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Molecular Genetics and Metabolism... Jun 2024Introduction Cobalamin c deficiency (cblC), an inborn error of vitamin B12 metabolism, is caused by mutations of the MMACHC gene. It usually leads to a multisystemic...
Introduction Cobalamin c deficiency (cblC), an inborn error of vitamin B12 metabolism, is caused by mutations of the MMACHC gene. It usually leads to a multisystemic disease; 50% of all patients with cblC have various structural heart defects. Severe congestive heart failure (HF) may also occur and its prognosis is poorly documented. Case report We present the case of a young man who had been diagnosed with cblC due to C331T mutation in the MMACHC gene at the age of 3 days and had been treated with substitution therapy (OH-Cbl, mecobalamine, carnitine, betaine, and calcium folinate) since then. He had mildly impaired cognitive function; an ectopic hypophysis/pituitary insufficiency, with adequate hormone replacement therapy; obstructive sleep apnea syndrome, treated with CPAP, bronchial asthma, and obesity (BMI of 30). The liver and kidney functions were normal. He developed severe dilated cardiomyopathy and HF at the age of 12y. With medical treatment, his condition improved and he was stable (NYHA class II) for several years. Six years later, his status deteriorated rapidly, as he developed advanced HF, INTERMACS 3. The cardiac ultrasound revealed dilated ventricles with severely depressed ejection fraction (EF), increased filling pressures, and pulmonary hypertension (sPAP 60 mmHg). Cardiac MRI showed extremely dilated chambers (LVedv 609 mL, RVedv 398 mL) with pronounced non-compaction, and a left ventricle EF of 13%. A primary prophylactic ICD and a left ventricular assist device (LVAD/HM3) were implanted, and the patient was subsequently listed for heart transplantation (HTx). After 25 months on the waiting list, he underwent an uncomplicated HTx. However postoperatively, he got two episodes of cardiac tamponade, as well as mediastinitis, treated with antibiotics and vaccum assisted closure. He developed severe kidney failure, which fully recovered after two months, and was treated successfully for an early moderate allograft rejection (ISHT 2). At the latest outward visit, twelve months after HTx, the patient was doing excellent. Summary To the best of our knowledge, this is the first ever reported case of a patient with CblC undergoing an LVAD implantation and subsequently a HTx. Although both interventions were complicated with bleeding events, this seems to be a treatment option for advanced HF in patients with CblC.
PubMed: 38745823
DOI: 10.1016/j.ymgmr.2024.101089 -
BMC Microbiology May 2024Globally, drought stress poses a significant threat to crop productivity. Improving the drought tolerance of crops with microbial biostimulants is a sustainable strategy...
Globally, drought stress poses a significant threat to crop productivity. Improving the drought tolerance of crops with microbial biostimulants is a sustainable strategy to meet a growing population's demands. This research aimed to elucidate microbial biostimulants' (Plant Growth Promoting Rhizobacteria) role in alleviating drought stress in oil-seed crops. In total, 15 bacterial isolates were selected for drought tolerance and screened for plant growth-promoting (PGP) attributes like phosphate solubilization and production of indole-3-acetic acid, siderophore, hydrogen cyanide, ammonia, and exopolysaccharide. This research describes two PGPR strains: Acinetobacter calcoaceticus AC06 and Bacillus amyloliquefaciens BA01. The present study demonstrated that these strains (AC06 and BA01) produced abundant osmolytes under osmotic stress, including proline (2.21 and 1.75 µg ml), salicylic acid (18.59 and 14.21 µg ml), trehalose (28.35 and 22.74 µg mg FW) and glycine betaine (11.35 and 7.74 mg g) respectively. AC06 and BA01 strains were further evaluated for their multifunctional performance by inoculating in Arachis hypogaea L. (Groundnut) under mild and severe drought regimes (60 and 40% Field Capacity). Inoculation with microbial biostimulants displayed distinct osmotic-adjustment abilities of the groundnut, such as growth parameters, plant biomass, photosynthetic pigments, relative water content, proline, and soluble sugar in respective to control during drought. On the other hand, plant sensitivity indexes such as electrolyte leakage and malondialdehyde (MDA) contents were decreased as well as cooperatively conferred plant drought tolerance by induced alterations in stress indicators such as catalase (CAT), ascorbate peroxidase (APX), and superoxide dismutase (SOD). Thus, Acinetobacter sp. AC06 and Bacillus sp. BA01 can be considered as osmolyte producing microbial biostimulants to simultaneously induce osmotic tolerance and metabolic changes in groundnuts under drought stress.
Topics: Arachis; Droughts; Stress, Physiological; Proline; Bacillus amyloliquefaciens; Soil Microbiology; Osmotic Pressure; Betaine; Indoleacetic Acids; Salicylic Acid; Acinetobacter; Hydrogen Cyanide; Trehalose
PubMed: 38745279
DOI: 10.1186/s12866-024-03320-6 -
Heliyon May 2024The extent of drought tolerance in the seedlings of three wheat cultivars (WMRI-1, BARI GOM-33 and BARI GOM-21) was investigated by seed and root priming using abscisic...
The extent of drought tolerance in the seedlings of three wheat cultivars (WMRI-1, BARI GOM-33 and BARI GOM-21) was investigated by seed and root priming using abscisic acid (ABA) and glycine betaine (GB). The seeds were primed with ABA (10 and 20 μM) and GB (50 and 100 mM) and grown in pots maintaining control (0 % PEG) and drought (10 % PEG) conditions. Under drought, the root and shoot length, root and shoot biomass were significantly increased in ABA and GB primed seedlings than non-primed seedlings in all cultivars. Among the priming agents, either 20 μM ABA or 50 mM GB triggered better seedling growth in all wheat cultivars. These two levels were then applied with the nutrient solution in the hydroponics following four treatments: Control, Drought, Drought + ABA and Drought + GB. The seedling growth significantly declined in drought, while an improved seedling growth was observed in ABA and GB-treated plants in all cultivars. A considerable increase in lipid peroxidation, proline content, total antioxidant capacity and total flavonoid content in roots and leaves were recorded in all drought conditions, while these values were considerably reduced in ABA and GB treatments. Hierarchical clustering heatmap using stress tolerance index (STI) values showed that Drought + ABA and Drought + GB secured higher STI scores suggesting a greater degree of drought tolerance in all cultivars. In conclusion, seed and root priming of ABA and GB enhanced drought tolerance in the wheat seedlings by improving seedling growth and antioxidative defense suggesting a declined state of oxidative damage.
PubMed: 38742073
DOI: 10.1016/j.heliyon.2024.e30598 -
Scientific Reports May 2024Pea, member of the plant family Leguminosae, play a pivotal role in global food security as essential legumes. However, their production faces challenges stemming from...
Pea, member of the plant family Leguminosae, play a pivotal role in global food security as essential legumes. However, their production faces challenges stemming from the detrimental impacts of abiotic stressors, leading to a concerning decline in output. Salinity stress is one of the major factors that limiting the growth and productivity of pea. However, biochar amendment in soil has a potential role in alleviating the oxidative damage caused by salinity stress. The purpose of the study was to evaluate the potential role of biochar amendment in soil that may mitigate the adverse effect of salinity stress on pea. The treatments of this study were, (a) Pea varieties; (i) V1 = Meteor and V2 = Green Grass, Salinity Stress, (b) Control (0 mM) and (ii) Salinity (80 mM) (c) Biochar applications; (i) Control, (ii) 8 g/kg soil (56 g) and (iii) 16 g/kg soil (112 g). Salinity stress demonstrated a considerable reduction in morphological parameters as Shoot and root length decreased by (29% and 47%), fresh weight and dry weight of shoot and root by (85, 63%) and (49, 68%), as well as area of leaf reduced by (71%) among both varieties. Photosynthetic pigments (chlorophyll a, b, and carotenoid contents decreased under 80 mM salinity up to (41, 63, 55 and 76%) in both varieties as compared to control. Exposure of pea plants to salinity stress increased the oxidative damage by enhancing hydrogen peroxide and malondialdehyde content by (79 and 89%), while amendment of biochar reduced their activities as, (56% and 59%) in both varieties. The activities of catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD) were increased by biochar applications under salinity stress as, (49, 59, and 86%) as well as non-enzymatic antioxidants as, anthocyanin and flavonoids improved by (112 and 67%). Organic osmolytes such as total soluble proteins, sugars, and glycine betaine were increased up to (57, 83, and 140%) by biochar amendment. Among uptake of mineral ions, shoot and root Na uptake was greater (144 and 73%) in saline-stressed plants as compared to control, while shoot and root Ca and K were greater up to (175, 119%) and (77, 146%) in biochar-treated plants. Overall findings revealed that 16 g/kg soil (112 g) biochar was found to be effective in reducing salinity toxicity by causing reduction in reactive oxygen species and root and shoot Na ions uptake and improving growth, physiological and anti-oxidative activities in pea plants (Fig. 1). Figure 1 A schematic diagram represents two different mechanisms of pea under salinity stress (control and 80 mM NaCl) with Biochar (8 and 16 g/kg soil).
Topics: Pisum sativum; Charcoal; Soil; Photosynthesis; Salt Stress; Salinity; Chlorophyll; Plant Roots; Antioxidants; Plant Leaves; Plant Shoots
PubMed: 38740776
DOI: 10.1038/s41598-024-59891-x -
JIMD Reports May 2024Methionine synthase reductase deficiency (cblE) is a rare autosomal recessive inborn error of cobalamin metabolism caused by pathogenic variants in the methionine...
Late-onset refractory hemolytic anemia in siblings treated for methionine synthase reductase deficiency: A rare complication possibly prevented by hydroxocobalamin dose escalation?
Methionine synthase reductase deficiency (cblE) is a rare autosomal recessive inborn error of cobalamin metabolism caused by pathogenic variants in the methionine synthase reductase gene (). Patients usually exhibit early-onset bone marrow failure with pancytopenia including megaloblastic anemia. The latter can remain isolated or patients may present developmental delay and rarely macular dysfunction. Treatment mostly includes parenteral hydroxocobalamin to maximize the residual enzyme function and betaine to increase methionine concentrations and decrease homocysteine accumulation. We report herein 2 cblE siblings diagnosed in the neonatal period with isolated pancytopenia who, despite treatment, exhibited in adulthood hemolytic anemia (LDH >11 000 U/L, undetectable haptoglobin, elevated unconjugated bilirubin) which could finally be successfully treated by hydroxocobalamin dose escalation. There was no obvious trigger apart from a parvovirus B19 infection in one of the patients. This is the first report of such complications in adulthood. The use of LDH for disease monitoring could possibly be an additional useful biomarker to adjust hydroxocobalamin dosage. Bone marrow infection with parvovirus B19 can complicate this genetic disease with erythroblastopenia even in the absence of an immunocompromised status, as in other congenital hemolytic anemias. The observation of novel hemolytic features in this rare disease should raise awareness about specific complications in remethylation disorders and plea for hydroxocobalamin dose escalation.
PubMed: 38736634
DOI: 10.1002/jmd2.12422 -
Plants (Basel, Switzerland) Apr 2024In regions facing water scarcity and soil salinity, mitigating these abiotic stresses is paramount for sustaining crop production. This study aimed to unravel the...
Unveiling the Synergistic Effects of Phosphorus Fertilization and Organic Amendments on Red Pepper Growth, Productivity and Physio-Biochemical Response under Saline Water Irrigation and Climate-Arid Stresses.
In regions facing water scarcity and soil salinity, mitigating these abiotic stresses is paramount for sustaining crop production. This study aimed to unravel the synergistic effects of organic matter and phosphorus management in reducing the adverse effect of saline water for irrigation on red pepper ( L.) production, fruit quality, plant physiology, and stress tolerance indicators. The study was carried out in the arid Tadla region of Morocco and involved two key experiments: (i) a field experiment during the 2019 growing season, where red pepper plants were subjected to varying phosphorus fertilizer rates (120, 140, and 170 kg of PO.ha) and saline water irrigation levels (0.7; 1.5; 3; and 5 dS.m); and (ii) a controlled pot experiment in 2021 for examining the interaction of saline water irrigation levels (EC values of 0.7, 2, 5, and 9 dS.m), phosphorus rates (30, 36, and 42 kg of PO.ha), and the amount of organic matter (4, 8, 12, and 16 t.ha). The field study highlighted that saline irrigation significantly affected red pepper yields and fruit size, although phosphorus fertilization helped enhance productivity. Additionally, biochemical markers of stress tolerance, such as proline and glycine betaine, along with stomatal conductance, were impacted by increasing salinity levels. The pot experiment showed that combining organic amendments and phosphorus improved soil properties and stimulated red pepper growth and root weight across all salinity levels. The integration of phosphorus fertilization and organic amendments proved instrumental for counteracting salinity-induced constraints on red pepper growth and yield. Nonetheless, caution is necessary as high salinity can still negatively impact red pepper productivity, necessitating the establishment of an irrigation water salinity threshold, set at 5 dS.m.
PubMed: 38732423
DOI: 10.3390/plants13091209 -
International Journal of Molecular... May 2024One-carbon (1-C) metabolic deficiency impairs homeostasis, driving disease development, including infertility. It is of importance to summarize the current evidence... (Review)
Review
One-carbon (1-C) metabolic deficiency impairs homeostasis, driving disease development, including infertility. It is of importance to summarize the current evidence regarding the clinical utility of 1-C metabolism-related biomolecules and methyl donors, namely, folate, betaine, choline, vitamin B12, homocysteine (Hcy), and zinc, as potential biomarkers, dietary supplements, and culture media supplements in the context of medically assisted reproduction (MAR). A narrative review of the literature was conducted in the PubMed/Medline database. Diet, ageing, and the endocrine milieu of individuals affect both 1-C metabolism and fertility status. In vitro fertilization (IVF) techniques, and culture conditions in particular, have a direct impact on 1-C metabolic activity in gametes and embryos. Critical analysis indicated that zinc supplementation in cryopreservation media may be a promising approach to reducing oxidative damage, while female serum homocysteine levels may be employed as a possible biomarker for predicting IVF outcomes. Nonetheless, the level of evidence is low, and future studies are needed to verify these data. One-carbon metabolism-related processes, including redox defense and epigenetic regulation, may be compromised in IVF-derived embryos. The study of 1-C metabolism may lead the way towards improving MAR efficiency and safety and ensuring the lifelong health of MAR infants.
Topics: Humans; Reproductive Techniques, Assisted; Carbon; Vitamin B 12; Fertilization in Vitro; Female; Homocysteine; Folic Acid; Dietary Supplements; Choline; Zinc; Betaine; Biomarkers
PubMed: 38732193
DOI: 10.3390/ijms25094977 -
Cells Apr 2024Impaired neuronal plasticity and cognitive decline are cardinal features of Alzheimer's disease and related Tauopathies. Aberrantly modified Tau protein and...
Impaired neuronal plasticity and cognitive decline are cardinal features of Alzheimer's disease and related Tauopathies. Aberrantly modified Tau protein and neurotransmitter imbalance, predominantly involving acetylcholine, have been linked to these symptoms. In Drosophila, we have shown that dTau loss specifically enhances associative long-term olfactory memory, impairs foot shock habituation, and deregulates proteins involved in the regulation of neurotransmitter levels, particularly acetylcholine. Interestingly, upon choline treatment, the habituation and memory performance of mutants are restored to that of control flies. Based on these surprising results, we decided to use our well-established genetic model to understand how habituation deficits and memory performance correlate with different aspects of choline physiology as an essential component of the neurotransmitter acetylcholine, the lipid phosphatidylcholine, and the osmoregulator betaine. The results revealed that the two observed phenotypes are reversed by different choline metabolites, implying that they are governed by different underlying mechanisms. This work can contribute to a broader knowledge about the physiologic function of Tau, which may be translated into understanding the mechanisms of Tauopathies.
Topics: Animals; Choline; tau Proteins; Memory; Drosophila Proteins; Habituation, Psychophysiologic; Drosophila melanogaster; Drosophila; Acetylcholine
PubMed: 38727282
DOI: 10.3390/cells13090746 -
Frontiers in Microbiology 2024Valsa canker, caused by , is a destructive disease in apple production. However, the mechanism by which apple defend against infection remains unclear.
INTRODUCTION
Valsa canker, caused by , is a destructive disease in apple production. However, the mechanism by which apple defend against infection remains unclear.
METHODS
In this study, the integrative transcriptional and metabolic analysis were used to investigate the responses of the 'Jin Hong' apple branches to the invasion of .
RESULTS AND DISCUSSION
Results showed that the differentially expressed genes were mainly enriched in the pathways of carbon metabolism, photosynthesis-antenna proteins, and biosynthesis of amino acids pathways. Additionally, the differentially accumulated metabolites were significantly enriched in aminoacyl-tRNA biosynthesis, fructose and mannose metabolism, and alanine, aspartate, and glutamate metabolism pathways. Conjoint analysis revealed that infection significantly altered 5 metabolic pathways, 8 highly relevant metabolites and 15 genes of apples. Among which the transcription factors WRKY and basic domain leucine zipper transcription family were induced, the α-linolenic acid and betaine were significantly accumulated in infected apple stems. This work presents an overview of the changes in gene expression and metabolic profiles in apple under the inoculation of , which may help to further screen out the mechanism of plant-pathogen interaction at the molecular level.
PubMed: 38721601
DOI: 10.3389/fmicb.2024.1394447 -
Frontiers in Plant Science 2024L., commonly known as wolfberry, is not only a traditional Chinese medicine but also a highly nutritious food. Its main nutrients include polysaccharide, flavonoid...
L., commonly known as wolfberry, is not only a traditional Chinese medicine but also a highly nutritious food. Its main nutrients include polysaccharide, flavonoid polyphenols, carotenoids, alkaloids, and other compounds, demonstrating its wide application value. This study investigated the effects of nitrogen application on the accumulation of the main nutrients and metabolites in wolfberry fruits under three different nitrogen application rates, namely, N1 (20% nitrogen (N) reduction, 540 kg·ha), N2 (medium N, 675 kg·ha), and N3 (20% nitrogen increase, 810 kg·ha,which is a local conventional nitrogen application amount.). Additionally, due to continuous branching, blossoming, and fruiting of wolfberry plants during the annual growth period, this research also explored the variation in nutritional composition among different harvesting batches. The contents of total sugar and polysaccharide in wolfberry fruit were determined by Fehling reagent method and phenol-sulfuric acid method, respectively;The content of betaine in fruit was determined by high-performance liquid chromatography,and the flavonoids and carotene in the wolfberry fruits were determined by spectrophotometry. Analysis of data over three consecutive years revealed that as nitrogen application increased, the total sugar content in wolfberry fruits initially decreased and then increased. The levels of polysaccharides, total flavonoids, and total carotenoids initially increased and then decreased, while the betaine content consistently increased. Different picking batches significantly impacted the nutrient content of wolfberry fruits. Generally, the first batch of summer wolfberry fruits had greater amounts of total sugar and flavonoids, whereas other nutrients peaked in the third batch. By employing a broadly targeted metabolomics approach, 926 different metabolites were identified. The top 20 differentially abundant metabolites were selected for heatmap generation, revealing that the contents of L-citrulline, 2-methylglutaric acid, and adipic acid increased proportionally to the nitrogen gradient. Conversely, the dibutyl phthalate and 2, 4-dihydroxyquinoline contents significantly decreased under high-nitrogen conditions. The remaining 15 differentially abundant metabolites, kaempferol-3-O-sophorosid-7-O-rhamnoside, trigonelline, and isorhamnosid-3-O-sophoroside, initially increased and then decreased with increasing nitrogen levels. Isofraxidin, a common differentially abundant metabolite across all treatments, is a coumarin that may serve as a potential biomarker for wolfberry fruit response to nitrogen. Differentially abundant metabolites were analyzed for GO pathway involvement, revealing significant enrichment in metabolic pathways and biosynthesis of secondary metabolites under different nitrogen treatments. In conclusion, a nitrogen application of 675 kg·ha, 20% less than the local farmers' actual application, was most beneficial for the quality of four-year-old Ningqi 7 wolfberry fruits. Consumers who purchase wolfberry-dried fruit for health benefits should not consider only the first batch of summer wolfberry fruits. These results offer a broader perspective for enhancing the quality and efficiency of the wolfberry industry.
PubMed: 38721340
DOI: 10.3389/fpls.2024.1355832