Estradiol-induced hypophagia is associated with the differential mRNA expression of hypothalamic neuropeptides

Estradiol participates in the control of energy homeostasis, as demonstrated by an increase in food intake and in body weight gain after ovariectomy in rats. In the present study, female Wistar rats (200-230 g, N = 5-15 per group), with free access to chow, were individually housed in metabolic cages. We investigated food intake, body weight, plasma leptin levels, measured by specific radioimmunoassay, and the hypothalamic mRNA expression of orexigenic and anorexigenic neuropeptides, determined by real-time PCR, in ovariectomized rats with (OVX+E) and without (OVX) estradiol cypionate treatment (10 µg/kg body weight, sc, for 8 days). Hormonal and mRNA expression were determined at pre-feeding and 4 h after food intake. OVX+E rats showed lower food intake, less body weight gain and lower plasma leptin levels. In the OVX+E group, we also observed a reduction of neuropeptide Y (NPY), agouti-related protein (AgRP) and cocaine- and amphetamine-regulated transcript (CART) mRNA expression in the arcuate nucleus and a decrease in orexin A in the lateral hypothalamic area (LHA). There was an increase in leptin receptor (LepRb), melanocortin-4 receptor (MC4-R), CART, and mainly corticotropin-releasing hormone (CRH) mRNA in the paraventricular nucleus and LepRb and CART mRNA in the LHA. These data show that hypophagia induced by estradiol treatment is associated with reduced hypothalamic expression of orexigenic peptides such as NPY, AgRP and orexin A, and increased expression of the anorexigenic mediators MC4-R, LepRb and CRH. In conclusion, estradiol decreases food intake, and this effect seems to be mediated by peripheral factors such as leptin and the differential mRNA expression of neuropeptides in the hypothalamus.

Transcriptional regulation of bidirectional gene pairs by 17-β-estradiol in MCF-7 breast cancer cells

Using cDNA microarray analysis, we previously identified a set of differentially expressed genes in primary breast tumors based on the status of estrogen and progesterone receptors. In the present study, we performed an integrated computer-assisted and manual search of potential estrogen response element (ERE) binding sites in the promoter region of these genes to characterize their potential to be regulated by estrogen receptors (ER). Publicly available databases were used to annotate the position of these genes in the genome and to extract a 5’flanking region 2 kb upstream to 2 kb downstream of the transcription start site for transcription binding site analysis. The search for EREs and other binding sites was performed using several publicly available programs. Overall, approximately 40% of the genes analyzed were potentially able to be regulated by estrogen via ER. In addition, 17% of these genes are located very close to other genes organized in a head-to-head orientation with less than 1.0 kb between their transcript units, sharing a bidirectional promoter, and could be classified as bidirectional gene pairs. Using quantitative real-time PCR, we further investigated the effects of 17β-estradiol and antiestrogens on the expression of the bidirectional gene pairs in MCF-7 breast cancer cells. Our results showed that some of these gene pairs, such as TXNDC9/EIF5B, GALNS/TRAPPC2L, and SERINC1/PKIB, are modulated by 17β-estradiol via ER in MCF-7 breast cancer cells. Here, we also characterize the promoter region of potential ER-regulated genes and provide new information on the transcriptional regulation of bidirectional gene pairs.

Overexpression of kermit/dGIPC is associated with lethality in Drosophila melanogaster

Insertional mutagenesis is an important tool for functional genomics in Drosophila melanogaster. The insertion site in the KG00562 mutant fly line has been mapped to the CG8709 (herein named DmLpin) locus and to the 3’ of kermit (also called dGIPC). This mutant line presents a high lethality rate resulting from a gain of function. To obtain some insight into the biological role of the mutated locus, we have characterized the mutation and its relation to the high mortality of the KG00562 fly line. In this mutant, we did not detect one of the DmLpin transcripts, namely DmLpinK, but we did detect an unusual 2.3-kb mRNA (LpinK-w). Further investigation revealed that the LpinK-w transcript results from an aberrant splicing between the untranslated first exon of DmLpinK and the mini-white marker gene. Lack of DmLpinK or LpinK-w expression does not contribute to lethality, since heterozygous KG00562/Def7860 animals presented lethality rates comparable to those of the wild type. In contrast, the overexpression of kermit was associated with lethality of the KG00562 fly line. Significantly higher levels of kermit were detected in the Malpighian tubules of KG00562/+ flies that presented higher lethality rates than wild-type or KG00562/Def7860 animals, in which the lethality was rescued. In agreement with a recently reported study, our data support the hypothesis that misexpression of kermit/dGIPC could interfere with Drosophila development, with further investigations being needed in this direction.

The consensus sequence of FAMLF alternative splice variants is overexpressed in undifferentiated hematopoietic cells

The familial acute myeloid leukemia related factor gene (FAMLF) was previously identified from a familial AML subtractive cDNA library and shown to undergo alternative splicing. This study used real-time quantitative PCR to investigate the expression of the FAMLF alternative-splicing transcript consensus sequence (FAMLF-CS) in peripheral blood mononuclear cells (PBMCs) from 119 patients with de novo acute leukemia (AL) and 104 healthy controls, as well as in CD34+cells from 12 AL patients and 10 healthy donors. A 429-bp fragment from a novel splicing variant of FAMLF was obtained, and a 363-bp consensus sequence was targeted to quantify total FAMLF expression. Kruskal-Wallis, Nemenyi, Spearman's correlation, and Mann-Whitney U-tests were used to analyze the data. FAMLF-CS expression in PBMCs from AL patients and CD34+ cells from AL patients and controls was significantly higher than in control PBMCs (P<0.0001). Moreover,FAMLF-CS expression in PBMCs from the AML group was positively correlated with red blood cell count (rs=0.317, P=0.006), hemoglobin levels (rs=0.210, P=0.049), and percentage of peripheral blood blasts (rs=0.256, P=0.027), but inversely correlated with hemoglobin levels in the control group (rs=–0.391, P<0.0001). AML patients with high CD34+ expression showed significantly higherFAMLF-CS expression than those with low CD34+ expression (P=0.041). Our results showed thatFAMLF is highly expressed in both normal and malignant immature hematopoietic cells, but that expression is lower in normal mature PBMCs.

Changes in gene expression during drying and imbibition of desiccation sensitive Magnolia ovata (A. St.-Hil.) spreng. seeds

Seeds of Magnolia ovata were dried to different water contents to assess the viability and transcript abundance of genes related to seed development, cell cycle, cytoskeleton and desiccation tolerance.The expression of development, cell cycle and cytoskeleton relative genes (ABI3, CDC2-like and ACT2) alone could not explain the germination behaviour of M. ovata seeds in relation to drying damage. Irrespective of their initial water content, the seeds performed in the same way during the initial period of germination and the deleterious effects of desiccation only occurred in later stages. Expression of PKABA1, sHSP17.5 and 2-Cys-PRX did not show a relationship with desiccation. However, the expression patterns of PKABA1 and sHSP17.5 suggested the participation of these genes in protective mechanisms during the imbibition of M. ovata seeds.

Catalogues.

Contient : 1 « Inventaire des livres de la bibliotecque de la feue royne mère (Catherine de Médicis) ; A la suite on lit : « Nous soubssignez, commis et nommez pour la prisée et evaluation de la bibliothecque et livres hebreux, arabes, grecz, latins, françois et italiens qui ont appartenu à la royne mere deffuncte, Catherine de Medicis, certiffions à tous qu'il appartiendra avoir veu, visité et feuilleté ensemblement au logis du sieur abbé de Bellebranche, tous et ung chacun les volumes, livres et papiers, desquelz le cathalogue et indice est cy dessus transcript, (qui sont pour la pluspart grecz, escriptz à la main, antiens [et] nous ont esté representez par ledict sieur abbé), et que tous lesdictz livres, volumes et papiers à nous representez, vallent bien argent contant cinq mil quatre cens escuz, encores qu'ils ne se puissent assez estimer... Faict le XXe mars 1597 ». Ont signé : « J. Pellerin, Pithou, P. Laffilé » ; Puis vient la liste des mss. délivrés par l'abbé de Bellebranche, « par le commandement exprès de la royne mère », à « Mr Duret, medecin... à Mr le president Fauchet,... à Mr Du Perron, à present evesque d'Evreux... à M. le president de Thou d'Emery,... à M. l'advocat Servin,... à monseigneur le chancelier... lesquelz susdictz livres nous n'avons peu priser ny evalluer, pour ne nous avoir encores estez representez. Faict le 29e juillet 1597 ». Ont signé : « J. Pellerin, Pithou, P. Laffilé » ; Note sur le ms. de Colbert 3769 (devenu grec 3074), lequel contient « Catalogus graecus librorum Nicolai Rodulphi, cardinalis cum hoc conferendus, nam reginae bibliotheca tota fere ex Rodulphi libris constabat » ; 2 Inventaire, dressé par NICOLAS RIGAULT, des livres non compris dans les classements de la Bibliothèque du roi antérieurs à 1620. Cet inventaire contient 2643 cotes. Lesdites cotes mises à la suite de chaque notice, sont inscrites en tête des mss. correspondants soit en toutes lettres, soit en chiffres romains non surmontés d'une barre

Cloning of actin genes from a genomic library of the newt, Notophthalmus viridescens

The regenerating urodele limb is a useful model system in which to study, in vivo, the controls of cell proliferation and differentiation. Techniques are available which enable one to experimentally manipulate mitogenic influences upon the blastema, as well the morphogenesis of the regenerating 11mb. Although classical regeneration studies have generated a wealth of knowledge concerning tissue interactions, little 1s known about the process at the level of gene expression. The aim of this project was to clone potentially developmentally regulated genes from a newt genomic library for use in future studies of gene expression during limb regeneration. We decided to clone the cytoskeletal actin gene for the following reasons: 1. its expression reflects the proliferative and differentiatlve states of cells in other systems 2. the high copy number of cytoplasmic actin pseudogenes in other vertebrates and the high degree of evolutionary sequence conservation among actin genes increased the chance of cloning one of the newt cytoplasmic actin genes. 3. Preliminary experiments indicated that a newt actin could probably be identified using an available chick ~-actln gene for a molecular probe. Two independent recombinant phage clones, containing actin homologous inserts, were isolated from a newt genomic library by hybridization with the chick actin probe. Restriction mapping identified actin homologous sequences within the newt DNA inserts which were subcloned into the plasmid pTZ19R. The recombinant plasmids were transformed into the Escherichia coli strain, DHsa. Detailed restriction maps were produced of the 5.7Kb and 3.1Kb newt DNA inserts in the plasmids, designated pTNAl and pTNA2. The short «1.3 Kb) length of the actin homologous sequence in pTNA2 indicated that it was possibly a reverse transcript pseudogene. Problems associated with molecular cloning of DNA sequences from N. viridescens are discussed with respect to the large genome size and abundant highly repetitive DNA sequences.

Isolation of DNA sequences with homology to a degenerate FaRP oligonucleotide from the crayfish Procambarus clarkii

The neuropeptide Th1RFamide with the sequence Phe-Met-Arg-Phe-amide was originally isolated in the clam Macrocallista nimbosa (price and Greenberg, 1977). Since its discovery, a large family ofFl\1RFamide-related peptides termed FaRPs have been found to be present in all major animal phyla with functions ranging from modulation of neuronal activity to alteration of muscular contractions. However, little is known about the genetics encoding these peptides, especially in invertebrates. As FaRP-encoding genes have yet to be investigated in the invertebrate Malacostracean subphylum, the isolation and characterization ofFaRP-encoding DNA and mRNA was pursued in this project. The immediate aims of this thesis were: (1) to amplify mRNA sequences of Procambarus clarkii using a degenerate oligonucleotide primer deduced from the common amino acid sequence ofisolated Procambarus FaRPS, (2) to determine if these amplification products encode FaRP gene sequences, and (3) to create a selective cDNA library of sequences recognized by the degenerate oligonucleotide primer. The polymerase chain reaction - rapid amplification of cDNA ends (PCR-RACE) is a procedure in which a single gene-specific primer is used in conjunction with a generalized 3' or 5' primer to amplify copies ofthe region between a single point in the transcript and the 3' or 5' end of cDNA of interest (Frohman et aI., 1988). PCRRACE reactions were optimized with respect to primers used, buffer composition, cycle number, nature ofgenetic substrate to be amplified, annealing, extension and denaturation temperatures and times, and use of reamplification procedures. Amplification products were cloned into plasmid vectors and recombinant products were isolated, as were the recombinant plaques formed in the selective cDNA library. Labeled amplification products were hybridized to recombinant bacteriophage to determine ligated amplification product presence. When sequenced, the five isolated PCR-RACE amplification products were determined not to possess FaRP-encoding sequences. The 200bp, 450bp, and 1500bp sequences showed homology to the Caenorhabditis elegans cosmid K09A11, which encodes for cytochrome P450; transfer-RNA; transposase; and tRNA-Tyr, while the 500bp and 750bp sequences showed homology with the complete genome of the Vaccinia virus. Under the employed amplification conditions the degenerate oligonucleotide primer was observed to bind to and to amplify sequences with either 9 or 10bp of 17bp identity. The selective cDNA library was obselVed to be of extremely low titre. When library titre was increased, white. plaques were isolated. Amplification analysis of eight isolated Agt11 sequences from these plaques indicated an absence of an insertion sequence. The degenerate 17 base oligonucleotide primer synthesized from the common amino acid sequence ofisolated Procambarus FaRPs was thus determined to be non-specific in its binding under the conditions required for its use, and to be insufficient for the isolation and identification ofFaRP-encoding sequences. A more specific primer oflonger sequence, lower degeneracy, and higher melting temperature (TJ is recommended for further investigation into the FaRP-encoding genes of Procambarlls clarkii.

Oath of Allegiance to King George III

Transcript (original spelling and grammar retained): We the Commissioned Officers belonging to the Second Regiment of Lincoln Militia - Do sincerely promise and swear that we will be faithful and bear true allegiance to his Majesty King George, and heirs will defend to the utmost of our power against all traitorous conspiracies and attempts whatsoever which shall be made against his Person, Crown or Dignity; and we will do our utmost endeavours to disclose and make them known to his Majesty, His Heirs and successors, all treasons and traitorous conspiracies and attempts, which we shall know to be against Him or them. So help us God. Thomas Clark - Lt. Col. David Secord - Major John Crysler - Capt James Macklin - Capt John [Ross] - [Captain] [Abraham] Bowman - Lieut Gilbert McMicking - Quartmaster John [Misiner] - Ensign Robert Campbell - Capt John [Couke] - Ensign Nicholas Smith - Lieut I certify that the officers who have here [subscribed] the oath took it before me at Chippawa 4 Sept 1812 Thomas Dickson JP

Isolation and analysis of a corprinus cinereus DNA fragment showing homology to a fimbrial cDNA from ustilago violacea

Surface proteinaceous fibrils, termed fimbriae, were first identified on gram negative bacteria in the 1940s. Fungal fimbriae, discovered some 25 years later, are found on members of all fungal classes. In the present study, polyclonal antiserum raised against the fimbrial proteins of U. vio/acea were used in order to identify antigenically related proteins from Coprinus cinereus and Schizophy//um commune. Two polypeptides with molecular masses of 37 and 39 kDa from C. cinereus were observed and confirm earlier results. A single previously unidentified 50 kDa polypeptide in S. commune crossreacted with the antiserum. The 50 kDa protein was found to consist of 3 isoforms with isoelectric points ranging from 5.6 to 5.8. A fimbrial cDNA derived from U. vio/acea was used to identify DNA restriction fragments from C. cinereus and S. commune showing homology to the fimbrial transcript of U. vio/acea. Heterologous hybridization with this cDNA was used in order to screen a C. cinereus genomic DNA library. A single clone, A2-3A, with a 14 kbp insert showed strong homology to the pfim3-1 cDNA. The region of homology, a 700 bp Xba I fragment, was subcloned into pUG19. This plasmid was refered to as pXX8. DNA sequence determinations of pXX8 and adjacent fragments from A2-3A suggested that the cloned DNA was a portion of the rONA repeat encoding the small subunit rRNA. DNA sequence analysis of pfim3-1 yielded an incomplete open reading frame. The predicted amino acid sequence codes for a 206 amino acid, 22 kDa polypeptide which contains a domain similar to a transmembrane domain from rat leukocyte antigen, GDS3. As well, an untranslated 576 nucleotide domain showed 81 % homology to pXX8 and 830/0 homology to the 188 rRNA sequence of Ustilago maydis. This sequence was found adjacent to a region of adenine-thymine base pairs presumed to represent the polyadenylation sequence of the fimbrial transcript. The size and extent of homology is sufficient to account for the hybridization of pfim3-1 to rDNA. It is suggested that this domain represents a completely novel regulatory domain within eukaryotes that may enable the observed rapid regeneration of fimbriae in U. violacea.

Letter - American soldier's account of battles at Chippewa, Lundy's Lane and Fort Erie, 1814

Transcript (original grammar and spelling retained): My dear wife I take this time to inform you that I am well hoping that these few lines will Reach you and find you the same I shall in form you of all our Battles that we have had sence I left home we crossed in to Canada the 2 day of July and took fort Erie on the 3 day of July without loss of one man. We then marched down to Chipway eighteen miles below the Fort Erie we got there on the forth day and had our first battle on the 5 day our loss was not jistly known But the inemy loss was double to ours. The 6 day we started with the 2 Brigade to make a bridge a crost the crick two miles a bove the fort in Building the Bridge the inemy Brought up their Canon and playd upon us with their artiliery a bout two hours We drove them from the fort our loss was none the inemy loss was nineteen ciled dead on the ground we then marched to Queenston when we got thare our inemy had fledfrom the fort we then remained thair to Queenston ten days then we marched down to Fort George But that caurdly Chaney did not a rive with the fleet so we had to return back to Queenston thare was a bout six hundred militia formed on the heights of land thay fired up on us from their pickets and retreated to the mane body our flankers ciled and wounded and took about twenty before they got to the Maine body we then marched up the hill they gave us two firs but did not damage and then retreated from the field we stayed there one knight and then marched to Chipway and stayed there one night and the next day just as the sun set the first Brigade marched up in order to give them Battle a bout two miles from the Crick and began the Battle the 2 Brigade has to March up to the Niagara path and ingaged them we charged up on their artlery and took all their Canon Miller commanded the four companys that charged....the battles lasted three hours and forty minutes our loss was about 8 hundred cild and wounded our inemies loss was a bout fourteen hundred cild and wounded the next morning we Marched up in order to give them Battle a gin but thay was afraid to ingage us we then marched to Fort Erie and went to fortiffing and made a strong place the inemy folered us up and Began to cananade and held it fifty three days thay a tacked the fort the fifteenth of august thay atacked a bout one hiour be fore day Light we saw them and Blue up our maggerzean & two hundred of our inemy our loss wasa bout forty cild and wounded and our inemy loss was a bout one thousand on the 7 Day of September we atacked them and took their batteries and Broke all their canon and drove them from the field our loss was a Bout two hundred cild and wounded our inemy loss was a Bout 8 hundred cild and wounded...we crossed in to Canada with five thousand and came out with fifteen hundred we then Marched to Sackett’s harbor....am well and harty for the present....a bout comming home it uncarting for there is not any....given this winter as yet But I shall try to Come home if I Can But if I Cant I want you should take good car of the Phiddness[?] I have not Received any Money as yet But soon as I do receive some I send some home. I want you should write to me as soon as you receive this and and how Much Stock you wintor I Received your Letter with Great pleasure I feel uneasy a bout you I am a frade that you are sick or dead this is from your husband Chase Clough

Manuscript of James Cummings- August 28, 1860

Transcript (spelling and grammar retained): Chippawa [Chippewa] 28th August 1860 My Dear Sir I duly received your very kind letter of the 24th [June] asking me to communicate such facts of general interest connected with my career during the War with the United States. I have no objection to afford you such information as came under my own observation; nevertheless I do so, with the understanding, I have no desire to be my own trumpeter. With respect to your circular wherein you state you have been for several years collecting materials for a History of the late War between the United States & Great Britain, for which you are now gathering further materials to add to your collection, concerning the Second War for Independence. I am rather at a loss to know, what is meant by the second war; If you allude to the petty Rebellion, it could not be called a War, Those that caused the outbreak were very soon put down, by the Loyal people of the Province without the aid of Regular Troops being satisfied with the Independence they enjoyed. With respect to the several questions names in your circular: To the 1st I would say, this locality is made memorable by the battle of Chippawa [Chippewa] which took place about a mile above the village on the ground I pointed out to you, when I had the pleasure of seeing you a few days ago, with Mr Porter of the Niagara Falls, of which I believe you took sketches at the time. 2nd I have no historical documents of any value; so many years having gone past, the most of my old papers have either been lost or destroyed, I however came across two letters, one dated Queenston 9th July 1812 from Lt. Col. Nicholl Quarter Master General of Militia, the other from Lt. Col Myers Deputy Quarter Master General of the Regular Army date Fort George 23rd same month, directed to me in the hand writing of each of those officers as Deputy Quarter Master General of Militia, which letters I shall be obliged you would return at as early a day possible, as I wish to place them with tome others in the case, I have had made to hold the cocked hat & feather I wore during that eventful period, which I am sorry I did not exhibit when you was at my house; with reference to it I now enclose a letter from Lt. Col. Clark, residing at Port Dalhousie he was Captain & Adjutant of Militia in the War of 1812__ I send the letter in proof of the cock’d hat it is a lengthy one, but you may find time to turn over it, as I shall also place it in the hat case__ 3rd Where are [but] [for] traditionary [sic] witnesses residing in this vicinity – Col Clark above named Mr Merritt of St. Catharines, & Mr Kerby of Brantford are the only ones I now recollect, who could offord [sic] you any statistical information. 4th I have no pictorial sketches of any Military Movements or fortifications. As regards my own career, which you appear [ ? ] of knowing__ I was first a Lieutenant in a volunteer flank company stationed on the river side opposite [Navy] Island not far from the battle ground of Chippawa [Chippewa], I got promotion as Lieutenant of Cavalry before I got my Cavalry dress completed in three days more, I was called by General Brock to Fort George, was appointed Deputy Quarter Master General of Militia with the rank of Captain s the accompanying letters will show. I was at the battle of Stony Creek, several skirmishes at the Cross Roads, when the American army [ ? ] Fort George, at the taking of Col. Boerstler at the Beaver Dam, & had the honor of receiving Colonel Chapens sword at the surrender, who commanded a company of volunteer Horse Men was at the taking of 15 regulars & two officers at Fort Schlosser—was with Col. Bishop at the taking of Black Rock, near him when he fell, three men of the 8th Reg. more killed in the Boat I was in – I was at Chippawa battle, and the last, not the least in Lundy’s lane battle, which the Americans call the battle of Bridge [Waters]. I had forgot; there was another small affair at Corks Mill where I was. I could write a little history of events, but have not the time to do so. If what I have stated will be of any service for the purpose you require I shall feel happy. The history of the late War was published at Toronto in the Anglo American Magazine. Did you ever see it, I have the Books, there were however several errors which came under my notice, which I could have corrected. If my time would permit I could give you a more detailed statement of events. I trust however you may succeed with your publication , and I shall be most happy to hear from you at all times—I related many little occurances verbally to you when here, which I thought not necessary to repeat again as you would have a perfect recollection of them. Be pleased to return the letters for the purpose I require them. I am My Dear Sir Your respectful friend James Cummings

Letter from Lt.Col. Chewett to Ensign Kuck- 6 Sept 1814

Transcript (spelling and grammar retained): York 6th Sepber [September] 1814 Sir I will thank your for the Rolls and Returns of the Pickering Company due on the 1st instance that I may Make up mine to be returned to the Adjutant General – I have the honor to be Sir Your Most Obed [Obedient] W Chewett Lt Col 3rd Reg Yk [York] Militia

Letter From Sir Isaac Brock to James FitzGibbon - July 29, 1812

A two page letter written by Sir Isaac Brock in York, Upper Canada to James FitzGibbon on July 29, 1812. The name of the recipient is not included but according to Mary Agnes FitzGibbon, one can find a transcript of the letter in her "A Veteran of 1812", page 60.[1812], 29 July: Major-General Isaac Brock, York, to James FitzGibbon. I lament that you should have been so long impressed with the idea that I possessed the means of being serviceable to you. I had scarcely heard of Mr. Johnson having declined a Company in the Glengarry (which would have given me the nomination) but I received account of his being reinstated. I consequently thought no more of the business thinking that officer was enjoying the fruits of his good fortune. I know not positively whether Mr. Johnson is reinstated, but being under obligations to promote his views, I cannot possibly interfere to his prejudice. I rather wonder you did not hear that Lieut Lamont had long ago my promise of nominating him to the Company provided it became vacant, which of course would have precluded my application in your behalf. Altho you must be sensible of the impossibility of my taking any step to forward your views in the present case, yet be assured I shall always feel happy in any opportunity that may offer to do your service. To a person unaccustomed to my writing I scarcely would hazard sending this scrawl. I am, Dear Sir, Yours faithfully, Isaac Brock I should like to be among the 49th at this moment. I am satisfied they will support and even add to their former fame. They have my very best wishes. The 41st are behaving nobly at Amherstburg.

Letter from David Todd to Colonel Proctor, Commanding Officer of the 41st Regiment- 9 Feb 1812

Transcript (spelling and grammar retained): “Col Proctor Sir I hope your goodness will excuse the Liberty I have taken of Enclosing a Letter for my nephew Mr. Hailes to your care, and begging the favor of you to forward it to him, - not knowing myself at what Post he is – With Great Respect I am Sir Your Most Obed Serv David Todd”