The earlier neolithic in Central Europe: a study of the linear pottery cultures and their relationships with the contemporary cultures of South-East Europe

SCOPE OF THE THESIS: The scope of the thesis in geographical terms is concerned with the region east of the Rhine as far as the Dniester basin;it discusses the earliest agricultural settlements as far north as the lower Rhine,and the middle courses of the Elbe,Oder and Vistula rivers,and,for comparative purposes,as far south as central Greece and south -west Anatolia.The study is concentrated,however,in the basin of the river Danube and its tributaries which flow from the Alps and the Carpathians. Chronological,;,the thesis begins with the earliest development of agriculture in the Near East and ends with the beginning of metallurgy in the Carpathian area,that is from approximately 7500 b.c. to 3500 b.c.; however,the study is concerned especially with the earliest agricultural communities of south -east and central Europe, and the immediate subsequent development of these, so that chronologically it is concentrated in the period 4500 - 3800 b.c.TOPOGRAPHICAL DESCRIPTION: The river Danube rises in the western Alps,i , the region of south -west Germany known as Wurtternburg;it flows eastwards through a relatively narrow valley until the "Vienna Gates ", when it is joined by the large river Morava which flows from the western Carpathians;in its middle course, the Danube, and its tributary the Tisza, have made an important lowland basin separating the Alps from the Carpathian :ountains.The middle course of the river is separated from the lower course by the narrow gorge ruade by the hard underlying rocks at the "Iron Gates ".Still flowing eastwards, the Danube separates the eastern Carpathians from the Balkan. range of mountains of Bulgaria and YuL;oslavia,and flows through a marshy delta into the Black Sea.The underlying deposits for much of the length of the Danube valley and that of its tributaries consist of wind -blown loess, deposited under periglacial conditions during the late glacial and immediate post - glacial period;leess deposits also occur in the basins of the large rivers, such as the Brut,Dniester, and southern Bug, which flow from the northern edge of the Carpathians to an 7: 11lack Sea,aud in the upper basins of the riversouch as the Elbe,Oder and Vistula,which flow from the northern edge of the Carpathians to the Baltic and the North Sea.(Butzer, 1965, fig.80). vi Loess deposits do not occur south of the Danube basia;except for one or two large r. ivers 3 such as the Maritsa and Struma in south Bulgaria, aa±d the Vardar in south Yugoslavia, and the narrow coastal plain of the Aegean coast, most of south -east _urope(the Balkan peninsular)consists of high bare dry -ountains,The middle Danube valley, which is the part referred to the most frequently in this study, consists of a wide loess plain west of its right bank known as the Pannonian Plain or Little Hungarian Plain,and a larger loess plain east of its tributary the Tisza, known as the Great Hungarian Plain (Alfòld);between the Tisza and the Danube, there is an alluvial area which was hardly settled in the period with which this study is concerned.THE NATURAL ENVIRONMENT IN CENTRAL EUROPE: In Europe, east cf the Alps, during the period 5000 - 3000 b.c., that is in the Atlantic climatic period(pollen zone VIT a), it is possible to distinguish two basic ecological regions with differing climates,geology, and vegetation.The two regions are divided roughly by the Danube below its bend at Osijek in north Yugoslavia:the central European, north of the Danube, having a temperate, humid climate;the south -east Turopean, south of the Danube, having a sub -tropical, Mediterranean ?humid to sub- humid climate;a transitional regional in between. The loess lowlands form one of the conspicuous characteristics of the geology of the central European temperate region whereas loess is markedly absent in south -east Europe.Soaaae of the central European loess is still covered with the rich, fertile, basic chernozem soil;during the Atlantic climatic period, when the climate was rather wetter than modern times, and the forest covering was largely preserved, the distribution of chernozem soil must have been very much greater,as is indicated on many prehistoric sites of the area.'xcept for the narrow coastal belt of sub -tropical woodland of the Mediterranean coast, and the high mountain flora, the natural vegetation of Europe is deciduous and mixed forest;but, because of the differing climatic and geological background, the density and dominant species of vegetation vary with each region.On the loess lands of temperate central Europe although during the Atlantic climatic Periód the climate was warmer and wetter than at present, vii the soil was very permeable, and, in sore' of the drier basins, such as the Great Hungarian P1aii(Alföld) and the Bohemian- Moravian plain,the loess soils would have supported open oak woodland ;in the moister loess basins, however, the natural vegetation would have been thicker oak woodland grading to forest. (Butzer, 1965,446 -447).The difference between the two .ecological regions, especially the Mediterranean woodland and the temperate woodland of the drier loess basins, would not have been so great as to discourage or impede colonisation from one region to the other ;rather the contrary,in fact:the temperate woodlands must have seemed to colonists from the Mediterranean region to be a natural continuation of their native woodlands,with rich soil underneath.The difference,as Butzer remarks, is "im degree rather than in kind; especially with increasing latitude.(Butzer, 1965, 449).The winters of temperate Europe,even in the Atlantic cli matic period,were definitely colder than those further south,the summers were wtter,and the hours of sunshine per annum were less.Thus, some form of conscious or unconscious adaptation and response to the natural environment of temperate Europe was inevitable for colonists whose economy and material culture had been developed in a more southern natural region.HISTORY OF RESEARCH IN THE PROBLEMS OF THE EARLY PREHISTORY OF CENTRAL AND SOUTH-EAST EUROPE: The first and only prehistory specifically of the Danube valley was written by V.Gordon Childe in 19291this consisted of a synthesis of the material found in the regions described above, and their interpretation in human terms, or, as the Americans prefer it,in terms of human dynardics.Such a synthesis has not been attempted since,even though the mass of material and hypotheses which accompany it must have increased a hundredfold since then.(Childe,1929).The various "Chronologies" of Vladimir Milojcié do synthesise the material of this region to a certain extent, and chronologically correlate the material of each area;but they could hardly be called prehistory, since very few aspects of the material culture,besides pottery and other tangible features, are referred to, and there is very little interpretation of the material in human terma.(Milojcic, 1949 a.;1959 e, 68 -84).Although there have been monographs published concerning specific cultures, such as the Starcevo and Vinca cultures, these have all been based on a detailed analysis of one region rather than a detailed analysis of the material of all regions of the culture.(e.g.Garaganin, M.,1951 ;Garaganin D.,1954). east Europe.Before these problems and their significance can be understood, however, it is necessary to provide the background in an analysis of the Linear Pottery culture itself.For the sake of complete*ess,it has been thought more satisfactory to include the Linear Pottery cultures of all regions and phases in this analysis,so that the problems.may be seen in the true perspective of their relative position in the earlier prehistory of central and south east Europe.The first two parts of the'study describe the features of the material culture of the Linear Pottery cultures as a whole 's in their `suropean setting,and especially in relation to their prototypes in south -east Europe and their adaptation in temperate central Europe.The third part brings together all these features, and arranges then historically with reference to the internal development of the Linear Pottery cultures in time and space,and their relationships with each other and with neighbouring cultures ;this part maybe said to describe the dynamics of the Linear Pottery populations.ery populations. The fourth part represents the original purpose of the thesis,for which, in effect, the first three parts are the preparatory basis ;this is to analyse the long -term effect of the Linear Pottery cultures on the subsequent developments of the later neolithic and even copper -using cultures of southeast Europe.The last two parts are obviously based on specific material from a large number of sites ;it would clearly be unnecessarily laborious, len_gthy,and of little value to describe this material in detail: ;the text consists of putting forward the main trends in development and content of the material culture ;the actual source of evidence is- expressed in chart form and catalogues at the end of each chapter,and by illustrations and distribution maps at the . end of the text

The effects of mutated cationic amino acid transporter y+LAT1 at the cellular and systemic level

y+LAT1 is a transmembrane protein that, together with the 4F2hc cell surface antigen, forms a transporter for cationic amino acids in the basolateral plasma membrane of epithelial cells. It is mainly expressed in the kidney and small intestine, and to a lesser extent in other tissues, such as the placenta and immunoactive cells. Mutations in y+LAT1 lead to a defect of the y+LAT1/4F2hc transporter, which impairs intestinal absorbance and renal reabsorbance of lysine, arginine and ornithine, causing lysinuric protein intolerance (LPI), a rare, recessively inherited aminoaciduria with severe multi-organ complications. This thesis examines the consequences of the LPI-causing mutations on two levels, the transporter structure and the Finnish patients’ gene expression profiles. Using fluorescence resonance energy transfer (FRET) confocal microscopy, optimised for this work, the subunit dimerisation was discovered to be a primary phenomenon occurring regardless of mutations in y+LAT1. In flow cytometric and confocal microscopic FRET analyses, the y+LAT1 molecules exhibit a strong tendency for homodimerisation both in the presence and absence of 4F2hc, suggesting a heterotetramer for the transporter’s functional form. Gene expression analysis of the Finnish patients, clinically variable but homogenic for the LPI-causing mutation in SLC7A7, revealed 926 differentially-expressed genes and a disturbance of the amino acid homeostasis affecting several transporters. However, despite the expression changes in individual patients, no overall compensatory effect of y+LAT2, the sister y+L transporter, was detected. The functional annotations of the altered genes included biological processes such as inflammatory response, immune system processes and apoptosis, indicating a strong immunological involvement for LPI.Kationisten aminohappojen kuljetinproteiini y+LAT1:n mutaatioiden vaikutus systeemisellä ja solutasolla y+LAT1 on solukalvoproteiini, joka yhdessä solun pinnan yleisen 4F2hc-antigeenin kanssa muodostaa epiteelisolujen basolateraalikalvolle paikantuvan kationisten aminohappojen kuljettimen. Sen pääasialliset ilmenemiskudokset ovat munuainen ja ohutsuoli, mutta se toimii pienemmässä määrin myös joissakin muissa kudoksissa, kuten istukassa ja immuuniaktiivisissa soluissa. y+LAT1:n mutaatiot aiheuttavat virheen y+LAT1/4F2hc-kuljettimeen heikentäen lysiinin, arginiinin ja ornitiinin imeytymistä ohutsuolesta verenkiertoon sekä niiden takaisinottoa alkuvirtsasta munuaisissa Tämä johtaa lysinuurisen proteiini-intoleranssiin: harvinaiseen perinnölliseen aminohappoaineenvaihduntasairauteen, johon liittyy vakavia monielinkomplikaatioita. Tämä väitöskirja tarkastelee LPI-mutaatioiden seurauksia kahdella eri tasolla: toisaalta aminohappokuljettimen rakenteen tasolla ja toisaalta suomalaisten LPI-potilaiden geeniekspressioprofiilien kautta kuljettimen toiminnan tasolla. Tässä työssä optimoitiin fluorescence resonance energy transfer (FRET) –konfokaalimikroskopiamenetelmä, jota käyttäen havaittiin kuljettimen alayksiköiden dimerisoituvan keskenään y+LAT1:n mutaatioista huolimatta. Virtaussytometriset ja FRET-konfokaalimikroskopiakokeet osoittivat y+LAT1-molekyylien pyrkivän muodostamaan homodimeerejä sekä ilman 4F2hc:ta että sen läsnä ollessa viitaten vahvasti siihen, että kuljettimen toiminnallinen kokonaisuus on heterotetrameeri. Suomalaisilla LPI-potilailla on kaikilla SLC7A7-geenissä sama LPI-mutaatio, mutta heidän kliiniset taudinkuvansa eroavat toisistaan suuresti. Potilaiden geeniekspressioanalyysi paljasti 926 ekspressioltaan muuttunutta geeniä sekä laajan, useita aminohappokuljettimia koskevan aminohappotasapainon häiriön. Yksittäisten potilaiden y+LAT2-kuljettimen ekspressiomuutoksista huolimatta tämän kuljettimen ei havaittu yleisesti kompensoivan y+LAT1:n vähentynyttä ekspressiota. Muuttuneiden geenien toiminnot liittyivät mm. tulehdusvasteeseen, immuunipuolustustoimintoihin ja apoptoosiin, mikä viittaa siihen, että LPI:llä on vahva yhteys immuunipuolustukseen.Siirretty Doriast

Screening for type 2 diabetes in a multiethnic setting using known risk factors to identify those at high risk: a cross-sectional study

Screening enables the identification of type 2 diabetes mellitus (T2DM) during its asymptomatic stage and therefore allows early intervention which may lead to fewer complications and improve outcomes. A targeted screening program was carried out in a United Kingdom (UK) multiethnic population to identify those with abnormal glucose tolerance

APOE Genotypes, Lipid Profiles, and Associated Clinical Markers in a Finnish Population with Cardiovascular Disease Risk Factors

Introduction: The APOE ε4 allele predisposes to high cholesterol and increases the risk for lifestyle-related diseases such as Alzheimer’s disease and cardiovascular diseases (CVDs). The aim of this study was to analyse interrelationships of APOE genotypes with lipid metabolism and lifestyle factors in middle-aged Finns among whom the CVD risk factors are common. Methods: Participants (n = 211) were analysed for APOE ε genotypes, physiological parameters, and health- and diet-related plasma markers. Lifestyle choices were determined by a questionnaire. Results: APOE genotypes ε3/ε4 and ε4/ε4 (ε4 group) represented 34.1% of the participants. Genotype ε3/ε3 (ε3 group) frequency was 54.5%. Carriers of ε2 (ε2 group; ε2/ε2, ε2/ε3 and ε2/ε4) represented 11.4%; 1.9% were of the genotype ε2/ε4. LDL and total cholesterol levels were lower (p < 0.05) in the ε2 carriers than in the ε3 or ε4 groups, while the ε3 and ε4 groups did not differ. Proportions of plasma saturated fatty acids (SFAs) were higher (p < 0.01), and omega-6 fatty acids lower (p = 0.01) in the ε2 carriers compared with the ε4 group. The ε2 carriers had a higher (p < 0.05) percentage of 22:4n-6 and 22:5n-6 and a lower (p < 0.05) percentage of 24:5n-3 and 24:6n-3 than individuals without the ε2 allele. Conclusions: The plasma fatty-acid profiles in the ε2 group were characterized by higher SFA and lower omega-6 fatty-acid proportions. Their lower cholesterol values indicated a lower risk for CVD compared with the ε4 group. A novel finding was that the ε2 carriers had different proportions of 22:4n-6, 22:5n-6, 24:5n-3, and 24:6n-3 than individuals without the ε2 allele. The significance of the differences in fatty-acid composition remains to be studied.Peer reviewe