. This could be related to the decrease in white wine colour observed. Sensory analysis indicated that only the wines treated with potassium caseinate and polyvinylpolypyrrolidone showed a significant decrease in colour attribute.Supported by FCT project UID/AGR/04033/2013, CQ-VR, FCT funding of UID/BIO/04469/2013 unit, COMPETE 2020 (POCI-01-0145-FEDER-006684) and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by European Regional Development Fund under the scope of Norte2020 – Programa Operacional Regional do Norte. Additional thanks to the Project NORTE-01-0145- FEDER-000038 (I&D INNOVINE&WINE – Innovation Platform of Vine & Wine).info:eu-repo/semantics/publishedVersio

Avaliação do efeito dos agentes de colagem não-alergénios na composição volátil e no perfil sensorial de vinho branco

A operação de colagem no vinho branco é importante para a estabilização da cor, por remover compostos fenólicos responsáveis pelo acastanhamento do vinho. No entanto, a escolha do agente de colagem é cada vez mais importante, uma vez que os consumidores estão preocupados com a segurança alimentar. Devido a problemas de reações alérgicas por partes dos consumidores, juntamente com as restrições da Legislação Europeia [1] e a especificação da Legislação de determinados Países, na indústria dos vinhos os agentes de colagem não-alergénios estão a ser utilizados em detrimento dos agentes de colagem tradicionais. No entanto, o impacto dos agentes de colagem não-alergénios na composição volátil do vinho e no perfil sensorial não é ainda bem conhecido. Portanto o objetivo deste trabalho foi avaliar o impacto de seis agentes de colagem (um tradicionalmente utilizado na indústria vinícola caseinato de potássio e cinco não alergénios polivinilpolipirrolidona (PVPP), proteína de ervilha, paredes de levedura, associação de proteína vegetal com paredes de levedura e associação de PVPP com proteína vegetal) na composição volátil e perfil sensorial de um vinho branco da Região Demarcado do Douro. Os agentes de colagem foram testados na dose máxima recomendado pelo fabricante. Os resultados mostraram que a concentração de ésteres, quando comparado com o vinho controlo, foi menor nos vinhos tratados com os diferentes agentes de colagem. Em relação aos álcoois superiores verificou- se uma diminuição na concentração do vinho tratado com caseinato de potássio, PVPP, paredes de levedura e associação de PVPP com proteína vegetal. A concentração de 2-feniletanol diminui no vinho tratado com paredes de levedura, associação de proteína vegetal com paredes de levedura e associação de PVPP com proteína vegetal. Individualmente, os álcoois superiores não dão aromas agradáveis ao vinho, com exceção do 2-feniletanol, mas juntos podem contribuir positivamente para o aroma do vinho. O perfil sensorial do vinho mostra que o vinho mais pontuado para o atributo frutado foi o vinho tratado com proteína de ervilha e o mais pontuado para o atributo floral foi o vinho tratado com paredes de levedura. Assim, os resultados obtidos incentivam a implementação desse tipo de agente de colagem à escala industrial.Este trabalho é apoiado por Fundos Nacionais pela FCT – Fundação Portuguesa para a Ciência e a Tecnologia, no âmbito do UID/AGR/04033/2013 e pelo Centro de Química-Vila Real (CQ-VR).info:eu-repo/semantics/publishedVersio

Interaction of silver atomic quantum clusters with living organisms: bactericidal effect of Ag3 clusters mediated by disruption of topoisomerase–DNA complexes

Essential processes for living cells such as transcription and replication depend on the formation of specific protein–DNA recognition complexes. Proper formation of such complexes requires suitable fitting between the protein surface and the DNA surface. By adopting doxorubicin (DOX) as a model probe, we report here that Ag3 atomic quantum clusters (Ag-AQCs) inhibit the intercalation of DOX into DNA and have considerable influence on the interaction of DNA-binding proteins such as topoisomerase IV, Escherichia coli DNA gyrase and the restriction enzyme HindIII. Ag-AQCs at nanomolar concentrations inhibit enzyme activity. The inhibitory effect of Ag-AQCs is dose-dependent and occurs by intercalation into DNA. All these effects, not observed in the presence of Ag+ ions, can explain the powerful bactericidal activity of Ag-AQCs, extending the knowledge of silver bactericidal properties. Lastly, we highlight the interest of the interaction of Ag clusters with living organisms, an area that should be further explored due to the potential consequences that it might have, both beneficial and harmful.This work was supported by Obra Social“la Caixa” (OSLC-2012-007), European Commission through FEDER program (0681 InveNNta 1 E); Ministerio de Ciencia e Innovación, Spain (MAT2010-20442, MAT2011-28673-C02-01); MINECO, Spain (MAT2012-36754-C02-01 and CTQ2014-58812-C2-2-R), Xunta de Galicia, Spain (GRC2013-044, FEDER Funds). C. P.-A. is grateful for the FPU grant from Ministry of Education, Culture and Sports, Madrid, Spain (FPU13/00180)S

Ag2 and Ag3 Clusters: Synthesis, Characterization, and Interaction with DNA

Subnanometric samples, containing exclusively Ag2 and Ag3 clusters, were synthesized for the first time by kinetic control using an electrochemical technique without the use of surfactants or capping agents. By combination of thermodynamic and kinetic measurements and theoretical calculations, we show herein that Ag3 clusters interact with DNA through intercalation, inducing significant structural distortion to the DNA. The lifetime of Ag3 clusters in the intercalated position is two to three orders of magnitude longer than for classical organic intercalators, such as ethidium bromide or proflavine.Fil: Buceta, David. Universidad de Santiago de Compostela; EspañaFil: Busto, Natalia. Universidad de Burgos; EspañaFil: Barone, Giampaolo. Università di Palermo; ItaliaFil: Leal, José M.. Universidad de Burgos; EspañaFil: Domínguez, Fernando. Universidad de Santiago de Compostela; EspañaFil: Giovanetti, Lisandro Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina. Universidad Nacional de la Plata; ArgentinaFil: Requejo, Felix Gregorio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina. Universidad Nacional de la Plata; ArgentinaFil: García, Begoña. Universidad de Burgos; EspañaFil: López-Quintela, M. Arturo. Universidad de Santiago de Compostela; Españ

Genetic and microenvironmental intra-tumor heterogeneity impacts colorectal cancer evolution and metastatic development

© The Author(s) 2022 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Colorectal cancer (CRC) is a highly diverse disease, where different genomic instability pathways shape genetic clonal diversity and tumor microenvironment. Although intra-tumor heterogeneity has been characterized in primary tumors, its origin and consequences in CRC outcome is not fully understood. Therefore, we assessed intra- and inter-tumor heterogeneity of a prospective cohort of 136 CRC samples. We demonstrate that CRC diversity is forged by asynchronous forms of molecular alterations, where mutational and chromosomal instability collectively boost CRC genetic and microenvironment intra-tumor heterogeneity. We were able to depict predictor signatures of cancer-related genes that can foresee heterogeneity levels across the different tumor consensus molecular subtypes (CMS) and primary tumor location. Finally, we show that high genetic and microenvironment heterogeneity are associated with lower metastatic potential, whereas late-emerging copy number variations favor metastasis development and polyclonal seeding. This study provides an exhaustive portrait of the interplay between genetic and microenvironment intra-tumor heterogeneity across CMS subtypes, depicting molecular events with predictive value of CRC progression and metastasis development.This work was financed by national funds from FCT - Fundação para a Ciência e a Tecnologia, I.P., in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences - UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy - i4HB. This research was also funded by: PTDC/MED-ONC/28660/2017 from Fundação para a Ciência e Tecnologia (FCT) to A.R.G. A.R.G is recipient of Researcher Grant CEECIND/02699/2017 from FCT. The biobanking of CRC samples from Hospital Santa Maria, Lisbon, Portugal was supported by FCT research grant PIC/IC/82821/2007. This work was produced with the support of INCD funded by FCT and FEDER under the project 22153-01/SAICT/2016.info:eu-repo/semantics/publishedVersio

Critically short telomeres and toxicity of chemotherapy in early breast cancer

Cumulative toxicity from weekly paclitaxel (myalgia, peripheral neuropathy, fatigue) compromises long-term administration. Preclinical data suggest that the burden of critically short telomeres ( 21.9% CSTs) had 2-fold higher number of neuropathy (P = 0.04) or fatigue (P = 0.019) episodes and >3-fold higher number of myalgia episodes (P = 0.005). The average telomere length was unrelated to the incidence of side effects.The percentage of CSTs, but not the average telomere size, is associated with weekly paclitaxel-derived toxicity.This work was supported by the Fondo de Investigación Sanitaria [FIS PI10/00288 and FIS PI13/00430]; AECC Scientific Foundation [Beca de Retorno-2010, to MQF]; Spanish Ministry of Economy and Competitiveness Projects [SAF2013-45111-R]; Madrid Regional Government Projects [S2010/BMD- 2303]; AXA Research Found; Fundación Botin; AVON Spain; and Boehringer-Ingelheim Spain.S

Silver clusters of five atoms as highly selective antitumoral agents through irreversible oxidation of thiols

Low atomicity clusters present properties dependent on the size, due to the quantum confinement, with well-defined electronic structures and high stability. Here it is shown that Ag5 clusters catalyze the complete oxidation of sulfur to S+6. Ag5 catalytic activity increases with different oxidant species in the order O2 ≪ H2O2 < OH•. Selective oxidation of thiols on the cysteine residues of glutathione and thioredoxin is the primary mechanism human cells have to maintain redox homeostasis. Contingent upon oxidant concentration, Ag5 catalyzes the irreversible oxidation of glutathione and thioredoxin, triggering apoptosis. Modification of the intracellular environment to a more oxidized state to mimic conditions within cancer cells through the expression of an activated oncogene (HRASG12V) or through ARID1A mutation, sensitizes cells to Ag5 mediated apoptosis. While cancers evolve to evade treatments designed to target pathways or genetic mutations that drive them, they cannot evade a treatment that takes advantage of aberrant redox homeostasis, which is essential for tumor progression and metastasis. Ag5 has antitumor activity in mice with orthotopic lung tumors reducing primary tumor size, and the burden of affected lymphatic nodes. The findings suggest the unique intracellular redox chemistry of Ag5 may lead to new redox-based approaches to cancer therapyThis research was partially supported by 1) “la Caixa” Foundation, Ref. LCF/PR/PR12/11070003 to F.D. and M.A.L.Q.; 2) Ministerio de Ciencia, Innovación y Universidades (MAT2017-89678-R, AEI/FEDER, UE) to F.D. and A.V.; 3) the Consellería de Educación (Xunta de Galicia), Grants No. Grupos Ref. Comp. ED431C 2017/22, ED431C 2019/13 and AEMAT-ED431E2018/08 to M.A.L.Q.; and ED431C 2019/13 to A.V. This project has received funding from the European Union's Horizon 2020 Research and Innovation Programme (Bac-To-Fuel) under Grant Agreement No. 825999 (M.A.L.Q.). J.C.H. acknowledge financial support from European Union's Horizon 2020 research and innovation programme under grant agreement no. 823717-ESTEEM3, and the MICIIN (projects PID2019-107578GA-100 and PID-110018GA-100). J.M.D, L.J.G., and F.G.R. thank to the ANPCyT (PICT 2015-2285 and 2017-3944), UNLP (Project 11/X790) and the partial support by the Laboratório Nacional de Luz Síncrotron (LNLS, Brazil) under proposal SXS-20180280. G.B. acknowledges the CINECA Award N. IsC51, year 2017, under the ISCRA initiative, for the availability of high-performance computing resources and support. D.B. expresses gratitude for a postdoctoral grant from Xunta de Galicia, Spain (POS-A/2013/018). B.D. expresses gratitude for a predoctoral grant from MICINN, Spain (BES-2016-076765). F.D. and A.V. also acknowledged Xunta de Galicia (Centro singular de investigación de Galicia accreditation 2019-2022 ref ED431G 2019/02) and the European Union (European Regional Development Fund – ERDF). Work in M.P.M.'s lab was supported by the Medical Research Council UK (MC_U105663142). T.G.C. gratefully acknowledges the technical assistance of María José Otero-Fraga (FIDIS)S

Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Patients with Non–Small Cell Lung Carcinoma: the ROSING Study

Introduction: The ROS1 gene rearrangement has become an important biomarker in NSCLC. The College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology testing guidelines support the use of ROS1 immunohistochemistry (IHC) as a screening test, followed by confirmation with fluorescence in situ hybridization (FISH) or a molecular test in all positive results. We have evaluated a novel anti-ROS1 IHC antibody (SP384) in a large multicenter series to obtain real-world data. Methods: A total of 43 ROS1 FISH-positive and 193 ROS1 FISH-negative NSCLC samples were studied. All specimens were screened by using two antibodies (clone D4D6 from Cell Signaling Technology and clone SP384 from Ventana Medical Systems), and the different interpretation criteria were compared with break-apart FISH (Vysis). FISH-positive samples were also analyzed with next-generation sequencing (Oncomine Dx Target Test Panel, Thermo Fisher Scientific). Results: An H-score of 150 or higher or the presence of at least 70% of tumor cells with an intensity of staining of 2+ or higher by the SP384 clone was the optimal cutoff value (both with 93% sensitivity and 100% specificity). The D4D6 clone showed similar results, with an H-score of at least 100 (91% sensitivity and 100% specificity). ROS1 expression in normal lung was more frequent with use of the SP384 clone (p < 0.0001). The ezrin gene (EZR)-ROS1 variant was associated with membranous staining and an isolated green signal FISH pattern (p = 0.001 and p = 0.017, respectively). Conclusions: The new SP384 ROS1 IHC clone showed excellent sensitivity without compromising specificity, so it is another excellent analytical option for the proposed testing algorithm