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1.
Br J Haematol ; 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38664944

RESUMEN

This updated British Society for Haematology guideline provides an up-to-date literature review and recommendations regarding the identification and management of preoperative anaemia. This includes guidance on thresholds for the diagnosis of anaemia and the diagnosis and management of iron deficiency in the preoperative context. Guidance on the appropriate use of erythropoiesis-stimulating agents and preoperative transfusion is also provided.

2.
J Proteome Res ; 23(3): 999-1013, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38354288

RESUMEN

The value of synthetic microbial communities in biotechnology is gaining traction due to their ability to undertake more complex metabolic tasks than monocultures. However, a thorough understanding of strain interactions, productivity, and stability is often required to optimize growth and scale up cultivation. Quantitative proteomics can provide valuable insights into how microbial strains adapt to changing conditions in biomanufacturing. However, current workflows and methodologies are not suitable for simple artificial coculture systems where strain ratios are dynamic. Here, we established a workflow for coculture proteomics using an exemplar system containing two members, Azotobacter vinelandii and Synechococcus elongatus. Factors affecting the quantitative accuracy of coculture proteomics were investigated, including peptide physicochemical characteristics such as molecular weight, isoelectric point, hydrophobicity, and dynamic range as well as factors relating to protein identification such as varying proteome size and shared peptides between species. Different quantification methods based on spectral counts and intensity were evaluated at the protein and cell level. We propose a new normalization method, named "LFQRatio", to reflect the relative contributions of two distinct cell types emerging from cell ratio changes during cocultivation. LFQRatio can be applied to real coculture proteomics experiments, providing accurate insights into quantitative proteome changes in each strain.


Asunto(s)
Microbiota , Proteoma , Técnicas de Cocultivo , Peso Molecular , Proteómica
3.
J Biol Chem ; 300(1): 105529, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38043796

RESUMEN

Clostridioides difficile is the leading cause of antibiotic-associated diarrhea worldwide with significant morbidity and mortality. This organism is naturally resistant to several beta-lactam antibiotics that inhibit the polymerization of peptidoglycan, an essential component of the bacteria cell envelope. Previous work has revealed that C. difficile peptidoglycan has an unusual composition. It mostly contains 3-3 cross-links, catalyzed by enzymes called L,D-transpeptidases (Ldts) that are poorly inhibited by beta-lactams. It was therefore hypothesized that peptidoglycan polymerization by these enzymes could underpin antibiotic resistance. Here, we investigated the catalytic activity of the three canonical Ldts encoded by C. difficile (LdtCd1, LdtCd2, and LdtCd3) in vitro and explored their contribution to growth and antibiotic resistance. We show that two of these enzymes catalyze the formation of novel types of peptidoglycan cross-links using meso-diaminopimelic acid both as a donor and an acceptor, also observed in peptidoglycan sacculi. We demonstrate that the simultaneous deletion of these three genes only has a minor impact on both peptidoglycan structure and resistance to beta-lactams. This unexpected result therefore implies that the formation of 3-3 peptidoglycan cross-links in C. difficile is catalyzed by as yet unidentified noncanonical Ldt enzymes.


Asunto(s)
Proteínas Bacterianas , Clostridioides difficile , Peptidoglicano , Peptidil Transferasas , Proteínas Bacterianas/química , Resistencia betalactámica , beta-Lactamas/farmacología , Catálisis , Clostridioides difficile/enzimología , Clostridioides difficile/genética , Peptidoglicano/química , Peptidil Transferasas/química , Peptidil Transferasas/genética
4.
J Biol Chem ; 300(1): 105494, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38006948

RESUMEN

Peptidoglycan is an essential component of the bacterial cell envelope that contains glycan chains substituted by short peptide stems. Peptide stems are polymerized by D,D-transpeptidases, which make bonds between the amino acid in position four of a donor stem and the third residue of an acceptor stem (4-3 cross-links). Some bacterial peptidoglycans also contain 3-3 cross-links that are formed by another class of enzymes called L,D-transpeptidases which contain a YkuD catalytic domain. In this work, we investigate the formation of unusual bacterial 1-3 peptidoglycan cross-links. We describe a version of the PGFinder software that can identify 1-3 cross-links and report the high-resolution peptidoglycan structure of Gluconobacter oxydans (a model organism within the Acetobacteraceae family). We reveal that G. oxydans peptidoglycan contains peptide stems made of a single alanine as well as several dipeptide stems with unusual amino acids at their C-terminus. Using a bioinformatics approach, we identified a G. oxydans mutant from a transposon library with a drastic reduction in 1-3 cross-links. Through complementation experiments in G. oxydans and recombinant protein production in a heterologous host, we identify an L,D-transpeptidase enzyme with a domain distantly related to the YkuD domain responsible for these non-canonical reactions. This work revisits the enzymatic capabilities of L,D-transpeptidases, a versatile family of enzymes that play a key role in bacterial peptidoglycan remodelling.


Asunto(s)
Proteínas Bacterianas , Gluconobacter oxydans , Modelos Moleculares , Peptidoglicano , Peptidil Transferasas , Aminoácidos/genética , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Dominio Catalítico/genética , Peptidoglicano/química , Peptidoglicano/genética , Peptidoglicano/metabolismo , Peptidil Transferasas/química , Peptidil Transferasas/genética , Peptidil Transferasas/metabolismo , Programas Informáticos , Gluconobacter oxydans/enzimología , Gluconobacter oxydans/genética , Biología Computacional , Prueba de Complementación Genética , Estructura Terciaria de Proteína
5.
Biotechnol Biofuels Bioprod ; 16(1): 166, 2023 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-37925447

RESUMEN

BACKGROUND: Microalgae are emerging hosts for the sustainable production of lutein, a high-value carotenoid; however, to be commercially competitive with existing systems, their capacity for lutein sequestration must be augmented. Previous attempts to boost microalgal lutein production have focussed on upregulating carotenoid biosynthetic enzymes, in part due to a lack of metabolic engineering targets for expanding lutein storage. RESULTS: Here, we isolated a lutein hyper-producing mutant of the model green microalga Chlamydomonas reinhardtii and characterized the metabolic mechanisms driving its enhanced lutein accumulation using label-free quantitative proteomics. Norflurazon- and high light-resistant C. reinhardtii mutants were screened to yield four mutant lines that produced significantly more lutein per cell compared to the CC-125 parental strain. Mutant 5 (Mut-5) exhibited a 5.4-fold increase in lutein content per cell, which to our knowledge is the highest fold increase of lutein in C. reinhardtii resulting from mutagenesis or metabolic engineering so far. Comparative proteomics of Mut-5 against its parental strain CC-125 revealed an increased abundance of light-harvesting complex-like proteins involved in photoprotection, among differences in pigment biosynthesis, central carbon metabolism, and translation. Further characterization of Mut-5 under varying light conditions revealed constitutive overexpression of the photoprotective proteins light-harvesting complex stress-related 1 (LHCSR1) and LHCSR3 and PSII subunit S regardless of light intensity, and increased accrual of total chlorophyll and carotenoids as light intensity increased. Although the photosynthetic efficiency of Mut-5 was comparatively lower than CC-125, the amplitude of non-photochemical quenching responses of Mut-5 was 4.5-fold higher than in CC-125 at low irradiance. CONCLUSIONS: We used C. reinhardtii as a model green alga and identified light-harvesting complex-like proteins (among others) as potential metabolic engineering targets to enhance lutein accumulation in microalgae. These have the added value of imparting resistance to high light, although partially compromising photosynthetic efficiency. Further genetic characterization and engineering of Mut-5 could lead to the discovery of unknown players in photoprotective mechanisms and the development of a potent microalgal lutein production system.

6.
Inflamm Bowel Dis ; 2023 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-37889841

RESUMEN

INTRODUCTION AND AIMS: Risk stratification of subjects with a history of inflammatory bowel disease (IBD) into those likely to relapse and those who will remain quiescent continues to be a significant challenge. The aim of this study was to investigate whether certain proteomic signature profiles or biomarkers during remission are associated with future disease relapse in patients with ulcerative colitis (UC). METHODS: Endoscopic rectal samples from patients with UC in clinical, endoscopic, and histological remission at index endoscopy were collected, as well as samplers from normal control individuals. The patients were stratified to early relapsers (ERs) if they developed clinical signs of UC flare within 6 months of index endoscopy or nonrelapsers (NRs) if there was no relapse after 36 months of follow-up. The pooled rectal samples from ERs, NRs, and control individuals were subjected to nano-liquid chromatography and tandem mass spectrometry as per standard iTRAQ (isobaric tags for relative and absolute quantitation) workflow methodology. Selected proteomics-yielded candidates were subjected to orthogonal validation via immunoblotting, in a biomarker discovery exercise. RESULTS: Sixty-one patients were included, of whom 8 had clinical relapse within 6 months from the index endoscopy, and 43 patients had no clinical symptoms of relapse within the 36-month follow-up period. Ten patients who had clinical signs of relapse between 6 and 36 months were excluded. Seventeen control individuals were also included. Soluble proteomics analyses between ERs, NRs, and control individuals revealed a series of upregulated and downregulated proteins. Following orthogonal validation, upregulated TRX (P = .001) and IGHA1 (P = .001) were observed in ERs relative to NRs. CONCLUSIONS: Several novel candidate tissue biomarkers have been identified in this study, which could discriminate patients with UC at risk of early relapse from those in long-term sustained remission. Our findings may pave the way for pre-emptive UC disease monitoring and therapeutic decision making.


This study aimed to investigate if certain proteins (biomarkers) could predict whether patients with Ulcerative Colitis (UC) would have a disease relapse. Rectal samples were collected from UC patients who were in remission and from healthy individuals. The patients were categorised into two groups: those who had a flare-up within 6 months (early relapsers) and those who did not have a relapse after 36 months (non-relapsers). Using proteomics methodology, it was found that certain proteins were more common in the early relapsers compared to the non-relapsers and healthy individuals. Two proteins, TRX and IGHA1, were significantly higher in the early relapsers. These proteins could potentially be used as markers to identify UC patients who are at risk of having an early relapse. This could help monitoring UC patients more effectively and making better treatment decisions.

7.
Reprod Fertil Dev ; 35(6): 416-421, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36843010

RESUMEN

CONTEXT: Systemic events resulting from mother-embryo relation at the peri-implantation period may result in specific changes to the protein composition of serum and thus provide a source of biomarkers for early detection of pregnancy. AIMS: We set out to use two different quantitative proteomic approaches to test this hypothesis by comparing heifer serum at the peri-implantation period to that from cycling heifers. METHODS: Two-dimensional electrophoresis (2-DE) and isobaric tags were used for relative and absolute quantitation (iTRAQ) of proteins. KEY RESULTS: These methods yielded complementary data indicating biomarker candidate proteins. CONCLUSIONS: Different proteomic methods provide different and complementary information that needs to be analysed in order to consider proteins as potential biomarkers. IMPLICATIONS: In order to characterise the proteome under specific conditions, the use of complementary techniques is advisable.


Asunto(s)
Proteoma , Proteómica , Embarazo , Femenino , Animales , Bovinos , Proteómica/métodos , Biomarcadores , Proteoma/metabolismo
8.
Br J Anaesth ; 130(2): 115-119, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36593165

RESUMEN

The Centre for Perioperative Care (CPOC) has published in September 2022 guidance addressing perioperative anaemia. This editorial addresses the definition of anaemia for women and management of borderline anaemia in women. We also address implications of the CPOC guidance for anaesthetists and the future direction of anaemia research and management.


Asunto(s)
Anemia , Anestesia , Humanos , Femenino , Transfusión Sanguínea , Anemia/diagnóstico , Anemia/terapia , Atención Perioperativa
9.
Clin Psychol Rev ; 99: 102233, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36495737

RESUMEN

This systematic review and meta-analysis aims to synthesize the efficacy of culturally sensitive prevention programs for substance use outcomes among U.S. adolescents of color (aged 11 to 18 years old) and explore whether the intervention effects vary by participant and intervention characteristics. Eight electronic databases and grey literature were searched for eligible randomized controlled trials through September 2022. Robust variance estimation in meta-regression was used to synthesize treatment effect size estimates and to conduct moderator analysis. After screening, 30 unique studies were included. The average treatment effect size across all substance use outcomes (including 221 effect sizes) was Hedges's g = -0.20, 95% CI = [-0.24, -0.16]. The synthesized effect sizes were statistically significant across types of substances (alcohol, cigarette, marijuana, illicit and other drugs, and unspecified substance use), racial/ethnic groups (Hispanic, Black, and Native American), and different follow-ups (0-12 months, >12 months). Very few studies reported substance use consequences as outcomes and the synthesized effect size was non-significant. Meta-regression findings suggest that the intervention effects may vary based on the type of substance. This meta-analysis found supportive evidence of culturally sensitive prevention programs' efficacy in preventing or reducing substance use among Black, Hispanic, and Native American adolescents. More substance use prevention efforts and evidence is needed for Asian American, Pacific Islander, and multiracial adolescents.


Asunto(s)
Trastornos Relacionados con Sustancias , Humanos , Adolescente , Niño , Ensayos Clínicos Controlados Aleatorios como Asunto , Trastornos Relacionados con Sustancias/prevención & control , Consumo de Bebidas Alcohólicas , Asiático Americano Nativo Hawáiano y de las Islas del Pacífico
10.
Front Bioeng Biotechnol ; 10: 838445, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35646838

RESUMEN

The marine microalga Nannochloropsis oculata is a bioproducer of eicosapentaenoic acid (EPA), a fatty acid. EPA is incorporated into monogalactosyldiacylglycerol within N. oculata thylakoid membranes, and there is a biotechnological need to remodel EPA synthesis to maximize production and simplify downstream processing. In this study, random mutagenesis and chemical inhibitor-based selection method were devised to increase EPA production and accessibility for improved extraction. Ethyl methanesulfonate was used as the mutagen with selective pressure achieved by using two enzyme inhibitors of lipid metabolism: cerulenin and galvestine-1. Fatty acid methyl ester analysis of a selected fast-growing mutant strain had a higher percentage of EPA (37.5% of total fatty acids) than the wild-type strain (22.2% total fatty acids), with the highest EPA quantity recorded at 68.5 mg/g dry cell weight, while wild-type cells had 48.6 mg/g dry cell weight. Label-free quantitative proteomics for differential protein expression analysis revealed that the wild-type and mutant strains might have alternative channeling pathways for EPA synthesis. The mutant strain showed potentially improved photosynthetic efficiency, thus synthesizing a higher quantity of membrane lipids and EPA. The EPA synthesis pathways could also have deviated in the mutant, where fatty acid desaturase type 2 (13.7-fold upregulated) and lipid droplet surface protein (LDSP) (34.8-fold upregulated) were expressed significantly higher than in the wild-type strain. This study increases the understanding of EPA trafficking in N. oculata, leading to further strategies that can be implemented to enhance EPA synthesis in marine microalgae.

11.
Int J Mol Sci ; 23(4)2022 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-35216078

RESUMEN

Metastasising cells express the intermediate filament protein vimentin, which is used to diagnose invasive tumours in the clinic. We aimed to clarify how vimentin regulates the motility of metastasising fibroblasts. STED super-resolution microscopy, live-cell imaging and quantitative proteomics revealed that oncogene-expressing and metastasising fibroblasts show a less-elongated cell shape, reduced cell spreading, increased cell migration speed, reduced directionality, and stronger coupling between these migration parameters compared to normal control cells. In total, we identified and compared 555 proteins in the vimentin interactome. In metastasising cells, the levels of keratin 18 and Rab5C were increased, while those of actin and collagen were decreased. Inhibition of HDAC6 reversed the shape, spreading and migration phenotypes of metastasising cells back to normal. Inhibition of HDAC6 also decreased the levels of talin 1, tropomyosin, Rab GDI ß, collagen and emilin 1 in the vimentin interactome, and partially reversed the nanoscale vimentin organisation in oncogene-expressing cells. These findings describe the changes in the vimentin interactome and nanoscale distribution that accompany the defective cell shape, spreading and migration of metastasising cells. These results support the hypothesis that oncogenes can act through HDAC6 to regulate the vimentin binding of the cytoskeletal and cell-extracellular matrix adhesion components that contribute to the defective motility of metastasising cells.


Asunto(s)
Movimiento Celular/fisiología , Fibroblastos/metabolismo , Fibroblastos/patología , Vimentina/metabolismo , Actinas/metabolismo , Animales , Adhesión Celular/fisiología , Forma de la Célula/fisiología , Uniones Célula-Matriz/metabolismo , Células Cultivadas , Colágeno/metabolismo , Citoesqueleto/metabolismo , Histona Desacetilasa 6/metabolismo , Humanos , Ratones , Oncogenes/fisiología
12.
Health Soc Care Community ; 30(3): e739-e748, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34028915

RESUMEN

This study explored a community perception of the facilitators and inhibitors of Getting to Zero (GTZ) in rural Zambia, sub-Saharan Africa. Data were collected in 2017. We use the Social Determinants of Health framework to guide organisation of key themes emerging from semistructured, focus group interviews with community members (N = 52). Data were analysed through an iterative descriptive/thematic approach which allowed for the highlighting of key themes. Emerging themes point to the significance of (a) individual, (b) sociocultural, (c) environmental and (d) economic factors, for example, treatment adherence, gender norms, food security and access to health care as important in GTZ. Implications for policy, practise and scholarship are suggested.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , África del Sur del Sahara , Grupos Focales , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Humanos , Población Rural , Determinantes Sociales de la Salud
13.
Semin Cell Dev Biol ; 128: 103-111, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-34481710

RESUMEN

The colon mucosa is lined with crypts of circa 300 cells, forming a continuous barrier whose roles include absorption of water, recovery of metabolic energy sources (notably short chain fatty acids), secretion of a protective mucus barrier, and physiological signalling. There is high turnover and replenishment of cells in the mucosa, disruption of this may lead to bowel pathologies including cancer and inflammatory bowel disease. Keratins have been implicated in the processes of cell death, epithelial integrity, response to inflammation and as a result are often described as guardians of the colonic epithelium. Keratin proteins carry extensive post-translational modifications, the cofactors for kinases, acetyl transferases and other modification-regulating enzymes are themselves products of metabolism. A cluster of studies has begun to reveal a bidirectional relationship between keratin form and function and metabolism. In this paper we hypothesise a mechanistic interaction between keratins and metabolism is governed through regulation of post-translational modifications and may contribute significantly to the normal functioning of the colon, placing keratins at the centre of a nutrition-metabolism-health triangle.


Asunto(s)
Colon , Queratinas , Recto , Colon/fisiología , Neoplasias Colorrectales , Humanos , Enfermedades Inflamatorias del Intestino , Mucosa Intestinal/fisiología , Queratinas/fisiología , Recto/fisiología
14.
Youth Soc ; 53(5): 784-810, 2021 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-34556892

RESUMEN

Although research advocates for comprehensive cross sector youth violence prevention efforts, mobilizing across sectors to translate scientific recommendations into practice has proven challenging. A unifying framework may provide a foundational step towards building a shared understanding of the risk and protective factors that impact youth violence. We conducted two empirical tests of the nurturing environment framework on youth violence across ethnic and geographically diverse rural and urban adolescent samples. Results show that overall the characteristics of nurturing environments are associated with lower levels of aggression and violence. In addition, minimizing exposure to socially toxic conditions had the strongest associations with lower aggression and violence. Findings were supported across both samples, suggesting that this framework may apply in urban and rural, economically disadvantaged contexts.

15.
J Biotechnol ; 340: 1-12, 2021 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-34390759

RESUMEN

Inflammatory bowel disease (IBD) is a set of immunological disorders which can generate chronic pain and fatigue associated with the inflammatory symptoms. The treatment of IBD remains a significant hurdle with current therapies being only partially effective or having significant side effects, suggesting that new therapies that elicit different modes of action and delivery strategies are required. TGM1 is a TGF-ß mimic that was discovered from the intestinal helminth parasite Heligmosomoides polygyrus and is thought to be produced by the parasite to suppress the intestinal inflammation response to help evade host immunity, making it an ideal candidate to be developed as a novel anti-inflammatory bio-therapeutic. Here we utilized the expression system of the edible green algae Chlamydomonas reinhardtii in order to recombinantly produce active TGM1 in a form that could be ingested. C. reinhardtii robustly expressed TGM1, and the resultant recombinant protein is biologically active as measured by regulatory T cell induction. When delivered orally to mice, the algal expressed TGM1 is able to ameliorate weight loss, lymphadenopathy, and disease symptoms in a mouse model of DSS-induced colitis, demonstrating the potential of this biologic as a novel treatment of IBD.


Asunto(s)
Colitis , Factor de Crecimiento Transformador beta/administración & dosificación , Administración Oral , Animales , Chlamydomonas reinhardtii , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Modelos Animales de Enfermedad , Ratones , Nematospiroides dubius , Proteínas Recombinantes/administración & dosificación , Linfocitos T Reguladores
16.
Future Healthc J ; 8(1): e1-e4, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33791464

RESUMEN

The NHS is currently in the midst of a global health crisis that requires rapid action from its staff and systems. The Royal College of Physicians' chief registrars, in their role as middle leaders that bridge the gap between junior doctors and senior leadership in NHS trusts nationwide, are uniquely positioned to respond to the COVID-19 crisis. Our strategies fall into three overlapping categories: our roles as middle leaders, developing effective communication techniques and promoting staff wellbeing. We discuss lessons of good leadership in a time of crisis, from embracing new ways of working and new technologies, to utilising professional networks to drive change, to providing tools to support the wellbeing of the colleagues we both lead and care for. The lessons of our initial response are being shared across our national network. We also hope that the novel approaches we have developed will inform the practice of future middle leaders.

17.
Mol Ecol ; 29(22): 4428-4441, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32939895

RESUMEN

Despite holding a central role in fertilization, reproductive traits often show elevated rates of evolution and diversification. The rapid evolution of seminal fluid proteins (Sfps) within populations is predicted to cause mis-signalling between the male ejaculate and the female during and after mating resulting in postmating prezygotic (PMPZ) isolation between populations. Crosses between Drosophila montana populations show PMPZ isolation in the form of reduced fertilization success in both noncompetitive and competitive contexts. Here we test whether male ejaculate proteins produced in the accessory glands or ejaculatory bulb differ between populations using liquid chromatography tandem mass spectrometry. We find more than 150 differentially abundant proteins between populations that may contribute to PMPZ isolation, including a number of proteases, peptidases and several orthologues of Drosophila melanogaster Sfps known to mediate fertilization success. Males from the population that elicit the stronger PMPZ isolation after mating with foreign females typically produced greater quantities of Sfps. The accessory glands and ejaculatory bulb show enrichment for different gene ontology (GO) terms and the ejaculatory bulb contributes more differentially abundant proteins. Proteins with a predicted secretory signal evolve faster than nonsecretory proteins. Finally, we take advantage of quantitative proteomics data for three Drosophila species to determine shared and unique GO enrichments of Sfps between taxa and which potentially mediate PMPZ isolation. Our study provides the first high-throughput quantitative proteomic evidence showing divergence of reproductive proteins between populations that exhibit PMPZ isolation.


Asunto(s)
Proteínas de Drosophila , Proteómica , Aislamiento Reproductivo , Animales , Drosophila/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Femenino , Masculino , Conducta Sexual Animal
18.
Anal Chim Acta ; 1129: 158-180, 2020 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-32891386

RESUMEN

Significant technical advancements in phosphopeptide enrichment have enabled the identification of thousands of p-peptides (mono and multiply phosphorylated) in a single experiment. However, it is still not possible to enrich all p-peptide species in a single step. A range of new techniques and materials has been developed, with the potential to provide a step-change in phosphopeptide enrichment. The first half of this review contains a tutorial for new potential phosphoproteomic researchers; discussing the key steps of a typical phosphoproteomic experiment used to investigate canonical phosphorylation sites (serine, threonine and tyrosine). The latter half then show-cases the latest developments in p-peptide enrichment including: i) Strategies to mitigate non-specific binding in immobilized metal ion affinity chromatography and metal oxide affinity chromatography protocols; ii) Techniques to separate multiply phosphorylated peptides from monophosphorylated peptides (including canonical from non-canonical phosphorylated peptides), or to simultaneously co-enrich other post-translational modifications; iii) New hybrid materials and methods directed towards enhanced selectivity and efficiency of metal-based enrichment; iv) Novel materials that hold promise for enhanced phosphotyrosine enrichment. A combination of well-understood techniques and materials is much more effective than any technique in isolation; but the field of phosphoproteomics currently requires benchmarking of novel materials against current methodologies to fully evaluate their utility in peptide based proteoform analysis.


Asunto(s)
Fosfopéptidos , Proteómica , Cromatografía de Afinidad , Fosforilación , Procesamiento Proteico-Postraduccional , Titanio
19.
Am J Community Psychol ; 66(3-4): 392-403, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32691885

RESUMEN

In this paper, we describe the assessment and planning phase of the Thrive community-based initiative to reduce violence and address other determinants of health in a community in the Southwestern United States. Using community-based participatory research (CBPR) and an implementation science framework, we engaged residents and other key stakeholders as equal partners in the assessment and planning process. The Thrive assessment and planning phase involved collaboration among researchers, residents, law enforcement, nonprofit agencies, public health, local government, and other cross-sector partners. We used implementation science in order to examine the barriers and facilitators to addressing community health and safety, to assess the nature and scope of health and safety issues, to review existing solutions, to assess the acceptability and necessary adaptations of selected interventions, and to assess feasibility and sustainability of the initiative. Through interviews, focus groups, analysis of crime incident data, geomapping, and direct observations, our findings highlighted the presence of an open-air drug market, the high-stress nature of the community, concern for the lack of opportunities for youth, the lack of trust between residents and law enforcement, and a need to address the built environment to promote safety and well-being.


Asunto(s)
Investigación Participativa Basada en la Comunidad , Crimen/prevención & control , Ciencia de la Implementación , Violencia/prevención & control , Arizona , Grupos Focales , Humanos , Determinantes Sociales de la Salud
20.
Br J Anaesth ; 124(3): 243-250, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31902590

RESUMEN

BACKGROUND: Preoperative anaemia affects one third of patients undergoing cardiac surgery and is associated with increased mortality and morbidity. Although it is recommended that perioperative teams should identify and treat patients with preoperative anaemia before surgery, introducing new treatment protocols can be challenging in surgical pathways. The aim of this study was to assess the feasibility and effectiveness of introducing a preoperative intravenous iron service as a national initiative in cardiac surgery. METHODS: We performed a multicentre, stepped, observational study using the UK Association of Cardiothoracic Anaesthesia and Critical Care Research Network. The primary feasibility outcome was the ability to set up an anaemia and intravenous iron clinic at each site. The primary efficacy outcome was change in haemoglobin (Hb) concentration between intervention and operation. Secondary outcomes included blood transfusion and hospital stay. Patients with anaemia were compared with non-anaemic patients and with those who received intravenous iron as part of their routine treatment protocol. RESULTS: Seven out of 11 NHS hospitals successfully set up iron clinics over 2 yr, and 228 patients were recruited into this study. Patients with anaemia who received intravenous iron were at higher surgical risk, were more likely to have a known previous history of iron deficiency or anaemia, had a higher rate of chronic kidney disease, and were slightly more anaemic than the non-treated group. Intravenous iron was administered a median (inter-quartile range, IQR [range]) of 33 (15-53 [4-303]) days before surgery. Preoperative intravenous iron increased [Hb] from baseline to pre-surgery; mean (95% confidence interval) change was +8.4 (5.0-11.8) g L-1 (P<0.001). Overall, anaemic compared with non-anaemic patients were more likely to be transfused (49% [59/136] vs 27% (22/92), P=0.001) and stayed longer in hospital (median days [IQR], 9 [7-15] vs 8 [6-11]; P=0.014). The number of days alive and at home was lower in the anaemic group (median days [IQR], 20 [14-22] vs 21 [17-23]; P=0.033). CONCLUSION: The development of an intravenous iron pathway is feasible but appears limited to selected high-risk cardiac patients in routine NHS practise. Although intravenous iron increased [Hb], there is a need for an appropriately powered clinical trial to assess the clinical effect of intravenous iron on patient-centred outcomes.


Asunto(s)
Anemia Ferropénica/tratamiento farmacológico , Procedimientos Quirúrgicos Cardíacos , Hierro/administración & dosificación , Cuidados Preoperatorios/métodos , Administración Intravenosa , Anciano , Anciano de 80 o más Años , Anemia Ferropénica/sangre , Anemia Ferropénica/complicaciones , Transfusión Sanguínea/estadística & datos numéricos , Vías Clínicas/organización & administración , Estudios de Factibilidad , Femenino , Hemoglobinas/metabolismo , Humanos , Hierro/uso terapéutico , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Complicaciones Posoperatorias/prevención & control , Estudios Prospectivos , Medicina Estatal/organización & administración
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