Transforming Bodies, Wandering Desires. Intra-actions of Gender and Sexuality in Non-heterosexual Transgender Embodiment

Pro gradu -tutkielmani käsittelee sukupuolen ja seksuaalisuuden keskinäisiä intraaktiivisia vuorovaikutussuhteita elettyjen, ei-heteroseksuaalisten transsukupuolisten ruumiiden kokemuksissa. Tutkielmani haastaa sukupuolen ja seksuaalisuuden pysyvyyden käsityksiä sekä niihin liittyviä yhteiskunnallisia normeja kuvaten tapoja, joilla seksuaalisuuden ja sukupuolen kokeminen ja käytännöt liikkuvat, kehittyvät ja vuorovaikuttavat eletyissä transsukupuolisuuden ruumiillistumissa. Haastattelen kuutta suomalaista, syntymässä naiseksi määriteltyä transsukupuolista henkilöä liittyen heidän kokemuksiinsa sukupuolesta, seksuaalisuudesta ja näiden muutoksista heidän tähänastisen elämänsä aikana. Tarkastelen nauhoitettuja ja litteroituja haastattelutekstejä transtutkimusta, queer-teoriaa ja feminististä uusmaterialistista filosofiaa yhdistävän teoreettisen kehyksen kautta keskittyen siihen, miten sukupuoli ja seksuaalisuus vaikuttavat toistensa kehitykseen, muutokseen ja materialisoitumiseen eri elämänvaiheissa ja tilanteissa. Erityisen tärkeiksi teoreettisiksi vaikuttajiksi tutkielmassani muodostuvat Judith Butlerin Gender Trouble (2006 [1990]) -teoksessaan hahmottelema performatiivisen sukupuolen teoria, Sara Ahmedin analyysi teoksessa Queer Phenomenology. Orientations, Objects, Others (2006) ja Karen Baradin teoksessa Meeting the Universe Halfway. Quantum Physics and the Entanglement of Matter and Meaning (2007) teoretisoima toimijuudellinen realismi. Päästäkseni kiinni sukupuolen ja seksuaalisuuden yhtymäkohtiin erittelen ensin niitä ominaisuuksia ja kokemuksia, jotka näyttäytyvät haastatteluteksteissäni oleellisina seksuaalisuuden ja sukupuolen kannalta. Tarkastelen seksuaalisuutta suuntautumisen, halun ja seksuaalisten käytäntöjen näkökulmasta: vaikka nämä seksuaalisuuden aspektit ovat kiinteästi kytköksissä toisiinsa, niitä ei voi kokonaan palauttaa toisiinsa. Sukupuolta käsittelen performatiivisuuden näkökulmasta painottaen transsukupuolisiin ruumiisiin ja niiden materiaalisuuteen liittyviä erityispiirteitä. Sukupuolen ja seksuaalisuuden suhteita toisiinsa tarkastelen sekä sellaisissa tilanteissa, joissa niitä on vaikea erottaa toisistaan, että sellaisissa, joissa niiden voidaan nähdä tuottavan toinentoisiaan. Tutkielmallani on etnografisia, filosofisia ja poliittisia ulottuvuuksia. Yhtäältä tahdon kuvata ja analysoida elettyjä transsukupuolisia kokemuksia ja tuottaa tietoa vähän tutkitun ihmisryhmän todellisuudesta. Toisaalta osallistun sukupuolifilosofiseen keskusteluun ruumiillisuudesta ja sukupuolen ja seksuaalisuuden olemuksesta. Lähestyn tutkimusprosessiani niin sanotusta transgender standpoint -näkökulmasta; kirjoitan transsukupuolisena ruumiina, transsukupuolisia ruumiita koskien, pyrkimyksenäni edistää elävien transsukupuolisten ruumiiden asemaa, toimijuutta ja näkyvyyttä yhteiskunnassa.

Renal actions of angiotensin-(1-7)

The heptapeptide angiotensin-(1-7) is considered to be a biologically active endproduct of the renin-angiotensin system. This angiotensin, which is devoid of the most known actions of angiotensin II such as induction of drinking behavior and vasoconstriction, has several selective effects in the brain and periphery. In the present article we briefly review recent evidence for a physiological role of angiotensin-(1-7) in the control of hydroelectrolyte balance

The photodynamic and non-photodynamic actions of porphyrins

Porphyrias are a family of inherited diseases, each associated with a partial defect in one of the enzymes of the heme biosynthetic pathway. In six of the eight porphyrias described, the main clinical manifestation is skin photosensitivity brought about by the action of light on porphyrins, which are deposited in the upper epidermal layer of the skin. Porphyrins absorb light energy intensively in the UV region, and to a lesser extent in the long visible bands, resulting in transitions to excited electronic states. The excited porphyrin may react directly with biological structures (type I reactions) or with molecular oxygen, generating excited singlet oxygen (type II reactions). Besides this well-known photodynamic action of porphyrins, a novel light-independent effect of porphyrins has been described. Irradiation of enzymes in the presence of porphyrins mainly induces type I reactions, although type II reactions could also occur, further increasing the direct non-photodynamic effect of porphyrins on proteins and macromolecules. Conformational changes of protein structure are induced by porphyrins in the dark or under UV light, resulting in reduced enzyme activity and increased proteolytic susceptibility. The effect of porphyrins depends not only on their physico-chemical properties but also on the specific site on the protein on which they act. Porphyrin action alters the functionality of the enzymes of the heme biosynthetic pathway exacerbating the metabolic deficiencies in porphyrias. Light energy absorption by porphyrins results in the generation of oxygen reactive species, overcoming the protective cellular mechanisms and leading to molecular, cell and tissue damage, thus amplifying the porphyric picture.

Bi-directional actions of estrogen on the renin-angiotensin system

Estrogen stimulates the renin-angiotensin system by augmenting both tissue and circulating levels of angiotensinogen and renin. We show, however, that angiotensin converting enzyme (ACE) activity in the circulation and in tissues is reduced in two animal models of postmenopausal chronic hormone replacement. We observed a reduction of ACE activity in association with a significant increase in plasma angiotensin I (Ang I) and hyperreninemia in ovariectomized monkeys treated with Premarin (conjugated equine estrogen) replacement for 30 months. Plasma angiotensin II (Ang II) levels were not increased in monkeys treated with estrogen, suggesting that the decrease in ACE curtailed the formation of the peptide. The Ang II/Ang I ratio, an in vivo index of ACE activity, was significantly reduced by estrogen treatment, further supporting the biochemical significance of estrogen's inhibition of ACE. In ovariectomized transgenic hypertensive (mRen2)27 rats submitted to estrogen replacement treatment for 3 weeks, ACE activity in plasma and tissue (aorta and kidney) and circulating Ang II levels were reduced, whereas circulating levels of angiotensin-(1-7) (Ang-(1-7) were increased. Ang-(1-7), the N-terminal fragment of Ang II, is a novel vasodilator and antihypertensive peptide. Thus, the net balance of these effects of estrogen on the renin-angiotensin vasoconstrictor/vasodilator system is to promote the antihypertensive effect.

Relationship between the actions of atrial natriuretic peptide (ANP), guanylin and uroguanylin on the isolated kidney

Guanylin and uroguanylin are peptides that bind to and activate guanylate cyclase C and control salt and water transport in many epithelia in vertebrates, mimicking the action of several heat-stable bacteria enterotoxins. In the kidney, both of them have well-documented natriuretic and kaliuretic effects. Since atrial natriuretic peptide (ANP) also has a natriuretic effect mediated by cGMP, experiments were designed in the isolated perfused rat kidney to identify possible synergisms between ANP, guanylin and uroguanylin. Inulin was added to the perfusate and glomerular filtration rate (GFR) was determined at 10-min intervals. Sodium was also determined. Electrolyte dynamics were measured by the clearance formula. Guanylin (0.5 µg/ml, N = 12) or uroguanylin (0.5 µg/ml, N = 9) was added to the system after 30 min of perfusion with ANP (0.1 ng/ml). The data were compared at 30-min intervals to a control (N = 12) perfused with modified Krebs-Hanseleit solution and to experiments using guanylin and uroguanylin at the same dose (0.5 µg/ml). After previous introduction of ANP in the system, guanylin promoted a reduction in fractional sodium transport (%TNa+, P<0.05) (from 78.46 ± 0.86 to 64.62 ± 1.92, 120 min). In contrast, ANP blocked uroguanylin-induced increase in urine flow (from 0.21 ± 0.01 to 0.15 ± 0.007 ml g-1 min-1, 120 min, P<0.05) and the reduction in fractional sodium transport (from 72.04 ± 0.86 to 85.19 ± 1.48, %TNa+, at 120 min of perfusion, P<0.05). Thus, the synergism between ANP + guanylin and the antagonism between ANP + uroguanylin indicate the existence of different subtypes of receptors mediating the renal actions of guanylins.

Binding sites and actions of Tx1, a neurotoxin from the venom of the spider Phoneutria nigriventer, in guinea pig ileum

Tx1, a neurotoxin isolated from the venom of the South American spider Phoneutria nigriventer, produces tail elevation, behavioral excitation and spastic paralysis of the hind limbs after intracerebroventricular injection in mice. Since Tx1 contracts isolated guinea pig ileum, we have investigated the effect of this toxin on acetylcholine release, as well as its binding to myenteric plexus-longitudinal muscle membranes from the guinea pig ileum. [125I]-Tx1 binds specifically and with high affinity (Kd = 0.36 ± 0.02 nM) to a single, non-interacting (nH = 1.1), low capacity (Bmax 1.1 pmol/mg protein) binding site. In competition experiments using several compounds (including ion channel ligands), only PhTx2 and PhTx3 competed with [125I]-Tx1 for specific binding sites (K0.5 apparent = 7.50 x 10-4 g/l and 1.85 x 10-5 g/l, respectively). PhTx2 and PhTx3, fractions from P. nigriventer venom, contain toxins acting on sodium and calcium channels, respectively. However, the neurotoxin PhTx2-6, one of the isoforms found in the PhTx2 pool, did not affect [125I]-Tx1 binding. Tx1 reduced the [3H]-ACh release evoked by the PhTx2 pool by 33%, but did not affect basal or KCl-induced [3H]-ACh release. Based on these results, as well as on the homology of Tx1 with toxins acting on calcium channels (w-Aga IA and IB) and its competition with [125I]-w-Cono GVIA in the central nervous system, we suggest that the target site for Tx1 may be calcium channels.

Co-creating value with customers as a new approach of entering new market

Global trends associated with development of information technology, globalization, industrial and economic changes are influencing on company and customer domains and thus transforming company-customer relationship. The company centric paradigm with a strong product focus shifts to a customer oriented one with a strong emphasis on customer collaboration. As a result, the customer role changes from a passive observer to an active player. Moreover, global trends contribute to transformation of competitive environment making it tougher and simplifying an access to resources previously considered as unique. All that factors push the companies towards cooperation with customers in order to identify unarticulated needs and finding the best possible solution to existing customer problems. The Master’s Thesis is done for Outotec (Lappeenranta) which considers extension of dewatering business in Russian coal market. Research aims to identify key features of coal preparation and dewatering of fine coal and tailings in Russian preparation plants; analyze the state of Russian coal market and evaluate market potential for Outotec dewatering solutions. The study has a qualitative nature and implements an action research methodology that involves both creation of knowledge and introduction of changes into the system. The base for taking actions is formed by theoretical framework that targets on describing company - customer interaction and has selected co-creation as the most appropriate method of customer involvement. The integration of co-creation approach into an action research cycle allows not only fulfilling the research objectives but also facilitates organizational learning and intraorganizational collaboration, assists in establishing customer contacts and making the first steps into the market, bringing new joint projects to the company and opening real business opportunities.

Pp2a: At The Crossroads Between Growth and Defence In Plants

Living organisms manage their resources in well evolutionary-preserved manner to grow and reproduce. Plants are no exceptions, beginning from their seed stage they have to perceive environmental conditions to avoid germination at wrong time or rough soil. Under favourable conditions, plants invest photosynthetic end products in cell and organ growth to provide best possible conditions for generation of offspring. Under natural conditions, however, plants are exposed to a multitude of environmental stress factors, including high light and insufficient light, drought and flooding, various bacteria and viruses, herbivores, and other plants that compete for nutrients and light. To survive under environmental challenges, plants have evolved signaling mechanisms that recognise environmental changes and perform fine-tuned actions that maintain cellular homeostasis. Controlled phosphorylation and dephosphorylation of proteins plays an important role in maintaining balanced flow of information within cells. In this study, I examined the role of protein phosphatase 2A (PP2A) on plant growth and acclimation under optimal and stressful conditions. To this aim, I studied gene expression profiles, proteomes and protein interactions, and their impacts on plant health and survival, taking advantage of the model plant Arabidopsis thaliana and the mutant approach. Special emphasis was made on two highly similar PP2A-B regulatory subunits, B’γ and B’ζ. Promoters of B’γ and B’ζ were found to be similarly active in the developing tissues of the plant. In mature leaves, however, the promoter of B’γ was active in patches in leaf periphery, while the activity of B’ζ promoter was evident in leaf edges. The partially overlapping expression patterns, together with computational models of B’γ and B’ζ within trimeric PP2A holoenzymes suggested that B’γ and B’ζ may competitively bind into similar PP2A trimmers and thus influence each other’s actions. Arabidopsis thaliana pp2a-b’γ and pp2a-b’γζ double mutants showed dwarfish phenotypes, indicating that B’γ and B’ζ are needed for appropriate growth regulation under favorable conditions. However, while pp2a-b’γ displayed constitutive immune responses and appearance of premature yellowings on leaves, the pp2a-b’γζ double mutant supressed these yellowings. More detailed analysis of defense responses revealed that B’γ and B’ζ mediate counteracting effects on salicylic acid dependent defense signalling. Associated with this, B’γ and B’ζ were both found to interact in vivo with CALCIUM DEPENDENT PROTEIN KINASE 1 (CPK1), a crucial element of salicylic acid signalling pathway against pathogens in plants. In addition, B’γ was shown to modulate cellular reactive oxygen species (ROS) metabolism by controlling the abundance of ALTERNATIVE OXIDASE 1A and 1D in mitochondria. PP2A B’γ and B’ζ subunits turned out to play crucial roles in the optimization of plant choices during their development. Taken together, PP2A allows fluent responses to environmental changes, maintenance of plant homeostasis, and grant survivability with minimised cost of redirection of resources from growth to defence.

Actions of Crotalus durissus terrificus venom and crotoxin on the isolated rat kidney

Many studies have reported the occurrence of lethal acute renal failure after snakebites. The aim of the present investigation was to determine alterations in renal function produced by Crotalus durissus terrificus venom and crotoxin as well as the histological alterations induced by these venoms. Isolated kidneys from Wistar rats weighing 240 to 280 g were perfused with Krebs-Henseleit solution containing 6 g% of previously dialyzed bovine serum albumin. The effects of Crotalus durissus terrificus venom and crotoxin were studied on glomerular filtration rate (GFR), urinary flow (UF), perfusion pressure (PP) and percentage sodium tubular transport (%TNa+). The infusion of Crotalus durissus terrificus venom (10 µg/ml) and crotoxin (10 µg/ml) increased GFR (control80 = 0.78 ± 0.07, venom80 = 1.1 ± 0.07, crotoxin80 = 2.0 ± 0.05 ml g-1 min-1, P<0.05) and UF (control80 = 0.20 ± 0.02, venom80 = 0.32 ± 0.03, crotoxin80 = 0.70 ± 0.05 ml g-1 min-1, P<0.05), and decreased %TNa+ (control100 = 75.0 ± 2.3, venom100 = 62.9 ± 1.0, crotoxin80 = 69.0 ± 1.0 ml g-1 min-1, P<0.05). The infusion of crude venom tended to reduce PP, although the effect was not significant, whereas with crotoxin PP remained stable during the 100 min of perfusion. The kidneys perfused with crude venom and crotoxin showed abundant protein material in the urinary space and tubules. We conclude that Crotalus durissus terrificus venom and crotoxin, its major component, cause acute nephrotoxicity in the isolated rat kidney. The current experiments demonstrate a direct effect of venom and crotoxin on the perfused isolated kidney.

Evaluation of the cholinomimetic actions of trimethylsulfonium, a compound present in the midgut gland of the sea hare Aplysia brasiliana (Gastropoda, Opisthobranchia)

Trimethylsulfonium, a compound present in the midgut gland of the sea hare Aplysia brasiliana, negatively modulates vagal response, indicating a probable ability to inhibit cholinergic responses. In the present study, the pharmacological profile of trimethylsulfonium was characterized on muscarinic and nicotinic acetylcholine receptors. In rat jejunum the contractile response induced by trimethylsulfonium (pD2 = 2.46 ± 0.12 and maximal response = 2.14 ± 0.32 g) was not antagonized competitively by atropine. The maximal response (Emax) to trimethylsulfonium was diminished in the presence of increasing doses of atropine (P<0.05), suggesting that trimethylsulfonium-induced contraction was not related to muscarinic stimulation, but might be caused by acetylcholine release due to presynaptic stimulation. Trimethylsulfonium displaced [³H]-quinuclidinyl benzilate from rat cortex membranes with a low affinity (Ki = 0.5 mM). Furthermore, it caused contraction of frog rectus abdominis muscles (pD2 = 2.70 ± 0.06 and Emax = 4.16 ± 0.9 g), which was competitively antagonized by d-tubocurarine (1, 3 or 10 µM) with a pA2 of 5.79, suggesting a positive interaction with nicotinic receptors. In fact, trimethylsulfonium displaced [³H]-nicotine from rat diaphragm muscle membranes with a Ki of 27.1 µM. These results suggest that trimethylsulfonium acts as an agonist on nicotinic receptors, and thus contracts frog skeletal rectus abdominis muscle and rat jejunum smooth muscle via stimulation of postjunctional and neuronal prejunctional nicotinic cholinoreceptors, respectively.

The Possibility of Greenhouse Gas Mitigation in Ethiopian Cement Industry

Cement industry significantly associated with high greenhouse gas (GHG) emissions. Considering the environmental impact, particularly global warming potential, it is important to reduce these emissions to air. The aim of the study is to investigate the mitigation possibility of GHG emissions in Ethiopian cement industry. Life cycle assessment (LCA) method used to identify and quantify GHG emissions during one ton of ordinary portland cement (OPC) production. Three mitigation scenarios: alternative fuel use, clinker substitution and thermal energy efficiency were applied on a representative gate-to-gate flow model developed with GaBi 6 software. The results of the study indicate that clinker substitution and alternative fuel use play a great role for GHG emissions mitigation with affordable cost. Applying most energy efficient kiln technology, which in turn reduces the amount of thermal energy use, has the least GHG emissions reduction intensity and high implementation cost comparing to the other scenarios. It was found that the cumulative GHG emissions mitigation potential along with other selected mitigation scenarios can be at least 48.9% per ton of cement production.

Hemodynamic and hormonal actions of adrenomedullin

Adrenomedullin, a 52-amino acid residue peptide, has numerous biological actions which are of potential importance to cardiovascular homeostasis, growth and development of cardiovascular tissues and bone, prevention of infection, and regulation of body fluid and electrolyte balance. Studies in man using intravenous infusion of the peptide have demonstrated that, at plasma levels detected after myocardial infarction or in heart failure, adrenomedullin reduces arterial pressure, increases heart rate and cardiac output, and activates the sympathetic and renin-angiotensin systems but suppresses aldosterone. The thresholds for these responses differ, being lower under some experimental circumstances for arterial pressure than for the other biological effects. Adrenomedullin administration inhibits the pressor and aldosterone-stimulating action of angiotensin II in man. By contrast, the pressor effect of norepinephrine is little altered by concomitant adrenomedullin administration. Although in the absence of a safe, specific antagonist of the actions of endogenous adrenomedullin it is difficult to be certain about the physiological and pathophysiological importance of this peptide in man, current evidence suggests that it serves to protect against cardiovascular overload and injury. Hope has been expressed that adrenomedullin or an agonist specific for adrenomedullin receptors might find a place in the treatment of cardiovascular disorders.

Cardiovascular actions of angiotensin-(1-7)

Angiotensin-(1-7) (Ang-(1-7)) is now considered to be a biologically active member of the renin-angiotensin system. The functions of Ang-(1-7) are often opposite to those attributed to the main effector component of the renin-angiotensin system, Ang II. Chronic administration of angiotensin-converting enzyme inhibitors (ACEI) increases 10- to 25-fold the plasma levels of this peptide, suggesting that part of the beneficial effects of ACEI could be mediated by Ang-(1-7). Ang-(1-7) can be formed from Ang II or directly from Ang I. Other enzymatic pathways for Ang-(1-7) generation have been recently described involving the novel ACE homologue ACE2. This enzyme can form Ang-(1-7) from Ang II or less efficiently by the hydrolysis of Ang I to Ang-(1-9) with subsequent Ang-(1-7) formation. The biological relevance of Ang-(1-7) has been recently reinforced by the identification of its receptor, the G-protein-coupled receptor Mas. Heart and blood vessels are important targets for the formation and actions of Ang-(1-7). In this review we will discuss recent findings concerning the biological role of Ang-(1-7) in the heart and blood vessels, taking into account aspects related to its formation and effects on these tissues. In addition, we will discuss the potential of Ang-(1-7) and its receptor as a target for the development of new cardiovascular drugs.

To divide or differentiate? : nestin-mediated regulation of Cdk5 in cell fate decisions

The molecular functions of the non-cell cycle-related Cyclin-dependent kinase 5 (Cdk5) have been of primary interest within the neuroscience field, but novel undertakings are constantly emerging for the kinase in tissue homeostasis, as well as in diseases such as diabetes and cancer. Although Cdk5 activation is predominantly regulated by specific non-cyclin activator protein binding, additional mechanisms have proved to orchestrate Cdk5 signaling in cells. For example, the interaction between the intermediate filament protein nestin and Cdk5 has been proposed to determine cellular fate during neuronal apoptosis through nestin-dependent adjustment of the sensitive balance and turnover of Cdk5 activators. While nestin constitutes a crucial regulatory scaffold for appropriate Cdk5 activation in apoptosis, Cdk5 itself phosphorylates nestin with the consequence of filament reorganization in both neuronal progenitors and differentiating muscle cells. Interestingly, the two proteins are often found coexpressed in various tissues and cell types, proposing that nestin-mediated scaffolding of Cdk5 and its activators may be applicable to other tissue systems as well. In the literature, the molecular functions of nestin have remained in the shade, as it is mostly exploited as a marker protein for progenitor cells. In light of these studies, the aim of this thesis was to assess the importance of the nestin scaffold in regulation of Cdk5 actions in cell fate decisions. This thesis can be subdivided into two major projects: one that studied the nature of the Cdk5-nestin interplay in muscle, and one that assessed their role in prostate cancer. During differentiation of a myoblast cell line, the filament formation properties of nestin was found to be crucial in directing Cdk5 activity, with direct consequences on the process of differentiation. Also the genetic knockout of nestin was found to influence Cdk5 activity, although differentiation per se was not affected. Instead, the genetic ablation of nestin had broad consequences on muscle homeostasis and regeneration. While the nestin-mediated regulation of Cdk5 in muscle was found to act in multiple ways, the connection remained more elusive in cancer models. Cdk5 was, however, established as a significant determinant of prostate cancer proliferation; a behavior uncharacteristic for this differentiation-associated kinase. Through complex and simultaneous regulation of two major prostate cancer pathways, Cdk5 was placed upstream of both Akt kinase and the androgen receptor. Its action on proliferation was nonetheless mainly exerted through the Akt signaling pathway in various cancer models. In summary, this thesis contributed to the knowledge of Cdk5 regulation and functions in two atypical settings; proliferation (in a cancer framework) and muscle differentiation, which is a poorly understood model system in the Cdk5 field. This balance between proliferation and differentiation implemented by Cdk5 is ultimately regulated (where present) by the dynamics of the cytoskeletal nestin scaffold.

Central actions of glucocorticoids in the control of body fluid homeostasis: Review

The involvement of the hypothalamic-pituitary-adrenal axis in the control of body fluid homeostasis has been extensively investigated in the past few years. In the present study, we reviewed the recent results obtained using different approaches to investigate the effects of glucocorticoids on the mechanisms of oxytocin and vasopressin synthesis and secretion in response to acute and chronic plasma volume and osmolality changes. The data presented here suggest that glucocorticoids are not only involved in the mechanisms underlying the fast release but also in the transcriptional events that lead to decreased synthesis and secretion of these neuropeptides, particularly oxytocin, under diverse experimental conditions of altered fluid volume and tonicity. The endocannabinoid system, through its effects on glutamatergic neurotransmission within the hypothalamus and the nuclear factor κB-mediated transcriptional activity, seems to be also involved in the specific mechanisms by which glucocorticoids exert their central effects on neurohypophyseal hormone synthesis and secretion.