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Diagnostic and treatment protocol for bile duct cancer
No full textBile duct cancer encompasses a heterogeneous group of epithelial neoplasms originating in the biliary tree, including the gallbladder. It is considered a rare tumor in Western countries, although its incidence has increased in recent years. There are different anatomical subgroups with differences in risk factors, clinical presentation, molecular characteristics, and locoregional treatments. Most cases will be diagnosed in advanced stages and there will be recurrence in up to 80% of resected tumors, so they are neoplasms with a poor prognosis.Peer reviewe
Supplementary Material: Effect of shell thickness on the oxygen evolution activity of Core@shell Fe3O4@CoFe2O4 nanoparticles
No full textGranulometric volume distribution, XRD patterns, thermogravimetric analysis, additional TEM data, EELS spectra, Tafel plots, rotating ring disk electrode analysis, chronoamperometric curves, and additional XAS spectra.Peer reviewe
[Dataset] Cyclic peptide inhibitors function as molecular glues to stabilize Gq/11 heterotrimers
No full textHeterotrimeric Gα:Gβγ G proteins function as molecular switches downstream of G protein-coupled receptors (GPCRs). They alternate between a heterotrimeric GDP-bound OFF-state and a GTP-bound ON-state in which GαGTP is separated from the Gβγ dimer. Consequently, pharmacological tools to securely prevent the OFF-ON transition are of utmost importance to investigate their molecular switch function, specific contribution to GPCR signal transduction, and potential as drug targets. FR900359 (FR) and YM-254890 (YM), two natural cyclic peptides and highly specific inhibitors of Gq/11 heterotrimers, are exactly such tools. To date, their efficient and long-lasting inhibition of Gq/11 signaling has been attributed solely to a wedge-like binding to Gα, thereby preventing separation of the GTPase and α-helical domains and thus GDP release. Here, we use X-ray crystallography, biochemical and signaling assays, and BRET-based biosensors to show that FR and YM also function as stabilizers of the Gα:Gβγ subunit interface. Our high-resolution structures reveal a network of residues in Gα and two highly conserved amino acids in Gβ that are targeted by FR and YM to glue the Gβγ complex to the inactive GαGDP subunit. Unlike all previously developed nucleotide-state specific inhibitors that sequester Gα in its OFF-state but compete with Gβγ, FR and YM actively promote the inhibitory occlusion of GαGDP by Gβγ. In doing so, they securely lock the entire heterotrimer, not just Gα, in its inactive state. Our results identify FR and YM as molecular glues for Gα and Gβγ that combine simultaneous binding to both subunits with inhibition of G protein signaling.We thank the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Project numbers 290827466/FOR2372 (Grants CR464/7-1 to M.C., KO 902/17-2 to G.M.K., 216619161 to G.S., 418513893 to X.D., 290847012 to E.K., and 494832089/GRK2873 to E.K. and L.J.), and the Swiss NSF—Project numbers 192780 (to X.D.) and 183563 (to G.S., under the Sinergia program) for funding. M.J.R. received funding from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie Grant agreement No. 701647. We thank the SLS beamline scientists for their support during crystallography data collection.Peer reviewe
The role of laminins in cancer pathobiology: a comprehensive review
No full textLaminins (LMs) are a family of heterotrimeric glycoproteins that form the structural foundation of basement membranes (BM). By acting as molecular bridges between cells and the extracellular matrix (ECM) through integrins and other surface receptors, they regulate key cellular signals that influence cell behavior and tissue architecture. Despite their physiological importance, our understanding of the role of LMs in cancer pathobiology remains fragmented. In this article, we review the diverse functions of LMs in promoting cancer cell proliferation, adhesion, and migration-critical steps in cancer metastasis. Beyond their direct effects on tumor cells, LMs influence stromal interactions and modulate tumor microenvironment dynamics, affecting processes such as angiogenesis, immune cell infiltration, cancer-associated fibroblast activation, and immune evasion. Understanding the complex roles of LMs in cancer biology, as well as their differential expression patterns in malignancies, could provide new diagnostic tools for predicting disease outcomes and pave the way for innovative therapeutic strategies, such as targeting LM-receptor interactions or modulating ECM dynamics to impede tumor growth and metastasis.The work was supported by the Spanish Ministry of Science, Innovation and Universities (MICIU/AEI/ https://doi.org/10.13039/501100011033 ) under grants PID2020-116303RB-I00, PID2023-147125OB-I00, EU Next Generation (EU/PRTR) CPP2021-009090, and CEX2023-001386-S (Severo Ochoa Programme); and the Asociación Española Contra el Cancer Foundation under grant PRYGN211240MA\u00D1E. Elena Nonnast is supported by a predoctoral fellowship from the Formaci\u00F3n de Personal Investigador (PRE2021-097603), from the Spanish Ministry of Science, Innovation and Universities with the support of the EU European Social Fund. SM belongs to the Spanish National Research Council (CSIC)\u2019s Cancer Hub.Peer reviewe
Tracing the biographies of textiles in the transition of medieval to modern times: Wool fabrics and brigandines from an Iberian castle
No full textFindings of archaeological textiles and fibres in Northern Iberia are extremely rare. The occurrence of a set of textile fragments, dated between the 14th and 16th centuries CE at the Pambre castle (Palas de Rei, Lugo, Spain) is exceptional. The original stone roof of the southeastern tower was intact. The dark, cold and moist conditions inside the tower favoured the preservation of a unique series of waterlogged textile remains. In addition, a set of pseudomorphs preserved by mineral replacement were recovered from the east edge of the north wing in the main hall of the castle. Fibres have been identified using optical and scanning electron microscopy (SEM), and they have been chemically characterised using Energy Dispersive X-Ray Spectroscopy (EDX). We also performed analytical pyrolysis-GC-MS (Py-GC-MS) and thermally assisted hydrolysis and methylation (THM-GC-MS) of the wool fabrics and pseudomorphs to assess their state of degradation and the presence of chemical markers associated to the use of these textile remains. High performance liquid chromatography with diode array detection (HPLC-DAD-MS) and ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS/MS) analysis were applied on wool fabrics to identify the chemical markers of dyes but without success. To expand the information related to raw material identification and the technical aspects of the fabrics, further evidence such as adherences identified as opal phytoliths, seeds, and insect remains associated to wool fabrics were examined. These findings offer a unique glimpse into the clothing dated to the end of the Medieval period, and its life-cycle. Wool scraps were probably part of at least two different garments, whereas the mineralised textiles probably formed part of at least two brigandines which were made of bast fibres, flax, or hemp.Los hallazgos de textiles y fibras arqueológicas en el norte de la península ibérica son extremadamente raros. La aparición de un conjunto de fragmentos textiles, datados entre los siglos XIV y XVI d.C. en el castillo de Pambre (Palas de Rei, Lugo, España), resulta excepcional. La cubierta original de piedra de la torre sureste se conservaba intacta, y las condiciones oscuras, frías y húmedas en su interior favorecieron la preservación de una serie única de restos textiles anegados. Además, se recuperaron pseudomorfos conservados por reemplazo mineral en el ala norte del salón principal. Las fibras fueron identificadas mediante microscopía óptica y electrónica de barrido (SEM), y caracterizadas químicamente con espectroscopía de rayos X de dispersión de energía (EDX). También se realizaron análisis de pirólisis analítica-GC-MS y metilación asistida térmicamente (THM-GC-MS) sobre los tejidos y pseudomorfos para evaluar su degradación y la presencia de marcadores químicos asociados a su uso. El análisis HPLC-DAD-MS y UHPLC-HRMS/MS en lanas no permitió identificar los tintes. Para ampliar la información sobre la materia prima y los aspectos técnicos de los tejidos, se examinaron adherencias identificadas como fitolitos de ópalo, semillas y restos de insectos asociados a las lanas. Estos hallazgos ofrecen una visión única sobre la indumentaria de finales de la Edad Media y su ciclo de vida. Los retales de lana formaron probablemente parte de al menos dos prendas distintas, mientras que los textiles mineralizados correspondían posiblemente a dos brigantinas confeccionadas con fibras de cáñamo, lino o fibras bastas
An Imidazolium Dication Affords a Stable UWY-like Zeolite and Enables a Subtle Structure Direction Towards EMM-17 [data]
No full textPeer reviewe
Functional insights of an uncommon hypomorphic variant in IL2RG as a monogenic cause of CVID-like disease with antibody deficiency and T CD4 lymphopenia
No full textThe Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fimmu.2025.1544863/full#supplementary-materialOver the last decade, the identification of hypomorphic variants in patients previously diagnosed with Common Variable Immunodeficiency (CVID) has led to the association of milder phenotypes with variants of the IL2RG gene that are usually related to severe combined immunodeficiency. Indeed, several revertant mosaicisms have been described in cases with hypomorphic variants in that gene. Our main objective herein was the functional characterization of p. (Pro58Thr) variant in the IL2RG gene in an adult patient with antibody deficiency and moderate CD4+ T cell lymphopenia.This study has been funded by the \u201CAyudas a la Investigacion Fundacion Mutua Madrile\u00F1a\u201D (AP180562022) and the Institutode Salud Carlos III (Carlos III Health Institute) (ISCIII) through project PI22/0157. LdP-M is supported by CIBERER (CB19-07-00042). AG-T is supported by the Instituto de Salud Carlos III (Carlos III Health Institute) (ISCIII) through project PI20/01371 and co-funded by the European Union. KR-Y was supported by the Fundaci\u00F3 Marat\u00F3 de TV3 (565/C/2021). AC-B is supported by the SEPE Programa Investigo funded by Next Generation UE. YS was supported by PEJD2019_PRE, cofinanced by the European Social Found through the Youth Employment Operational Program and the Youth Initiative (YEI) Comunidad de Madrid. The publication of this study has been funded by \u201CAyudas Luis \u00C1lvarez\u201D promoted by La Paz Institute for Health Research (IdiPAZ).Peer reviewe
A European Survey to Identify Challenges in the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease
No full text[Background and Aims]
Metabolic dysfunction-associated steatotic liver disease (MASLD) and its more severe subtype, metabolic dysfunction-associated steatohepatitis (MASH), are highly prevalent and strongly associated with obesity and type 2 diabetes (T2D). This study sought to identify challenges to the diagnosis, treatment and management of people living with MASLD and MASH and understand the key barriers to adopting relevant clinical guidelines.[Methods]
A real-world, cross-sectional study (BARRIERS-MASLD) consisting of a quantitative survey and qualitative interviews of physicians in France, Germany, Italy, Spain and the United Kingdom was conducted from March to September 2023. Descriptive statistics were used for data analysis.[Results]
A total of 626 physicians completed the survey; n = 10 from each country participated in the qualitative interviews. Physicians considered the presence of MASH to be highly impactful on how they treated people living with obesity (66%) and T2D (69%). Over one-third (35%) of the respondents could not identify any MASH-specific clinical guidelines issued by medical societies or associations top-of-mind, but overall awareness rose when prompted about country-specific guidelines. Physicians said they would need evidence of success (48%) and clinical guidelines that address common MASLD comorbidities (38%) to increase their adoption.[Conclusions]
This study found that lack of awareness around MASLD and MASH clinical guidelines and clearly established care pathways, particularly for addressing common comorbidities, was a key factor preventing physicians from optimising care for people living with MASH in Europe. This research highlights opportunities to improve education and training about clinical guidelines and care coordination.The authors wish to thank Stephanie Burkhead, MPH and Ladan Panahi, PharmD, for their medical writing support and Andrea Stoltz, MS, of KJT Group Inc. (Rochester, NY, USA) for data analysis and support, both of which were funded by Novo Nordisk.Peer reviewe
Chapter 2 - Evolution of analytical strategies in food sciences
No full textGreen chemistry and green analytical chemistry principles have promoted the development of environmentally friendly processes for the analysis of food samples, from sample preparation followed by extraction and characterization of target compounds. Particularly, predictive tools to select the best extraction solvent for the recovery of target compounds have contributed to massive time, solvent, and energy savings. Besides, the combination of green extraction solvents with advanced extraction techniques, the use of green separation techniques for—omics platforms, as well as the use of novel technologies for food analysis offers the opportunity to reduce energy consumption, the use of toxic solvents and unit operations, among other aspects. Moreover, the environmental impact of analytical processes employed can be quantified using green metric tools considering solvent use, energy consumption, waste generation, emissions, and the type of analytical technique selected. Despite the sophisticated methods for food analysis, the democratization of analytical chemistry makes it more accessible and simple and accelerates the evaluation of food safety, quality, and authenticity, facilitating knowledge sharing and public collaboration. In general, this chapter describes how food analysis has been slowly moving towards the implementation of green chemistry and green analytical chemistry principles.Peer reviewe
Quantitative study of ESBL and carbapenemase producers in wastewater treatment plants in Seville, Spain: a culture-based detection analysis of raw and treated water
No full textAntibiotics can modify populations of multidrug-resistant microorganism (MDRO) in urban wastewater. Our objectives were to quantify the differences in MDR Gram-negative bacteria between influents and effluents of WWTPs of a Spanish city and to evaluate the influence of human antibiotic prescriptions, as well as the persistence of these bacteria after treatment and their genetic relatedness to clinical isolates. The mean count of ESBL producers and carbapenemase producers were 3.77 and 2.74 log 10 CFU/ml, respectively. The reduction achieved by water treatment of ESBL-producing organisms was 1.4-log (96.11 %), whereas a 1.8-log reduction (98.36 %) was obtained regarding carbapenemase producing organisms. Aeromonas spp. predominated among MDROs and blaKPC-2 was the main carbapenemase detected in the influent wastewater samples. Among Escherichia coli and Klebsiella pneumoniae influent isolates, 44 % and 30 %, respectively, belonged to high-risk clones. Regarding Enterobacteriaceae, 10.6 % matched clinical isolates and one strain from an ongoing hospital outbreak was identified among raw samples. New MDROs and persistence of certain strains were detected in effluent samples. Quinolone and third-generation cephalosporin prescriptions, flow rate and population density were associated with higher OXA-48 producer counts. Despite reductions, additional technologies should be implemented in WWTPs receiving hospital discharges. Given the prevalence of environmental species, culture-based and metagenomic approaches should be combined to distinguish between human and sewage sources for antibiotic resistance monitoring. Overall, this study shows that WWTPs with secondary treatment are effective at removing MDRO, and antibiotic stewardship is a potential strategy to reduce the release of MDROs.This research was supported by PY20_01346 2020- I+D+i projects (PAIDI 2020 from Consejería de Universidad, Investigación e Innovación. 80 % financed by FEDER funds “Andalucía se mueve con Europa”) with the project title: “Proyecto Vastum: Detección de Gram negativos productores de carbapenemasas en aguas residuales: estudio poblacional de Sevilla y medición del impacto en vertidos”, and by the Fundación Francisco Soria Melguizo with the project title: “Nuevas estrategias para limitar la selección y transmisión de poblaciones microbianas productoras de carbapenemasas desde una perspectiva One-Health (MicroCarbaFlux, CC23140547)”.Peer reviewe