In Healthy Pathways of Dietary Changes, a Very Rapid Reduction of Red Meat Is Possible, but Specific Diet Changes Are Required for Full Reduction-A Graph-Based Analysis.

BACKGROUND: Although reducing meat consumption is becoming increasingly popular in Western countries, such a transition to a sustainable diet may pose some nutritional risks. OBJECTIVES: We aim to analyze the pathways for reaching a low-meat healthy diet and the changes in other food categories needed to rapidly decrease total red meat consumption. METHODS: We used a recently developed method based on graph theory to represent all possible pathways of stepwise changes that avoid nutritional deficiencies toward a target healthy diet. Initial and target diets were defined as the daily consumption of 33 food groups. For each sex, 3 initial diets were taken from the French representative survey third individual and national study on food consumption survey as the mean observed diet and low (first quintile) and high (fifth quintile) meat consumption. Target diets were identified using multicriteria optimization to minimize the long-term health risk (HR) of chronic diseases while ensuring nutritional adequacy. The Dijkstra algorithm was used to identify the optimal pathways between the initial and target diets, with the aim of reducing meat consumption as quickly as possible and thus minimizing long-term HRs. RESULTS: Unprocessed red meat was easily minimized in the first steps of the pathways regardless of sex and initial level of meat consumption. However, processed meat could only be decreased later and required prior changes such as increases in fruit, vegetables, and oily fish. During total red meat minimization in females, securing adequate intakes of bioavailable iron had the most substantial impact on the other dietary changes needed. CONCLUSIONS: Immediate reduction of red meat consumption is possible on the pathway to a healthy diet that avoids any nutrient deficiency. However, early increases in fruit, vegetables, and fish are required before minimizing total red meat early in the diet.

Plant to animal protein ratio in the diet: nutrient adequacy, long-term health and environmental pressure.

Background: Animal and plant protein sources have contrasting relationships with nutrient adequacy and long-term health, and their adequate ratio is highly debated. Objective: We aimed to explore how the percentage of plant protein in the diet (%PP) relates to nutrient adequacy and long-term health but also to environmental pressures, to determine the adequate and potentially optimal %PP values. Methods: Observed diets were extracted from the dietary intakes of French adults (INCA3, n = 1,125). Using reference values for nutrients and disease burden risks for foods, we modeled diets with graded %PP values that simultaneously ensure nutrient adequacy, minimize long-term health risks and preserve at best dietary habits. This multi-criteria diet optimization was conducted in a hierarchical manner, giving priority to long-term health over diet proximity, under the constraints of ensuring nutrient adequacy and food cultural acceptability. We explored the tensions between objectives and identified the most critical nutrients and influential constraints by sensitivity analysis. Finally, environmental pressures related to the modeled diets were estimated using the AGRIBALYSE database. Results: We find that nutrient-adequate diets must fall within the ~15-80% %PP range, a slightly wider range being nevertheless identifiable by waiving the food acceptability constraints. Fully healthy diets, also achieving the minimum-risk exposure levels for both unhealthy and healthy foods, must fall within the 25-70% %PP range. All of these healthy diets were very distant from current typical diet. Those with higher %PP had lower environmental impacts, notably on climate change and land use, while being as far from current diet. Conclusion: There is no single optimal %PP value when considering only nutrition and health, but high %PP diets are more sustainable. For %PP > 80%, nutrient fortification/supplementation and/or new foods are required.

Identifying the most Efficient Detailed Trajectories toward Healthy Diets-A Graph-Based Analysis.

BACKGROUND: Much effort has been devoted to defining healthy diets, which could lower the burden of disease and provide targets for populations. However, these target diets are far removed from current diets, so at best, the population is expected to move slowly along a trajectory. OBJECTIVE: Our aim was to characterize the different possible trajectories toward a target diet and identify the most efficient one for health to point out the first dietary changes being the most urgent to implement. METHODS: Using graph theory, we have developed a new method to represent in a graph all stepwise change trajectories toward a target healthy diet, with trajectories all avoiding risk of nutrient deficiency. Then, we have identified and characterized the trajectory with the highest value for long-term health. Observed male and female average diets are from the French representative survey INCA3, and target diets were set using multicriteria optimization. The best trajectories were found using the Dijkstra algorithm with the Health risk criteria based on epidemiological data. RESULTS: Within ∼2.6M diets in the graphs, we found optimal trajectories that were rather similar for males and females regarding the most efficient changes in the first phase of the pathways. In particular, we found that a 1-step increase in the consumption of whole/semirefined bread (60 g) was the first step in all healthiest trajectories. In males, the subsequent decrease in red meat was immediately preceded by increases in legumes. CONCLUSIONS: We show simple practical dietary changes that can be prioritized along an integral pathway that is the most efficient overall for health when transiting toward a distant healthy diet. We put forward a new method to analyze dietary strategy for public health transition and highlight the first critical steps to prioritize.

Dietary protein consumption profiles show contrasting impacts on environmental and health indicators.

Patterns of protein intake are strong characteristics of diets, and protein sources have been linked to the environmental and nutrition/health impacts of diets. However, few studies have worked on protein profiles, and most of them have focused on specific diets like vegetarian or vegan diets. Furthermore, the description of the environmental impact of diets has often been limited to greenhouse gas emissions (GHGe) and land use. This paper analyzes the alignment of environmental pressures and nutritional impacts in a diversity of representative protein profiles of a western population. Using data from a representative survey in France (INCA3, n = 1125), we identified protein profiles using hierarchical ascendant classification on protein intake (g) from main protein sources (refined grains, whole grains, dairy, eggs, ruminant meat, poultry, pork, processed meat, fish, fruits & vegetables, pulses). We assessed their diet quality using 6 dietary scores, including assessment of long-term risk for health, and associated 14 environmental pressure indicators using the Agribalyse database completed by the SHARP database for GHGe. Five protein profiles were identified according to the high contributions of ruminant meat, pork, poultry, fish, or, conversely, as low contribution from meat. The profile including the lowest protein from meat had the lowest impact on almost all environmental indicators and had the lowest long-term risk. Conversely, the profile with high protein from ruminant-based foods had the highest pressures on most environmental indicators, including GHGe. We found that the protein profile with low contribution from meat has great potential for human health and environment preservation. Shifting a large part of the population toward this profile could be an easy first step toward building a more sustainable diet.

Synthesis of Unnatural α-Amino Acids from (Pyridin-2-yl) Carbamate via CIPE-Induced Carbonyl Migration.

Synthetic methods of unnatural α-amino acids have always been the focus of extensive research due to their significant bioactivities. However, convenient transition-metal-free catalyzed methods are still in demand. Herein, we report a novel strategy for the construction of an unnatural α-amino acid skeleton via intramolecular rearrangement of carbamates, which are readily available from amines and their common protecting groups. This rearrangement could afford a variety of amino ester products in up to 98% yield, even in gram-scale reaction. The reaction mechanism was studied in detail through experiments and theoretical calculations. The complex-induced proximity effect (CIPE) from the 2-pyridyl group is shown to be indispensable for this transformation.

Plant and Animal Protein Intakes Largely Explain the Nutritional Quality and Health Value of Diets Higher in Plants: A Path Analysis in French Adults.

Diets higher in plants are associated with lower risks of chronic diseases. However, animal foods, which are rich in protein, are also rich in some important minerals and vitamins. Using data from a representative survey in France (INCA3, n = 1,125), we used path analyses as a mediation-like approach to decipher the importance of plant and animal proteins in the relationship between the plant-based diet index (PDI) and diet quality. We used three types of diet quality scores, namely, nutrient security, positive nutrient adequacy, and long-term mortality risk of four diet-related diseases (i.e., coronary heart disease, stroke, type 2 diabetes, and colorectal cancer). We identified positive and negative mediations, i.e., changes in plant/animal protein intake that are associated with changes in PDI, and favor or limit the association with the diet quality score. The PDI was positively associated with the risk of long-term mortality but not significantly with nutrient adequacy or nutrient security. A positive mediation by plant protein was found for all diet quality scores (specific indirect effects (SIEs) ranging from 0.04 to 0.10 SD). Conversely, the association between PDI and nutrient adequacy (but not nutrient security) was negatively mediated by animal protein intake (SIE: -0.06 SD). In further detailed models, the association between PDI and diet quality was mainly positively mediated by protein foods from the fruit-vegetables-legumes group (0.01 SD for the nutrient security and 0.02 SD for the nutrient adequacy) and whole grains (0.02 SD for the nutrient adequacy). Our data suggest that the positive impact of plant-based diets on diet quality is largely driven by higher intakes of plant protein foods, especially from fruits-vegetables-legumes and whole grains. Conversely, lower animal protein intake tends to limit the positive impact of plant-based diets on overall positive nutrient adequacy but not security. Protein sources appear critical to healthy plant-based diets.

Modeled healthy eating patterns are largely constrained by currently estimated requirements for bioavailable iron and zinc-a diet optimization study in French adults.

BACKGROUND: Healthier dietary patterns involve more plant-based foods than current Western diets rich in animal products containing high amounts of bioavailable iron and zinc. Little consideration is given to the bioavailability of iron and zinc when studying healthy eating patterns. OBJECTIVES: Our aim was to determine whether currently estimated requirements for bioavailable iron and zinc limit the identification of healthier dietary patterns. METHODS: Using dietary data from a representative French survey and multicriteria nonlinear optimization, we identified diets that maximize health criteria based on food-based dietary guidelines and concomitantly depart only minimally from the observed diet while complying with all nutrient reference values either strictly (nonflexible optimization) or by allowing bioavailable iron and zinc below the current reference values, but to a limited extent (flexible optimization). Using a comparative risk assessment model, we estimated the resulting impact on cardiometabolic and colorectal cancer mortality/morbidity and changes to iron-deficiency anemia. RESULTS: Under nonflexible optimization, reference values for bioavailable iron and zinc were the most binding of the 35 nutrient constraints, and modeled diets displayed considerable redistributions within grains and meat. With flexible optimization, modeled diets were healthier as they contained less red meat and more whole-grain products, but would increase iron-deficiency anemia to 5.0% (95% CI: 3.9%, 6.4%). Globally, in terms of disability adjusted life years (DALYs), as the loss due to anemia would represent <30% of the gain otherwise made on chronic diseases, adding flexibility in the iron and zinc reference values would result in a further 18% decrease in the disease burden from 84,768 [95% uncertainty interval (UI): 81,066, 88,470] to 99,689 (95% UI: 95,787, 103,591) DALYs averted. CONCLUSIONS: Currently estimated requirements for bioavailable iron and zinc proved to be critical factors when modeling healthy eating patterns. Considering lower reference values enables the identification of diets that are apparently healthier overall.

Resveratrol induces proliferation in preosteoblast cell MC3T3-E1 via GATA-1 activating autophagy.

Resveratrol (RSV) could promote osteogenic activity, but its clinical application has been hampered in view of its poor bioavailability. Therefore, it is desirable to identify with certainty the molecular target of its bone mass boosting function, which is crucial to the design of an effective therapeutic strategy for the optimal treatment of osteoporosis. Emerging evidence has indicated that GATA-1, an important transcription factor in megakaryocyte and erythrocyte differentiation, can directly activate autophagy in erythrocytes, alluding to its impact on bone metabolism. In light of this, we sought to determine whether GATA-1 would be a putative target by which RSV would act on osteoblast proliferation and, if so, to explore the underlying mechanism involved in the process. We examined the cell viability, colony formation, cell cyclin expression, autophagy level, and the expression levels of GATA-1 and adenosine 5'-monophosphate (AMP)-activated protein kinase α (AMPKα) in osteoblastic cell strain MC3T3-E1. The results showed that RSV promoted the proliferation process in MC3T3-E1 coupled with increased expression of GATA-1 and phosphorylated AMPKα and activated autophagy. When GATA-1 was interfered with siRNA, both autophagy and proliferation were decreased. Administration of the agonist of phosphorylated AMPKα1 (Thr172) promoted the translocation of GATA-1 into the nucleus. Based on the above results, we concluded that RSV induces the proliferation of MC3T3-E1 by increasing GATA-1 expression, which thence activates autophagy; and of note, AMPKα is one of the upstream regulators of GATA-1.

Contrary to ultra-processed foods, the consumption of unprocessed or minimally processed foods is associated with favorable patterns of protein intake, diet quality and lower cardiometabolic risk in French adults (INCA3).

PURPOSE: While the consumption of ultra-processed foods is steadily increasing, there is a growing interest in more sustainable diets that would include more plant protein. We aimed to study associations between the degree of food processing, patterns of protein intake, diet quality and cardiometabolic risk. METHODS: Using the NOVA classification, we assessed the proportion of energy from unprocessed/minimally processed foods (MPFp), processed foods (PFp) and ultra-processed foods (UPFp) in the diets of 1774 adults (18-79 years) from the latest cross-sectional French national survey (INCA3, 2014-2015). We studied the associations between MPFp, PFp and UPFp with protein intakes, diet quality (using the PANDiet scoring system, the global (PDI), healthful (hPDI) and unhealthful (uPDI) plant-based diet indices) and risk of cardiometabolic death (using the EpiDiet model). RESULTS: MPFp was positively associated with animal protein intake and plant protein diversity, whereas PFp was positively associated with plant protein intake and negatively with plant protein diversity. The PANDiet was positively associated with MPFp (ß = 0.14, P < 0.0001) but negatively with UPFp (ß = - 0.05, P < 0.0001). These associations were modified by adjustment for protein intakes and plant protein diversity. As estimated with comparative risk assessment modeling between extreme tertiles of intake, mortality from cardiometabolic diseases would be decreased with higher MPFp (e.g. by 31% for ischemic heart diseases) and increased with higher UPFp (by 42%) and PFp (by 11%). CONCLUSIONS: In the French population, in contrast with UPFp, higher MPFp was associated with higher animal protein intake, better plant protein diversity, higher diet quality and markedly lower cardiometabolic risk.

Cellular organization of the trophoblastic epithelium in elongating conceptuses of ruminants.

We present a computational approach to analyze the cellular organization during the elongation process of the ovine conceptus. First, we selected a set of mathematical descriptors to quantify cell geometry and cell neighborhood within the external epithelial layer of the conceptus: the trophoblast. Second, we established a hybrid image segmentation framework, and analyzed the extracted features with statistical tools to describe and compare the spatio-temporal dynamics of cellular organization within this epithelium. The main results indicated that the average geometry and neighborhood of the trophoblast cells are relatively stable from a sampling position to another and from a stage of development to another. Further, their elongation axes are randomly distributed. The cellular organization fits the Poisson's process. Moreover, no clustering structures or grid-like regular point patterns are found inside the studied cell population. This suggests that the trophoblast elongation observed in ruminants is not due to the geometrical change of cell shape but might be the consequence of cell addition associated with peculiar plans of cell division or intercalation.

Proteomic signature of Lactococcus lactis NCDO763 cultivated in milk.

We have compared the proteomic profiles of L. lactis subsp. cremoris NCDO763 growing in the synthetic medium M17Lac, skim milk microfiltrate (SMM), and skim milk. SMM was used as a simple model medium to reproduce the initial phase of growth of L. lactis in milk. To widen the analysis of the cytoplasmic proteome, we used two different gel systems (pH ranges of 4 to 7 and 4.5 to 5.5), and the proteins associated with the cell envelopes were also studied by two-dimensional electrophoresis. In the course of the study, we analyzed about 800 spots and identified 330 proteins by mass spectrometry. We observed that the levels of more than 50 and 30 proteins were significantly increased upon growth in SMM and milk, respectively. The large redeployment of protein synthesis was essentially associated with an activation of pathways involved in the metabolism of nitrogenous compounds: peptidolytic and peptide transport systems, amino acid biosynthesis and interconversion, and de novo biosynthesis of purines. We also showed that enzymes involved in reactions feeding the purine biosynthetic pathway in one-carbon units and amino acids have an increased level in SMM and milk. The analysis of the proteomic data suggested that the glutamine synthetase (GS) would play a pivotal role in the adaptation to SMM and milk. The analysis of glnA expression during growth in milk and the construction of a glnA-defective mutant confirmed that GS is an essential enzyme for the development of L. lactis in dairy media. This analysis thus provides a proteomic signature of L. lactis, a model lactic acid bacterium, growing in its technological environment.

PARIS: a proteomic analysis and resources indexation system.

UNLABELLED: We developed a system for managing data from two-dimensional electrophoresis-based proteomic experiments. Named PARIS, the system stores gel image and information about experiments and analysis procedures, allows the user to search and navigate in genomic and proteomic data, supports visual verification and validation of the analysis results, and provides tools for cross multi-experiment and multi-experimenter data validation and exploration. AVAILABILITY: The software is freely available from http://www.inra.fr/bia/J/imaste/Projets/PARIS/index.html

3-D aggregated object detection and labeling from multivariate confocal microscopy images: a model validation approach.

One essential assumption used in object detection and labeling by imaging is that the photometric properties of the object are homogeneous. This homogeneousness requirement is often violated in microscopy imaging. Classical methods are usually of high computational cost and fail to give a stable solution. This paper presents a low computational complexity and robust method for three-dimensional (3-D) biological object detection and labeling. The developed approach is based on a statistical, nonparametric framework. Image is first divided into regular nonoverlapped regions and each region is evaluated according to a general photometric variability model. The regions not consistent with this model are considered as aberration in the data and excluded from the analysis procedure. Simultaneously, the interior parts of the object are detected, they correspond to regions where the supposed model is valid. In the second stage, the valid regions from a same object are merged together depending on a set of hypotheses. These hypotheses are generated by taking into account photometric and geometric properties of objects of interest and the merging is achieved according to an iterative algorithm. The approach has been applied in investigations of spatial distribution of nuclei within colonic glands of rats observed with the help of confocal fluorescence microscopy.