Introduction: Heavy metal pollution including lead (Pb) has become one of the serious global issues threatening food security, human health, and the ecosystem. Exogenous application of astaxanthin (ATX), a potent natural antioxidant, has been shown to enhance plant tolerance to various abiotic stresses. However, the role of endogenous ATX in alleviating Pb stress and the underlying molecular mechanisms remain poorly understood. Objectives: This study aimed to systematically investigate the effects and mechanism of endogenous ATX in biofortified tobacco (T-ATX) in promoting plant growth, particularly enhancing plant tolerance to Pb toxicity and blocking Pb pollution. Methods: Pot experiments were employed to investigate plant growth and Pb tolerance as well as Pb absorption and translocation in T-ATX and wild-type (SNN) tobacco seedlings subjected to various doses of Pb stress. Multiple physiological and cellular examinations were conducted, followed by integrated omics approaches in this study. Results: T-ATX plants exhibited an increased plant height, root length, leaf area, and biomass compared to SNN under Pb stress. T-ATX displayed higher levels of chlorophyll, photosynthetic efficiency, antioxidant enzyme activities, and non-enzymatic antioxidants, with improved integrity of subcellular structures. Remarkably, Pb content in various organs and Pb translocation coefficient were significantly reduced in T-ATX. Multiple genes and metabolites associated with antioxidant defense mechanisms, detoxification pathways, carotenoid metabolism, Pb ion transport, and plant hormone signal transduction were significantly upregulated in T-ATX tobacco plants. Conclusion: Endogenous ATX enriched in the T-ATX genotype significantly confers plant healthy performance and high tolerance to Pb stress by enhancing the antioxidant defense system, maintaining cellular structural integrity, reducing Pb absorption and translocation, upregulating detoxification and the related signaling pathways. These findings provide new insights into the endogenous ATX-mediated molecular mechanisms to promote plant growth and mitigate Pb toxicity, establishing a foundation for using ATX-fortified crops for green control technology of heavy metal pollution.
Sjoerd J.D. Tjalsma, Niels J. Rinzema, Marjon J.A.M. Verstegen
et al.
Summary: Cell-type-specific gene activation is regulated by enhancers, sometimes located at large genomic distances from target gene promoters. Whether distal enhancers require specific factors to orchestrate gene regulation remains unclear. Here, we used enhancer distance-controlled reporter screens to find candidate factors. We depleted them and employed activity-by-contact predictions to genome-wide classify genes based on enhancer distance. Predicted distal enhancers typically control tissue-restricted genes and often are strong enhancers. We find cohesin, but also mediator, most specifically required for long-range activation, with cohesin repressing short-range gene activation and prioritizing distal over proximal HBB genes competing for shared enhancers. Long-range controlled genes are also most sensitive to perturbations of other regulatory proteins and to BET inhibitor JQ1, this being more a consequence of their distinct enhancer features than distance. Our work predicts that lengthening of intervening sequences can help limit the expression of target genes to specialized cells with optimal trans-factor environments.
Abstract Yellow lupine (Lupinus luteus L.) is a promising protein crop, but domestication has increased flower abscission. Flowers in higher whorls are more likely to abscise, providing a model to study factors influencing flower fate before abscission zone formation. We hypothesise that auxin localisation and miRNA-modulated signal transduction orchestrate flower development and abscission, particularly under drought. We investigated the indole-3-acetic acid (IAA) distribution in ovules and tested the effects of IAA, NPA (auxin transport inhibitor), and PCIB (auxin signalling blocker) on flower retention. Bioinformatic analyses of transcriptome data profiled miRNA-regulated auxin pathway elements (TIR1/AFBs, ARFs), with domain structures analysed for functional divergence. Selected miRNA-mRNA modules were analysed for their role in inflorescence drought response. IAA accumulation exhibited slight differences in upper pre-anthesis flowers. In the field experiment, PCIB treatment led to increased retention of generative organs, suggesting the vital role of auxin nuclear signalling in flower fate. Bioinformatic analyses identified miRNAs (MIR393, MIR160, MIR167, one novel) regulating TIR1/AFB and ARF6,8,17,18. qPCR revealed the differential expression of AFB3-, ARF6-, and ARF18-encoding transcripts and corresponding miR393, miR167, and miR160 during flower development and drought stress. However, miRNA-target expression lacked a strictly negative correlation, indicating other regulating players.
Cassandra Upton, Gerhard Prinsloo, Paul Anton Steenkamp
et al.
IntroductionSea cucumbers are ecologically and economically significant marine invertebrates, yet the metabolic diversity and bioactive potential of noncommercialized, endemic species remains poorly understood.MethodsThis study presents the first intra-species metabolomic analysis of Pseudocnella sykion, a species endemic to the Eastern coast of Southern Africa, using untargeted 1HNMR metabolomics and full-scan UPLC-QTOF-HR-MS.ResultsThe analysis revealed a diverse array of metabolites associated with protein synthesis, tissue growth, osmoregulation, and energy utilization, with distinct tissue-specific patterns across the body wall, gonad, and gut/mesentery. The gut/mesentery tissue showed higher levels of amino acids and energy-related compounds. UPLCQTOF-HR-MS tentatively identified several metabolites, including triterpene glycosides and rosmarinic acid, a phenolic compound typically associated with plants. Online resources, including the Dictionary of Marine Natural Products, contained no previously recorded compounds for P. sykion.DiscussionThese findings underscore the untapped potential of P. sykion as a source of novel metabolites and demonstrate the utility of untargeted metabolomics in generating baseline profiles for underexplored marine species. The results offer a foundation for future research into bioactivity, environmental monitoring, and cultivation strategies. While this study provides critical baseline data, challenges in metabolite identification and extraction underscore the need for further targeted analyses. Overall, this research enhances our understanding of the metabolic dynamics of sea cucumbers and advocates for continued exploration of lesser-known species to support conservation, bioprospecting, and sustainable aquaculture. It represents a pioneering effort in metabolomic profiling of Southern African sea cucumber species and lays the groundwork for future investigations into their metabolic pathways and potential bioactivities.
Science, General. Including nature conservation, geographical distribution
Abstract Background Post-traumatic headache (PTH) is a common comorbid symptom affecting at least one-third of patients with mild traumatic brain injury (mTBI). While neuroinflammation is known to contribute to the development of PTH, the cellular mechanisms in the trigeminal system crucial for understanding the pathogenesis of PTH remain unclear. Methods A non-invasive repetitive mTBI (4 times with a 24-h interval) was induced in male mice and effect of mTBI was tested on either bregma or pre-bregma position on the head. Periorbital allodynia and spontaneous pain behavior were assessed using von Frey test and grimace score, respectively. Quantitative PCR was used to assess extent of mTBI pathology. RNA sequencing was performed to obtain transcriptomic profile of the trigeminal ganglion (TG), trigeminal nucleus caudalis (Sp5C) and periaqueductal gray (PAG) at 7 days post-TBI. Subsequently, quantitative PCR, in situ hybridization and immunohistochemistry were used to examine mRNA and protein expression of glia specific markers and pain associated molecules. Results The repetitive impacts at the bregma, but not pre-bregma site led to periorbital hypersensitivity, which was correlated with enhanced inflammatory gene expression in multiple brain regions. RNA sequencing revealed mTBI induced distinct transcriptomic profiles in the peripheral TG and central Sp5C and PAG. Using gene set enrichment analysis, positive enrichment of non-neuronal cells in the TG and neuroinflammation in the Sp5C were identified to be essential in the pathogenesis of PTH. In situ assays also revealed that gliosis of satellite glial cells in the TG and astrocytes in the Sp5C were prominent days after injury. Furthermore, immunohistochemical study revealed a close interaction between activated microglia and reactive astrocytes correlating with increased calretinin interneurons in the Sp5C. Conclusions Transcriptomics analysis indicated that non-neuronal cells in peripheral TG and successive in situ assays revealed that glia in the central Sp5C are crucial in modulating headache-like symptoms. Thus, selective targeting of glia cells can be a therapeutic strategy for PTH attributed to repetitive mTBI.
Heat stress is one of the most important climatic conditions which adversely affects agricultural and livestock production worldwide. High ambient temperature with direct and indirect solar radiation, wind speed and relative humidity impose thermal stress in animals. The foremost reaction of animals under thermal weather is increased respiration and pulse rate, and rectal temperature. It directly affects feed intake thereby, reduces growth rate, milk yield, reproductive performance and even death in extreme cases. Heat stress suppresses the immune system thereby enhances susceptibility of an animal to various diseases. It is very important to control the impacts of thermal stress for sustainable dairy farming. Advances in environmental modifications and nutritional management in part alleviate the impact of thermal stress on animal performance during the hotter seasons. However, long-term strategies have to be evolved for adaptation to climate change. Differences in thermal tolerance between livestock species provide clues to select thermotolerant animals using genetic tools. There are heat shock gene related to thermotolerance that was identified and being used as marker in marker-assisted selection and genome-wide selection to develop thermotolerant bull that is used in breeding program. The present review collates and synthesizes information pertaining to thermal shock and possible ameliorative strategies to combat the impacts in livestock.
Abstract Background Epithelial mesenchymal transformation (EMT) in alveolar type 2 epithelial cells (AT2) is closely associated with pulmonary fibrosis (PF). Histone deacetylase 3 (HDAC3) is an important enzyme that regulates protein stability by modulating the acetylation level of non-histones. Here, we aimed to explore the potential role and regulatory mechanisms associated with HDAC3 in PF. Methods We quantified HDAC3 expression both in lung tissues from patients with PF and from bleomycin (BLM)-treated mice. HDAC3 was also detected in TGF-β1-treated AT2. The mechanistic activity of HDAC3 in pulmonary fibrosis and EMT was also explored. Results HDAC3 was highly expressed in lung tissues from patients with PF and bleomycin (BLM)-treated mice, especially in AT2. Lung tissues from AT2-specific HDAC3-deficient mice stimulated with BLM showed alleviative fibrosis and EMT. Upstream of HDAC3, TGF-β1/SMAD3 directly promoted HDAC3 transcription. Downstream of HDAC3, we also found that genetic or pharmacologic inhibition of HDAC3 inhibited GATA3 expression at the protein level rather than mRNA. Finally, we found that intraperitoneal administration of RGFP966, a selective inhibitor of HDAC3, could prevent mice from BLM-induced pulmonary fibrosis and EMT. Conclusion TGF-β1/SMAD3 directly promoted the transcription of HDAC3, which aggravated EMT in AT2 and pulmonary fibrosis in mice via deacetylation of GATA3 and inhibition of its degradation. Our results suggest that targeting HDAC3 in AT2 may provide a new therapeutic target for the prevention of PF.
SUMMARY: Re-evaluating management practices to highlight opportunities for improving bird welfare is a necessary response to changing genetics, evolving standards, and increasing consumer interest in how poultry is raised. The aim of this study was to evaluate the impact of stocking density (SD) on the welfare and productivity of broilers. The SD treatments were 31, 34.5, 38, and 41.5 kg/m2. Litter moisture decreased and footpad dermatitis improved as SD was reduced, indicating an improvement in welfare. Results from the novel object test suggest birds reared at lower SD were less fearful. Heterophil/lymphocyte ratios were highest in the 31 and 41.5 kg/m2 treatments, indicating these birds experienced more chronic stress. At 20 d as SD was decreased, birds spent more time at the drinker and less time resting. When older (31 d), birds preened more in the 31 and 41.5 kg/m2 treatments. Stretching behavior decreased while ruffling increased at lower SD. Final body weights were heaviest in the 31 and 34.5 kg/m2 treatments. Overall, body weight gain increased as SD was reduced, and feed intake was greatest in the 34.5 kg/m2 treatment. From 21 to 24 d, infectious mortality was reduced in the low SD treatments. The impacts of SD are dependent on environmental management; however, even under research conditions, differences between treatments were observed. The results of this study suggest that reducing SD for broilers results in improved welfare and performance as evidenced by reductions in litter moisture, footpad dermatitis, fear, stress, and infectious mortality as well as greater market body weights and feed consumption.
Thrombocytopenia 2 (THC2) is one of the most prevalent forms of inherited thrombocytopenia. It is caused by a heterogeneous group of ANKRD26 gene mutation and shows a heterogeneous clinical and laboratory characteristics. We present a big Chinese family with 10 THC2 patients carrying c.-128G > T heterozygous substitution in the 5-untranslated region of the ANKRD26 gene. Although the platelets are fewer than 50 × 109/L in 8 THC2 family members, only the proband and her son show a higher WHO bleeding score. The proband and her son are also beta-thalassemia carriers with heterozygous c.52A > T mutation of HBB, which might not be associated with the increased bleeding tendency since 3 other family members with low bleeding tendency also carried both ANKRD26 c.-128G > T and HBB c.52A > T mutations. However, the proband and her son also show hypofibrinogenaemia, which is likely the cause of their more severe clinical manifestation. HID1 c.442G > T mutation was detected not only in these two hypofibrinogenaemia family members but also in the other 8 family members with normal blood fibrinogen levels. Our study suggests that the co-occurrence of other inherited genetic conditions associated with blood coagulation might contribute to the heterogeneity of clinical and laboratory characteristics in THC2 patients. Considering the hematologic and myeloid malignancy predisposition of THC2 patients and a large population of immune thrombocytopenia in China, we urge more attention to be paid to the diagnosis of THC2 patients to avoid misdiagnosis and mistreatment.
Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) have a strong clinical, genetic and pathological overlap. This review focuses on the current understanding of structural, functional and molecular neuroimaging signatures of genetic FTD and ALS. We overview quantitative neuroimaging studies on the most common genes associated with FTD (MAPT, GRN), ALS (SOD1), and both (C9orf72), and summarize visual observations of images reported in the rarer genes (CHMP2B, TARDBP, FUS, OPTN, VCP, UBQLN2, SQSTM1, TREM2, CHCHD10, TBK1).
Poonam Malhotra, Graham H. Read, Joanne B. Weidhaas
Recent studies in cancer diagnostics have identified microRNAs (miRNAs) as promising cancer biomarkers. Single nucleotide polymorphisms (SNPs) in miRNA binding sites, seed regions, and coding sequences can help predict breast cancer risk, aggressiveness, response to stimuli, and prognosis. This review also documents significant known miR-SNPs in miRNA biogenesis genes and their effects on gene regulation in breast cancer, taking into account the genetic background and ethnicity of the sampled populations. When applicable, miR-SNPs are evaluated in the context of other patient factors, including mutations, hormonal status, and demographics. Given the power of miR-SNPs to predict patient cancer risk, prognosis, and outcomes, further study of miR-SNPs is warranted to improve efforts towards personalized medicine.
Katharina T. Prochazka, Gudrun Pregartner, Frank G. Rücker
et al.
The role of subclonal TP53 mutations, defined by a variant allele frequency of 40%, 20%-40% and 40%, 19 had variant allele frequencies between 20%-40% and 18 had frequencies
L-Tryptophan, is one of the amino acids, also is one of the 9 essential amino acids of human which cannot be synthesized internally by him, microbial production is the main method for obtaining tryptophan for commercial uses. Typical microorganisms used for tryptophan production are E. coli and C. glutamicum. In this study, random mutations is performed on two strains of C. glutamicum to increase tryptophan production, the produced tryptophan measured by bioassay using tryptophan auxotroph E. coli (JW1254-2) strain, the mutations are performed using UV radiation. To detect and compare the difference between the parent strains and the muted strains genetically two molecular markers were used start codon targeted polymorphism (SCoT) and Inter-simple sequence repeats (ISSR). Tryptophan remarkably increased after C. glutamicum mutation to reach 278.4 µg/ml (1257.4% increment) from one mutated strain. Molecular genetics methods showed an ability to distinguish between the two original strains and their mutants and it showed the importance of the mutation by UV radiation for increasing the productivity of the bacteria to tryptophan.