Comparative Performances of Beneficial Microorganisms on the Induction of Durum Wheat Tolerance to Fusarium Head Blight

Durum wheat production is seriously threatened by Fusarium head blight (FHB) attacks in Tunisia, and the seed coating by bio-agents is a great alternative for chemical disease control. This study focuses on evaluating, under field conditions, the effect of seed coating with Trichoderma harzianum, Meyerozyma guilliermondii and their combination on (i) FHB severity, durum wheat grain yield and TKW in three crop seasons, and (ii) on physiological parameters and the carbon and nitrogen content and isotope composition in leaves and grains of durum wheat. The results indicated that the treatments were effective in reducing FHB severity by 30 to 70% and increasing grain yield with an increased rate ranging from 25 to 68%, compared to the inoculated control. The impact of treatments on grain yield improvement was associated with higher NDVI and chlorophyll content and lower canopy temperature. Furthermore, the treatments mitigated the FHB adverse effects on N and C metabolism by resulting in a higher δ13Cgrain (13C/12Cgrain) and δ15Ngrain (15N/14Ngrain). Overall, the combination outperformed the other seed treatments by producing the highest grain yield and TKW. The high potency of seed coating with the combination suggests that the two microorganisms have synergetic or complementary impacts on wheat.

Prospects for studying the pharmacokinetics, pharmacodynamics and pharmacogenetics of vitamin C in patients with neurological diseases and mental disorders

Ascorbic acid (vitamin C) is a vital nutrient that belongs to the group of antioxidants. Vitamin C plays an important role in the functioning of the central (CNS) and peripheral nervous system (PNS), including maturation and differentiation of neurons, formation of myelin, synthesis of catecholamines, modulation of neurotransmission and antioxidant protection. Neurological diseases and mental disorders are characterized by increased generation of free radicals. At the same time, the highest concentrations of vitamin C are found in the brain and neuroendocrine tissues. It is believed that vitamin C can affect the age of debut and the course of many neurological diseases and mental disorders. However, its potential therapeutic role continues to be studied. The efficacy and safety of vitamin C is likely influenced by the pharmacogenetic profile of the patient, including the carriage of single-nucleotide variants (SNVS), candidate genes associated with vitamin C metabolism in the human body in normal and neuropsychic disorders. The purpose of this thematic review is to update current knowledge about the role of vitamin C pharmacogenetics in the efficacy and safety of its use in neurological diseases (amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Huntington's disease, Alzheimer's disease, etc.) and mental disorders (depression, anxiety, schizophrenia, etc.). Special attention is paid to the possibility of translating the results of pharmacogenetic studies into real clinical practice in neurology and psychiatry.

Transcriptomic and Biochemical Analysis Reveal Integrative Pathways Between Carbon and Nitrogen Metabolism in Guzmania monostachia (Bromeliaceae) Under Drought

Most epiphytes are found in low-nutrient environments with an intermittent water supply. To deal with water limitation, many bromeliads perform crassulacean acid metabolism (CAM), such as Guzmania monostachia, which shifts from C3 to CAM and can recycle CO2 from the respiration while stomata remain closed during daytime and nighttime (CAM-idling mode). Since the absorbing leaf trichomes can be in contact with organic (urea) and inorganic nutrients (NO3−, NH4+) and the urea hydrolysis releases NH4+ and CO2, we hypothesized that urea can integrate the N and C metabolism during periods of severe drought. Under this condition, NH4+ can be assimilated into amino acids through glutamine synthetase (GS), while the CO2 can be pre-fixated by phosphoenolpyruvate carboxylase (PEPC). In this context, we evaluated the foliar transcriptome of G. monostachia to compare the relative gene expression of some genes involved with CAM and the N metabolism when bromeliads were submitted to 7days of drought. We also conducted a controlled experiment with an extended water deficit period (21days) in which bromeliads were cultivated in different N sources (urea, NH4+, and NO3−). Our transcriptome results demonstrated an increment in the expression of genes related to CAM, particularly those involved in the carboxylation metabolism (PEPC1, PPCK, and NAD-MDH), the movement of malate through vacuolar membrane (ALMT9), and the decarboxylation process (PEPCK). Urea stimulated the expression of PEPC1 and ALMT9, while Urease transcripts increased under water deficit. Under this same condition, GS1 gene expression increased, indicating that the NH4+ from urea hydrolysis can be assimilated in the cytosol. We suggest that the link between C and N metabolism occurred through the supply of carbon skeleton (2-oxoglutarate, 2-OG) by the cytosolic isocitrate dehydrogenase since the number of NADP-ICDH transcripts was also higher under drought conditions. These findings indicate that while urea hydrolysis provides NH4+ that can be consumed by glutamine synthetase-cytosolic/glutamate synthase (GS1/GOGAT) cycle, the CO2 can be used by CAM, maintaining photosynthetic efficiency even when most stomata remain closed 24h (CAM-idling) as in the case of a severe water deficit condition. Thus, we suggest that urea could be used by G. monostachia as a strategy to increase its survival under drought, integrating N and C metabolism.

FLEXIBLE SOIL MICROBIAL CARBON METABOLISM ACROSS AN ASIAN ELEVATION GRADIENT

ABSTRACT The function and change of global soil carbon (C) reserves in natural ecosystems are key regulators of future carbon-climate coupling. Microbes play a critical role in soil carbon cycling and yet there is poor understanding of their roles and C metabolism flexibility in many ecosystems. We wanted to determine whether vegetation type and climate zone influence soil microbial community composition (fungi and bacteria) and carbon resource preference. We used a biomarker (phospholipid fatty acids, PLFAs), natural abundance 13C and 14C probing approach to measure soil microbial composition and C resource use, along a 1900–4167-m elevation gradient on Mount Gongga (7556 m asl), China. Mount Gongga has a vertical mean annual temperature gradient of 1.2–10.1°C and a diversity of typical vegetation zones in the Tibetan Plateau. Soils were sampled at 10 locations along the gradient capturing distinct vegetation types and climate zones from lowland subtropical-forest to alpine-meadow. PLFA results showed that microbial communities were composed of 2.1–51.7% bacteria and 2.0–23.2% fungi across the elevation gradient. Microbial biomass was higher and the ratio of soil fungi to bacteria (F/B) was lower in forest soils compared to meadow soils. δ13C varied between −33‰ to −17‰ with C3 plant carbon sources dominant across the gradient. Soil organic carbon (SOC) turnover did not vary among three soils we measured from three forest types (i.e., evergreen broadleaved subtropical, mixed temperate, coniferous alpine) and dissolved organic carbon (DOC) turnover decreased with soil elevation. Forest soil microbial PLFA 14C and δ13C measurements showed that forest type and climate were related to different microbial C use. The 14C values of microbial PLFAs i15, a15, 16:1, br17 decreased with elevation while those of C16:0, cyC17, and cyC19 did not show much difference among three forest ecosystems. Bacteria and bacillus represented by C16:1 and brC17 showed considerable microbial C metabolism flexibility and tended to use ancient carbon at higher altitudes. Anaerobes represented by cyC17 and cyC19 showed stronger C metabolism selectivity. Our findings reveal specific C source differences between and within soil microbial groups along elevation gradients.

One-Carbon Metabolism Associated Vulnerabilities in Glioblastoma: A Review

Altered cell metabolism is a hallmark of cancer cell biology, and the adaptive metabolic strategies of cancer cells have been of recent interest to many groups. Metabolic reprogramming has been identified as a critical step in glial cell transformation, and the use of antimetabolites against glioblastoma has been investigated. One-carbon (1-C) metabolism and its associated biosynthetic pathways, particularly purine nucleotide synthesis, are critical for rapid proliferation and are altered in many cancers. Purine metabolism has also been identified as essential for glioma tumourigenesis. Additionally, alterations of 1-C-mediated purine synthesis have been identified as commonly present in brain tumour initiating cells (BTICs) and could serve as a phenotypic marker of cells responsible for tumour recurrence. Further research is required to elucidate mechanisms through which metabolic vulnerabilities may arise in BTICs and potential ways to therapeutically target these metabolic processes. This review aims to summarize the role of 1-C metabolism-associated vulnerabilities in glioblastoma tumourigenesis and progression and investigate the therapeutic potential of targeting this pathway in conjunction with other treatment strategies.

Silicon modifies C:N:P stoichiometry, and increases nutrient use efficiency and productivity of quinoa

Recognizably, silicon has a beneficial effect on plant growth and productivity. In this respect, it is also known that the C, N and, P stoichiometric ratios and nutrient conversion efficiency allow identifying the interactions between elements while helping to understand the role Si plays in plant growth. This study aims to investigate whether increasing Si concentrations (0, 1, 2, and 3 mmol L−1) supplied in the nutrient solution is uptaken by quinoa, modifies the C:N:P stoichiometry while increasing nutritional efficiency and crop productivity as well. Our results revealed that the Si supply by promoting a decline in the C levels, associated with greater uptake of N and P, especially decreased the C:N and C:P ratios, favoring the C metabolism efficiency, and modulated the N and P use efficiency for biomass accumulation. This improved nutritional performance and greater use efficiency of C directly favored quinoa productivity. The future perspective is to encourage new field studies with this species to adjust silicon fertilization management to different soils aiming at enhancing quinoa productivity on a sustainable basis.

Ex-Vivo Pharmacological Defatting of the Liver: A Review

The ongoing organ shortage has forced transplant teams to develop alternate sources of liver grafts. In this setting, ex-situ machine perfusion has rapidly developed as a promising tool to assess viability and improve the function of organs from extended criteria donors, including fatty liver grafts. In particular, normothermic machine perfusion represents a powerful tool to test a liver in full 37 °C metabolism and add pharmacological corrections whenever needed. In this context, many pharmacological agents and therapeutics have been tested to induce liver defatting on normothermic machine perfusion with promising results even on human organs. This systematic review makes a comprehensive synthesis on existing pharmacological therapies for liver defatting, with special focus on normothermic liver machine perfusion as an experimental ex-vivo translational model.

Crtc modulates fasting programs associated with 1-C metabolism and inhibition of insulin signaling

Fasting in mammals promotes increases in circulating glucagon and decreases in circulating insulin that stimulate catabolic programs and facilitate a transition from glucose to lipid burning. The second messenger cAMP mediates effects of glucagon on fasting metabolism, in part by promoting the phosphorylation of CREB and the dephosphorylation of the cAMP-regulated transcriptional coactivators (CRTCs) in hepatocytes. In Drosophila, fasting also triggers activation of the single Crtc homolog in neurons, via the PKA-mediated phosphorylation and inhibition of salt-inducible kinases. Crtc mutant flies are more sensitive to starvation and oxidative stress, although the underlying mechanism remains unclear. Here we use RNA sequencing to identify Crtc target genes that are up-regulated in response to starvation. We found that Crtc stimulates a subset of fasting-inducible genes that have conserved CREB binding sites. In keeping with its role in the starvation response, Crtc was found to induce the expression of genes that inhibit insulin secretion (Lst) and insulin signaling (Impl2). In parallel, Crtc also promoted the expression of genes involved in one-carbon (1-C) metabolism. Within the 1-C pathway, Crtc stimulated the expression of enzymes that encode modulators of S-adenosyl-methionine metabolism (Gnmt and Sardh) and purine synthesis (ade2 and AdSl). Collectively, our results point to an important role for the CREB/CRTC pathway in promoting energy balance in the context of nutrient stress.

1-C Metabolism—Serine, Glycine, Folates—In Acute Myeloid Leukemia

Metabolic reprogramming contributes to tumor development and introduces metabolic liabilities that can be exploited to treat cancer. Studies in hematological malignancies have shown alterations in fatty acid, folate, and amino acid metabolism pathways in cancer cells. One-carbon (1-C) metabolism is essential for numerous cancer cell functions, including protein and nucleic acid synthesis and maintaining cellular redox balance, and inhibition of the 1-C pathway has yielded several highly active drugs, such as methotrexate and 5-FU. Glutamine depletion has also emerged as a therapeutic approach for cancers that have demonstrated dependence on glutamine for survival. Recent studies have shown that in response to glutamine deprivation leukemia cells upregulate key enzymes in the serine biosynthesis pathway, suggesting that serine upregulation may be a targetable compensatory mechanism. These new findings may provide opportunities for novel cancer treatments.