Neo-Timm staining in the thalamus of chronically epileptic rats

The thalamus is an important modulator of seizures and is severely affected in cholinergic models of epilepsy. In the present study, chronically epileptic rats had their brains processed for neo-Timm and acetylcholinesterase two months after the induction of status epilepticus with pilocarpine. Both controls and pilocarpine-treated animals presented neo-Timm staining in the anterodorsal nucleus, laterodorsal nucleus, reticular nucleus, most intralaminar nuclei, nucleus reuniens, and rhomboid nucleus of the thalamus, as well as in the zona incerta. The intensity of neo-Timm staining was similar in control and pilocarpine-treated rats, except for the nucleus reuniens and the rhomboid nucleus, which had a lower intensity of staining in the epileptic group. In animal models of temporal lobe epilepsy, zinc seems to modulate glutamate release and to decrease seizure activity. In this context, a reduction of neo-Timm-stained terminals in the midline thalamus could ultimately result in an increased excitatory activity, not only within its related nuclei, but also in anatomical structures that receive their efferent connections. This might contribute to the pathological substrate observed in chronic pilocarpine-treated epileptic animals.

Rankapuun ja -hakkeen laadun vaihtelu terminaalivarastoinnissa

Työssä tutkittiin polttoaineterminaalissa varastoitavan puupolttoaineen laadunmuutoksia. Tutkimuksessa tarkasteltiin hakettamattomien rankapuiden ja rankapuuhakkeen kosteuden ja lämpöarvon muutosta. Myös kuiva-ainetappiota tutkittiin aikaisempien tutkimusten perusteella. Tutkimusaineisto kerättiin Etelä-Savon Energian polttoaineterminaaleista. Kosteus-pitoisuuksia mitattiin Hydromette M2050 -pikakosteusmittarilla ja uunikuivaus-menetelmällä standardin SFS-EN 14774 mukaisesti. Tutkimuksessa huomattiin pikakosteusmittarin toimivan riittävän luotettavalla tasolla rankapuiden mittauksissa, mutta hakkeen mittauksissa mittari osoittautui toimimattomaksi. Varastointiaika ei vaikuttanut polttoaineiden lämpöarvoihin, mutta kosteuspitoisuus vaihteli suuresti. Tutkimustuloksista pääteltiin rangan kuivuvan terminaalivarastossa ja hakkeen kosteuden pysyvän vakiona. Energiasisällön puolesta rankapuuta voidaan varastoida yli 2 vuotta, mutta hakkeen varastointiaika tulisi pitää mahdollisimman lyhyenä.

Dendritic thickness: a morphometric parameter to classify mouse retinal ganglion cells

To study the dendritic morphology of retinal ganglion cells in wild-type mice we intracellularly injected these cells with Lucifer yellow in an in vitro preparation of the retina. Subsequently, quantified values of dendritic thickness, number of branching points and level of stratification of 73 Lucifer yellow-filled ganglion cells were analyzed by statistical methods, resulting in a classification into 9 groups. The variables dendritic thickness, number of branching points per cell and level of stratification were independent of each other. Number of branching points and level of stratification were independent of eccentricity, whereas dendritic thickness was positively dependent (r = 0.37) on it. The frequency distribution of dendritic thickness tended to be multimodal, indicating the presence of at least two cell populations composed of neurons with dendritic diameters either smaller or larger than 1.8 µm ("thin" or "thick" dendrites, respectively). Three cells (4.5%) were bistratified, having thick dendrites, and the others (95.5%) were monostratified. Using k-means cluster analysis, monostratified cells with either thin or thick dendrites were further subdivided according to level of stratification and number of branching points: cells with thin dendrites were divided into 2 groups with outer stratification (0-40%) and 2 groups with inner (50-100%) stratification, whereas cells with thick dendrites were divided into one group with outer and 3 groups with inner stratification. We postulate, that one group of cells with thin dendrites resembles cat ß-cells, whereas one group of cells with thick dendrites includes cells that resemble cat a-cells.

The inhibitory role of sympathetic nervous system in the Ca2+-dependent proteolysis of skeletal muscle

Mammalian cells contain several proteolytic systems to carry out the degradative processes and complex regulatory mechanisms to prevent excessive protein breakdown. Among these systems, the Ca2+-activated proteolytic system involves the cysteine proteases denoted calpains, and their inhibitor, calpastatin. Despite the rapid progress in molecular research on calpains and calpastatin, the physiological role and regulatory mechanisms of these proteins remain obscure. Interest in the adrenergic effect on Ca2+-dependent proteolysis has been stimulated by the finding that the administration of β2-agonists induces muscle hypertrophy and prevents the loss of muscle mass in a variety of pathologic conditions in which calpains are activated. This review summarizes evidence indicating that the sympathetic nervous system produces anabolic, protein-sparing effects on skeletal muscle protein metabolism. Studies are reviewed, which indicate that epinephrine secreted by the adrenal medulla and norepinephrine released from adrenergic terminals have inhibitory effects on Ca2+-dependent protein degradation, mainly in oxidative muscles, by increasing calpastatin levels. Evidence is also presented that this antiproteolytic effect, which occurs under both basal conditions and in stress situations, seems to be mediated by β2- and β3-adrenoceptors and cAMP-dependent pathways. The understanding of the precise mechanisms by which catecholamines promote muscle anabolic effects may have therapeutic value for the treatment of muscle-wasting conditions and may enhance muscle growth in farm species for economic and nutritional purposes.

The immunomodulator glatiramer acetate influences spinal motoneuron plasticity during the course of multiple sclerosis in an animal model

The immunomodulador glatiramer acetate (GA) has been shown to significantly reduce the severity of symptoms during the course of multiple sclerosis and in its animal model - experimental autoimmune encephalomyelitis (EAE). Since GA may influence the response of non-neuronal cells in the spinal cord, it is possible that, to some extent, this drug affects the synaptic changes induced during the exacerbation of EAE. In the present study, we investigated whether GA has a positive influence on the loss of inputs to the motoneurons during the course of EAE in rats. Lewis rats were subjected to EAE associated with GA or placebo treatment. The animals were sacrificed after 15 days of treatment and the spinal cords processed for immunohistochemical analysis and transmission electron microscopy. A correlation between the synaptic changes and glial activation was obtained by performing labeling of synaptophysin and glial fibrillary acidic protein using immunohistochemical analysis. Ultrastructural analysis of the terminals apposed to alpha motoneurons was also performed by electron transmission microscopy. Interestingly, although the GA treatment preserved synaptophysin labeling, it did not significantly reduce the glial reaction, indicating that inflammatory activity was still present. Also, ultrastructural analysis showed that GA treatment significantly prevented retraction of both F and S type terminals compared to placebo. The present results indicate that the immunomodulator GA has an influence on the stability of nerve terminals in the spinal cord, which in turn may contribute to its neuroprotective effects during the course of multiple sclerosis.

Classification of brain tumor extracts by high resolution ¹H MRS using partial least squares discriminant analysis

High resolution proton nuclear magnetic resonance spectroscopy (¹H MRS) can be used to detect biochemical changes in vitro caused by distinct pathologies. It can reveal distinct metabolic profiles of brain tumors although the accurate analysis and classification of different spectra remains a challenge. In this study, the pattern recognition method partial least squares discriminant analysis (PLS-DA) was used to classify 11.7 T ¹H MRS spectra of brain tissue extracts from patients with brain tumors into four classes (high-grade neuroglial, low-grade neuroglial, non-neuroglial, and metastasis) and a group of control brain tissue. PLS-DA revealed 9 metabolites as the most important in group differentiation: γ-aminobutyric acid, acetoacetate, alanine, creatine, glutamate/glutamine, glycine, myo-inositol, N-acetylaspartate, and choline compounds. Leave-one-out cross-validation showed that PLS-DA was efficient in group characterization. The metabolic patterns detected can be explained on the basis of previous multimodal studies of tumor metabolism and are consistent with neoplastic cell abnormalities possibly related to high turnover, resistance to apoptosis, osmotic stress and tumor tendency to use alternative energetic pathways such as glycolysis and ketogenesis.

GABA-induced inactivation of Cebus apella V2 neurons: effects on orientation tuning and direction selectivity

We investigated the GABA-induced inactivation of V2 neurons and terminals on the receptive field properties of this area in an anesthetized and paralyzedCebus apella monkey. Extracellular single-unit activity was recorded using tungsten microelectrodes in a monkey before and after pressure-injection of a 0.25 or 0.5 M GABA solution. The visual stimulus consisted of a bar moving in 8 possible directions. In total, 24 V2 neurons were studied before and after blocker injections in 4 experimental sessions following GABA injection into area V2. A group of 10 neurons were studied over a short period. An additional 6 neurons were investigated over a long period after the GABA injection. A third group of 8 neurons were studied over a very long period. Overall, these 24 neurons displayed an early (1-20 min) significant general decrease in excitability with concomitant changes in orientation or direction selectivity. GABA inactivation in area V2 produced robust inhibition in 80% and a significant change in directional selectivity in 60% of the neurons examined. These GABA projections are capable of modulating not only levels of spontaneous and driven activity of V2 neurons but also receptive field properties such as direction selectivity.

A spheroid-based 3-D culture model for pancreatic cancer drug testing, using the acid phosphatase assay

Current therapy for pancreatic cancer is multimodal, involving surgery and chemotherapy. However, development of pancreatic cancer therapies requires a thorough evaluation of drug efficacy in vitro before animal testing and subsequent clinical trials. Compared to two-dimensional culture of cell monolayer, three-dimensional (3-D) models more closely mimic native tissues, since the tumor microenvironment established in 3-D models often plays a significant role in cancer progression and cellular responses to the drugs. Accumulating evidence has highlighted the benefits of 3-D in vitro models of various cancers. In the present study, we have developed a spheroid-based, 3-D culture of pancreatic cancer cell lines MIAPaCa-2 and PANC-1 for pancreatic drug testing, using the acid phosphatase assay. Drug efficacy testing showed that spheroids had much higher drug resistance than monolayers. This model, which is characteristically reproducible and easy and offers rapid handling, is the preferred choice for filling the gap between monolayer cell cultures and in vivo models in the process of drug development and testing for pancreatic cancer.

Whole transcriptome organisation in the dehydrated supraoptic nucleus

The supraoptic nucleus (SON) is part of the central osmotic circuitry that synthesises the hormone vasopressin (Avp) and transports it to terminals in the posterior lobe of the pituitary. Following osmotic stress such as dehydration, this tissue undergoes morphological, electrical and transcriptional changes to facilitate the appropriate regulation and release of Avp into the circulation where it conserves water at the level of the kidney. Here, the organisation of the whole transcriptome following dehydration is modelled to fit Zipf's law, a natural power law that holds true for all natural languages, that states if the frequency of word usage is plotted against its rank, then the log linear regression of this is -1. We have applied this model to our previously published euhydrated and dehydrated SON data to observe this trend and how it changes following dehydration. In accordance with other studies, our whole transcriptome data fit well with this model in the euhydrated SON microarrays, but interestingly, fit better in the dehydrated arrays. This trend was observed in a subset of differentially regulated genes and also following network reconstruction using a third-party database that mines public data. We make use of language as a metaphor that helps us philosophise about the role of the whole transcriptome in providing a suitable environment for the delivery of Avp following a survival threat like dehydration.

Morphometric analysis of feedforward pathways from the primary somatosensory area (S1) of rats

We used biotinylated dextran amine (BDA) to anterogradely label individual axons projecting from primary somatosensory cortex (S1) to four different cortical areas in rats. A major goal was to determine whether axon terminals in these target areas shared morphometric similarities based on the shape of individual terminal arbors and the density of two bouton types: en passant (Bp) and terminaux (Bt). Evidence from tridimensional reconstructions of isolated axon terminal fragments (n=111) did support a degree of morphological heterogeneity establishing two broad groups of axon terminals. Morphological parameters associated with the complexity of terminal arbors and the proportion of beaded Bp vs stalked Bt were found to differ significantly in these two groups following a discriminant function statistical analysis across axon fragments. Interestingly, both groups occurred in all four target areas, possibly consistent with a commonality of presynaptic processing of tactile information. These findings lay the ground for additional work aiming to investigate synaptic function at the single bouton level and see how this might be associated with emerging properties in postsynaptic targets.

Tracing Innovation Practices in Seaports: the Ports of Klaipeda and Stockholm as Case Studies

This study explores variegated means through which ports have become increasingly entangled in the planning logic of neoliberal innovation-driven economy. The research topic belongs to the academic disciplines of economics and human geography. The aim of the thesis is to analyse how the notion of innovation, adopted in a variety of supranational and national port policy documents, is deployed in operational port environment in two different ports of the Baltic Sea Region: the port of Stockholm, Sweden, and the port of Klaipeda, Lithuania. This novel innovation agenda is visible in several topics I examine in the study, that is, port governance, environmental issues, and seaport – port-city interface. The gathered primary source material on port policy documents, strategies, development planning documents and reports is analysed by utilizing the qualitative content analysis research method. Moreover, the empirical part of the case study, that is, tracing innovation practices in mundane port activities is based on collected qualitative semi-structured interviews with port authorities in Klaipeda and Stockholm, researchers and other port experts. I examine the interview material by employing the theoretical reading research method. In my analysis, I have reframed port-related policy development by tracing and identifying the port transformation from “functional terminals” to “engines for growth”. My results show that this novel innovation-oriented rhetoric imprinted in the narrative “engines for growth” is often contested in daily port practices. In other words, my analysis reveals that the port authorities’ and other port actors’ attitudes towards innovations do not necessarily correspond to the new narrative of innovation and do not always “fit” within a framework of neoliberal economic thinking that glorifies the “culture of innovations”. I argue that the ability to develop innovative initiatives in the ports of Klaipeda and Stockholm is strongly predetermined by local conditions, a port’s governance model, the way port actors perceive the importance of innovations per se, demand factors and new regulations.

Paisagens de ausência e de vazio

Este estudo procura evidenciar a natureza lacunar e intersticial da espacialidade própria à experiência sensível, segundo o último Merleau-Ponty, aquele da notas de trabalho de Le visible et l'invisible. Para tanto, são discutidos os momentos em que, no trato tanto com a perceptibilidade quanto com a intersubjetividade, Merleau-Ponty evoca a vida intencional a partir da analogia com a experiência estética em sua selvagem polissemia. O estudo especula que, apesar da evidência de que a plasticidade multimodal da arte moderna fornece renovado suporte para a interpretação da experiência sensorial, tarefa impossível para a racionalidade, a teoria do último Merleau-Ponty parece incapaz de propor uma noção consistente de negatividade.

Litteracitet i fem högstadieungdomars en-till-en-datorpraktiker

The study focuses on five lower secondary school pupils’ daily use of their one-toone computers, the overall aim being to investigate literacy in this form of computing. Theoretically, the study is rooted in the New Literacy tradition with an ecological perspective, in combination with socio-semiotic theory in a multimodal perspective. New Literacy in the ecological perspective focuses on literacy practices and place/space and on the links between them. Literacy is viewed as socially based, in specific situations and in recurring social practices. Socio-semiotic theory embodying the multimodal perspective is used for the text analysis. The methodology is known as socio-semiotic ethnography. The ethnographic methods encompass just over two years of fieldwork with participating observations of the five participants’ computing activities at home, at school and elsewhere. The participants, one boy and two girls from the Blue (Anemone) School and two girls from the White (Anemone) School, were chosen to reflect a broad spectrum in terms of sociocultural and socioeconomic background. The study shows the existence of a both broad and deep variation in the way digital literacy features in the participants’ one-to-one computing. These variations are associated with experience in relation to the home, the living environment, place, personal qualities and school. The more varied computer usage of the Blue School participants is connected with the interests they developed in their homes and living environments and in the computing practices undertaken in school. Their more varied usage of the computer is reflected in their broader digital literacy repertoires and their greater number and variety of digital literacy abilities. The Blue School participants’ text production is more multifaceted, covers a wider range of subjects and displays a broader palette of semiotic resources. It also combines more text types and the texts are generally longer than those of the White School participants. The Blue School girls have developed a text culture that is close to that of the school. In their case, there is clear linkage between school-initiated and self-initiated computing activities, while other participants do not have the same opportunities to link and integrate self-initiated computing activities into the school context. It also becomes clear that the Blue School girls can relate and adapt their texts to different communicative practices and recipients. In addition, the study shows that the Blue School girls have some degree of scope in their school practice as a result of incorporating into it certain communicative practices that they have developed in nonschool contexts. Quite contrary to the hopes expressed that one-to-one computing would reduce digital inequality, it has increased between these participants. Whether the same or similar results apply in a larger perspective, on a more structural level, is a question that this study cannot answer. It can only draw attention to the need to investigate the matter. The study shows in a variety of ways that the White School participants do not have the same opportunity to develop their digital literacy as the Blue School participants. In an equivalence perspective, schools have a compensational task to perform. It is abundantly clear from the study that investing in one-to-one projects is not enough to combat digital inequality and achieve the digitisation goals established for school education. Alongside their investments in technology, schools need to develop a didactic that legitimises and compensates for the different circumstances of different pupils. The compensational role of schools in this connection is important not only for the present participants but also for the community at large, in that it can help to secure a cohesive, open and democratic society.

Evaluation of a treatment program for individuals with an intellectual disability who have high risk behaviours

In the past two decades numerous programs have emerged to treat individuals with developmental disabilities who have sexual offending behaviours. There has, however been very few studies that systematically examine the effectiveness of long term treatment with this population. The present research examines the therapeutic outcomes of a multi-modal behaviour approach with six individuals with intellectual disabilities previously charged with sexual assault. The participants also exhibited severe behavioural challenges that included verbal aggression, physical aggression, destruction and self-injury. These six participants (5 males, 1 female) were admitted to a Long Term Residential Treatment Program (LTRTP), due to the severity of their behaviours and due to their lack of treatment success in other programs. Individualized treatment plans focused on the reduction of maladaptive behaviours and the enhancing of skills such as positive coping strategies, socio-sexual knowledge, life skills, recreation and leisure skills. The treatment program also included psychiatric, psychological, medical, behavioural and educational interventions. The participants remained in the Long Term Residential Treatment Program (LTRTP) program from 181 to 932 days (average of 1.5 years). Pre and post treatment evaluations were conducted using the following tools: frequency of target behaviours, Psychopathology Inventory for Mentally Retarded Adults (PIMRA), Emotional Problems Scale (EPS), Socio-Sexual Knowledge and Attitudes Assessment Tool (SSKAAT-R) and Quality of Life Questionnaire (QOL-Q). Recidivism rates and the need for re-hospitalization were also noted for each participant. By offering high levels of individualized interventions, all six participants showed a 37 % rate of reduction in maladaptive behaviours with zero to low rates of inappropriate sexualbehaviour, there were no psychiatric hospitalizations, and there was no recidivism for 5 of 6 participants. In addition, medication was reduced. Mental health scores on the PIMRA were reduced across all participants by 25 % and scores on the Quality of Life Questionnaire increased for all participants by an average of 72 %. These findings add to and build upon the existing literature on long term treatment benefits for individuals with a intellectual disability who sexually offend. By utilizing an individualized and multimodal treatment approach to reduce severe behavioural challenges, not only can the maladaptive behaviours be reduced, but adaptive behaviours can be increased, mental health concerns can be managed, and overall quality of life can be improved.