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1.
Microorganisms ; 12(3)2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38543628

ABSTRACT

Vitis vinifera, an economically significant grapevine species, is known for wine, juice, and table grape production. The berries of wine grapes host a diverse range of microorganisms influencing both grapevine health and the winemaking process. Indigenous to Greece, the emblematic variety Assyrtiko, renowned for high-quality white wines, originated from Santorini and spread to various Greek regions. Despite existing studies on the microbiota of several varieties, the carposphere microbiota of Assyrtiko grapes remains unexplored. Thus, we conducted a spatiotemporal metagenomic study to identify the epiphytic microbial community composition of Assyrtiko grapes. The study was conducted in two consecutive vintage years (2019 and 2020) across three different and distinct viticulture regions in Greece (Attica, Thessaloniki, Evros). We performed amplicon sequencing, targeting the 16S rRNA gene for bacteria and the ITS region for fungi, with subsequent comprehensive bioinformatic analysis. Our data indicate that the distribution and relative abundance of the epiphytic carposphere microbial communities of the Assyrtiko variety are shaped both by vintage and biogeography.

2.
BMC Nurs ; 23(1): 96, 2024 Feb 06.
Article in English | MEDLINE | ID: mdl-38321491

ABSTRACT

BACKGROUND: Nurses play an important role in interprofessional pharmaceutical care. Curricula related to pharmaceutical care, however, vary a lot. Mapping the presence of pharmaceutical care related domains and competences in nurse educational programs can lead to a better understanding of the extent to which curricula fit expectations of the labour market. The aim of this study was to describe 1) the presence of pharmaceutical care oriented content in nursing curricula at different educational levels and 2) nursing students' perceived readiness to provide nurse pharmaceutical care in practice. METHODS: A quantitative cross-sectional survey design was used. Nursing schools in 14 European countries offering educational programs for levels 4-7 students were approached between January and April 2021. Through an online survey final year students had to indicate to what extent pharmaceutical care topics were present in their curriculum. RESULTS: A total of 1807 students participated, of whom 8% had level 4-5, 80% level 6, 12% level 7. Up to 84% of the students indicated that pharmaceutical care content was insufficiently addressed in their curriculum. On average 14% [range 0-30] felt sufficiently prepared to achieve the required pharmaceutical care competences in practice. In level 5 curricula more pharmaceutical care domains were absent compared with other levels. CONCLUSIONS: Although several pharmaceutical care related courses are present in current curricula of level 4-7 nurses, its embedding should be extended. Too many students perceive an insufficient preparation to achieve pharmaceutical care competences required in practice. Existing gaps in pharmaceutical care should be addressed to offer more thoroughly prepared nurses to the labour market.

3.
Nurs Rep ; 13(4): 1500-1510, 2023 Oct 25.
Article in English | MEDLINE | ID: mdl-37987405

ABSTRACT

Breast cancer is the most common cancer in women. Cardiovascular diseases are common complications after chemotherapy due to the effect of the drug on lipid levels. This study aimed to explore the changes in lipid profiles in patients with breast cancer under chemotherapy. METHODS: In this prospective study, 50 patients with breast cancer participated. Three biochemical-lipid hematological tests were performed: total cholesterol (TC), triglycerides (TGs), High-Density Lipoprotein (HDL-C), and Low-Density Lipoprotein (LDL-C) before initiation (pre-chemotherapy), at the start (first follow-up), and at the completion (second follow-up) of the first cycle of chemotherapy. Statistical significance was set at p < 0.05. Analyses were conducted using SPSS Statistical Software (version 22.0). RESULTS: Mean TC values increased significantly at second follow-up. TGs values decreased significantly from first to second follow-up. HDL-C was significantly lower at first follow-up compared with pre-chemotherapy and was similar to the pre-chemotherapy levels at second follow-up. LDL-C values were significantly higher at second follow-up compared with pre-chemotherapy measurement. Significantly positive correlations of BMI with pre-chemotherapy LDL-C, first follow-up TC, first follow-up LDL-C, second follow-up TC, and second follow-up LDL-C were found. CONCLUSIONS: There is a statistically significant increase in the levels of TC and LDL-C in breast cancer patients during chemotherapy. This study was not registered.

4.
Biol Psychiatry ; 2023 Feb 02.
Article in English | MEDLINE | ID: mdl-36738982

ABSTRACT

BACKGROUND: Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder of complex genetic architecture and is characterized by multiple motor tics and at least one vocal tic persisting for more than 1 year. METHODS: We performed a genome-wide meta-analysis integrating a novel TS cohort with previously published data, resulting in a sample size of 6133 individuals with TS and 13,565 ancestry-matched control participants. RESULTS: We identified a genome-wide significant locus on chromosome 5q15. Integration of expression quantitative trait locus, Hi-C (high-throughput chromosome conformation capture), and genome-wide association study data implicated the NR2F1 gene and associated long noncoding RNAs within the 5q15 locus. Heritability partitioning identified statistically significant enrichment in brain tissue histone marks, while polygenic risk scoring of brain volume data identified statistically significant associations with right and left thalamus volumes and right putamen volume. CONCLUSIONS: Our work presents novel insights into the neurobiology of TS, thereby opening up new directions for future studies.

5.
Front Biosci (Elite Ed) ; 14(4): 31, 2022 12 02.
Article in English | MEDLINE | ID: mdl-36575848

ABSTRACT

BACKGROUND: Cheese microbiome plays a key role in determining the organoleptic and physico-chemical properties and may be also used as an authenticity tool for distinguishing probiotic cultures. Due to significant reduction of cell viability often witnessed during food production processes and storage, immobilization is proposed to ascertain high probiotic cell loads required to confer the potential health benefits. Hence, the aim of the present study was to investigate the effect of free or immobilized Lactiplantibacillus plantarum T571 on whey protein on feta cheese microbiome. METHODS: Next-Generation Sequencing technology was used to investigate cheese microbiome. Cheese samples containing free or immobilized Lactiplantibacillus plantarum T571 (a wild type strain isolated from Feta cheese brine) on whey protein, along with products containing commercial starter culture, were analyzed. RESULTS: The results showed a great diversity of bacteria and fungi genera among the samples. An increased presence of Lactobacillus OTUs in cheese with immobilized cells on whey protein was witnessed, highlighting the survival of the strain in the final product. The immobilized culture had also a significant impact on other genera, such as Lactococcus, Leuconostoc and Debaryomyces, which are associated with improved technological characteristics and health benefits. CONCLUSIONS: Enrichment of feta cheese with immobilized potential probiotics to secure cell viability consists of an industrial challenge and leads to distinct microbiome composition that may be used as a valuable food authenticity tool.


Subject(s)
Cheese , Cheese/analysis , Cheese/microbiology , Whey Proteins , Food Handling/methods
6.
Nurse Educ Pract ; 65: 103485, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36334523

ABSTRACT

BACKGROUND: Safe pharmaceutical care requires competent nurses with specific knowledge, skills and attitudes. It is unclear whether nursing students are adequately prepared to perform pharmaceutical care in practice. Mapping their pharmaceutical care competences can lead to a better understanding of the extent to which curricula fit expectations of the labour market. OBJECTIVES: To assess pharmaceutical care competences of final-year nursing students of different educational levels. DESIGN: A cross-sectional survey design. SETTINGS: In 14 European countries, nursing schools who offer curricula for level 4 to 7 students were approached. PARTICIPANTS: Through convenience sampling 1741 final-year student nurses of level 4 to 7 were included. Sampling strategies were country-specific. METHODS: A web-platform was developed with an assessment of the level in which students mastered pharmaceutical care competences. Knowledge questions, case studies (basic/advanced level), self-reported practical skills and attitudes were evaluated. RESULTS: Mean scores for knowledge questions differed significantly (p < 0.001) between level 5 (56/100), level 6 (68/100) and level 7 students (72/100). For basic cases level 5 students reached lower scores (64/100) compared with level 6 (71/100) and level 7 (72/100) students (p = 0.002 and p = 0.005). For more advanced cases no difference between levels was observed (overall mean 61/100). Most students (63-90 %) considered themselves skilled to perform pharmaceutical care and had positive attitudes towards their participation in pharmaceutical care (65-97 %). CONCLUSIONS: Relatively low knowledge scores were calculated for final-year student nurses. In some domains, lower levels of students might be insufficiently prepared to take up responsibilities in pharmaceutical care. Our assessment can be used as a tool for educators to evaluate how prepared nursing students are for pharmaceutical care. Its further implementation for students of different educational levels will allow benchmarking between the levels, both within and between countries.


Subject(s)
Education, Nursing, Baccalaureate , Pharmaceutical Services , Students, Nursing , Humans , Cross-Sectional Studies , Surveys and Questionnaires , Europe
7.
Cancers (Basel) ; 14(20)2022 Oct 14.
Article in English | MEDLINE | ID: mdl-36291831

ABSTRACT

Transcription Factors (TFs) are the main regulators of gene expression, controlling among others cell homeostasis, identity, and fate. TFs may either act synergistically or antagonistically on nearby regulatory elements and their interplay may activate or repress gene expression. The family of NF-κB TFs is among the most important TFs in the regulation of inflammation, immunity, and stress-like responses, while they also control cell growth and survival, and are involved in inflammatory diseases and cancer. The family of E2F TFs are major regulators of cell cycle progression in most cell types. Several studies have suggested the interplay between these two TFs in the regulation of numerous genes controlling several biological processes. In the present study, we compared the genomic binding landscape of NF-κB RelA/p65 subunit and E2F1 TFs, based on high throughput ChIP-seq and RNA-seq data in different cell types. We confirmed that RelA/p65 has a binding profile with a high preference for distal enhancers bearing active chromatin marks which is distinct to that of E2F1, which mostly generates promoter-specific binding. Moreover, the RelA/p65 subunit and E2F1 cistromes have limited overlap and tend to bind chromatin that is in an active state even prior to immunogenic stimulation. Finally, we found that a fraction of the E2F1 cistrome is recruited by NF-κΒ near pro-inflammatory genes following LPS stimulation in immune cell types.

8.
Front Microbiol ; 13: 922689, 2022.
Article in English | MEDLINE | ID: mdl-35783439

ABSTRACT

The Lacticaseibacillus paracasei species is comprised by nomadic bacteria inhabiting a wide variety of ecological niches, from fermented foodstuffs to host-associated microenvironments. Lc. paracasei SP5 is a novel strain, originally isolated from kefir grains that presents desirable probiotic and biotechnological attributes. In this study, we applied genomic tools to further characterize the probiotic and biotechnological potential of the strain. Firstly, whole genome sequencing and assembly, were performed to construct the chromosome map of the strain and determine its genomic stability. Lc. paracasei SP5 carriers several insertion sequences, however, no plasmids or mobile elements were detected. Furthermore, phylogenomic and comparative genomic analyses were utilized to study the nomadic attributes of the strain, and more specifically, its metabolic capacity and ability to withstand environmental stresses imposed during food processing and passage through the gastrointestinal (GI) tract. More specifically, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Carbohydrate-active enzyme (CAZymes) analyses provided evidence for the ability of the stain to utilize an array of carbohydrates as growth substrates. Consequently, genes for heat, cold, osmotic shock, acidic pH, and bile salt tolerance were annotated. Importantly bioinformatic analysis showed that the novel strain does not harbor acquired antimicrobial resistance genes nor virulence factors, in agreement with previous experimental data. Putative bacteriocin biosynthesis clusters were identified using BAGEL4, suggesting its potential antimicrobial activity. Concerning microbe-host interactions, adhesins, moonlighting proteins, exopolysaccharide (EPS) biosynthesis genes and pilins mediating the adhesive phenotype were, also, pinpointed in the genome of Lc. paracasei SP5. Validation of this phenotype was performed by employing a microbiological method and confocal microscopy. Conclusively, Lc. paracasei SP5 harbors genes necessary for the manifestation of the probiotic character and application in the food industry. Upcoming studies will focus on the mechanisms of action of the novel strain at multiple levels.

9.
Front Pediatr ; 10: 881287, 2022.
Article in English | MEDLINE | ID: mdl-35615634

ABSTRACT

Congenital diaphragmatic hernia is a structural birth defect of the diaphragm, with lung hypoplasia and persistent pulmonary hypertension. Aside from vascular defects, the lungs show a disturbed balance of differentiated airway epithelial cells. The Sry related HMG box protein SOX2 is an important transcription factor for proper differentiation of the lung epithelium. The transcriptional activity of SOX2 depends on interaction with other proteins and the identification of SOX2-associating factors may reveal important complexes involved in the disturbed differentiation in CDH. To identify SOX2-associating proteins, we purified SOX2 complexes from embryonic mouse lungs at 18.5 days of gestation. Mass spectrometry analysis of SOX2-associated proteins identified several potential candidates, among which were the Chromodomain Helicase DNA binding protein 4 (CHD4), Cut-Like Homeobox1 (CUX1), and the Forkhead box proteins FOXP2 and FOXP4. We analyzed the expression patterns of FOXP2, FOXP4, CHD4, and CUX1 in lung during development and showed co-localization with SOX2. Co-immunoprecipitations validated the interactions of these four transcription factors with SOX2, and large-scale chromatin immunoprecipitation (ChIP) data indicated that SOX2 and CHD4 bound to unique sites in the genome, but also co-occupied identical regions, suggesting that these complexes could be involved in co-regulation of genes involved in the respiratory system.

10.
Biomedicines ; 9(11)2021 Nov 19.
Article in English | MEDLINE | ID: mdl-34829947

ABSTRACT

Lactiplantibacillus plantarum is a diverse species that includes nomadic strains isolated from a variety of environmental niches. Several L. plantarum strains are being incorporated in fermented foodstuffs as starter cultures, while some of them have also been characterized as probiotics. In this study, we present the draft genome sequence of L. plantarum L125, a potential probiotic strain presenting biotechnological interest, originally isolated from a traditional fermented meat product. Phylogenetic and comparative genomic analysis with other potential probiotic L. plantarum strains were performed to determine its evolutionary relationships. Furthermore, we located genes involved in the probiotic phenotype by whole genome annotation. Indeed, genes coding for proteins mediating host-microbe interactions and bile salt, heat and cold stress tolerance were identified. Concerning the potential health-promoting attributes of the novel strain, we determined that L. plantarum L125 carries an incomplete plantaricin gene cluster, in agreement with previous in vitro findings, where no bacteriocin-like activity was detected. Moreover, we showed that cell-free culture supernatant (CFCS) of L. plantarum L125 exerts anti-proliferative, anti-clonogenic and anti-migration activity against the human colon adenocarcinoma cell line, HT-29. Conclusively, L. plantarum L125 presents desirable probiotic traits. Future studies will elucidate further its biological and health-related properties.

11.
Front Microbiol ; 12: 746659, 2021.
Article in English | MEDLINE | ID: mdl-34764945

ABSTRACT

Lactobacillus is a diverse genus that includes species of industrial and biomedical interest. Lactiplantibacillus pentosus, formerly known as Lactobacillus pentosus, is a recently reclassified species, that contains strains isolated from diverse environmental niches, ranging from fermented products to mammalian gut microbiota. Importantly, several L. pentosus strains present health-promoting properties, such as immunomodulatory and antiproliferative activities, and are regarded as potential probiotic strains. In this study, we present the draft genome sequence of the potential probiotic strain L. pentosus L33, originally isolated from fermented sausages. Comprehensive bioinformatic analysis and whole-genome annotation were performed to highlight the genetic loci involved in host-microbe interactions and the probiotic phenotype. Consequently, we found that this strain codes for bile salt hydrolases, adhesins and moonlighting proteins, and for Class IIb bacteriocin peptides lacking the GxxxG and GxxxG-like motifs, crucial for their inhibitory activity. Its adhesion ability was also validated in vitro, on human cancer cells. Furthermore, L. pentosus L33 contains an exopolysaccharide (EPS) biosynthesis cluster, and it does not carry transferable antibiotic resistance genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and CAZymes analyses showed that L. pentosus L33 possesses biosynthetic pathways for seven amino acids, while it can degrade a wide array of carbohydrates. In parallel, Clusters of Orthologous Groups (COGs) and KEGG profiles of L. pentosus L33 are similar to those of 26 L. pentosus strains, as well as of two well documented L. plantarum probiotic strains. Conclusively, L. pentosus L33 exhibits good probiotic potential, although further studies are needed to elucidate the extent of its biological properties.

12.
Front Cell Dev Biol ; 9: 723859, 2021.
Article in English | MEDLINE | ID: mdl-34422840

ABSTRACT

Chromatin domains and loops are important elements of chromatin structure and dynamics, but much remains to be learned about their exact biological role and nature. Topological associated domains and functional loops are key to gene expression and hold the answer to many questions regarding developmental decisions and diseases. Here, we discuss new findings, which have linked chromatin conformation with development, differentiation and diseases and hypothesized on various models while integrating all recent findings on how chromatin architecture affects gene expression during development, evolution and disease.

13.
Article in English | MEDLINE | ID: mdl-34360162

ABSTRACT

Clear role descriptions promote the quality of interprofessional collaboration. Currently, it is unclear to what extent healthcare professionals consider pharmaceutical care (PC) activities to be nurses' responsibility in order to obtain best care quality. This study aimed to create and evaluate a framework describing potential nursing tasks in PC and to investigate nurses' level of responsibility. A framework of PC tasks and contextual factors was developed based on literature review and previous DeMoPhaC project results. Tasks and context were cross-sectionally evaluated using an online survey in 14 European countries. A total of 923 nurses, 240 physicians and 199 pharmacists responded. The majority would consider nurses responsible for tasks within: medication self-management (86-97%), patient education (85-96%), medication safety (83-95%), monitoring adherence (82-97%), care coordination (82-95%), and drug monitoring (78-96%). The most prevalent level of responsibility was 'with shared responsibility'. Prescription management tasks were considered to be nurses' responsibility by 48-81% of the professionals. All contextual factors were indicated as being relevant for nurses' role in PC by at least 74% of the participants. No task nor contextual factor was removed from the framework after evaluation. This framework can be used to enable healthcare professionals to openly discuss allocation of specific (shared) responsibilities and tasks.


Subject(s)
Nurses , Pharmaceutical Services , Cross-Sectional Studies , Europe , Humans , Nurse's Role , Pharmacists
14.
Methods Mol Biol ; 2351: 165-179, 2021.
Article in English | MEDLINE | ID: mdl-34382189

ABSTRACT

Targeted chromatin capture (T2C) is a 3C-based method and is used to study the 3D chromatin organization, interactomes and structural changes associated with gene regulation, progression through the cell cycle, and cell survival and development. Low input targeted chromatin capture (low-T2C) is an optimized version of the T2C protocol for low numbers of cells. Here, we describe the protocol for low-T2C, including all experimental steps and bioinformatics tools in detail.


Subject(s)
Chromatin Assembly and Disassembly , Chromatin/genetics , Computational Biology/methods , Chromatin/chemistry , Chromatin/metabolism , Chromosome Mapping , Gene Expression Regulation , Gene Library , Genomics/methods , Reproducibility of Results
15.
Nurse Educ Today ; 104: 104926, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34274774

ABSTRACT

BACKGROUND: Nurses play an important role in pharmaceutical care. They are involved in: detecting clinical change; communicating/discussing pharmacotherapy with patients, their advocates, and other healthcare professionals; proposing and implementing medication-related interventions; and ensuring follow-up of patients and medication regimens. To date, a framework of nurses' competences on knowledge, skills, and attitudes as to interprofessional pharmaceutical care tasks is missing. OBJECTIVES: To reach agreement with experts about nurses' competences for tasks in interprofessional pharmaceutical care. METHODS: A two-phase study starting with a scoping review followed by five Delphi rounds was performed. Competences extracted from the literature were assessed by an expert panel on relevance by using the RAND/UCLA method. The experts (n = 22) involved were healthcare professionals, nurse researchers, and educators from 14 European countries with a specific interest in nurses' roles in interprofessional pharmaceutical care. Descriptive statistics supported the data analysis. RESULTS: The expert panel reached consensus on the relevance of 60 competences for 22 nursing tasks. Forty-one competences were related to 15 generic nursing tasks and 33 competences were related to seven specific nursing tasks. CONCLUSIONS: This study resulted in a competence framework for competency-based nurse education. Future research should focus on imbedding these competences in nurse education. A structured instrument should be developed to assess students' readiness to achieve competence in interprofessional pharmaceutical care in clinical practice.


Subject(s)
Nurses , Pharmaceutical Services , Clinical Competence , Delphi Technique , Europe , Humans , Nurse's Role
16.
PLoS One ; 16(5): e0251982, 2021.
Article in English | MEDLINE | ID: mdl-34043650

ABSTRACT

OBJECTIVES: To understand healthcare professionals' experiences and perceptions of nurses' potential or ideal roles in pharmaceutical care (PC). DESIGN: Qualitative study conducted through semi-structured in-depth interviews. SETTING: Between December 2018 and October 2019, interviews were conducted with healthcare professionals of 14 European countries in four healthcare settings: hospitals, community care, mental health and long-term residential care. PARTICIPANTS: In each country, pharmacists, physicians and nurses in each of the four settings were interviewed. Participants were selected on the basis that they were key informants with broad knowledge and experience of PC. DATA COLLECTION AND ANALYSIS: All interviews were conducted face to face. Each country conducted an initial thematic analysis. Consensus was reached through a face-to-face discussion of all 14 national leads. RESULTS: 340 interviews were completed. Several tasks were described within four potential nursing responsibilities, that came up as the analysis themes, being: 1) monitoring therapeutic/adverse effects of medicines, 2) monitoring medicines adherence, 3) decision making on medicines, including prescribing 4) providing patient education/information. Nurses' autonomy varied across Europe, from none to limited to a few tasks and emergencies to a broad range of tasks and responsibilities. Intended level of autonomy depended on medicine types and level of education. Some changes are needed before nursing roles can be optimised and implemented in practice. Lack of time, shortage of nurses, absence of legal frameworks and limited education and knowledge are main threats to European nurses actualising their ideal role in PC. CONCLUSIONS: European nurses have an active role in PC. Respondents reported positive impacts on care quality and patient outcomes when nurses assumed PC responsibilities. Healthcare professionals expect nurses to report observations and assessments. This key patient information should be shared and addressed by the interprofessional team. The study evidences the need of a unique and consensus-based PC framework across Europe.


Subject(s)
Health Knowledge, Attitudes, Practice , Nurse's Role/psychology , Nurses/psychology , Pharmaceutical Services/organization & administration , Pharmacists/psychology , Physicians/psychology , Adult , Aged , Europe , Female , Hospitals , Humans , Male , Middle Aged , Patient Compliance , Qualitative Research , Surveys and Questionnaires
17.
iScience ; 24(3): 102210, 2021 Mar 19.
Article in English | MEDLINE | ID: mdl-33733070

ABSTRACT

Transcription factors are key players in a broad range of cellular processes such as cell-fate decision. Understanding how they act to control these processes is of critical importance for therapy purposes. FLI-1 controls several hematopoietic lineage differentiation including megakaryopoiesis and erythropoiesis. Its aberrant expression is often observed in cancer and is associated with poor prognosis. We showed that FLI-1 interacts with the LDB1 complex, which also plays critical roles in erythropoiesis and megakaryopoiesis. In this study, we aimed to unravel how FLI-1 and the LDB1 complex act together in murine erythroleukemia cells and in megakaryocyte. Combining omics techniques, we show that FLI-1 enables the recruitment of the LDB1 complex to regulatory sequences of megakaryocytic genes and to enhancers. We show as well for the first time that FLI-1 is able to modulate the 3D chromatin organization by promoting chromatin looping between enhancers and promoters most likely through the LDB1 complex.

18.
Genome Res ; 30(8): 1119-1130, 2020 08.
Article in English | MEDLINE | ID: mdl-32747411

ABSTRACT

Polycomb group proteins are important for maintaining gene expression patterns and cell identity in metazoans. The mammalian Polycomb repressive deubiquitinase (PR-DUB) complexes catalyze removal of monoubiquitination on lysine 119 of histone H2A (H2AK119ub1) through a multiprotein core comprised of BAP1, HCFC1, FOXK1/2, and OGT in combination with either of ASXL1, 2, or 3. Mutations in PR-DUB components are frequent in cancer. However, mechanistic understanding of PR-DUB function in gene regulation is limited. Here, we show that BAP1 is dependent on the ASXL proteins and FOXK1/2 in facilitating gene activation across the genome. Although PR-DUB was previously shown to cooperate with PRC2, we observed minimal overlap and functional interaction between BAP1 and PRC2 in embryonic stem cells. Collectively, these results demonstrate that PR-DUB, by counteracting accumulation of H2AK119ub1, maintains chromatin in an optimal configuration ensuring expression of genes important for general functions such as cell metabolism and homeostasis.


Subject(s)
Chromatin/metabolism , Deubiquitinating Enzymes/metabolism , Gene Expression Regulation/genetics , Histones/metabolism , Polycomb-Group Proteins/metabolism , Animals , Cell Proliferation/genetics , Cells, Cultured , Chromatin/genetics , Deubiquitinating Enzymes/genetics , Forkhead Transcription Factors/metabolism , Gene Knockout Techniques , Mice , Mice, Inbred BALB C , Mice, Knockout , Mouse Embryonic Stem Cells , Polycomb-Group Proteins/genetics , Repressor Proteins/metabolism , Tumor Suppressor Proteins/metabolism , Ubiquitin Thiolesterase/metabolism
19.
Hum Mol Genet ; 29(15): 2535-2550, 2020 08 29.
Article in English | MEDLINE | ID: mdl-32628253

ABSTRACT

The transcription factor zinc finger E-box binding protein 2 (ZEB2) controls embryonic and adult cell fate decisions and cellular maturation in many stem/progenitor cell types. Defects in these processes in specific cell types underlie several aspects of Mowat-Wilson syndrome (MOWS), which is caused by ZEB2 haplo-insufficiency. Human ZEB2, like mouse Zeb2, is located on chromosome 2 downstream of a ±3.5 Mb-long gene-desert, lacking any protein-coding gene. Using temporal targeted chromatin capture (T2C), we show major chromatin structural changes based on mapping in-cis proximities between the ZEB2 promoter and this gene desert during neural differentiation of human-induced pluripotent stem cells, including at early neuroprogenitor cell (NPC)/rosette state, where ZEB2 mRNA levels increase significantly. Combining T2C with histone-3 acetylation mapping, we identified three novel candidate enhancers about 500 kb upstream of the ZEB2 transcription start site. Functional luciferase-based assays in heterologous cells and NPCs reveal co-operation between these three enhancers. This study is the first to document in-cis Regulatory Elements located in ZEB2's gene desert. The results further show the usability of T2C for future studies of ZEB2 REs in differentiation and maturation of multiple cell types and the molecular characterization of newly identified MOWS patients that lack mutations in ZEB2 protein-coding exons.


Subject(s)
Chromatin/ultrastructure , Enhancer Elements, Genetic/genetics , Hirschsprung Disease/genetics , Intellectual Disability/genetics , Microcephaly/genetics , Zinc Finger E-box Binding Homeobox 2/genetics , Animals , Cell Differentiation/genetics , Cell Lineage/genetics , Chromatin/genetics , Facies , Gene Expression Regulation/genetics , Hirschsprung Disease/pathology , Homeodomain Proteins/genetics , Humans , Intellectual Disability/pathology , Mice , Microcephaly/pathology , Neural Stem Cells/metabolism , Neural Stem Cells/pathology , Pluripotent Stem Cells/metabolism , Pluripotent Stem Cells/ultrastructure , Regulatory Sequences, Nucleic Acid
20.
BMJ Open ; 10(6): e036269, 2020 06 03.
Article in English | MEDLINE | ID: mdl-32499269

ABSTRACT

OBJECTIVES: Safe pharmaceutical care (PC) requires an interprofessional team approach, involving physicians, nurses and pharmacists. Nurses' roles however, are not always explicit and clear, complicating interprofessional collaboration. The aim of this study is to describe nurses' practice and interprofessional collaboration in PC, from the viewpoint of nurses, physicians and pharmacists. DESIGN: A cross-sectional survey. SETTING: The study was conducted in 17 European countries, each with their own health systems. PARTICIPANTS: Pharmacists, physicians and nurses with an active role in PC were surveyed. MAIN OUTCOME MEASURES: Nurses' involvement in PC, experiences of interprofessional collaboration and communication and views on nurses' competences. RESULTS: A total of 4888 nurses, 974 physicians and 857 pharmacists from 17 European countries responded. Providing patient education and information (PEI), monitoring medicines adherence (MMA), monitoring adverse/therapeutic effects (ME) and prescribing medicines were considered integral to nursing practice by 78%, 73%, 69% and 15% of nurses, respectively. Most respondents were convinced that quality of PC would be improved by increasing nurses' involvement in ME (95%), MMA (95%), PEI (91%) and prescribing (53%). Mean scores for the reported quality of collaboration between nurses and physicians, collaboration between nurses and pharmacists and interprofessional communication were respectively <7/10, ≤4/10, <6/10 for all four aspects of PC. CONCLUSIONS: ME, MMA, PEI and prescribing are part of nurses' activities, and most healthcare professionals felt their involvement should be extended. Collaboration between nurses and physicians on PC is limited and between nurses and pharmacists even more.


Subject(s)
Cross-Sectional Studies , Interprofessional Relations , Nurse's Role , Patient Care Team/statistics & numerical data , Pharmaceutical Services/statistics & numerical data , Cross-Cultural Comparison , Europe , Humans , Interdisciplinary Communication , Surveys and Questionnaires
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