Fluctuations In Nutrient Availability Research Articles

Fire-modulated fluctuations in nutrient availability stimulate biome-scale floristic turnover in time, and elevated species richness, in low-nutrient fynbos heathland.

In many systems, postfire vegetation recovery is characterized by temporal changes in plant species composition and richness. We attribute this to changes in resource availability with time since fire, with the magnitude of species turnover determined by the degree of resource limitation. Here, we test the hypothesis that postfire species turnover in South African fynbos heathland is powered by fire-modulated changes in nutrient availability, with the magnitude of turnover in nutrient-constrained fynbos being greater than in fertile renosterveld shrubland. We also test the hypothesis that floristic overlaps between fynbos and renosterveld are attributable to nutritional augmentation of fynbos soils immediately after fire. We use vegetation survey data from two sites on the Cape Peninsula to compare changes in species richness and composition with time since fire. Fynbos communities display a clear decline in species richness with time since fire, whereas no such decline is apparent in renosterveld. In fynbos, declining species richness is associated with declines in the richness of plant families having high foliar concentrations of nitrogen, phosphorus and potassium and possessing attributes that are nutritionally costly. In contrast, families that dominate late-succession fynbos possess adaptations for the acquisition and retention of sparse nutrients. At the family level, recently burnt fynbos is compositionally more similar to renosterveld than is mature fynbos. Our data suggest that nutritionally driven species turnover contributes significantly to fynbos community richness. We propose that the extremely low baseline fertility of fynbos soils serves to lengthen the nutritional resource axis along which species can differentiate and coexist, thereby providing the opportunity for low-nutrient extremophiles to coexist spatially with species adapted to more fertile soil. This mechanism has the potential to operate in any resource-constrained system in which episodic disturbance affects resource availability.

Deciphering the decline of metabolic elasticity in aging and obesity

Organisms must adapt to fluctuating nutrient availability to maintain energy homeostasis. Here, we term the capacity for such adaptation and restoration "metabolic elasticity" and model it through ad libitum-fasting-refeeding cycles. Metabolic elasticity is achieved by coordinate versatility in gene expression, which we call "gene elasticity." We have developed the gene elasticity score as a systematic method to quantify the elasticity of the transcriptome across metabolically active tissues in mice and non-human primates. Genes involved in lipid and carbohydrate metabolism show high gene elasticity, and their elasticity declines with age, particularly with PPARγ dysregulation in adipose tissue. Synchronizing PPARγ activity with nutrient conditions through feeding-timed agonism optimizes their metabolic benefits and safety. We further broaden the conceptual scope of metabolic and gene elasticity to dietary challenges, revealing declines in diet-induced obesity similar to those in aging. Altogether, our findings provide a dynamic perspective on the dysmetabolic consequences of aging and obesity.

A Single Residue within the MCR-1 Protein Confers Anticipatory Resilience.

The envelope stress response (ESR) of Gram-negative enteric bacteria senses fluctuations in nutrient availability and environmental changes to avert damage and promote survival. It has a protective role toward antimicrobials, but direct interactions between ESR components and antibiotic resistance genes have not been demonstrated. Here, we report interactions between a central regulator of ESR viz., the two-component signal transduction system CpxRA (conjugative pilus expression), and the recently described mobile colistin resistance protein (MCR-1). Purified MCR-1 is specifically cleaved within its highly conserved periplasmic bridge element, which links its N-terminal transmembrane domain with the C-terminal active-site periplasmic domain, by the CpxRA-regulated serine endoprotease DegP. Recombinant strains harboring cleavage site mutations in MCR-1 are either protease resistant or degradation susceptible, with widely differing consequences for colistin resistance. Transfer of the gene encoding a degradation-susceptible mutant to strains that lack either DegP or its regulator CpxRA restores expression and colistin resistance. MCR-1 production in Escherichia coli imposes growth restriction in strains lacking either DegP or CpxRA, effects that are reversed by transactive expression of DegP. Excipient allosteric activation of the DegP protease specifically inhibits growth of isolates carrying mcr-1 plasmids. As CpxRA directly senses acidification, growth of strains at moderately low pH dramatically increases both MCR-1-dependent phosphoethanolamine (PEA) modification of lipid A and colistin resistance levels. Strains expressing MCR-1 are also more resistant to antimicrobial peptides and bile acids. Thus, a single residue external to its active site induces ESR activity to confer resilience in MCR-1-expressing strains to commonly encountered environmental stimuli, such as changes in acidity and antimicrobial peptides. Targeted activation of the nonessential protease DegP can lead to the elimination of transferable colistin resistance in Gram-negative bacteria. IMPORTANCE The global presence of transferable mcr genes in a wide range of Gram-negative bacteria from clinical, veterinary, food, and aquaculture environments is disconcerting. Its success as a transmissible resistance factor remains enigmatic, because its expression imposes fitness costs and imparts only moderate levels of colistin resistance. Here, we show that MCR-1 triggers regulatory components of the envelope stress response, a system that senses fluctuations in nutrient availability and environmental changes, to promote bacterial survival in low pH environments. We identify a single residue within a highly conserved structural element of mcr-1 distal to its catalytic site that modulates resistance activity and triggers the ESR. Using mutational analysis, quantitative lipid A profiling and biochemical assays, we determined that growth in low pH environments dramatically increases colistin resistance levels and promotes resistance to bile acids and antimicrobial peptides. We exploited these findings to develop a targeted approach that eliminates mcr-1 and its plasmid carriers.

Effects of nutrient pulses on exotic species shift from positive to neutral with decreasing water availability.

Temporal fluctuation in nutrient availability generally promotes the growth of exotic plant species and has been recognized as an important driver of exotic plant invasions. However, little is known about how the impact of fluctuating nutrients on exotic species is dependent on the availability of other resources, although most ecosystems are experiencing dramatic variations in a wide variety of resources due to global change and human disturbance. Here, we explored how water availability mediates the effect of nutrient pulses on the growth of six exotic and six native plant species. We subjected individual plants of exotic and native species to well watered or water stressed conditions. For each level of water availability, we added equivalent amounts of nutrients at a constant rate, as a single large pulse, or in multiple small pulses. Under well watered conditions, nutrient pulses promoted exotic plant growth relative to nutrients supplied constantly, while they had no significant effect on natives. In contrast, under water stressed conditions, water deficiency inhibited the growth of all exotic and native species. More importantly, nutrient pulses did not increase plant growth relative to nutrients supplied constantly and these phenomena were observed for both exotic and native species. Taken together, our study shows that the impact of fluctuating nutrient availability on the growth of exotic plant species strongly depends on the variation of other resources, and that the positive effect of nutrient pulses under well watered conditions disappears under water stressed conditions. Our findings suggest that the variation in multiple resources may have complex feedback on exotic plant invasions and, therefore, it is critical to encompass multiple resources for the evaluation of fluctuating resource availability effects on exotic plant species. This will allow us to project the invasive trajectory of exotic plant species more accurately under future global change and human disturbance.

Simulated seasonal diets alter yak rumen microbiota structure and metabolic function.

Yak is the only ruminant on the Qinghai-Tibetan Plateau that grazes year-round. Although previous research has shown that yak rumen microbiota fluctuates in robust patterns with seasonal foraging, it remains unclear whether these dynamic shifts are driven by changes in environment or nutrient availability. The study examines the response of yak rumen microbiota (bacteria, fungi, and archaea) to simulated seasonal diets, excluding the contribution of environmental factors. A total of 18 adult male yaks were randomly divided into three groups, including a nutrition stress group (NSG, simulating winter pasture), a grazing simulation group (GSG, simulating warm season pasture), and a supplementation group (SG, simulating winter pasture supplemented with feed concentrates). Volatile fatty acids (VFAs) profiling showed that ruminal acetate, propionate and total VFA contents were significantly higher (p < 0.05) in GSG rumen. Metagenomic analysis showed that Bacteroidetes (53.9%) and Firmicutes (37.1%) were the dominant bacterial phyla in yak rumen across dietary treatments. In GSG samples, Actinobacteriota, Succinivibrionaceae_UCG-002, and Ruminococcus albus were the most abundant, while Bacteroides was significantly more abundant in NSG samples (p < 0.05) than that in GSG. The known fiber-degrading fungus, Neocallimastix, was significantly more abundant in NSG and SG samples, while Cyllamyces were more prevalent in NSG rumen than in the SG rumen. These findings imply that a diverse consortium of microbes may cooperate in response to fluctuating nutrient availability, with depletion of known rumen taxa under nutrient deficiency. Archaeal community composition showed less variation between treatments than bacterial and fungal communities. Additionally, Orpinomyces was significantly positively correlated with acetate levels, both of which are prevalent in GSG compared with other groups. Correlation analysis between microbial taxa and VFA production or between specific rumen microbes further illustrated a collective response to nutrient availability by gut microbiota and rumen VFA metabolism. PICRUSt and FUNGuild functional prediction analysis indicated fluctuation response of the function of microbial communities among groups. These results provide a framework for understanding how microbiota participate in seasonal adaptations to forage availability in high-altitude ruminants, and form a basis for future development of probiotic supplements to enhance nutrient utilization in livestock.

Adipose mitochondrial metabolism controls body growth by modulating systemic cytokine and insulin signaling.

Animals must adapt their growth to fluctuations in nutrient availability to ensure proper development. These adaptations often rely on specific nutrient-sensing tissues that control whole-body physiology through inter-organ communication. While the signaling mechanisms that underlie this communication are well studied, the contributions of metabolic alterations in nutrient-sensing tissues are less clear. Here, we show how the reprogramming of adipose mitochondria controls whole-body growth in Drosophila larvae. We find that dietary nutrients alter fat-body mitochondrial morphology to lower their bioenergetic activity, leading to rewiring of fat-body glucose metabolism. Strikingly, we find that genetic reduction of mitochondrial bioenergetics just in the fat body is sufficient to accelerate body growth and development. These growth effects are caused by inhibition of the fat-derived secreted peptides ImpL2 and tumor necrosis factor alpha (TNF-α)/Eiger, leading to enhanced systemic insulin signaling. Our work reveals how reprogramming of mitochondrial metabolism in one nutrient-sensing tissue can couple nutrient availability to whole-body growth.

The role of morphological changes in Microcystis adaptation to nutrient availability at the colonial level

Colony formation is a key trait facilitating the formation of Microcystis blooms. However, the role of morphological changes (e.g., colony size and tightness) in the adaptation to nutrient availability is not fully understood. In this study, we analyzed the morphological changes under both nutrient sufficiency and deficiency. Accordant morphological changes were found with both an isolated colonial strain and mixed field colonies. Colonies that were limited by nutrients became bloated and uncompacted structures, and this change was more pronounced under N deficiency. This looser morphology increased the availability of intra-colony light and relieved the size effect. When nutrients were sufficient, small colonies emerged, which helped to maintain rapid growth (0.32 day−1). Our study highlighted probable role of morphological variations in: (1) diminishing intra-colony self-shading when facing nutrient deficiency; and (2) enlarging the population under high trophic levels by generating daughter colonies. These roles were also verified using field data from Lake Taihu, which further indicated that the seasonal succession of morphospecies was probably the result of adaptive morphological changes. Adaptive morphological changes offer advantages against fluctuations in nutrient availability, which should be considered when attempting to restrain bloom formation.

The Molecular Brakes of Adipose Tissue Lipolysis.

Adaptation to changes in energy availability is pivotal for the survival of animals. Adipose tissue, the body’s largest reservoir of energy and a major source of metabolic fuel, exerts a buffering function for fluctuations in nutrient availability. This functional plasticity ranges from energy storage in the form of triglycerides during periods of excess energy intake to energy mobilization via lipolysis in the form of free fatty acids for other organs during states of energy demands. The subtle balance between energy storage and mobilization is important for whole-body energy homeostasis; its disruption has been implicated as contributing to the development of insulin resistance, type 2 diabetes and cancer cachexia. As a result, adipocyte lipolysis is tightly regulated by complex regulatory mechanisms involving lipases and hormonal and biochemical signals that have opposing effects. In thermogenic brown and brite adipocytes, lipolysis stimulation is the canonical way for the activation of non-shivering thermogenesis. Lipolysis proceeds in an orderly and delicately regulated manner, with stimulation through cell-surface receptors via neurotransmitters, hormones, and autocrine/paracrine factors that activate various intracellular signal transduction pathways and increase kinase activity. The subsequent phosphorylation of perilipins, lipases, and cofactors initiates the translocation of key lipases from the cytoplasm to lipid droplets and enables protein-protein interactions to assemble the lipolytic machinery on the scaffolding perilipins at the surface of lipid droplets. Although activation of lipolysis has been well studied, the feedback fine-tuning is less well appreciated. This review focuses on the molecular brakes of lipolysis and discusses some of the divergent fine-tuning strategies in the negative feedback regulation of lipolysis, including delicate negative feedback loops, intermediary lipid metabolites-mediated allosteric regulation and dynamic protein–protein interactions. As aberrant adipocyte lipolysis is involved in various metabolic diseases and releasing the brakes on lipolysis in thermogenic adipocytes may activate thermogenesis, targeting adipocyte lipolysis is thus of therapeutic interest.

Herbivory may mediate the effects of nutrients on the dominance of alien plants

Abstract Numerous studies have highlighted the roles of nutrient availability and fluctuations therein for invasion success of alien plants. Many others also highlighted the role of herbivores in invasion success. However, how herbivory and the level and fluctuations in nutrient availability interact in driving alien plant invasion into native communities remains largely unexplored. We grew eight invasive alien species as target species in pot‐mesocosms with five different synthetic native communities in a three‐factorial design with two levels of nutrient availability (low vs. high), two levels of nutrient fluctuation (constant vs. pulsed) and two levels of above‐ground insect herbivory (with vs. without herbivores). As natural communities have both specialist and generalist herbivores, we simulated this using both a generalist and a specialist herbivorous grasshopper. The relative biomass production of the alien target plants to the total biomass production (i.e. alien biomass/total biomass) decreased in response to an increase in nutrient availability, but increased in response to the presence of herbivores. Furthermore, we found indications that the dominance of the alien target species may depend on interactions of herbivory with changes in nutrient availability and nutrient fluctuations, although these interactions were only marginally significant. Our multi‐trophic multi‐species experiment suggests that herbivory could mediate the interactive effect of nutrient enrichment and variability in nutrient supply on invasion of alien plants into native communities. Therefore, we recommend that studies testing the effects of resources on plant invasion should also consider interactive effects of other trophic levels. Read the free Plain Language Summary for this article on the Journal blog.

Improving the Robustness of Engineered Bacteria to Nutrient Stress Using Programmed Proteolysis.

The use of short peptide tags in synthetic genetic circuits allows for the tuning of gene expression dynamics and release of amino acid resources through targeted protein degradation. Here, we use elements of the Escherichia coli and Mesoplasma florum transfer-mRNA (tmRNA) ribosome rescue systems to compare endogenous and foreign proteolysis systems in E. coli. We characterize the performance and burden of each and show that, while both greatly shorten the half-life of a tagged protein, the endogenous system is approximately 10 times more efficient. On the basis of these results we then demonstrate using mathematical modeling and experiments how proteolysis can improve cellular robustness through targeted degradation of a reporter protein in auxotrophic strains, providing a limited secondary source of essential amino acids that help partially restore growth when nutrients become scarce. These findings provide avenues for controlling the functional lifetime of engineered cells once deployed and increasing their tolerance to fluctuations in nutrient availability.

Year-round dynamics of amplicon sequence variant communities differ among eukaryotes, Imitervirales and prokaryotes in a coastal ecosystem.

Coastal microbial communities are affected by seasonal environmental change, biotic interactions and fluctuating nutrient availability. We investigated the seasonal dynamics of communities of eukaryotes, a major group of double-stranded DNA viruses that infect eukaryotes (order Imitervirales; phylum Nucleocytoviricota), and prokaryotes in the Uranouchi Inlet, Kochi, Japan. We performed metabarcoding using ribosomal RNA genes and viral polB genes as markers in 43 seawater samples collected over 20 months. Eukaryotes, prokaryotes and Imitervirales communities characterized by the compositions of amplicon sequence variants (ASVs) showed synchronic seasonal cycles. However, the community dynamics showed intriguing differences in several aspects, such as the recovery rate after a year. We also showed that the differences in community dynamics were at least partially explained by differences in recurrence/persistence levels of individual ASVs among eukaryotes, prokaryotes and Imitervirales. Prokaryotic ASVs were the most persistent, followed by eukaryotic ASVs and Imitervirales ASVs, which were the least persistent. We argue that the differences in the specificity of interactions (virus-eukaryote vs prokaryote-eukaryote) as well as the niche breadth of community members were at the origin of the distinct community dynamics among eukaryotes, their viruses and prokaryotes.

Lipid Droplet-Organelle Contact Sites as Hubs for Fatty Acid Metabolism, Trafficking, and Metabolic Channeling.

Cells prepare for fluctuations in nutrient availability by storing energy in the form of neutral lipids in organelles called Lipid Droplets (LDs). Upon starvation, fatty acids (FAs) released from LDs are trafficked to different cellular compartments to be utilized for membrane biogenesis or as a source of energy. Despite the biochemical pathways being known in detail, the spatio-temporal regulation of FA synthesis, storage, release, and breakdown is not completely understood. Recent studies suggest that FA trafficking and metabolism are facilitated by inter-organelle contact sites that form between LDs and other cellular compartments such as the Endoplasmic Reticulum (ER), mitochondria, peroxisomes, and lysosomes. LD-LD contact sites are also sites where FAs are transferred in a directional manner to support LD growth and expansion. As the storage site of neutral lipids, LDs play a central role in FA homeostasis. In this mini review, we highlight the role of LD contact sites with other organelles in FA trafficking, channeling, and metabolism and discuss the implications for these pathways on cellular lipid and energy homeostasis.

Mitochondrial cristae-remodeling protein OPA1 in POMC neurons couples Ca2+ homeostasis with adipose tissue lipolysis

SummaryAppropriate cristae remodeling is a determinant of mitochondrial function and bioenergetics and thus represents a crucial process for cellular metabolic adaptations. Here, we show that mitochondrial cristae architecture and expression of the master cristae-remodeling protein OPA1 in proopiomelanocortin (POMC) neurons, which are key metabolic sensors implicated in energy balance control, is affected by fluctuations in nutrient availability. Genetic inactivation of OPA1 in POMC neurons causes dramatic alterations in cristae topology, mitochondrial Ca2+ handling, reduction in alpha-melanocyte stimulating hormone (α-MSH) in target areas, hyperphagia, and attenuated white adipose tissue (WAT) lipolysis resulting in obesity. Pharmacological blockade of mitochondrial Ca2+ influx restores α-MSH and the lipolytic program, while improving the metabolic defects of mutant mice. Chemogenetic manipulation of POMC neurons confirms a role in lipolysis control. Our results unveil a novel axis that connects OPA1 in POMC neurons with mitochondrial cristae, Ca2+ homeostasis, and WAT lipolysis in the regulation of energy balance.

Interactive effects of nutrient availability, fluctuating supply, and plant parasitism on the post-invasion success of Bidens pilosa

The post-invasion success of alien plant species is determined by many biotic and abiotic factors, but no study has tested the interactive effect of nutrient availability, fluctuating nutrient supply and parasitic plants. Testing this effect is important because parasitic plants are proposed as a promising agent for biocontrol of alien plant invasions. We constructed an experimental native community under constant or fluctuating conditions as well as high or low nutrient availability and let them be invaded by an alien annual plant Bidens pilosa or not and parasitized by Cuscuta australis or not. High nutrient availability significantly increased the invasion success of B. pilosa (as indicated by its increased biomass fraction, i.e., invader biomass divided by total biomass of all plants) by benefiting the invader more than the native plant community. Fluctuating nutrient supply also significantly enhanced the invasion success of B. pilosa by suppressing the growth of the natives while improving that of the invader. Parasitism by C. australis decreased the growth of the invader and thus its invasion success in the native community when nutrient availability was low and fluctuating, but parasitism had little impact under other nutrient conditions. Our study offers further evidence that high and fluctuating nutrient availability can increase the invasion success of alien plant species in native plant communities, but also demonstrates that the impact of parasitic plants depends on environmental conditions. Thus, reducing nutrient loading and the extent of fluctuating nutrient supply can help native plant communities resist alien plant invasions, but introducing parasitic plants may only be successful if reduced loads are also fluctuating.

Regulation and metabolic functions of mTORC1 and mTORC2

Cells metabolize nutrients for biosynthetic and bioenergetic needs to fuel growth and proliferation. The uptake of nutrients from the environment and their intracellular metabolism is a highly controlled process that involves cross talk between growth signaling and metabolic pathways. Despite constant fluctuations in nutrient availability and environmental signals, normal cells restore metabolic homeostasis to maintain cellular functions and prevent disease. A central signaling molecule that integrates growth with metabolism is the mechanistic target of rapamycin (mTOR). mTOR is a protein kinase that responds to levels of nutrients and growth signals. mTOR forms two protein complexes, mTORC1, which is sensitive to rapamycin, and mTORC2, which is not directly inhibited by this drug. Rapamycin has facilitated the discovery of the various functions of mTORC1 in metabolism. Genetic models that disrupt either mTORC1 or mTORC2 have expanded our knowledge of their cellular, tissue, as well as systemic functions in metabolism. Nevertheless, our knowledge of the regulation and functions of mTORC2, particularly in metabolism, has lagged behind. Since mTOR is an important target for cancer, aging, and other metabolism-related pathologies, understanding the distinct and overlapping regulation and functions of the two mTOR complexes is vital for the development of more effective therapeutic strategies. This review discusses the key discoveries and recent findings on the regulation and metabolic functions of the mTOR complexes. We highlight findings from cancer models but also discuss other examples of the mTOR-mediated metabolic reprogramming occurring in stem and immune cells, type 2 diabetes/obesity, neurodegenerative disorders, and aging.

Modulation of plant root growth by nitrogen source-defined regulation of polar auxin transport.

Availability of the essential macronutrient nitrogen in soil plays a critical role in plant growth, development, and impacts agricultural productivity. Plants have evolved different strategies for sensing and responding to heterogeneous nitrogen distribution. Modulation of root system architecture, including primary root growth and branching, is among the most essential plant adaptions to ensure adequate nitrogen acquisition. However, the immediate molecular pathways coordinating the adjustment of root growth in response to distinct nitrogen sources, such as nitrate or ammonium, are poorly understood. Here, we show that growth as manifested by cell division and elongation is synchronized by coordinated auxin flux between two adjacent outer tissue layers of the root. This coordination is achieved by nitrate‐dependent dephosphorylation of the PIN2 auxin efflux carrier at a previously uncharacterized phosphorylation site, leading to subsequent PIN2 lateralization and thereby regulating auxin flow between adjacent tissues. A dynamic computer model based on our experimental data successfully recapitulates experimental observations. Our study provides mechanistic insights broadening our understanding of root growth mechanisms in dynamic environments.

Interorgan Metabolism of Amino Acids in Human Health and Disease.

Amino acids are integral for human health, influencing an array of physiological processes from gene expression to vasodilation to the immune response. In accordance with this expansive range of unique functions, the tissues of the body engage in a complex interplay of amino acid exchange and metabolism to respond to the organism's dynamic needs for a range of nitrogenous products. Interorgan amino acid metabolism is required for numerous metabolic pathways, including the synthesis of functional amino acids like arginine, glutamate, glutamine, and glycine. This physiological process requires the cooperative handling of amino acids by organs (e.g., the small intestine, skeletal muscle, kidneys, and liver), as well as the complete catabolism of nutritionally essential amino acids such as the BCAAs, with their α-ketoacids shuttled from muscle to liver. These exchanges are made possible by several mechanisms, including organ location, as well as the functional zonation of enzymes and the cell-specific expression of amino acid transporters. The cooperative handling of amino acids between the various organs does not appear to be under the control of any centralized regulation, but is instead influenced by factors such as fluctuations in nutrient availability, hormones, changes associated with development, and altered environmental factors. While the normal function of these pathways is associated with health and homeostasis, affected by physical activity, diet and body composition, dysregulation is observed in numerous disease states, including cardiovascular disease and cancer cachexia, presenting potential avenues for the manipulation of amino acid consumption as part of the therapeutic approach to these conditions in individuals.

Transcriptome assisted label free proteomics of hepatic tissue in response to both dietary restriction and compensatory growth in cattle

Compensatory growth (CG) is a naturally occurring phenomenon where, following a period of under nutrition, an animal exhibits accelerated growth upon re-alimentation. The objective was to identify and quantify hepatic proteins involved in the regulation of CG in cattle. Forty Holstein Friesian bulls were equally assigned to one of four groups. Groups; A1 and A2 had ad libitum access to feed for 125 days, groups R1 and R2 were feed restricted. Following this, R1 and A1 animals were slaughtered. Remaining animals (R2 and A2) were slaughtered following ad libitum feeding for a successive 55 days. At slaughter hepatic tissue samples were collected and label-free quantitative proteomics undertaken with spectra searched against a custom built transcriptome database specific to the animals in this study. 24 differentially abundant proteins were identified during CG (R2 vs. R1) including; PSPH, ASNS and GSTM1, which are involved in nutrient metabolism, immune response and cellular growth. Proteins involved in biochemical pathways related to nutrient metabolism were down-regulated during CG, indicating a possible adaptive response by the liver to a period of fluctuating nutrient availability. The livers ability to regulate its metabolic activity may have profound effects on the efficiency of whole body energy utilization during CG. SignificanceThis study is the first to unravel the effect of compensatory growth on the hepatic proteome of cattle using transcriptome-assisted shot gun proteomics. Proteins identified as being affected by dietary restriction and subsequent expression of compensatory growth in this study may, following appropriate validation, contribute to the identification of functional genetic variants. Such information could be harnessed within the context of genomic selection in cattle breeding programs to identify animals with a greater genetic potential to undergo compensatory growth, thus increasing the profitability of the beef sector and accelerating genetic gain.

Coupled metabolic-hydrodynamic modeling enabling rational scale-up of industrial bioprocesses.

Metabolomics aims to address what and how regulatory mechanisms are coordinated to achieve flux optimality, different metabolic objectives as well as appropriate adaptations to dynamic nutrient availability. Recent decades have witnessed that the integration of metabolomics and fluxomics within the goal of synthetic biology has arrived at generating the desired bioproducts with improved bioconversion efficiency. Absolute metabolite quantification by isotope dilution mass spectrometry represents a functional readout of cellular biochemistry and contributes to the establishment of metabolic (structured) models required in systems metabolic engineering. In industrial practices, population heterogeneity arising from fluctuating nutrient availability frequently leads to performance losses, that is reduced commercial metrics (titer, rate, and yield). Hence, the development of more stable producers and more predictable bioprocesses can benefit from a quantitative understanding of spatial and temporal cell-to-cell heterogeneity within industrial bioprocesses. Quantitative metabolomics analysis and metabolic modeling applied in computational fluid dynamics (CFD)-assisted scale-down simulators that mimic industrial heterogeneity such as fluctuations in nutrients, dissolved gases, and other stresses can procure informative clues for coping with issues during bioprocessing scale-up. In previous studies, only limited insights into the hydrodynamic conditions inside the industrial-scale bioreactor have been obtained, which makes case-by-case scale-up far from straightforward. Tracking the flow paths of cells circulating in large-scale bioreactors is a highly valuable tool for evaluating cellular performance in production tanks. The "lifelines" or "trajectories" of cells in industrial-scale bioreactors can be captured using Euler-Lagrange CFD simulation. This novel methodology can be further coupled with metabolic (structured) models to provide not only a statistical analysis of cell lifelines triggered by the environmental fluctuations but also a global assessment of the metabolic response to heterogeneity inside an industrial bioreactor. For the future, the industrial design should be dependent on the computational framework, and this integration work will allow bioprocess scale-up to the industrial scale with an end in mind.

Feedforward Control of Plant Nitrate Transporter NRT1.1 Biphasic Adaptive Activity

Defective nitrate signaling in plants causes disorder in nitrogen metabolism, and it negatively affects nitrate transport systems, which toggle between high- and low-affinity modes in variable soil nitrate conditions. Recent discovery of a plasma membrane nitrate transceptor protein NRT1.1—a transporter cum sensor—provides a clue on this toggling mechanism. However, the general mechanistic description still remains poorly understood. Here, we illustrate adaptive responses and regulation of NRT1.1-mediated nitrate signaling in a wide range of extracellular nitrate concentrations. The results show that the homodimeric structure of NRT1.1 and its dimeric switch play an important role in eliciting specific cytosolic calcium waves sensed by the calcineurin-B-like calcium sensor CBL9, which activates the kinase CIPK23, in low nitrate concentration that is, however, impeded in high nitrate concentration. Nitrate binding at the high-affinity unit initiates NRT1.1 dimer decoupling and priming of the Thr101 site for phosphorylation by CIPK23. This phosphorylation stabilizes the NRT1.1 monomeric state, acting as a high-affinity nitrate transceptor. However, nitrate binding in both monomers, retaining the unmodified NRT1.1 state through dimerization, attenuates CIPK23 activity and thereby maintains the low-affinity mode of nitrate signaling and transport. This phosphorylation-led modulation of NRT1.1 activity shows bistable behavior controlled by an incoherent feedforward loop, which integrates nitrate-induced positive and negative regulatory effects on CIPK23. These results, therefore, advance our molecular understanding of adaptation in fluctuating nutrient availability and are a way forward for improving plant nitrogen use efficiency.