Woody invasion into grasslands has been reported world-wide and has affected both the magnitude and spatial heterogeneity of soil carbon (C) and nitrogen (N). Since grasslands cover a large portion of the Earth's land surface, invasion of woody plants could have impacts on regional and global biogeochemistry. To understand large-scale ecological and policy implications of woody invasion, it is critical to understand the spatial pattern and uncertainty of soil C and N and their relationship with vegetation and soil attributes, as well as develop effective approaches to estimate soil C and N over large landscapes and regions. The goal of this study was to improve our understanding of the spatial pattern of soil organic carbon (SOC) and total nitrogen (TN) and their controlling factors in savanna landscapes and develop efficient sampling strategies for evaluating the effects of woody invasion. Specific objectives of this study were to: (1) Quantify the spatial pattern and uncertainty associated with SOC and develop efficient sampling strategies to estimate SOC storage; (2) Assess the influence of soil and vegetation factors on spatial distribution of SOC and TN; and (3) Determine the influence of physical variables related to landscape position and soil on woody vegetation structure. Conditional sequential indicator simulations indicated that woody encroachment into grassland increased both spatial heterogeneity and uncertainty of SOC, which increased errors in estimating SOC storage. Stratified random sampling with higher density in woody patches, plus structured sampling in cluster with strong spatial pattern, substantially increased estimation accuracy. Efficient sampling strategies for estimating SOC storage were developed based on these findings. Direct and spatial correlation and scaling analyses showed that SOC and TN were strongly correlated with litter and root biomass. Invaded woody vegetation has the most impact on spatial distribution of SOC and TN. Canonical correspondence analysis showed that variables related to landscape position were the primary factors determining the spatial distribution of woody species. These new insights will facilitate the estimation of soil C and N pools at landscape and regional scales, and will help evaluate the potential impacts of woody plant encroachment on the biogeochemistry of C and N.

Thyroid growth and function is partly regulated by growth factors binding to receptors on the cell surface. In the present thesis, the transforming growth factor-β (TGF-β) superfamily members have been studied for their role in regulation of growth and differentiation of both normal and neoplastic thyroid epithelial cells. TGF-β1 is a negative regulator of thyrocyte growth and function. However, the importance of other TGF-β superfamily members has not been fully investigated. TGF-β1, activin A, bone morphogenetic protein (BMP)-7 and their receptors were found to be expressed in porcine thyrocytes. In addition to TGF-β1, activin A was also found to be a negative regulator of thyroid growth and function, and both stimulated phosphorylation and nuclear translocation of Smad proteins. Furthermore, TGF-β1 and epidermal growth factor (EGF) demonstrated a synergistic negative effect on thyrocyte differentiation. Simultaneous addition of the two factors resulted in a loss of the transepithelial resistance and expression of the epithelial marker E-cadherin. This was followed by a transient expression of N-cadherin. Despite the extremely malignant character of anaplastic thyroid carcinoma (ATC) tumor cells, established cell lines are still responsive to TGF-β1. A majority of the cell lines were also found to be growth inhibited by BMP-7. BMP-7 induced cell cycle arrest of the ATC cell line HTh 74 in a dose- and cell density-dependent manner. This was associated with upregulation of p21CIP1 and p27KIP1, decreased cyclin-dependent kinase (Cdk) activity and hypophosphorylation of the retinoblastoma protein (pRb). TGF-β1, and to some extent also BMP-7, induced the expression of N-cadherin and matrix metalloproteinase (MMP)-2 and -9. Stimulation of HTh 74 cells with TGF-β1 increased the migration through a reconstituted basement membrane indicating an increased invasive phenotype of the cells. Taken together, these data show that TGF-β superfamily members not only affect growth and function of normal thyroid follicle cells but may also, in combination with EGF, play a role in cell dedifferentiation. This study additionally suggests that the TGF-β superfamily members may be important for the invasive properties of ATC cells.

La déficience du système de réparation des mésappariements de bases aboutit à une instabilité des séquences répétées ou microsatellites (MSI) qui engendre des mutations au niveau de gènes cibles de l'oncogenèse MSI. L'objectif de ma Thèse consistait à définir les conséquences fonctionnelles des mutations d'un nouveau gène cible de la tumorigenèse colorectale MSI : le gène SMAP1 (Small ArfGAP1) qui code une protéine de la famille ArfGAP (ADP ribosylation factor GTPase Activating Protein) spécifique d'Arf6, protéine impliquée dans de nombreux mécanismes cellulaires. Les mutations de SMAP1 sont spécifiques des tumeurs MSI de différentes origines tissulaires et n'apparaissent qu'au niveau de la répétition (A10). Dans les tumeurs colorectales primaires, la fréquence de mutations de SMAP1 observées diminue au cours de la progression tumorale suggérant que les tumeurs dépourvues de mutations de SMAP1 sont plus invasives. D'un point de vue fonctionnel, les mutations de SMAP1 ont pour conséquences un défaut dans le recyclage rapide du récepteur à la transferrine, une augmentation de la prolifération cellulaire et une diminution du pouvoir invasif en maintenant les jonctions adhérentes. Ainsi, nos observations montrant que les mutations de SMAP1 augmentent le pouvoir prolifératif mais diminuent le pouvoir invasif des lignées cellulaires issues de CCR MSI pourraient expliquer certaines caractéristiques cliniques des CCR MSI, les tumeurs MSI étant en effet des tumeurs volumineuses, ayant un faible pouvoir métastatique.

With the reproduction of severe deprivation among the campesinado in Latin America as a starting-point,the report explores the mechanisms of impoverishment in the eastern rural region of the department of Cauca in Colombia and the forms of resistance initiated by the Regional Indigenous Council of Cauca (CRIC). It is postulated that the continued existence of poverty derives its root-causes not from lacking integration of the traditional sector of the national economy into the modern sector, but from the processes through which the poor indigenous staple-food producer and agricultural worker by way of his actual participation within the capitalistic system is continously deprived of his energy and capacity by the power elite as he himself lacks the means to realize his own developmental power* Sham-participation, refering to the dysfunctionality of systemic participation performed by the poor who lack access to the bases for accumulating social power, is a concept applied to understand these mechanisms. Participation per se does not necessarily correspond to influence and power. Rather, systemic political participation can give legitimacy to the very system and to those structural conditions oppressing the indigenous small-holders and workers and consequently contributes to the consolidation of the transfer-process of power and thereby the reproduction of deprivation. Thus the poor indigenous population in Cauca cannot expect to be given access to the fundaments of social power. Thus the elements of real participation and the conditions for resisting deprivation are less likely to be obtained only through the creation of new institutions and channels for popular participation# In the case of the indigenous movement in Colombia, the problem is rather to revoke the repression of the indigenous organizations which have emerged from below and instead promote their spontaneous mobilization. / digitalisering@umu

Denna magisteruppsats, skriven för Stockholms universitets magisterkurs i historia som ett led iFörsvarshögskolans chefsprogram, har som syfte att beskriva och diskutera svensk luftoperativkrigsplanering 1958-1966 utifrån ett doktrinbegrepp. Någon uttalad luftoperativ doktrin fanns intevid denna tid varför denna får rekonstrueras utifrån en metod där ett antal faktorer beskrivs.Exempel på dessa är högre säkerhetspolitiska och militärstrategiska nivåer, lägre taktiska nivåer,upplevd hotbild, ledning, flygvapnets krigsplanläggning, samverkan med andra försvarsgrenar ochutveckling av nya vapensystem. Källmaterialet består i huvudsak av flygstabens hemliga arkivfrån samma år, vilket inte har studerats tidigare utifrån ett liknande syfte. Vidare problematiserasdoktrinutvecklingen genom att den även diskuteras utifrån olika perspektiv vars värde för ökadförståelse prövas.De konkreta frågeställningarna lyder:- Hur kan flygvapnets luftoperativa doktrinutveckling 1958-1966 beskrivas?- I vilken mån kan denna doktrinutveckling förstås utifrån rationalistiskt respektiveorganisatoriskt synsätt?Utifrån det överordnade säkerhetspolitiska ställningstagandet om alliansfrihet följde ett relativtstarkt försvar och den så kallade svenska linjen. Detta innebar dels ett relativt starkt flygvapen ochdels att flygvapnet kunde utvecklas efter en egen linje, inklusive doktrinärt, men i vilkenutsträckning så skedde har inte undersökts. Dimensionerande för flygvapnet var en sovjetiskinvasion, inkluderande kärnvapenanfall. Kort förvarningstid betonades ofta.Bärande element i Sveriges luftoperativa doktrin 1958-1966 kan kortfattat beskrivas som:- En strävan efter en relativt centraliserad ledning i syfte att kunna kraftsamla i tid och rum.- Ett prioriterat och väl utvecklat defensivt luftförsvarssystem, i huvudsak bestående av stril,luftvärn och jaktflyg som fokuserade på snabba bombplan på hög höjd ochluftlandsättningar, delvis till priset av en inte efterfrågad offensiv jaktförmåga.- En offensiv komponent i ett centralt sammanhållet attackflyg som under perioden i allthögre grad fokuserades mot sjömål vid en kustinvasion, alternativt indirekt samverkan viden gränsinvasion i norr. Tankar på massförstörelsevapen, anfall mot motståndarensbasområden samt direktsamverkande arméunderstöd övergavs under perioden, mensamtidigt utvecklades för framtiden ett nytt lätt attacksystem för den senare uppgiften.- Ett av kärnvapenhotet betingat bassystem som byggde på stor spridning, både på mångabaser och inom dessa, samt som skulle kunna få flygplanen i luften på mycket kort tid.Både ett rationalistiskt och ett organisatoriskt perspektiv har befunnits ge värdefulla bidrag till enökad förståelse för doktrinutvecklingen. Vissa skillnader perspektiven emellan har dockidentifierats. / This essay is written for Stockholm’s University as a part of the advanced level course in Historywhen attending the National Defence College Senior Staff Course. The purpose of the essay is todescribe the Swedish Air Force war planning and Air Power Doctrine during 1958 to 1966. TheSwedish Doctrine was then not formally expressed, and must consequently be reconstructed. Amethod is used that describes a number of factors, including higher levels of political guidanceand orders from the Supreme Commander, lower tactical levels, fighters, Command and Controlsystems and procedures, the threat to Sweden as it was experienced at the time, war planning,cooperation with the Army and Navy and development of new systems. Furthermore this Doctrineis discussed from different perspectives in order to see their contribution to the understanding ofthe complex conception of a Doctrine. The source of information is mainly the Air Staff TopSecret Archives. Neither that archive nor the period 1958-1966 have been examined by historianswith reasonably similar purpose.Starting with the question of how a Swedish Air Operations Doctrine of 1958 to 1966 can bedescribed, this essay comes to the following conclusions:The supreme doctrine of non-alignment resulted in a relatively strong defence and an ambition tobecome as independent as possible regarding weapon systems. This meant a strong Air Force thatcould develop independently, including doctrinaire. Dimensioning for the Air Force was aninvasion by the Soviet Union, including nuclear attacks.With this as a background the Swedish Air Operations Doctrine 1958 to 1966 included thefollowing leading elements:- An aspiration for a relatively centralized command with the purpose to be able to masspower when and where needed.- A prioritized and developed Air Defence System, including air surveillance, tacticalcontrol, fighters and SAM systems, which focused on Soviet fast and high bombers andairborne invasion. Air to air aspects of Offensive Air Operations did not have priority.- The tasks of the fighter-bomber force changed somewhat during the period. An invasionover the Baltic Sea was in focus during the whole period, but in 1958 the range of taskscould include everything from Close Air Support to base attack on the other side of theBaltic Sea, preferably with nuclear weapons which the Air Force pleaded for. 1966 the AirForce completely focused on invasion by sea, with a secondary role of Air Interdiction incase of a ground invasion in the far north. The new trainer, SAAB 105, that was developedduring this period was however designated as a light attack aircraft for CAS.- A very dispersed base system, including the use of roads, considering the nuclear threat,which was designated to get the fighters airborne as fast as possible.Both a rationalistic and an organizational perspective have been found to add elements ofunderstanding to the development of the Doctrine. However have some differences in theircontribution been identified. / Avdelning: ALB - Slutet Mag 3 C-upps.Hylla: Upps. ChP 06-08

Woody invasion into grasslands has been reported world-wide and has affected both the magnitude and spatial heterogeneity of soil carbon (C) and nitrogen (N). Since grasslands cover a large portion of the Earth's land surface, invasion of woody plants could have impacts on regional and global biogeochemistry. To understand large-scale ecological and policy implications of woody invasion, it is critical to understand the spatial pattern and uncertainty of soil C and N and their relationship with vegetation and soil attributes, as well as develop effective approaches to estimate soil C and N over large landscapes and regions. The goal of this study was to improve our understanding of the spatial pattern of soil organic carbon (SOC) and total nitrogen (TN) and their controlling factors in savanna landscapes and develop efficient sampling strategies for evaluating the effects of woody invasion. Specific objectives of this study were to: (1) Quantify the spatial pattern and uncertainty associated with SOC and develop efficient sampling strategies to estimate SOC storage; (2) Assess the influence of soil and vegetation factors on spatial distribution of SOC and TN; and (3) Determine the influence of physical variables related to landscape position and soil on woody vegetation structure. Conditional sequential indicator simulations indicated that woody encroachment into grassland increased both spatial heterogeneity and uncertainty of SOC, which increased errors in estimating SOC storage. Stratified random sampling with higher density in woody patches, plus structured sampling in cluster with strong spatial pattern, substantially increased estimation accuracy. Efficient sampling strategies for estimating SOC storage were developed based on these findings. Direct and spatial correlation and scaling analyses showed that SOC and TN were strongly correlated with litter and root biomass. Invaded woody vegetation has the most impact on spatial distribution of SOC and TN. Canonical correspondence analysis showed that variables related to landscape position were the primary factors determining the spatial distribution of woody species. These new insights will facilitate the estimation of soil C and N pools at landscape and regional scales, and will help evaluate the potential impacts of woody plant encroachment on the biogeochemistry of C and N.

Prostate cancer is the most common cancer in men, with the incidence rapidly increasing in Europe over the past two decades. Reliable biomarkers for prostate cancer are currently unavailable. Thus, there is an urgent need for improved biomarkers to diagnose prostate cancer at an early stage and to determine the best treatment options. Higher expression of transforming growth factor-β (TGFβ) has been reported in patients with aggressive cancer. TGFβ is a multifunctional cytokine that acts as a tumor suppressor during early tumor development, and as a tumor promoter at later stages of cancer. TGFβ signals through the canonical Smad or non-Smad cascade via TGFβ type II and type I receptors. The TGFβ signaling cascade is regulated by various post-translational modifications of its key components. The present investigation aimed to identify a potential function of TRAF6 in TGFβ-induced responses in prostate cancer. The first two articles of this thesis unveil the proteolytic cleavage of TGFβ type I receptor (TβRI), and the biological importance of the liberated TβRI intracellular domain (TβRI-ICD) in the nucleus. We found that tumor necrosis factor receptor-associated factor 6 (TRAF6) polyubiquitinates TβRI, which leads to cleavage of TβRI by tumor necrosis factor alpha converting enzyme (TACE) in a protein kinase C zeta (PKCζ)-dependent manner. Following ectodomain shedding, TβRI undergoes a second cleavage by presenilin 1 (PS1), which liberates TβRI-ICD. TβRI-ICD translocates to the nucleus, where it regulates its own expression as well as expression of the pro-invasive gene Snail1, thereby promoting invasion. We further found that TβRI-ICD associates with Notch intracellular domain (NICD) to drive expression of the pro-invasive gene Snail1, as well as Notch1 ligand Jag1. The third article provides evidence that TRAF6 promotes Lys63-linked polyubiquitination of TβRI at Lys178 in a TGFβ-dependent manner. TβRI polyubiquitination was found to be a prerequisite for TβRI nuclear translocation, and thus for regulation of the genes involved in cell cycle, differentiation, and invasion of prostate cancer cells. In the fourth article we investigated the role of the pro-invasive gene Snail1 in TGFβ-induced epithelial-to-mesenchymal transition (EMT) in prostate cancer cells.

Η σεργλυκίνη (SG) είναι η κύρια πρωτεογλυκάνη που εκφράζεται από τα αιμοποιητικά κύτταρα και συμμετέχει στη ρύθμιση διαφόρων παραγόντων που εμπλέκονται στις αντιδράσεις φλεγμονής. Επιπλέον, φαίνεται ότι διαδραματίζει σημαντικό ρόλο στη βιολογία του πολλαπλού μυελώματος αφού αναστέλλει τη δραστικότητα της κλασικής οδού και της λεκτινικής οδού του συμπληρώματος και προάγει την προσκόλληση των μυελωματικών κυττάρων στο κολλαγόνο τύπου Ι. Παράλληλα, η αυξημένη έκφρασή της σχετίζεται με τον επιθετικό φαινότυπο των κυττάρων καρκίνου του ρινοφάρυγγα. Στην παρούσα διατριβή μελετήθηκε η έκφραση της SG σε κακοήθειες. Τα αποτελέσματά μας αναδεικνύουν την έντονη παρουσία της σε συμπαγείς όγκους λόγω της αυξημένης έκφρασή της είτε από τα καρκινικά κύτταρα είτε από τα κύτταρα φλεγμονής και τα κύτταρα του στρώματος τα οποία επιστρατεύονται κατά την ανάπτυξη του όγκου. Επιπλέον, η αυξημένη έκφρασή της και η έκκρισή της σχετίσθηκαν με το μεταστατικό δυναμικό των κυτταρικών σειρών διαφόρων τύπων καρκίνου. Παράλληλα, ταυτοποιήθηκε η έκφραση του μεταγράφου της SG που προκύπτει από εναλλακτικό μάτισμα με απαλοιφή του εξωνίου 2. Επιπροσθέτως, μελετήθηκε ο βιολογικός ρόλος της SG σε επιθετικά καρκινικά κύτταρα μαστού. Βρέθηκε ότι η SG αλληλεπιδρά με πρωτεΐνες που διαδραματίζουν σημαντικό ρόλο σε κυτταρικές λειτουργίες όπως η αναδιοργάνωση του κυτταροσκελετού, η μεταφορά και ανακύκλωση μορίων από και προς την κυτταρική επιφάνεια και η γονιδιακή ρύθμιση. Η ίδια πρωτεογλυκάνη εκκρίνεται ιδιοσυστατικά από αυτά τα κύτταρα. Τόσο η γλυκοζαμινογλυκανική της σύσταση όσο και η ανασταλτική της δράση έναντι της ενεργοποίησης του συστήματος του συμπληρώματος είναι παρόμοιες με τη SG που εκκρίνεται από τα μυελωματικά κύτταρα. Η συμβολή της SG στον επιθετικό φαινότυπο των καρκινικών κυττάρων επιβεβαιώθηκε με την υπερέκφρασή της σε χαμηλής επιθετικότητας κύτταρα καρκίνου του μαστού. Λειτουργίες όπως ο κυτταρικός πολλαπλασιασμός, η μετανάστευση και η διήθηση των καρκινικών κυττάρων σχετίσθηκαν θετικά με την αυξημένη έκφραση και έκκριση της SG από αυτά τα κύτταρα. Οι επαγωγικές της ιδιότητες καταργήθηκαν με την απαλοιφή των θέσεων πρόσδεσης των γλυκοζαμινογλυκανών από τον πρωτεϊνικό της κορμό. Επιπλέον, διερευνήθηκε το πρωτεολυτικό δυναμικό αυτών των κυττάρων με τη μελέτη της έκφρασης πρωτεολυτικών ενζύμων του εξωκυττάριου χώρου, όπως οι tPA, uPA, MMP-1, MMP-2, MMP-3, MMP-9, MT1-MMP και του αναστολέα των μεταλλοπρωτεϊνασών TIMP-1. Παρουσιάσθηκε ότι η υπερέκφραση του πλήρους μορίου της SG αλλά και της μη γλυκοζυλιωμένης της μορφής οδηγούν στη διαφοροποίηση της έκφρασης και της ενεργότητας των μορίων αυτών με τρόπο που ποικίλει ανάλογα με την κυτταρική πυκνότητα. Παρόλα αυτά, τα δεδομένα που προέκυψαν από τη μελέτη της έκφρασης του uPA και της MT1-MMP συσχέτισαν την αυξημένη τους ενεργότητα με την υπερέκφραση της γλυκοζυλιωμένης μορφής της SG και ανέδειξαν την πιθανή συμβολή τους στην επιθετικότητα των καρκινικών κυττάρων μαστού. Συμπερασματικά, η παρουσία της SG είναι έντονη σε πληθώρα συμπαγών όγκων και καρκινικών κυτταρικών σειρών και φαίνεται να σχετίζεται με το μεταστατικό δυναμικό των κυττάρων. Η συμβολή της στον επιθετικό φαινότυπο των καρκινικών κυττάρων περιλαμβάνει τόσο ενδοκυττάριες όσο και εξωκυττάριες δράσεις που μεσολαβούνται από τη γλυκοζυλιωμένη της μορφή. / Serglycin (SG) is the major proteoglycan of hematopoietic origin cells and contributes to the regulation of several inflammatory proteins. Moreover, SG has a significant role in the biology of Multiple Myeloma; It inhibits the activation of the classical and the lectin pathway of complement system. Enhanced SG expression is correlated with the aggressive phenotype of nasopharyngeal cancer cells. In the present study, the expression of SG in several malignancies was investigated. The strong presence of SG in solid tumors due to its elevated expression either by cancer cells or by inflammatory and stomal cells was revealed. Furthermore, SG elevated expression and secretion was correlated with the high metastatic potential of several cancer cell lines. The expression of the alternatively spliced SG mRNA (variant 2) was identified. This variant lacks exon 2. The role of SG in the biology of aggressive breast cancer cells was studied. SG interacts with significant mediators of actin cytoskeleton reorganization, protein transport and regulation of gene expression. This proteoglycan is constitutively secreted by aggressive breast cancer cells and shares the same glycosaminoglycan (GAG) moieties and inhibitory effects torward complement system activation as the secreted SG by myeloma cells. SG contribution in the aggressive phenotype of cancer cells was studied via the overexpression of the moleclule in the low aggressive breast cancer cells. Cellular functions such as proliferation, migration and invasion of cancer cells were positively correlated with the elevated expression and secretion of SG. These properties were abolished by the deletion of GAG binding sites from SG core protein. Moreover, the proteolytic potential of the overexpressing cells was examined via the expression of ECM degrading molecules, such as tPA, uPA, MMP-1, MMP-2, MMP-3, MMP-9, MT1-MMP, and TIMP-1 MMP inhibitor. Altered expression and activity rates of these enzymes correlated with the overexpression of either the full length or the truncated form of SG in a manner which depends on the cellular density. Interestingly, enhanced MT1-MMP activity followed only the overexpression of the full length molecule indicating the contribution of this MMP in breast cancer cell aggressiveness. The data above revealed the intense presence of SG in several solid tumors and cancer cell lines and the correlation of SG expression with the metastatic potential of cancer cells. Its contribution to cancer cells aggressive phenotype includes both intracellular and extracellular functions which are mediated by the glycanated form of SG.

No description available.

No description available.