The Weekly Messenger, Vol.2 No.39- July 16, 1813

A weekly newspaper that was published every Friday from 1811 to 1815.

The Weekly Messenger, 13 December 1811 (vol. 1, no. 8) - Newspaper

Volumes of interest were published between 1812 and 1815 with articles about the War of 1812. Issue for Dec. 13, 1811 has a report of the battle with the Indians at Tippecanoe (Indiana). The Battle of Tippecanoe was fought on November 7, 1811, between United States forces led by Governor William Henry Harrison of the Indiana Territory and forces of Tecumseh's growing American Indian confederation led by his younger brother Tenskwatawa.

The Weekly Messenger, 26 June 1812 (vol. 1, no.36) - Newspaper

Volumes of interest were published between 1812 and 1815 with articles about the War of 1812. Issue for June 26, 1812 includes a proclamation issued by President James Madison confirming the Congress declaration of war against Great Britain.

The Weekly Messenger, 5 February 1813 (vol. 2, no. 16) - Newspaper

Volumes of interest were published between 1812 and 1815 with articles about the War of 1812.

The Weekly Messenger, 2 April 1813 (vol. 2, no. 24) - Newspaper

Volumes of interest were published between 1812 and 1815 with articles about the War of 1812.

The Weekly Messenger, 16 April 1813 (vol. 2, no. 26) - Newspaper

Volumes of interest were published between 1812 and 1815 with articles about the War of 1812.

The Weekly Messenger, 23 April 1813 (vol. 2, no. 27) - Newspaper

Volumes of interest were published between 1812 and 1815 with articles about the War of 1812.

The Weekly Messenger, 30 April 1813 (vol. 2, no. 28) - Newspaper

Volumes of interest were published between 1812 and 1815 with articles about the War of 1812.

The Weekly Messenger, 30 July 1813 (vol. 2, no. 41) - Newspaper

Volumes of interest were published between 1812 and 1815 with articles about the War of 1812.

The American Weekly Messenger; or Register of State Papers, History and Politics for 1813 - 1814 Volume 1

Register of state papers, history, and politics for the years 1813 - 1814.

American Messenger, April 1859

American Messenger published by the American Tract Society. The name Alex Stobo is written on the front page. The newspaper is torn in half and torn again, but it is legible when pieced together, April 1859.

Mode of action of FMRFamide-like peptide on drosophila body wall muscle conractions

Neuropeptides are the largest group of signalling chemicals that can convey the information from the brain to the cells of all tissues. DPKQDFMRFamide, a member of one of the largest families of neuropeptides, FMRFamide-like peptides, has modulatory effects on nerve-evoked contractions of Drosophila body wall muscles (Hewes et aI.,1998) which are at least in part mediated by the ability of the peptide to enhance neurotransmitter release from the presynaptic terminal (Hewes et aI., 1998, Dunn & Mercier., 2005). However, DPKQDFMRFamide is also able to act directly on Drosophila body wall muscles by inducing contractions which require the influx of extracellular Ca 2+ (Clark et aI., 2008). The present study was aimed at identifying which proteins, including the membrane-bound receptor and second messenger molecules, are involved in mechanisms mediating this myotropic effect of the peptide. DPKQDFMRFamide induced contractions were reduced by 70% and 90%, respectively, in larvae in which FMRFamide G-protein coupled receptor gene (CG2114) was silenced either ubiquitously or specifically in muscle tissue, when compared to the response of the control larvae in which the expression of the same gene was not manipulated. Using an enzyme immunoassay (EIA) method, it was determined that at concentrations of 1 ~M- 0.01 ~M, the peptide failed to increase cAMP and cGMP levels in Drosophila body wall muscles. In addition, the physiological effect of DPKQDFMRFamide at a threshold dose was not potentiated by 3-lsobutyl-1-methylxanthine, a phosphodiesterase inhibitor, nor was the response to 1 ~M peptide blocked or reduced by inhibitors of cAMP-dependent or cGMP-dependent protein kinases. The response to DPKQDFMRFamide was not affected in the mutants of the phosholipase C-~ (PLC~) gene (norpA larvae) or IP3 receptor mutants, which suggested that the PLC-IP3 pathway is not involved in mediat ing the peptide's effects. Alatransgenic flies lacking activity of calcium/calmodul in-dependent protein kinase (CamKII showed an increase in muscle tonus following the application of 1 JlM DPKQDFMRFamide similar to the control larvae. Heat shock treatment potentiated the response to DPKQDFMRFamide in both ala1 and control flies by approximately 150 and 100 % from a non heat-shocked larvae, respectively. Furthermore, a CaMKII inhibitor, KN-93, did not affect the ability of peptide to increase muscle tonus. Thus, al though DPKQDFMRFamide acts through a G-protein coupled FMRFamide receptor, it does not appear to act via cAMP, cGMP, IP3, PLC or CaMKl1. The mechanism through which the FMRFamide receptor acts remains to be determined.

Additional Return for Ordnance Stores for the Use of Capt. Thos. Biddle’s Compy Corps of Artillery, June 24, 1814

Jacob Hindman (1789-1827) was an American military officer who was a captain of the Second U.S. Artillery during the War of 1812. He commanded troops at the battles at Fort George and Stony Creek in 1813, and in June of that year became the major of the Second Artillery. He remained in this position until May of 1814 when the regiment was merged with the Corps of Artillery. During the Niagara campaign in 1814, Hindman’s company commanders included Nathan Towson, Thomas Biddle, John Ritchie, and Alexander Williams. During the British attack on Fort Erie in August 1814, Hindman led an assault for which he later received a brevet promotion to lieutenant colonel for “gallant conduct in the defense of Fort Erie”. In 1815, he received an additional brevet for “meritorious services”. He is generally regarded as one of the most successful artillerists of the War of 1812. James Hall (1793-1868) served with the U.S. military as a second lieutenant in the Second Artillery during the War of 1812. He fought in the Battle of Lundy’s Lane and was General Brown’s messenger during the attack on Fort Erie. He left the military in 1818 and became a newspaper editor and author. His experiences during the War of 1812 provided material for two stories, The Bearer of Despatches and Empty Pockets. Much of his work sought to popularize the West and promote western authors.

The γ-tocopherol-like family of N-methyltransferases: A taxonomically clustered gene family encoding enzymes responsible for N-methylation of monoterpene indole alkaloids

The plant family Apocynaceae accumulates thousands of monoterpene indole alkaloids (MIAs) which originate, biosynthetically, from the common secoiridoid intermediate, strictosidine, that is formed from the condensation of tryptophan and secologanin molecules. MIAs demonstrate remarkable structural diversity and have pharmaceutically valuable biological activities. For example; a subunit of the potent anti-neoplastic molecules vincristine and vinblastine is the aspidosperma alkaloid, vindoline. Vindoline accumulates to trace levels under natural conditions. Research programs have determined that there is significant developmental and light regulation involved in the biosynthesis of this MIA. Furthermore, the biosynthetic pathway leading to vindoline is split among at least five independent cell types. Little is known of how intermediates are shuttled between these cell types. The late stage events in vindoline biosynthesis involve six enzymatic steps from tabersonine. The fourth biochemical step, in this pathway, is an indole N-methylation performed by a recently identified N-methyltransfearse (NMT). For almost twenty years the gene encoding this NMT had eluded discovery; however, in 2010 Liscombe et al. reported the identification of a γ-tocopherol C-methyltransferase homologue capable of indole N-methylating 2,3-dihydrotabersonine and Virus Induced Gene Silencing (VIGS) suppression of the messenger has since proven its involvement in vindoline biosynthesis. Recent large scale sequencing initiatives, performed on non-model medicinal plant transcriptomes, has permitted identification of candidate genes, presumably involved, in MIA biosynthesis never seen before in plant specialized metabolism research. Probing the transcriptome assemblies of Catharanthus roseus (L.)G.Don, Vinca minor L., Rauwolfia serpentine (L.)Benth ex Kurz, Tabernaemontana elegans, and Amsonia hubrichtii, with the nucleotide sequence of the N-methyltransferase involved in vindoline biosynthesis, revealed eight new homologous methyltransferases. This thesis describes the identification, molecular cloning, recombinant expression and biochemical characterization of two picrinine NMTs, one from V. minor and one from R. serpentina, a perivine NMT from C. roseus, and an ajmaline NMT from R. serpentina. While these TLMTs were expressed and functional in planta, they were active at relatively low levels and their N-methylated alkaloid products were not apparent our from alkaloid isolates of the plants. It appears that, for the most part, these TLMTs, participate in apparently silent biochemical pathways, awaiting the appropriate developmental and environmental cues for activity.

Investigating the role of apoptosis regulator EndoG on exogenous DNA uptake, stability, replication and recombination

Endonuclease G (EndoG) is a well conserved mitochondrial nuclease with dual lethal and vital roles in the cell. It non-specifically cleaves endogenous DNA following apoptosis induction, but is also active in non-apoptotic cells for mitochondrial DNA (mtDNA) replication and may also be important for replication, repair and recombination of genomic DNA. The aim of our study was to examine whether EndoG exerts similar activities on exogenous DNA substrates such as plasmid DNA (pDNA) and viral DNA vectors, considering their importance in gene therapy applications. The effects of EndoG knockdown on pDNA stability and levels of encoded reporter gene expression were evaluated in the cervical carcinoma HeLa cells. Transfection of pDNA vectors encoding short-hairpin RNAs (shRNAs) reduced levels of EndoG mRNA and nuclease activity in HeLa cells. In physiological circumstances, EndoG knockdown did not have an effect on the stability of pDNA or the levels of encoded transgene expression as measured over a four day time-course. However, when endogenous expression of EndoG was induced by an extrinsic stimulus (a cationic liposome transfection reagent), targeting of EndoG by shRNA improved the perceived stability and transgene expression of pDNA vectors. Therefore, EndoG is not a mediator of exogenous DNA clearance, but in non-physiological circumstances it may non-specifically cleave intracellular DNA regardless of its origin. To investigate possible effects of EndoG on viral DNA vectors, we constructed and evaluated AdsiEndoG, a first generation adenovirus (Ad5 ΔE1) vector encoding a shRNA directed against EndoG mRNA, along with appropriate Ad5 ΔE1 controls. Infection of HeLa cells with AdsiEndoG at a multiplicity of infection (MOI) of 10 p.f.u./cell resulted in an early cell proliferation defect, absent from cells infected at equivalent MOI with control Ad5 ΔE1 vectors. Replication of Ad5 ΔE1 DNA was detected for all vectors, but AdsiEndoG DNA accumulated to levels that were 50 fold higher than initially, four days after infection, compared to 14 fold for the next highest control Ad5 ΔE1 vector. Deregulation of the cell cycle by EndoG depletion, which is characterized by an accumulation of cells in the G2/M transition, is the most likely reason for the observed cell proliferation defect. The enhanced replication of AdsiEndoG is consistent with this conclusion, as Ad5 ΔE1 DNA replication is intimately related to cell cycling and prolongation or delay in G2/M greatly enhances this process. Furthermore, infection of HeLa with AdsiEndoG at MOI of 50 p.f.u./cell resulted in an almost complete disappearance of viable, adherent tumour cells from culture, whereas almost a third of the cells were still adherent after infection with control Ad5 ΔE1 vectors, relative to the non-infected control. Therefore, targeting of EndoG by RNAi is a viable strategy for improving the oncolytic properties of first generation adenovirus vectors. In addition, AdsiEndoG-mediated knockdown of EndoG reduced homologous recombination between pDNA substrates in HeLa cells. The effect was modest but, nevertheless demonstrated that the proposed role of EndoG in homologous recombination of cellular DNA also extends to exogenous DNA substrates.