Space Marker Research Articles

Age-related changes in choroid plexus and blood–cerebrospinal fluid barrier function in the sheep

Dysfunction of the choroid plexuses (CPs) and the blood–cerebrospinal fluid barrier (BCSFB) might contribute to age-related cognitive decline and neurodegenerative disease. We used the CPs from young (1–2 years), middle-aged (3–6 years) and old (7–10 years) sheep to explore effects of aging on various aspects of CP and BCSFB functions. Total protein in the cerebrospinal fluid (CSF) was significantly higher in old compared to young sheep and CSF secretion by the CP perfused in situ was significantly lower in both old and middle-aged when compared to young sheep, which correlated with reduced 22Na + uptake and efflux by the CP. Steady-state extractions of a low and medium size molecular weight extracellular space marker, 14C-mannitol and 3H-polyethylene glycol, respectively, were significantly higher in CPs from old compared to young animals; however, there was no significant difference in steady-state extraction of a high molecular weight marker, 125I-bovine serum albumin. This indicates increased passive BCSFB permeability for small and medium sized molecules in old sheep. CP redox activity was significantly lower in the old animals as assessed by the MTT assay, however, there was no significant difference in ATP content and energy charge of the CP with age suggesting adequate baseline energy reserve capacity. These data indicate that normal aging processes alter protein content in the CSF, CSF secretion, integrity of the BCSFB and Na + flux in the epithelial layer, which could impact on CSF homeostasis and turnover.

Events in Space

No abstract.

Martin Luther King Jr. Streets in the South: A New Landscape of Memory

By laying bare the racial fault lines in one community after another, by calling attention to the circumstances of life in the heart of the black community while demanding better, the streets that bear his name are Martin Luther King's greatest living memorial.--Haki R. Madhubuti Traditionally, public commemoration in the South has been devoted largely to remembering the region's role in the Civil War and the mythic Old South plantation culture supposedly lost as a result of that conflict. These memories remain deeply ingrained in the southern landscape of monuments, museums, historical markers, and place names. Yet, African Americans who seek to make their own claim to the South and its history increasingly challenge Civil War-centered conceptions of the past. Perhaps the best known of these struggles involve ongoing calls to remove public symbols of the Confederacy. At the same time, African American southerners are using direct political action to build memorials that recognize their own historical experiences, struggles, and achievements. A major pillar in this trend is the commemoration of another, quite different revolution from that of the Civil War--the Civil Rights Movement. The naming of streets after slain Civil Rights leader Martin Luther King Jr. is the most widespread example of African American efforts to rewrite the landscape of southern commemoration. Despite the growing frequency of naming streets in honor of Dr. King, this new cultural phenomenon has received limited attention, even though the inscription of King's legacy onto streets is a potentially valuable indicator of where the South is in terms of race relations. On the one hand, communities name streets after King as a result of the increased cultural and political power of African Americans and the liberalization of white attitudes. While the commemorative movement is driven predominantly by the activism of African Americans, there are noteworthy instances of whites not only supporting the cause but leading it. On the other hand, naming streets for King is often a controversial process that exposes continued racial divisions. activists who seek to rename thoroughfares that cut through and connect different communities have confronted significant public opposition. This frequently leads to the placement of King's name on minor streets or portions of roads located entirely within the African American community. At the same time that Martin Luther King streets speak to how far the South has come since the Movement, they also speak to how far the region still has to go in reaching the dream of racial equality and social justice. The emergence of Martin Luther King streets increasingly marks the symbolic place that these streets occupy within the lives of southerners and Americans in general. Martin Luther King Drives, Boulevards, and Avenues are important centers of African American identity, activity, and community--constituting what journalist Jonathan Tilove has called Black America's Main Street. These streets are memorial arenas--public spaces for interpreting and debating King's legacies, grappling with questions of race and racism. For many activists, finding the most appropriate street to identify with him comes with the difficulty of convincing the white establishment that King's name belongs on major roads, that his legacy has relevance and resonance to everyone's lives. To marginalize the commemoration of King on side streets within the black community, particularly in the face of African American requests not to do so, is to perpetuate the same force of segregation that the Civil Rights leader battled. (1) Martin Luther King streets serve as points of pride and struggle in the contemporary South. The photographs here challenge negative representations of these roads. As Tilove so keenly observed in Along Martin Luther King, It has become a commonplace of popular culture to identify a Martin Luther King street as a generic marker of black space and not incidentally, of ruin, as a sad signpost of danger, failure, and decline. …

Trastornos de la personalidad y conducta interpersonal : un análisis dimensional a partir del circumplex interpersonal

The circumplex model of Interpersonal Adjective Scales (IAS, Wiggins, 1996) is an integrative model which allows research into the interpersonal contents associated with the categories of personality disorders, through the substantive analysis of the interpersonal contents of these psychopathological categories. This study purports to explore the relationship between the Interpersonal Circumplex of J.S. Wiggins and the scales of personality disorders in clinical subjects and taking advantage of the geometrical properties of circle variables. We used the Millon Clinical Multiaxial Inventory (MCMI-II) to evaluate the scales of personality disorders and the IAS as markers of interpersonal space. We found that many personality disorders scales measured the MCMI-II could be identified in the IAS circum-plex.

National Identity and the Geo‐Soul: Spiritually Mapping Siam

AbstractThis paper investigates the re‐centring of religious identity within the geo‐body in the developing world through the case study of Thailand, formerly Siam. Although by 1932, monarchic rule and colonial powers had demarcated the ‘geo‐body’ of Siam, the national soul was not yet fully cultivated. After the fall of the absolute monarchy, Prime Minister Phibunsongkhram sought to mould the religio‐national identity of Thailand until the religious community's borders coincided with those of the nation‐state. One focus of nationalist leaders' efforts was the adaptation and promotion of Buddhist temples throughout the state. These temples became markers of both geographic and cosmological space, serving to infuse the geographic body with a religio‐national soul. Thus, the nationalism that developed embraced the fusion of the religious identity with the national identity.

Transport of [ 14C]hypoxanthine by sheep choroid plexus epithelium as a monolayer in primary culture: Na +-dependent and Na +-independent uptake by the apical membrane and rapid intracellular metabolic conversion to nucleotides

Hypoxanthine is the main product of purine metabolic degradation and previous studies have revealed that it is present in the sheep CSF and plasma in micromolar concentrations. The aim of this study was to elucidate the transport of this molecule across the sheep choroid plexus epithelium (CPE) as a monolayer in primary culture, to explore the mechanism of uptake by the apical side of the CPE and investigate the metabolic changes inside the cell. The estimated permeability of the CPE monolayer for [ 14C]hypoxanthine, [ 14C]adenine and [ 14C]guanine was low and comparable to the permeability towards the extracellular space markers. The study of [ 14C]hypoxanthine uptake by the CPE revealed two components: Na +-dependent and Na +-independent, the latter being partially mediated by the equilibrative nucleoside transporter 2. HPLC with simultaneous detection of radioactivity revealed that the majority of [ 14C]hypoxanthine inside the CPE is metabolised into [ 14C]nucleotides and [ 14C]inosine. The remaining intact [ 14C]hypoxanthine was transported across the opposite, basolateral side of CPE and appeared in the lower chamber buffer together with [ 14C]inosine. These findings indicate two possible roles of hypoxanthine uptake from the CSF by the CP epithelium in vivo: to provide material for nucleotide synthesis through the salvage pathways in the CPE, as well as to transfer excess hypoxanthine from CSF to blood.

Hypoxia effects on cell volume and ion uptake of cerebral microvascular endothelial cells

Increased transport of Na across an intact blood-brain barrier (BBB) contributes to cerebral edema formation in ischemic stroke. Our previous studies have shown that ischemic factors stimulate activity of a luminal BBB Na-K-Cl cotransporter, and we have hypothesized that during ischemia, the cotransporter together with the abluminal Na/K pump mediates increased transport of Na from blood into the brain. However, it is possible that elevated Na-K-Cl cotransporter activity could also cause cell swelling if it outpaces ion efflux pathways. The present study was conducted to evaluate the effects of hypoxia on intracellular volume of BBB cells. Cerebral microvascular endothelial cell (CMEC) monolayers were exposed to varying levels of hypoxia for 1 to 5 h in an O(2)-controlled glove box, and cell volume was assessed using 3-O-methyl-D-[(3)H]glucose and [(14)C]sucrose as markers of total and extracellular water space, respectively. Cells exposed to either 7.5%, 3%, or 1% O(2) showed gradual increases in volume (compared with 19% O(2) normoxic controls) that became significant after 3 or more hours. By ion chromatography methods, we also found that a 30-min exposure to 7.5% O(2) caused an increase in bumetanide-sensitive net Na uptake by the cells without increasing cell Na content. CMEC Na content was significantly increased, however, following 3 or more hours of exposure to 7.5% O(2). These findings are consistent with the hypothesis that during cerebral ischemia, the BBB Na-K-Cl cotransporter is stimulated to mediate transendothelial uptake of Na into the brain and that increased cotransporter activity also contributes to gradual swelling of the cells.

Polar positional information in Escherichia coli spherical cells

Shigella surface protein IcsA and its cytoplasmic derivatives are localized to the old pole of rod-shaped cells when expressed in Escherichia coli. In spherical mreB cells, IcsA is targeted to ectopic sites and close to one extremity of actin-like MamK filament. To gain insight into the properties of the sites containing polar material, we studied the IcsA localization in spherical cells. GFP was exported into the periplasm via the Tat pathway and used as a periplasmic space marker. GFP displayed zonal fluorescence in both mreB and rodA-pbpA spherical E. coli cells, indicating an uneven periplasmic space. Deconvolution images revealed that the cytoplasmic IcsA fused to mCherry was localized outside or at the edge of the GFP zones. These observations strongly suggest that polar material is restricted to the positions where the periplasm possesses particular structural or biochemical properties.

Streptozotocin-induced diabetes progressively increases blood-brain barrier permeability in specific brain regions in rats

This study investigated the effects of streptozotocin-induced diabetes on the functional integrity of the blood-brain barrier in the rat at 7, 28, 56, and 90 days, using vascular space markers ranging in size from 342 to 65,000 Da. We also examined the effect of insulin treatment of diabetes on the formation and progression of cerebral microvascular damage and determined whether observed functional changes occurred globally throughout the brain or within specific brain regions. Results demonstrate that streptozotocin-induced diabetes produced a progressive increase in blood-brain barrier permeability to small molecules from 28 to 90 days and these changes in blood-brain barrier permeability were region specific, with the midbrain most susceptible to diabetes-induced microvascular damage. In addition, results showed that insulin treatment of diabetes attenuated blood-brain barrier disruption, especially during the first few weeks; however, as diabetes progressed, it was evident that microvascular damage occurred even when hyperglycemia was controlled. Overall, results of this study suggest that diabetes-induced perturbations to cerebral microvessels may disrupt homeostasis and contribute to long-term cognitive and functional deficits of the central nervous system.

Transepithelial flux of early and advanced glycation compounds across Caco-2 cell monolayers and their interaction with intestinal amino acid and peptide transport systems

Maillard products arise from condensation reactions between amino acids or proteins with reducing sugars during food processing. As ubiquitous components of human food, these early or advanced glycation products may be subject to intestinal absorption. The present study was performed to investigate the intestinal uptake of Maillard products and to determine whether they are substrates for peptide and amino acid transporters expressed at the apical membrane of Caco-2 cells. At a concentration of 10 mM, N(epsilon)-(carboxymethyl)-L-lysine, N(alpha)-hippuryl-N(epsilon)-(1-deoxy-D-fructosyl)-L-lysine, N(alpha)-hippuryl-N(epsilon)-(carboxymethyl)-L-lysine and N(epsilon)-(1-deoxy-D-fructosyl)-L-lysine inhibited the [(14)C]glycylsarcosine uptake mediated by the H(+)-peptide co-transporter PEPT1 by 13 to 45%. For N(epsilon)-(1-deoxy-D-fructosyl)-L-lysine, an inhibitory constant of 8.7 mM was determined, reflecting a low affinity to PEPT1 in comparison with natural dipeptides. Uptake of L-[(3)H]lysine was weakly affected by N(epsilon)-(carboxymethyl)-L-lysine, N(alpha)-hippuryl-L-lysine and N(alpha)-hippuryl-N(epsilon)-(carboxymethyl)-L-lysine but strongly inhibited by N(epsilon)-(1-deoxy-D-fructosyl)-L-lysine (81%). None of the Maillard products was able to inhibit the uptake of L-[(3)H]leucine by more than 15%. We also studied the transepithelial flux of Maillard products across Caco-2 cell monolayers cultured on permeable filters. The flux rates of Maillard products ranged from 0.01 to 0.3%/cm(2) per h and were shown to be much lower than those of carrier substrates such as glycylsarcosine, L-proline and the space marker [(14)C]mannitol. We conclude that the Maillard products investigated in the present study are neither transported by PEPT1 nor by carriers for neutral amino acids. The low transepithelial flux measured for these compounds most probably occurs by simple diffusion.

Mitochondrial iPLA2 Activity Modulates the Release of Cytochrome c from Mitochondria and Influences the Permeability Transition

The mitochondrial Ca(2+)-independent phospholipase A(2) is activated during energy-dependent Ca(2+) accumulation under conditions where there is a sustained depression of the membrane potential. This activation is not dependent on induction of the mitochondrial permeability transition. Bromoenol lactone, which inhibits the phospholipase, is effective as an inhibitor of the transition, and this action can be overcome by low levels of exogenous free fatty acids. Apparently, activation of the Ca(2+)-independent phospholipase is a factor in the mechanisms by which depolarization and Ca(2+) accumulation promote opening of the permeability transition pore. Sustained activity of the Ca(2+)-independent phospholipase A(2) promotes rupture of the outer mitochondrial membrane and spontaneous release of cytochrome c on a time scale similar to that of apoptosis occurring in cells. However, more swelling of the matrix space must occur to provoke release of a given cytochrome c fraction when the enzyme is active, compared with when it is inhibited. Through its effects on the permeability transition and release of intermembrane space proteins, the mitochondrial Ca(2+)-independent phospholipase A(2) may be an important factor governing cell death caused by necrosis or apoptosis.

Transit time dispersion in pulmonary and systemic circulation: effects of cardiac output and solute diffusivity

We present an in vivo method for analyzing the distribution kinetics of physiological markers into their respective distribution volumes utilizing information provided by the relative dispersion of transit times. Arterial concentration-time curves of markers of the vascular space [indocyanine green (ICG)], extracellular fluid (inulin), and total body water (antipyrine) measured in awake dogs under control conditions and during phenylephrine or isoproterenol infusion were analyzed by a recirculatory model to estimate the relative dispersions of transit times across the systemic and pulmonary circulation. The transit time dispersion in the systemic circulation was used to calculate the whole body distribution clearance, and an interpretation is given in terms of a lumped organ model of blood-tissue exchange. As predicted by theory, this relative dispersion increased linearly with cardiac output, with a slope that was inversely related to solute diffusivity. The relative dispersion of the flow-limited indicator antipyrine exceeded that of ICG (as a measure of intravascular mixing) only slightly and was consistent with a diffusional equilibration time in the extravascular space of approximately 10 min, except during phenylephrine infusion, which led to an anomalously high relative dispersion. A change in cardiac output did not alter the heterogeneity of capillary transit times of ICG. The results support the view that the relative dispersions of transit times in the systemic and pulmonary circulation estimated from solute disposition data in vivo are useful measures of whole body distribution kinetics of indicators and endogenous substances. This is the first model that explains the effect of flow and capillary permeability on whole body distribution of solutes without assuming well-mixed compartments.

A chronotopic approach to genre analysis: An exploratory study

This paper will examine Bakhtin’s theory that a genre’s unity is defined by its chronotope [Bakhtin, M. M. (1981). Forms of time and of the chronotope in the novel. In M. Holquist (Ed.), The dialogic imagination: Four essays (pp. 84–258). Austin: University of Texas Press] and assume that, if this is true, the rhetorical unity within a specific genre could also be defined by its chronotope. Central to this theory will be the idea that the individual ‘moves’ [Swales, J. M. (1981). Aspects of article introduction. Birmingham, UK: University of Aston Language Studies Unit] within genres are defined by their use of time and space. In this way, the chronotope can be used as a device to analyze specific genres that are of interest to ESP composition, and can then be used as an instructional tool for the teaching of these particular genres to students within the ESP community. A corpus of L1 and L2 cover letters will be reviewed and linguistic markers of time and space will be compared to establish chronotopic move markers and chronotopic generic differences. The research summarized will consider what the pedagogical and semantic implications of these generic differences might be.

Film also ages: time and images in Chris Marker's Sans soleil

Considered today as a seminal and essential figure for an understanding of the implications of our visual culture, Chris Marker and his films have only recently received widespread critical attention. However; many aspects of his work in non-fiction still remain under-studied, most notably his complex reflections on the temporal nature of cinematic images and their (in)ability to recreate past events, aspects that are essential to Marker's understanding of cinema. Focusing on what is arguably his most important non-fiction film treating this theme, Sans soleil/Sunless (1982), and drawing on the work of thinkers such as Gilles Deleuze, this article examines the film-maker's ideas on time and cinematic representation, as well as the strategies used in the film to expose the profound range of philosophical meanings we have attached to film images over the last century. Central to Sans soleil is the space Marker terms ‘The Zone’, in which are found not only many of his insights into the possibility of using film as a valid document to access a contingent past, but also an original cinematic mechanism that attempts to restore to film images their own entity.

Radiosurgery for pituitary adenomas

Radiosurgery for pituitary adenomas

The Territorial Impulse

The Territorial Impulse Stephanie Kane (bio) Folk performances—and folkloristic discourse about them—abound with place and space markers. The latter may refer to a refuge, a stage, a community, an epicenter; to a genealogical landscape, a bureaucratic maze, or an ideological split.1 These markers help orient and ground our activities, but to what extent are they also a means of claiming the places and spaces we reference? I believe that it is useful to analyze the ways in which territorial impulses, such as mapping, structure our fieldwork, writing, and social action so that we may begin to contemplate their effects. Following the writings of David Harvey, "Cartography [or mapping] is about locating, identifying and bounding phenomena and thereby situating events, processes and things within a coherent spatial frame" (2001:220). These operations impose a spatial order on phenomena and play a key role in the formation of personal and political subjectivities. In this sense, mapping includes mental and cognitive maps, as well as externally visualized representations based on grids. My hypothesis is that culturally specific spatial codes underlie the intertwining discursive currents of folklore and ethnography in particular ways; that the folk—those elusive, embodied objects of our disciplinary desire—are textually realized (in part) by us through patterned invocations of place and space. Take, for example, de Certeau's mythic surveillance peak on the 110th floor of the World Trade Center in New York City. He brings our attention to the textured land of urban folk as surveyed with a pilot's-eye view: The ordinary practitioners of the city live "down below," below the thresholds at which visibility begins. They walk—an elementary form of this experience of the city; they are walkers, Wandersmänner, whose bodies follow the thicks and thins of an urban "text" they write without being able to read it. These practitioners make use of spaces that cannot be seen; their knowledge of them is as blind as that of lovers in each other's arms. The paths that correspond in this intertwining, unrecognized poems in which each body is an element signed by many others, elude legibility. It is as though the practices organizing a bustling city were characterized by their blindness. The networks of these moving intersecting writings compose a manifold story that has neither author nor spectator, shaped out of fragments of trajectories and alterations of spaces: in relation to representations, it remains daily and indefinitely other. (1984:92) [End Page 274] I would like to use this panoptic portal as an entry into the uniquely imagined, empirically verifiable, and walkable set of landscapes in which Martha Norkunas, Barbara Chandler and Carl Lindahl, Kwesi Yankah, Philip Nusbaum, and Rachel Fleming engage with various folks and institutions. This commentary builds on my observation that the impulse to tie image and narrative to some cognitive and/or geographical map is a methodological necessity for an engaged research logistics (see Kane 2004). Here, I consider this collection as a composite semantic domain within which the territorial impulse can be explored. It is testimony to the richness and depth of these essays that one can approach them experimentally in this manner. What follows is a series of space-code readings that focus on 1) the range of ways that folklorists imagine the spaces and places of the folk, their audiences, and funders; 2) how spatial concepts function as implicit ordering principles in folklore discourse; and 3) how territoriality—the naming and claiming of places and spaces—is emplotted in the narratives that result from fieldwork exchange. Linking Silenced Ancestral Narratives to Public Sites On Martha Norkunas's "Narratives of Resistance and the Consequences of Resistance" By drawing three narratives from the heirs of those once silenced by sexism and racism into the world of the Journal of Folklore Research readers, Norkunas turns life histories of apparently ordinary people into history-writ-large. Each narrative is founded on a displacement and/or a disappearance involving some refusal, alienation, or forgetting communicated across a landscape. She creates intimacy in her essay by beginning with, and in a sense repairing, her own "broken home" story, which is also her mother's 1960s "single mom" story. The...

Insertion of MP20 into lens fibre cell plasma membranes correlates with the formation of an extracellular diffusion barrier

It is known that during lens differentiation a number of fibre cell specific membrane proteins change their expression profiles. In this study we have investigated how the profiles of the two most abundant fibre cell membrane proteins AQP0 (formerly known as Major Intrinsic Protein, MIP) and MP20 change as a function of fibre cell differentiation. While AQP0 was always found associated with fibre cell membranes, MP20 was initially found in the cytoplasm of peripheral fibre cells before becoming inserted into the membranes of deeper fibre cells. To determine at what stage in fibre cell differentiation MP20 becomes inserted into the membrane, sections were double-labelled with an antibody against MP20, and propidium iodide, a marker of cell nuclei. This showed that membrane insertion of MP20 occurs in a discrete transition zone that coincided with the degradation of cell nuclei. To test the significance of the membrane insertion of MP20 to overall lens function, whole lenses were incubated for varying times in a solution containing either Texas Red-dextran or Lucifer yellow as markers of extracellular space. Lenses were fixed and then processed for immunocytochemistry. Analysis of these sections showed that both tracer dyes were excluded from the extracellular space in an area that coincided with insertion of MP20 into the plasma membrane. Our results suggest that the insertion of MP20 into fibre cell membranes coincides with the creation of a barrier that restricts the diffusion of molecules into the lens core via the extracellular space.

Manganese Distribution Across the Blood–Brain Barrier: I. Evidence for Carrier-Mediated Influx of Manganese Citrate as Well as Manganese and Manganese Transferrin

Manganese (Mn) is an essential element and a neurotoxicant. Regulation of Mn movement across the blood–brain barrier (BBB) contributes to whether the brain Mn concentration is functional or toxic. In plasma, Mn associates with water, small molecular weight ligands and proteins. Mn speciation may influence the kinetics of its movement through the BBB. In the present work, the brain influx rates of 54Mn 2+, 54Mn citrate and 54Mn transferrin ( 54Mn Tf) were determined using the in situ brain perfusion technique. The influx rates were compared to their predicted diffusion rates, which were determined from their octanol/aqueous partitioning coefficients and molecular weights. The in situ brain perfusion fluid contained 54Mn 2+, 54Mn citrate or 54Mn Tf and a vascular volume/extracellular space marker, 14C -sucrose, which did not appreciably cross the BBB during these short experiments (15–180 s). The influx transfer coefficient ( K in) was determined from four perfusion durations for each Mn species in nine brain regions and the lateral ventricular choroid plexus. The brain K in was (5–13)×10 −5, (3–51)×10 −5, and (2–13)×10 −5 ml/s/g for 54Mn 2+, 54Mn citrate, and 54Mn Tf, respectively. Brain K in values for any one of the three Mn species generally did not significantly differ among the nine brain regions and the choroid plexus. However, the brain K in for Mn citrate was greater than Mn 2+ and Mn Tf K in values in a number of brain regions. When compared to calculated diffusion rates, brain K in values suggest carrier-mediated brain influx of 54Mn 2+, 54Mn citrate and 54Mn Tf. 55Mn citrate inhibited 54Mn citrate uptake, and 55Mn 2+ inhibited 54Mn 2+ uptake, supporting the conclusion of carrier-mediated brain Mn influx. The greater K in values for Mn citrate than Mn 2+ and its presence as a major non-protein-bound Mn species in blood plasma suggest Mn citrate may be a major Mn species entering the brain.

The Wild and Homely Siberia. How Siberian Estonians Perceive their Natural Environment

Culture is traditionally connected with a specific place. When we speak of Estonian culture, we usually mean the culture that is practised in Estonia. Culture presumes the environment and although in principle such environment could be artificial or virtual, we are not independent enough from real living space to create an absolutely independent culture in this virtual world. This is because in order to create worlds we need archetypes, athough in some cases their influence has diminished after multiple copying. Estonian culture is associated with Estonia. An important source for Estonian culture is the nature of Estonia. Patriotic poems from the time of the national awakening cherished the homeland’s nature, filling it with a profound symbolic content. Nature denoted the historical experience of Estonians – natural objects as markers of space, rivers, lakes, hills and landscapes carried deep meaning, evidenced centuries-long existence in the specific area. Yet it would be wrong to associate Estonian culture with Estonia only, because since the mid-19th century Estonians have, time and again, moved to different corners of the world, where Estonian culture developed further, despite being far from its historical homeland. Leaving their home area did not mean becoming independent from that environment: the alternative to an environment is just another environment. Like Estonia provided material and conditions for the development of the homeland culture, so did the destination country’s environment for the culture of the diaspora. The nature of the new homeland had a significant role in adaptation. In the following we shall observe the relationship of Siberian Estonians with their natural environment. We shall study the relations between the activities in the landscape and the environmental conditions. Not only the living space and what is going on there describes people’s relationships with the environment, but also the

Permeability of Proteins at the Blood–Brain Barrier in the Normal Adult Mouse and Double Transgenic Mouse Model of Alzheimer's Disease

The permeability of albumin, insulin, and human Aβ 1–40 at the blood–brain barrier (BBB) was determined in the normal adult mouse (B6/SJL) and in the double transgenic Alzheimer mouse (APP, PS1) by using an I.V. bolus injection technique to quantify the permeability coefficient-surface area (PS) product for each protein after correction for the residual plasma volume (Vp) occupied by the protein in the blood vessels of different brain regions using a second aliquot of the same protein radiolabeled with a different isotope of iodine (125I vs 131I) as a vascular space marker. This technology for quantifying BBB permeability of proteins was adapted from the rat to the mouse and involved catheterizing the femoral artery and vein of the mouse instead of the brachial artery and vein as for the rat. Because of the smaller blood volume in the mouse, serial sampling (20 μl) of blood from the femoral artery of the mouse was performed and directly TCA precipitated to generate a whole blood washout curve for the intact protein. When similar blood sampling techniques were used in the rat, the PS values for albumin and insulin at the BBB were similar in these two species. In the double transgenic mouse, the Vp values for albumin were significantly increased 1.4- to 1.6-fold in five of six brain regions compared to the normal adult mouse, which indicated increased adherence of albumin to vessel walls. As a result, the PS values were significantly decreased, from 1.4- to 3.2-fold, which likely reflected decreased transport of albumin by passive diffusion. In contrast, insulin, which is taken up into the brain by a receptor-mediated transport mechanism at the BBB, showed no significant difference in the Vp values but a significant increase in the PS values in four of six brain regions. This suggests a compensatory mechanism in the Alzheimer's transgenic brain whereby there is an increased permeability to insulin at the BBB. Surprisingly, there was no significant difference in the Vp or PS values for human Aβ 1–40 at the BBB in the double transgenic Alzheimer mouse at 24, 32, or 52 weeks of age, when there is both significant Aβ levels in the plasma and amyloid burden in the brains of these animals. These data suggest that there is not an alteration in permeability to human Aβ 1–40 at the BBB with increasing amyloid burden in the double transgenic Alzheimer mouse. Although these observations suggest structural alterations at the BBB, they do not support the concept of extensive BBB damage with substantial increases in BBB permeability in Alzheimer's disease.