John B. Goodenough's Role in Solid State Chemistry Community: A Thrilling Scientific Tale Told by a French Chemist.

In this tribute to John B. Goodenough I will describe how John's talk on the metal-to-nonmetal transition of vanadium oxide VO2, presented at the Bordeaux Conference (September 1964) attended by inorganic chemists, metallurgists, crystallographers, thermodynamicists and physicists, provided a pioneering vision of interdisciplinary research to come. John gave a complete description of the paradigm on how the physical properties of a solid depend on its structure and bonding, by employing the chemical notions as local distortions and interatomic distances as well as the physics notions such as band width and the Hubbard on-site repulsion U. I will illustrate how inspiring John's ideas were, by discussing the research examples of my own research group in the sixties-seventies. The fundamental approach of John B. Goodenough to Solid State Chemistry, leading particularly to lithium battery applications, is at the heart of the 2019 Nobel Prize awarded to John.

Paul Hagenmuller.

Paul Hagenmuller, honorary professor at the Université de Bordeaux, passed away at the age of 95 on January 7, 2017. Hagenmuller was one of the founders of solid-state chemistry at the interface between chemistry, physics, and material science, with contributions including high oxidation states in transition metal oxides, magnesium hydride for hydrogen-storage applications, and synthesis of copper perovskites.

Status of trivalent copper and charge-transfer excitons in high-TC cuprates.

A chemical bonding approach based on tight-binding cluster and band calculations, taking into account on-site Coulomb repulsion (Hubbard U parameter) to differentiate doubly and singly occupied states, was applied to high- T C superconducting cuprates and related compounds. This work provides rational insight and explanations for issues such as (i) the actual oxidation number Cu (I+) for formally trivalent copper in oxides such as La 2Li 1/2Cu 1/2O 4, (ii) the dominant oxygen character of the doping holes in (CuO 2) ( n- ) planes, (iii) the Mott-Hubbard character of the insulator-to-metal transition triggered by hole doping, leading to an oxygen-to-copper charge transfer of avalanche type, (iv) the occurrence of an excitonic phase with anisotropic Frenkel-type excitons, (v) the role of Coulomb interactions between excitons and between doping holes and their exciton surroundings, and (vi) the on-time pairing of doping holes by means of an "excitonic glue".

Real-space pairing through charge transfer excitons in high-TC cuprates.

While approaching a Mott-Hubbard transition by hole doping of the pristine La(2)CuO(4) cuprate, excitons are created because of exciton-exciton and exciton-doping hole stabilizing interactions. Here, excitons are of charge-transfer Frenkel-type, with effective Cu(+)O(-) electrical dipoles that solvate the doping charges. Assuming a moderate screening by charge carriers, we show that mobile exciton-solvated doping holes should be associated in pairs either by a deep energy well or as thermodynamically stable pairs that can glide in the [100] or [010] direction after Bose condensation. Exciton-exciton dipolar interactions constitute thus the "pairing glue" in this model, which is based on instantaneous interactions and intrinsically differs from the previous excitonic models, in which BCS virtual phonons were replaced by virtual excitons.

Plasma palmitoleic acid, a product of stearoyl-coA desaturase activity, is an independent marker of triglyceridemia and abdominal adiposity.

BACKGROUND AND AIM: In an animal model VLDL-triglyceride secretion is highly dependent on stearoyl-coA desaturase (SCD) activity and could explain abdominal fattening. The aim was to assess the relationship of plasma palmitoleic acid content, a product of SCD activity, with triglyceridemia and abdominal adiposity in humans. METHODS: We evaluated 134 healthy men. Plasma palmitoleic acid content was used as an indirect measurement of SCD activity because that enzyme catalyzes the desaturation from saturated to monounsaturated fatty acids and palmitoleic acid intake is very small. RESULTS: Subjects with triglycerides > or =75th percentile had a higher palmitoleic acid content than those with triglycerides <75th percentile (3.8+/-0.8 vs 2.8+/-0.9%, p<0.0001). Triglyceridemia was strongly correlated with palmitoleic acid content (PAC) (r=0.533, p<0.001). Mean triglyceridemia was 114% higher (1.43+/-0.75 vs 0.67+/-0.22 mmol/l) in the fourth quartile than in the first quartile of palmitoleic acid content. In a stepwise logistic regression analysis, palmitoleic acid content was the most strongly and independently associated parameter with triglyceridemia, and also with waist circumference when triglyceridemia was not included in the analysis. CONCLUSION: Plasma palmitoleic acid content, a product of SCD activity, is an independent marker of triglyceridemia and abdominal adiposity in men. This enzyme (SCD) could represent a target for prevention and treatment of these metabolic disorders in particular in subjects at risk of developing a metabolic syndrome.

Sigma ESR: an erythrocyte sedimentation rate adjusted for the hematocrit and hemoglobin concentration.

The aim of the study was to simplify the first Sigma erythrocyte sedimentation rate (ESR) method (manual hematocrit adjustment to 0.35, sum of 4 sedimentation levels) and to confirm its clinical relevance. The erythrocyte sedimentation rate of undiluted blood samples from 576 patients was measured simultaneously with and without manual hematocrit adjustment to 0.35 to identify an approximate expression of the area under the curve and a formula for calculating the Sigma ESR. The Sigma ESR formula was based on the sum of 2 unadjusted sedimentation levels, at 30 and 60 minutes, together with the hematocrit value and the hemoglobin concentration. Sigma ESR values in 274 healthy subjects showed a gaussian distribution, no difference between men and women, and no significant increase with age. In recent-onset arthritis or disk-related lumbosciatic syndrome, Sigma ESR seemed to be a more reliable marker of inflammation than the Westergren ESR and C-reactive protein. We also obtained data clarifying the controversial relationship of ESR with lipid levels and arterial hypertension.

Association between estrogen and androgen receptor genes and prostate cancer risk.

OBJECTIVE: Prostate cancer (PC) is one of the principal causes of death among men. Steroid hormones are involved in normal prostate growth and carcinogenesis. The purpose of our study was to investigate the effects on PC risk of polymorphisms from three steroid hormone receptor genes: the androgen (AR), and the alpha (ESR1) and beta (ESR2) estrogen receptors. DESIGN AND METHODS: The study was performed on a Caucasian population of 1045 PC patients and 814 controls. Using a logistic regression model, the different alleles and genotypes from those polymorphisms were analyzed according to case/control status, the tumor aggressiveness, and the age at onset. RESULTS: A significant association between PC risk and the pooled 4/5, 5/6, and 6/6 genotypes of the GGGA repeat located in the first intron of ESR1 (odds ratio (OR)=3.00, 95% CI=1.32-6.82, P=0.008) was observed. When we stratified the cases, this association was confined to patients with a Gleason score of 2-4 (OR=8.34, 95% CI=2.91-23.91, P<0.0001) or late onset PC (OR=2.91, 95% CI=1.22-6.93, P=0.016). An association between a short AR CAG repeat (less than 17 repeats) was also observed among patients with late onset PC (OR=2.34, 95% CI=1.15-4.76, P=0.019). CONCLUSIONS: These findings suggest that the GGGA repeat from ESR1 and the CAG repeat from AR may be associated with risk of late onset PC.

Fiber evanescent wave spectroscopy using the mid-infrared provides useful fingerprints for metabolic profiling in humans.

Fiber evanescent wave spectroscopy (FEWS) explores the mid-infrared domain, providing information on functional chemical groups represented in the sample. Our goal is to evaluate whether spectral fingerprints obtained by FEWS might orientate clinical diagnosis. Serum samples from normal volunteers and from four groups of patients with metabolic abnormalities are analyzed by FEWS. These groups consist of iron overloaded genetic hemochromatosis (GH), iron depleted GH, cirrhosis, and dysmetabolic hepatosiderosis (DYSH). A partial least squares (PLS) logistic method is used in a training group to create a classification algorithm, thereafter applied to a test group. Patients with cirrhosis or DYSH, two groups exhibiting important metabolic disturbances, are clearly discriminated from control groups with AUROC values of 0.94+/-0.05 and 0.90+/-0.06, and sensibility/specificity of 8684% and 8787%, respectively. When pooling all groups, the PLS method contributes to discriminate controls, cirrhotic, and dysmetabolic patients. Our data demonstrate that metabolic profiling using infrared FEWS is a possible way to investigate metabolic alterations in patients.

Combination of polymorphisms from genes related to estrogen metabolism and risk of prostate cancers: the hidden face of estrogens.

PURPOSE: The association between common functional polymorphisms from the CYP17, CYP19, CYP1B1, and COMT genes involved in the estrogen metabolism and the risk of prostate carcinoma was evaluated. PATIENTS AND METHODS: The study investigated 1,983 white French men (1,101 patients with prostate cancer and 882 healthy controls) aged between 40 and 98 years. The different alleles and genotypes were analyzed according to case-control status, aggressiveness pattern of the tumors, age at onset, and family history of cancers. RESULTS: The VV (high activity) genotype of the V432L polymorphism from CYP1B1 (odds ratio [OR] = 1.36; 95% CI, 1.03 to 1.79; P = .031), and the long allele (> 175 bp) of the TTTA repeat from CYP19 (OR, 1.26; 95% CI, 1.08 to 1.47; P = .003) were significantly associated with the risk of prostate cancer. An additive effect was observed when we combined the two at-risk alleles (OR = 1.63; 95% CI, 1.24 to 2.13; P < .001). The association was stronger for the CYP1B1 VV genotype (OR = 1.55; 95% CI, 1.13 to 2.13; P = .007) among the group of patients with highly aggressive disease. Stratification by age at onset showed that the associations of CYP1B1 and CYP19 variants were largely confined to the younger prostate cancer patients. CONCLUSION: This association between polymorphisms from genes related to estrogen metabolism and prostate cancer risk suggest new clinical considerations in the management of prostate cancer: the development of new prevention trials based on genetic profiling and the evaluation of specific inhibitors involving the estrogen pathways.

Relative validity and reproducibility of a 14-item semi-quantitative food frequency questionnaire for cardiovascular prevention.

BACKGROUND: Dietary habits play a major role in cardiovascular disease risk but few simple nutrition assessment tools are available for clinical practice. We developed a 14-item food frequency questionnaire to evaluate dietary patterns in relation with coronary risk in a French population. DESIGN AND METHODS: This food frequency questionnaire gave different scores of intake: saturated fatty acids (six questions), mono-unsaturated fatty acids, Omega-3 and Omega-6/Omega-3 polyunsaturated fatty acids (five questions), and fruits and vegetables (three questions). Validity was assessed against a 7-day dietary history (n = 49 subjects) and against biomarkers (n = 181). The food frequency questionnaire was also administered twice with an interval of 15 days to evaluate its reproducibility (n = 20). RESULTS: Validity against dietary history was assessed with Spearman correlation coefficients which ranged from 0.47 (fruits and vegetables) to 0.63 (polyunsaturated fatty acids/saturated fatty acids) (all P < 0.05), with a mean value of 0.54. On average, 39% of the subjects were classified in the same quartile with the food frequency questionnaire and the dietary history and 84% in the same or adjacent quartile. Biomarker-based validity using Spearman correlation coefficients varied from 0.21 (saturated fatty acids) to 0.53 (Omega-3 polyunsaturated fatty acids) (all P < 0.05), with a mean value of 0.35. On average, 37% of the participants were classified in the same quartile with the food frequency questionnaire and the corresponding biomarkers and 73% in the same or adjacent quartile. Reproducibility assessed by the intraclass correlation coefficient ranged from 0.71 (mono-unsaturated fatty acids) to 0.93 (global score), with a mean value of 0.81. CONCLUSION: We validated a short food frequency questionnaire for dietary pattern assessment in coronary prevention.

Structural trends and chemical bonding in Te-doped silicon clathrates.

The recently discovered tellurium-doped silicon clathrates, Te7+xSi20-x and Te16Si38, both low- and high-temperature forms (cubic and rhombohedral, respectively), exhibit original structures that are all derived from the parent type I clathrate G8Si46 (G = guest atom). The similarities and differences between the structures of these compounds and that of the parent one are analyzed and discussed on the basis of charge distribution and chemical bonding considerations. Because of the particular character of the Te atom, these compounds appear to be at the border between the clathrate and polytelluride families.

Phenotypic expression in detected C282Y homozygous women depends on body mass index.

BACKGROUND/AIMS: In HFE-related haemochromatosis, a large proportion of C282Y homozygotes, especially women, are not detected by phenotypic screening using transferrin saturation. The aim of this study was to identify the clinical and biochemical factors associated with non-expression of the disease as defined as transferrin saturation <45%. METHODS: The study was performed in 78 (57 women and 21 men) C282Y homozygotes identified through a large-scale screening program conducted on 19,644 French subjects. Biometric, clinical and biochemical variables including those susceptible to influence body iron stores were tested for association with transferrin saturation levels <45%. RESULTS: Non-expression was observed in 26/57 (46%) women and in 5/21 (24%) men. At multivariate analysis, female gender (OR: 16.5, 95%CI 1.8-146.5; P = 0.012), body mass index (OR: 1.21, 95%CI 1.02-1.44; P = 0.027), haemoglobin levels (OR: 0.88, 95%CI 0.81-0.97; P = 0.012) and serum ferritin levels (OR: 0.99, 95%CI 0.98-1.00; P = 0.007) were significantly and independently associated with a non-expressing phenotype. CONCLUSIONS: Excess body mass is commonly associated with the lack of phenotypic expression in detected C282Y homozygotes. This should be kept in mind with respect to the design and cost-effectiveness of phenotypic screening programs for haemochromatosis.

Redox active plasma iron in C282Y/C282Y hemochromatosis.

Labile plasma iron (LPI) represents the redox active component of non-transferrin-bound iron (NTBI). Its presence in thalassemic patients has been recently reported. The aim of the present study was to quantify LPI in HFE genetic hemochromatosis (GH) and to characterize the mechanisms accounting for its appearance. We studied 159 subjects subdivided into the following groups: (1) 23 with iron overloaded GH; (2) 14 with iron-depleted GH; (3) 26 with dysmetabolic hepatosiderosis; (4) 33 with alcoholic cirrhosis; (5) 63 healthy controls. Both NTBI and LPI were substantially higher in patients with iron-overloaded GH than in those with iron-depleted GH or in healthy controls. LPI was significantly correlated with serum transaminase increase in this group. LPI was elevated in the alcoholic cirrhosis subgroup of severely affected patients. LPI was found essentially when transferrin saturation exceeded 75%, regardless of the etiologic condition. Transferrin saturation above 75% was related to iron overload in GH and to liver failure in alcoholic cirrhosis. LPI is present in C282Y/C282Y hemochromatosis and may be a marker of toxicity due to its potential for catalyzing the generation of reactive oxygen radicals in vivo.

Serum ceruloplasmin and ferroxidase activity are not decreased in hepatic failure related to alcoholic cirrhosis: clinical and pathophysiological implications.

BACKGROUND: A decrease in serum ceruloplasmin (Cp), a protein involved in iron metabolism through its ferroxidase activity, is classically claimed to be observed in severe hepatic failure of non-wilsonian chronic liver disease and therefore to be a confounding factor for the diagnosis of Wilson's disease. Moreover, a simultaneous decrease in ferroxidase activity could be hypothesized as playing a role in the development of the hepatic siderosis frequently observed in advanced chronic liver diseases. The aim of this study was to test the validity of these two statements. METHODS: This study investigated Cp, determined by immunonephelometry, and its ferroxidase 1 activity determined by Erel's method in 33 male patients with severe alcoholic cirrhosis compared with 66 healthy male volunteers, selected on strict criteria. Each patient was age-matched with two controls. Nonparametric tests were used for statistical analysis. RESULTS: The mean values of Cp were significantly higher in cirrhotic patients as compared with control subjects. A significant elevation of Cp was also observed in the subgroup of 11 cirrhotic patients who had normal serum C-reactive protein levels. The mean values of ferroxidase 1 activity were similar to those obtained in control subjects. CONCLUSIONS: Low serum Cp should not be expected in severe hepatic cirrhosis of non-wilsonian origin. Hepatic siderosis in advanced chronic liver disease is likely to be unrelated to decreased ferroxidase activity.

Serum ceruloplasmin and ferroxidase activity are decreased in HFE C282Y homozygote male iron-overloaded patients.

BACKGROUND/AIMS: A body of evidence suggests that ceruloplasmin (Cp), the major serum copper-containing protein, acts in iron metabolism due to its ferroxidase activity which appears essential for iron movements and exchanges. METHODS: The present study investigated the serum levels of Cp and its ferroxidase activity in 53 C282Y homozygote genetic hemochromatosis (38 iron overloaded, 15 iron depleted) patients as compared to age and sex-matched healthy volunteers. RESULTS: Serum levels of Cp were significantly decreased in iron-overloaded male hemochromatotic patients vs. the control group (P=0.02). Furthermore, serum ferroxidase activity was strongly and significantly lower in iron-overloaded male hemochromatotic patients (P<0.001). In contrast, in iron-depleted male hemochromatotic patients, who were under maintenance therapy by regular phlebotomies, serum levels of Cp and ferroxidase activity were not statistically different from those observed in controls. CONCLUSIONS: These data: (i) show that serum Cp and ferroxidase activity are decreased when C282Y homozygote men are iron overloaded and normal when iron depleted; (ii) suggest that iron may modulate the Cp gene expression; and (iii) raise the issue of the putative role of decreased serum ferroxidase activity in the phenotypic expression of HFE-1 hereditary hemochromatosis.

Gender-specific phenotypic expression and screening strategies in C282Y-linked haemochromatosis: a study of 9396 French people.

Most features of C282Y-linked haemochromatosis support the implementation of population screening of the disorder in Caucasians. However, the penetrance of C282Y homozygosity is poorly documented and the strategy for population screening remains debated. Nine thousand three hundred and ninety-six subjects (3367 men, aged 25-40 years, and 6029 women, aged 35-50 years), attending three Health Appraisal Centres, were genotyped and assessed with respect to clinical and biochemical signs of haemochromatosis. Discriminant, logistic regression and graphic analysis were used to predict homozygosity. Results were validated in 135 homozygotes detected through other family and population studies. Fifty-four subjects (10 men and 44 women) were homozygous for C282Y. All men had abnormal iron status and most had mild clinical symptoms compatible with haemochromatosis. Identification of all homozygous men required a transferrin saturation (TS) threshold of 50% in the study group (90% specificity) and of 40% in the validation group. Homozygous women differed clinically from non-homozygotes for the presence of distal arthralgias only (18%vs 6%, P < 0.03). Thirteen (29%) were iron-deficient (serum ferritin < 13 micro g/l) and undetectable by biochemical tests. Although the population studied was not fully representative of the general population, our data strongly suggests that, in young men, large-scale screening for C282Y homozygosity is justified and can be achieved by using TS prescreening. However, in premenopausal women, large-scale screening remains to be justified with respect to the natural history of haemochromatosis and should be directly genotypic.