OpenFold: retraining AlphaFold2 yields new insights into its learning mechanisms and capacity for generalization.

AlphaFold2 revolutionized structural biology with the ability to predict protein structures with exceptionally high accuracy. Its implementation, however, lacks the code and data required to train new models. These are necessary to (1) tackle new tasks, like protein-ligand complex structure prediction, (2) investigate the process by which the model learns and (3) assess the model's capacity to generalize to unseen regions of fold space. Here we report OpenFold, a fast, memory efficient and trainable implementation of AlphaFold2. We train OpenFold from scratch, matching the accuracy of AlphaFold2. Having established parity, we find that OpenFold is remarkably robust at generalizing even when the size and diversity of its training set is deliberately limited, including near-complete elisions of classes of secondary structure elements. By analyzing intermediate structures produced during training, we also gain insights into the hierarchical manner in which OpenFold learns to fold. In sum, our studies demonstrate the power and utility of OpenFold, which we believe will prove to be a crucial resource for the protein modeling community.

Digital Twins in Agriculture: Orchestration and Applications.

Digital Twins have emerged as an outstanding opportunity for precision farming, digitally replicating in real-time the functionalities of objects and plants. A virtual replica of the crop, including key agronomic development aspects such as irrigation, optimal fertilization strategies, and pest management, can support decision-making and a step change in farm management, increasing overall sustainability and direct water, fertilizer, and pesticide savings. In this review, Digital Twin technology is critically reviewed and framed in the context of recent advances in precision agriculture and Agriculture 4.0. The review is organized for each step of agricultural lifecycle, edaphic, phytotechnologic, postharvest, and farm infrastructure, with supporting case studies demonstrating direct benefits for agriculture production and supply chain considering both benefits and limitations of such an approach. Challenges and limitations are disclosed regarding the complexity of managing such an amount of data and a multitude of (often) simultaneous operations and supports.

The role of plant vasculature in tackling N2O emissions.

Rising demand for protein-rich foods can impact N2O emissions from croplands. Recent research has pointed to the role of modified plant vasculature in grain protein increase. Here we highlight how discovering the mechanistic role of plant vasculature in protein improvement and nitrogen-use efficiency could reduce global N2O emissions.

Challenges facing sustainable protein production: Opportunities for cereals.

Rising demands for protein worldwide are likely to drive increases in livestock production, as meat provides ∼40% of dietary protein. This will come at a significant environmental cost, and a shift toward plant-based protein sources would therefore provide major benefits. While legumes provide substantial amounts of plant-based protein, cereals are the major constituents of global foods, with wheat alone accounting for 15-20% of the required dietary protein intake. Improvement of protein content in wheat is limited by phenotyping challenges, lack of genetic potential of modern germplasms, negative yield trade-offs, and environmental costs of nitrogen fertilizers. Presenting wheat as a case study, we discuss how increasing protein content in cereals through a revised breeding strategy combined with robust phenotyping could ensure a sustainable protein supply while minimizing the environmental impact of nitrogen fertilizer.

OpenProteinSet: Training data for structural biology at scale.

Multiple sequence alignments (MSAs) of proteins encode rich biological information and have been workhorses in bioinformatic methods for tasks like protein design and protein structure prediction for decades. Recent breakthroughs like AlphaFold2 that use transformers to attend directly over large quantities of raw MSAs have reaffirmed their importance. Generation of MSAs is highly computationally intensive, however, and no datasets comparable to those used to train AlphaFold2 have been made available to the research community, hindering progress in machine learning for proteins. To remedy this problem, we introduce OpenProteinSet, an open-source corpus of more than 16 million MSAs, associated structural homologs from the Protein Data Bank, and AlphaFold2 protein structure predictions. We have previously demonstrated the utility of OpenProteinSet by successfully retraining AlphaFold2 on it. We expect OpenProteinSet to be broadly useful as training and validation data for 1) diverse tasks focused on protein structure, function, and design and 2) large-scale multimodal machine learning research.

Effects of agro-forestry systems on the physical and chemical characteristics of green coffee beans.

Twenty agroforestry systems consisting of different management practices (conventional and organic) and shade types were set up for coffee plantations in 2,000 at the Tropical Agricultural Research and Higher Education Center (CATIE), Turrialba, Costa Rica. The physical (density, bulk density, moisture content, and roasting loss) and chemical attributes (mineral, total lipid, fatty acids, caffeine, and carbohydrate contents) of harvested green coffee beans were investigated. The full sun and Erythrina shade tree systems significantly improved (p < 0.05) the density of the green coffee beans and decreased (p < 0.05) the moisture content and roasting loss of the green coffee beans. The intensive organic (IO) management practice significantly increased some mineral contents, such as K, P, and Ca, in green coffee beans. The full sun system also significantly promoted (p < 0.05) some mineral contents, such as Ca and Mn, in green coffee beans. In terms of total lipid and fatty acids (FAs), compared with the moderate conventional (MC) management practice, the IO management practice was beneficial as it significantly increased (p < 0.05) the total lipid and FAs contents in the green coffee beans, while the Erythrina shade tree system significantly increased (p < 0.05) the total lipid and FAs contents of green coffee beans more efficiently than the other shade types. The caffeine content of green coffee beans was significantly higher (p < 0.05) under the intensive conventional (IC) and IO management practices than under the MC management practice and higher under the full sun system than under the shaded system. The Erythrina shade tree system significantly improved (p < 0.05) the carbohydrate content of green coffee beans. Overall, in consideration of sustainability, the IO management practice associated with the Erythrina shade tree system would be a useful combination for the local farmers to grow coffee trees.

Sequence-structure-function relationships in the microbial protein universe.

For the past half-century, structural biologists relied on the notion that similar protein sequences give rise to similar structures and functions. While this assumption has driven research to explore certain parts of the protein universe, it disregards spaces that don't rely on this assumption. Here we explore areas of the protein universe where similar protein functions can be achieved by different sequences and different structures. We predict ~200,000 structures for diverse protein sequences from 1,003 representative genomes across the microbial tree of life and annotate them functionally on a per-residue basis. Structure prediction is accomplished using the World Community Grid, a large-scale citizen science initiative. The resulting database of structural models is complementary to the AlphaFold database, with regards to domains of life as well as sequence diversity and sequence length. We identify 148 novel folds and describe examples where we map specific functions to structural motifs. We also show that the structural space is continuous and largely saturated, highlighting the need for a shift in focus across all branches of biology, from obtaining structures to putting them into context and from sequence-based to sequence-structure-function based meta-omics analyses.

Microfluidic Spontaneous Emulsification for Generation of O/W Nanoemulsions-Opportunity for In-Space Manufacturing.

The use of microfluidics for oil-in-water (O/W) nanoemulsification via spontaneous self-assembly is demonstrated. As this is known to be a longish process, both single- and multicontact microfluidic reactors are tested, the latter providing a longsome, constant microfluidic treatment to maintain advanced phase and interfacial mass transfer. Microfluidic devices provide strong advantages above conventional systems for spontaneous emulsification, with droplet sizes of 62 nm at desired surfactant-to-oil ratios (SOR) and a decrease of 90% in process time. Multicontact microfluidics have better performance than their single-contact counterparts, while critical aspects, e.g., process robustness, are also discussed. Ternary phase diagram analysis of the three components (oil, water, surfactant) allow to decide for the right mixing ratio and sequence of mixing steps for the nanoemulsions. Microfluidic spontaneous emulsification meets objective functions of the intended application to provide fortified beverages to astronauts in space exploration. In that viewpoint, an advantage is to achieve stable nanoemulsions at a level of concentrations much higher as compared to application (human intake), allowing a dilution factor to the final product of up to 100. This decreases notably the process time and allows for process flexibility, e.g., to dilute or tailor Earth-prepared nanoemulsion concentrate payloads in space.

Effect of sweeteners and carbonation on aroma partitioning and release in beverage systems.

The effect of monosaccharides (glucose, fructose and galactose) and disaccharides (sucrose and lactose) at 10, 20 and 30 % w/v on the in-vitro aroma partitioning of C4 - C10 aldehydes and ethyl esters, as well as limonene (concentration of aroma compounds at 1 µg mL-1), was studied using atmospheric pressure chemical ionisation-mass spectrometry. An increase in sugar concentration from 0 to 30 % w/v resulted in a significant increase in partitioning under static headspace conditions for the majority of the compounds (p < 0.05), an effect generally not observed when 10 % w/v sucrose was substituted with low-calorie sweeteners (p > 0.05). The complexity of the system was increased to model a soft drink design - comprising water, sucrose (10, 20 and 30 % w/v), acid (0.15 % w/v), carbonation (∼7.2 g/L CO2) and aroma compounds representative of an apple style flavouring, namely ethyl butanoate and hexanal (10 µg mL-1 each). Although the addition of sucrose had no significant in-vivo effect, carbonation significantly decreased breath-by-breath (in-vivo) aroma delivery (p < 0.05). To understand the physical mechanisms behind aroma release from the beverage matrix, the effect of sucrose on the kinetics of the matrix components was explored. An increase in sucrose concentration from 0 to 30 % w/v resulted in a significant decrease in water activity (p < 0.05), which accounted for the significantly slower rate of self-diffusion of aroma compounds (p < 0.05), measured using diffusion-ordered spectroscopy-nuclear magnetic resonance spectroscopy. No significant effect of sucrose on carbon dioxide volume flux was found (p > 0.05).

Space farming: Horticulture systems on spacecraft and outlook to planetary space exploration.

Successful human space exploration requires more products than can be taken as payload. There is a need, therefore, for in-space circular manufacturing. Requirements for this include limited resource inflow, from either Earth or other planets and the generation of minimal waste. The provision of nutritious food is a clear need for human survival on the Moon or Mars and is one of the most complex to solve. Demand in large quantities, constant and reliable provision of food requires the development of specialist agricultural technologies. Here, we first review the history of space farming over the past five decades. This survey assesses the technologies which have been tested under the harsh conditions of space, identifying which modern horticultural components are applicable for in-space plant growth. We then outline which plants have been grown and under what conditions, and speculate upon the types of plants that could be selected to best nourish astronauts. Current systems are focussed on experimentation and exploration, but do not yet provide turn-key solutions for efficient food production within a long-term space exploration scenario. With that take, this review aims to provide a perspective on how an engineered closed circular environmental life-support system (ECCLES) might be constructed. To exemplify the latter, nutrient auto accumulation by biofortification is proposed through the integration of space farming and space mining, which is uncharted on Earth.

A flavour perspective of Tiepishihu (Dendrobium officinale) - an emerging food ingredient from popular traditional Chinese medicinal plants: a review.

Many Dendrobium orchid stems are used in Traditional Chinese Medicine (TCM). The most popular and premium species is Dendrobium officinale, and its stem in TCM is called Tiepishihu. Tiepishihu has a sweet flavour and is an ingredient in Chinese tea and desserts. There is no comprehensive understanding of its flavour compounds. It is, therefore, essential to understand compounds responsible for its flavour, and how they are formed. This review assesses twelve diverse studies in Tiepishihu flavour (2013-2022). Thirty aroma compounds were compared - furfural and nonanal were identified as common compounds. Four of seven essential amino acids were taste-active, with lysine being the most potent. Pre-harvest factors such as environment impact specific aroma compounds. Post-harvest processing methods, including drying and grinding, can control Tiepishihu's flavour. Methodological consistency is a challenge, but controlling Tiepishihu's flavour could increase its commercial value as a food ingredient.

Reviving grain quality in wheat through non-destructive phenotyping techniques like hyperspectral imaging.

A long-term goal of breeders and researchers is to develop crop varieties that can resist environmental stressors and produce high yields. However, prioritising yield often compromises improvement of other key traits, including grain quality, which is tedious and time-consuming to measure because of the frequent involvement of destructive phenotyping methods. Recently, non-destructive methods such as hyperspectral imaging (HSI) have gained attention in the food industry for studying wheat grain quality. HSI can quantify variations in individual grains, helping to differentiate high-quality grains from those of low quality. In this review, we discuss the reduction of wheat genetic diversity underlying grain quality traits due to modern breeding, key traits for grain quality, traditional methods for studying grain quality and the application of HSI to study grain quality traits in wheat and its scope in breeding. Our critical review of literature on wheat domestication, grain quality traits and innovative technology introduces approaches that could help improve grain quality in wheat.

The role of inorganic-phosphate, potassium and magnesium in yeast-flavour formation.

Inorganic-phosphate, potassium, and magnesium are key-minerals required for yeast growth, metabolism, and survival, the present work investigated its impact in yeast-flavour formation using a multi-factor experimental design, which was used to generate a range of phosphorous-potassium-magnesium resulting in a 28-point D-optimal design. Samples were evaluated using HPLC (ethanol), GC-MS (aroma), and CountStar (total yeast cell). Results revealed that yeast requires a minimal amount of inorganic-phosphate, potassium, and magnesium (250, 500, and 70 mg/L, respectively) to support yeast-growth and ethanol/flavour formation. Inorganic-phosphate was important for fatty acid esters formation/short chain fatty acid (SCFA) reduction. Potassium was important in the formation of acetate esters/higher alcohols. Magnesium was the most important inorganic element for ester formation/SCFA reduction; furthermore, ethanol production is magnesium-dependent. In conclusion, inorganic phosphate, potassium and magnesium play an important role in yeast-growth, esters and higher alcohols formation; and SCFA reduction. Ethanol formation is Mg-dependent.

Impact of agro-forestry systems on the aroma generation of coffee beans.

A long experiment has been established since 2000 at CATIE (Tropical Agricultural Research and Higher Education Center), Turrialba, Costa Rica. Twenty agro-forestry systems with different shade types and managements (organic and non-organic) consisting of an incomplete randomized block-design with shade tree as main effect and subplots represented by management were set up. The effects of different managements and shade types on the aroma and color generation of roasted coffee beans were investigated. The total protein content was significantly higher (P < 0.05) under the intensive conventional (IC) (168 g/Kg) and intensive organic (IO) (167 g/Kg) managements than under the moderate conventional (MC) (153 g/Kg in IC vs. MC group, 157 g/Kg in MC vs. IO group). Comparing with the moderate conventional (MC) management, the intensive organic (IO) management had a stronger ability to generate more flavor and color. The total protein content was significantly higher (P < 0.05) under the full sun system (172 g/Kg) than under the shaded (159 g/Kg) and Erythrina system (155 g/Kg), under the service system (165 g/Kg) than under the timber system (146 g/Kg), under the legume timber system (170 g/Kg) than under the non-legume timber system (152 g/Kg). The full sun system had a greater flavor generation and color after roasting. Comparing with the timber system, the service system produced roasted beans with the more flavor and color. Comparing with the non-legume shade tree, the legume shade tree improved the performance of flavor and color in the roasted coffee beans.

Volatile profiles of commercial vetch prepared via different processing methods.

Vicia sativa (Common Vetch) is currently an underutilised leguminous crop species with high protein content and superior drought tolerance. This study aimed to understand the mechanisms behind vetch flavor development following processing to facilitate its uptake as a future source of dietary protein. A total of 95 volatile compounds were identified by solid-phase microextraction gas chromatography-mass spectrometry (SPME GC-MS) for a range of vetches processed by dehulling, soaking, germination, microwaving, and fermentation.2-pentyl furan, benzyl alcohol, benzaldehyde, 1-octen-3-ol and 1-hexanol were found to be characteristic aroma compounds of V. sativa. Analysis of a V. sativa landrace demonstrated significant intraspecies variation in volatile abundance, three-fold that of commercial varieties. Both natto and tempeh fermentation produced significant quantities of alcohols, esters, and carboxylic acids with specifically natto generating significant pyrazines. Concentrations of 1-octen-3-ol significantly decreased after tempeh fermentation indicating its potential to reduce documented off flavor generating volatiles within V. sativa.

The role of capsaicin stimulation on the physicochemical properties of saliva and aroma release in model aqueous and oil systems.

Capsaicin increases saliva production, but the impact of this additional saliva on the food matrix is unknown. This study aimed to explain the impact of capsaicin on saliva properties and in-vivo release of 14 aroma compounds in aqueous [aqu] and oil systems [oil]. To investigate the physicochemical effect from diverse properties of aroma compounds, one healthy subject participated in all the sessions to minimise large variations between individuals. Capsaicin enhanced saliva flow rate (by 172% [aqu] and 85% [oil]) and salivary protein concentration (by 142% [aqu] and 149% [oil]). Furthermore, capsaicin-in-oil stimulated saliva formed a more stable emulsion in the mouth (17% higher zeta-potential and 15% smaller particle size). In-nose release concentrations measured by APCI-MS for certain esters were reduced by capsaicin (e.g., isoamyl acetate was reduced by 65% [aqu] and 76% [oil]), which suggests that capsaicin may induce stronger oral interactions between specific aroma compounds and salivary proteins.

Sensory perception and consumer acceptance of commercial and salt-reduced potato crisps formulated using salt reduction design rules.

Successful salt (NaCl) reduction strategies are required to reduce the salt content of snacks while maintaining saltiness perception and consumer acceptance. Previous research suggests that particle physicochemical design rules (small particle size, low density, low hydrophobicity, optimised particle shape) can be leveraged to produce salt particles that enhance saltiness perception. This study aimed to validate these design rules by applying optimised model salts to unsalted potato crisps at a 30% reduced salt content to produce prototype products. A selection of commercial products were also chosen to represent the salt content and crisp style of the broader market, with the aim to investigate the potential of other salt reduction strategies including; direct salt removal without compensation for loss of salt content and increasing time in mouth, while exploring the impact of consumer mouth behaviour type on consumer product preference. Nine products varying in salt content (6 standard, 1 crinkle-cut, 1 thick-cut batch-fried, 1 baked reconstituted potato) were subject to descriptive sensory analysis with a trained panel (n = 11). A subset (seven products) were assessed for consumer acceptance (n = 93). A salt reduction of 30% was achieved while maintaining saltiness perception and consumer acceptance using model salts, while direct removal of salt without perceptual impact was only achievable by 15%. To investigate key drivers of liking, consumers were segmented based on product liking and mouth behaviour. Results suggested that whilst salt content was the primary driver, specific texture profiles were polarising. However, mouth behaviour had minimal influence on preference. These results validate previously described physicochemical design rules for developing novel salt particles for salt reduction and inform ingredient design for the food and flavour industries.

Flavour compounds affect protein structure: The effect of methyl anthranilate on bovine serum albumin conformation.

This study aims to understand possible effects of flavour compounds on the structure and conformation of endogenous proteins. Using methyl anthranilate (a grape flavour compound added to drinks, confectionery, and vape-liquids) and bovine serum albumin (BSA, a model serum protein) we designed experimental investigations using analytical ultracentrifugation, size exclusion chromatography small angle X-ray scattering, and fluorescence spectroscopy to reveal that methyl anthranilate spontaneously binds to BSA (ΔG°, ca. -21 KJ mol-1) which induces a conformational compactness (ca. 10 %) in the monomer structure. Complementary molecular modelling and dynamics simulations suggested the binding occurs at Sudlow II of BSA via establishment of hydrogen bonds with arginine409, lysine413 and serine488 leading to an increased conformational order in domains IA, IIB and IIIB. This work aims to set the foundation for future research on flavour-protein interactions and offer new sets of opportunities for understanding the effects of small compounds on protein structure.

Dynamic release and perception of key odorants in grilled eel during chewing.

The release mechanism of odorants in the oral cavity during consumption directly affects sensory attributes, consumers' preferences, and ultimately purchase intent. Targets was set to monitor in real-time the key odorants released from grilled eel during mastication via an atmospheric pressure chemical ionization mass spectrometry (APCI-MS) connected with a nose interface. The release and perception of odorants during mastication were divided into three distinct phases. Dimethyl sulfide was the main odorant in the first stage. The release and perception of fishy aromas were predominant in the middle and last stages of mastication contributed by trimethylamine, 1-penten-3-ol, and 2-methyl-1-butanol. Chewing behavior experiments suggested that extending the chewing period to >20 s and having a chewing frequency of 2 cycles/s could enhance the aroma delivery of grilled eel and optimize the consumer experience. Consequently, the results explained the relationship between aroma release and the optimal chewing behavior for grilled eel consumption.

Mechanisms of umami taste perception: From molecular level to brain imaging.

Due to unique characteristics, umami substances have gained much attention in the food industry during the past decade as potential replacers to sodium or fat to increase food palatability. Umami is not only known to increase appetite, but also to increase satiety, and hence could be used to control food intake. Therefore, it is important to understand the mechanism(s) involved in umami taste perception. This review discusses current knowledge of the mechanism(s) of umami perception from receptor level to human brain imaging. New findings regarding the molecular mechanisms for detecting umami tastes and their pathway(s), and the peripheral and central coding to umami taste are reviewed. The representation of umami in the human brain and the individual variation in detecting umami taste and associations with genotype are discussed. The presence of umami taste receptors in the gastrointestinal tract, and the interactions between the brain and gut are highlighted. The review concludes that more research is required into umami taste perception to include not only oral umami taste perception, but also the wider "whole body" signaling mechanisms, to explore the interaction between the brain and gut in response to umami perception and ingestion.