Follistatin-like 1 (FSTL1) levels as potential early biomarker of cardiovascular disease in a Mexican population.

Cardiovascular diseases (CVD) are the leading cause of death globally. In recent years, follistatin-like protein 1 (FSTL1) has been proposed as an emerging potential clinical biomarker of CVD, since its concentration is upregulated in heart failure. The aim of the present study was to evaluate the association of FSTL1 levels and classic biomarkers with the risk of CVD in Mexican population. A case-control study was carried out in patients with cardiovascular diseases (CVD), arterial hypertension, but not CVD (cardiovascular risk factor-CRF), and healthy controls (control group) from the Mexican Institute of Social Security. Lipid profile, homocysteine (Hcys), serum amyloid A (SAA), FSTL1 concentration, PON1 concentration and activities [Arylesterase (ARE), and Lactonase (LAC)] were evaluated. High levels of FSTL1 were found in the CRF group and a positive association of FSTL1 (OR = 4.55; 95% CI 1.29-16.04, p = 0.02) with the presence of arterial hypertension, as well as Hcys (OR, 3.09; 95% CI 1.23-7.76, p = 0.02) and SAA (OR, 1.03; 95% CI 1.01-1.05, p < 0.01) with the presence of CVD. LAC activity (OR, 0.26; 95% CI 0.07-0.94, p = 0.04) and PON1 concentration (OR, 0.17; 95% CI 0.05-0.62, p = 0.01) were associated with a decrease in OR belonging to the group with CVD. Our results suggest that FSTL1 may be a useful biomarker for monitoring cardiovascular risk in clinical settings. However, longitudinal studies are needed to evaluate how FSTL1 could influence the association of PON1 activity and Hcys with CVD.

Metal-free design of a multilayered metamaterial with chirped Bragg grating for enhanced radiative cooling.

A wideband, all-dielectric metamaterial structure for enhancing radiative cooling is investigated. The structure is optimized to reflect most of the solar irradiance window (between 0.3 µm-3 µm), which is one of the biggest challenges in highly efficient radiative cooling coatings. The design is based on the principles of Bragg gratings, which constitutes a simple synthesis procedure to make a broadband reflector of reduced dimensions, without metallic layers, while keeping a flat enough response in the entire bandwidth. Numerical results show that reflection of solar irradiation can be easily tailored and maximized using this method, as well as the net cooling power of the device, about ∼79 W/m2 at daytime (about double at night-time) and a temperature reduction of 23 K (assuming no heat exchange) and 7 K assuming a heat exchange coefficient of 10 W/m2/K, for a device and ambient temperatures of 300 K and 303 K, respectively. This occurs even in detriment of absorption in the atmospheric window (8 µm-13 µm). Results also show the importance of efficiently reflecting solar irradiance for such technologies and its relevance in synthesis and design without using metallic components.

Preliminary survey of the occurrence of mycotoxins in cereals and estimated exposure in a northwestern region of Mexico.

Mycotoxins have several toxicological implications. In the present study, we evaluate the presence of aflatoxin B1 (AFB1), ochratoxin A (OTA), and fumonisin (FB1) in paddy rice, polished rice, and maize from the fields and markets in Nayarit State (Mexico). The results indicated the presence of AFB1 in 21.21% of paddy rice samples and 11.11% of market maize samples. OTA was present in only 3.03% (one sample) of paddy rice samples. FB1 was detected in 87.50% and 88.88% of maize samples from field and market, respectively. The estimated human exposure was calculated for FB1 using the probable daily intake (PDI), which suggested that FB1 could contribute to the development of diseases through the consumption of contaminated maize. Positive samples indicated that some rice and maize samples were not suitable for human consumption. Further efforts are needed to continue monitoring mycotoxins and update national legislation on mycotoxins accordingly.

Metabolic shifts toward fatty-acid usage and increased thermogenesis are associated with impaired adipogenesis in mice expressing human APOE4.

BACKGROUND: The Apolipoprotein E (APOE) gene encodes for three isoforms in the human population (APOE2, APOE3 and APOE4). Whereas the role of APOE in lipid metabolism is well characterized, the specific metabolic signatures of the APOE isoforms during metabolic disorders, remain unclear. OBJECTIVE: To elucidate the molecular underpinnings of APOE-directed metabolic alterations, we tested the hypothesis that APOE4 drives a whole-body metabolic shift toward increased lipid oxidation. METHODS: We employed humanized mice in which the Apoe gene has been replaced by the human APOE*3 or APOE*4 allele to produce human APOE3 or APOE4 proteins and characterized several mechanisms of fatty-acid oxidation, lipid storage, substrate utilization and thermogenesis in those mice. RESULTS: We show that, whereas APOE4 mice gained less body weight and mass than their APOE3 counterparts on a Western-type diet (P<0.001), they displayed elevated insulin and homeostatic model assessment, markers of insulin resistance (P=0.004 and P=0.025, respectively). APOE4 mice also demonstrated a reduced respiratory quotient during the postprandial period (0.95±0.03 versus 1.06±0.03, P<0.001), indicating increased usage of lipids as opposed to carbohydrates as a fuel source. Finally, APOE4 mice showed increased body temperature (37.30±0.68 versus 36.9±0.58 °C, P=0.039), augmented cold tolerance and more metabolically active brown adipose tissue compared with APOE3 mice. CONCLUSION: These data suggest that APOE4 mice may resist weight gain via an APOE4-directed global metabolic shift toward lipid oxidation and enhanced thermogenesis, and may represent a critical first step in the development of APOE-directed therapies for a large percentage of the population affected by disorders with established links to APOE and metabolism.

Assessment of pollution of the Boca de Camichin Estuary in Nayarit (Mexico) and its influence on oxidative stress in Crassostrea corteziensis oysters.

Boca de Camichin Estuary is one of the main producers of Crassostrea corteziensis oysters in Mexico, but the presence of pollutants can affect oyster production. Molluscs produce reactive oxygen species (ROS) in response to changes in the environment and pollution. These ROS induce oxidative damage in biomolecules. The main objective of this study was to evaluate pollution in the estuary and the subsequent oxidative stress in C. corteziensis oysters during the 2010 production cycle. For this aim, we performed monthly samplings in the oyster farms from January to May. We took water samples to quantify polycyclic aromatic hydrocarbon (PAH) and metal content; also, we evaluated oxidative damage (lipoperoxidation, lipidic hydroperoxides, protein oxidation) and enzyme activity (CAT, SOD, GPx, GST and AChE) in oyster gills. The results show the presence of Cu, Fe, Mn, naphthalene, benz[a]anthracene, pyrene, benz[a]pyrene and benzo[k]fluoranthene. On the other hand, AChE activity was not inhibited, which suggests that organophosphorus pollutants or carbamates were absent. Regarding oxidative stress, oysters from the estuary had oxidative damage in lipids, not proteins, and altered antioxidant enzyme activity, when compared to control organisms. Interestingly, we did not observe any correlation between the pollutants and the oxidative stress parameters evaluated in this study. Thus, we cannot rule out that a synergistic effect between the environmental variables and the pollutants is causing the oxidative stress in these oysters.

Campylobacter infection of young children in Colombia and its impact on the gastrointestinal environment.

Campylobacter infections are a leading cause of bacterial-derived gastroenteritis worldwide with particularly profound impacts on pediatric patients in low-and-middle income countries. It remains unclear how Campylobacter impacts these hosts, though it is becoming increasingly evident that it is a multifactorial process that depends on the host immune response, the gastrointestinal microbiota, various bacterial factors, and host nutritional status. Since these factors likely vary between adult and pediatric patients in different regions of the world, it is important that studies define these attributes in well characterized clinical cohorts in diverse settings. In this study, we analyzed the fecal microbiota and the metabolomic and micronutrient profiles of asymptomatic and symptomatic pediatric patients in Colombia that were either infected or uninfected with Campylobacter during a case-controlled study on acute diarrheal disease. Here, we report that the microbiome of Campylobacter- infected children only changed in their abundance of Campylobacter spp. despite the inclusion of children with or without diarrhea. In addition to increased Campylobacter, computational models were used to identify fecal metabolites that were associated with Campylobacter infection and found that glucose-6-phosphate and homovanillic acid were the strongest predictors of infection in these pediatric patients, which suggest that colonocyte metabolism are impacted during infection. Despite changes to the fecal metabolome, the concentrations of intestinal minerals and trace elements were not significantly impacted by Campylobacter infection, but were elevated in uninfected children with diarrhea. Importance: Gastrointestinal infection with pathogenic Campylobacter species has long been recognized as a significant cause of human morbidity. Recently, it has been observed that pediatric populations in low-and-middle income countries are uniquely impacted by these organisms in that infected children can be persistently colonized, develop enteric dysfunction, and exhibit reduced development and growth. While the association of Campylobacter species with these long-term effects continues to emerge, the impact of infection on the gastrointestinal environment of these children remains uncharacterized. To address this knowledge gap, our group leveraged clinical samples collected during a previous study on gastrointestinal infections in pediatric patients to examine the fecal microbiota, metabolome, and micronutrient profiles of those infected with Campylobacter species, and found that the metabolome was impacted in a way that suggests gastrointestinal cell metabolism is affected during infection, which is some of the first data indicating how gastrointestinal health in these patients may be affected.

Evaluation of pollution in Camichin estuary (Mexico): pro-oxidant and antioxidant response in oyster (Crassostrea corteziensis).

The physiological system of molluscs, particularly pro-oxidant and antioxidant mechanisms, could be altered by pollutants and induce disturbance on health status and productive parameters of aquatic organisms, such as oyster. Therefore, the aim of this study was to evaluate the chemical contamination in water (total metals and polycyclic aromatic hydrocarbons) and oxidative stress parameters in oysters (Crassostrea corteziensis) in Camichin estuary, located in Mexican Tropical Pacific. The results obtained showed the presence of arsenic, lead and zinc, as well as naphthalene, pyrene and benzo[a]pyrene in concentrations relatively higher than criteria established by local and international guidelines. Regarding the biomarkers of oxidative stress response (H2O2 and O2 concentration, catalase activity, lipid peroxidation, and hydroperoxide concentration), differences between oyster from estuary and control group were significant. These results indicate that these pollutants could be related with oxidative stress detected in oyster.

Protein stability at a carbon nanotube interface.

The interactions of proteins with solid surfaces occur in a variety of situations. Motivated by the many nanoengineering applications of protein-carbon nanotube hybrids, we investigate the conformational transitions of hen egg white lysozyme adsorbed on a carbon nanotube. Using a C(α) structure-based model and replica exchange molecular dynamics, we show how the folding/unfolding equilibrium of the adsorbed protein varies with the strength of its coupling to the surface. The stability of the native state depends on the balance between the favorable entropy and unfavorable enthalpy change on adsorption. In the case of a weakly attractive surface when the former dominates, the protein is stabilized. In this regime, the protein can fold and unfold while maintaining the same binding fraction. With increasing surface attraction, the unfavorable enthalpic effect dominates, the native state is destabilized, and the protein has to extensively unbind before changing states from unfolded to folded. At the highest surface coupling, the entropic penalty of folding vanishes, and a folding intermediate is strongly stabilized. In this intermediate state, the α-domain of lysozyme is disrupted, while the ß-sheet remains fully structured. We rationalize the relative stability of the two domains on the basis of the residue contact order.

Acetylcholinesterase and metallothionein in oysters (Crassostrea corteziensis) from a subtropical Mexican Pacific estuary.

Substantial efforts have been devoted to developing and applying biomarkers for ecological risk assessment. Bivalve mollusks, such as mussels and oysters, are commonly used in environmental monitoring programs because of their wide geographical distribution, great sensitivity to environmental pollutants, and ability to accumulate anthropogenically derived chemicals at a high rate. Acetylcholinesterase (AChE) activity and metallothionein (MT's) content are representative specific biomarkers that indicate the presence of anticholinesterasic compounds (like organophosphorus and carbamate pesticides) and metals, respectively. The aim of this study was to evaluate AChE activity and MT's content in Crassostrea corteziensis from Boca de Camichín estuary. The results obtained here showed that AChE activity was 65% lower in oysters from Boca de Camichín than in control organisms. In contrast, MT's content in collected organisms was not statistically different from that in control organisms. AChE activity and MT's content in oysters could be used as early biomarkers of effects and exposure to pesticides and heavy metals, respectively, in aquatic environments.

PON1 status and homocysteine levels as potential biomarkers for cardiovascular disease.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death. The mainly risks factors for CVD are diabetes, hypertension and high levels of homocysteine (Hcys), among others. Paraoxonase 1 (PON1) has been proposed as an antiatherogenic target for its ability to hydrolyzing oxi-Low-Density-Lipoproteins (LDL) and Hcys-thiolactone. Thus, the aim of the present study was to evaluate the association of Hcys levels, and the activities and concentration of PON1, as well as vitamin B from the diet with a risk for CVD. METHODS: A case-control study was carry out in patients with cardiovascular diseases (CVD), Arterial hypertension, but not CVD (AH), and in healthy controls (control group) from the Mexican Institute of Social Security. Lipid profile, intake of vitamin B, Hcys, serum amyloid A (SAA), PON1 concentration, and PON1 activities (Arylesterase activity (ARE), Lactonase activity (LAC), and CMPA activity (CMPA)) were evaluated. RESULTS: The CVD group had the highest concentration of Hcys and SAA than in the AH and control groups (p < 0.01). ARE, LAC, and CMPA activities and PON1 concentration were lowest in the CVD group. A positive-independent association between Hcys levels and CVD was found (OR = 2.09; 95% CI: 1.69-2.56) and this increase when it was adjusted by age, BMI, ApoA1, vitamin B intake, SAA, and PON1 (OR = 14.41; 95% CI: 1.75-118.71). LAC and CMPA, as well as PON1 concentration, were inversely associated with CVD. CONCLUSION: LAC activity, PON1 concentration, and Hcys levels might be good biomarkers for CVD and their association could be modified by the intake of vitamin B.

Ib-M6 Antimicrobial Peptide: Antibacterial Activity against Clinical Isolates of Escherichia coli and Molecular Docking.

The Ib-M6 peptide has antibacterial activity against non-pathogenic Escherichia coli K-12 strain. The first part of this study determines the antibacterial activity of Ib-M6 against fourteen pathogenic strains of E. coli O157:H7. Susceptibility assay showed that Ib-M6 had values of Minimum Inhibitory Concentration (MIC) lower than streptomycin, used as a reference antibiotic. Moreover, to predict the possible interaction between Ib-M6 and outer membrane components of E. coli, we used molecular docking simulations where FhuA protein and its complex with Lipopolysaccharide (LPS-FhuA) were used as targets of the peptide. FhuA/Ib-M6 complexes had energy values between -39.5 and -40.5 Rosetta Energy Units (REU) and only one hydrogen bond. In contrast, complexes between LPS-FhuA and Ib-M6 displayed energy values between -25.6 and -40.6 REU, and the presence of five possible hydrogen bonds. Hence, the antimicrobial activity of Ib-M6 peptide shown in the experimental assays could be caused by its interaction with the outer membrane of E. coli.

PON1 lactonase activity and its association with cardiovascular disease.

BACKGROUND: Paraoxonase 1 (PON1) is important in the development of atherosclerosis, and it has become the subject of intensive research. Our aim was to evaluate the association of serum PON1 activity and polymorphisms with cardiovascular disease (CVD) using four different substrates. MATERIALS AND METHODS: Activity of PON1-related to arylesterase (AREase and 4-CMPAse), paraoxonase (PONase), and lactonase (LACase), and polymorphisms (A-162G, T-108C, L55M, and Q192R) were evaluated in subjects with CVD, cardiovascular risk factor (CFR), and controls. An ordered logistic-regression analysis of PON1 phenotypes was performed in the CVD group with respect to the control group. RESULTS AND CONCLUSIONS: Logistic-regression analysis showed that CC-108 genotype was associated with CRF and CVD. The CVD group had the lowest activities of PON1. The LACase might be a better biomarker for CVD (OR, 0.52; 95% CI, 0.44-0.61) followed by CMPAse (OR, 0.82; 95% CI, 0.77-0.86), AREase (OR, 0.98; 95% CI, 0.97-0.99) and PONase (OR, 0.99, 95% CI, 0.99-0.99). Logistic regression of PON1 phenotypes by haplotypes showed that LACase activity was not influenced by the polymorphisms and that it could be a new potential biomarker in the development of CVD. Larger scale longitudinal studies are required.

Arginine-rich peptides destabilize the plasma membrane, consistent with a pore formation translocation mechanism of cell-penetrating peptides.

Recent molecular-dynamics simulations have suggested that the arginine-rich HIV Tat peptides translocate by destabilizing and inducing transient pores in phospholipid bilayers. In this pathway for peptide translocation, Arg residues play a fundamental role not only in the binding of the peptide to the surface of the membrane, but also in the destabilization and nucleation of transient pores across the bilayer. Here we present a molecular-dynamics simulation of a peptide composed of nine Args (Arg-9) that shows that this peptide follows the same translocation pathway previously found for the Tat peptide. We test experimentally the hypothesis that transient pores open by measuring ionic currents across phospholipid bilayers and cell membranes through the pores induced by Arg-9 peptides. We find that Arg-9 peptides, in the presence of an electrostatic potential gradient, induce ionic currents across planar phospholipid bilayers, as well as in cultured osteosarcoma cells and human smooth muscle cells. Our results suggest that the mechanism of action of Arg-9 peptides involves the creation of transient pores in lipid bilayers and cell membranes.

Transcriptional regulation of human Paraoxonase 1 by nuclear receptors.

Paraoxonase 1 (PON1) is a calcium-dependent lactonase synthesized primarily in the liver and secreted into the plasma, where it is associates with high density lipoproteins (HDL). PON1 acts as antioxidant preventing low-density lipoprotein (LDL) oxidation, a process considered critical in the initiation and progression of atherosclerosis. Additionally, PON1 hydrolyzes and detoxifies some toxic metabolites of organophosphorus compounds (OPs). Thus, PON1 activity and expression levels are important for determining susceptibility to OPs intoxication and risk of developing diseases related to inflammation and oxidative stress. Increasing evidence has demonstrated the modulation of PON1 expression by many factors is due to interaction with nuclear receptors (NRs). Here, we briefly review the studies in this area and discuss the role of nuclear receptors in the regulation of PON1 expression, as well as how understanding these mechanisms may allow us to manipulate PON1 levels to improve drug efficacy and treat disease.

Delta-aminolevulinic Acid dehydratase genotype and its relationship with blood lead and zinc protoporphyrin levels in lead-exposed children living in a smelter community in northern Mexico.

The implications of delta-aminolevulinic acid dehydratase (ALAD) polymorphism for lead kinetics and toxicity have been mainly studied in occupationally exposed adults. Therefore, our purpose was to evaluate the distribution of ALAD genotype and its association with biomarkers of exposure (PbB levels) and effect (Blood ZPP) among children living in a smelter community in Mexico. We recruited 569 children from nine elementary schools close to a smelter site. PbB was determined by electrothermal atomic absorption spectrometry. A polymerase chain reaction (PCR)-based protocol was used for ALAD genotyping. Zinc protoporphyrin (ZPP) in blood was measured by direct fluorometry. Most children (93.15%) were homozygous for ALAD (1-1), 6.67% were heterozygous for ALAD for (1-2), and one child was homozygous for ALAD (2-2). There was an increased proportion of ALAD (1-2/2-2) genotype with respect to PbB levels. The ZPP geometric mean was slightly higher in ALAD (1-1) genotype children (63.48 mu mol ZPP/mol Hb) than in those having the ALAD-2 genotype (58.22 mu mol ZPP/mol Hb; p = 0.051). Linear and quadratic models showed significant relationships between ZPP and PbB. A significant increase in the odds ratio (OR) for the effect of lead exposure on ZPP levels was observed for ALAD (1-1) children having PbB values above 20 mu g/dL, as compared to those having PbB levels below 10 mu g/dL (OR = 2.95, 95% CI = 1.45-5.97; p = 0.003), whereas no significant increases were observed for the ALAD (1-2/2-2) children. In summary, our results suggest that heme biosynthesis was less affected in ALAD (1-2/2-2) lead-exposed children than in those carrying the ALAD (1-1) genotype.

Effects of diazinon on the lymphocytic cholinergic system of Nile tilapia fish (Oreochromis niloticus).

Fish rearing under intensive farming conditions can be easily disturbed by pesticides, substances that have immunotoxic properties and may predispose to infections. Organophosphorus pesticides (OPs) are widely used in agricultural activities; however, the mechanism of immunotoxicity of these substances is unclear. The aim of this study was to evaluate the effect of diazinon pesticides (OPs) on the cholinergic system of immune cells as a possible target of OP immunotoxicity. We evaluated ACh levels and cholinergic (nicotinic and muscarinic) receptor concentration. Additionally, AChE activity was evaluated in mononuclear cells of Nile tilapia (Oreochromis niloticus), a freshwater fish mostly cultivated in tropical regions around the world. The obtained results indicate that acute exposure to diazinon induces an increase in ACh concentration and a decrease in nAChR and mAChR concentrations and AChE activity in fish immune cells, This suggests that the non-neuronal lymphocytic cholinergic system may be the main target in the mechanism of OP immunotoxicity. This study contributes to the understanding of the mechanisms of immunotoxicity of pollutants and may help to take actions for animal health improvement.

Transcriptional regulation of human paraoxonase 1 by PXR and GR in human hepatoma cells.

Human paraoxonase 1 (PON1) is A-esterase synthesized in the liver and secreted into the plasma, where it associates with HDL. PON1 acts as an antioxidant preventing lipid oxidation and detoxifies a wide range of substrates, including organophosphate compounds. The variability of PON1 (enzyme activity/serum levels) has been attributed to internal and external factors. However, the molecular mechanisms involved in the transcriptional regulation of PON1 have not been well-studied. The aim of this study was to evaluate and characterize the transcriptional activation of PON1 by nuclear receptors (NR) in human hepatoma cells. In silico analysis was performed on the promoter region of PON1 to determine the response elements of NR. Real-time PCR was used to evaluate the effect of specific NR ligands on the mRNA levels of genes regulated by NR and PON1. The results indicated that NR response elements had 95% homology to pregnenolone (PXR), glucocorticoids (GR), retinoic acid (RXR) and peroxisomes proliferator-activated receptor alpha (PPARα). Treatments with Dexamethasone (GR ligand), Rifampicin (PXR ligand) and TCDD (AhR ligand) increased the mRNA levels of PON1 at 24 and 48 h. We showed that the activation of GR by Dexamethasone results in PON1 gene induction accompanied by an increase in activity levels. In conclusion, these results demonstrate that GR regulates PON1 gene transcription through directly binding to NR response elements at -95 to -628 bp of the PON1 promoter. This study suggests new molecular mechanisms for the transcriptional regulation of PON1 through a process involving the activation of PXR.

Cytostatic and genotoxic effect of temephos in human lymphocytes and HepG2 cells.

Temephos is an organophosphorus pesticide that is used in control campaigns against Aedes aegypti mosquitoes, which transmit dengue. In spite of the widespread use of temephos, few studies have examined its genotoxic potential. The aim of this study was to evaluate the cytotoxic, cytostatic and genotoxic effects of temephos in human lymphocytes and hepatoma cells (HepG2). The cytotoxicity was evaluated with simultaneous staining (FDA/EtBr). The cytostatic and genotoxic effects were evaluated using comet assays and the micronucleus technique. We found that temephos was not cytotoxic in either lymphocytes or HepG2 cells. Regarding the cytostatic effect in human lymphocytes, temephos (10 µM) caused a significant decrease in the percentage of binucleated cells and in the nuclear division index as well as an increase in the apoptotic cell frequency, which was not the case for HepG2 cells. The comet assay showed that temephos increased the DNA damage levels in human lymphocytes, but it did not increase the MN frequency. In contrast, in HepG2 cells, temephos increased the tail length, tail moment and MN frequency in HepG2 cells compared to control cells. In conclusion, temephos causes stable DNA damage in HepG2 cells but not in human lymphocytes. These findings suggest the importance of temephos biotransformation in its genotoxic effect.

Simulations of CRP:(cAMP)2 in noncrystalline environments show a subunit transition from the open to the closed conformation.

The CRP:cAMP complex functions as a transcription factor that facilitates RNA polymerase recognition of several bacterial promoters. Detailed crystal structure information is available for CRP:(cAMP)2 and for CRP:(cAMP)2 complexed with DNA. In the crystalline environment, CRP:(cAMP)2 subunits are asymmetrically related; one subunit has a closed conformation and the other has an open conformation. The CRP:(cAMP)2 complexed with DNA shows both subunits in a closed conformation. We have studied the molecular dynamics of CRP:(cAMP)2 in noncrystalline environments. CRP:(cAMP)2 was simulated for 625 ps in vacuo and for 140 ps in solution. The crystal structure of CRP:(cAMP)2 in the absence of DNA was used as the initial conformation. Molecule optimal dynamic coordinates (MODCs) (García A, 1992, Phys Rev Lett 68:2696) were used to analyze protein conformations sampled during the course of the simulations. Two MODCs define a transition of the open subunit to a closed subunit conformation during the first 125 ps of simulation in vacuo; the resulting subunit conformation is similar to that observed in CRP:(cAMP)2:DNA crystals. Simulation of CRP:(cAMP)2 in solution showed that a transition from the open to the closed state also occurs when water is explicitly included in the calculations. These calculations suggest that the asymmetric conformation of CRP:(cAMP)2 is stabilized by crystal lattice interactions. The predicted solution conformation is more symmetric, with both subunits in a closed conformation.

Temperature dependence of the solubility of non-polar gases in water.

An explanation is provided for the experimentally observed temperature dependence of the solubility and the solubility minimum of non-polar gases in water. The influence of solute size and solute-water attractive interactions on the solubility minimum temperature is investigated. The transfer of a non-polar solute from the ideal gas into water is divided into two steps: formation of a cavity in water with the size and shape of the solute and insertion of the solute in this cavity which is equivalent to 'turning on' solute-water attractive interactions. This two step process divides the excess chemical potential of the non-polar solute in water into repulsive and attractive contributions, respectively. The reversible work for cavity formation is modeled using an information theory model of hydrophobic hydration. Attractive contributions are calculated by modeling the water structure in the vicinity of non-polar solutes. These models make a direct connection between microscopic quantities and macroscopic observables. Moreover, they provide an understanding of the peculiar temperature dependences of the hydration thermodynamics from properties of pure water; specifically, bulk water density and the water oxygen-oxygen radial distribution function.