Cancer mortality in chrysotile miners and millers, Russian Federation: main results (Asbest Chrysotile Cohort-Study).

BACKGROUND: We investigated mortality in workers of the world's largest chrysotile mine and enrichment factories located in the town of Asbest, Russian Federation. METHODS: This historical cohort study included all workers employed for at least 1 year between 1975 and 2010 and follow-up until the end of 2015. Cumulative exposure to dust was estimated based on workers' complete occupational history linked to dust measurements systematically collected from the 1950s. Exposure to chrysotile fibers was estimated using dust-to-fiber conversion factors. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated as mortality rate ratios in Poisson regression models. RESULTS: A total of 30 445 (32% women) workers accumulated 721 312 person-years at risk and 11 110 (36%) died. Of the workers, 54% had more than 30 years since their first exposure. We found an exposure-response between cumulative dust and lung cancer mortality in men. No clear association with dust exposure but a modest increase in the highest category of fiber exposure was seen for lung cancer in women. Mesothelioma mortality was increased (RR = 7.64, 95% CI = 1.18 to 49.5, to at least 80 fibers per cm3 years and RR = 4.56, 95% CI = 0.94 to 22.1, to at least 150 mg/m3 years [dust]), based on 13 deaths. For colorectal and stomach cancer, there were inconsistent associations. No associations were seen for laryngeal or ovarian cancer. CONCLUSION: In this large-scale epidemiological study in the world's largest active asbestos mine, we confirmed an increased risk of mesothelioma with high fiber exposure and an increasing mortality for lung cancer in men with increasing dust exposure. Less clear-cut increased lung cancer mortality was seen in the women. Continued mortality follow-up is warranted.

Structural and Dynamical Properties of Elastin-Like Peptides near Their Lower Critical Solution Temperature.

Elastin-like peptides (ELPs) are artificially derived intrinsically disordered proteins (IDPs) mimicking the hydrophobic repeat unit in the protein elastin. ELPs are characterized by a lower critical solution temperature (LCST) in aqueous media. Here, we investigate the sequence GVG(VPGVG)3 over a wide range of temperatures (below, around, and above the LCST) and peptide concentrations employing all-atom molecular dynamics simulations, where we focus on the role of intra- and interpeptide interactions. We begin by investigating the structural properties of a single peptide that demonstrates a hydrophobic collapse with temperature, albeit moderate, because the sequence length is short. We observe a change in the interaction between two peptides from repulsive to attractive with temperature by evaluating the potential of mean force, indicating an LCST-like behavior. Next, we explore dynamical and structural properties of peptides in multichain systems. We report the formation of dynamical aggregates with coil-like conformation, in which valine central residues play an important role. Moreover, the lifetime of contacts between chains strongly depends on the temperature and can be described by a power-law decay that is consistent with the LCST-like behavior. Finally, the peptide translational and internal motion are slowed by an increase in the peptide concentration and temperature.

Surface-Mediated Molecular Transport of a Lipophilic Fluorescent Probe in Polydisperse Oil-in-Water Emulsions.

Emulsions often act as carriers for water-insoluble solutes that are delivered to a specific target. The molecular transport of solutes in emulsions can be facilitated by surfactants and is often limited by diffusion through the continuous phase. We here investigate this transport on a molecular scale by using a lipophilic molecular rotor as a proxy for solutes. Using fluorescence lifetime microscopy we track the transport of these molecules from the continuous phase toward the dispersed phase in polydisperse oil-in-water emulsions. We show that this transport comprises two time scales, which vary significantly with droplet size and surfactant concentration, and, depending on the type of surfactant used, can be limited either by transport across the oil-water interface or by diffusion through the continuous phase. By studying the time-resolved fluorescence of the fluorophore, accompanied by molecular dynamics simulations, we demonstrate how the rate of transport observed on a macroscopic scale can be explained in terms of the local environment that the probe molecules are exposed to.

A massive bloom of Karenia species (Dinophyceae) off the Kamchatka coast, Russia, in the fall of 2020.

In the fall of 2020, a long-lasting and massive harmful algal bloom (HAB) with extensive fields of yellow sea foam was observed in relatively cold waters (7-13 °C) off the coasts of the Kamchatka Peninsula, Russia. According to the estimates based on bio-optical parameters in satellite imagery, the Kamchatka bloom 2020 lasted for two months and covered a vast area of more than 300 × 100 km. An abundance of dead fish and invertebrates, including sea urchins, sea anemones, chitons, cephalopods, bivalves were found on shore during the bloom. Animals suffered almost 100% mortality within a depth range between 5 and 20 m. To identify the causative microalgal species, light and scanning electron microscopy, Raman spectroscopy, and molecular phylogenetic approaches were used. The HAB area was estimated by the spectral analysis of satellite-derived imagery. The causative organisms were unarmored dinoflagellates of Karenia species. Their density and biomass reached 100-620 cells·mL-1 and 1300-7700 mg·m-3, respectively, which accounted for 31-99% of the total cell density and 82-99% of the total phytoplankton biomass in late September to mid-October. The dominant species was Karenia selliformis, and the other co-occurring kareniacean species were K. cf. cristata, K. mikimotoi, K. papilionacea, K. longicanalis, and two unidentified morphotypes of Karenia spp. The molecular phylogeny inferred from LSU rDNA and ITS region showed that K. selliformis from Kamchatka in 2020 belonged to the cold-water group I and was identical to K. selliformis strains from Hokkaido, Japan, identified in 2021. This is the first HAB event caused by K. selliformis recorded from Russian coastal waters.

Effect of CYP2C9, PTGS-1 and PTGS-2 gene polymorphisms on the efficiency and safety of postoperative analgesia with ketoprofen.

OBJECTIVES: Patients undergoing cardiac surgery develop post-sternotomy pain syndrome. The aim of this study was evaluation of the influence of CYP2C9, PTGS-1 and PTGS-2 genes polymorphisms on the efficacy and safety of postoperative analgesia with ketoprofen in patients with coronary artery disease after cardiac surgery. METHODS: The study included 90 patients undergoing cardiac surgery. A real-time polymerase chain reaction was used for the detection of single nucleotide polymorphisms (SNP). Pain intensity was measured by the Numeric Rating Scale (NRS). Dyspeptic symptoms were evaluated using the Gastrointestinal Symptom Rating Scale (GSRS). Acute kidney injury (AKI) was determined by Kidney Disease Improving Global Outcomes criteria. RESULTS: Pain intensity by the NRS score was significantly higher in patients with CYP2C9*3 АA genotype compared to АC genotype: 7 [1,10] and 6 [2,7] (p=0.003); 7 [1,10] and 6 [2,7] (p=0.04); 6 [0; 10] and 5 [2,6] (p=0.04); 5 [0; 8] and 3 [0; 8] (p=0.02), on days 1, 2, 3 and 5 in the postoperative period, respectively. GSRS score was higher in patients with CYP2C9*2 CT genotype compared to CС genotype: 19 [15; 42] and 18 [15,36] (p=0.04), respectively. There were no significant differences in the pain intensity, dyspepsia severity and AKI frequency in patients with homozygous and heterozygous genotypes for PTGS-1 rs10306135, PTGS-1 rs12353214, PTGS-2 rs20417. CONCLUSIONS: CYP2C9*3 and CYP2C9*2 gene polymorphisms may affect efficacy and safety of postoperative analgesia with ketoprofen in patients with coronary artery disease after cardiac surgery.

Modulation of the Drosophila transcriptome by developmental exposure to alcohol.

BACKGROUND: Prenatal exposure to ethanol can cause fetal alcohol spectrum disorder (FASD), a prevalent, preventable pediatric disorder. Identifying genetic risk alleles for FASD is challenging since time, dose, and frequency of exposure are often unknown, and manifestations of FASD are diverse and evident long after exposure. Drosophila melanogaster is an excellent model to study the genetic basis of the effects of developmental alcohol exposure since many individuals of the same genotype can be reared under controlled environmental conditions. RESULTS: We used 96 sequenced, wild-derived inbred lines from the Drosophila melanogaster Genetic Reference Panel (DGRP) to profile genome-wide transcript abundances in young adult flies that developed on ethanol-supplemented medium or standard culture medium. We found substantial genetic variation in gene expression in response to ethanol with extensive sexual dimorphism. We constructed sex-specific genetic networks associated with alcohol-dependent modulation of gene expression that include protein-coding genes, Novel Transcribed Regions (NTRs, postulated to encode long non-coding RNAs) and female-specific coordinated regulation of snoRNAs that regulate pseudouridylation of ribosomal RNA. We reared DGRP lines which showed extreme upregulation or downregulation of snoRNA expression during developmental alcohol exposure on standard or ethanol supplemented medium and demonstrated that developmental exposure to ethanol has genotype-specific effects on adult locomotor activity and sleep. CONCLUSIONS: There is significant and sex-specific natural genetic variation in the transcriptional response to developmental exposure to ethanol in Drosophila that comprises networks of genes affecting nervous system development and ethanol metabolism as well as networks of regulatory non-coding RNAs.

Temperature dependence of thermodynamic, dynamical, and dielectric properties of water models.

We investigate the temperature dependence of thermodynamic (density and isobaric heat capacity), dynamical (self-diffusion coefficient and shear viscosity), and dielectric properties of several water models, such as the commonly employed TIP3P water model, the well-established four-point water model TIP4P-2005, and the recently developed four-point water model TIP4P-D. We focus on the temperature range of interest for the field of computational biophysics and soft matter (280-350 K). The four-point water models lead to a spectacularly improved agreement with experimental data, strongly suggesting that the use of more modern parameterizations should be favored compared to the more traditional TIP3P for modeling temperature-dependent phenomena in biomolecular systems.

Genome-Wide Analysis in Drosophila Reveals the Genetic Basis of Variation in Age-Specific Physical Performance and Response to ACE Inhibition.

Despite impressive results in restoring physical performance in rodent models, treatment with renin-angiotensin system (RAS) inhibitors, such as Lisinopril, have highly mixed results in humans, likely, in part, due to genetic variation in human populations. To date, the genetic determinants of responses to drugs, such as RAS inhibitors, remain unknown. Given the complexity of the relationship between physical traits and genetic background, genomic studies which predict genotype- and age-specific responses to drug treatments in humans or vertebrate animals are difficult. Here, using 126 genetically distinct lines of Drosophila melanogaster, we tested the effects of Lisinopril on age-specific climbing speed and endurance. Our data show that functional response and sensitivity to Lisinopril treatment ranges from significant protection against physical decline to increased weakness depending on genotype and age. Furthermore, genome-wide analyses led to identification of evolutionarily conserved genes in the WNT signaling pathway as being significantly associated with variations in physical performance traits and sensitivity to Lisinopril treatment. Genetic knockdown of genes in the WNT signaling pathway, Axin, frizzled, nemo, and wingless, diminished or abolished the effects of Lisinopril treatment on climbing speed traits. Our results implicate these genes as contributors to the genotype- and age-specific effects of Lisinopril treatment and because they have orthologs in humans, they are potential therapeutic targets for improvement of resiliency. Our approach should be widely applicable for identifying genomic variants that predict age- and sex-dependent responses to any type of pharmaceutical treatment.

Adsorption and Desorption of Polymers on Bioinspired Chemically Structured Substrates.

Natural biological surfaces exhibit interesting properties due to their inhomogeneous chemical and physical structure at the micro- and nanoscale. In the case of hair or skin, this also influences how waterborne macromolecules ingredients will adsorb and form cosmetically performing deposits (i.e., shampoos, cleansers, etc.). Here, we study the adsorption of hydrophilic flexible homopolymers on heterogeneous, chemically patterned substrates that represent the surface of the hair by employing coarse-grained molecular dynamics simulations. We develop a method in which the experimental images of the substrate are used to obtain information about the surface properties. We investigate the polymer adsorption as a function of polymer chain length and polymer concentration spanning both dilute and semidilute regimes. Adsorbed structures are quantified in terms of trains, loops, and tails. We show that upon increasing polymer concentration, the length of tails and loops increases at the cost of monomers belonging to trains. Furthermore, using an effective description, we probe the stability of the resulting adsorbed structures under a linear shear flow. Our work is a first step toward developing models of complex macromolecules interacting with realistic biological surfaces, as needed for the development of more ecofriendly industrial products.

Occupational cohort study of current and former workers exposed to chrysotile in mine and processing facilities in Asbest, the Russian Federation: Cohort profile of the Asbest Chrysotile Cohort study.

A historical cohort study in workers occupationally exposed to chrysotile was set up in the town of Asbest, the Russian Federation, to study their cause-specific mortality, with a focus on cancer. Chrysotile has different chemical and physical properties compared with other asbestos fibres; therefore it is important to conduct studies specifically of chrysotile and in different geographical regions to improve the knowledge about its carcinogenicity. Setting was the town of Asbest, Sverdlovsk oblast, the Russian Federation. Participants were all current and former employees with at least one year of employment between 1/1/1975 and 31/12/2010 in the mine, enrichment factories, auto-transport and external rail transportation departments, the central laboratory, and the explosives unit of the company. Of the 35,837 cohort members, 12,729 (35.5%) had died (2,373 of them of cancer, including 10 of mesothelioma), 18,799 (52.5%) were known to be alive at the end of the observation period (2015), and 4,309 (12.0%) were censored before the end of 2015. Mean follow-up duration was 21.7 years in men and 25.9 years in women. The mean age at death was 59.4 years in men and 66.5 years in women. This is the largest occupational cohort of chrysotile workers to date, and the only one with a large proportion of exposed female workers.

In Silico Design Enables the Rapid Production of Surface-Active Colloidal Amphiphiles.

A new technology platform built on the integration of theory and experiments to enable the design of Janus colloids with precision control of surface anisotropy and amphiphilicity could lead to a disruptive transformation in the next generation of surfactants, photonic or phononic materials, and coatings. Here, we exploit molecular dynamics (MD) simulations to guide the rational design of amphiphilic polymer Janus colloids by Flash NanoPrecipitation (FNP), a method capable of the production of colloids with complex structure without the compromise of reduced scalability. Aided by in silico design, we show in experiments that amphiphilic Janus colloids can be produced using a unique blend of hydrophobic homopolymers and the addition of an amphiphilic block copolymer. The final structure of the colloids depends on the mass fraction of each homopolymer as well as the concentration and composition of the block copolymer additive. To confirm the surface activity of the colloids, we demonstrate their potential to stabilize Pickering emulsions. This hybrid approach of simulations and experiments provides a pathway to designing and manufacturing complex polymeric colloids on an industrial scale.

Cardiac tumours - a brief review.

This short review of cardiac tumours presents a case that clearly demonstrates the manifestation of embolic and cardiac symptoms of an intracardiac mass. Acute onset and rapid progression of a neoplastic process in the heart leading to arrhythmia, cardiac conduction disorders and heart failure combined with highly mobile fragments of tumour, which can cause emboli in cerebral vessels, are characteristic signs of an intracardiac mass. Early diagnosis and immediate treatment may improve the long-term prognosis, but overall the prognosis is poor. Cardiac tumours present to the cardiologist when the patient presents with cardiac symptoms, and the neurologist when there are cerebral symptoms. Most cardiac masses are not amenable to percutaneous biopsy; therefore, definitive diagnosis often awaits surgical excision.

Surface Activity of Soft Polymer Colloids.

We investigate the behavior of polymer colloids at the interface between two immiscible liquids using molecular dynamics simulations. We study several colloid morphologies with various degrees of amphiphilicity, that is, purely solvophobic homogeneous and Janus particles and amphiphilic Janus and core-shell particles. Regardless of the specific morphology, the polymer colloids irreversibly anchor at the liquid-liquid interface, accompanied by a marked reduction of the interfacial tension, γ. Purely solvophobic particles lower γ because they reduce the interfacial area shared by the two immiscible liquids, whereas amphiphilic colloids have an additional enthalpic contribution. At the liquid-liquid interface, the solvophobic particles deform into oblate ellipsoids to maximize the occluded area at the interface. In contrast, amphiphilic Janus colloids orient their solvophobic/solvophilic parts toward the preferred liquids and form a prolate particle shape. The amphiphilic core-shell particles undergo a morphological transition to a prolate Janus-like structure as they anchor at the interface. We rationalize the deformation of the polymer colloids by considering a simple model system of spheroidal particles pinned at the liquid-liquid interface. We systematically compute the interfacial free energy for the various colloids as a function of their asphericity and find excellent qualitative agreement with the simulation findings. Our results show that solvophobic homoparticles can be almost as efficient surface-active agents as amphiphilic Janus colloids.

Lisinopril Preserves Physical Resilience and Extends Life Span in a Genotype-Specific Manner in Drosophila melanogaster.

Physical resiliency declines with age and comorbid conditions. In humans, angiotensin-converting enzyme (ACE) has been associated with attenuation of the decline in physical performance with age. ACE-inhibitor compounds, commonly prescribed for hypertension, often have beneficial effects on physical performance however the generality of these effects are unclear. Here, we tested the effects of the ACE-inhibitor Lisinopril on life span, and age-specific speed, endurance, and strength using three genotypes of the Drosophila melanogaster Genetic Reference Panel. We show that age-related decline in physical performance and survivorship varies with genetic background. Lisinopril treatment increased mean life span in all Drosophila Genetic Reference Panel lines, but its effects on life span, speed, endurance, and strength depended on genotype. We show that genotypes with increased physical performance on Lisinopril treatment experienced reduced age-related protein aggregation in muscle. Knockdown of skeletal muscle-specific Ance, the Drosophila ortholog of ACE, abolished the effects of Lisinopril on life span, implying a role for skeletal muscle Ance in survivorship. Using transcriptome profiling, we identified genes involved in stress response that showed expression changes associated with genotype and age-dependent responsiveness to Lisinopril. Our results demonstrate that Ance is involved in physical decline and demonstrate genetic variation in phenotypic responses to an ACE inhibitor.

On the Stability of Polymeric Nanoparticles Fabricated through Rapid Solvent Mixing.

We study the stability of polymeric nanoparticles fabricated through the rapid mixing of polymers in a good solvent with a poor solvent that is miscible with the good solvent. In previous experiments where water was used as the poor solvent, a negative surface charge was measured on the precipitated nanoparticles, which led to the long-time stability of the dispersion. It was argued that these charges originate presumably from either water or hydroxide adsorption at the hydrophobic nanoparticle surface or from impurities in the feed streams that preferentially adsorb on the precipitated nanoparticles. To elucidate the origin of this stabilization mechanism, we performed experiments wherein we replaced water with a nonpolar poor solvent. The polymers aggregated into stable nanoparticles for a range of processing parameters. We investigated theoretically three possible explanations for this stability, i.e., electrostatic stabilization, conditional thermodynamic equilibrium, and steric stabilization. Our experiments and considerations suggest that steric stabilization is the most likely candidate.

Effects of ABCB1 rs1045642 polymorphisms on the efficacy and safety of amlodipine therapy in Caucasian patients with stage I-II hypertension.

PURPOSE: The aim of this study was to determine the impact of ABCB1 (MDR1) rs1045642 polymorphisms on the efficacy and safety of amlodipine in Caucasian patients. PATIENTS AND METHODS: The 12-week study included 100 patients. Patients with the newly diagnosed stage I-II hypertension (HT) were recruited to complete genotyping of the rs1045642 single-nucleotide polymorphism (SNP). The study design did not include a control group. Before treatment, all patients either did not undergo antihypertensive treatment at all or did not receive regular antihypertensive therapy. The initial dose was 5 mg/day. Four office blood pressure measurements, two 24-hour noninvasive ambulatory blood pressure measurements, and questionnaires of Tsvetov were used to evaluate the efficacy and safety of amlodipine. RESULTS AND CONCLUSION: The highest antihypertensive effect in combination with the lowest incidence of adverse reactions was observed in the TT group, while patients with the CC genotype showed a low antihypertensive effect and the highest incidence of adverse effects. Patients with the CC genotype presented with adverse effects predominantly in the form of edema. A total of 33 patients reached the target blood pressure (SBP <140 mmHg; DBP <90 mmHg): two patients with the CC genotype (12%); 18 patients with the CT genotype (34%); and 13 patients with the TT genotype (43%). The intergroup differences were: CC vs CT, P=0.02; CC vs TT, P=0.02; and CT vs TT, P=0.05. The results of this study indicate the potential of pharmacogenetic testing for rs1045642 SNP when prescribing amlodipine for the first time in Caucasian patients with stage I-II arterial HT.

A Cyclin E Centered Genetic Network Contributes to Alcohol-Induced Variation in Drosophila Development.

Prenatal exposure to ethanol causes a wide range of adverse physiological, behavioral and cognitive consequences. However, identifying allelic variants and genetic networks associated with variation in susceptibility to prenatal alcohol exposure is challenging in human populations, since time and frequency of exposure and effective dose cannot be determined quantitatively and phenotypic manifestations are diverse. Here, we harnessed the power of natural variation in the Drosophila melanogaster Genetic Reference Panel (DGRP) to identify genes and genetic networks associated with variation in sensitivity to developmental alcohol exposure. We measured development time from egg to adult and viability of 201 DGRP lines reared on regular or ethanol- supplemented medium and identified polymorphisms associated with variation in susceptibility to developmental ethanol exposure. We also documented genotype-dependent variation in sensorimotor behavior after developmental exposure to ethanol using the startle response assay in a subset of 39 DGRP lines. Genes associated with development, including development of the nervous system, featured prominently among genes that harbored variants associated with differential sensitivity to developmental ethanol exposure. Many of them have human orthologs and mutational analyses and RNAi targeting functionally validated a high percentage of candidate genes. Analysis of genetic interaction networks identified Cyclin E (CycE) as a central, highly interconnected hub gene. Cyclin E encodes a protein kinase associated with cell cycle regulation and is prominently expressed in ovaries. Thus, exposure to ethanol during development of Drosophila melanogaster might serve as a genetic model for translational studies on fetal alcohol spectrum disorder.

Coil-Globule Collapse of Polystyrene Chains in Tetrahydrofuran-Water Mixtures.

We study the coil and globule states of a single polymer chain in solution by performing molecular dynamics simulations with a united atom model. Specifically, we characterize the structural properties of atactic polystyrene chains with N = 20-150 monomers in tetrahydrofuran-water mixtures at varying mixing ratios. We find that the hydrophobic polymers form rather open coils when the mole fraction of water, XW, is roughly below 0.25, whereas the chains collapse into globules when XW ≳ 0.75. We confirm the theoretically expected scaling laws for the radius of gyration, Rg, in these regimes, i.e., Rg ∝ N3/5 and Rg ∝ N1/3 for good and poor solvent conditions, respectively. For poor solvent conditions with XW = 0.75, we find a sizable fraction of residual tetrahydrofuran trapped inside the collapsed polymer chains with an excess amount located at the globule surface, acting as a protective layer between the hydrophobic polystyrene and the surrounding water-rich mixture. These findings have important implications for nanoparticle fabrication techniques where solvent exchange is exploited to drive polymer aggregation, since residual solvent can significantly influence the physical properties of the precipitated nanoparticles.

Editor's Highlight: Genetic Targets of Acute Toluene Inhalation in Drosophila melanogaster.

Interpretation and use of data from high-throughput assays for chemical toxicity require links between effects at molecular targets and adverse outcomes in whole animals. The well-characterized genome of Drosophila melanogaster provides a potential model system by which phenotypic responses to chemicals can be mapped to genes associated with those responses, which may in turn suggest adverse outcome pathways associated with those genes. To determine the utility of this approach, we used the Drosophila Genetics Reference Panel (DGRP), a collection of ∼200 homozygous lines of fruit flies whose genomes have been sequenced. We quantified toluene-induced suppression of motor activity in 123 lines of these flies during exposure to toluene, a volatile organic compound known to induce narcosis in mammals via its effects on neuronal ion channels. We then applied genome-wide association analyses on this effect of toluene using the DGRP web portal (http://dgrp2.gnets.ncsu.edu), which identified polymorphisms in candidate genes associated with the variation in response to toluene exposure. We tested ∼2 million variants and found 82 polymorphisms located in or near 66 candidate genes that were associated with phenotypic variation for sensitivity to toluene at P < 5 × 10-5, and human orthologs for 52 of these candidate Drosophila genes. None of these orthologs are known to be involved in canonical pathways for mammalian neuronal ion channels, including GABA, glutamate, dopamine, glycine, serotonin, and voltage sensitive calcium channels. Thus this analysis did not reveal a genetic signature consistent with processes previously shown to be involved in toluene-induced narcosis in mammals. The list of the human orthologs included Gene Ontology terms associated with signaling, nervous system development and embryonic morphogenesis; these orthologs may provide insight into potential new pathways that could mediate the narcotic effects of toluene.

Genetic and Genomic Response to Selection for Food Consumption in Drosophila melanogaster.

Food consumption is an essential component of animal fitness; however, excessive food intake in humans increases risk for many diseases. The roles of neuroendocrine feedback loops, food sensing modalities, and physiological state in regulating food intake are well understood, but not the genetic basis underlying variation in food consumption. Here, we applied ten generations of artificial selection for high and low food consumption in replicate populations of Drosophila melanogaster. The phenotypic response to selection was highly asymmetric, with significant responses only for increased food consumption and minimal correlated responses in body mass and composition. We assessed the molecular correlates of selection responses by DNA and RNA sequencing of the selection lines. The high and low selection lines had variants with significantly divergent allele frequencies within or near 2081 genes and 3526 differentially expressed genes in one or both sexes. A total of 519 genes were both genetically divergent and differentially expressed between the divergent selection lines. We performed functional analyses of the effects of RNAi suppression of gene expression and induced mutations for 27 of these candidate genes that have human orthologs and the strongest statistical support, and confirmed that 25 (93 %) affected the mean and/or variance of food consumption.