Edinburgh Research Explorer

Trill, Suzanne

     Edinburgh Research Explorer                                      Lady Anne Halkett: A Life in WritingCitation for published version:Trill, S 2008, 'Lady Anne Halkett: A Life in Writing', pp. 23-25, nls discover, 7.Link:Link to publication record in Edinburgh Research ExplorerDocument Version:Publisher final version (usually the publisher pdf)Published In:nls discoverPublisher Rights Statement:© Trill, S. (2008). Lady Anne Halkett: A Life in Writing. nls discover 7 (pp. 23-25).General rightsCopyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s)and / or other copyright owners and it is a condition of accessing these publications that users recognise andabide by the legal requirements associated with these rights.Take down policyThe University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorercontent complies with UK legislation. If you believe that the public display of this file breaches copyright pleasecontact openaccess@ed.ac.uk providing details, and we will remove access to the work immediately andinvestigate your claim.Download date: 20. Feb. 201522Henry Kirby did not survive to see thesechanges himself as he died at Forsinard Lodge inSeptember 1912 a few hours after shooting a stag.As a later note in his albums records, ‘On returning from the moor to the Lodge he suddenlygot ill and fell down in the smoke room. Wyld andFox got him to bed but he died shortly afterwards.He was buried at the Crofters’ Graveyard a pretty spot near the River he so often fished. Theceremony was attended by many of the localGhillies who held him in great esteem.’ nlssporting leases and factors’ correspondence to specifications and plans for sporting lodges. HenryKirby’s albums with their illustrations of the visitors’ daily activities on the moor and in the Lodge complement these records. Fox’s lease gave him ‘the exclusive right ofshooting all kinds of Game and Deer (Hindsexcepted) and the right of Angling on the RiverHalladale.’ The moor ‘was to be shot over in a fairand sportsman-like manner and a good stock lefton the ground for breeding’. No more than tenstags per year were to be shot. As tenant, Foxagreed to ‘appoint and pay an efficient Keeper toact as a watcher over the ground’ throughout theyear. Exclusive use of Forsinard Shooting Lodgecame with the lease. Where previously sportsmenhad found accommodation where they could, nowlandowners provided furnished housing as part ofan attractive package for their sporting tenants.Much of this property was built specially for theseasonal visitors and sparked a mini buildingboom. Forsinard Lodge offered ample accommodation for Fox, his family, friends andservants together with a Keeper’s House, Kennelsand Ghillies’ Bothy. Again, the tenant was responsible for employing staff and Fox was to‘appoint and pay a competent housekeeper to keepthe lodge in good order and properly aired.’With transport, accommodation, staff andsport arranged, William Fox and his party headednorth each August returning in October. A typicalday at Forsinard involved a hearty early breakfastfollowed by a long pony ride with the ghillies whohad local knowledge of the best place to find deer.The deer-stalkers would stay on the moor for mostof the day, returning exhausted in the evening having ridden, walked or even crawled for miles.Generally, the men shot and fished while thewomen and children remained at the Lodge. Therewas little for them to do there save wait for theirmen folk to return and recount their exploits.The attraction of deer-stalking, as for otherholidays, lay principally in the freedom from everyday routine; it was also exciting and exotic,offering vigorous outdoor exercise and mentalstimulation. This was the sport of the élite but wasalso within reach of relatively wealthy individualswith plenty of free time. However, with the outbreak of the First World War in 1914, thedemand for sporting holidays inevitably declinedand sheep grazed the hillsides previously clearedfor deer. Although tourists returned with the peacethere was never again such an appetite for shootingand fishing.Discover moreHenry Kirby’s albums, 1869-1912 Shelfmark: Acc.12786The National Library of Scotland holds the estate papersof many Scottish landholding families. In addition to theSutherland papers, the Ellice of Invergarry papers are ofparticular significance for sporting tourism with gamebooks for 1841-1909, and Katharine Jane Ellice’s drawingsof hunting and domestic scenes.Sutherland Estates papers:Shelfmarks: Dep.313; Dep.314 Shelfmarks: Acc.10225; Acc.10853; Acc.12173Ellice of Invergarry papers:Shelfmark:MSS.15001-15195Learn more about the Library’s Manuscript collectionsonline at: www.nls.uk/collections/manuscriptsHart-Davis, Duff, Monarchs of the Glen (London, 1978)Shelfmark: H3.78.5149Durie,Alastair J. Scotland for the Holidays.Tourism in Scotland, c.1780-1939 (East Linton, 2003)Shelfmark: HP2.203.03366Above: Documents fromthe Sutherland Estatespapers relating to WilliamFox’s tenancy of ForsinardShootings and Fishings.Courtesy of theCountess of Sutherland.From religious wrangling, to the trials of daily domestic life, Dr Suzanne Trill, Senior Lecturer inEnglish Literature at the University of Edinburgh, profiles the work of early Dunfermline essayistand diarist Lady Anne Halkett, and shows how her ‘Meditations’ were anything but ‘Occasional.’A Life in WritingLady Anne Halkett:23nlsfeaturemight make ill use of them’ .9 Couper did indeedpublish some of Halkett’s ‘Select Meditations’between 1701 and 1704. Useful as these textswere to Couper for his political agenda in the leadup to the 1707 Act of Union, their contents arenot the most stimulating to a modern reader. This is perhaps partly why the true worth ofHalkett’s writing has not so far been fully recognised. Add to this that the art of the ‘occasional meditation’ had become so ubiquitousby the early 18th century that Jonathan Swiftsatirised the practice in Upon a Broom-Stick(1710), it is perhaps understandable that criticshave not been immediately drawn to this material.However, I contend that the contents of Halkett’sextensive writings deserve far more detailed consideration from early modern literary scholars,historians and linguists, as well as those interestedin women’s history in general or the local historyof Dunfermline in particular. Despite her financialdifficulties, Lady Anne Halkett spent a large partof her lengthy widowhood at Abbot House, in her room inscribing her life in writing. nlsday and night; her good works included operatinga weekly surgery for the poor, sending medical supplies to those in need, and acting as a midwifefor women of different social positions; she alsobrought up children and lodged ‘strangers’ whenshe took in young boarders, who could thenattend the local grammar school. These activitieslikewise testify to her assisting the afflicted, whichshe also endeavoured to do with regular alms giving.Although Halkett continues to refer to theselater entries as ‘occasional meditations’, it is striking that the volumes written during herlengthy widowhood are primarily organised bydate rather than subject matter. To the moderneye, this associates them with diary entries. Thishabit also reveals the frequency of Halkett’s writing practice: in one volume, for example, nearly half of the entries were written on eitherMonday or Saturday.  Her record of daily eventsincreasingly reveals her financial difficulties, herfrustration with the religious policies of William of Orange, and her active support of her favouriteEpiscopalian ministers Simon Couper and James Græme during their disputes with thePresbyterians. In addition, Halkett spent the restof her allotted five hours of devotion a day towriting ‘select meditations’ which were predominantly concerned with analysis of specificbiblical books (including Exodus, Jonah andNehemiah). In the final existing volume, Halkettrecords her decision to give her books to her ministers, ‘fearing when I was dead if undisposed of, they might fall into such hands as Right: Abbot Housein Dunfermline,where Halkettspent most of herlife.Left: One of 14 surviving volumesof Halkett's writings.Below: A waxworkof Halkett posed ather writing desk atAbbot House, theonly verified likeness of her.ady Anne Halkett will be an unfamiliar figure to many readers, but those who have visited Abbot House in Dunfermline may recall that she is immortalised there in ‘a room ofher own’ which represents her, surrounded bydevotional texts, as engaged in the act of writing.Tucked among the extensive Pifirrane papers inthe NLS manuscript collection are a series of 14volumes of her devotional writing, which certainly bear testimony to her apparently life-long habit of daily writing. In fact, according to her biographer SimonCouper, Halkett actually produced a series of 21volumes in total, plus ‘about thirty stitchedBooks, some in Folio, some in Quarto, most of them of 10 or 12 sheets, all containing occasional Meditations’1. Mysteriously, seven ofthese volumes are missing, but it is perhaps moremysterious that the 14 extant volumes have, sofar, received hardly any attention. For, whileCouper and Halkett define their contents as‘select’ and ‘occasional’ meditations, from a modern perspective, the occasional entries in particular appear to have more in common withthe essay, diary or autobiography. Collectively,they represent a veritable treasure trove of information about local, national and international political events; the theological disputes between the Presbyterians andEpiscopalians (especially in Dunfermline) throughthe 1670s to the 1690s; the difficulties involved inorganising the household; and the intensity ofemotional attachments and personal experiences.In short, they depict Halkett’s life in writing. Like Halkett, this genre of the ‘occasionalmeditation’ has so far received little critical attention but it was first brought to popular attention by the publication of Bishop JosephHall’s Occasional Meditations in 1606. It wasrevitalised in 1665 when Robert Boyle publishedhis Occasional Reflections. Halkett saw herselfwriting in this tradition and her writing atteststhat it was Hall’s ‘example’ which first drew herto this practice. The influence of both writers canbe seen in parallel subjects: Hall’s book includes a meditation ‘upon the sight of a grave digged up’2,Halkett’s ‘Upon a Grave maker’3; and Boyle’supon ‘His Horse stumbling in a very fair way’ 4has its analogue in Halkett’s ‘upon a fall Sr Jameshad off a Mare’ .5However, even from her earliest surviving volume of such meditations, Halkett moves waybeyond the generally innocuous subject mattersdiscussed by Hall and Boyle. She comments on‘the peace made betwixt France & Spaine’ and‘upon the return of his Mast afftir his long banishment’ .6 She also regularly alludes to Lwww.nls.uk discovernls issue 7   2008contemporary debates over the matter of churchgovernment: considering the 1669 Act ofSupremacy, she begins ‘there is few things thathave been done of Late that have occationedmore variety of opinions then this late Act andmost is unsattisfied with itt, because itt seemes toCrose [cross] what either party aimed att in having absolute power in the Church’.7Unlike any of the published materials by malecontemporaries, Halkett also makes space forconsideration of household events, as well as intimate and personal experiences including miscarriage and childbirth. Dissent amongst servants is also a recurrent theme. Possibly themost heart-rending entry in her entire collection isthat which records her grief at the death of herbeloved daughter Betty just months before herfourth birthday: this was, she writes, ‘like tearinga great piece of my soule from mee’ .8The lengthiest entries among the OccasionalMeditations also focus on personal experience:specifically, they record her devastation at thedeath of her husband, Sir James Halkett ofPitfirrane, in 1670, her ‘deplorable’ state in having become a widow; and her difficulty in reconciling herself to leaving Pitfirrane House and moving to Dunfermline. From her husband’sdeath until her own in April 1699, Halkett regularly commemorates this event not onlyannually but also sets aside Saturdays for weekly contemplation of both it and God’s graciousness to her. Following St. Paul’s advice in1 Timothy 5 from the New Testament, Halkett isdetermined to be ‘a Widow Indeed’. That this was her primary sense of self-identification is witnessed not only in her continual reiteration ofthis phrase but also in her actions. For, like the ideal widow described by StPaul, the extent of Halkett’s ‘Meditations’ and thetime she spent on them (as well as her time instructing her household in prayer and devotion)indicate that she continued her supplications25nlsfeature24Discover more1. Simon Couper. The Life of the Lady Halkett. Edinburgh, 1701.2. Joseph Hall. Occasional Meditations. London, 1630.4. Robert Boyle. Occasional Reflections Upon Several Subjects.London, 1665.3, 5, 6, 7, 8 and 9 from Lady Anne Halkett's 'OccasionalMeditations.'Shelfmarks and pages:3 Shelfmark: Ms. 6491 (pp. 71-5)5 Shelfmark: Ms. 6490 (pp. 84-9)6 Shelfmark: Ms. 6490 (pp. 64-75 and 366-80)7 Shelfmark: Ms. 6492 (p 83)8 Shelfmark: Ms. 6491.2 - or page 2?9 Shelfmark: Ms. 6502. (p 263)Abbot House, Heritage Centre, Maygate, Dunfermline,Fife, KY12 7NE.www.abbothouse.co.uk  01383 733266

English

Lady Anne Halkett: A Life in Writing

Dubrulle, J

McGrew, M J

Pourquié, O

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Lowe, H.

Bundy, Alan

A Science of Reasoning, Alan Bundy ,

System Manuals, written for CompAir Reavel,

The application of proof plans to computer configuration problems, Helen Lowe,

Proof Planning and Industrial Configuration

Riggio, V.

Bishop, S. C.

Finocchiaro, R.

     Edinburgh Research Explorer                                      Genetic analysis of early lamb survival in extensively rearedlambsCitation for published version:Riggio, V, Bishop, SC & Finocchiaro, R 2005, 'Genetic analysis of early lamb survival in extensively rearedlambs' Italian Journal of Animal Science, vol 4, no. SUPPL. 2, pp. 73-75.Link:Link to publication record in Edinburgh Research ExplorerDocument Version:Publisher final version (usually the publisher pdf)Published In:Italian Journal of Animal ScienceGeneral rightsCopyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s)and / or other copyright owners and it is a condition of accessing these publications that users recognise andabide by the legal requirements associated with these rights.Take down policyThe University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorercontent complies with UK legislation. If you believe that the public display of this file breaches copyright pleasecontact openaccess@ed.ac.uk providing details, and we will remove access to the work immediately andinvestigate your claim.Download date: 20. Feb. 2015ITAL.J.ANIM.SCI. VOL. 4 (SUPPL. 2), 73-75, 2005 73Genetic analysis of early lamb survivalin extensively reared lambsV. Riggio1, S.C. Bishop2, R. Finocchiaro11Dipartimento Scienze Entomologiche, Fitopatologiche, Microbiologiche e Zootecniche,Università di Palermo, Italy2Roslin Institute, Edinburgh, ScotlandCorresponding author: Valentina Riggio. Dipartimento Scienze Entomologiche, Fitopatologiche, Microbiologiche eZootecniche, Sezione Produzioni Animali. Viale delle Scienze 13, 90128 Palermo, Italy – Tel: +39 091 7028861 –Fax: +39 091 7028873 – Email: vriggio@unipa.itRIASSUNTO – Analisi genetica della sopravvivenza in agnelli allevati in condizioni estensive. La soprav-vivenza degli agnelli è uno dei caratteri economici più importanti nell’allevamento ovino. A questo scopo sonostate esaminate 4.583 osservazioni di agnelli Scottish Blackface di cui erano noti i dati ripetuti di sopravvivenza(nascita, 1, 4, 8 e 12 settimane) e di peso (nascita, 4, 8, 12, 16, 20 e 24 settimane). Sono stati utilizzati un siremodel per la stima dei parametri genetici della sopravvivenza e un animal model per la stima delle correlazionigenetiche tra la sopravvivenza e gli incrementi ponderali degli agnelli. Le ereditabilità stimate sono risultatepiù alte di quelle riportate in bibliografia e le correlazioni genetiche tra la sopravvivenza e gli incrementi pon-derali sempre positive e moderate (in media 37,5%), confermando la possibilità di inserire la sopravvivenzadegli agnelli nei programmi di selezione della razza Scottish Blackface.KEY WORDS: lamb survival, binary trait, genetic parameters, live weight.INTRODUCTION – In sheep production, lamb survival is an important economic trait (Conington et al.,2004). Therefore, this trait has been studied by many scientists, especially in countries with an extensive hus-bandry system. In the United Kingdom, the number of lambs dying before weaning has been estimated rang-ing from 5 to 40% (Eales et al., 1983). The genetic evaluation of survival is complicated because this trait hasa binomial distribution whereas most analytical procedures assume normality. Although a lot of studies havebeen carried out on lamb survival, very little is available in literature on estimates of genetic parameters andnon-genetic effects. Further, little has been reported about the genetic correlations between this trait andweight at fixed ages. The object of this study was to estimate genetic parameters for lamb survival and thegenetic relationships with early growth in Scottish Blackface sheep.MATERIAL AND METHODS – The dataset accounted for 4,583 records collected from 1988 to 2003 in aScottish Blackface flock. It contained animal identification, sire, dam, sex (S), death-date, date of birth (DB),year of birth (YB), age of dam (AD), husbandry group at lambing (G) and litter size (LS). Five traits were cal-culated, showing if lambs were alive or dead (coded with 0 or 1 respectively) at birth, and at 1, 4, 8 and 12weeks. The lambs’ weights at birth, and at 4, 8, 12, 16, 20, 24 weeks of age were also available. The pedigreefile comprised 1,416 dams and 178 sires. Binary analyses were carried out, fitting a Generalized Linear Model(GLM), assuming a Bernoulli distribution and using a logit link function with Genstat software (LawesAgricultural Trust, 1983). Several models were fitted and compared using the deviance values. In Model 1 theeffect of YB, LS, YB×LS×G interaction, S, AD, DB (covariate) and YB×DB interaction were fitted as fixed effects.The other models were similar to Model 1, except a fixed effect (S, LS, AD and YB from Model 2, 3, 4 and 5,ASPA_imp01_02_03  15-07-2005  9:54  Pagina 73PROC. 16th NAT. CONGR. ASPA, TORINO, ITALY74 ITAL.J.ANIM.SCI. VOL. 4 (SUPPL. 2), 73-75, 2005respectively) was eliminated in each in order to determine its significance using the χ2 test. Genetic parame-ters were estimated using ASREML (Gilmour et al., 2000). The heritabilities (h2) of survival traits were esti-mated using the same fixed effects of the Model 1, fitting sire as a random effect. Analyses were first carried outassuming lamb survival as normally distributed and later using probit transformation within a GLM frame-work. A logit transformation was fitted, but it produced h2 estimates outside the parameter space and thereforeit was discarded. Genetic correlations were estimated fitting the same model with the sire as a random effect inanalyses of survival traits and animal as a random effect in analyses of survival and weight traits.RESULTS AND CONCLUSIONS – Results from GLM demonstrated that the most important factor forthe survival at birth was S: it was highlighted that males were more likely to die than females. For the othersurvival traits, the most important factor was LS. Single-born and twin-born were less likely to die thantriplet-born. Hinch et al. (1983) also reported that mortality usually increases with LS. AD was also importantand lambs born from two-years-old ewes were more likely to die than lambs born from older ewes. A commonobservation is that very young ewes have lower lamb survival (Atkins, 1980), probably because lambs bornfrom young ewes receive less attention from the mother.Table 1. Heritability estimates for survival traits both with probit and normal analyses.Normal analyses (*) Probit analyses Expected underlying valueh2 h2 h2Birth 0.09 ± 0.03 0.33 ± 0.11 0.301 week 0.10 ± 0.03 0.22 ± 0.09 0.274 weeks 0.07 ± 0.03 0.17 ± 0.07 0.178 weeks 0.07 ± 0.03 0.14 ± 0.07 0.1612 weeks 0.05 ± 0.03 0.08 ± 0.06 0.10(*) treating survival as a continuous variableHeritabilities for survival traits, estimated using a sire model, considering these traits both as binary and con-tinuous traits are shown in Table 1. The estimates from the probit analyses are very close to the expectedunderlying h2 values, calculated with Dempster and Lerner’s formula (1950). Note that the h2 estimates declinefrom birth onwards. These results show that at birth the genetic component has a more significant influenceon survival than at higher ages; this probably confirms the large influence of environmental factors on subse-quent survival. Several results for survival have been reported in the literature, but generally we haveobtained higher heritabilities than comparable studies. For example, Matika et al. (2003), fitting a sire thresh-old model, estimated a h2 of 0.04 in Sabi sheep and Snyman et al. (1998) in Afrino sheep found h2=0.02.Table 2. Genetic correlations with s.e. between survival traits and weight traits.Birth Weight 4 Weight 8 Weight Weight Weight WeightWeight weeks weeks 12 weeks 16 weeks 20 weeks 24 weeksBirth 0.37±0.10 0.75±0.05 0.52±0.07 0.52±0.08 0.30±0.10 0.29±0.08 0.35±0.121 week 0.06±0.10 0.71±0.05 0.53±0.07 0.45±0.09 0.15±0.10 0.26±0.08 0.32±0.114 weeks 0.09±0.11 0.66±0.06 0.47±0.09 0.44±0.10 0.26±0.11 0.31±0.08 0.47±0.128 weeks 0.18±0.12 0.33±0.12 0.26±0.11 0.46±0.11 0.41±0.12 0.32±0.10 0.59±0.1312 weeks 0.16±0.13 0.31±0.12 0.14±0.12 0.37±0.12 0.40±0.12 0.32±0.11 0.58±0.13ASPA_imp01_02_03  15-07-2005  9:54  Pagina 74ITAL.J.ANIM.SCI. VOL. 4 (SUPPL. 2), 73-75, 2005 75PROC. 16th NAT. CONGR. ASPA, TORINO, ITALYThe estimated genetic correlations between survival traits were high, in particular those between survival at1, 4, 8 and 12 weeks converged to the boundary value set in ASREML (0.99). The genetic correlations betweensurvival at birth and other survival traits were lower but their standard errors were rather high. More inter-esting results were obtained in terms of correlation between survival traits and weight traits (Table 2). Theestimates resulted always moderately positive, so there seem to be no antagonism between survival traits andweight traits. Many authors have suggested a positive relationship between survival and birth weight (e.g. Mukasa-Mugerwa et al., 2000), but no published estimate of this relationship appears to be available. Inconclusion, the results of this study have shown that lamb survival is a heritable trait in the Scottish Blackfacesheep. It is most heritable at birth and declines later on due to environmental factors. Therefore it might bepossible to include early lamb survival in a selection programme for this breed. Moreover, the moderate andpositive genetic correlations between survival and weight traits suggest that including survival traits in breed-ing programmes could lead to indirect improvement of weight traits in Blackface sheep.REFERENCES – Atkins, K.D., 1980. The comparative productivity of five ewe breeds. 1. Lamb growthand survival. Austr. J. Exp. Agric. Anim. Husb. 20:272-279. Conington, J., Bishop, S.C., Waterhouse, A., Simm,G., 2004. A bioeconomic approach to derive economic values for pasture-based sheep genetic improvement pro-grams. J. Anim. Sci. 82:1290-1304. Dempster, E.R., Lerner, I.M., 1950. Heritability of threshold characters.Genetics. 35:212-236. Eales, F.A., Small, J., Gilmour, J., 1983. Neonatal mortality of lambs and its causes. InSheep Production (ed. W.Haresign), pp. 289-298. Butterworths, London. Gilmour, A., Thompson B., Cullis S.,Welham S.J., 2000. AS-REML Reference Manual. Orange 2800. Australia: NSW Agriculture. Hinch, G.N.,Kelly, R.W., Owens, R.W., Crosbie, S.F., 1983. Patterns of lamb survival in high fecundity Boorola Merino flocks.Proc. N.Z. Soc. Anim. Prod. 43:29-32. Lawes Agricultural Trust, 1983. GENSTAT a general statistical pro-gram. Numerical Algorithms Group. Matika, O., Van Wyk, J.B., Erasmus, G.J., Baker, R.L., 2003. Geneticparameter estimates in Sabi sheep. Livest. Prod. Sci. 79:17-28. Mukasa-Mugerwa, E., Lahlou-Kassi, A.,Anindo, D., Rege, J.E.O., Tembely, S., Tibbo, M., Baker, R.L., 2000. Between and within breed variation in lambsurvival and the risk factors associated with major causes of mortality in indigenous Horro and Menz sheepin Ethiopia. Small Rumin. Res. 37:1-12. Snyman, M.A., Erasmus, G.J., Van Wyk, J.B., Olivier, J.J., 1995. Directand maternal (co)variance components and heritability estimates for body weight at different ages and fleecetraits in Afrino sheep. Livest. Prod. Sci. 44:229-235.ASPA_imp01_02_03  15-07-2005  9:54  Pagina 75

Genetic analysis of early lamb survival in extensively reared lambs

Freeman, T C

Curry, B J

Calam, J

Woodburn, J R

An evaluation of natural vs. synthetic substrates for measuring the antitryptic activity of soybean samples.

Demonstration of pancreatic secretory trypsin inhibitor in serum-free culture medium conditioned by the human 1420

Epidermal growth factor: internal duplication and probable relationship to pancreatic trypsin inhibitor.

Excretion of a tumour-associated trypsin inhibitor (TATI) in the urine of patients with gynaecological malignancy.

Expression of pancreatic secretory trypsin inhibitor gene in neoplastic tissues.

Growth stimulating activity on 3T3 fibroblasts of the molecular weight 6,500-peptide purified from rat pancreatic juice. Biochem Biophys Res Commun 1986;139:545-550.

Immunochemical demonstration of an ovarian cancer-associated peptide.

Immunohistochemical localisation of pancreatic secretory trypsin inhibitor in fetal and adult pancreatic and extrapancreatic tissues.

Isolation of a crystalline trypsin inhibitor-anticoagulant protein from the pancreas.

Pancreatic secretory trypsin inhibitor as an acute phase reactant. Clin Biochem 1988;21:19-27. 24. Satake

Primary amino acid sequence similarity between human epidermal growth factor-urogastrone. human pancreatic secretory trypsin inhibitor and members of the porcine secretin family.

Purification and characterisation and amino acid sequencing of two pancreatic secretory trypsin inhibitors in rat pancreatic juice. Biol Chem HoppeSeyler

Purification and characterisation of a tumour-associated trypsin inhibitor from the urine of a patient with ovarian cancer.

Purification and sequencing of a trypsin-sensitive cholecystokinin-releasing peptide from pancreatic juice.

Release of pancreatic secretory trypsin inhibitor from human hepatoblastoma cells on stimulation with cytokines.

Specific binding of human pancreatic secretory trypsin inhibitor to various cultured cells.

Sugimoto EL Competition of a growth stimulating-/cholecystokinin (CCK) releasing peptide (monitor peptide) with epidermal growth factor binding to 3T3 fibroblasts.

The measurement of serum immunoreactive pancreatic secretory trypsin inhibitor in gastrointestinal cancer and pancreatic disease.

The primary structure of the human pancreatic secretory trypsin inhibitor.

Two apparent human endothelial cell growth factors from hepatoma cells are tumour-associated proteinase inhibitors.

Varying occurrence of gastroduodenal immunoreactive pancreatic secretory trypsin inhibitor.

Pancreatic secretory trypsin inhibitor stimulates the growth of rat pancreatic carcinoma cells

Doeschl, A.

Davison, M.

Rasmussen, H.

Reid, G.

A cellular model of braided rivers,

A computational investigations of river braiding,

A hyperbolic PDE with parabolic behaviour,

A Monograph of Sediment Transport in Alluvial Streams, Teknisk Forlag,

A new quantitative test of geomorphic models, applied to a model of braided streams,

An Introduction to Nonlinear Partial Differential Equations,

Assessing Braided River Dynamics With a Cellular Model,

Cellular automata approaches to biological modeling,

Contrasting the goal, strategies, and predictions associated with simplified numerical models and detailed simulations,

Fluvial Processes and Environmental Change,

Gravel-bed Rivers 5, Hydrological

Numerical Analysis, Chapter 7.8.2,

Numerical Methods for Partial Differential Equations,

Numerical solution of partial differential equations: Finite difference methods,

Process and form in gravel braided streams: Laboratory modelling and field observations,

Properties of a cellular braided stream model,

Similarity Solutions of Nonlinear Partial Differential Equations,

Simulating Clastic Sedimentation,

The dynamics of Runge-Kutta methods,

The relative efficiency of alternative defect control schemes for high order continuous RungeKutta formulas,

Universality and complexity in cellular automata,

Validation of braided-stream models: Spatial state-space plots, self-affine scaling and island shape comparison,

Assessing cellular automata based models using partial differential equations

Dale, J K

Fraboulet, S

     Edinburgh Research Explorer                                      The lunatic fringe gene is a target of the molecular clock linkedto somite segmentation in avian embryosCitation for published version:McGrew, MJ, Dale, JK, Fraboulet, S & Pourquié, O 1998, 'The lunatic fringe gene is a target of themolecular clock linked to somite segmentation in avian embryos' Current biology : CB, vol 8, no. 17, pp.979-82.Link:Link to publication record in Edinburgh Research ExplorerDocument Version:Publisher final version (usually the publisher pdf)Published In:Current biology : CBPublisher Rights Statement:© 1998 Current Biology PublicationsGeneral rightsCopyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s)and / or other copyright owners and it is a condition of accessing these publications that users recognise andabide by the legal requirements associated with these rights.Take down policyThe University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorercontent complies with UK legislation. If you believe that the public display of this file breaches copyright pleasecontact openaccess@ed.ac.uk providing details, and we will remove access to the work immediately andinvestigate your claim.Download date: 20. Feb. 2015Brief Communication 979The lunatic Fringe gene is a target of the molecular clock linkedto somite segmentation in avian embryosMichael J. McGrew, J. Kim Dale, Sandrine Fraboulet and Olivier PourquiéThe most obvious segments of the vertebrate embryoare the trunk mesodermal somites which give rise tothe segmented vertebral column and the skeletalmuscles of the body. Mechanistic insights intovertebrate somitogenesis have recently been gainedfrom observations of rhythmic expression of the avianhairy-related gene (c-hairy1) in chick presomiticmesoderm (PSM), suggesting the existence of amolecular clock linked to somite segmentation ([1];reviewed in [2]). Here, we show that lunatic Fringe(lFng), a vertebrate homolog of the Drosophila Fringegene, is also expressed rhythmically in PSM. The PSMexpression of lFng was observed as coordinated pulsesof mRNA resembling the expression of c-hairy1. Weshow that c-hairy1 and lFng expression in the PSM arecoincident, indicating that both genes are responding tothe same segmentation clock. The genes were found todiffer in their regulation, however; in contrast to c-hairy1, lFng mRNA oscillations required continuedprotein synthesis, suggesting that lFng could be actingdownstream of c-hairy1 in the clock mechanism. InDrosophila, Fringe has been shown to play a role inmodulating Notch–Delta signalling [3,4], a pathwaywhich in vertebrates has been implicated in definingsomite boundaries [5–9]. These observations place thesegmentation clock upstream of the Notch–Deltapathway during vertebrate somitogenesis.Address: Laboratoire de génétique et de physiologie dudéveloppement (LGPD), Developmental Biology Institute of Marseille(IBDM), CNRS-INSERM-Université de la méditerranée-AP de Marseille,Campus de Luminy, Case 907, 13288 Marseille Cedex 09, France.Correspondence: Olivier PourquiéE-mail: pourquie@ibdm.univ-mrs.frReceived: 6 July 1998Revised: 4 August 1998Accepted: 4 August 1998Published: 17 August 1998Current Biology 1998, 8:979–982http://biomednet.com/elecref/0960982200800979© Current Biology Publications ISSN 0960-9822Results and discussionGenetic studies in the mouse have implicated theNotch–Delta signalling pathway as playing a role in seg-mentation [10]. Mice harbouring mutations in the Notch1,RBP-J kappa, or Delta1 genes retain a basic metamerismof paraxial mesoderm derivatives [5–7]. The somites inthese mutants are, however, uncoordinated and theiranterior–posterior compartments are incorrectly specified.Thus, the Notch–Delta pathway is thought to act laterthan the segmentation clock to both coordinate somite for-mation and specify boundaries during the segmentationprocess. Therefore, genes in this pathway are potentialdownstream targets of the segmentation clock; however,the chick genes c-Notch1 and c-Delta1 do not display rhyth-mic expression in the PSM [11]. A link between the twosystems has yet to be established. To explore such a link,we analysed the expression of lFng during somitogenesisin the chick embryo. The lFng gene is expressed in thePSM [12–15] and has recently been shown to play a role inmouse somitogenesis [8,9]. We show that lFng transcriptsare expressed in a rhythmic fashion in the PSM and thusappear to be directly regulated by the segmentation clock.Expression of lFng is cyclical in the PSMTo analyse the expression of lFng in the PSM, a series ofembryos (n = 49) were hybridised with an lFng probe.Expression of lFng was found to vary considerably evenamong embryos of the same somite number (Figure 1).Some embryos showed expression in two domains: a broadcaudal domain extending from the tail bud region up tothe rostral third of the PSM, and a narrower band locatedmore rostrally in the PSM. In other embryos, the broadexpression domain appeared to narrow, by becoming pro-gressively downregulated caudally, while moving anteri-orly. Concomitantly, the rostral-most domain becamenarrower and progressively faded in intensity. Weakexpression was also observed within the anterior part ofnewly formed somites. Therefore, in the chick PSM, lFngdisplays a dynamic expression pattern.In order to demonstrate the cyclical nature of this expres-sion profile, the caudal portion of chick embryos wasdivided into two halves by sectioning along the midline;one half was fixed immediately, while the other half wascultured in vitro (Figure 2). When the experimental halfwas cultured for 30 minutes (n = 15), a very differentprofile of lFng expression was observed in each of the twohalves (Figure 2a). This analysis enabled us to order theexpression sequence of lFng in the PSM (Figure 1).When the experimental half was incubated for 90 minutes(n = 5), a new somite was generated in the explant, andthe two halves showed identical lFng expression patterns(Figure 2b). These experiments demonstrate that, like c-hairy1, lFng expression appears as a cyclical wavefrontthat sweeps along the PSM once during the formation ofeach somite.Cyclical expression of lFng is an autonomous property ofthe PSMIn order to analyse further the regulation of this expres-sion pattern, we tested whether progression of the wave-front results from the propagation of a signal in the PSM.To that end, the expression of lFng was assayed in caudal-half embryo explants in which, on one side, the posteriorpart including the tailbud was surgically ablated. Bothsides were then cultured for the same time. In all cases(n = 7), the same expression pattern of lFng was observedin the operated and control sides, indicating that themovement of the lFng wavefront does not rely on signalpropagation (Figure 2c). This suggests that cyclicalexpression of lFng is an intrinsic property of the PSM. Toverify this, we compared lFng expression in caudal-halfembryo explants (n = 10) in which, on one side, the PSMwas microdissected and isolated from the surroundingtissues. After culture under these conditions, the expres-sion pattern in the isolated PSM was found to be the sameas that of the intact side (Figure 2d). Therefore, like c-hairy1, rhythmic expression of lFng is an autonomousproperty of the PSM.Tandem oscillation of lFng and c-hairy1 in the PSMA precise comparison of the lFng expression domain withthat of c-hairy1 in the PSM was performed in the caudalhalves of chick embryos. Except in the rostral-most PSM,the expression domain of lFng on one side of the embryowas similar to that of c-hairy1 on the other side (n = 20,Figure 3a–c). These findings indicate that the oscillationsof both c-hairy1 and lFng are coordinated in both time and980 Current Biology, Vol 8 No17Figure 1Expression of lFng appears as a wavefront sweeping across thepresomitic mesoderm. Upper panels show the dorsal view of thecaudal region of (a–d) 17 somite stage and (e) 18 somite stage chickembryos hybridised with the lFng probe. In each panel, the last formedsomite (SI) is indicated by an arrowhead. Expression in the PSMappears as a broad caudal domain, which progressively movesanteriorly while narrowing as the caudal cleft of somite S0 forms. Therostral domain corresponds to the residual expression domain of theprevious wavefront (see panel e) and progressively fades in intensity asthe caudal domain moves anteriorly. The rostral domain subsequentlybecomes anteriorly restricted in SI. Rostral is to the top. Bar = 200 µm.The lower panel illustrates schematically the correlation between lFngexpression in the PSM with the progression of somite formation. SIIindicates the last-but-one somite.SIS0SIS0 SISII90 min17 somites 18 somites   Current BiologyS0SISIIS0(a) (b) (c) (d) (e)Figure 2The lFng gene is expressed in a rhythmic fashion, correlating withsomite formation, and is independent of adjacent structures. Caudal-half embryo explants were sagittally divided so that one half (left side)was either (a,b) fixed immediately or (c,d) cultured for the same timeperiod as the right half. In all panels, both halves were hybridised withthe lFng probe. (a) The right half was cultured for 30 min, and showeda different pattern of lFng expression from the left half. (b) When theright half was cultured for 90 min, a new somite formed, and the twohalves showed identical lFng expression patterns. Red arrowheadsindicate segmented somites. (c) The caudal part of the right explantwas surgically removed and the remainder cultured in parallel with itscontralateral half for 30 min. (d) Isolated PSM explant cultured for thesame time period as the intact contralateral half (30 min). Theexpression pattern of lFng in the PSM is similar in operated and controlhalves in panels c and d. Rostral is to the top. The scale bar represents260 µm in (a–c) and 130 µm in (d).(a) 30 min(b) 90 min(c) 30 minCurrent Biology   (d) 30 minspace and, thus, are controlled by the same segmentationclock. In the rostral-most PSM, in contrast, the expressiondomains of these two genes progressively diverge at theforming border of somite S0 (Figure 3d,e). Cycloheximide blocks lFng oscillationsThe c-hairy1 gene encodes a transcription factor of thebasic helix-loop-helix (bHLH) family whereas lFngencodes a secreted molecule. As both genes are expressedwith similar dynamics in PSM, one hypothesis might bethat lFng acts downstream of c-hairy1. Such a model impliesthat translation of the c-hairy1 product will be required inorder to drive lFng expression. To address this idea, weexamined whether blocking protein synthesis with cyclo-heximide affects lFng expression. Progression of the lFngwavefront was found to be retarded in cycloheximide-treated explants compared with the controls (10 out of 15cases, Figure 4a). To confirm that the dynamic expressionof lFng in PSM was indeed blocked, one explant half wasfixed immediately while the other half was cultured for30 minutes in the presence of cycloheximide. The expres-sion pattern of lFng was similar on both sides, indicating arapid and effective block of the lFng wavefront (9 out of 10cases, Figure 4b). In similar experiments, c-hairy1 expres-sion was not affected (n = 7; data not shown, and [1]).These experiments show that the regulation of c-hairy1 andlFng differ: both genes appear to be downstream of thesegmentation clock, but only lFng requires protein synthe-sis to drive its dynamic expression. It is therefore possiblethat lFng acts downstream of c-hairy1 in the PSM, althoughwe cannot rule out the possibility that these genes are reg-ulated by parallel pathways.Our results demonstrate that lFng is a target of the recentlyidentified segmentation clock, leading to periodic expres-sion of lFng in the region where the prospective somiteboundaries will form. In the fly, Fringe acts to differentiallymodulate Notch reception of Delta and Serrate ligands[3,4]. During vertebrate somitogenesis, Notch–Delta sig-nalling is required for specification of the anterior and pos-terior somitic compartments, which occurs in therostral-most PSM [10]. The lFng gene has also been shownto be essential for this process in the mouse [8,9]. The dis-crete expression domains of Notch and its ligands in thisregion where lFng oscillates suggests that, in the chickrostral PSM, lFng also modulates Notch signalling to estab-lish the somite boundary. Thus, clock control on this localmodulation of the Notch–Delta signalling pathway wouldconfer the periodic arrangement of the boundaries thatunderlie the segmental body plan.Brief Communication 981Figure 3The expression domains of lFng and c-hairy1are similar in the PSM except in the rostral-most region. (a–c) Caudal portions ofembryos were sagittally divided along themidline; each left half was hybridised with alFng probe whereas each right half washybridised with a c-hairy1 probe. The twogenes share the same expression domain inthe PSM. Panels a, b and c show threedifferent stages in the progression of the c-hairy1 and lFng wavefronts in the PSM. Redarrowheads indicate somite SI. (d,e) Alternateparasagittal sections hybridised with (d) lFngand (e) c-hairy1. The expression domainshave clearly diverged along the formingsomitic cleft. Black arrowheads indicate therostral border of somite S0. White arrowheadsindicate the forming caudal boundary ofsomite S0. Rostral is to the top. The scale barin (c) represents 230 µm and applies to (a–c);the scale bar in (e) represents 115 µm andapplies to (d,e).Current Biology  (a) (b) (c) (d) (e)Figure 4Dynamic expression of lFng in the PSM depends on de novo proteinsynthesis. (a) Half-embryo explants cultured for 30 min with (right side)or without (left side) cycloheximide (CHX). Expression of lFng differsbetween the control and CHX-treated sides. (b) The control explant(left) was fixed immediately while the right side was cultured for 30 minin the presence of cycloheximide. Expression of lFng was similar ineach half. Note that cycloheximide treatment results in the stabilisationof mRNA transcripts within the expression domain [19]. Rostral is tothe top. Bar = 140 µm.Current Biology   (a) (b)Control CHX Control CHXMaterials and methodsEggs, embryos and somite nomenclatureFertilised chick eggs (Gallus gallus, JA57, Institut de SélectionAnimale, Lyon, France), obtained from commercial sources, were incu-bated for up to 48 h in a humidified atmosphere at 38°C. The embryoswere staged by the number of somite pairs formed. Chick embryos atstages ranging from 15 to 20 somite pairs were used throughout thisstudy. The somite staging system [16] has been used for numberingsomites. In this system, the newly formed somite is referred to assomite SI. We refer to somite S0 as being the forming somite whosecaudal clefts are not yet completely formed.In vitro culture and cycloheximide treatment of explantsMicrosurgical operations on the embryonic halves and in vitro culturewere carried out as described [1]. The caudal portion of chick embryoswas separated along the midline. The experimental half was incubatedin the presence of 10 µM cycloheximide and the contralateral half waseither cultured for the same period of time or fixed immediately. In allseries, explants were processed for whole mount in situ hybridisationwith c-hairy1 or lFng probes. Efficiency of protein synthesis inhibition inthese conditions has been previously established [1]. In situ hybridisationThe c-hairy1 probe has been described [1]. The lFng/c-Fringe1 probewas produced as described [15]. Whole-mount in situ hybridisationwas performed as described [17]. Embryos were photographed aswhole mounts using a Leica MZ10 stereomicroscope. In situ hybridisa-tions on 20 µm cryosections were carried out as described [18].AcknowledgementsWe thank Ken-Ichi Katsube for the kind gift of the lFng/c-Fringe1 probe,Stephen Kerridge and David Ish-Horowicz for critical reading of the manu-script. M.J.M. is the recipient of a postdoctoral EMBO fellowship. J.K.D. is arecipient of a Wellcome Travelling Research Fellowship. Financial supportwas provided by the Centre National de la Recherche Scientifique (CNRS),the Association Française contre les myopathies (AFM), the Associationpour la Recherche contre le Cancer (ARC) and the Fondation pour laRecherche Médicale (FRM).References1. Palmeirim I, Henrique D, Ish-Horowicz D, Pourquie O: Avian hairygene expression identifies a molecular clock linked tovertebrate segmentation and somitogenesiss. Cell 1997,91:639-648.2. Cooke J: A gene that resuscitates a theory – somitogenesis and amolecular oscillator. Trends Genet 1998, 14:85-88.3. Panin VM, Papayannopoulos V, Wilson R, Irvine KD: Fringemodulates Notch–ligand interactions. Nature 1997, 387:908-912.4. Fleming RJ, Gu Y, Hukriede NA: Serrate-mediated activation ofNotch is specifically blocked by the product of the gene fringe inthe dorsal compartment of the Drosophila wing imaginal disc.Development 1997, 124:2973-2981.5. 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