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1.
Are nitrogen and carbon cycle processes impacted by common stream antibiotics? A comparative assessment of single vs. mixture exposures.
Gray, AD, Bernhardt, E
PloS one. 2022;(1):e0261714
Abstract
A variety of antibiotics are ubiquitous in all freshwater ecosystems that receive wastewater. A wide variety of antibiotics have been developed to kill problematic bacteria and fungi through targeted application, and their use has contributed significantly to public health and livestock management. Unfortunately, a substantial fraction of the antibiotics applied to humans, pets and livestock end up in wastewater, and ultimately many of these chemicals enter freshwater ecosystems. The effect of adding chemicals that are intentionally designed to kill microbes, on freshwater microbial communities remains poorly understood. There are reasons to be concerned, as microbes play an essential role in nutrient uptake, carbon fixation and denitrification in freshwater ecosystems. Chemicals that reduce or alter freshwater microbial communities might reduce their capacity to degrade the excess nutrients and organic matter that characterize wastewater. We performed a laboratory experiment in which we exposed microbial community from unexposed stream sediments to three commonly detected antibiotics found in urban wastewater and urban streams (sulfamethoxazole, danofloxacin, and erythromycin). We assessed how the form and concentration of inorganic nitrogen, microbial carbon, and nitrogen cycling processes changed in response to environmentally relevant doses (10 μg/L) of each of these antibiotics individually and in combination. We expected to find that all antibiotics suppressed rates of microbial mineralization and nitrogen transformations and we anticipated that this suppression of microbial activity would be greatest in the combined treatment. Contrary to our expectations we measured few significant changes in microbially mediated functions in response to our experimental antibiotic dosing. We found no difference in functional gene abundance of key nitrogen cycling genes nosZ, mcrA, nirK, and amoA genes, and we measured no treatment effects on NO3- uptake or N2O, N2, CH4, CO2 production over the course of our seven-day experiment. In the mixture treatment, we measured significant increases in NH4+ concentrations over the first 24 hours of the experiment, which were indistinguishable from controls within six hours. Our results suggest remarkable community resistance to pressure antibiotic exposure poses on naïve stream sediments.
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2.
Interactions between Radiation and One-Carbon Metabolism.
Korimerla, N, Wahl, DR
International journal of molecular sciences. 2022;(3)
Abstract
Metabolic reprogramming is a hallmark of cancer. Cancer cells rewire one-carbon metabolism, a central metabolic pathway, to turn nutritional inputs into essential biomolecules required for cancer cell growth and maintenance. Radiation therapy, a common cancer therapy, also interacts and alters one-carbon metabolism. This review discusses the interactions between radiation therapy, one-carbon metabolism and its component metabolic pathways.
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3.
Harnessing root architecture to address global challenges.
Lynch, JP
The Plant journal : for cell and molecular biology. 2022;(2):415-431
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Abstract
Root architecture can be targeted in breeding programs to develop crops with better capture of water and nutrients. In rich nations, such crops would reduce production costs and environmental pollution and, in developing nations, they would improve food security and economic development. Crops with deeper roots would have better climate resilience while also sequestering atmospheric CO2 . Deeper rooting, which improves water and N capture, is facilitated by steeper root growth angles, fewer axial roots, reduced lateral branching, and anatomical phenotypes that reduce the metabolic cost of root tissue. Mechanical impedance, hypoxia, and Al toxicity are constraints to subsoil exploration. To improve topsoil foraging for P, K, and other shallow resources, shallower root growth angles, more axial roots, and greater lateral branching are beneficial, as are metabolically cheap roots. In high-input systems, parsimonious root phenotypes that focus on water capture may be advantageous. The growing prevalence of Conservation Agriculture is shifting the mechanical impedance characteristics of cultivated soils in ways that may favor plastic root phenotypes capable of exploiting low resistance pathways to the subsoil. Root ideotypes for many low-input systems would not be optimized for any one function, but would be resilient against an array of biotic and abiotic challenges. Root hairs, reduced metabolic cost, and developmental regulation of plasticity may be useful in all environments. The fitness landscape of integrated root phenotypes is large and complex, and hence will benefit from in silico tools. Understanding and harnessing root architecture for crop improvement is a transdisciplinary opportunity to address global challenges.
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4.
Carbon nanohorns as nanocontainers for cisplatin: insight into their interaction with the plasma membranes of normal and breast cancer cells.
Almeida, ER, Dos Santos, HF, Capriles, PVSZ
Physical chemistry chemical physics : PCCP. 2021;(30):16376-16389
Abstract
Cisplatin (cddp)-based chemotherapy is one of the most effective therapeutic alternatives for breast cancer treatment, the most common form of cancer, despite the severe side effects related to the high toxicity and low selectivity of cddp. To circumvent these drawbacks, the encapsulation of cddp into oxidized carbon nanohorns (CNHoxs) has been shown as a promising formulation with biocompatibility and low toxicity. However, there is still a lack of studies regarding the behavior of this cddp@CNHox nanovector on the cell membranes. This study presents an in silico description of the interactions between cddp@CNHox and membrane models of cancer (C_memb) and normal (N_memb) cells referring to a typical human breast. The results revealed the interaction mechanism of the inclusion complex 3cddp@CNHox (three cddp molecules are included in the CNHox cavity) with these biomembranes, which is a multistep process including approach, landing, insertion, and penetration. The 3cddp@CNHox stability was monitored over time, and demonstrated the trapping of cddp molecules inside the CNHox cavity over all simulations. The van der Waals contribution played a primary role (∼74%) for the complex stability. Moreover, the binding free energy calculations indicated that the interaction of the 3cddp@CNHox complex with the C_memb model was slightly more favorable, on average, than with the N_memb model. Analysis of the hydrogen bonds (HBs) formed over simulations of 800 ns explains the selectivity for the C_memb model, since the total number of HBs established between the inclusion complex and the C_memb model was about three times greater than that with the N_memb model. By reinforcing the potentiality of oxidized CNHox as a nanovector of cddp, the results presented in this study may assist and drive new experimental studies with this nanomaterial, focusing on the development of less aggressive formulations for breast cancer treatment.
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5.
The 5-formyl-tetrahydrofolate proteome links folates with C/N metabolism and reveals feedback regulation of folate biosynthesis.
Li, W, Liang, Q, Mishra, RC, Sanchez-Mu Oz, R, Wang, H, Chen, X, Van Der Straeten, D, Zhang, C, Xiao, Y
The Plant cell. 2021;(10):3367-3385
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Abstract
Folates are indispensable for plant development, but their molecular mode of action remains elusive. We synthesized a probe, "5-F-THF-Dayne," comprising 5-formyl-tetrahydrofolate (THF) coupled to a photoaffinity tag. Exploiting this probe in an affinity proteomics study in Arabidopsis thaliana, we retrieved 51 hits. Thirty interactions were independently validated with in vitro expressed proteins to bind 5-F-THF with high or low affinity. Interestingly, the interactors reveal associations beyond one-carbon metabolism, covering also connections to nitrogen (N) metabolism, carbohydrate metabolism/photosynthesis, and proteostasis. Two of the interactions, one with the folate biosynthetic enzyme DIHYDROFOLATE REDUCTASE-THYMIDYLATE SYNTHASE 1 (AtDHFR-TS1) and another with N metabolism-associated glutamine synthetase 1;4 (AtGLN1;4), were further characterized. In silico and experimental analyses revealed G35/K36 and E330 as key residues for the binding of 5-F-THF in AtDHFR-TS1 and AtGLN1;4, respectively. Site-directed mutagenesis of AtGLN1;4 E330, which co-localizes with the ATP-binding pocket, abolished 5-F-THF binding as well as AtGLN1;4 activity. Furthermore, 5-F-THF was noted to competitively inhibit the activities of AtDHFR-TS1 and AtGLN1;4. In summary, we demonstrated a regulatory role for 5-F-THF in N metabolism, revealed 5-F-THF-mediated feedback regulation of folate biosynthesis, and identified a total of 14 previously unknown high-affinity binding cellular targets of 5-F-THF. Together, this sets a landmark toward understanding the role of folates in plant development.
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Epiphytic Bacteria Are Essential for the Production and Transformation of Algae-Derived Carboxyl-Rich Alicyclic Molecule (CRAM)-like DOM.
Liu, Y, Kan, J, He, C, Shi, Q, Liu, YX, Fan, ZC, Sun, J
Microbiology spectrum. 2021;(2):e0153121
Abstract
The microbial carbon pump (MCP) provides a mechanistic illustration of transformation of recalcitrant dissolved organic matter (DOM) in the ocean. Here, we explored and demonstrated the key roles of algae-associated microorganisms (mainly heterotrophic bacteria) in the production and transformation of carboxyl-rich alicyclic molecule (CRAM)-like DOM through a laboratory experiment involving cultures of Skeletonema dohrnii. Without the participation of the associated bacteria, CRAM-like DOM molecules were not detected via Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS) in algal cultures treated with antibiotics. Similarly, CRAM-like DOM were not detected in cultures of bacteria alone. Our experimental results showed that algae-associated bacteria are important in the process of converting algal-derived organic matter into CRAM-like DOM during S. dohrnii culture. Bacteroidetes (mainly Flavobacteriia) dominated the bacterial community in the stationary and degradation phases, where the predicted metabolic pathways for bacterial assemblages were mainly involved in biosynthesis, metabolism, and degradation. Facilitated by these heterotrophic bacteria, the amount and the chemodiversity of CRAM-like DOM derived from algae varied during the growth and decomposition of algal cells, and CRAM-like DOM were enriched at the later growth stage. The properties and characteristics of these CRAM-like DOM, including molecular weight, double bond equivalent, hydrogen-carbon ratio, carbon-nitrogen ratio, carbon-sulfur ratio, and modified aromaticity index increased with the growth and decay of algal cells, indicating the transformation from active to recalcitrant DOM. In contrast, the organic matter in axenic cultures of S. dohrnii mainly existed in the form of particulate organic matters (POM), and small amounts of CRAM-like DOM were detected. This study provides the first laboratory evidence to reveal and confirm the direct involvement of algae-associated microbiomes in the production and transformation of algae-derived refractory DOM, highlighting the significance of these epiphytic bacteria in marine carbon sequestration and global carbon cycling. IMPORTANCE Dissolved organic matter (DOM) serves as a major carbon and nutrient pool in oceans, and recalcitrant DOM are the primary sources for carbon sequestration in depths. Here, we demonstrate the critical roles of algae-associated microorganisms (mainly heterotrophic bacteria) in the transformation of recalcitrant dissolved organic matter through laboratory cultures of a model diatom, Skeletonema dohrnii. Our experimental results showed that in addition to affecting the growth and the physiology of S. dohrnii, algae-associated bacteria are important in processing and converting algal DOM into CRAM-like DOM. Facilitated by the associated bacteria, the amount and the chemodiversity of DOM derived from algae varied during the growth and decomposition of algal cells, and enriched recalcitrant DOM formed in the later growth stage. The properties and diversity of DOM increased with the growth and decay of algal cells, indicating the transformation from active DOM to inert organic matter. Our results confirmed that the direct involvement of algae-associated microbes in the production of CRAM-like DOM. Detailed community structure analysis of the algae-associated bacterial community and its predicted functions confirmed the involvement of certain bacterial groups (e.g., Flavobacteriia) in biosynthesis, metabolism, and degradation.
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7.
From Embryo to Adult: One Carbon Metabolism in Stem Cells.
Altundag, Ö, Çelebi-Saltik, B
Current stem cell research & therapy. 2021;(2):175-188
Abstract
Stem cells are undifferentiated cells with self-renewal property and varying differentiation potential that allow the regeneration of tissue cells of an organism throughout adult life beginning from embryonic development. Through the asymmetric cell divisions, each stem cell replicates itself and produces an offspring identical with the mother cell, and a daughter cell that possesses the characteristics of a progenitor cell and commits to a specific lineage to differentiate into tissue cells to maintain homeostasis. To maintain a pool of stem cells to ensure tissue regeneration and homeostasis, it is important to regulate the metabolic functioning of stem cells, progenitor cells and adult tissue stem cells that will meet their internal and external needs. Upon fertilization, the zygote transforms metabolic reprogramming while implantation, embryonic development, organogenesis processes and after birth through adult life. Metabolism in stem cells is a concept that is relatively new to be enlightened. There are no adequate and comprehensive in vitro studies on the comparative analysis of the effects of one-carbon (1-C) metabolism on fetal and adult stem cells compared to embryonic and cancer stem cells' studies that have been reported recently. Since 1-C metabolism is linking parental environmental/ dietary factors and fetal development, investigating the epigenetic, genetic, metabolic and developmental effects on adult period is necessary. Several mutations and abnormalities in 1-C metabolism have been noted in disease changing from diabetes, cancer, pregnancy-related outcomes such as pre-eclampsia, spontaneous abortion, placental abruption, premature delivery, and cardiovascular diseases. In this review, the effects of 1-C metabolism, mainly the methionine and folate metabolism, in stem cells that exist in different developmental stages will be discussed.
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Waste-derived volatile fatty acids as carbon source for added-value fermentation approaches.
Chalima, A, de Castro, LF, Burgstaller, L, Sampaio, P, Carolas, AL, Gildemyn, S, Velghe, F, Ferreira, BS, Pais, C, Neureiter, M, et al
FEMS microbiology letters. 2021;(9)
Abstract
The establishment of a sustainable circular bioeconomy requires the effective material recycling from biomass and biowaste beyond composting/fertilizer or anaerobic digestion/bioenergy. Recently, volatile fatty acids attracted much attention due to their potential application as carbon source for the microbial production of high added-value products. Their low-cost production from different types of wastes through dark fermentation is a key aspect, which will potentially lead to the sustainable production of fuels, materials or chemicals, while diminishing the waste volume. This article reviews the utilization of a volatile fatty acid platform for the microbial production of polyhydroxyalkanoates, single cell oil and omega-3 fatty acids, giving emphasis on the fermentation challenges for the efficient implementation of the bioprocess and how they were addressed. These challenges were addressed through a research project funded by the European Commission under the Horizon 2020 programme entitled 'VOLATILE-Biowaste derived volatile fatty acid platform for biopolymers, bioactive compounds and chemical building blocks'.
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The potential of resilient carbon dynamics for stabilizing crop reproductive development and productivity during heat stress.
Ferguson, JN, Tidy, AC, Murchie, EH, Wilson, ZA
Plant, cell & environment. 2021;(7):2066-2089
Abstract
Impaired carbon metabolism and reproductive development constrain crop productivity during heat stress. Reproductive development is energy intensive, and its requirement for respiratory substrates rises as associated metabolism increases with temperature. Understanding how these processes are integrated and the extent to which they contribute to the maintenance of yield during and following periods of elevated temperatures is important for developing climate-resilient crops. Recent studies are beginning to demonstrate links between processes underlying carbon dynamics and reproduction during heat stress, consequently a summation of research that has been reported thus far and an evaluation of purported associations are needed to guide and stimulate future research. To this end, we review recent studies relating to source-sink dynamics, non-foliar photosynthesis and net carbon gain as pivotal in understanding how to improve reproductive development and crop productivity during heat stress. Rapid and precise phenotyping during narrow phenological windows will be important for understanding mechanisms underlying these processes, thus we discuss the development of relevant high-throughput phenotyping approaches that will allow for more informed decision-making regarding future crop improvement.
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10.
One-carbon pathway and cognitive skills in children with Down syndrome.
Antonaros, F, Lanfranchi, S, Locatelli, C, Martelli, A, Olivucci, G, Cicchini, E, Carosi Diatricch, L, Mannini, E, Vione, B, Feliciello, A, et al
Scientific reports. 2021;(1):4225
Abstract
This work investigates the role of metabolite levels in the intellectual impairment of subjects with Down syndrome (DS). Homocysteine, folate, vitamin B12, uric acid (UA), creatinine levels and MTHFR C677T genotype were analyzed in 147 subjects with DS. For 77 subjects, metabolite levels were correlated with cognitive tests. Griffiths-III test was administered to 28 subjects (3.08-6.16 years) and WPPSI-III test was administered to 49 subjects (7.08-16.08 years). Significant correlations were found among some metabolite levels and between homocysteine levels and MTHFR C677T genotype. Moreover, homocysteine, UA and creatinine levels resulted increased with age. We did not find any correlation between metabolites and cognitive test score in the younger group. Homocysteine showed statistically significant correlation with WPPSI-III subtest scores when its level is ≥ 7.35 µmol/L, remaining correlated in higher thresholds only for non-verbal area scores. Vitamin B12 showed correlations with all WPPSI-III subtest scores when its level is < 442 pg/mL. The relevance of the present findings is the detection of a specific metabolite threshold related with a better or worse cognitive score, suggesting that vitamin B12 and homocysteine may have a role in cognitive development in children with DS.