So Many Brands and Varieties to Choose from:Does This Compromise the Control of Food Intake in Humans?

The recent rise in obesity is widely attributed to changes in the dietary environment (e.g., increased availability of energy-dense foods and larger portion sizes). However, a critical feature of our “obesogenic environment” may have been overlooked - the dramatic increase in “dietary variability” (the tendency for specific mass-produced foods to be available in numerous varieties that differ in energy content). In this study we tested the hypothesis that dietary variability compromises the control of food intake in humans. Specifically, we examined the effects of dietary variability in pepperoni pizza on two key outcome variables; i) compensation for calories in pepperoni pizza and ii) expectations about the satiating properties of pepperoni pizza (expected satiation). We reasoned that dietary variability might generate uncertainty about the postingestive effects of a food. An internet-based questionnaire was completed by 199 adults. This revealed substantial variation in exposure to different varieties of pepperoni pizza. In a follow-up study (n= 66; 65% female), high pizza variability was associated with i) poorer compensation for calories in pepperoni pizza and ii) lower expected satiation for pepperoni pizza. Furthermore, the effect of uncertainty on caloric compensation was moderated by individual differences in decision making (loss aversion). For the first time, these findings highlight a process by which dietary variability may compromise food-intake control in humans. This is important because it exposes a new feature of Western diets (processed foods in particular) that might contribute to overeating and obesity

No difference in compensation for sugar in a drink versus sugar in semi-solid and solid foods

AbstractIt is claimed that sugar consumed in a drink is poorly compensated for by a reduction in subsequent energy intake, however very little research has tested directly the effect on appetite of adding sugar to a drink versus food. In this between subjects study, 144 participants (72 men) consumed preloads sweetened with either sucrose or the low-energy sweetener, sucralose (preload energy difference 162kcal) in the form of a blackcurrant drink, jelly or candy. The different preload viscosities were achieved by varying the amount of thickener (carrageenan) and water in the recipes. Participants completed hunger ratings before and 5, 10 and 20min after consuming their preload. After the 20-minute rating they were served a test-meal comprising an excess of bite-sized sandwiches and a sweet dessert. Energy intake measured for the same meal consumed the previous day (baseline day, no preload consumed) was used in the data analyses to control for individual differences in energy intake. Overall, there was 36% compensation for the energy difference in the preloads, but this did not vary with preload viscosity — if anything compensation was greater for the drink preload, and greater in men. The drink preload also showed an effect of sucrose versus sucralose for hunger. The lack of the predicted effect of viscosity on compensation could not be explained by differences in blood-glucose concentration 20min after the preload (measured in a separate study) or by differences in preload sweetness, flavour intensity, liking or familiarity. Comparison of baseline and test-meal food intakes indicated that, irrespective of energy content, the sweet drinks reduced the relative intake of sweet food. In conclusion, short-term energy compensation did not differ across a set of realistic drink and food stimuli

An Information-theoretic Approach to Prompt Engineering Without Ground Truth Labels

Pre-trained language models derive substantial linguistic and factual knowledge from the massive corpora on which they are trained, and prompt engineering seeks to align these models to specific tasks. Unfortunately, existing prompt engineering methods require significant amounts of labeled data, access to model parameters, or both. We introduce a new method for selecting prompt templates \textit{without labeled examples} and \textit{without direct access to the model}. Specifically, over a set of candidate templates, we choose the template that maximizes the mutual information between the input and the corresponding model output. Across 8 datasets representing 7 distinct NLP tasks, we show that when a template has high mutual information, it also has high accuracy on the task. On the largest model, selecting prompts with our method gets 90\% of the way from the average prompt accuracy to the best prompt accuracy and requires no ground truth labels

Complex Evolutionary History With Extensive Ancestral Gene Flow in an African Primate Radiation

Understanding the drivers of speciation is fundamental in evolutionary biology, and recent studies highlight hybridization as an important evolutionary force. Using whole-genome sequencing data from 22 species of guenons (tribe Cercopithecini), one of the world's largest primate radiations, we show that rampant gene flow characterizes their evolutionary history and identify ancient hybridization across deeply divergent lineages that differ in ecology, morphology, and karyotypes. Some hybridization events resulted in mitochondrial introgression between distant lineages, likely facilitated by cointrogression of coadapted nuclear variants. Although the genomic landscapes of introgression were largely lineage specific, we found that genes with immune functions were overrepresented in introgressing regions, in line with adaptive introgression, whereas genes involved in pigmentation and morphology may contribute to reproductive isolation. In line with reports from other systems that hybridization might facilitate diversification, we find that some of the most species-rich guenon clades are of admixed origin. This study provides important insights into the prevalence, role, and outcomes of ancestral hybridization in a large mammalian radiation

Identification of constrained sequence elements across 239 primate genomes

Noncoding DNA is central to our understanding of human gene regulation and complex diseases1,2, and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome3–9. Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA10, the relatively short timescales separating primate species11, and the previously limited availability of whole-genome sequences12. Here we construct a whole-genome alignment of 239 species, representing nearly half of all extant species in the primate order. Using this resource, we identified human regulatory elements that are under selective constraint across primates and other mammals at a 5% false discovery rate. We detected 111,318 DNase I hypersensitivity sites and 267,410 transcription factor binding sites that are constrained specifically in primates but not across other placental mammals and validate their cis-regulatory effects on gene expression. These regulatory elements are enriched for human genetic variants that affect gene expression and complex traits and diseases. Our results highlight the important role of recent evolution in regulatory sequence elements differentiating primates, including humans, from other placental mammals

Phylogenomic analyses provide insights into primate evolution

Comparative analysis of primate genomes within a phylogenetic context is essential for understanding the evolution of human genetic architecture and primate diversity. We present such a study of 50 primate species spanning 38 genera and 14 families, including 27 genomes first reported here, with many from previously less well represented groups, the New World monkeys and the Strepsirrhini. Our analyses reveal heterogeneous rates of genomic rearrangement and gene evolution across primate lineages. Thousands of genes under positive selection in different lineages play roles in the nervous, skeletal, and digestive systems and may have contributed to primate innovations and adaptations. Our study reveals that many key genomic innovations occurred in the Simiiformes ancestral node and may have had an impact on the adaptive radiation of the Simiiformes and human evolution

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead