A review of the potential involvement of small RNAs in transgenerational abiotic stress memory in plants.

Crop production is increasingly threatened by the escalating weather events and rising temperatures associated with global climate change. Plants have evolved adaptive mechanisms, including stress memory, to cope with abiotic stresses such as heat, drought, and salinity. Stress memory involves priming, where plants remember prior stress exposures, providing enhanced responses to subsequent stress events. Stress memory can manifest as somatic, intergenerational, or transgenerational memory, persisting for different durations. The chromatin, a central regulator of gene expression, undergoes modifications like DNA acetylation, methylation, and histone variations in response to abiotic stress. Histone modifications, such as H3K4me3 and acetylation, play crucial roles in regulating gene expression. Abiotic stresses like drought and salinity are significant challenges to crop production, leading to yield reductions. Plant responses to stress involve strategies like escape, avoidance, and tolerance, each influencing growth stages differently. Soil salinity affects plant growth by disrupting water potential, causing ion toxicity, and inhibiting nutrient uptake. Understanding plant responses to these stresses requires insights into histone-mediated modifications, chromatin remodeling, and the role of small RNAs in stress memory. Histone-mediated modifications, including acetylation and methylation, contribute to epigenetic stress memory, influencing plant adaptation to environmental stressors. Chromatin remodeling play a crucial role in abiotic stress responses, affecting the expression of stress-related genes. Small RNAs; miRNAs and siRNAs, participate in stress memory pathways by guiding DNA methylation and histone modifications. The interplay of these epigenetic mechanisms helps plants adapt to recurring stress events and enhance their resilience. In conclusion, unraveling the epigenetic mechanisms in plant responses to abiotic stresses provides valuable insights for developing resilient agricultural techniques. Understanding how plants utilize stress memory, histone modifications, chromatin remodeling, and small RNAs is crucial for designing strategies to mitigate the impact of climate change on crop production and global food security.

Maternal and perinatal health research during emerging and ongoing epidemic threats: a landscape analysis and expert consultation.

INTRODUCTION: Pregnant women and their offspring are often at increased direct and indirect risks of adverse outcomes during epidemics and pandemics. A coordinated research response is paramount to ensure that this group is offered at least the same level of disease prevention, diagnosis, and care as the general population. We conducted a landscape analysis and held expert consultations to identify research efforts relevant to pregnant women affected by disease outbreaks, highlight gaps and challenges, and propose solutions to addressing them in a coordinated manner. METHODS: Literature searches were conducted from 1 January 2015 to 22 March 2022 using Web of Science, Google Scholar and PubMed augmented by key informant interviews. Findings were reviewed and Quid analysis was performed to identify clusters and connectors across research networks followed by two expert consultations. These formed the basis for the development of an operational framework for maternal and perinatal research during epidemics. RESULTS: Ninety-four relevant research efforts were identified. Although well suited to generating epidemiological data, the entire infrastructure to support a robust research response remains insufficient, particularly for use of medical products in pregnancy. Limitations in global governance, coordination, funding and data-gathering systems have slowed down research responses. CONCLUSION: Leveraging current research efforts while engaging multinational and regional networks may be the most effective way to scale up maternal and perinatal research preparedness and response. The findings of this landscape analysis and proposed operational framework will pave the way for developing a roadmap to guide coordination efforts, facilitate collaboration and ultimately promote rapid access to countermeasures and clinical care for pregnant women and their offspring in future epidemics.

Assessment of salt and drought stress on the biochemical and molecular functioning of onion cultivars.

BACKGROUND: Salt and drought stress are the main environmental constraints that limit onion growth and productivity. Türkiye is the fifth largest onion producer, whereas the stress conditions are increasing in the region, resulting in poor crop growth. METHODS AND RESULTS: A current study was conducted under greenhouse conditions according to a completely randomized design with factorial arrangements to evaluate the performance of onion cultivars. Plants were subjected to salt stress with an application of 750 mM NaCl and drought stress was applied by depriving plants of irrigation water for 20 days to measure biochemical and transcript changes. The antioxidant activities of the cultivars were quantified by using four different methods, i.e., 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assays, cupric reducing antioxidant capacity, 2,2-Diphenyl-1-picrylhydrazyl, and ferric reducing antioxidant power (FRAP). The damage to pigments, phenolic, osmolytes, and hydrogen peroxide (H2O2) accumulation was also evaluated. Results revealed that the cultivars "Elit and Hazar" had higher H2O2, maximum damage to pigments, and least accumulation of phenolics and osmolytes under both stress conditions. The cultivar "Sampiyon" performance was better under salt stress but exhibited a poor antioxidant defensive mechanism under drought stress conditions. The remaining cultivars suggested a resilient nature with a higher accumulation of osmolytes, antioxidants and phenolics. The change in transcript levels further strengthened the response of resilient cultivars; for instance, they showed higher transcript levels of superoxide dismutase, ascorbate oxidase and transcription factors (WRKY70, NAC29). It helped alleviate the oxidative stress in tolerant cultivars and maintained the physio-biochemical functioning of the cultivars.. CONCLUSION: The results of the current study will fill the gap of missing literature in onion at biochemical and molecular levels. Additionally, resilient cultivars can effectively cope with abiotic stresses to ensure future food security.

Developing future heat-resilient vegetable crops.

Climate change seriously impacts global agriculture, with rising temperatures directly affecting the yield. Vegetables are an essential part of daily human consumption and thus have importance among all agricultural crops. The human population is increasing daily, so there is a need for alternative ways which can be helpful in maximizing the harvestable yield of vegetables. The increase in temperature directly affects the plants' biochemical and molecular processes; having a significant impact on quality and yield. Breeding for climate-resilient crops with good yields takes a long time and lots of breeding efforts. However, with the advent of new omics technologies, such as genomics, transcriptomics, proteomics, and metabolomics, the efficiency and efficacy of unearthing information on pathways associated with high-temperature stress resilience has improved in many of the vegetable crops. Besides omics, the use of genomics-assisted breeding and new breeding approaches such as gene editing and speed breeding allow creation of modern vegetable cultivars that are more resilient to high temperatures. Collectively, these approaches will shorten the time to create and release novel vegetable varieties to meet growing demands for productivity and quality. This review discusses the effects of heat stress on vegetables and highlights recent research with a focus on how omics and genome editing can produce temperature-resilient vegetables more efficiently and faster.

Retrospective Comparison of Patients ≥ 80 Years With Atrial Fibrillation Prescribed Either an FDA-Approved Reduced or Full Dose Direct-Acting Oral Anticoagulant.

Direct-acting oral anticoagulants (DOACs) represent the standard for preventing stroke and systemic embolization (SSE) in patients with atrial fibrillation (AF). There is limited information for patients ≥ 80 years. We report a retrospective analysis of AF patients ≥ 80 years prescribed either a US Food and Drug Administration (FDA)-approved reduced (n = 514) or full dose (n = 199) DOAC (Dabigatran, Rivaroxaban, or Apixaban) between January 1st, 2011 (first DOAC commercially available) and May 31st, 2017. The following multivariable differences in baseline characteristics were identified: patients prescribed a reduced dose DOAC were older (p < 0.001), had worse renal function (p = 0.001), were more often prescribed aspirin (p = 0.004) or aspirin and clopidogrel (p < 0.001), and more often had new-onset AF (p = 0.001). SSE and central nervous system (CNS) bleed rates were low and not different (1.02 vs 0 %/yr and 1.45 vs 0.44 %/yr) for the reduced and full dose groups, respectively. For non-CNS bleeds, rates were 10.89 vs 4.15 %/yr (p < 0.001, univariable) for the reduced and full doses, respectively. The mortality rate was 6.24 vs 1.75 %/yr (p = 0.001, univariable) for the reduced and full doses. Unlike the non-CNS bleed rate, mortality rate differences remained significant when adjusted for baseline characteristics. Thus, DOACs in patients ≥ 80 with AF effectively reduce SSE with a low risk of CNS bleeding, independent of DOAC dose. The higher non-CNS bleed rate and not the mortality rate is explained by the higher risk baseline characteristics in the reduced DOAC dose group. Further investigation of the etiology of non-CNS bleeds and mortality is warranted.

Assessment of Heavy Metal Accumulation in Soil and Garlic Influenced by Waste-Derived Organic Amendments.

In South Asia, the high costs of synthetic fertilizers have imposed research on alternative nutrient inputs. We aimed to identify potential trace elements (PTE) present in some organic manure that might be a source of environmental pollutions and risk to public health following consumption. The study aims to evaluate how different organic waste (poultry waste, PW; press mud, PM; and farmyard manure, FYM) influences the heavy metal migration in soil, the accumulation in garlic, and their potential health risks. Organic waste caused a higher accumulation of certain metals (Zn, Cu, Fe, and Co), whereas Mn, Cd, Cr, and Pb were in lower concentrations in soil. Amendments of soil with PM revealed a higher accumulation of Cd, Cr, Fe, and Pb, whereas PW resulted in Cu and Zn accumulation in garlic. Treatment of soil with FYM exhibited higher metal concentration of Co and Mn. An environmental hazard indices study revealed that pollution load index (PLI) was highest for Cu following treatment with PM. The health risk index (HRI) was greater for Cd following amendment with PM. Maximum daily intake of metals (DIM) was observed for Zn after treatment with PW. The Pb exhibited maximum bioconcentration factor (BCF) in PM-amended plants. Based on these findings, we concluded that garlic grown on contaminated soil with organic waste may pose serious health hazards following consumption.

Comparative transcriptomics of drought stress response of taproot meristem region of contrasting purple carrot breeding lines supported by physio-biochemical parameters.

Carrot is one of the nutritious vegetable crops sensitive to drought stress resulting in loss of quality and yield. There are a lot of studies on detailed molecular mechanisms of drought stress response of main crops; however, very little information available on vegetables, including carrots. Hence, in this study, we investigated root transcriptome profiles from the meristematic region of two contrasting purple carrot (B7262A, drought tolerant; P1129, drought sensitive) lines under varying stress levels (85% and 70%) by using RNA-Seq technique. The morpho-physiological and biochemical response of B7262A line exhibited tolerance behavior to both DS (85% and 70%). RNA-Seq analysis revealed that 15,839 genes were expressed commonly in both carrot lines. The carrot line B7262A showed regulation of 514 genes in response to 85% DS, whereas P1129 showed differential regulation of 622 genes under 70% DS. The B7262A carrot line showed higher upregulation of transcripts that suggested its resilient behavior contrary to P1129 line. Furthermore, validation of transcript gene by qRT-PCR also confirmed the RNA-Seq analysis resulting in elevated expression levels of MYB48 transcription factor, MAPK mitogen-activated protein kinase ANP1, GER geraniol 8-hydroxylase, ABA ABA-induced in somatic embryo 3, FBOX putative F-box protein, FRO ferric reduction oxidase, and PDR probable disease resistance protein. Current study provided unprecedented insights of purple carrot lines that can be potentially exploited for the screening and development of resilient carrot.

Moving Beyond DNA Sequence to Improve Plant Stress Responses.

Plants offer a habitat for a range of interactions to occur among different stress factors. Epigenetics has become the most promising functional genomics tool, with huge potential for improving plant adaptation to biotic and abiotic stresses. Advances in plant molecular biology have dramatically changed our understanding of the molecular mechanisms that control these interactions, and plant epigenetics has attracted great interest in this context. Accumulating literature substantiates the crucial role of epigenetics in the diversity of plant responses that can be harnessed to accelerate the progress of crop improvement. However, harnessing epigenetics to its full potential will require a thorough understanding of the epigenetic modifications and assessing the functional relevance of these variants. The modern technologies of profiling and engineering plants at genome-wide scale provide new horizons to elucidate how epigenetic modifications occur in plants in response to stress conditions. This review summarizes recent progress on understanding the epigenetic regulation of plant stress responses, methods to detect genome-wide epigenetic modifications, and disentangling their contributions to plant phenotypes from other sources of variations. Key epigenetic mechanisms underlying stress memory are highlighted. Linking plant response with the patterns of epigenetic variations would help devise breeding strategies for improving crop performance under stressed scenarios.

Use of cone beam computed tomography imaging for airway measurement to predict obstructive sleep apnea.

Objective: This retrospective chart review examined whether airway parameters were correlated with scores on the STOP-Bang questionnaire.Methods: Minimal upper airway area, upper airway volume, minimal retropalatal area, retropalatal volume, minimal retroglossal area, and retroglossal volume were calculated from cone beam computed tomography (CBCT) images. Patients were grouped based on their STOP-Bang scores (<3 or ≥3) for obstructive sleep apnea (OSA), and airway parameters were compared across the 2 groups.Results: Thirty-one (43%) of 72 patients with a minimal upper airway area of <110 mm2 had STOP-Bang scores of ≥3. Most patients (90%) with STOP-Bang scores of ≥3 had minimal retropalatal areas of <110 mm2. Differences were found between groups for minimal upper airway area (p = 0.03), upper airway volume (p = 0.04), and minimal retropalatal area (p = 0.001).Discussion: To assess OSA risk, dentists should compare CBCT images with STOP-Bang scores.

Unraveling Sorghum Allelopathy in Agriculture: Concepts and Implications.

Allelopathy is an ecological phenomenon that involves the production and release of biomolecules from different crops, cultivated plants, and bacteria or fungi into the soil rhizosphere and impacts other organisms in the vicinity. Sorghum possesses vital allelopathic characteristics due to which it produces and releases different biomolecules from its root hairs, stems, and grains. Several studies have reported that sorghum acts as an allelopathic crop, decreasing the growth and eco-physiological attributes of surrounding plants and weeds growing simultaneously or subsequently in the field. Sorghum allelopathy has been exploited in the context of green manure, crop rotations, cover crops, and intercropping or mulching, whereas plant aqueous extracts or powder might be an alternate method of weed control. A diverse group of allelochemicals, including benzoic acid, p-hydroxybenzoic acid, vanillic acid, ferulic acid, chlorogenic acid, m-coumaric acid, p-coumaric acid, gallic acid, caffeic acid, p-hydroxibenzaldehyde, dhurrin, sorgoleone, m-hydroxybenzoic acid and protocatechuic acid, have been isolated and identified from different plant tissues of sorghum and root exudates. These allelochemicals, especially sorgoleone, have been investigated in terms of their mode(s) of action, specific activity and selectivity, release in the rhizosphere and uptake and translocation in sensitive species. The present review describes the importance of sorghum allelopathy as an ecological tool in managing weeds, highlighting the most recent advances in the allelochemicals present in sorghum, their modes of action, and their fate in the ecosystem. Further research should focus on the evaluation and selection of sorghum cultivars with high allelopathic potential, so that sorghum allelopathy can be better utilized for weed control and yield enhancement.

Comparison of Low-Dose Direct Acting Anticoagulant and Warfarin in patients Aged ≥80 years With Atrial Fibrillation.

Low dose direct acting oral anticoagulants (LDDOACS) were approved for elderly atrial Fibrillation (AF) patients with limited information. A retrospective analysis collecting baseline characteristics and outcomes in AF patients ≥ 80 prescribed LDDOAC or warfarin (W), from a multidisciplinary practice between 1/1/11 (First LDDOAC available) and 5/31/17 was conducted. From 9660 AF patients, 514 ≥ 80 received a LDDOAC and 422 W. A multivariable comparison found LDDOAC patients were older (p <0.001), had lower creatinine clearance (CrCl) (p = 0.006), used more anti-platelet drugs (p <0.001), and more often had new onset AF verses those prescribed W (p <0.001). There were no clinically significant differences among those patients receiving Dabigatran 75 mgs BID (D), Rivaroxaban 15mgs (R) or Apixaban 2.5mgs BID (A). Forty-eight and 50% of the patients remained on their LDDOAC or W for the observation period (p = 0.55). Stroke/systemic embolism (SSE) and CNS bleeds were 1.16 vs 2.22%/yr., (p = 0.143) and 1.46 vs 0.93%/yr., (p = 0.24). Mortality and major bleeds were 6.26 vs 1.67%/yr., and 12.3vs 3.77%/yr. (p <0.001). SSE were 1.1%/yr for D, R, and A (p = 0.94). CNS bleeds were 2.2 for D, 1.7 for R and 0.8%/yr. for A: p = 0.53. Major bleeding was: 14.3 for D, 14.1 for R and 9.1%/yr. for A, p = 0.048 (with A < R, p = 0.01). Mortality was 5.5 for D, 4.2 for R and 9.5% for A, p = 0.031. In conclusion, half the patients remained on their assigned anti-coagulant. SSE and intracranial bleed rates were similar and low. Major bleeds and deaths were different between groups emphasizing the need for prospective randomized trials in this growing population with AF.

Dupilumab progressively improves systemic and cutaneous abnormalities in patients with atopic dermatitis.

BACKGROUND: Dupilumab is an IL-4 receptor α mAb inhibiting signaling of IL-4 and IL-13, key drivers of type 2-driven inflammation, as demonstrated by its efficacy in patients with atopic/allergic diseases. OBJECTIVE: This placebo-controlled, double-blind trial (NCT01979016) evaluated the efficacy, safety, and effects of dupilumab on molecular/cellular lesional and nonlesional skin phenotypes and systemic type 2 biomarkers of patients with moderate-to-severe atopic dermatitis (AD). METHODS: Skin biopsy specimens and blood were evaluated from 54 patients randomized 1:1 to weekly subcutaneous doses of 200 mg of dupilumab or placebo for 16 weeks. RESULTS: Dupilumab (vs placebo) significantly improved clinical signs and symptoms of AD, was well tolerated, and progressively shifted the lesional transcriptome toward a nonlesional phenotype (weeks 4-16). Mean improvements in a meta-analysis-derived AD transcriptome (genes differentially expressed between lesional and nonlesional skin) were 68.8% and 110.8% with dupilumab and -10.5% and 55.0% with placebo (weeks 4 and 16, respectively; P < .001). Dupilumab significantly reduced expression of genes involved in type 2 inflammation (IL13, IL31, CCL17, CCL18, and CCL26), epidermal hyperplasia (keratin 16 [K16] and MKi67), T cells, dendritic cells (ICOS, CD11c, and CTLA4), and TH17/TH22 activity (IL17A, IL-22, and S100As) and concurrently increased expression of epidermal differentiation, barrier, and lipid metabolism genes (filaggrin [FLG], loricrin [LOR], claudins, and ELOVL3). Dupilumab reduced lesional epidermal thickness versus placebo (week 4, P = .001; week 16, P = .0002). Improvements in clinical and histologic measures correlated significantly with modulation of gene expression. Dupilumab also significantly suppressed type 2 serum biomarkers, including CCL17, CCL18, periostin, and total and allergen-specific IgEs. CONCLUSION: Dupilumab-mediated inhibition of IL-4/IL-13 signaling through IL-4 receptor α blockade significantly and progressively improved disease activity, suppressed cellular/molecular cutaneous markers of inflammation and systemic measures of type 2 inflammation, and reversed AD-associated epidermal abnormalities.

Effects of the time interval between prostate brachytherapy and postimplant dosimetric evaluation in community practice: analysis of the Pro-Qura database.

OBJECTIVE: To evaluate the influence of postimplant dosimetric timing on prostate brachytherapy quality in community practice. MATERIALS AND METHODS: The Pro-Qura database was stratified by multiple time intervals between the implant and postimplant dosimetric analysis. Postimplant dosimetry was performed in a standardized fashion. Criteria for implant adequacy included V(100) >80%, D(90) >90%, and V(150) <60% for I-125 and <75% for Pd-103. Implants with V(100) <80% and D(90) <90% were deemed "too cool." Implants were considered "too hot" if D(90) >140% of prescription dose and/or V(150) >150% for I-125 and >75% for Pd-103. RESULTS: For I-125, the average V(100) and D(90) increased from 88.6% to 89.8%, and 102.8% to 103.1% for day 0 and day 30 dosimetry. For Pd-103 implants the change was more pronounced, with V(100) and D(90) increasing from 81.6% to 87.8% (P < 0.001) and 88.7% to 100.0% (P < 0.001) for day 0, and day 30, respectively. The percentage of implants considered too cool based on a V(100) and D(90) criteria decreased from 18.8% and 26.9% on day 0 to 11.0% and 19.7% on day 30, respectively. Implants determined to be too hot based on a V(150) >60% (I-125)/>75% (Pd-103) or D(90) >140% were 16.4% and 2.2% on day 0 and 16.0% and 0.7% on day 30, respectively. CONCLUSION: In community-based brachytherapy programs, postimplant dosimetry performed at day 30 resulted in a statistically and clinically significant improvement in postimplant dosimetry compared with day 0. The influence of timing is substantially greater for Pd-103 than I-125.

Initial analysis of Pro-Qura: a multi-institutional database of prostate brachytherapy dosimetry.

PURPOSE: The study aimed to analyze the Pro-Qura database in terms of patient implant sequence number for each institution to determine evidence for a dosimetric learning curve. METHODS AND MATERIALS: In the Pro-Qura database, 2833 of a total of 4614 postplans from 57 brachytherapists were analyzed for evidence of a dosimetric learning curve. The median time between implant and postimplant CT scan was 30 days. I-125 was used in 2123 patients (1687 monotherapy and 536 boost) and Pd-103 in 710 patients (367 monotherapy and 343 boost). Preimplant prostate volume was 35.3 and 32.9 cm3 in the I-125 and Pd-103 cohorts, respectively. The mean I-125 seed activity was 0.32 and 0.26 mCi for monotherapy and boost, whereas for Pd-103 the mean seed activity was 1.59 and 1.27 mCi, respectively. Postimplant dosimetry was performed in a standardized fashion by overlaying the preimplant ultrasound and the postimplant CT scan. Criteria for implant adequacy included a D90 >90% and a V100 >80% for both isotopes. An adequate V150 was defined as <60% for I-125 and <75% for Pd-103. RESULTS: The mean V100 and D90 were 88.9% and 101.9% of prescription dose, respectively. When analyzed in terms of patient sequence number for each institution, the mean V100 for the first 10 patients was 87.4% and increased to 88.6% for patients 11-20 (p = 0.036). Similarly, the mean D90 for the first 10 patients was 98.9%, whereas for the second cohort of 10 patients the mean D90 increased to 102.2% (p = 0.001). In terms of mean V100 and D90, there was minimal further change for subsequent 10 patient institutional groupings of patient sequence numbers. For the first 10 cases, 27.2% were deemed "too cool" (V100 <80% and/or D90 <90%). Approximately 16% of all implants were deemed "too hot" (D90 >140% or V150 >60% for I-125 or >75% for Pd-103). CONCLUSIONS: Although a learning curve exists for prostate brachytherapy, high-quality brachytherapy is achievable in approximately 75-80% of patients treated at community centers.