• Haugaard Holmgaard opublikował 5 miesięcy, 3 tygodnie temu

    Flower sepals are critical for flower development and vary greatly in lifespan depending on their function post-pollination. Very little is known about what controls sepal longevity. Using a sepal senescence mutant screen, we identified two Arabidopsis mutants with delayed senescence directly connecting strigolactones (SL) with senescence regulation in a novel floral context that hitherto has not been explored. The mutations were in the SL biosynthetic gene MORE AXILLARY GROWTH1 (MAX1) and in the SL receptor DWARF14 (AtD14). The mutation in AtD14 changed the catalytic Ser97 to Phe in the enzyme active site, which is the first mutation of its kind in planta. The lesion in MAX1 was in the haem-iron ligand signature of the cytochrome P450 protein, converting the highly conserved Gly469 to Arg, which was shown in a transient expression assay to substantially inhibit activity of MAX1. The two mutations highlighted the importance of SL activity for driving to completion senescence initiated both developmentally and in response to carbon-limiting stress, as has been found for the more well-known senescence-associated regulators ethylene and abscisic acid. Analysis of transcript abundances in excised inflorescences during an extended night suggested an intricate relationship among sugar starvation, senescence and SL biosynthesis and signalling.Antimicrobial resistance (AMR) has become a global medical priority that needs urgent resolution. Pseudomonas aeruginosa is a versatile, adaptable bacterial species with widespread environmental occurrence, strong medical relevance, a diverse set of virulence genes and a multitude of intrinsic and possibly acquired antibiotic resistance traits. P. aeruginosa causes a wide variety of infections and has an epidemic-clonal population structure. Several of its dominant global clones have collected a wide variety of resistance genes rendering them multi-drug resistant (MDR) and particularly threatening groups of vulnerable individuals including surgical patients, immunocompromised patients, Caucasians suffering from cystic fibrosis (CF) and more. AMR and MDR especially are particularly problematic in P. aeruginosa significantly complicating successful antibiotic treatment. In addition, antimicrobial susceptibility testing (AST) of P. aeruginosa can be cumbersome due to its slow growth or the massive production of exopolysaccharides and other extracellular compounds. For that reason, phenotypic AST is progressively challenged by genotypic methods using whole genome sequences (WGS) and large-scale phenotype databases as a framework of reference. We here summarize the state of affairs and the quality level of WGS-based AST for P. aeruginosa mostly from clinical origin.

    The health, well-being and safety of the general population are important goals for society, but forecasting outcomes and weighing up the costs and benefits of effective promotional programmes is challenging. This study aimed to identify and describe the cost-effectiveness calculators that analyze interventions that promote health, well-being and safety.

    Our systematic review used the CINAHL, PsycINFO, SocINDEX, EconLit, PubMed and Scopus databases to identify peer-reviewed studies published in English between January 2010 and April 2020. The data were analyzed with narrative synthesis.

    The searches identified 6880 papers and nine met our eligibility and quality criteria. All nine calculators focussed on interventions that promoted health and well-being, but no safety promotion tools were identified. Five calculators were targeted at group-level initiatives, two at regional levels and two at national levels. The calculators combined different data sources, in addition to data inputted by users. This inck accurately in different contexts might be challenging. Further research should identify how to assess sustainable evaluation of health, well-being and safety strategies.Electrocutions injuries are frequently encountered in a domestic setting or as an occupational hazard. Electrocutions injuries sustained in occupational settings are often associated with significant morbidity and mortality globally. Autopsy diagnosis of electrocution is mostly based on gross and histopathological changes in the entry and exit wounds. Gross changes in form of entry and exit wounds, however, may not be present in all cases of electrocution. In such cases, histopathological changes in the internal organs along the path of current can be useful. We report a case of fatal electrocution involving a 23-year-old young male in which remarkable gross and microscopic changes were appreciated in the lung due to the passage of electric current through it. Such observations are rarely reported in literature and highlight on the significance of autopsy pathology in the diagnosis of electrocution.Stachys pilifera Benth is an endemic species of Stachys family found in Iran with a wide application as an herbal tea. The objective of this research was to evaluate the antimicrobial, antioxidant and cytotoxic activity of the essential oil from the aerial parts of S. pilifera. Essential oil (EO) composition analysis showed that cis-Chrysanthenyl acetate (24.9%), viridiflorol (18.3%), trans-Caryophyllene (9.8%), caryophyllene oxide (4.6%), α-terpineol (3.3%) and linalool (3.1%) were the most abundant components. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the EO showed a higher antimicrobial activity against Gram-positive bacteria (Bacillus cereus and Staphylococcus aureus) than Gram-negative organisms (Escherichia coli, Shigella sonnei, Pseudomonas aeruginosa and Salmonella enterica subsp. Enterica). The antioxidant activity of EO was studied using DPPH, FRAP and β-carotene/linoleic acid assays. IC50 for the DPPH, FRAP and β-carotene/linoleic acid tests were 23.2, 28.7 and 16.1 µg/mL, respectively, that it was higher than the results for BHT (P ≤ 0.05). The cytotoxic activity of the EO was evaluated using HT29 and HUVEC cells and it was observed that by increasing in EO concentration from 0.026 to 19.4 ug/mL, the viability of the cells for HT29 and HUVEC reduced to 6.8 and 7.1%, respectively. The results from this study suggest the possibility to use the essential oils from S. pilifera Benth as a natural preservative in processed or packaged food due to its high antibacterial, antioxidant and cytotoxic activities.Neurogenerative diseases are characterized by diverse protein aggregates with a variety of microscopic morphologic features. Although ultrastructural studies of human neurodegenerative disease tissues have been conducted since the 1960s, only recently have near-atomic resolution structures of neurodegenerative disease aggregates been described. Solid-state nuclear magnetic resonance spectroscopy and X-ray crystallography have provided near-atomic resolution information about in vitro aggregates but pose logistical challenges to resolving the structure of aggregates derived from human tissues. Recent advances in cryo-electron microscopy (cryo-EM) have provided the means for near-atomic resolution structures of tau, amyloid-β (Aβ), α-synuclein (α-syn), and transactive response element DNA-binding protein of 43 kDa (TDP-43) aggregates from a variety of diseases. Importantly, in vitro aggregate structures do not recapitulate ex vivo aggregate structures. Ex vivo tau aggregate structures indicate individual tauopathies have a consistent aggregate structure unique from other tauopathies. α-syn structures show that even within a disease, aggregate heterogeneity may correlate to disease course. Ex vivo structures have also provided insight into how posttranslational modifications may relate to aggregate structure. Though there is less cryo-EM data for human tissue-derived TDP-43 and Aβ, initial structural studies provide a basis for future endeavors. This review highlights structural variations across neurodegenerative diseases and reveals fundamental differences between experimental systems and human tissue derived protein inclusions.

    There is a critical need for objective and reliable biomarkers of outcome in meningiomas beyond WHO classification. Loss of H3K27me3 has been reported as a prognostically unfavorable alteration in meningiomas. We sought to independently evaluate the reproducibility and prognostic value of H3K27me3 loss by immunohistochemistry (IHC) in a multi-center study.

    IHC staining for H3K27me3 and analyses of whole slides from 181 meningiomas across three centers was performed. Staining was analyzed by dichotomization into loss and retained immunoreactivity, and using a 3-tiered scoring system in 151 cases with clear staining. Associations of grouping with outcome was performed using Kaplan-Meier survival estimates.

    A total of 21 of 151 tumours (13.9%) demonstrated complete loss of H3K27me3 staining in tumour with retained endothelial staining. Overall, loss of H3K27me3 portended a worse outcome with shorter times to recurrence in our cohort, particularly for WHO grade 2 tumours which were enriched in our study. There were no differences in recurrence-free survival (RFS) for WHO grade 3 patients with retained versus loss of H3K27me3. Scoring by a 3-tiered system did not add further insights into the prognostic value of this H3K27me3 loss. Overall, loss of H3K27me3 was not independently associated with RFS after controlling for WHO grade, extent of resection, sex, age, and recurrence status of tumour on multivariable Cox regression analysis.

    Loss of H3K27me3 identifies a subset of WHO grade 2 and possibly WHO grade 1 meningiomas with increased recurrence risk. Pooled analyses of a larger cohort of samples with standardized reporting of clinical definitions and staining patterns is warranted.

    Loss of H3K27me3 identifies a subset of WHO grade 2 and possibly WHO grade 1 meningiomas with increased recurrence risk. Pooled analyses of a larger cohort of samples with standardized reporting of clinical definitions and staining patterns is warranted.Autosomal recessive osteopetrosis (ARO) is a severe inherited bone disease characterized by defective osteoclast resorption or differentiation. Clinical manifestations include dense and brittle bones, anemia and progressive nerve compression, which hamper the quality of patients’ lives and cause death in the first 10 years of age. This Review describes the pathogenesis of ARO and highlights the strengths and weaknesses of the current standard of care, namely hematopoietic stem cell transplantation (HSCT). Despite an improvement in the overall survival and outcomes of HSCT, transplant-related morbidity and the pre-existence of neurological symptoms significantly limit the success of HSCT, while the availability of human leukocyte antigen (HLA)-matched donors still remains an open issue. Novel therapeutic approaches are needed for ARO patients, especially for those that cannot benefit from HSCT. Here, we review preclinical and proof-of-concept studies, such as gene therapy, systematic administration of deficient protein, in utero HSCT and gene editing.Programs that provide affordable and stable housing may contribute to better child health and thus to fewer missed days of school. Drawing on a unique linkage of survey and administrative data, we use a quasi-experimental approach to examine the impact of rental assistance programs on missed days of school due to illness. We compare missed school days due to illness among children receiving rental assistance with those who will enter assistance within two years of their interview, the average length of waitlists for federal rental assistance. Overall, we find that children who receive rental assistance miss fewer days of school due to illness relative to those in the pseudo-waitlist group. We demonstrate that rental assistance leads to a reduction in the number of health problems among children and thus to fewer days of school missed due to illness. We find that the effect of rental assistance on missed school days is stronger for adolescents than for younger children. Additionally, race-stratified analyses reveal that rental assistance leads to fewer missed days due to illness among non-Hispanic White and Hispanic/Latino children; this effect, however, is not evident for non-Hispanic Black children, the largest racial/ethnic group receiving assistance.

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