RESUMEN
This study highlights the substantially improved hydrothermal stability of 7-methyl-1,5,7-triazabicyclo[4.4.0] dec-5-enium [mTBDH]+ in [mTBDH][MeOCH2COO] compared to [mTBDH][OAc], as well as the strong cellulose dissolution capability of [mTBDH][MeOCH2COO] and excellent spinnability with a maximum draw ratio of 14. These findings demonstrate the high potential of using [mTBDH][MeOCH2COO] as the solvent to advance Ioncell fiber spinning technology by reducing the hydrolysis rate of [mTBDH]+, thereby minimizing loss during solvent recycling processes.
RESUMEN
Despite advancements in precision medicine, many cancer patients globally, particularly those in resource-constrained environments, face significant challenges in accessing high-quality molecular testing and targeted therapies. The considerable heterogeneity in molecular testing highlights the urgent need to harmonize practices across Europe and beyond, establishing a more standardized and consistent approach in MP laboratories. Professionals, especially molecular pathologists, must move beyond traditional education to cope with this heterogeneity. This perspective addresses critical issues in molecular pathology (MP), such as limited access to high-quality molecular testing, leading to disparities in cancer treatment, and the consequences of inconsistent practices. Recognizing the necessity for a standardized framework for education to address these issues, educational programs play a pivotal role in updating professionals' skills to achieve standardization in MP. European experts from the Steering Committee, the Pathology Section of the European Union of Medical Specialists, and the European Society of Pathology have proposed creating a comprehensive Master's degree program called the "European Masters in Molecular Pathology" (EMMP). This program emerges as a strategic response to the demand for a specialized and standardized framework for education in MP, catering to professionals who concurrently work and study. The program's design aligns with evidence-based education methods, ensuring effective learning and engagement while integrating computational pathology to analyze complex molecular data, enhance diagnostic accuracy, and improve treatment outcomes. EMMP's structured curriculum, strategic partnerships, and regular updates underscore its significance in standardizing MP practices. Exploring future developments, this perspective delves into technology integration and interdisciplinary collaboration, anticipating ongoing advances and harmonization. Challenges and future directions in MP education are discussed, emphasizing the necessity for dynamic curriculum updates, seamless technology integration, and interdisciplinary cooperation. This perspective underscores EMMP's pivotal role in preparing pathologists for this dynamic field, advocating continuous advancements in education and training to uphold excellence in MP practices and maintain the highest patient care standards.
Asunto(s)
Obesidad , Humanos , Obesidad/terapia , Obesidad/complicaciones , Diabetes Mellitus Tipo 2/terapiaRESUMEN
Estimated 20 % of global clean water pollution is attributed to textile production. Dyeing and finishing processes use an extensive amount of water and chemicals, and most of the effluents and wastewater is released into the environment. In this study, we explore spin-dyeing of man-made cellulosic fibres (MMCFs) with vat dyes using the Ioncell process, circumventing the ubiquitous use of fresh water and potentially reducing effluents streams to a great extent. Spin-dyeing is an established process for synthetic polymers but is not common for MMCFs. Regenerated cellulose fibres were produced through dissolution of dissolving pulp in the ionic liquid 1,5-diazabicyclo[4.3.0]non-5-ene acetate. The produced fibres were processed into yarn and a jersey fabric was knitted. Mechanical and colour fastness properties were tested. The fibres properties were also assessed through SEM, birefringence, and crystallinity measurements. Fibres with excellent mechanical properties (tenacity higher than 50 cN/tex) and colour fastness were produced, with most samples receiving the highest or next highest performance grade. The spun-dyed fibres also hold great potential to be recycled themselves without colour change or loss in colour intensity. Textiles with colours produced in large quantities such as black or navy blue could be the first market entry point.
RESUMEN
A combination of maleic acid and sodium hypophosphite as a durable press finishing agent has been reported as a safer but equally effective alternative to conventional formaldehyde-based cross-linking agents for applications in cellulose-based fiber and textile finishing. However, the mechanistic details of this system have not yet been fully elucidated to allow optimization of the conditions. Effective cross-linking treatment requires high curing temperatures of ≥160 °C, which enhances oxidative and thermal degradation of cellulose. In this work, the sequential steps of the cross-linking mechanism were investigated both with model compounds and cellulosic substrates. Extensive NMR studies on model compounds revealed several side reactions alongside the synthesis of the targeted cross-linkable moiety. As an alternative, to circumvent side reactions, a two-step procedure was used by synthesizing the cross-linker sodium 2-[(1,2-dicarboxyethyl)phosphinate]succinic acid in a well-defined pre-condensation reaction before application onto the cellulosic substrate. Further, the effect of the cross-linking treatment on the molecular weight distribution of cellulose was studied by gel permeation chromatography, which showed degradation due to maleic acid/sodium hypophosphite treatment. By using sodium 2-[(1,2-dicarboxyethyl)phosphinate]succinic acid and sodium hypophosphite, this degradation could be significantly limited.
RESUMEN
In the early phase of the COVID-19 pandemic, many local collections of clinical data on patients infected with SARS-CoV-2 were initiated in Germany. As part of the National Pandemic Cohort Network (NAPKON) of the University Medicine Network, the "Integration Core" was established to design the legal, technical and organisational requirements for the integration of inventory data into ongoing prospective data collections and to test the feasibility of the newly developed solutions using use cases (UCs). Detailed study documents of the data collections were obtained. After structured document analysis, a review board evaluated the integrability of the data in NAPKON according to defined criteria. Of 30 university hospitals contacted, 20 responded to the request. Patient information and consent showed a heterogeneous picture with regard to the pseudonymised transfer of data to third parties and re-contact. The majority of the data collections (n=13) met the criteria for integration into NAPKON; four studies would require adjustments to the regulatory documents. Three cohorts were not suitable for inclusion in NAPKON. The legal framework for retrospective data integration and consent-free data use via research clauses (§27 BDSG) was elaborated by a legal opinion by TMF - Technology, Methods and Infrastructure for Networked Medical Research, Berlin. Two UCs selected by the NAPKON steering committee (CORKUM, LMU Munich; Pa-COVID-19, Charité- Universitätsmedizin Berlin) were used to demonstrate the feasibility of data integration in NAPKON by the end of 2021. Quality assurance and performance-based reimbursement of the cases were carried out according to the specifications. Based on the results, recommendations can be formulated for various contexts in order to create technical-operational prerequisites such as interoperability, interfaces and data models for data integration and to fulfil regulatory requirements on ethics, data protection, medical confidentiality and data access when integrating existing cohort data. The possible integration of data into research networks and their secondary use should be taken into account as early as the planning phase of a study - particularly with regard to informed consent - in order to maximise the benefits of the data collected.
Asunto(s)
COVID-19 , Pandemias , Sistema de Registros , Alemania , COVID-19/epidemiología , Humanos , Estudios de Cohortes , SARS-CoV-2 , Recolección de DatosRESUMEN
In the quest for greener and more efficient energy storage solutions, the exploration and utilization of renewable raw materials is essential. In this context, cellulose-derived separators play a central role in enhancing the performance of green energy storage devices. However, these often exhibit disadvantageous porosity and limited wet strength. Here, we demonstrate a facile approach to tailor thickness (ca. 40 µm), air permeability (0.1-200 cm3 s-1), and mechanical properties of separators by integration of up to 50 wt% microfibrillated cellulose (MFC) into paper sheets. While the MFC enhanced the formation of dense networks, these separators show a poor dimensional stability (folding and creasing) concomitant with a low strength under wet conditions, crucial for assembly and operation. Crosslinking with 1,2,3,4-butanetetracarboxylic acid (BTCA) however, led to an increase in wet strength by up to 6700 % while ensuring dimensional stability. The electrochemical performance, evaluated by impedance spectroscopy and galvanostatic cycling (7500 repetitions) showed comparable results as commercially available glass and polypropylene separators in terms of ion diffusion, charge-discharge rate performance, Ohmic loss and capacitance retention %. The approach demonstrates that disadvantages of paper-based separators in terms of dimensional stability and wet strength can be overcome by a paper technological approach using crosslinking strategies.
RESUMEN
BACKGROUND: This study outlines the development of a highly interoperable federated IT infrastructure for academic biobanks located at the major university hospital sites across Germany. High-quality biosamples linked to clinical data, stored in biobanks are essential for biomedical research. We aimed to facilitate the findability of these biosamples and their associated data. Networks of biobanks provide access to even larger pools of samples and data even from rare diseases and small disease subgroups. The German Biobank Alliance (GBA) established in 2017 under the umbrella of the German Biobank Node (GBN), has taken on the mission of a federated data discovery service to make biosamples and associated data available to researchers across Germany and Europe. METHODS: In this context, we identified the requirements of researchers seeking human biosamples from biobanks and the needs of biobanks for data sovereignty over their samples and data in conjunction with the sample donor's consent. Based on this, we developed a highly interoperable federated IT infrastructure using standards such as Fast Healthcare Interoperability Resources (HL7 FHIR) and Clinical Quality Language (CQL). RESULTS: The infrastructure comprises two major components enabling federated real-time access to biosample metadata, allowing privacy-compliant queries and subsequent project requests. It has been in use since 2019, connecting 16 German academic biobanks, with additional European biobanks joining. In production since 2019 it has run 4941 queries over the span of one year on more than 900,000 biosamples collected from more than 170,000 donors. CONCLUSION: This infrastructure enhances the visibility and accessibility of biosamples for research, addressing the growing demand for human biosamples and associated data in research. It also underscores the need for improvements in processes beyond IT infrastructure, aiming to advance biomedical research and similar infrastructure development in other fields.
Asunto(s)
Bancos de Muestras Biológicas , Humanos , Europa (Continente) , Alemania , Investigación Biomédica , Bases de Datos FactualesRESUMEN
Jute is an inherent lignocellulosic fiber, consisting of hemicellulose, α-cellulose, and lignin. Industrial ventilation, automotive composites, upholstery, carpets, military uniforms, hospital furnishings, and curtains necessitate the integration of flame-retardance properties into jute fibers. In this investigation, seven weave-structured jute fabrics were treated using an organophosphorus-based flame-retardant (FR) chemical (ITOFLAM CPN) and a crosslinking agent (KNITTEX CHN) by the pad-dry-cure method. The thermal stability, degradation and pyrolysis behavior of jute was measured using a thermogravimetric analyzer (TGA). Surface morphology and element distribution were scrutinized utilizing a scanning electron microscope (SEM) and an energy-dispersive spectrometer (EDS). The ATR-FTIR (Attenuated Total Reflection-Fourier Transform Infrared Spectrometer) technique has been employed for analyzing the composition of chemicals in the jute fabrics. According to the protocols specified in ISO 14184-1, free formaldehyde detection was carried out on the jute fabrics. The flame-retardance property was significantly improved on all of the jute fabrics after FR treatment. FTIR and SEM-EDS studies revealed the presence of FR chemical deposition on the surface of the jute fabrics. TGA analysis indicated that the fabrics treated with FR exhibited premature degradation, leading to the generation of more char compared to untreated samples. The jute fabrics specifically demonstrated a notable enhancement in residual mass, exceeding 50% after FR treatment. However, it is noteworthy that the FR-treated fabrics exhibited an elevated level of free formaldehyde content, surpassing the permissible limit of formaldehyde in textiles intended for direct skin contact. The residual mass loss percentage after ten washes of FR-treated fabrics remained in a range from 32% to 36%. Twill weave designed fabrics (FRD4 and FRD5) clearly showed a lower thermal degradation temperature than the other weaves used in this study.
RESUMEN
Currently the textile industry relies strongly on synthetic fibres and cotton, which contribute to many environmental problems. Man-made cellulosic fibres (MMCF) can offer sustainable alternatives. Herein, the development of Lyocell-type MMCF using bacterial cellulose (BC) as alternative raw material in the Ioncell® spinning process was investigated. BC, known for its high degree of polymerization (DP), crystallinity and strength was successfully dissolved in the ionic liquid (IL) 1,5-diazabicyclo[4.3.0]non-5-enium acetate [DBNH][OAc] to produce solutions with excellent spinnability. BC staple fibres displayed good mechanical properties and crystallinity (CI) and were spun into a yarn which was knitted into garments, demonstrating the potential of BC as suitable cellulose source for textile production. BC is also a valuable additive when recycling waste cellulose textiles (viscose fibres). The high DP and Cl of BC enhanced the spinnability in a viscose/BC blend, consequently improving the mechanical performance of the resulting fibres, as compared to neat viscose fibres.
Asunto(s)
Celulosa , Textiles , Celulosa/química , Bacterias , Líquidos Iónicos/química , Industria TextilRESUMEN
PURPOSE: Poly(ADP-ribose) polymerase inhibitors (PARPi) have shown promising clinical results in the treatment of ovarian cancer. Analysis of biomarker subgroups consistently revealed higher benefits for patients with homologous recombination deficiency (HRD). The test that is most often used for the detection of HRD in clinical studies is the Myriad myChoice assay. However, other assays can also be used to assess biomarkers, which are indicative of HRD, genomic instability (GI), and BRCA1/2 mutation status. Many of these assays have high potential to be broadly applied in clinical routine diagnostics in a time-effective decentralized manner. Here, we compare the performance of a multitude of alternative assays in comparison with Myriad myChoice in high-grade serous ovarian cancer (HGSOC). METHODS: DNA from HGSOC samples was extracted from formalin-fixed paraffin-embedded tissue blocks of cases previously run with the Myriad myChoice assay, and GI was measured by multiple molecular assays (CytoSNP, AmoyDx, Illumina TSO500 HRD, OncoScan, NOGGO GISv1, QIAseq HRD Panel and whole genome sequencing), applying different bioinformatics algorithms. RESULTS: Application of different assays to assess GI, including Myriad myChoice, revealed high concordance of the generated scores ranging from very substantial to nearly perfect fit, depending on the assay and bioinformatics pipelines applied. Interlaboratory comparison of assays also showed high concordance of GI scores. CONCLUSION: Assays for GI assessment not only show a high concordance with each other but also in correlation with Myriad myChoice. Thus, almost all of the assays included here can be used effectively to assess HRD-associated GI in the clinical setting. This is important as PARPi treatment on the basis of these tests is compliant with European Medicines Agency approvals, which are methodologically not test-bound.
Asunto(s)
Proteína BRCA1 , Neoplasias Ováricas , Humanos , Femenino , Proteína BRCA1/genética , Mutación , Proteína BRCA2/genética , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/genética , Neoplasias Ováricas/tratamiento farmacológico , Inestabilidad Genómica/genética , Recombinación Homóloga/genéticaRESUMEN
The 9th Cardiovascular Outcome Trial (CVOT) Summit: Congress on Cardiovascular, Kidney, and Metabolic Outcomes was held virtually on November 30-December 1, 2023. This reference congress served as a platform for in-depth discussions and exchange on recently completed outcomes trials including dapagliflozin (DAPA-MI), semaglutide (SELECT and STEP-HFpEF) and bempedoic acid (CLEAR Outcomes), and the advances they represent in reducing the risk of major adverse cardiovascular events (MACE), improving metabolic outcomes, and treating obesity-related heart failure with preserved ejection fraction (HFpEF). A broad audience of endocrinologists, diabetologists, cardiologists, nephrologists and primary care physicians participated in online discussions on guideline updates for the management of cardiovascular disease (CVD) in diabetes, heart failure (HF) and chronic kidney disease (CKD); advances in the management of type 1 diabetes (T1D) and its comorbidities; advances in the management of CKD with SGLT2 inhibitors and non-steroidal mineralocorticoid receptor antagonists (nsMRAs); and advances in the treatment of obesity with GLP-1 and dual GIP/GLP-1 receptor agonists. The association of diabetes and obesity with nonalcoholic steatohepatitis (NASH; metabolic dysfunction-associated steatohepatitis, MASH) and cancer and possible treatments for these complications were also explored. It is generally assumed that treatment of chronic diseases is equally effective for all patients. However, as discussed at the Summit, this assumption may not be true. Therefore, it is important to enroll patients from diverse racial and ethnic groups in clinical trials and to analyze patient-reported outcomes to assess treatment efficacy, and to develop innovative approaches to tailor medications to those who benefit most with minimal side effects. Other keys to a successful management of diabetes and comorbidities, including dementia, entail the use of continuous glucose monitoring (CGM) technology and the implementation of appropriate patient-physician communication strategies. The 10th Cardiovascular Outcome Trial Summit will be held virtually on December 5-6, 2024 ( http://www.cvot.org ).
Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Insuficiencia Cardíaca , Insuficiencia Renal Crónica , Humanos , Insuficiencia Cardíaca/complicaciones , Automonitorización de la Glucosa Sanguínea , Volumen Sistólico , Glucemia , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Obesidad/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/terapia , Diabetes Mellitus/tratamiento farmacológico , Riñón , Diabetes Mellitus Tipo 2/tratamiento farmacológicoRESUMEN
Even small amounts of elastane in cotton-elastane blended textiles can prevent fiber-to-fiber recycling strategies in textile recycling. Herein, the selective separation of elastane from cotton blends was addressed by the aminolytic degradation of the synthetic component. Polar aprotic solvents were tested as elastane solvents, but side reactions impeded aminolysis with some of them. Aminolysis of elastane succeeded under mild conditions using dimethyl sulfoxide in combination with diethylenetriamine and 1,5-diazabicyclo[4.3.0]non-5-ene as a cleaving agent and catalyst, respectively. The analysis of the nitrogen content in the recovered cellulose fraction demonstrated that 2 h of reaction at 80 °C reduced the elastane content to values lower than 0.08%. The characterization of the recovered cellulose showed that the applied conditions did not affect the macromolecular properties of cellulose and maintained a cellulose I crystal structure. Degraded elastane products were recovered through precipitation with water. Finally, the cellulosic component was turned into new fibers by dry-jet wet spinning with excellent tensile properties.
Asunto(s)
Fibra de Algodón , Textiles , Reciclaje , Solventes , Celulosa/químicaRESUMEN
Valorization of the lignocellulosic side and waste streams is key to making industrial processes more efficient from both an economic and ecological perspective. Currently, the production of sugars from beets results in pulps in large quantities. However, there is a lack of promising opportunities for upcycling these materials despite their promising properties. Here, we investigate beet pulps from two different stages of the sugar manufacturing process as raw materials for supercapacitor electrodes. We demonstrate that these materials can be efficiently converted to activated, highly porous carbons. The carbons exhibit pore dimensions approaching the size of the desolvated K+ and SO42- ions with surface areas up to 2600 m2 g-1. These carbons were subsequently manufactured into electrodes, assembled in supercapacitors, and tested with environmentally friendly aqueous electrolytes (6 M KOH and 1 M H2SO4). Further analysis demonstrated the presence of capacitance-enhancing functionalities, and up to 193 and 177 F g-1 in H2SO4 and KOH, respectively, were achieved, which outperformed supercapacitors prepared from commercial YP80 F. Overall, our study suggests that side streams from sugar manufacturing offer a hidden potential for use in high-performance energy storage devices.
RESUMEN
Introduction: Somatostatin analogues (SSAs) are commonly used in the treatment of hormone hypersecretion in neuroendocrine tumors (NETs), however the extent to which they inhibit proliferation is much discussed. Objective: We studied the antiproliferative effects of novel SSA lanreotide in bronchopulmonary NETs (BP-NETs). We focused on assessing whether pretreating cells with inhibitors for phosphatidylinositol 3-kinase (PI3K) and mammalian target for rapamycin (mTOR) could enhance the antiproliferative effects of lanreotide. Methods: BP-NET cell lines NCI-H720 and NCI-H727 were treated with PI3K inhibitor BYL719 (alpelisib), mTOR inhibitor everolimus and SSA lanreotide to determine the effect on NET differentiation markers, cell survival, proliferation and alterations in cancer-associated pathways. NT-3 cells, previously reported to express somatostatin receptors (SSTRs) natively, were used as control for SSTR expression. Results: SSTR2 was upregulated in NCI-H720 and NT-3 cells upon treatment with BYL719. Additionally, combination treatment consisting of BYL719 and everolimus plus lanreotide tested in NCI-H720 and NCI-H727 led to diminished cell proliferation in a dose-dependent manner. Production of proteins activating cell death mechanisms was also induced. Notably, a multiplexed gene expression analysis performed on NCI-H720 revealed that BYL719 plus lanreotide had a stronger effect on the downregulation of mitogens than lanreotide alone. Discussion/Conclusion: We report a widespread analysis of changes in BP-NET cell lines at the genetic/protein expression level in response to combination of lanreotide with pretreatment consisting of BYL719 and everolimus. Interestingly, SSTR expression reinduction could be exploited in therapeutic and diagnostic applications. The overall results of this study support the evaluation of combination-based therapies using lanreotide in preclinical studies to further increase its antiproliferative effect and ultimately facilitate its use in high-grade tumors.
RESUMEN
In high-income countries, mosaic chromosomal alterations in peripheral blood leukocytes are associated with an elevated risk of adverse health outcomes, including hematologic malignancies. We investigate mosaic chromosomal alterations in sub-Saharan Africa among 931 children with Burkitt lymphoma, an aggressive lymphoma commonly characterized by immunoglobulin-MYC chromosomal rearrangements, 3822 Burkitt lymphoma-free children, and 674 cancer-free men from Ghana. We find autosomal and X chromosome mosaic chromosomal alterations in 3.4% and 1.7% of Burkitt lymphoma-free children, and 8.4% and 3.7% of children with Burkitt lymphoma (P-values = 5.7×10-11 and 3.74×10-2, respectively). Autosomal mosaic chromosomal alterations are detected in 14.0% of Ghanaian men and increase with age. Mosaic chromosomal alterations in Burkitt lymphoma cases include gains on chromosomes 1q and 8, the latter spanning MYC, while mosaic chromosomal alterations in Burkitt lymphoma-free children include copy-neutral loss of heterozygosity on chromosomes 10, 14, and 16. Our results highlight mosaic chromosomal alterations in sub-Saharan African populations as a promising area of research.
Asunto(s)
Linfoma de Burkitt , Masculino , Niño , Humanos , Linfoma de Burkitt/genética , Linfoma de Burkitt/patología , Ghana , Aberraciones Cromosómicas , Leucocitos/patología , Inmunoglobulinas/genética , Translocación GenéticaRESUMEN
Introduction: Diabetes technology improves glycemic control and quality of life for many people with type 1 diabetes (T1D). However, inequalities in access to diabetes technology exist in many countries. In Germany, disparities in technology use have been described in pediatric T1D, but no data for adults are available so far. We therefore aimed to analyze whether demographic factors and area deprivation are associated with technology use in a representative population of adults with T1D. Materials and methods: In adults with T1D from the German prospective diabetes follow-up registry (DPV), we analyzed the use of continuous subcutaneous insulin infusion (CSII), continuous glucose monitoring (CGM), and sensor augmented pump therapy (SAP, with and without automated insulin delivery) in 2019-2021 by age group, gender, migration background, and area deprivation using multiple adjusted regression models. Area deprivation, defined as a relative lack of area-based resources, was measured by quintiles of the German index of Multiple Deprivation (GIMD 2015, from Q1, least deprived, to Q5, most deprived districts). Results: Among 13,351 adults with T1D, the use of technology decreased significantly with older age: CSII use fell from 56.1% in the 18-<25-year age group to 3.1% in the ≥80-year age group, CGM use from 75.3% to 28.2%, and SAP use from 45.1% to 1.5% (all p for trend <0.001). The use of technology was also significantly higher in women than in men (CSII: 39.2% vs. 27.6%; CGM: 61.9% vs. 58.0%; SAP: 28.7% vs. 19.6%, all p <0.001), and in individuals without migration background than in those with migration background (CSII: 38.8% vs. 27.6%; CGM: 71.1% vs. 61.4%; SAP: 30.5% vs. 21.3%, all p <0.001). Associations with area deprivation were not linear: the use of each technology decreased only from Q2 to Q4. Discussion: Our real-world data provide evidence that higher age, male gender, and migration background are currently associated with lower use of diabetes technology in adults with T1D in Germany. Associations with area deprivation are more complex, probably due to correlations with other factors, like the higher proportion of migrants in less deprived areas or the federal structure of the German health care system.
Asunto(s)
Diabetes Mellitus Tipo 1 , Adulto , Femenino , Masculino , Humanos , Niño , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/epidemiología , Automonitorización de la Glucosa Sanguínea , Estudios Prospectivos , Calidad de Vida , Glucemia , Insulina , Alemania/epidemiología , TecnologíaRESUMEN
Recent exome-wide studies discovered frequent somatic mutations in the epigenetic modifier ZNF217 in primary mediastinal B cell lymphoma (PMBCL) and related disorders. As functional consequences of ZNF217 alterations remain unknown, we comprehensively evaluated their impact in PMBCL. Targeted sequencing identified genetic lesions affecting ZNF217 in 33% of 157 PMBCL patients. Subsequent gene expression profiling (n = 120) revealed changes in cytokine and interferon signal transduction in ZNF217-aberrant PMBCL cases. In vitro, knockout of ZNF217 led to changes in chromatin accessibility interfering with binding motifs for crucial lymphoma-associated transcription factors. This led to disturbed expression of interferon-responsive and inflammation-associated genes, altered cell behavior, and aberrant differentiation. Mass spectrometry demonstrates that ZNF217 acts within a histone modifier complex containing LSD1, CoREST and HDAC and interferes with H3K4 methylation and H3K27 acetylation. Concluding, our data suggest non-catalytic activity of ZNF217, which directs histone modifier complex function and controls B cell differentiation-associated patterns of chromatin structure.
Asunto(s)
Histonas , Linfoma de Células B , Humanos , Histonas/metabolismo , Transactivadores/metabolismo , Interferones/genética , Línea Celular Tumoral , Mutación , Transducción de Señal/genética , Cromatina/genética , Linfoma de Células B/genéticaRESUMEN
The reaction of reducing end groups in cellulose nanocrystals with dodecylamine was examined. Using a direct-dissolution solution-state NMR protocol, the regioselective formation of glucosylamines was shown. This provides an elegant approach to sustainably functionalize these bio-based nanomaterials, that may not require further reduction to more stable secondary amines.