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Also, Bik, when tagged with a blue-fluorescent protein, was only detected in green cells. Bik phosphorylation mutants at threonine 33 or serine 35 demonstrated that phosphorylation activated Bik to induce death even in quiescent cells. Immunoprecipitation and proteomic approaches identified casein kinase IIα to be responsible for phosphorylating and activating Bik to kill cells in S/G2/M. As casein kinase 2 alpha (CKIIα) is expressed only during the G2/M phase, we conclude that Bik activation in airway epithelial cells selectively targets hyperplastic epithelial cells, while leaving resting airway cells unaffected.
Garlic (Allium sativum L.), whose bioactive components are mainly organosulfur compounds (OSCs), is a herbaceous perennial widely consumed as a green vegetable and a condiment. Yet, the metabolic enzymes involved in the biosynthesis of OSCs are not identified in garlic.
Here, a full-length transcriptome of purple garlic was generated via PacBio and Illumina sequencing, to characterize the garlic transcriptome and identify key proteins mediating the biosynthesis of OSCs. Overall, 22.56 Gb of clean data were generated, resulting in 454 698 circular consensus sequence (CCS) reads, of which 83.4% (379 206) were identified as being full-length non-chimeric reads - their further transcript clustering facilitated identification of 36 571 high-quality consensus reads. Once corrected, their genome-wide mapping revealed that 6140 reads were novel isoforms of known genes, and 2186 reads were novel isoforms from novel genes. We detected 1677 alternative splicing events, finding 2902 genes possessing either two or more timely genetic resources that could advance future exploration into garlic's genetic improvement and breeding. © 2021 Society of Chemical Industry.Jacaric acid, a conjugated linolenic acid (CLNA) present in jacaranda oil (JO), is considered a potent anticarcinogenic agent. Several studies have focused on its biological effects, but the metabolism once consumed is not clear yet. The aim of this work was to evaluate the effects of two different daily doses of JO on serum parameters and fatty acid (FA) profile of mice tissues after 4 weeks of feeding. No significant changes on body weight gain, food intake, or tissue weight were determined after 0.7 or 2 ml/kg of JO supplementation compared to control animals. Significantly lower blood low-density lipoproteins-cholesterol (20 mg/dl) and glucose (~147-148 mg/dl) levels were detected in both oil-treated groups compared to control (31.2 and 165 mg/dl, respectively). Moreover, jacaric acid was partially converted into cis9, trans11 conjugated linoleic acid (CLA) and thus further incorporated into tissues. Liver evidenced the highest total conjugated fatty acid content (1.1%-2.2%), followed by epididymal (0.7%-1.9%) and mesenteric (1.4%-1.8%) fat. Lower saturated and higher unsaturated fatty acid content was detected in both oil-treated groups compared to control. Our results support the safety of JO and its potential application with a functional or nutraceutical propose, by increasing human CLNA consumption and further availability of CLA.
Gadolinium-based contrast agents (GBCAs) may add value to magnetic resonance (MR)-only radiotherapy (RT) workflows including on hybrid machines such as the MR Linac. The impact of GBCAs on RT dose distributions however have not been well studied. This work used retrospective GBCA-enhanced datasets to assess the dosimetric effect of GBCAs on head and neck plans.
Ten patients with oropharyngeal squamous cell carcinoma receiving RT from November 2018 to April 2020 were included in this study. RT planning included contrast-enhanced computed tomography (CT) and MR scans. A contrast agent "contour" was defined by delineating GBCA-enhanced regions using an agreed window/level threshold, transferred to the planning CT and given a standardized electron density (ED) of 1.149 in the Monaco treatment planning system (Elekta AB). Four plans were per patient calculated and compared using two methods (1) optimized without contrast (Plan A) then recalculated with ED (Plan B), and (2) optimized with contrast ED (Plan C) ting for GBCAs may not be needed in daily adaptive workflows on the MR Linac.
Dose differences to targets and OARs in oropharyngeal cancer treatment due to the presence of GBCA were minimal, and this work suggests that prospective in vivo evaluations of impact may not be necessary in this clinical site. Accounting for GBCAs may not be needed in daily adaptive workflows on the MR Linac.
Pea sprouts are considered a healthy food. Sucrose is a key nutritional factor affecting taste and flavor. Meanwhile, selenium (Se) is an essential micronutrient that plays multiple roles in wide variety of physiological processes and improves crop quality and nutritional value. Nonetheless, the effects of the combination of sucrose and Se treatment on growth, quality, and sugar metabolism of pea sprouts have not been explored.
The results revealed that sucrose at 10mg L
obviously increased fresh weight, vitamin C, soluble protein, soluble sugar, fructose, glucose, and sucrose contents. Se treatments also improved nutritional quality, but higher Se (2.5mg L
) significantly inhibited the growth of seedlings. Interestingly, the combined application of sucrose (10mg L
) and Se (1.25 mg L
) could effectively promote vitamin C, sucrose, and fructose contents, especially the Se content, compared with Se application alone. Additionally, there were significant differences in the regulation of sugar metabolism between Se alone and combined application of sucrose and Se. Acid invertase and neutral invertase play a pivotal role in the accumulation of soluble sugar under Se treatments alone, and acid invertase might be the key enzyme to limit sugar accumulation under combined application of sucrose and Se.
The moderate combined application of sucrose (10mg L
) and Se (1.25 mg L
) more effectively regulated sugar metabolism and improved nutritional quality than Se application alone did. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
The moderate combined application of sucrose (10 mg L-1 ) and Se (1.25 mg L-1 ) more effectively regulated sugar metabolism and improved nutritional quality than Se application alone did. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.Congenital heart defects (CHD) are the most commonly occurring birth defect and can occur in isolation or with additional clinical features comprising a genetic syndrome. Autosomal dominant variants in TAB2 are recognized by the American Heart Association as causing nonsyndromic CHD, however, emerging data point to additional, extra-cardiac features associated with TAB2 variants. We identified 15 newly reported individuals with pathogenic TAB2 variants and reviewed an additional 24 subjects with TAB2 variants in the literature. Analysis showed 64% (25/39) of individuals with disease resulting from TAB2 single nucleotide variants (SNV) had syndromic CHD or adult-onset cardiomyopathy with one or more extra-cardiac features. click here The most commonly co-occurring features with CHD or cardiomyopathy were facial dysmorphism, skeletal and connective tissue defects and most subjects with TAB2 variants present as a connective tissue disorder. Notably, 53% (8/15) of our cohort displayed developmental delay and we suspect this may be a previously unappreciated feature of TAB2 disease. We describe the largest cohort of subjects with TAB2 SNV and show that in addition to heart disease, features across multiple systems are present in most TAB2 cases. In light of our findings, we recommend that TAB2 be included on the list of genes that cause syndromic CHD, adult-onset cardiomyopathy, and connective tissue disorder.
Molecular-based tests used to identify symptomatic or asymptomatic patients infected by SARS-CoV-2 are characterized by high specificity but scarce sensitivity, generating false negative results. We aimed to estimate, through a systematic review of the literature, the rate of RT-PCR false-negatives at initial testing for COVID-19.
We systematically searched Pubmed, Embase, and CENTRAL as well as a list of reference literature. We included observational studies collected samples from respiratory tract to detect SARS-CoV-2 RNA using RT-PCR, reporting the number of false negative subjects and the number of final patients with a COVID-19 diagnosis. Reported rates of false negatives were pooled in a meta-analysis as appropriate. We assessed the risk of bias of included studies and graded the quality of evidence according to the GRADE method. All information in this article is current up to February 2021.
We included 32 studies, enrolling more than 18,000 patients infected by SARS-CoV-2. The overall false negative rate was of 0.12 (95%CI from 0.10 to 0.14) with very low certainty of evidence. The impact of misdiagnoses was estimated according to disease prevalence; a range between 2 -58/1,000 subjects could be misdiagnosed with a disease prevalence of 10%, increasing to 290/1,000 misdiagnosed subjects with a disease prevalence of 50%.
This systematic review showed that up to 58% of COVID-19 patients may have initial false-negative RT-PCR results, suggesting the need to implement a correct diagnostic strategy to correctly identify suspected cases, thereby reducing false negative results and decreasing the disease burden among the population.
This systematic review showed that up to 58% of COVID-19 patients may have initial false-negative RT-PCR results, suggesting the need to implement a correct diagnostic strategy to correctly identify suspected cases, thereby reducing false negative results and decreasing the disease burden among the population.
No studies have examined the longitudinal association between the persistence of pain and its relationship to cognitive problems in older adults. The objective of this study was to examine how the persistent of pain associates with cognitive performance, cognitive impairment, and subjective memory decline.
Across 10 biennial waves, 8515 adults ages 65 and over were assessed from the Health and Retirement Study (M
=74.17, SD=6.87, 59.2% female). At each wave, individuals were asked to report on pain presence, and if present, rate its intensity and interference with daily activities such as housework or chores. Using running frequencies or averages, we calculated the persistence of pain using these three pain measures. Cognition was assessed using cognitive performance and different cognitive impairment cutoffs. Incident subjective memory decline was additionally measured as new self-reported memory change in the last 2 years. General estimating equations examined concurrent associations between persistens and work. Facilitating pain management might be important for helping to maintain later-life cognition and reduce dementia risk.
Focal cortical dysplasia (FCD) Type 1 and its three subtypes have yet not been fully characterized at the clinical, anatomopathological, and molecular level (International League Against Epilepsy [ILAE] FCD classification from 2011). We aimed to describe the clinical phenotype of patients with histopathologically confirmed FCD1A obtained from a single epilepsy center between 2002 and 2016.
Medical records were retrieved from the hospital's archive. Results from electroencephalography (EEG) video recordings, neuroimaging, and histopathology were reevaluated. Magnetic resonance imaging (MRI) post-processing was retrospectively performed in nine patients. DNA methylation studies were carried out from archival surgical brain tissue in 11 patients.
Nineteen children with a histopathological diagnosis of FCD1A were included. The average onset of epilepsy was 0.9years (range 0.2-10years). All children had severe cognitive impairment and one third had mild motor deficits, yet fine finger movements were preserved in all patients.
