Ca(2+) sparks promote myogenic tone in retinal arterioles

Background and Purpose: Ca(2+) imaging reveals subcellular Ca(2+) sparks and global Ca(2+) waves/oscillations in vascular smooth muscle. It is well established that Ca(2+) sparks can relax arteries, but we have previously reported that sparks can summate to generate Ca(2+) waves/oscillations in unpressurized retinal arterioles, leading to constriction. We have extended these studies to test the functional significance of Ca(2+) sparks in the generation of myogenic tone in pressurized arterioles.

Experimental Approach: Isolated retinal arterioles (25-40 μm external diameter) were pressurized to 70 mmHg, leading to active constriction. Ca(2+) signals were imaged from arteriolar smooth muscle in the same vessels using Fluo4 and confocal laser microscopy.

Key Results: Tone development was associated with an increased frequency of Ca(2+) sparks and oscillations. Vasomotion was observed in 40% of arterioles and was associated with synchronization of Ca(2+) oscillations, quantifiable as an increased cross-correlation coefficient. Inhibition of Ca(2+) sparks with ryanodine, tetracaine, cyclopiazonic acid or nimodipine, or following removal of extracellular Ca(2+) , resulted in arteriolar relaxation. Cyclopiazonic acid-induced dilatation was associated with decreased Ca(2+) sparks and oscillations but with a sustained rise in the mean global cytoplasmic [Ca(2+) ] ([Ca(2+) ]c ), as measured using Fura2 and microfluorimetry.

Conclusions and Implications: This study provides direct evidence that Ca(2+) sparks can play an excitatory role in pressurized arterioles, promoting myogenic tone. This contrasts with the generally accepted model in which sparks promote relaxation of vascular smooth muscle. Changes in vessel tone in the presence of cyclopiazonic acid correlated more closely with changes in spark and oscillation frequency than global [Ca(2+) ]c , underlining the importance of frequency-modulated signalling in vascular smooth muscle.

Role of basal extracellular Ca2+ entry during 5-HT-induced vasoconstriction of canine pulmonary arteries.

1. Measurements of artery contraction, cytosolic [Ca(2+)], and Ca(2+) permeability were made to examine contractile and cytosolic [Ca(2+)] responses of canine pulmonary arteries and isolated cells to 5-hydroxytryptamine (5-HT), and to determine the roles of intracellular Ca(2+) release and extracellular Ca(2+) entry in 5-HT responses. 2. The EC(50) for 5-HT-mediated contractions and cytosolic [Ca(2+)] increases was approximately 10(-7) M and responses were inhibited by ketanserin, a 5-HT(2A)-receptor antagonist. 3. 5-HT induced cytosolic [Ca(2+)] increases were blocked by 20 microM Xestospongin-C and by 2-APB (IC(50)=32 microM inhibitors of InsP(3) receptor activation. 4. 5-HT-mediated contractions were reliant on release of InsP(3) but not ryanodine-sensitive Ca(2+) stores. 5. 5-HT-mediated contractions and cytosolic [Ca(2+)] increases were partially inhibited by 10 microM nisoldipine, a voltage-dependent Ca(2+) channel blocker. 6. Extracellular Ca(2+) removal reduced 5-HT-mediated contractions further than nisoldipine and ablated cytosolic [Ca(2+)] increases and [Ca(2+)] oscillations. Similar to Ca(2+) removal, Ni(2+) reduced cytosolic [Ca(2+)] and [Ca(2+)] oscillations. 7. Mn(2+) quench of fura-2 and voltage-clamp experiments showed that 5-HT failed to activate any significant voltage-independent Ca(2+) entry pathways, including store-operated and receptor-activated nonselective cation channels. Ni(2+) but not nisoldipine or Gd(3+) blocked basal Mn(2+) entry. 8. Voltage-clamp experiments showed that simultaneous depletion of both InsP(3) and ryanodine-sensitive intracellular Ca(2+) stores activates a current with linear voltage dependence and a reversal potential consistent with it being a nonselective cation channel. 5-HT did not activate this current. 9. Basal Ca(2+) entry, rather than CCE, is important to maintain 5-HT-induced cytosolic [Ca(2+)] responses and contraction in canine pulmonary artery.

Efficacy of cecropin A-melittin peptides on a sepsis model of infection by pan-resistant Acinetobacter baumannii

Pan-resistant Acinetobacter baumannii have prompted the search for therapeutic alternatives. We evaluate the efficacy of four cecropin A-melittin hybrid peptides (CA-M) in vivo. Toxicity was determined in mouse erythrocytes and in mice (lethal dose parameters were LD(0), LD(50), LD(100)). Protective dose 50 (PD(50)) was determined by inoculating groups of ten mice with the minimal lethal dose of A. baumannii (BMLD) and treating with doses of each CA-M from 0.5 mg/kg to LD(0). The activity of CA-Ms against A. baumannii was assessed in a peritoneal sepsis model. Mice were sacrificed at 0 and 1, 3, 5, and 7-h post-treatment. Spleen and peritoneal fluid bacterial concentrations were measured. CA(1-8)M(1-18) was the less haemolytic on mouse erythrocytes. LD(0) (mg/kg) was 32 for CA(1-8)M(1-18), CA(1-7)M(2-9), and Oct-CA(1-7)M(2-9), and 16 for CA(1-7)M(5-9). PD(50) was not achieved with non-toxic doses (= LD(0)). In the sepsis model, all CA-Ms were bacteriostatic in spleen, and decreased bacterial concentration (p <0.05) in peritoneal fluid, at 1-h post-treatment; at later times, bacterial regrowth was observed in peritoneal fluid. CA-Ms showed local short-term efficacy in the peritoneal sepsis model caused by pan-resistant Acinetobacter baumannii.

Activation of MAPK by modified low-density lipoproteins in vascular smooth muscle cells

A high concentration of circulating low-density lipoproteins (LDL) is a major risk factor for atherosclerosis. Native LDL and LDL modified by glycation and/or oxidation are increased in diabetic individuals. LDL directly stimulate vascular smooth muscle cell (VSMC) proliferation; however, the mechanisms remain undefined. The extracellular signal-regulated kinase (ERK) pathway mediates changes in cell function and growth. Therefore, we examined the cellular effects of native and modified LDL on ERK phosphorylation in VSMC. Addition of native, mildly modified (oxidized, glycated, glycoxidized) and highly modified (highly oxidized, highly glycoxidized) LDL at 25 microg/ml to rat VSMC for 5 min induced a fivefold increase in ERK phosphorylation. To elucidate the signal transduction pathway by which LDL phosphorylate ERK, we examined the roles of the Ca(2+)/calmodulin pathway, protein kinase C (PKC), src kinase, and mitogen-activated protein kinase kinase (MEK). Treatment of VSMC with the intracellular Ca(2+) chelator EGTA-AM (50 micromol/l) significantly increased ERK phosphorylation induced by native and mildly modified LDL, whereas chelation of extracellular Ca(2+) by EGTA (3 mmol/l) significantly reduced LDL-induced ERK phosphorylation. The calmodulin inhibitor N-(6-aminohexyl)-1-naphthalenesulfonamide (40 micromol/l) significantly decreased ERK phosphorylation induced by all types of LDL. Downregulation of PKC with phorbol myristate acetate (5 micromol/l) markedly reduced LDL-induced ERK phosphorylation. Pretreatment of VSMC with a cell-permeable MEK inhibitor (PD-98059, 40 micromol/l) significantly decreased ERK phosphorylation in response to native and modified LDL. These findings indicate that native and mildly and highly modified LDL utilize similar signaling pathways to phosphorylate ERK and implicate a role for Ca(2+)/calmodulin, PKC, and MEK. These results suggest a potential link between modified LDL, vascular function, and the development of atherosclerosis in diabetes.

Activation of protease calpain by oxidized and glycated LDL increases the degradation of endothelial nitric oxide synthase

Oxidation and glycation of low-density lipoprotein (LDL) promote vascular injury in diabetes; however, the mechanisms underlying this effect remain poorly defined. The present study was conducted to determine the effects of 'heavily oxidized' glycated LDL (HOG-LDL) on endothelial nitric oxide synthase (eNOS) function. Exposure of bovine aortic endothelial cells with HOG-LDL reduced eNOS protein levels in a concentration- and time-dependent manner, without altering eNOS mRNA levels. Reduced eNOS protein levels were accompanied by an increase in intracellular Ca(2+), augmented production of reactive oxygen species (ROS) and induction of Ca(2+)-dependent calpain activity. Neither eNOS reduction nor any of these other effects were observed in cells exposed to native LDL. Reduction of intracellular Ca(2+) levels abolished eNOS reduction by HOG-LDL, as did pharmacological or genetic through calcium channel blockers or calcium chelator BAPTA or inhibition of NAD(P)H oxidase (with apocynin) or inhibition of calpain (calpain 1-specific siRNA). Consistent with these results, HOG-LDL impaired acetylcholine-induced endothelium-dependent vasorelaxation of isolated mouse aortas, and pharmacological inhibition of calpain prevented this effect. HOG-LDL may impair endothelial function by inducing calpain-mediated eNOS degradation in a ROS- and Ca(2+)-dependent manner.

Flexibility of Continental Navigation and Migration in European Mallards

The ontogeny of continent-wide navigation mechanisms of the individual organism, despite being crucial for the understanding of animal movement and migration, is still poorly understood. Several previous studies, mainly conducted on passerines, indicate that inexperienced, juvenile birds may not generally correct for displacement during fall migration. Waterbirds such as the mallard (Anas platyrhynchos, Linnaeus 1758) are more flexible in their migration behavior than most migratory songbirds, but previous experiments with waterbirds have not yet allowed clear conclusions about their navigation abilities. Here we tested whether immature mallard ducks correct for latitudinal displacement during fall migration within Europe. During two consecutive fall migration periods, we caught immature females on a stopover site in southeast Sweden, and translocated a group of them ca. 1,000 km to southern Germany. We followed the movements of the ducks via satellite GPS-tracking and observed their migration decisions during the fall and consecutive spring migration. The control animals released in Ottenby behaved as expected from banding recoveries: they continued migration during the winter and in spring returned to the population's breeding grounds in the Baltics and Northwest Russia. Contrary to the control animals, the translocated mallards did not continue migration and stayed at Lake Constance. In spring, three types of movement tactics could be observed: 61.5% of the ducks (16 of 26) stayed around Lake Constance, 27% (7 of 26) migrated in a northerly direction towards Sweden and 11.5% of the individuals (3 of 26) headed east for ca. 1,000 km and then north. We suggest that young female mallards flexibly adjust their migration tactics and develop a navigational map that allows them to return to their natal breeding area.

Synchronous records of pCO2 and Δ14C suggest rapid, ocean-derived pCO2 fluctuations at the onset of Younger Dryas

Just before the onset of the Younger Dryas (YD) cold event, several stomatal proxy-based pCO2 records have shown a sharp increase in atmospheric CO2 concentration (pCO2) of between ca 50 and 100 ppm, followed by a rapid decrease of similar or even larger magnitude. Here we compare one of these records, a high-resolution pCO2 record from southern Sweden, with the IntCal13 record of radiocarbon (Δ14C). The two records show broadly synchronous fluctuations at the YD onset. Specifically, the IntCal13 record documents decreasing Δ14C just before the YD onset when pCO2 peaks, consistent with a source of “old” CO2 from the deep ocean. We propose that this fluctuation occurred due to a major ocean flushing event. The cause of the flushing event remains speculative but could be related to the hypothesis of the glacial ocean as a thermobaric capacitor. We confirm that the earth system can produce such large multi-decadal timescale fluctuations in pCO2 through simulating an artificial ocean flushing event with the GENIE Earth System Model. We suggest that sharp transitions of pCO2 may have remained undetected so far in ice cores due to inter-firn gas exchange and time-averaging. The stomatal proxy record is a powerful complement to the ice core records for the study of rapid climate change.

The Complete Works of John Milton: Volume III: The Shorter Poems (826pp.)

Stephen B. Dobranski, Milton Quarterly 49.3 (October, 2015), 181-4:

'By addressing classical and neo-Latin works with which Milton's poems appear to engage, Haan has pursued something unattempted yet. Her erudite and engaging commentary on the Poemata is the most extensive and impressive that I have encountered in any edition ... Haan's discussion of Milton's Poemata - including the Testimonia, the one Italian and four Latin encomia by the poet's acquaintances published in 1645 and 1673 - is remarkably detailed and well-researched. In these sections, readers learn, for example, how Milton's Epitaphium Damonis borrows from both classical writers (Theocritus, Moschus) and contemporary models (Castiglione, Zanchi) while transcending all of them through a pattern of resurrection motifs. Or, readers can discover affinities between Milton's lament on the death of the Bishop of Ely and a poem by the Italian humanist Hieronymo Aleander, Jr., or learn about the connections between Milton's Elegia Quinta and George Buchanan's Maiae Calendae ... The Shorter Poems is a scholarly achievement of the highest order.'

Noam Reisner, Review of English Studies 65 (2014), 744-5:
‘Haan shines with her Neo-Latinist expertise by offering a vivid separate introduction to the Latin poems, which sets up Milton’s poemata specifically within the Neo-Latin contexts of the seventeenth century, thereby dispelling any remaining view of these poems as juvenilia (a view which results from reading the poems chronologically). … The present volume will instantly establish itself as the definitive resource for any reader interested in Milton’s shorter poems, and it is scarcely imaginable that it will ever be eclipsed or be in need of replacing. Its contribution is important in all areas, especially in providing for the first time in a single volume truly valuable documents which can teach us a lot more about Milton’s poetic development than simply reading the poems in chronological sequence. But perhaps, this edition’s greatest achievement is the way in which it succeeds in giving Milton’s Latin poems the pride of place they have long deserved as fully integral to Milton’s complete poetic imagination. Haan’s specific achievement in this regard is less in updating the translations than in providing a different context through which to look at the Latin poems themselves. Haan’s detailed commentaries set the Latin poems in a completely fresh light which looks beyond the obvious classical references and allusions, noted by Carey and many other editors, to Milton’s complex engagement with the Neo-Latin literary culture of his time. It is this aspect of the volume, more than anything else, which vindicates its essentialness.'

Novel role of androgens in mitochondrial fission and apoptosis

Androgen and androgen receptors (AR) play critical roles in the proliferation of prostate cancer through transcriptional regulation of target genes. Here, we found that androgens upregulated the expression of dynamin-related protein 1 (Drp1), which is involved in the induction of mitochondrial fission, a common event in mitosis and apoptosis. Clinical tissue samples and various prostate cancer cell lines revealed a positive correlation between Drp1 and AR levels. Treatment of androgen-sensitive cells with an AR agonist, R1881, and antagonist, bicalutamide, showed that Drp1 is transcriptionally regulated by androgens, as confirmed by an AR ChIP-seq assay. Live imaging experiments using pAcGFP1-Mito stably transfected LNCaP (mito-green) cells revealed that androgen did not induce significant mitochondrial fission by itself, although Drp1 was upregulated. However, when treated with CGP37157 (CGP), an inhibitor of mitochondrial Ca��⁺ efflux, these cells exhibited mitochondrial fission, which was further enhanced by pretreatment with R1881, suggesting that androgen-induced Drp1 expression facilitated CGP-induced mitochondrial fission. This enhanced mitochondrial fission was correlated with increased apoptosis. Transfection with dominant-negative (DN-Drp1, K38A) rescued cells from increased apoptosis, confirming the role of androgen-induced Drp1 in the observed apoptosis with combination treatment. Furthermore, we found that CGP reduced the expression of Mfn1, a protein that promotes mitochondrial fusion, a process which opposes fission. We suggest that androgen-increased Drp1 enhanced mitochondrial fission leading to apoptosis. The present study shows a novel role for androgens in the regulation of mitochondrial morphology that could potentially be utilized in prostate cancer therapy.

Blacklisting and its legacy in the UK construction industry: employment relations in the aftermath of exposure of the Consulting Association

This paper explores responses to the exposure of blacklisting in the UK construction industry in the period following the closure of the Consulting Association (CA) in 2009. It asks whether employer collusion to blacklist in this way has been terminated and concludes that it is now largely of historical interest although other forms of anti-union activity continue. It highlights particularly the historic and continuing importance of ‘double breasting’ and reports on divergent employer paths in the aftermath of the exposure and subsequent closure of the activities of the CA.

Molecular imprinted nanoelectrodes for ultra sensitive detection of ovarian cancer marker

The relentless discovery of cancer biomarkers demands improved methods for their detection. In this work, we developed protein imprinted polymer on three-dimensional gold nanoelectrode ensemble (GNEE) to detect epithelial ovarian cancer antigen-125 (CA 125), a protein biomarker associated with ovarian cancer. CA 125 is the standard tumor marker used to follow women during or after treatment for epithelial ovarian cancer. The template protein CA 125 was initially incorporated into the thin-film coating and, upon extraction of protein from the accessible surfaces on the thin film, imprints for CA 125 were formed. The fabrication and analysis of the CA 125 imprinted GNEE was done by using cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) techniques. The surfaces of the very thin, protein imprinted sites on GNEE are utilized for immunospecific capture of CA 125 molecules, and the mass of bound on the electrode surface can be detected as a reduction in the faradic current from the redox marker. Under optimal conditions, the developed sensor showed good increments at the studied concentration range of 0.5–400 U mL−1. The lowest detection limit was found to be 0.5 U mL−1. Spiked human blood serum and unknown real serum samples were analyzed. The presence of non-specific proteins in the serum did not significantly affect the sensitivity of our assay. Molecular imprinting using synthetic polymers and nanomaterials provides an alternative approach to the trace detection of biomarker proteins.

Recueil de titres et pièces diverses concernant le comté de CLERMONT, la ville de REIMS, l'abbaye de MORIENVAL, diverses églises de SENLIS, la ville et l'université d'ANGERS, la famille des URSINS ; Pierre RAMUS, Jean-Antoine DE BAÏF, Ange POLITIEN ; les bibliothèques de François Savary DE BREVES, et de la cathédrale de CHARTRES ; différentes affaires de SORCELLERIE, etc. — De 1269 à 1635 environ.

Originaux et copies. On remarque dans ce volume les pièces suivantes : Lettres patentes de saint Louis, portant donation, à son fils Robert et à ses descendants, du château de Clermont et autres terres par lui possédées dans le comté de Clermont, Paris, mars 1269 (3) ; — Vidimus, par les échevins de Reims, des lettres d'abolition octroyées à cette ville par Charles VII, « Septfaux-lez-Reims », 16 juillet 1429 (4) ; — Lettres patentes de Philippe VI, relatives à la messe célébrée au Palais, par les soins des conseillers des Enquêtes, pour le salut du Roi et de la famille royale, Paris, 4 janv. 1340, en latin, et 22 août 1341, en français (6) ; — Instructions pour « ceulx qui sont ordenez à aller par le royaume demander ayde pour la guerre » ; « extr. du Registre + de la Chambre des comptes, fol. VIIXXX » (8) ; — « Anniex et décime » : dettes contractées par la Papauté envers la France ; extrait du même registre, fol. VIXXXIII V° (10) ; Documents et notes, de la main de Laurent Bouchel : « Extraict du dénombrement rendu au Roy en l'an 1524, le dernier may, par D. Jeanne Darson, abbesse de Morguienval... » (14) ; — Épitaphe, en vers latins, de Jeanne de Mansigni, abbesse de Morienval, décédée en 1485 (14 v°) ; — Notes historiques sur l'abbaye N.-D. de Morienval (15) ; sur la maladrerie de Saint-Lazare, de Crespy-en-Valois (16) ; sur Saint-Thomas de Crespy (17) ; sur plusieurs églises de Senlis (18) ; sur Saint-Nicolas d'Acy (21) ; Extraits de la « Chronique scandaleuse », de la main de P. Dupuy (22) ; — « Vérification des priviléges d'Angers soubz le roy Louys XI, faicte le 7 mars 1474, au Grand Conseil tenu en l'hostel du Roy, à Paris... » (24) ; — Extraits des lettres d'Abbon de Fleury et de Gerbert, par P. Pithou (28) ; — « Extraict d'un viel chartulaire de l'Église de Paris », par P. Pithou (32) ; — « Ex libro coenobii S. Petri de Valle Carnotensis, qui Aganonis appellatur... », de la main de P. Pithou (34) ; — Notes sur les manuscrits de l'église de Chartres ; sur les antiquités de l'église de Hautes-Bruyères et de Saint-Père de Chartres, par P. Pithou (35) ; « Animadversiones Hadriani Valesii in libr[um] P[atris Francisci] Macedo, cui titulus Propugnaculum Lusitano-gallicum » (36) ; — « Extraict d'un registre en parchemin, qui est en la Chambre des comptes et est un inventaire des fiefs, hommages et aultres tiltres estans en la Chambre des comptes de Fourez, en la ville de Montbrison, ledict inventaire faict l'an 1473 », de la main de P. Dupuy (42) ; — « Extraict de certaines escritures produites par Guillaume Bourrelier, procureur fiscal du duc et comte de Bourgongne, contre les chapelains de l'église de Seurre... », de la main de P. Dupuy (44) ; Actes de prise de possession de divers biens, situés à Sognolles et à Coutençon, par le procureur de Guillaume Juvénal des Ursins, orig. (47) ; — Acte relatif aux bois de Coutençon, 30 déc. 1454, orig. (48) ; — Lettres de M[ichel] Juvénal des Ursins, bailli de Troyes, à son frère le chancelier Guillaume, Troyes, 9 oct. 1456 et 30 juin 1469, autogr. (50 et 55) ; — Lettres de [Jean Juvénal des Ursins], archevêque de Reims, à son frère le chancelier Guillaume, Reims, 10 août 1468, autogr., et Paris, 14 juillet 1468, orig. (51 et 56) ; — Traité de mariage entre Jean Juvénal des Ursins, fils du chancelier, et Guyonne de Beauvau, Paris, 29 janv. 1469, orig. (52) ; — Testament de Guillaume Juvénal des Ursins, chancelier de France, Paris, 2 nov. 1471, et codicille, 13 juin 1472, copies (57) ; — Testament de Jean Juvénal des Ursins, archevêque de Reims, Reims, 18 sept. 1472, copie authentique (63) ; — Testament de Jean Juvénal des Ursins, sieur d'Autry, Tours, 14 juin 1474, copie (67) ; — « Inventoire des lettres mises et délaissées à Mr maistre Jehan Lardet,... lieutenant de Mgr le séneschal de Poictou à son siège de Niort,... pour icelles lettres garder en ses mains au prouffit desdicts héritiers [de Jeanne Juvénal des Ursins, en son vivant dame d'Appelvoisin] », Niort, 29 mars 1475 (69) ; Acte de vente à Pierre Doriole, chancelier de France, et à sa femme Charlotte de Bar, par Jean Juvénal des Ursins, de divers biens provenant de l'héritage du chancelier Guillaume Juvénal des Ursins et de sa femme Geneviève Héron, 4 janv. 1478 (73) ; — Transaction amiable passée entre les héritiers de Jacques Juvénal des Ursins, patriarche d'Antioche et évêque de Poitiers, s. d., minute (75) ; — Acte de vente à Jean Jallon, marchand à Tours, par le procureur de Jean Juvénal des Ursins, seigneur de Traînel, de biens provenant de la succession du chancelier Guillaume, Tours, 31 déc. 1478, copie authentique (76) ; — « Inventaire des lettres et tiltres de l'acquest fait par... Pierre Doriole,... chancecelier de France, et dame Charlote de Bar, sa femme, de la maison, court, boucherie, jardin..., que Guion Coeffart, ou nom et comme procureur de noble seigneur Jehan Juvenel des Ursins..., a vendu à mondit seigneur le chancelier..., fait cedit inventaire par nous Guillaume Barbotin et Jehan Pavin, clercs, notaires jurez des contractz royaulx de ceste ville de Tours », 16 janv. 1478, orig. (78) ; — Lettre de [Nicolas] Camusat à [P. Dupuy], au sujet de la famille des Ursins, s. d., autogr. (84) ; Lettres de Henri III, portant nouvelle érection et création d'un conservateur des privilèges royaux en l'Université d'Angers, avec droit de juridiction, Chenonceaux, mai 1577 (85) ; — Lettres de François Ier, concernant les ouvrages de Ramus contre Aristote, Paris, 10 mars 1543, de la main de Laurent Bouchel (87) ; — Note sur le baptême du fils du dauphin Henri de Valois [plus tard François II], 10 fév. 1543, par L. Bouchel (88) ; — Mémoire sur les deniers payés comptant aux rois de France, 1525-1633 (89) ; et lettres de Henri IV et du chancelier Philippe Hurault de Cheverny, au sujet d'un de ces versements, camp devant Laon, 14 juillet 1594 (93) ; — Notes sur divers mots et expressions : « Ad staplum Regis, estal, mallus, placitum, conventus, missi, marchiones, comites, vassi, pares », de la main de Peiresc (96) ; — Notes diverses de P. Dupuy (107), entre autres sur le déchiffrement des alphabets secrets (113) ; Minute d'une lettre latine de Jean-Antoine de Baïf au Pape [Grégoire XIII], autogr. (114) ; — Armes de Strasbourg (115) ; — Blasons des gentilshommes de la sénéchaussée de Beaucaire, tirés des sceaux d'un acte du Trésor des chartes, daté du 6 kal. aug. 1303 ; dessins (116) ; — Blasons coloriés (118-120) ; — Lettres du dauphin Charles [plus tard Charles VII], portant anoblissement de Jean Vaché, bourgeois de Saint-Marcellin en Dauphiné, Melunsur-Yèvre, 4 oct. 1420, parchemin, copie (122) ; — Requête adressée au Roi par Pierre Turquant, marchand de Châtellerault, orig. XVIe s. (123) ; — Note de P. Dupuy sur la part prise à la Ligue par la famille Hennequin (124) ; — Mémoire sur la construction du cadran solaire, de la main de N. Pithou (125) ; — Extraits d'Artémidore, par Ange Politien, Fiesole, 12 sept. 1483, autogr. [anc. feuillets 249 et 250 du ms. grec 3069] (129-130) ; « Illustrissimi domini de Brèves [François Savary] libri arabici, persici et turcici ms. celebriores » (131) ; — « Libri manuscripti bibliothecae ecclesiae Beatae Mariae Carnotensis » (133) ; — « Memoriale librorum Montis Rivi » (139) ; « Histoire au vray de la prévosté d'Orléans, et les jugements contre les imposteurs », 1533, de la main de Laurent Bouchel (142) ; — « Procès-verbal de l'ordre tenu, depuis le 23e febvrier jusqu'au 24e avril 1611, en l'instruction du procès faict à Louis Gauffridy, prebstre, convaincu de sorcellerie, magie et rapt de la personne de Madeleine de La Palu », Aix, fév. 1611 (148) ; — « Depposition d'un prebstre de Marseille..., recognu pour prince des magiciens par des pères Capucins... » (172) ; — « Jugement rendu en Lorraine contre André des Bordes. pour prétendu crime de magie », château de Condé, 28 janv. 1625 (178) ; — Pièce de procédure contre Jean Ralbon, dit Saldetarde, détenu au château de Condé sous l'accusation de magie et sortilège, vers 1635 (180) ; — Décret de Don Andres Pacheco, inquisiteur général d'Espagne, contre la secte des « Alumbrados », 1623, en espagnol (181) ; — Lette du sieur de Villiers à un moine, sur « un point qui regarde les exorcismes », Sens, 6 mars 1635, autogr. (187) ; etc.

Bishop Fuller’s Charge, n.d.

Thomas Brock Fuller was born in 1810 in Kingston, Ont. and died in 1884 in Hamilton, Ont. At the age of seven he was adopted by his aunt Margaret and her husband Rev. William Leeming, a Church of England missionary in Niagara. Fuller would go on to become a minister himself, serving in Montreal, Lachine, Chatham, Thorold and Toronto. In 1875 he became the first bishop of the new diocese of Niagara. Thomas Brock Fuller was married to Cynthia Street, daughter of well-known merchant Samuel Street. Together they raised a family of six sons and three daughters. The poem may have been written by Thomas Brock Fuller himself.

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.

Grant of Permission for lease of military lands from Sir Robert Prescott to Thomas Clark, 1798-1801.

Transcript (original spelling and grammar retained): By His Excellency Robert Prescott Esquire, Captain General and Governor in Chief in and over His Majestys Provinces of Upper and Lower Canada, General and Commander in Chief of all His Majesty’s forces in the Provinces of Upper and Lower Canada, Nova Scotia, New Brunswick and their several Dependencies and in the Island of Newfoundland &ca. &ca. &ca. I do hereby authorise and permit Thomas Clark of Queenstown in the County of Lincoln in the Province of Upper Canada merchant to take possession of all that Lot, piece and parcel of Land (being part of the land reserved by his Majesty for Military purposes) situate, lying and being at Queenstown in the Township of Newark, in the Home District in the said Province of Upper Canada, bounded and abutted as follows, that is to say beginning at the Distance of two Chains and ninety links from the South East End of his Majesty’s Store House, the said distance being measured along the Bank up Stream, thence South thirty nine degrees and an half West one Chain and fifty links thence south fifty degrees and an half East one Chain and thirty links thence North thirty nine degrees and an half East to the Edge of the Bank and from thence along the Bank to the place of beginning, containing thirty one perches and one hundred and twenty five square links and to occupy and hold the said Lot, piece and parcel of Land during pleasure subject nevertheless to the provisoes and Conditions herein after contained, that is to say. First on condition that it shall and may be lawful to and for His Majesty his Heirs and Successors and to and for the Commander in Chief of His Majesty Forces for the time being and to and for the Officer commanding his Majesty’s Forces in Upper Canada for the time being and to and for either of them to determine and make void this present permission to occupy during pleasure the said Lot, Piece or Parcel of Land above described at any time hereafter whenever he or they shall see fit so to do without any compensation or indemnification to the said Thomas Clark or any other Person or Persons whosoever for any Loss Injury or Damage which he the said Thomas Clark or any other Person or Persons whosoever may thereby sustain. Secondly on this further Condition that it shall and may be lawful to and for His Majesty his Heirs and Successors and to and for his and their Officers, Soldiers and Servants at any time hereafter by order of the Commander in Chief of His Majesty’s Forces for the time being or by order of the Officer commanding his Majesty’s forces in Upper Canada for the time being or by order of the Officer of His Majesty’s Corps of Royal Engineers commanding in the said Province of Upper Canada for the time being to enter upon the said Lot Piece and parcel of Land which the said Thomas Clark is hereby permitted to occupy during pleasure or upon any part thereof and to take down and from the said Lot piece and parcel of Land or from any part thereof to remove any dwelling House Store or other Buildings on the said Lot, piece or Parcel of Land or any part thereof erected and to remove any goods or Chattels on the said Lot piece and parcel of Land or on any part thereof or on any such dwelling House Store or other building found or being and that His Majesty his Heirs and Successors or any other Person or Persons whosoever shall not be liable or responsible to the said Thomas Clark or to any other Person or Persons whosoever for any Loss, Injury or Damage which he or they shall or may in such case sustain. Thirdly on this further Condition that the said Thomas Clark shall not erect on the said Lot Piece or Parcel of Land which the said Thomas Clark is hereby permitted to occupy during pleasure or upon any part thereof at any time or times hereafter any dwelling House store or other Building whatsoever of Stone or brick or of any other materials wood only exccepted and that if any dwelling House or Store or other building of Stone or brick or of any other materials except wood shall at any time be erected on the said Lot, piece or parcel of Land or upon any part thereof, then and in such case, this present permission and every Clause and Article thereof shall from thenceforth cease and determine and be absolutely and entirely null and void. And lastly on this further Condition that the said Thomas Clark or any other Person whosoever shall not assign this permission to occupy the said Lot, Piece or Parcel of Land above described to any Person of Persons whosoever, and if any such assignment shall be made by the said Thomas Clark or by any other Person in his right, or on his behalf, that then and in such case such assignment and this permission to occupy during pleasure the said Lot piece and parcel of Land above described, and every Clause and Article thereof shall from thenceforth cease and determine and be absolutely and entirely null and void. Given under my hand at the Castle of St. Lewis in the City of Quebec in the Province of Lower Canada this Ninth day of July in the year of our Lord one thousand seven hundred and ninety eight and in the thirty eighth year of His Majesty’s Reign. [Signed here by Robert Prescott] By Order of the Commander in Chief [Signed here by James Green (Illegible signature)] I the said Thomas Clark above named do hereby accept the above written Permission to occupy during pleasure the said Lot piece and parcel of Land above described upon and subject to the several Provisioes and Conditions above written and each and every of them severally and respectively. In witness whereof I have hereunto set my hand the Sixteenth day of August in the year of our Lord one thousand seven hundred and ninety eight and in the thirty eighth year of His Majesty’s Reign. [Signed here by Thomas Clark] Signed in the presence of [Illegible signature – looks like J. M Donell Lt. Col.] [Illegible – looks like 2d. Battn R. C. Sm?] [Signed here by C. Anderson] Whereas Inconveniences did arise from the peculiar situation of the Ground contiguous to the above described Lot of Land and the occupation thereof, if estimated by the above Limits would prove highly disadvantageous to Mr. Thomas Clark be it known that in consideration thereof we do permit the above Lot to extend one half Chain more in length up stream so as to comprehend the space allowed for the Road between Lots Two + Three, and we do hereby appropriate the said additional space wholly to the use of the said Thomas Clark. In witness whereof we have hereunto subscribed this Thirteenth Day of October in the Year of our Lord one thousand Eight Hundred and one. [Signed here by J. M’Donell Lt. Col] 2d. Battn. R. C. [in?] Com of Fort George + Dependencies Robt. Pilkington Captain Royal Engineers