Arabidopsis ecotype Ct-1, with its altered nitrate sensing ability, exhibits enhanced growth under low nitrate conditions in comparison to Col-0.

To address the urgent need for sustainable solutions to the increased use of nitrogen fertilizers in agriculture, it is imperative to acquire an in-depth comprehension of the intricate interplay between plants and nitrogen. In this context, our research aimed to elucidate the molecular mechanism behind NO3- sensing/signaling in plants, which can enhance nitrogen utilization efficiency. Previous reports have revealed that the density and quantity of root hairs exhibit responsive behavior to varying levels of NO3-, while the precise molecular mechanisms governing these changes remain elusive. To further investigate this phenomenon, we specifically selected the Ct-1 ecotype, which manifested a greater abundance of root hairs compared to the Col-0 ecotype under conditions of low NO3-. Our investigations unveiled that the dissimilarities in the amino acid sequence of NRT1.1, a transceptor responsible for regulating nitrate signaling and transport, accounted for the observed variation in root hair numbers. These results suggest that NRT1.1 represents a promising target for gene editing technology, offering potential applications in enhancing the efficiency of nitrogen utilization in agricultural crops.

Antisense Oligonucleotide Modified with Disulfide Units Induces Efficient Exon Skipping in mdx Myotubes through Enhanced Membrane Permeability and Nucleus Internalization.

We have found that antisense oligonucleotides and siRNA molecules modified with repeat structures of disulfide units can be directly introduced into the cytoplasm and exhibit a suppressive effect on gene expression. In this study, we analyzed the mechanism of cellular uptake of these membrane-permeable oligonucleotides (MPONs). Time-course analysis by confocal microscopy showed that the uptake of MPONs from the plasma membrane to the cytoplasm reached 50 % of the total uptake in about 5 min. In addition, analysis of the plasma membrane proteins to which MPONs bind, identified several proteins, including voltage-dependent anion channel. Next, we analyzed the behavior of MPONs in the cell and found them to be abundant in the nucleus as early as 24 h after addition with the amount increasing further after 48 and 72 h. The amount of MPONs was 2.5-fold higher than that of unmodified oligonucleotides in the nucleus after 72 h. We also designed antisense oligonucleotides and evaluated the effect of MPONs on mRNA exon skipping using DMD model cells; MPONs caused exon skipping with 69 % efficiency after 72 h, which was three times higher than the rate of the control. In summary, the high capacity for intracytoplasmic and nuclear translocation of MPONs is expected to be useful for therapeutic strategies targeting exon skipping.

Impacts of Morally Distressing Experiences on the Mental Health of Canadian Health Care Workers During the COVID-19 Pandemic

ObjectiveResearch is urgently needed to understand health care workers (HCWs) experiences of moral-ethical dilemmas encountered throughout the COVID-19 pandemic, and their associations with organizational perceptions and personal well-being. The purpose of this research is to evaluate associations between workplace experiences during COVID-19, moral distress, and the psychological well-being of Canadian HCWs. MethodA total of 1383 French- and English-speaking Canadian HCWs employed during the COVID-19 pandemic were recruited to participate in an online survey. Participants completed measures reflecting moral distress, perceptions of organizational response to the pandemic, burnout, and symptoms of psychological disorders, including depression, anxiety, and posttraumatic stress disorder. ResultsStructural equation modeling showed that when organizational predictors were considered together, resource adequacy, positive work life impact, and ethical work environment negatively predicted severity of moral distress, whereas COVID-19 risk perception positively predicted severity of moral distress. Moral distress also significantly and positively predicted symptoms of depression, anxiety, PTSD, and burnout. ConclusionsOur findings highlight an urgent need for HCW organizations to implement strategies designed to prevent long-term moral and psychological distress within the workplace. Ensuring availability of adequate resources, reducing HCW risk of contracting COVID-19, providing organizational support regarding individual priorities, and upholding ethical considerations are crucial to reducing severity of moral distress in HCWs.

Lemon Grass Essential Oil Does not Modulate Cancer Cells Multidrug Resistance by Citral-Its Dominant and Strongly Antimicrobial Compound.

With strong antimicrobial properties, citral has been repeatedly reported to be the dominant component of lemongrass essential oil. Here, we report on a comparison of the antimicrobial and anticancer activity of citral and lemongrass essential oil. The lemongrass essential oil was prepared by the vacuum distillation of fresh Cymbopogon leaves, with a yield of 0.5% (w/w). Citral content was measured by gas chromatography/high-resolution mass spectrometry (GC-HRMS) and determined to be 63%. Antimicrobial activity was tested by the broth dilution method, showing strong activity against all tested bacteria and fungi. Citral was up to 100 times more active than the lemongrass essential oil. Similarly, both citral and essential oils inhibited bacterial communication and adhesion during P. aeruginosa and S. aureus biofilm formation; however, the biofilm prevention activity of citral was significantly higher. Both the essential oil and citral disrupted the maturated P. aeruginosa biofilm with the IC50 7.3 ± 0.4 and 0.1 ± 0.01 mL/L, respectively. Although it may seem that the citral is the main biologically active compound of lemongrass essential oil and the accompanying components have instead antagonistic effects, we determined that the lemongrass essential oil-sensitized methicillin-resistant S. aureus (MRSA) and doxorubicin-resistant ovarian carcinoma cells and that this activity was not caused by citral. A 1 mL/L dose of oil-sensitized MRSA to methicillin up to 9.6 times and a dose of 10 µL/L-sensitized ovarian carcinoma to doxorubicin up to 1.8 times. The mode of multidrug resistance modulation could be due to P-glycoprotein efflux pump inhibition. Therefore, the natural mixture of compounds present in the lemongrass essential oil provides beneficial effects and its direct use may be preferred to its use as a template for citral isolation.

dbVar structural variant cluster set for data analysis and variant comparison.

dbVar houses over 3 million submitted structural variants (SSV) from 120 human studies including copy number variations (CNV), insertions, deletions, inversions, translocations, and complex chromosomal rearrangements. Users can submit multiple SSVs to dbVAR  that are presumably identical, but were ascertained by different platforms and samples,  to calculate whether the variant is rare or common in the population and allow for cross validation. However, because SSV genomic location reporting can vary - including fuzzy locations where the start and/or end points are not precisely known - analysis, comparison, annotation, and reporting of SSVs across studies can be difficult. This project was initiated by the Structural Variant Comparison Group for the purpose of generating a non-redundant set of genomic regions defined by counts of concordance for all human SSVs placed on RefSeq assembly GRCh38 (RefSeq accession GCF_000001405.26). We intend that the availability of these regions, called structural variant clusters (SVCs), will facilitate the analysis, annotation, and exchange of SV data and allow for simplified display in genomic sequence viewers for improved variant interpretation. Sets of SVCs were generated by variant type for each of the 120 studies as well as for a combined set across all studies. Starting from 3.64 million SSVs, 2.5 million and 3.4 million non-redundant SVCs with count >=1 were generated by variant type for each study and across all studies, respectively. In addition, we have developed utilities for annotating, searching, and filtering SVC data in GVF format for computing summary statistics, exporting data for genomic viewers, and annotating the SVC using external data sources.

Genome-wide association study identifies susceptibility loci for dengue shock syndrome at MICB and PLCE1.

Hypovolemic shock (dengue shock syndrome (DSS)) is the most common life-threatening complication of dengue. We conducted a genome-wide association study of 2,008 pediatric cases treated for DSS and 2,018 controls from Vietnam. Replication of the most significantly associated markers was carried out in an independent Vietnamese sample of 1,737 cases and 2,934 controls. SNPs at two loci showed genome-wide significant association with DSS. We identified a susceptibility locus at MICB (major histocompatibility complex (MHC) class I polypeptide-related sequence B), which was within the broad MHC region on chromosome 6 but outside the class I and class II HLA loci (rs3132468, P(meta) = 4.41 × 10(-11), per-allele odds ratio (OR) = 1.34 (95% confidence interval: 1.23-1.46)). We identified associated variants within PLCE1 (phospholipase C, epsilon 1) on chromosome 10 (rs3765524, P(meta) = 3.08 × 10(-10), per-allele OR = 0.80 (95% confidence interval: 0.75-0.86)). We identify two loci associated with susceptibility to DSS in people with dengue, suggesting possible mechanisms for this severe complication of dengue.

The impact of health education on mother's knowledge, attitude and practice (KAP) of dengue haemorrhagic fever.

A mother’s knowledge, attitude and practice (KAP) study before and after health education of dengue haemorrhagic fever (DHF) was carried out in four communes in Southern Viet Nam. The study showed that health education had made a strong impact on the mothers’ KAP of DHF. The KAP of mothers (how to recognize the child with DHF, how to take care of the child at home, and how to prevent the disease) were improved significantly after health education. This effective programme of health education on DHF can be implemented in other communities as part of the national programme for dengue control.