Nutrient-regulated control of lysosome function by signaling lipid conversion.

Lysosomes serve dual antagonistic functions in cells by mediating anabolic growth signaling and the catabolic turnover of macromolecules. How these janus-faced activities are regulated in response to cellular nutrient status is poorly understood. We show here that lysosome morphology and function are reversibly controlled by a nutrient-regulated signaling lipid switch that triggers the conversion between peripheral motile mTOR complex 1 (mTORC1) signaling-active and static mTORC1-inactive degradative lysosomes clustered at the cell center. Starvation-triggered relocalization of phosphatidylinositol 4-phosphate (PI(4)P)-metabolizing enzymes reshapes the lysosomal surface proteome to facilitate lysosomal proteolysis and to repress mTORC1 signaling. Concomitantly, lysosomal phosphatidylinositol 3-phosphate (PI(3)P), which marks motile signaling-active lysosomes in the cell periphery, is erased. Interference with this PI(3)P/PI(4)P lipid switch module impairs the adaptive response of cells to altering nutrient supply. Our data unravel a key function for lysosomal phosphoinositide metabolism in rewiring organellar membrane dynamics in response to cellular nutrient status.

Metabolic Regulation of Transcription and Chromatin.

Although cell metabolism has been established as a major regulator of eukaryotic gene expression, the mechanisms underlying this regulation are still being uncovered. Recent years have seen great advances in our understanding of biochemical mechanisms of metabolic regulation of transcription and chromatin. Prime examples include insights into how nutrients and cellular energy status regulate synthesis of ribosomal RNAs by RNA polymerases I and III during ribosome biogenesis and how a variety of enzymes that catalyze modifications of histones in chromatin are regulated by the levels of certain metabolites. This volume of the Annual Review of Biochemistry includes a set of reviews describing these and other advances in understanding aspects of the metabolic regulation of RNA polymerases I and III transcription and chromatin.

mTOR Signaling in Growth, Metabolism, and Disease.

The mechanistic target of rapamycin (mTOR) coordinates eukaryotic cell growth and metabolism with environmental inputs, including nutrients and growth factors. Extensive research over the past two decades has established a central role for mTOR in regulating many fundamental cell processes, from protein synthesis to autophagy, and deregulated mTOR signaling is implicated in the progression of cancer and diabetes, as well as the aging process. Here, we review recent advances in our understanding of mTOR function, regulation, and importance in mammalian physiology. We also highlight how the mTOR signaling network contributes to human disease and discuss the current and future prospects for therapeutically targeting mTOR in the clinic.

Decoupled transcript and protein concentrations ensure histone homeostasis in different nutrients.

To maintain protein homeostasis in changing nutrient environments, cells must precisely control the amount of their proteins, despite the accompanying changes in cell growth and biosynthetic capacity. As nutrients are major regulators of cell cycle length and progression, a particular challenge arises for the nutrient-dependent regulation of 'cell cycle genes', which are periodically expressed during the cell cycle. One important example are histones, which are needed at a constant histone-to-DNA stoichiometry. Here we show that budding yeast achieves histone homeostasis in different nutrients through a decoupling of transcript and protein abundance. We find that cells downregulate histone transcripts in poor nutrients to avoid toxic histone overexpression, but produce constant amounts of histone proteins through nutrient-specific regulation of translation efficiency. Our findings suggest that this allows cells to balance the need for rapid histone production under fast growth conditions with the tight regulation required to avoid toxic overexpression in poor nutrients.

Latitudinal patterns in ocean C:N:P reflect phytoplankton acclimation and macromolecular composition.

The proportions of carbon (C), nitrogen (N), and phosphorus (P) in surface ocean particulate matter deviate greatly from the canonical Redfield Ratio (C:N:P = 106:16:1) in space and time with significant implications for global carbon storage as this matter reaches the deep ocean. Recent work has revealed clear latitudinal patterns in C:N:P, yet the relative importance of ecological, physiological, or biochemical processes in creating these patterns is unclear. We present high-resolution, concurrent measurements of particulate C:N:P, macromolecular composition, environmental conditions, and plankton community composition from a transect spanning a subtropical-subpolar boundary, the North Pacific Transition Zone. We find that the summed contribution of macromolecules to particulate C, N, and P is consistent with, and provides interpretation for, particulate C:N:P patterns. A decline in particulate C:N from the subtropical to subpolar North Pacific largely reflects an increase in the relative contribution of protein compared to carbohydrate and lipid, whereas variation in C:P and N:P correspond to shifts in protein relative to polyphosphate, DNA, and RNA. Possible causes for the corresponding trends in C:N and macromolecular composition include physiological responses and changes in community structure of phytoplankton, which represented approximately 1/3rd of particulate C across the transect. Comparison with culture experiments and an allocation-based model of phytoplankton macromolecular composition suggest that physiological acclimation to changing nutrient supply is the most likely explanation for the latitudinal trend in C:N, offering both a mechanistic interpretation and biochemical basis for large-scale patterns in C:N:P.

Long-term declines in chlorophyll a and variable phenology revealed by a 60-year estuarine plankton time series.

Long-term ecological time series provide a unique perspective on the emergent properties of ecosystems. In aquatic systems, phytoplankton form the base of the food web and their biomass, measured as the concentration of the photosynthetic pigment chlorophyll a (chl a), is an indicator of ecosystem quality. We analyzed temporal trends in chl a from the Long-Term Plankton Time Series in Narragansett Bay, Rhode Island, USA, a temperate estuary experiencing long-term warming and changing anthropogenic nutrient inputs. Dynamic linear models were used to impute and model environmental variables (1959 to 2019) and chl a concentrations (1968 to 2019). A long-term chl a decrease was observed with an average decline in the cumulative annual chl a concentration of 49% and a marked decline of 57% in winter-spring bloom magnitude. The long-term decline in chl a concentration was directly and indirectly associated with multiple environmental factors that are impacted by climate change (e.g., warming temperatures, water column stratification, reduced nutrient concentrations) indicating the importance of accounting for regional climate change effects in ecosystem-based management. Analysis of seasonal phenology revealed that the winter-spring bloom occurred earlier, at a rate of 4.9 ± 2.8 d decade-1. Finally, the high degree of temporal variation in phytoplankton biomass observed in Narragansett Bay appears common among estuaries, coasts, and open oceans. The commonality among these marine ecosystems highlights the need to maintain a robust set of phytoplankton time series in the coming decades to improve signal-to-noise ratios and identify trends in these highly variable environments.

Regulation and integration of membrane transport in marine diatoms.

Diatoms represent one of the most successful groups of marine phytoplankton and are major contributors to ocean biogeochemical cycling. They have colonized marine, freshwater and ice environments and inhabit all regions of the World's oceans, from poles to tropics. Their success is underpinned by a remarkable ability to regulate their growth and metabolism during nutrient limitation and to respond rapidly when nutrients are available. This requires precise regulation of membrane transport and nutrient acquisition mechanisms, integration of nutrient sensing mechanisms and coordination of different transport pathways. This review outlines transport mechanisms involved in acquisition of key nutrients (N, C, P, Si, Fe) by marine diatoms, illustrating their complexity, sophistication and multiple levels of control.

Balancing act: The dynamic relationship between nutrient availability and plant defence.

Plants depend heavily on soil nutrients for growth, development and defence. Nutrient availability is crucial not only for sustaining vital biochemical processes but also for mounting effective defences against a diverse array of pathogens. Macronutrients such as nitrogen, phosphorus and potassium significantly influence plant defence mechanisms by providing essential building blocks for the synthesis of defence compounds, immune signalling and physiological responses like stomatal regulation. Micronutrients like zinc, copper and iron are essential for balancing reactive oxygen species and other reactive compounds in plant immune responses. Although substantial circumstantial evidence links nutrient availability to plant defence, the molecular mechanisms underlying this process have only recently started to be understood. This review focuses on summarizing recent advances in understanding the molecular mechanisms by which nitrogen, phosphorus and iron interact with plant defence mechanisms and explores the potential for engineering nutritional immunity in crops to enhance their resilience against pathogens.

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.

A genomics perspective of personalized prevention and management of obesity.

This review discusses the landscape of personalized prevention and management of obesity from a nutrigenetics perspective. Focusing on macronutrient tailoring, we discuss the impact of genetic variation on responses to carbohydrate, lipid, protein, and fiber consumption. Our bioinformatic analysis of genomic variants guiding macronutrient intake revealed enrichment of pathways associated with circadian rhythm, melatonin metabolism, cholesterol and lipoprotein remodeling and PPAR signaling as potential targets of macronutrients for the management of obesity in relevant genetic backgrounds. Notably, our data-based in silico predictions suggest the potential of repurposing the SYK inhibitor fostamatinib for obesity treatment in relevant genetic profiles. In addition to dietary considerations, we address genetic variations guiding lifestyle changes in weight management, including exercise and chrononutrition. Finally, we emphasize the need for a refined understanding and expanded research into the complex genetic landscape underlying obesity and its management.

Dietary and Therapeutic Benefits of Edible Insects: A Global Perspective.

Edible insects are gaining traction worldwide for research and development. This review synthesizes a large and well-established body of research literature on the high nutritional value and variety of pharmacological properties of edible insects. Positive benefits of insect-derived products include immune enhancement; gastrointestinal protection; antitumor, antioxidant, and anti-inflammatory capacities; antibacterial activities; blood lipid and glucose regulation; lowering of blood pressure; and decreased risk of cardiovascular diseases. However, the pharmacological mechanisms of these active components of edible insects in humans have received limited research attention. In addition, we discuss health risks (safety); application prospects; regulations and policies governing their production and consumption with a view to promote innovations, intraglobal trade, and economic development; and suggestions for future directions for further pharmacological functional studies. The aim is to review the current state of knowledge and research trends on edible insects as functional ingredients beneficial to the nutrition and health of humans and animals (livestock, aquatic species, and pets).

Nutrient-Sensitive Reinforcement Learning in Monkeys.

In reinforcement learning (RL), animals choose by assigning values to options and learn by updating these values from reward outcomes. This framework has been instrumental in identifying fundamental learning variables and their neuronal implementations. However, canonical RL models do not explain how reward values are constructed from biologically critical intrinsic reward components, such as nutrients. From an ecological perspective, animals should adapt their foraging choices in dynamic environments to acquire nutrients that are essential for survival. Here, to advance the biological and ecological validity of RL models, we investigated how (male) monkeys adapt their choices to obtain preferred nutrient rewards under varying reward probabilities. We found that the nutrient composition of rewards strongly influenced learning and choices. Preferences of the animals for specific nutrients (sugar, fat) affected how they adapted to changing reward probabilities; the history of recent rewards influenced choices of the monkeys more strongly if these rewards contained the their preferred nutrients (nutrient-specific reward history). The monkeys also chose preferred nutrients even when they were associated with lower reward probability. A nutrient-sensitive RL model captured these processes; it updated the values of individual sugar and fat components of expected rewards based on experience and integrated them into subjective values that explained the choices of the monkeys. Nutrient-specific reward prediction errors guided this value-updating process. Our results identify nutrients as important reward components that guide learning and choice by influencing the subjective value of choice options. Extending RL models with nutrient-value functions may enhance their biological validity and uncover nutrient-specific learning and decision variables.SIGNIFICANCE STATEMENT RL is an influential framework that formalizes how animals learn from experienced rewards. Although reward is a foundational concept in RL theory, canonical RL models cannot explain how learning depends on specific reward properties, such as nutrients. Intuitively, learning should be sensitive to the nutrient components of the reward to benefit health and survival. Here, we show that the nutrient (fat, sugar) composition of rewards affects how the monkeys choose and learn in an RL paradigm and that key learning variables including reward history and reward prediction error should be modified with nutrient-specific components to account for the choice behavior observed in the monkeys. By incorporating biologically critical nutrient rewards into the RL framework, our findings help advance the ecological validity of RL models.

Inhibition of mitochondrial citrate shuttle alleviates metabolic syndromes induced by high-fat diet.

The mitochondrial citrate shuttle, which relies on the solute carrier family 25 member 1 (SLC25A1), plays a pivotal role in transporting citrate from the mitochondria to the cytoplasm. This shuttle supports glycolysis, lipid biosynthesis, and protein acetylation. Previous research has primarily focused on SLC25A1 in pathological models, particularly high-fat diet (HFD)-induced obesity. However, the impact of SLC25A1 inhibition on nutrient metabolism under HFD remains unclear. To address this gap, we used zebrafish (Danio rerio) and Nile tilapia (Oreochromis niloticus) to evaluate the effects of inhibiting Slc25a1. In zebrafish, we administered Slc25a1-specific inhibitors (CTPI-2) for 4 wk, whereas Nile tilapia received intraperitoneal injections of dsRNA to knock down slc25a1b for 7 days. Inhibition of the mitochondrial citrate shuttle effectively protected zebrafish from HFD-induced obesity, hepatic steatosis, and insulin resistance. Of note, glucose tolerance was unaffected. Inhibition of Slc25a1 altered hepatic protein acetylation patterns, with decreased cytoplasmic acetylation and increased mitochondrial acetylation. Under HFD conditions, Slc25a1 inhibition promoted fatty acid oxidation and reduced hepatic triglyceride (TAG) accumulation by deacetylating carnitine palmitoyltransferase 1a (Cpt1a). In addition, Slc25a1 inhibition triggered acetylation-induced inactivation of Pdhe1α, leading to a reduction in glucose oxidative catabolism. This was accompanied by enhanced glucose uptake and storage in zebrafish livers. Furthermore, Slc25a1 inhibition under HFD conditions activated the SIRT1/PGC1α pathway, promoting mitochondrial proliferation and enhancing oxidative phosphorylation for energy production. Our findings provide new insights into the role of nonhistone protein acetylation via the mitochondrial citrate shuttle in the development of hepatic lipid deposition and hyperglycemia caused by HFD.NEW & NOTEWORTHY The mitochondrial citrate shuttle is a crucial physiological process for maintaining metabolic homeostasis. In the present study, we found that inhibition of mitochondrial citrate shuttle (Slc25a1) could alleviate metabolic syndromes induced by high-fat diet (HFD) through remodeling hepatic protein acetylation modification. Briefly, Slc25a1 inhibition reduces hepatic triglyceride deposition by deacetylating Cpt1a and reduces glucose oxidative catabolism by acetylating Pdhe1α. Our study provides new insights into the treatment of diet-induced metabolic syndromes.

The roles of essential trace elements in T cell biology.

T cells are crucial for adaptive immunity to regulate proper immune response and immune homeostasis. T cell development occurs in the thymus and mainly differentiates into CD4+ and CD8+ T cell subsets. Upon stimulation, naive T cells differentiate into distinct CD4+ helper and CD8+ cytotoxic T cells, which mediate immunity homeostasis and defend against pathogens or tumours. Trace elements are minimal yet essential components of human body that cannot be overlooked, and they participate in enzyme activation, DNA synthesis, antioxidant defence, hormone production, etc. Moreover, trace elements are particularly involved in immune regulations. Here, we have summarized the roles of eight essential trace elements (iron, zinc, selenium, copper, iodine, chromium, molybdenum, cobalt) in T cell development, activation and differentiation, and immune response, which provides significant insights into developing novel approaches to modulate immunoregulation and immunotherapy.

Utilizing plasma-generated N2O5 gas from atmospheric air as a novel gaseous nitrogen source for plants.

Fixing atmospheric nitrogen for use as fertilizer is a crucial process in promoting plant growth and enhancing crop yields in agricultural production. Currently, the chemical production of nitrogen fertilizer from atmospheric N2 relies on the energy-intensive Haber-Bosch process. Therefore, developing a low-cost and easily applicable method for fixing nitrogen from the air would provide a beneficial alternative. In this study, we tested the utilization of dinitrogen pentoxide (N2O5) gas, generated from oxygen and nitrogen present in ambient air with the help of a portable plasma device, as a nitrogen source for the model plant Arabidopsis thaliana. Nitrogen-deficient plants supplied with medium treated with N2O5, were able to overcome nitrogen deficiency, similar to those provided with medium containing a conventional nitrogen source. However, prolonged direct exposure of plants to N2O5 gas adversely affected their growth. Short-time exposure of plants to N2O5 gas mitigated its toxicity and was able to support growth. Moreover, when the exposure of N2O5 and the contact with plants were physically separated, plants cultured under nitrogen deficiency were able to grow. This study shows that N2O5 gas generated from atmospheric nitrogen can be used as an effective nutrient for plants, indicating its potential to serve as an alternative nitrogen fertilization method for promoting plant growth.

Role of Nutrients Regulating Myeloid Derived Suppressor Cells in Cancer: A Scoping Review.

Myeloid-derived suppressor cells (MDSCs) are immature cells with an immunosuppressive function. MDSCs have been related to inflammation in many settings, including infections, transplantation, obesity, aging, or cancer. In oncological settings, MDSCs participate in tumor immunoescape, growth, and metastasis. Certain nutrients can modify chronic inflammation by their interaction with MDSCs. Therefore, the possible influence of certain nutrients on immune surveillance by their actions on MDSCs and how this may affect the prognosis of cancer patients were evaluated in this scoping review. We identified seven papers, six of which were murine model studies and only one was a human clinical trial. Globally, a significant reduction in cancer growth and progression was observed after achieving a reduction in both MDSCs and their immunosuppressive ability with nutrients such as selected vegetables, icaritin, retinoic acid, curdlan, active vitamin D, soy isoflavones, and green tea. In conclusion, the consumption of certain nutrients may have effects on MDSCs, with beneficial results not only in the prevention of tumor development and growth but also in improving patients' response.

Recent Advances in the Crosstalk between Brassinosteroids and Environmental Stimuli.

Due to their sessile lifestyle, plants need to optimize their growth in order to adapt to ever-changing environments. Plants receive stimuli from the environment and convert them into cellular responses. Brassinosteroids (BRs), as growth-promoting steroid hormones, play a significant role in the tradeoff between growth and environmental responses. Here, we provide a comprehensive summary for understanding the crosstalk between BR and various environmental stresses, including water availability, temperature fluctuations, salinization, nutrient deficiencies and diseases. We also highlight the bottlenecks that need to be addressed in future studies. Ultimately, we suppose to improve plant environmental adaptability and crop yield by excavating natural BR mutants or modifying BR signaling and its targets.

ANPS: machine learning based server for identification of anti-nutritional proteins in plants.

Anti-nutrient factors are inherently present in almost all major crops, which impede the absorption of crucial vitamins and minerals upon human consumption. The commonly found anti-nutrients in food crops are saponins, tannins, lectins, and phytates etc. Currently, there is a lack of computational server for identification of proteins that encode for anti-nutritional factors in plants. Consequently, this study represents a computational approach aimed at distinguishing between proteins encoding anti-nutritional factors and those providing essential nutrients. In this work, machine learning algorithms have been employed to identify plant specific anti-nutrient factor proteins from protein sequences by using compositional features. Achieving a five-fold cross-validation training performance of 94.34% AUC-ROC and 94.13% AUC-PR with extreme gradient boosting surpasses the performance of other methods such as support vector machine, random forest, and adaptive boosting. These results suggest the proposed approach is highly reliable in predicting plant-specific anti-nutritional factor proteins. The resulting prediction models have led to the development of an online server named ANPS, freely available at https://nipb-bi.icar.gov.in .

A Spatial Signal of Niche Differentiation in Tropical Forests.

AbstractExplaining diversity in tropical forests remains a challenge in community ecology. Theory tells us that species differences can stabilize communities by reducing competition, while species similarities can promote diversity by reducing fitness differences and thus prolonging the time to competitive exclusion. Combined, these processes may lead to clustering of species such that species are niche differentiated across clusters and share a niche within each cluster. Here, we characterize this partial niche differentiation in a tropical forest in Panama by measuring spatial clustering of woody plants and relating these clusters to local soil conditions. We find that species were spatially clustered and the clusters were associated with specific concentrations of soil nutrients, reflecting the existence of nutrient niches. Species were almost twice as likely to recruit in their own nutrient niche. A decision tree algorithm showed that local soil conditions correctly predicted the niche of the trees with up to 85% accuracy. Iron, zinc, phosphorus, manganese, and soil pH were among the best predictors of species clusters.

Maize/soybean intercropping increases nutrient uptake, crop yield and modifies soil physio-chemical characteristics and enzymatic activities in the subtropical humid region based in Southwest China.

Intercropping, a widely adopted agricultural practice worldwide, aims to increase crop yield, enhance plant nutrient uptake, and optimize the utilization of natural resources, contributing to sustainable farming practices on a global scale. However, the underlying changes in soil physio-chemical characteristics and enzymatic activities, which contribute to crop yield and nutrient uptake in the intercropping systems are largely unknown. Consequently, a two-year (2021-2022) field experiment was conducted on the maize/soybean intercropping practices with/without nitrogen (N) fertilization (i.e., N0; 0 N kg ha-1 and N1; 225 N kg ha-1 for maize and 100 N kg ha-1 for soybean ) to know whether such cropping system can improve the nutrients uptake and crop yields, soil physio-chemical characteristics, and soil enzymes, which ultimately results in enhanced crop yield. The results revealed that maize intercropping treatments (i.e., N0MI and N1MI) had higher crop yield, biomass dry matter, and 1000-grain weight of maize than mono-cropping treatments (i.e., N0MM, and N1MM). Nonetheless, these parameters were optimized in N1MI treatments in both years. For instance, N1MI produced the maximum grain yield (10,105 and 11,705 kg ha-1), biomass dry matter (13,893 and 14,093 kg ha-1), and 1000-grain weight (420 and 449 g) of maize in the year 2021 and 2022, respectively. Conversely, soybean intercropping treatments (i.e., N0SI and N1SI) reduced such yield parameters for soybean. Also, the land equivalent ratio (LER) and land equivalent ratio for N fertilization (LERN) values were always greater than 1, showing the intercropping system's benefits in terms of yield and improved resource usage. Moreover, maize intercropping treatments (i.e., N0MI and N1MI) and soybean intercropping treatments (i.e., N0SI and N1SI) significantly (p < 0.05) enhanced the nutrient uptake (i.e., N, P, K, Ca, Fe, and Zn) of maize and soybean, however, these nutrients uptakes were more prominent in N1MI and N1SI treatments of maize and soybean, respectively in both years (2021 and 2022) compared with their mono-cropping treatments. Similarly, maize-soybean intercropping treatments (i.e., N0MSI and N1MSI) significantly (p < 0.05) improved the soil-based N, P, K, NH4, NO3, and soil organic matter, but, reduced the soil pH. Such maize-soybean intercropping treatments also improved the soil enzymatic activities such as protease (PT), sucrose (SC), acid phosphatase (AP), urease (UE), and catalase (CT) activities. This indicates that maize-soybean intercropping could potentially contribute to higher and better crop yield, enhanced plant nutrient uptake, improved soil nutrient pool, physio-chemical characteristics, and related soil enzymatic activities. Thus, preferring intercropping to mono-cropping could be a preferable choice for ecologically viable agricultural development.