The role of adiposity in cardiometabolic traits:a Mendelian randomization analysis

The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach.

Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

Anti-TNF antibody-induced psoriasiform skin lesions in patients with inflammatory bowel disease are characterised by interferon-γ-expressing Th1 cells and IL-17A/IL-22-expressing Th17 cells and respond to anti-IL-12/IL-23 antibody treatment

Background We analysed incidence, predictors, histological features and specific treatment options of anti-tumour necrosis factor alpha (TNF-alpha) antibody-induced psoriasiform skin lesions in patients with inflammatory bowel diseases (IBD).

Design Patients with IBD were prospectively screened for anti-TNF-induced psoriasiform skin lesions. Patients were genotyped for IL23R and IL12B variants. Skin lesions were examined for infiltrating Th1 and Th17 cells. Patients with severe lesions were treated with the anti-interleukin (IL)-12/IL-23 p40 antibody ustekinumab.

Results Among 434 anti-TNF-treated patients with IBD, 21 (4.8%) developed psoriasiform skin lesions. Multiple logistic regression revealed smoking (p=0.007; OR 4.24, 95% CI 1.55 to 13.60) and an increased body mass index (p=0.029; OR 1.12, 95% CI 1.01 to 1.24) as main predictors for these lesions. Nine patients with Crohn's disease and with severe psoriasiform lesions and/or anti-TNF antibody-induced alopecia were successfully treated with the anti-p40-IL-12/IL-23 antibody ustekinumab (response rate 100%). Skin lesions were histologically characterised by infiltrates of IL-17A/IL-22-secreting T helper 17 (Th17) cells and interferon (IFN)-gamma-secreting Th1 cells and IFN-alpha-expressing cells. IL-17A expression was significantly stronger in patients requiring ustekinumab than in patients responding to topical therapy (p=0.001). IL23R genotyping suggests disease-modifying effects of rs11209026 (p.Arg381Gln) and rs7530511 (p.Leu310Pro) in patients requiring ustekinumab.

Conclusions New onset psoriasiform skin lesions develop in nearly 5% of anti-TNF-treated patients with IBD. We identified smoking as a main risk factor for developing these lesions. Anti-TNF-induced psoriasiform skin lesions are characterised by Th17 and Th1 cell infiltrates. The number of IL-17A-expressing T cells correlates with the severity of skin lesions. Anti-IL-12/IL23 antibody therapy is a highly effective therapy for these lesions.

Macrophage migration inhibitory factor (MIF) expression in human malignant gliomas contributes to immune escape and tumour progression

Macrophage migration inhibitory factor (MIF), which inhibits apoptosis and promotes angiogenesis, is expressed in cancers suppressing immune surveillance. Its biological role in human glioblastoma is, however, only poorly understood. We examined in-vivo expression of MIF in 166 gliomas and 23 normal control brains by immunohistochemistry. MIF immunoreactivity was enhanced in neoplastic astrocytes in WHO grade II glioma and increased significantly in higher tumour grades (III-IV). MIF expression was further assessed in 12 glioma cell lines in vitro. Quantitative RT-PCR showed that MIF mRNA expression was elevated up to 800-fold in malignant glioma cells compared with normal brain. This translated into high protein levels as assessed by immunoblotting of total cell lysates and by ELISA-based measurement of secreted MIF. Wild-type p53-retaining glioma cell lines expressed higher levels of MIF, which may be connected with the previously described role of MIF as a negative regulator of wild-type p53 signalling in tumour cells. Stable knockdown of MIF by shRNA in glioma cells significantly increased tumour cell susceptibility towards NK cell-mediated cytotoxicity. Furthermore, supernatant from mock-transfected cells, but not from MIF knockdown cells, induced downregulation of the activating immune receptor NKG2D on NK and CD8+ T cells. We thus propose that human glioma cell-derived MIF contributes to the immune escape of malignant gliomas by counteracting NK and cytotoxic T-cell-mediated tumour immune surveillance. Considering its further cell-intrinsic and extrinsic tumour-promoting effects and the availability of small molecule inhibitors, MIF seems to be a promising candidate for future glioma therapy.

Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated 1/42,000, 1/43,700 and 1/49,500 SNPs explained 1/421%, 1/424% and 1/429% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/I 2-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Prevalence of refractive error in Europe: the European Eye Epidemiology (E3) Consortium

To estimate the prevalence of refractive error in adults across Europe. Refractive data (mean spherical equivalent) collected between 1990 and 2013 from fifteen population-based cohort and cross-sectional studies of the European Eye Epidemiology (E³) Consortium were combined in a random effects meta-analysis stratified by 5-year age intervals and gender. Participants were excluded if they were identified as having had cataract surgery, retinal detachment, refractive surgery or other factors that might influence refraction. Estimates of refractive error prevalence were obtained including the following classifications: myopia ≤−0.75 diopters (D), high myopia ≤−6D, hyperopia ≥1D and astigmatism ≥1D. Meta-analysis of refractive error was performed for 61,946 individuals from fifteen studies with median age ranging from 44 to 81 and minimal ethnic variation (98 % European ancestry). The age-standardised prevalences (using the 2010 European Standard Population, limited to those ≥25 and <90 years old) were: myopia 30.6 % [95 % confidence interval (CI) 30.4–30.9], high myopia 2.7 % (95 % CI 2.69–2.73), hyperopia 25.2 % (95 % CI 25.0–25.4) and astigmatism 23.9 % (95 % CI 23.7–24.1). Age-specific estimates revealed a high prevalence of myopia in younger participants [47.2 % (CI 41.8–52.5) in 25–29 years-olds]. Refractive error affects just over a half of European adults. The greatest burden of refractive error is due to myopia, with high prevalence rates in young adults. Using the 2010 European population estimates, we estimate there are 227.2 million people with myopia across Europe.

Age- and Sex-Specific Causal Effects of Adiposity on Cardiovascular Risk Factors

Observational studies have reported different effects of adiposity on cardiovascular risk factors across age and sex. Since cardiovascular risk factors are enriched in obese individuals, it has not been easy to dissect the effects of adiposity from those of other risk factors. We used a Mendelian randomization approach, applying a set of 32 genetic markers to estimate the causal effect of adiposity on blood pressure, glycemic indices, circulating lipid levels, and markers of inflammation and liver disease in up to 67,553 individuals. All analyses were stratified by age (cutoff 55 years of age) and sex. The genetic score was associated with BMI in both nonstratified analysis (P = 2.8 × 10(-107)) and stratified analyses (all P < 3.3 × 10(-30)). We found evidence of a causal effect of adiposity on blood pressure, fasting levels of insulin, C-reactive protein, interleukin-6, HDL cholesterol, and triglycerides in a nonstratified analysis and in the <55-year stratum. Further, we found evidence of a smaller causal effect on total cholesterol (P for difference = 0.015) in the ≥55-year stratum than in the <55-year stratum, a finding that could be explained by biology, survival bias, or differential medication. In conclusion, this study extends previous knowledge of the effects of adiposity by providing sex- and age-specific causal estimates on cardiovascular risk factors.

Increasing Prevalence of Myopia in Europe and the Impact of Education

PURPOSE: To investigate whether myopia is becoming more common across Europe and explore whether increasing education levels, an important environmental risk factor for myopia, might explain any temporal trend.

DESIGN: Meta-analysis of population-based, cross-sectional studies from the European Eye Epidemiology (E(3)) Consortium.

PARTICIPANTS: The E(3) Consortium is a collaborative network of epidemiological studies of common eye diseases in adults across Europe. Refractive data were available for 61 946 participants from 15 population-based studies performed between 1990 and 2013; participants had a range of median ages from 44 to 78 years.

METHODS: Noncycloplegic refraction, year of birth, and highest educational level achieved were obtained for all participants. Myopia was defined as a mean spherical equivalent ≤-0.75 diopters. A random-effects meta-analysis of age-specific myopia prevalence was performed, with sequential analyses stratified by year of birth and highest level of educational attainment.

MAIN OUTCOME MEASURES: Variation in age-specific myopia prevalence for differing years of birth and educational level.

RESULTS: There was a significant cohort effect for increasing myopia prevalence across more recent birth decades; age-standardized myopia prevalence increased from 17.8% (95% confidence interval [CI], 17.6-18.1) to 23.5% (95% CI, 23.2-23.7) in those born between 1910 and 1939 compared with 1940 and 1979 (P = 0.03). Education was significantly associated with myopia; for those completing primary, secondary, and higher education, the age-standardized prevalences were 25.4% (CI, 25.0-25.8), 29.1% (CI, 28.8-29.5), and 36.6% (CI, 36.1-37.2), respectively. Although more recent birth cohorts were more educated, this did not fully explain the cohort effect. Compared with the reference risk of participants born in the 1920s with only primary education, higher education or being born in the 1960s doubled the myopia prevalence ratio-2.43 (CI, 1.26-4.17) and 2.62 (CI, 1.31-5.00), respectively-whereas individuals born in the 1960s and completing higher education had approximately 4 times the reference risk: a prevalence ratio of 3.76 (CI, 2.21-6.57).

CONCLUSIONS: Myopia is becoming more common in Europe; although education levels have increased and are associated with myopia, higher education seems to be an additive rather than explanatory factor. Increasing levels of myopia carry significant clinical and economic implications, with more people at risk of the sight-threatening complications associated with high myopia.

Adiposity as a cause of cardiovascular disease: a Mendelian randomization study

Background: Adiposity, as indicated by body mass index (BMI), has been associated with risk of cardiovascular diseases in epidemiological studies. We aimed to investigate if these associations are causal, using Mendelian randomization (MR) methods.

Methods: The associations of BMI with cardiovascular outcomes [coronary heart disease (CHD), heart failure and ischaemic stroke], and associations of a genetic score (32 BMI single nucleotide polymorphisms) with BMI and cardiovascular outcomes were examined in up to 22 193 individuals with 3062 incident cardiovascular events from nine prospective follow-up studies within the ENGAGE consortium. We used random-effects meta-analysis in an MR framework to provide causal estimates of the effect of adiposity on cardiovascular outcomes.

Results: There was a strong association between BMI and incident CHD (HR = 1.20 per SD-increase of BMI, 95% CI, 1.12–1.28, P = 1.9·10−7), heart failure (HR = 1.47, 95% CI, 1.35–1.60, P = 9·10−19) and ischaemic stroke (HR = 1.15, 95% CI, 1.06–1.24, P = 0.0008) in observational analyses. The genetic score was robustly associated with BMI (β = 0.030 SD-increase of BMI per additional allele, 95% CI, 0.028–0.033, P = 3·10−107). Analyses indicated a causal effect of adiposity on development of heart failure (HR = 1.93 per SD-increase of BMI, 95% CI, 1.12–3.30, P = 0.017) and ischaemic stroke (HR = 1.83, 95% CI, 1.05–3.20, P = 0.034). Additional cross-sectional analyses using both ENGAGE and CARDIoGRAMplusC4D data showed a causal effect of adiposity on CHD.

Conclusions: Using MR methods, we provide support for the hypothesis that adiposity causes CHD, heart failure and, previously not demonstrated, ischaemic stroke.

Pancreatic zymogen granules: new proteins in unexpected places

Os mecanismos de biogénese, distribuição apical e secreção regulada de enzimas digestivas dos grânulos de zimogénio são, atualmente, pouco conhecidos. De modo a esclarecer e descrever estes processos de elevada importância biológica e clínica, é necessária uma melhor compreensão dos componentes da membrana granular e as funções e interações destes. Neste trabalho, através de uma abordagem proteómica, foi possível identificar novas proteínas granulares previamente associadas ao transporte vesicular sináptico. Para estudar as funções destas proteínas na génese e secreção de grânulos, foram realizados estudos de sobre-expressão, assim como estudos bioquímicos (1D, 2D, and LC-MS/MS) e morfológicos, utilizando céluas de mamífero. Entre as proteínas descobertas, cinco foram selecionadas e analisadas: RMCP-1, Piccolo, Synaptojanin-1, APP e ZG16p. Destas proteínas, confirmou-se a presença da RMCP-1 e APP nos grânulos de zimogénio. Interessantamente, o lectin ZG16p da secreção pâncreatico, encontra-se expressa no cérebro de rato, estando localizada nos terminais pós-sinápticos e em grânulos de RNA, indicando uma possível função desta proteína na formação das vesículas sinápticas. Finalmente, demonstrei que a formação de grânulos de zimogénio pode ser modulada, no modelo de células pancreáticas AR42J, pelas condições de cultura. Em contraste com as proteínas de carga neuroendocrinas, a sobreexpressão de proteínas de carga ou da membrana dos grânulos de zimogénio não foi suficiente para induzir a formação de grânulos ou de estruturas granulares em células constitutivamente secretoras, indicando diferenças na biogénese de grânulos neuroendócrinos e exócrinos.

Emerging horizons for tick-borne pathogens: from the ‘one pathogen–one disease’ vision to the pathobiome paradigm

Ticks as vectors of several notorious zoonotic pathogens, represent an important and increasing threat for human, animal health in Europe. Recent application of new technology revealed the complexity of the tick microbiome that might impact upon its vectorial capacity. Appreciation of these complex systems is expanding our vision of tick-borne pathogens leading us to evolve a more integrated view that embraces the “pathobiome” representing the pathogenic agent integrated within its abiotic and biotic environments. In this review, we will explore how this new vision will revolutionize our understanding of tick-borne diseases. We will discuss the implications in terms of research approach for the future in order to efficiently prevent and control the threat posed by ticks.

Recueil de lettres originales et d'une copie de pièce indiquée comme telle dans le dépouillement qui suit.

Contient : 1 Lettre du roi « CHARLES » IX au « duc de Nemoux,... A Angers, le XXVIIe jour de janvier 1570 » ; 2 Lettre de « FRANÇOYS [duc D'ALENÇON]... à madame... de Ferrare,... A Paris, le XIXme janvier 1570 » ; 3 Lettre de « JAQUES DE SAVOYE [duc DE NEMOURS]... à madame [Renée de France, duchesse de Ferrare]... Du Boys de Vincennes, ce IIIe fevrier 1570 » ; 4 Lettre de « LEONOR D'ORLEANS [duc DE LONGUEVILLE]... à monseigneur... le duc de Nemoux,... De Gaillon, ce VIIIme jour de fevrier 1570 » ; 5 Lettre d'« E[MMANUEL] PHILIBERT [duc DE SAVOIE]... à... monseigneur le duc de Genevoys et d'Annemours,... De Thurin, ce XIIIe de febvrier 1570 » ; 6 Lettre de « JAQUES DE SAVOYE [duc DE NEMOURS]... à madame [Renée de France, duchesse de Ferrare]... De Vincennes, ce XXIIIe de fevrier 1570 » ; 7 Lettre de « MONTMORENCY,... à monsieur... le duc de Nemoux,... D'Angers, le XXIIIIme jour de febvrier 1570 » ; 8 Lettre, en italien, de « LUCRETIA DA ESTE,... a... madama di Ferrara, duchessa di Chiartres,... Di Ferrara, il primo di marzo LXX » ; 9 Lettre, en italien, de la « contessa DELLA MIRANDOLA,... all' illmo... duca di Nemours,... Della Mirandola, il primo di marzo 1570 » ; 10 Lettre de « CATERINE [DE MEDICIS]... à... madame de Nemours,... Du Plesi Masé, cet IIIme de mars 1570 » ; 11 Lettre, en italien, de la « contessa DELLA MIRANDOLA,... all' illmo... duca di Nemours,... Della Mirandola, il 3 di marzo 1570 » ; 12 Lettre du roi « CHARLES » IX au « duc de Nemours,... A Angers, le VIme jour de mars 1570 » ; 13 Lettre d'« ENTRAIGUES,... à monseigneur... le duc de Nemours,... A Marcossis, ce deuxme de mars 1570 » ; 14 Lettre de « FRANÇOYS [duc D'ALENÇON]... à... madame la duchesse de Ferrare,... De Paris, ce VIIme jour de mars 1570 » ; 15 Lettre de « CATERINE [DE MEDICIS]... à... monseigneur le duc de Nemoux,... D'Enger, cet VIme jour de mars 1570 » ; 16 « Coppie du pouvoir faict de par le roy pour le gouvernement de monseigneur le mareschal de Cossé » en Bretagne. « Donné à Angers, le dernier jour de janvier... mil cinq cens soixante dix » ; 17 Lettre de « JAQUES DE SAVOYE [duc DE NEMOURS]... à madame [Renée de France, duchesse de Ferrare]... De Paris, ce VIIe de mars 1570 » ; 18 Lettre, en italien, de « HIPPOLITO, cardinale DI FERRARA,... a... madama la duchessa di Nemours,... Di Roma, alli 10 d'aprile 1570 » ; 19 Lettre du maréchal « DE COSSE » à « madame [de Nemours]... De Bloys, le seizme jour de mars 1570 » ; 20 Lettre de « NIGOLAS DE LORRAINE [comte DE VAUDEMONT]... à monsieur... le duc de Nemoux et de Genefvois,... De Nommeni, ce XXIII mars 1570 » ; 21 Lettre de « MONTMORENCY,... à monsieur... le duc de Nemoux,... D'Angiers, le dernier jour de mars 1570 » ; 22 Lettre d'« ANNE D'EST [duchesse DE NEMOURS]... à madame [Renée de France, duchesse de Ferrare]... 1570 » ; 23 Lettre de « CLAUDE DE LORRAINE [duc D'AUMALE]... à monsieur... le duc de Nemours,... D'Ennet, le IIe jour d'avril 1570 » ; 24 Lettre du maréchal « DE COSSE,... à monsieur... le duc de Nemours,... D'Orleans, ce IIe avril 1570 » ; 25 Lettre, en italien, de « GUIDO UBALDO DE PUTTI,... al... signor Francesco Putti,... D'il Passetto, a di II de appril 1570 » ; 26 Lettre du maréchal « DE COSSE,... à madame... la duchesse de Ferrare,... D'Orleans, ce Ve apvril 1570 » ; 27 Lettre d'« ANNE D'EST,... à madame... la duchesse de Ferrare,... De Paris, ce VIIIe avril 1570 » ; 28 Lettre de « HENRY », duc D'ANJOU, au « duc de Nemoux,... A Chasteaubriant, le XIIme jour d'avril 1570 » ; 29 Lettre, en italien, de « CHIARA LAMBERTI,... à... madama Renea di Francia,... Di Ferrara, ad 6 maggio 1570 » ; 30 Lettre, en italien, de « BARRARA, duchessa DI FERRARA,... a madama di Ferrara, duchessa di Chiartres,... Di Ferrara, a XI di maggio del LXX » ; 31 Minute de lettre de « RENEE DE FRANCE,... à ma fille, madame la duchesse de Nemours,... De Montargis, ce XVIe jour de may 1570 » ; 32 Lettre du maréchal « DE COSSE,... à madame... la duchesse de Ferrare,... Du camp de Gien, ce XXIme jour de may 1570 » ; 33 Lettre de « CATERINE [DE MEDICIS]... à... madame de Nemours,... D'Argenten, cet XXme jour de jouyn 1570 » ; 34 Lettre, en italien, de « LEONORA DI ESTE,... a... madama di Ferrara,... Di Ferrara, il XXIX giugno nel LXX » ; 35 Lettre d'« E[MMANUEL] PHILIBERT [duc DE SAVOIE]... à madame la duchesse de Ferrare,... De Thurin, ce dernier d'aoust 1570 » ; 36 Lettre de « GATERINE [DE MEDICIS]... à... madame de Nemoux,... De Mouseaulx, cet XIIIme de settembre 1570 » ; 37 Lettre, en italien de « fratre AUGUSTINO rig°... » à « madama di Ferrara,... duchessa di Chiartres,... Di Ferrara, ai XXVIII di settembre M.D.LXX » ; 38 Lettre, en italien, du « duca D'URBINO [GUI-URALD II]... a... madama Renea [di Francia], duchessa di Ferrara,... Dell' Imperiale, il di VIII di ottobre del LXX » ; 39 Lettre, en italien, de « LUIGI, cardinale D'ESTE,... a... madama di Ferrara,... Di Ferrara, a XI d'ottobre del LXX » ; 40 Lettre de la reine « MARIE [STUART]... à... monseigneur le duc de Nemours,... A Chatysworth, le dernier jour d'octobre 1570 » ; 41 Lettre d'« E[MMANUEL] PHILIBERT [duc DE SAVOIE]... à... monsieur le duc de Genevoys et de Nemours,... De Thurin, le 28 novembre 1570 » ; 42 « Double de la minute des lettres de jussion » du roi CHARLES IX pour le payement des pensions de Renée de France, douairière de Ferrare, 1570 ; 43 Lettre, en italien, des « antiani e gonfalonier di giustizia della republica di Lucca... all' illme... duca di Nemors,... Del nostro palazzo, il di XIIII di decembre M.D.LXX » ; 44 Lettre de « CORNELIA CARACCIOLA,... à madame... la duchesse de Ferrare,... De Chasteauneuf, ce 21 jour de decembre 1570 » ; 45 Lettre des « generaulx des vivres, SERRES » et « LILENDOUZE » à « madame la duchesse de Ferrare,... A Orleans, le XIme avril 1570 » ; 46 Lettre, en italien, de « LUIGI, cardinale D'ESTE,... all' illme... duca di Nemours,... Di Ferrara, l'ultimo di giugno del LXX » ; 47 Lettre, en italien, de « FRANCESCHINO DAL GONDENO,... a... madama la duchessa di Ferrara,... Di Ferrara, a II di luglio M.D.LXX » ; 48 Lettre, en italien, de « ALFONSO D'ESTE,... a... madama di Ferrara,... Di Ferrara, il di III luglio nel LXX » ; 49 Lettre de « HENRY [duc D'ANJOU]... à... madame la duchesse de Ferrare,... A Gaillon, le VIe jour de juillet 1570 » ; 50 Lettre d'« ENTRAIGUES,... à madame [Renée de France, duchessè de Ferrare]... De Gyen, se XIIIe juillet 1570 » ; 51 Lettre du maréchal « A[RTUS] DE COSSE,... à madame... la duchesse de Ferrare,... Du camp de Villeneuve le Roy, le XVme de juillet 1570 » ; 52 Minute de lettre, sans signature ni adresse, sur la conclusion de la paix entre le roi Charles IX et « ceulx de la religion... De Montargis, ce IIe aoust 1570 » ; 53 Lettre du roi « CHARLES » IX au « duc de Nemoux,... A St Germain en Laye, le IIIe jour de aoust 1570 » ; 54 Lettre du roi « CHARLES [IX]... à monseigneur le president de Metz... A St Germain en Laye, le XIIIIe jour de aoust 1570 »

Letter to Mr. Henry H. Collier, 1837

Henry Haight Collier, was born in Howard, Steuben County, N. Y., November 28, 1818. His father, Richard Collier, was from Green County, in the same State. His grandfather, Isaac Collier, and his great-grandfather were originally from England. His mother, Mary Haight, was of Dutch origin. In 1835, Henry went to St. Catharines, where his elder brother, Richard Collier, resided. He spent two years at Grantham Academy, and then returned to Steuben County, to read law in Bath, with Edward Howell, and subsequently with Hammond and Campbell. Mr. Collier never opened a law office. He studied law for two years and in 1839 he went to Texas where he was connected with the State and Treasury Departments. In 1845 Mr. Collier returned to St. Catharines and opened a general store called St. Catharines Agricultural Works with his brother. The store remained open until May, 1877. He added the manufacturing of lumber in 1850, and manufacturing of agricultural implements in 1869. He built one of the first saw mills on the canal, on Lock No. 5, in St. Catharines. In July, 1877, he was appointed Collector of Customs. He became a Village Councilor for St. Paul’s Ward in 1859, and held that office from fifteen to twenty years. He was Deputy Reeve and member of the County Council for two terms. He was the Mayor of St. Catharines in 1872 and 1873. He was also Chairman of the Board of Water Commissioners of the city, during the time that the works were being built. He was a Justice of the Peace for twenty years or more. Mr. Collier was affiliated with the Reform Party and he was a Knight Templar in the Masonic fraternity and an Odd Fellow. He was also active in the Methodist Church. On June 1, 1858, he married Cornelia, daughter of Moses Cook, of "Westchester Place," St. Catharines, and had a daughter and son. Mary J. (married name: Mrs. Frank Camp) was a graduate of the Female Seminary at Hamilton, and Henry Herbert was a student in the University of Toronto. Henry H. Collier died on July 15, 1895 and is buried in Victoria Lawn Cemetery, St. Catharines, Ontario. Sources: www.accessgeneology.com "Historical Profiles from Victoria Lawn Cemetery" by Paul E. Lewis "Sincerely Lamented St. Catharines Obituaries 1817-1918" by Paul Hutchison