Metabolic Exchange Research Articles

Are the effects of catch-and-release angling evident in changes to mRNA abundances related to metabolism, acid-base regulation and stress in lake trout (Salvelinus namaycush) gills?

Catch-and-release (C&R) angling is a conservation-oriented practice intended to reduce the impact recreational angling has on fish populations. Even though most recreationally angled fish are released, little is known about how C&R angling impacts fish at the cellular or tissue level. As the first to explore the impacts of C&R angling on mRNA abundances, our study aimed to identify how the stress of angling influenced metabolism, acid-base regulation and cellular stress in the gills of lake trout (Salvelinus namaycush). Because gills are responsible for metabolic gas exchange, are crucial sites of acid-base homeostasis and respond to stressors quickly, we hypothesized that the relative mRNA abundance of genes related to these three physiological processes would be altered after angling. We took gill samples of live lake trout at 0, 2 or 48h after fish were angled by rod and reel, and then used quantitative PCR (qPCR) to measure the relative abundance of nine candidate mRNA transcripts. Heat shock protein 70 (hsp70) mRNA levels significantly increased over 5-fold 2h after angling, indicating a potential activation of a cytoprotective response. However, contrary to our hypothesis, we observed no change in the relative mRNA abundance of genes related to metabolism or acid-base regulation in response to C&R angling within a 48-h period. As C&R angling can negatively impact fish populations, further use of transcript-level studies will allow us to understand the impact C&R has on specific tissues and improve our knowledge of how C&R influences overall fish health.

Distribution of Connective Tissue Fibres in the Feline Ovary and Uterus

Connective tissue is significant because it is one of the supporting tissues, it connects organs and keeps them in place, it contains inflammatory response components, and it provides the environment in which metabolic exchange occurs between cells. Collagen fibres are the most common type of connective tissue component. Type 3 collagen, glycoproteins, and proteoglycans make up reticular fibres. They allow the uterus and ovaries to contract and stretch since they are situated in between the muscles and collagen fibres in these organs. According to the requirements of the microenvironment in which they are found, elastic fibers have persistent changeable functionalities and are resistant to tensile forces. After regular histological tissue follow-up after washing, tissues removed from the ovaries and uterus of cats were fixed in 10% formaldehyde and blocked in the paraplast. Sections from the prepared blocks were cut at a thickness of 5–6 µm. The distribution and structure of these yarns were studied using the methods of Orsein for the structure of elastic yarns derived from connective tissue yarns, Van Gieson's for the structure of collagen yarns, and Gordon and Sweet's dyeing process for the structure of reticulum yarns. It was determined that the ovary and uterus had increased collagen fiber dispersion. Less dispersion was observed in reticulum and elastic fibres. The collagen fibres in the elastic and reticulum fibres, which were arranged in thick bundles between the follicles in the ovary, were found to have a thinner structure. It was noted that the collagen fibres were more thickly distributed in the lamina propria of the uterine endometrium, where the elastic and reticulum fibres were formed from thin filaments.

Tumor and peritumoral adipose tissue crosstalk: De-differentiated adipocytes influence spread of colon carcinoma cells

Colorectal cancer is the second leading cause of cancer and often has a fatal course. There are many studies in the literature that have described a close functional relationship between the tumor mass and surrounding tissue, or tumor stroma, which is affected by the continuous metabolic exchange that occurs at the interface between tumor and tissues in contact with it. There is much evidence that the presence of adipose tissue in stroma plays a fundamental role in modulating the tumor microenvironment and promote tumor development, growth, and angiogenesis due to its endocrine characteristics. In this analysis, we have studied the alterations of adipose tissue surrounding colorectal tumors with MRI and optical imaging in vivo techniques to monitor tumor progression and also performed histological and molecular analysis. We detected differences in the principal adipose markers expressed by adipocytes residing around the rectal colon and observed that peritumoral adipose tissue is exposed to a mesenchymal transition process that leads to the acquisition of a less differentiated phenotype of adipocyte that represents the main cellular type present in tumor stroma. The mesenchymal transition correlated with the acquisition of more aggressive tumor phenotype and could represent a valid target for tumor therapy.

TMIC-56. TUMOR CELL ARCHITECTURAL HETEROGENEITY AND SPATIAL INTERACTIONS WITH THE TUMOR IMMUNE MICROENVIRONMENT IN GBM

Abstract INTRODUCTION Glioblastoma (GBM) contains cell populations with distinct metabolic requirements, with fast-cycling cells harnessing aerobic glycolysis, and treatment-resistant slow-cycling cells (SCCs) preferentially engaging lipid metabolism. The interaction between immune and tumor cells, and how their metabolic heterogeneity shapes the immune landscape in GBM has yet to be understood. Objectives: The primary objective of this project is to spatially and molecularly decode the GBM microenvironment heterogeneity with a specific focus on unraveling the metabolic links that underlie the interaction of SCCs with the immune compartment. METHODS Multiple murine glioma cell lines coupled with geospatial profiling were used to establish metabolic heterogeneity and communications, while various genetic and pharmacological approaches were applied to assess the effect of disrupting the metabolic interplay between SCCs and the immune system. RESULTS We determined that SCCs exhibit distinct metabolic dependencies, involving preferential lipid metabolism supported by enhanced fatty acid uptake. We also found that SCCs exhibit specific geospatial distribution and that tumor progression is regulated by their interactions with immune suppressive cells, which in turn work against tumor immune rejection by inhibiting T cell anti-tumor activity. The immune microenvironment shaped by SCCs is marked by specific metabolic features enhancing lipid exchange capacities that are exploited by SCCs to support their survival and functions. Importantly, disrupting lipid metabolic exchange sensitized tumors to chemotherapy. CONCLUSION Our results reveal that metabolic interactions between SCCs and tumor-associated immune suppressive cells within the GBM microenvironment play a critical role in the development of drug and immune resistant tumors. This study delineates these metabolic communications and assesses the potential therapeutic effect of disrupting these interactions to treat GBM. The insights generated from this project uncover fundamental principles of the emerging connections between the tumor microenvironment, cell metabolism, anti-tumor immunity, and associated therapeutic vulnerabilities.

Actinobacteria-Plant Interactions in Alleviating Abiotic Stress.

Abiotic stressors, such as drought, flooding, extreme temperature, soil salinity, and metal toxicity, are the most important factors limiting crop productivity. Plants use their innate biological systems to overcome these abiotic stresses caused by environmental and edaphic conditions. Microorganisms that live in and around plant systems have incredible metabolic abilities in mitigating abiotic stress. Recent advances in multi-omics methods, such as metagenomics, genomics, transcriptomics, and proteomics, have helped to understand how plants interact with microbes and their environment. These methods aid in the construction of various metabolic models of microbes and plants, resulting in a better knowledge of all metabolic exchanges engaged during interactions. Actinobacteria are ubiquitous and are excellent candidates for plant growth promotion because of their prevalence in soil, the rhizosphere, their capacity to colonize plant roots and surfaces, and their ability to produce various secondary metabolites. Mechanisms by which actinobacteria overcome abiotic stress include the production of osmolytes, plant hormones, and enzymes, maintaining osmotic balance, and enhancing nutrient availability. With these characteristics, actinobacteria members are the most promising candidates as microbial inoculants. This review focuses on actinobacterial diversity in various plant regions as well as the impact of abiotic stress on plant-associated actinobacterial diversity and actinobacteria-mediated stress mitigation processes. The study discusses the role of multi-omics techniques in expanding plant-actinobacteria interactions, which aid plants in overcoming abiotic stresses and aims to encourage further investigations into what may be considered a relatively unexplored area of research.

Insights into the spatio-temporal composition, diversity and function of bacterial communities in seawater from a typical laver farm

Laver is the most widely farmed seaweed with the largest culture area in China. The spatio-temporal variations in composition, diversity, and functional properties of bacteria in seawater as well as the environmental variables of seawater in a large-scale laver farm in China were studied. Both the community richness indices and Shannon index in the laver farming area remained at a relatively stable level during laver cultivation. Fifty-nine prokaryotic phyla were detected in all samples, however, only six of these phyla accounted for 98.84% of all sequences. Proteobacteria, Gammaproteobacteria, Rhodobacterales, Rhodobacteraceae, and Octadecabacter were the most predominant bacterial taxa at different levels of classification. The keystone bacterial taxa were Bacteroidetes, Pseudomonadales, Rhodobacterales, Flavobacteriales, Loktanella, and Pseudoruegeria based on network analysis. Members of representative bacterial biomarker taxa in November may be associated with degradation of algal cell wall polysaccharides. A significant increase in metabolic exchange and transformation nutrients occurred in the seawater during the early and late stage of laver cultivation, indicating that the laver reproductive activities (i.e. the formation/release activities of archeospores and zygotospores) probably drove the variation of metabolic functional diversity of bacterial communities. Based on Mantel test and redundancy analysis, we found the hydrographic parameters (e.g. salinity, temperature, DO, pH) as well as the key carbon (e.g. POC, DOC) and nitrogen parameters (e.g. nitrate, DIN, DON, TDN) were crucial environmental variables to shape the bacterial community composition in the surrounding seawater of laver farm. In a word, our results suggested that the microbial community structure and function significantly changed across the different succession stages during laver cultivation. This work provides new insights on the characteristics of bacterial communities in a large-scale laver farming system and solidifies the importance of laver farming in shaping seawater microbiomes.

In silico analysis of metabolic effects of bipolar disorder on prefrontal cortex identified altered GABA, glutamate-glutamine cycle, energy metabolism and amino acid synthesis pathways.

Bipolar disorder (BP) is a lifelong psychiatric condition, which often disrupts the daily life of the patients. It is characterized by unstable and periodic mood changes, which cause patients to display unusual shifts in mood, energy, activity levels, concentration and the ability to carry out day-to-day tasks. BP is a major psychiatric condition, and it is still undertreated. The causes and neural mechanisms of bipolar disorder are unclear, and diagnosis is still mostly based on psychiatric examination, furthermore the unstable character of the disorder makes diagnosis challenging. Identification of the molecular mechanisms underlying the disease may improve the diagnosis and treatment rates. Single nucleotide polymorphisms (SNP) and transcriptome profiles of patients were studied along with signalling pathways that are thought to be associated with bipolar disorder. Here, we present a computational approach that uses publicly available transcriptome data from bipolar disorder patients and healthy controls. Along with statistical analyses, data are integrated with a genome-scale metabolic model and protein-protein interaction network. Healthy individuals and bipolar disorder patients are compared based on their metabolic profiles. We hypothesize that energy metabolism alterations in bipolar disorder relate to perturbations in amino-acid metabolism and neuron-astrocyte exchange reactions. Due to changes in amino acid metabolism, neurotransmitters and their secretion from neurons and metabolic exchange pathways between neurons and astrocytes such as the glutamine-glutamate cycle are also altered. Changes in negatively charged (-1) KIV and KMV molecules are also observed, and it indicates that charge balance in the brain is highly altered in bipolar disorder. Due to this fact, we also hypothesize that positively charged lithium ions may stabilize the disturbed charge balance in neurons in addition to its effects on neurotransmission. To the best of our knowledge, our approach is unique as it is the first study using genome-scale metabolic models in neuropsychiatric research.

Towards the human nasal microbiome: Simulating D. pigrum and S. aureus.

The human nose harbors various microbes that decisively influence the wellbeing and health of their host. Among the most threatening pathogens in this habitat is Staphylococcus aureus. Multiple epidemiological studies identify Dolosigranulum pigrum as a likely beneficial bacterium based on its positive association with health, including negative associations with S. aureus. Carefully curated GEMs are available for both bacterial species that reliably simulate their growth behavior in isolation. To unravel the mutual effects among bacteria, building community models for simulating co-culture growth is necessary. However, modeling microbial communities remains challenging. This article illustrates how applying the NCMW fosters our understanding of two microbes' joint growth conditions in the nasal habitat and their intricate interplay from a metabolic modeling perspective. The resulting community model combines the latest available curated GEMs of D. pigrum and S. aureus. This uses case illustrates how to incorporate genuine GEM of participating microorganisms and creates a basic community model mimicking the human nasal environment. Our analysis supports the role of negative microbe-microbe interactions involving D. pigrum examined experimentally in the lab. By this, we identify and characterize metabolic exchange factors involved in a specific interaction between D. pigrum and S. aureus as an in silico candidate factor for a deep insight into the associated species. This method may serve as a blueprint for developing more complex microbial interaction models. Its direct application suggests new ways to prevent disease-causing infections by inhibiting the growth of pathogens such as S. aureus through microbe-microbe interactions.

The microbiome of the dinoflagellate Prorocentrum cordatum in laboratory culture and its changes at higher temperatures.

In the ocean, phytoplankton are dependent on communities of bacteria living in the phycosphere, a hot spot of metabolic and genetic exchange. Many types of interactions between phytoplankton and phycosphere bacteria have been shown, but it is unclear if the microbial communities associated with microalgae strains in culture collections are beneficial or harmful to the host strain. Here, we studied the microbial communities associated with four strains of the dinoflagellate Prorocentrum cordatum that had been isolated from distant geographical locations and maintained in culture collection for hundreds of generations. Community composition was determined by 16S rRNA gene amplicon sequencing. The dinoflagellate host strain was the strongest parameter separating communities, while growth phase, lifestyle (particle-attached versus free-living) and temperature had only a modulating effect. Although the strains had been isolated from distant locations in the Atlantic and Pacific Ocean, 14 ASVs were shared among all strains, the most abundant ones being Gilvibacter, Marivita, uncultivated Rhodobacteraceae, Marinobacter, Hyphomonadaceae, Cupriavidus, Variovorax, and Paucibacter. Adaptation to higher temperatures resulted in specific changes in each phycosphere microbiome, including increased abundance of rare community members. We then compared the growth of the four xenic cultures to that of the axenic P. cordatum CCMP1329. At 20°C, growth of the xenic cultures was similar or slower than that of CCMP1329. At 26°C, all four xenic cultures experienced a death phase, while the axenic culture stably remained in the stationary phase. At 30°C, only two of the xenic cultures were able to grow. A shift of dinoflagellate metabolism from autotrophy to mixotrophy and competition between dinoflagellate and bacteria for limiting nutrients, including essential vitamins, may contribute to these differences in growth patterns.

Circulating metabolites in the early stage of breast cancer were not related to cancer stage or subtypes but associated with ki67 level. Promising statistical discrimination from controls

It was documented that the presence of malignancy in an organism causes metabolomic alterations in blood plasma which applies also to breast cancer. Breast cancer is a heterogeneous disease and there are only limited known relations of plasma metabolomic signatures with the tumour characteristics in early BC and knowing them would be of great advantage in noninvasive diagnostics. In this study, we focused on the metabolic alterations in early BC in blood plasma with the aim to identify metabolomic characteristics of BC subtypes. We used 50 early BC patients (FIGO stage I and II), where no additional metabolomic changes from metastatically changed remote organs were to be expected. We compared plasma levels of metabolites against controls and among various molecular and histological BC subtypes. BC patients showed decreased plasma levels of branched-chain amino acids BCAAs (and related keto-acids), histidine pyruvate and alanine balanced with an increased level of 3-hydroxybutyrate. The levels of circulating metabolites were not related to BC molecular subtypes (luminal A/luminal B), histological finding or grade, eventually stage, which indicate that in early BC, the BC patients share common metabolomics fingerprint in blood plasma independent of grade, stage or molecular subtype of BC. We observed statistically significant correlations between tumour proliferation marker Ki-67 level and circulating metabolites: alanine, citrate, tyrosine, glutamine, histidine and proline. This may point out the metabolites those levels could be associated with tumour growth, and conversely, the rate of tumour proliferation could be potentially estimated from plasma metabolites. When analyzing metabolomic changes in BC, we concluded that some of them could be associated with the metabolomic features of cancer cells, but the other observed alterations in blood plasma are the results of the complex mutual biochemical pathways in the comprehensive inter-organ metabolic exchange and communication. In the end, statistical discrimination against controls performed with AUC >0.91 showed the very promising potential of plasma metabolomics in the search for biomarkers for oncologic diseases.

All dried up: The materiality of drought in Ladismith, South Africa

This paper conceptualises droughts as socioecological phenomena coproduced by the recursive engagement of human and non-human transformations. Through an interdisciplinary approach that integrates political ecology, material geographies and hydroclimatology, this work simultaneously apprehends the role of politics and power in reshaping drought, along with the agency of biophysical processes – soil, vegetation, hydrology and microclimate – that co-produce droughts and their spatiotemporal patterning. The drought-stricken Ladismith in Western Cape, South Africa, is the instrumental case study and point of departure of our empirical analysis. To advance a materiality of drought that seriously accounts for the coevolution of biophysical and political transformations, we alter the spatiotemporal and empirical foci of drought analyses thereby retracing Ladismith’s socioecological history since colonial times. In turn, such extended framework exposes the agency of soil, vegetation, hydrology and microclimate and their metabolic exchanges with processes of colonisation, apartheid, capitalist and neoliberal transformations of South African economy. We argue that the narrow pursuit of profits and capital accumulation of the few has produced a fundamental disruption between nature and society which contributed to transform Ladismith’s drought into a socioecological crisis. Whilst advancing debates on materiality, we note two fundamental contributions to the study of drought. First, our approach makes hydrological accounts of droughts less politically naive and socially blind. Second, it develops a political ecology of droughts and socioecological crises more attuned to the materiality of drought. We contend that apprehending the materiality of drought and the active role of its non-human processes can further understandings of the workings of power and the production of socioecological injustices.

Low-Ammonium Environment Increases the Nutrient Exchange between Diatom-Diazotroph Association Cells and Facilitates Photosynthesis and N2 Fixation-a Mechanistic Modeling Analysis.

Diatom–diazotroph associations (DDAs) are one of the most important symbiotic dinitrogen (N2) fixing groups in the oligotrophic ocean. Despite their capability to fix N2, ammonium (NH4+) remains a key nitrogen (N) source for DDAs, and the effect of NH4+ on their metabolism remains elusive. Here, we developed a coarse-grained, cellular model of the DDA with NH4+ uptake and quantified how the level of extracellular NH4+ influences metabolism and nutrient exchange within the symbiosis. The model shows that, under a fixed growth rate, an increased NH4+ concentration may lower the required level of N2 fixation and photosynthesis, and decrease carbon (C) and N exchange. A low-NH4+ environment leads to more C and N in nutrient exchange and more fixed N2 to support a higher growth rate. With higher growth rates, nutrient exchange and metabolism increased. Our study shows a strong effect of NH4+ on metabolic processes within DDAs, and thus highlights the importance of in situ measurement of NH4+ concentrations.

Cardiorespiratory Fitness Levels In Adolescent And Young Adult Cancer Survivors

PURPOSE: Adolescent and young adult (AYA) cure rates have greatly improved, leading to a growing population of survivors that are at risk for competing causes of death, notably cardiovascular disease (CVD). The purpose of this study was to assess levels of cardiorespiratory fitness, a prognostic indicator of CVD, among AYA survivors. METHODS: We studied 37 AYA cancer survivors presenting to the University of Texas MD Anderson Healthy Heart Program between 2017-2019 for cardiorespiratory fitness and heart risk factor assessment. All patients underwent a symptom-limited exercise treadmill testing with metabolic gas exchange to assess peak oxygen consumption (VO2peak). RESULTS: At the time of the clinic assessment, the mean age was 28.8 ± 5.9 years and mean time from diagnosis was 9.3 ± 7.1 years. Breast cancer (27.0%), sarcoma (24.3%), and Hodgkin’s Lymphoma (13.5%) were the most common cancer diagnoses and 94.5% had been treated with anthracycline-based chemotherapy. The mean BMI was 28.2 ± 5.4 kg/m2. 2D echocardiographic assessment of left ventricular ejection fraction (LVEF) performed within 2.5 years of clinic assessment was available in 29 participants and was 59% ± 0.3%. The mean VO2peak was 27.9 ± 7.8 ml · kg-1 · min-1, the equivalent of 35.6% below healthy, age-adjusted reference values. Mean VO2peak of the males (n = 19) was 30.7 ± 8.2 ml · kg-1 · min-1and 25.0 ± 4.6 for ml · kg-1 · min-1 for the females (n = 18). CONCLUSIONS: The large and growing population of AYA cancer survivors is at increased risk for CVD late effects. In the current study, cardiorespiratory fitness, an important marker of CVD risk, was markedly reduced among AYA cancer survivors. Strategies to promote exercise and fitness and cardiovascular health in this population are needed.

Research advances in communication interactions among the symbionts of "bacteria-zooxanthellae-coral"

"Bacteria-zooxanthellae-coral" is a pair of typical triangular relationships in the marine ecosystem. There are complex flows of material, information, and energy in this system. The balance and stability of the symbionts is an important guarantee for maintaining the health of coral reef ecosystems. Many studies have been conducted on the interaction of coral symbionts in the past 20 years, which help clarify the material metabolism and nutrient exchange between "bacteria-zooxanthellae-coral" and their interaction with the environment. Due to the complexity of this symbiotic system, the mechanisms of some phenomena are still not well understood, especially for the communication among the symbionts. The interaction mediated by signal molecules is the internal driving force for the homeostatic maintenance and efficient operation of coral symbionts. In this review, we tried to summarize the latest research progress by focusing on the chemical signaling molecules in coral symbiotic system, including the communications between the bacteria and bacteria, bacteria and corals, bacteria and zooxanthellae, and zooxanthellae and corals. The main signals molecules include quorum sensing (QS) molecules, dimethylsulfoniopropionate (DMSP), glycans signals, lipid signals, and the noncoding RNAs. We focused on the functional mode and ecological significance of signal molecules in symbionts, and selectively exemplified microbial cooperation and competition mediated by QS signals, the interaction between bacteria and corals under the regulation of DMSP, and the response process of corals and zooxanthellae to noncoding RNAs under environmental stresses. We proposed the future research focus and possible directions, including the expansion of research dimensions, the application of new technologies and new methods, and the construction of ecological models. This work would help improve the understanding of interactions between "bacteria-zooxanthellae-coral". The exploration about the ways based on communication language would provide new ideas for the restoration and protection of coral reef ecosystems.

Cell Size as a Primary Determinant in Targeted Nanoparticle Uptake.

Nanoparticle (NP) internalization by cells is complex, highly heterogeneous, and fundamentally important for nanomedicine. We report powerful probabilistic statistics from single-cell data on quantitative NP uptake of PEG-coated transferrin receptor-targeted gold NPs for cancer-derived and fibroblast cells according to their cell size, receptor expression, and receptor density. The smaller cancer cells had a greater receptor density and more efficient uptake of targeted NPs. However, simply due to fibroblasts being larger with more receptors, they exhibited greater NP uptake. While highly heterogeneous, targeted NP uptake strongly correlated with receptor expression. When uptake was normalized to cell size, no correlation existed. Consequently, skewed population distributions in cell sizes explain the distribution in NP uptake. Furthermore, exposure to the transferrin receptor-targeted NPs alters the fibroblast size and receptor expression, suggesting that the receptor-targeted NPs may interfere with the metabolic flux and nutrient exchange, which could assist in explaining the altered regulation of cells exposed to nanoparticles.

Dissolved organic metabolite extraction from high-salt media.

We describe considerations and strategies for developing a nuclear magnetic resonance (NMR) sample preparation method to extract low molecular weight metabolites from high-salt spent media in a model coculture system of phytoplankton and marine bacteria. Phytoplankton perform half the carbon fixation and oxygen generation on Earth. A substantial fraction of fixed carbon becomes part of a metabolite pool of small molecules known as dissolved organic matter (DOM), which are taken up by marine bacteria proximate to phytoplankton. There is an urgent need to elucidate these metabolic exchanges due to widespread anthropogenic transformations on the chemical, phenotypic, and species composition of seawater. These changes are increasing water temperature and the amount of CO2 absorbed by the ocean at energetic costs to marine microorganisms. Little is known about the metabolite-mediated, structured interactions occurring between phytoplankton and associated marine bacteria, in part because of challenges in studying high-salt solutions on various analytical platforms. NMR analysis is problematic due to the high-salt content of both natural seawater and culture media for marine microbes. High-salt concentration degrades the performance of the radio frequency coil, reduces the efficiency of some pulse sequences, limits signal-to-noise, and prolongs experimental time. The method described herein can reproducibly extract low molecular weight DOM from small-volume, high-salt cultures. It is a promising tool for elucidating metabolic flux between marine microorganisms and facilitates genetic screens of mutant microorganisms.

Entering the labyrinth: A hypothesis about the emergence of metabolism from protobiotic routes

The occurrence of organized chemical transformations defined as metabolism is one of the most important characteristics of life. Surprisingly though, there is not a consensus about how those transformations were originated in the origin of life. RNA world advocates suggest that biochemical pathways started with ribozymes that were further substituted by enzymes. However, most of the biosynthetic routes of ribozymes described do not overlap with the enzymatic routes, and there is not a clear theory about how this transition happened. An important step to solve this dilemma has been elucidated in the last decade when researchers found that some complex routes of chemical transformations, such as the glycolytic and the citric acid pathways, already existed in prebiotic Earth due to physicochemical forces alone. Defined here as protobiotic pathways, we propose that those metabolic exchanges working without the aiding of any biological catalysts were the ones that guided the origin of metabolism. Under this scenario, some quasi-randomly encoded peptides at the origins of translation systems would be capable to bind metabolites in protobiotic routes. When those bounds facilitated or accelerated the conversion of metabolites along the protobiotic path and the products were beneficial, then natural molecular selection acted to preserve the system. Thus, we propose that the origin of metabolism happened when peptides started to bind metabolites in protobiotic routes without disturbing (and possibly aiding) their chemical transformation paths. This should have been the entry point to the metabolic labyrinth, the key step that allowed peptides to come into the path of chemical transformations and further evolve into the enzymes that coordinate nowadays the biochemical pathways.

Integrating metagenomic binning with flux balance analysis to unravel syntrophies in anaerobic CO2 methanation

BackgroundCarbon fixation through biological methanation has emerged as a promising technology to produce renewable energy in the context of the circular economy. The anaerobic digestion microbiome is the fundamental biological system operating biogas upgrading and is paramount in power-to-gas conversion. Carbon dioxide (CO2) methanation is frequently performed by microbiota attached to solid supports generating biofilms. Despite the apparent simplicity of the microbial community involved in biogas upgrading, the dynamics behind most of the interspecies interaction remain obscure. To understand the role of the microbial species in CO2 fixation, the biofilm generated during the biogas upgrading process has been selected as a case study. The present work investigates via genome-centric metagenomics, based on a hybrid Nanopore-Illumina approach the biofilm developed on the diffusion devices of four ex situ biogas upgrading reactors. Moreover, genome-guided metabolic reconstruction and flux balance analysis were used to propose a biological role for the dominant microbes.ResultsThe combined microbiome was composed of 59 species, with five being dominant (> 70% of total abundance); the metagenome-assembled genomes representing these species were refined to reach a high level of completeness. Genome-guided metabolic analysis appointed Firmicutes sp. GSMM966 as the main responsible for biofilm formation. Additionally, species interactions were investigated considering their co-occurrence in 134 samples, and in terms of metabolic exchanges through flux balance simulation in a simplified medium. Some of the most abundant species (e.g., Limnochordia sp. GSMM975) were widespread (~ 67% of tested experiments), while others (e.g., Methanothermobacter wolfeii GSMM957) had a scattered distribution. Genome-scale metabolic models of the microbial community were built with boundary conditions taken from the biochemical data and showed the presence of a flexible interaction network mainly based on hydrogen and carbon dioxide uptake and formate exchange.ConclusionsOur work investigated the interplay between five dominant species within the biofilm and showed their importance in a large spectrum of anaerobic biogas reactor samples. Flux balance analysis provided a deeper insight into the potential syntrophic interaction between species, especially Limnochordia sp. GSMM975 and Methanothermobacter wolfeii GSMM957. Finally, it suggested species interactions to be based on formate and amino acids exchanges.AQaLxbUWFz91qWxiAB1_X5Video

RNA-seq Provides Novel Insights into Response to Acute Salinity Stress in Oriental River Prawn Macrobrachium nipponense.

The oriental river prawn Macrobrachium nipponense is an important aquaculture species in China, Vietnam, and Japan. This species could survive in the salinity ranging from 7 to 20 ppt and accelerate growth in the salinity of 7 ppt. To identify the genes and pathways in response to acute high salinity stress, M. nipponense was exposed to the acute high salinity of 25 ppt. Total RNA from hepatopancreas, gills, and muscle tissues was isolated and then sequenced using high-throughput sequencing method. Differentially expressed genes (DGEs) were identified, and a total of 632, 836, and 1246 DEGs with a cutoff of significant twofold change were differentially expressed in the hepatopancreas, gills, and muscle tissues, respectively. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome pathway enrichment analyses were conducted. These DEGs were involved in the GO terms of cellular process, metabolic process, membrane, organelle, binding, and catalytic activity. The DEGs of hepatopancreas and gill tissues were mainly enriched in PPAR signaling pathway, longevity regulating pathway, protein digestion and absorption, and the DEGs of muscle tissue in arginine biosynthesis, adrenergic signaling in cardiomyocytes, cardiac muscle contraction, and cGMP-PKG signaling pathway. Real-time PCR conducted with fifteen selected DEGs indicated high reliability of digital analysis using RNA-Seq. The results indicated that the M. nipponense may regulate essential mechanisms such as metabolism, oxidative stress, and ion exchange to adapt the alternation of environment, when exposed to acute high salinity stress. This work reveals the numbers of genes modified by salinity stress and some important pathways, which could provide a comprehensive insight into the molecular responses to high salinity stress in M. nipponense and further boost the understanding of the potential molecular mechanisms of adaptation to salinity stress for euryhaline crustaceans.

Circulating Metabolites in Relation to the Kidney Allograft Function in Posttransplant Patients.

End-stage kidney disease is preferably treated by kidney transplantation. The suboptimal function of the allograft often results in misbalances in kidney-controlled processes and requires long-term monitoring of allograft function and viability. As the kidneys are organs with a very high metabolomic rate, a metabolomics approach is suitable to describe systematic changes in post-transplant patients and has great potential for monitoring allograft function, which has not been described yet. In this study, we used blood plasma samples from 55 patients after primary kidney transplantation identically treated with immunosuppressants with follow-up 50 months in the mean after surgery and evaluated relative levels of basal plasma metabolites detectable by NMR spectroscopy. We were looking for the correlations between circulating metabolites levels and allograft performance and allograft rejection features. Our results imply a quantitative relationship between restricted renal function, insufficient hydroxylation of phenylalanine to tyrosine, lowered renal glutamine utilization, shifted nitrogen balance, and other alterations that are not related exclusively to the metabolism of the kidney. No link between allograft function and energy metabolism can be concluded, as no changes were found for glucose, glycolytic intermediates, and 3-hydroxybutyrate as a ketone body representative. The observed changes are to be seen as a superposition of changes in the comprehensive inter-organ metabolic exchange, when the restricted function of one organ may induce compensatory effects or cause secondary alterations. Particular differences in plasma metabolite levels in patients with acute cellular and antibody-mediated allograft rejection were considered rather to be related to the loss of kidney function than to the molecular mechanism of graft rejection since they largely follow the alterations observed by restricted allograft function. In the end, we showed using a simple mathematical model, multilinear regression, that the basal plasmatic metabolites correlated with allograft function expressed by the level of glomerular filtration rate (with creatinine: p-value = 4.0 × 10−26 and r = 0.94, without creatinine: p-value = 3.2 × 10−22 and r = 0.91) make the noninvasive estimation of the allograft function feasible.