Functional characterization of the precursor and spliced forms of RecA protein of Mycobacterium tuberculosis

The recA locus of pathogenic mycobacteria differs from that of nonpathogenic species because it contains large intervening sequences nested in the RecA homology region that are excised by an unusual protein-splicing reaction. In vivo assays indicated that Mycobacterium tuberculosis recA partially complemented Escherichia coli recA mutants for recombination and mutagenesis. Further, splicing of the 85 kDa precursor to 38 kDa MtRecA protein was necessary for the display of its activity, in vivo. To gain insights into the molecular basis for partial and lack of complementation by MtRecA and 85 kDa proteins, respectively, we purified both of them to homogeneity. MtRecA protein, but not the 85 kDa form, bound stoichiometrically to single-stranded DNA in the presence of ATP. MtRecA protein was cross-linked to 8-azidoadenosine 5'-triphosphate with reduced efficiency, and kinetic analysis of ATPase activity suggested that it is due to decreased affinity for ATP. In contrast, the 85 kDa form was unable to bind ATP, in the presence or absence of ssDNA and, consequently, was entirely devoid of ATPase activity. Molecular modeling studies suggested that the decreased affinity of MtRecA protein for ATP and the reduced efficiency of its hydrolysis might be due to the widening of the cleft which alters the hydrogen bonds and the contact area between the enzyme and the substrate and changes in the disposition of the amino acid residues around the magnesium ion and the gamma-phosphate. The formation of joint molecules promoted by MtRecA protein was stimulated by SSB when the former was added first. The probability of an association between the lack and partial levels of biological activity of RecA protein(s) to that of illegitimate recombination in pathogenic mycobacteria is considered.

Genetic analysis of chromosomal regions 2q33, 7q32 and 19q13 in multiple sclerosis susceptibility

Multiple sclerosis (MS) is an immune-mediated demyelinating disorder of the central nervous system (CNS) affecting 0.1-0.2% of Northern European descent population. MS is considered to be a multifactorial disease, both environment and genetics play a role in its pathogenesis. Despite several decades of intense research, the etiological and pathogenic mechanisms underlying MS remain still largely unknown and no curative treatment exists. The genetic architecture underlying MS is complex with multiple genes involved. The strongest and the best characterized predisposing genetic factors for MS are located, as in other immune-mediated diseases, in the major histocompatibility complex (MHC) on chromosome 6. In humans MHC is called human leukocyte antigen (HLA). Alleles of the HLA locus have been found to associate strongly with MS and remained for many years the only consistently replicable genetic associations. However, recently other genes located outside the MHC region have been proposed as strong candidates for susceptibility to MS in several studies. In this thesis a new genetic locus located on chromosome 7q32, interferon regulatory factor 5 (IRF5), was identified in the susceptibility to MS. In particular, we found that common variation of the gene was associated with the disease in three different populations, Spanish, Swedish and Finnish. We also suggested a possible functional role for one of the risk alleles with impact on the expression of the IRF5 locus. Previous studies have pointed out a possible role played by chromosome 2q33 in the susceptibility to MS and other autoimmune disorders. The work described here also investigated the involvement of this chromosomal region in MS predisposition. After the detection of genetic association with 2q33 (article-1), we extended our analysis through fine-scale single nucleotide polymorphism (SNP) mapping to define further the contribution of this genomic area to disease pathogenesis (article-4). We found a trend (p=0.04) for association to MS with an intronic SNP located in the inducible T-cell co-stimulator (ICOS) gene, an important player in the co-stimulatory pathway of the immune system. Expression analysis of ICOS revealed a novel, previously uncharacterized, alternatively spliced isoform, lacking the extracellular domain that is needed for ligand binding. The stability of the newly-identified transcript variant and its subcellular localization were analyzed. These studies indicated that the novel isoform is stable and shows different subcellular localization as compared to full-length ICOS. The novel isoform might have a regulatory function, but further studies are required to elucidate its function. Chromosome 19q13 has been previously suggested as one of the genomic areas involved in MS predisposition. In several populations, suggestive linkage signals between MS predisposition and 19q13 have been obtained. Here, we analysed the role of allelic variation in 19q13 by family based association analysis in 782 MS families collected from Finland. In this dataset, we were not able to detect any statistically significant associations, although several previously suggested markers were included to the analysis. Replication of the previous findings on the basis of linkage disequilibrium between marker allele and disease/risk allele appears notoriously difficult because of limitations such as allelic heterogeneity. Re-sequencing based approaches may be required for elucidating the role of chromosome 19q13 with MS. This thesis has resulted in the identification of a new MS susceptibility locus (IRF5) previously associated with other inflammatory or autoimmune disorders, such as SLE. IRF5 is one of the mediators of interferons biological function. In addition to providing new insight in the possible pathogenetic pathway of the disease, this finding suggests that there might be common mechanisms between different immune-mediated disorders. Furthermore the work presented here has uncovered a novel isoform of ICOS, which may play a role in regulatory mechanisms of ICOS, an important mediator of lymphocyte activation. Further work is required to uncover its functions and possible involvement of the ICOS locus in MS susceptibility.

The impact of communication technologies on life and relationship satisfaction

Previous studies have shown a relationship between the use of communications technology and well-being, particularly mediated through its effect on personal relationships. However, there is some debate over whether this effect is positive or negative. The present study explored this issue further, examining whether the effect varies depending on the type of communications technology, and the nature of the personal relationship. An online survey was conducted with 3,421 participants in three countries (Australia, UK and US). It examined the use of ten communication methods, overall satisfaction with life and satisfaction with four different kinds of relationships (close and extended family, and close and distant friends). Results indicate that richer communication methods, which include non-verbal cues, were positively associated with both overall satisfaction with life and satisfaction with relationships. These methods included face-to-face communication, and phone and video calls. Conversely, more restricted methods, such as text messaging and instant messaging, were negatively associated with both variables. Social networking was negatively associated with overall satisfaction, but not with satisfaction with relationships. The strength of the association between a communications method and satisfaction with a relationship varied depending on the type of relationship, but whether it was positive or negative did not change.

Modelling Cued-Target Recall using Quantum Inspired Models of Target Activation

This article presents and evaluates Quantum Inspired models of Target Activation using Cued-Target Recall Memory Modelling over multiple sources of Free Association data. Two components were evaluated: Whether Quantum Inspired models of Target Activation would provide a better framework than their classical psychological counterparts and how robust these models are across the different sources of Free Association data. In previous work, a formal model of cued-target recall did not exist and as such Target Activation was unable to be assessed directly. Further to that, the data source used was suspected of suffering from temporal and geographical bias. As a consequence, Target Activation was measured against cued-target recall data as an approximation of performance. Since then, a formal model of cued-target recall (PIER3) has been developed [10] with alternative sources of data also becoming available. This allowed us to directly model target activation in cued-target recall with human cued-target recall pairs and use multiply sources of Free Association Data. Featural Characteristics known to be important to Target Activation were measured for each of the data sources to identify any major differences that may explain variations in performance for each of the models. Each of the activation models were used in the PIER3 memory model for each of the data sources and was benchmarked against cued-target recall pairs provided by the University of South Florida (USF). Two methods where used to evaluate performance. The first involved measuring the divergence between the sets of results using the Kullback Leibler (KL) divergence with the second utilizing a previous statistical analysis of the errors [9]. Of the three sources of data, two were sourced from human subjects being the USF Free Association Norms and the University of Leuven (UL) Free Association Networks. The third was sourced from a new method put forward by Galea and Bruza, 2015 in which pseudo Free Association Networks (Corpus Based Association Networks - CANs) are built using co-occurrence statistics on large text corpus. It was found that the Quantum Inspired Models of Target Activation not only outperformed the classical psychological model but was more robust across a variety of data sources.

The effects of the 2004 reduction in the price of alcohol on alcohol-related harm in Finland : A natural experiment based on register data

Changes in alcohol pricing have been documented as inversely associated with changes in consumption and alcohol-related problems. Evidence of the association between price changes and health problems is nevertheless patchy and is based to a large extent on cross-sectional state-level data, or time series of such cross-sectional analyses. Natural experimental studies have been called for. There was a substantial reduction in the price of alcohol in Finland in 2004 due to a reduction in alcohol taxes of one third, on average, and the abolition of duty-free allowances for travellers from the EU. These changes in the Finnish alcohol policy could be considered a natural experiment, which offered a good opportunity to study what happens with regard to alcohol-related problems when prices go down. The present study investigated the effects of this reduction in alcohol prices on (1) alcohol-related and all-cause mortality, and mortality due to cardiovascular diseases, (2) alcohol-related morbidity in terms of hospitalisation, (3) socioeconomic differentials in alcohol-related mortality, and (4) small-area differences in interpersonal violence in the Helsinki Metropolitan area. Differential trends in alcohol-related mortality prior to the price reduction were also analysed. A variety of population-based register data was used in the study. Time-series intervention analysis modelling was applied to monthly aggregations of deaths and hospitalisation for the period 1996-2006. These and other mortality analyses were carried out for men and women aged 15 years and over. Socioeconomic differentials in alcohol-related mortality were assessed on a before/after basis, mortality being followed up in 2001-2003 (before the price reduction) and 2004-2005 (after). Alcohol-related mortality was defined in all the studies on mortality on the basis of information on both underlying and contributory causes of death. Hospitalisation related to alcohol meant that there was a reference to alcohol in the primary diagnosis. Data on interpersonal violence was gathered from 86 administrative small-areas in the Helsinki Metropolitan area and was also assessed on a before/after basis followed up in 2002-2003 and 2004-2005. The statistical methods employed to analyse these data sets included time-series analysis, and Poisson and linear regression. The results of the study indicate that alcohol-related deaths increased substantially among men aged 40-69 years and among women aged 50-69 after the price reduction when trends and seasonal variation were taken into account. The increase was mainly attributable to chronic causes, particularly liver diseases. Mortality due to cardiovascular diseases and all-cause mortality, on the other hand, decreased considerably among the-over-69-year-olds. The increase in alcohol-related mortality in absolute terms among the 30-59-year-olds was largest among the unemployed and early-age pensioners, and those with a low level of education, social class or income. The relative differences in change between the education and social class subgroups were small. The employed and those under the age of 35 did not suffer from increased alcohol-related mortality in the two years following the price reduction. The gap between the age and education groups, which was substantial in the 1980s, thus further broadened. With regard to alcohol-related hospitalisation, there was an increase in both chronic and acute causes among men under the age of 70, and among women in the 50-69-year age group when trends and seasonal variation were taken into account. Alcohol dependence and other alcohol-related mental and behavioural disorders were the largest category in both the total number of chronic hospitalisation and in the increase. There was no increase in the rate of interpersonal violence in the Helsinki Metropolitan area, and even a decrease in domestic violence. There was a significant relationship between the measures of social disadvantage on the area level and interpersonal violence, although the differences in the effects of the price reduction between the different areas were small. The findings of the present study suggest that that a reduction in alcohol prices may lead to a substantial increase in alcohol-related mortality and morbidity. However, large population group differences were observed regarding responsiveness to the price changes. In particular, the less privileged, such as the unemployed, were most sensitive. In contrast, at least in the Finnish context, the younger generations and the employed do not appear to be adversely affected, and those in the older age groups may even benefit from cheaper alcohol in terms of decreased rates of CVD mortality. The results also suggest that reductions in alcohol prices do not necessarily affect interpersonal violence. The population group differences in the effects of the price changes on alcohol-related harm should be acknowledged, and therefore the policy actions should focus on the population subgroups that are primarily responsive to the price reduction.

Work Stress in the Nursing Profession : An Evaluation of Organizational Causal Attribution

The goal of this study was to examine the role of organizational causal attribution in understanding the relation of work stressors (work-role overload, excessive role responsibility, and unpleasant physical environment) and personal resources (social support and cognitive coping) to such organizational-attitudinal outcomes as work engagement, turnover intention, and organizational identification. In some analyses, cognitive coping was also treated as an organizational outcome. Causal attribution was conceptualized in terms of four dimensions: internality-externality, attributing the cause of one’s successes and failures to oneself, as opposed to external factors, stability (thinking that the cause of one’s successes and failures is stable over time), globality (perceiving the cause to be operative on many areas of one’s life), and controllability (believing that one can control the causes of one’s successes and failures). Several hypotheses were derived from Karasek’s (1989) Job Demands–Control (JD-C) model and from the Job Demands–Resources (JD-R) model (Demerouti, Bakker, Nachreiner & Schaufeli, 2001). Based on the JD-C model, a number of moderation effects were predicted, stating that the strength of the association of work stressors with the outcome variables (e.g. turnover intentions) varies as a function of the causal attribution; for example, unpleasant work environment is more strongly associated with turnover intention among those with an external locus of causality than among those with an internal locuse of causality. From the JD-R model, a number of hypotheses on the mediation model were derived. They were based on two processes posited by the model: an energy-draining process in which work stressors along with a mediating effect of causal attribution for failures deplete the nurses’ energy, leading to turnover intention, and a motivational process in which personal resources along with a mediating effect of causal attribution for successes foster the nurses’ engagement in their work, leading to higher organizational identification and to decreased intention to leave the nursing job. For instance, it was expected that the relationship between work stressors and turnover intention could be explained (mediated) by a tendency to attribute one’s work failures to stable causes. The data were collected from among Finnish hospital nurses using e-questionnaires. Overall 934 nurses responded the questionnaires. Work stressors and personal resources were measured by five scales derived from the Occupational Stress Inventory-Revised (Osipow, 1998). Causal attribution was measured using the Occupational Attributional Style Questionnaire (Furnham, 2004). Work engagement was assessed through the Utrecht Work Engagement Scale (Schaufeli & al., 2002), turnover intention by the Van Veldhoven & Meijman (1994) scale, and organizational identification by the Mael & Ashforth (1992) measure. The results provided support for the function of causal attribution in the overall work stress process. Findings related to the moderation model can be divided into three main findings. First, external locus of causality along with job level moderated the relationship between work overload and cognitive coping. Hence, this interaction was evidenced only among nurses in non-supervisory positions. Second, external locus of causality and job level together moderated the relationship between physical environment and turnover intention. An opposite pattern of interaction was found for this interaction: among nurses, externality exacerbated the effect of perceived unpleasantness of the physical environment on turnover intention, whereas among supervisors internality produced the same effect. Third, job level also disclosed a moderation effect for controllability attribution over the relationship between physical environment and cognitive coping. Findings related to the mediation model for the energetic process indicated that the partial model in which work stressors have also a direct effect on turnover intention fitted the data better. In the mediation model for the motivational process, an intermediate mediation effect in which the effects of personal resources on turnover intention went through two mediators (e.g., causal dimensions and organizational identification) fitted the data better. All dimensions of causal attribution appeared to follow a somewhat unique pattern of mediation effect not only for energetic but also for motivational processes. Overall findings on mediation models partly supported the two simultaneous underlying processes proposed by the JD-R model. While in the energetic process the dimension of externality mediated the relationship between stressors and turnover partially, all the dimensions of causal attribution appeared to entail significant mediator effects in the motivational process. The general findings supported the moderation effect and the mediation effect of causal attribution in the work stress process. The study contributes to several research traditions, including the interaction approach, the JD-C, and the JD-R models. However, many potential functions of organizational causal attribution are yet to be evaluated by relevant academic and organizational research. Keywords: organizational causal attribution, optimistic / pessimistic attributional style, work stressors, organisational stress process, stressors in nursing profession, hospital nursing, JD-R model, personal resources, turnover intention, work engagement, organizational identification.

Microcalorimetric indications for ligand binding as a function of the protein for galactoside-specific plant and avian lectins

The process cascade leading to the final accommodation of the carbohydrate ligand in the lectin’s binding site comprises enthalpic and entropic contributions of the binding partners and solvent molecules. With emphasis on lactose, N-acetyllactosamine, and thiodigalactoside as potent inhibitors of binding of galactoside-specific lectins, the question was addressed to what extent these parameters are affected as a function of the protein. The microcalorimetric study of carbohydrate association to the galectin from chicken liver (CG-16) and the agglutinin from Viscum album (VAA) revealed enthalpy–entropy compensation with evident protein type-dependent changes for N-acetyllactosamine. Reduction of the entropic penalty by differential flexibility of loops or side chains and/or solvation properties of the protein will have to be reckoned with to assign a molecular cause to protein type-dependent changes in thermodynamic parameters for lectins sharing the same monosaccharide specificity.

Interrelations of micro-organisms and mulberry II. Phyllosphere microflora and nitrogen fixation in leaf and root surfaces

The mulberry leaves were shown to harbour substantial populations of bacteria, streptomycetes, yeasts, and moulds. Azotobacter and Beijerinckia were observed to contribute to nearly 5 to 10 per cent of the bacterial population. When grown in water culture under sterile conditions, Azotobacter inoculation on the leaf or root surface was found to increase plant growth, dry wt, and nitrogen content of the mulberry. The beneficial effect of Azotobacter was largely influenced by the presence of a carbon source in the plant nutrient solution. The root inoculation in comparison to leaf application was found to confer greater benefits to the growing plant. The presence of carbohydrates and amino acids in the leaf leachates of mulberry was shown. The mutual beneficial nature of the association of the plant and Azotobacter has been brought to light.

Evaluation of solute-solvent interactions from solvent blue-shifts of n → π* transitions of C=O, C=S, NO2 and N=N groups: hydrogen bond energies of various donor-acceptor systems

Effects of non-polar, polar and proton-donating solvents on the n → π* transitions of C=O, C=S, NO2 and N=N groups have been investigated. The shifts of the absorption maxima in non-polar and polar solvents have been related to the electrostatic interactions between solute and solvent molecules, by employing the theory of McRAE. In solvents which can donate protons the solvent shifts are mainly determined by solute-solvent hydrogen bonding. Isobestic points have been found in the n → π* bonds of ethylenetrithio-carbonate in heptane-alcohol and heptane-chloroform solvent systems, indicating the existence of equilibria between the hydrogen bonded and the free species of the solute. Among the different proton-donating solvents studied water produces the largest blue-shifts. The blue-shifts in alcohols decrease in the order 2,2,2-trifluoroethanol, methanol, ethanol, isopropanol and t-butanol, the blue-shift in trifluoroethanol being nearly equal to that in water. This trend is exactly opposite to that for the self-association of alcohols. It is suggested that electron-withdrawing groups not merely decrease the extent of self-association of alcohols, but also increase the ability to donate hydrogen bonds. The approximate hydrogen-bond energies for several donor-acceptor systems have been estimated. In a series of aliphatio ketones and nitro compounds studied, the blue-shifts and consequently the hydrogen bond energies decrease with the decrease in the electron-withdrawing power of the alkyl groups. It is felt that electron-withdrawing groups render the chromophores better proton acceptors, and the alcohols better donors. A linear relationship between n → π* transition frequency and the infrared frequency of ethylenetrithiocarbonate has been found. It is concluded that stabilization of the electronic ground states of solute molecules by electrostatic and/or hydrogen-bond interactions determines the solvent shifts.

Constructing Fair Tourism in Ecuador: The Case of Asoguabo

Tämän pro gradu-tutkielman tarkoitus on tutkia, miten reilun kaupan banaania tuottavan El Guabon pienten banaaninviljelijöiden järjestön Asoguabon reilun turismin projekti on rakennettu. Projektin muotoutumista tutkitaan tässä työssä kahdesta eri näkökulmasta: siitä, miksi ja miten Asoguabo on monipuolistanut viljelystä turismiin, sekä siitä, millainen kuva projektista on rakennettu markkinoinnin kautta ja miten reilun kaupan mainonnasta tuttuja ilmiöitä on hyödynnetty reilun turismin rakentamisessa. Tutkielman teoreettisena taustana on maaseudun muutoksia tarkasteleva uuden ruraliteetin käsite. Turismi on viime vuosikymmenten aikana muuttunut, ja matkailijat etsivät yhä enemmän aitoja ja autenttisia matkailukokemuksia. Samanaikaisesti turismia on tuotteistettu korostamalla sen tiettyjä, kestävän kehityksen mukaisia piirteitä, ja erityisesti kehittyvissä maissa turismia markkinoidaan usein vaihtoehtoisena, yhteisöpohjaisena tai ekoturismina. Reilu turismi on uutena käsitteenä tullut mukaan tähän laajaan kirjoon, ja tämä tutkielma käsitteleekin Asoguabon projektia nimenomaan reilun turismin näkökulmasta. Tämä tutkielma on tapaustutkimus Asoguabon turismiprojektista, ja pohjautuu kuukauden pituiseen kenttätyöhön Ecuadorissa tammikussa 2010 sekä kirjoittajan aiempiin kokemuksiin Asoguabosta. Aineisto koostuu 21 puoli-strukturoidusta laadullisesta haastattelusta kuudentoista informantin kanssa, joista suurin osa oli hyvin läheisesti tekemisissä projektin kanssa. Tämän lisäksi aineistonkeruussa on käytetty havainnointia sekä projektin markkinointimateriaalien sisällönanalyysia. Tutkielma osoittaa reilun turismin projektin sisältävän monia haasteita ennen kuin se voi saavuttaa tavoitteensa tuottaa lisätuloja Asoguabon toimintaan. Tutkimushetkellä projekti hyödytti suoraan pääasiassa muutamia järjestön viljelijöitä, lähinnä niitä, jotka toimivat projektissa oppaina. Nämä oppaat hyötyvät projektista saamalla pieniä lisätuloja, kasvattamalla sosiaalista pääomaansa, sekä saamalla mahdollisuuden oppia muun muassa osallistumalla kursseille. Tutkimuksen keskeiset tulokset osoittavat myös, kuinka vuorovaikutus-ongelmat projektin eri toimijoiden välillä vaikeuttavat tiedonkulkua ja täten reilun turismin toimintaa. Nämä ongelmat myös lisäävät epätietoisuutta Asoguabon muiden viljelijöiden parissa. Lisäksi tutkimus osoittaa, kuinka reilun turismin projektin mainonnassa käytetään osittain samoja keinoja kuin reilun kaupan tuotteiden mainonnassa, joskin tuottajia on kuvattu mainosmateriaaleissa yllättävän vähän ja pääosassa ovat usein eurooppalaiset turistit.

Folding a Polymer via Two-Point Interaction with an External Folding Agent: Use of H-Bonding and Charge-Transfer Interactions

A polymer containing electron-rich aromatic donors (1,5-dialkoxynaphthalene (DAN)) was coerced into a folded state by an external folding agent that contained an electron-deficient aromatic acceptor (pyromellitic diimide (PM)) unit. The donor-containing polymer was designed to carry a tertiary amine moiety in the linking segment, which served as an H-bonding site for reinforcing the interaction with the acceptor containing folding agent that also bore a carboxylic acid group. The H-bonding interaction of the carboxylic acid and the tertiary amine brings the PDI unit between two adjacent DAN units along the polymer backbone to induce charge-transfer (C-T) interactions, and this in turn causes the polymer chain to form a pleated structure. Evidence for the formation of such a pleated structure was obtained from NMR titration studies and also by monitoring the C-T band in their UV-visible spectra. By varying the length of the segment that links the PDI acceptor to the carboxylic acid group, we showed that the most effective folding agent was the one that had a single carbon spacer, as evident from the highest value of the association constant. Control experiments with propionic acid clearly demonstrated the importance of the additional C-T interactions for venerating the folded structures. Further, solution viscosity measurements in the presence of varying amounts of the folding agent revealed a gradual stiffening of the chain in the case of the PDI carrying carboxylic acid, whereas no such affect was seen in the case of simple propionic acid. These observations were supported by D FT calculations of the interactions of a dimeric model of the polymer with the various folding agents; here too the stability of the complex was seen to be highest in the case of the single carbon spacer.

Online association policies in IEEE 802.11 WLANs

In this paper, we study the performance of client-Access Point (AP) association policies in IEEE 802.11 based WLANs. In many scenarios, clients have a choice of APs with whom they can associate. We are interested in finding association policies which lead to optimal system performance. More specifically, we study the stability of different association policies as a function of the spatial distribution of arriving clients. We find for each policy the range of client arrival rates for which the system is stable. For small networks, we use Lyapunov function methods to formally establish the stability or instability of certain policies in specific scenarios. The RAT heuristic policy introduced in our prior work is shown to have very good stability properties when compared to several other natural policies. We also validate our analytical results by detailed simulation employing the IEEE 802.11 MAC.

Characterization of human symptomatic rotavirus isolates MP409 and MP480 having ‘long’ RNA electropherotype and subgroup I specificity, highly related to the P6[1],G8 type bovine rotavirus A5, from Mysore, India

In an epidemiological study of symptomatic human rotaviruses in Mysore, India during 1993 and 1994, isolates MP409 and MP480 were isolated from two children suffering from severe, acute dehydrating diarrhea. Both isolates exhibited 'long' RNA pattern and subgroup I specificity suggesting the likelihood of their animal origin. Both isolates did not react with monoclonal antibodies (MAbs) specific for serotypes G1 to G6 as well as CIO. To determine the genetic origin of these isolates, complete nucleotide sequences of genes encoding the outer capsid proteins VP4 and VP7, nonstructural proteins NSP1 and NSP3 and viral enterotoxin protein NSP4 from MP409 and partial sequences of genes from MP480 were determined. Comparison of the 5' and 3' terminal sequences of 250 nucleotides revealed complete identity of the gene sequences in both strains suggesting that MP409 and MP480 are two different isolates of a single strain. Comparison of the nucleotide and deduced amino acid sequences of VP4, VP7, NSP1 and NSP3 of MP409 with published sequences of strains belonging to different serotypes revealed that both outer capsid proteins VP4 and VP7 and NSP1 are highly related to the respective proteins from the P6[1], G8 type bovine rotavirus A5 isolated from a calf with diarrhoea in Thailand and that the NSP3 is highly homologous to that of bovine rotaviruses. The NSP 1 protein showed greatest sequence identity with NSP4s belonging to the KUN genetic group to which NSP4s from human G2 type strains and bovine rotaviruses belong. MP409 and MP480 likely signify interspecies transmission of P6[1], G8 type strains from cattle to humans and represent the first P6[1] type rotaviruses isolated in humans. These and our previous studies on the asymptomatic neonatal strain I321 are of evolutionary and epidemiological significance in the context of close association of majority of the Indian population with cattle.

Constructing Fair Tourism in Ecuador: The Case of Asoguabo

Tämän pro gradu-tutkielman tarkoitus on tutkia, miten reilun kaupan banaania tuottavan El Guabon pienten banaaninviljelijöiden järjestön Asoguabon reilun turismin projekti on rakennettu. Projektin muotoutumista tutkitaan tässä työssä kahdesta eri näkökulmasta: siitä, miksi ja miten Asoguabo on monipuolistanut viljelystä turismiin, sekä siitä, millainen kuva projektista on rakennettu markkinoinnin kautta ja miten reilun kaupan mainonnasta tuttuja ilmiöitä on hyödynnetty reilun turismin rakentamisessa. Tutkielman teoreettisena taustana on maaseudun muutoksia tarkasteleva uuden ruraliteetin käsite. Turismi on viime vuosikymmenten aikana muuttunut, ja matkailijat etsivät yhä enemmän aitoja ja autenttisia matkailukokemuksia. Samanaikaisesti turismia on tuotteistettu korostamalla sen tiettyjä, kestävän kehityksen mukaisia piirteitä, ja erityisesti kehittyvissä maissa turismia markkinoidaan usein vaihtoehtoisena, yhteisöpohjaisena tai ekoturismina. Reilu turismi on uutena käsitteenä tullut mukaan tähän laajaan kirjoon, ja tämä tutkielma käsitteleekin Asoguabon projektia nimenomaan reilun turismin näkökulmasta. Tämä tutkielma on tapaustutkimus Asoguabon turismiprojektista, ja pohjautuu kuukauden pituiseen kenttätyöhön Ecuadorissa tammikussa 2010 sekä kirjoittajan aiempiin kokemuksiin Asoguabosta. Aineisto koostuu 21 puoli-strukturoidusta laadullisesta haastattelusta kuudentoista informantin kanssa, joista suurin osa oli hyvin läheisesti tekemisissä projektin kanssa. Tämän lisäksi aineistonkeruussa on käytetty havainnointia sekä projektin markkinointimateriaalien sisällönanalyysia. Tutkielma osoittaa reilun turismin projektin sisältävän monia haasteita ennen kuin se voi saavuttaa tavoitteensa tuottaa lisätuloja Asoguabon toimintaan. Tutkimushetkellä projekti hyödytti suoraan pääasiassa muutamia järjestön viljelijöitä, lähinnä niitä, jotka toimivat projektissa oppaina. Nämä oppaat hyötyvät projektista saamalla pieniä lisätuloja, kasvattamalla sosiaalista pääomaansa, sekä saamalla mahdollisuuden oppia muun muassa osallistumalla kursseille. Tutkimuksen keskeiset tulokset osoittavat myös, kuinka vuorovaikutus-ongelmat projektin eri toimijoiden välillä vaikeuttavat tiedonkulkua ja täten reilun turismin toimintaa. Nämä ongelmat myös lisäävät epätietoisuutta Asoguabon muiden viljelijöiden parissa. Lisäksi tutkimus osoittaa, kuinka reilun turismin projektin mainonnassa käytetään osittain samoja keinoja kuin reilun kaupan tuotteiden mainonnassa, joskin tuottajia on kuvattu mainosmateriaaleissa yllättävän vähän ja pääosassa ovat usein eurooppalaiset turistit.

Studies on Causes of Multiple Sclerosis : From Genes to Transcriptome

Multiple sclerosis (MS) is the most common cause of neurological disability in young adults, affecting more than two million people worldwide. It manifests as a chronic inflammation in the central nervous system (CNS) and causes demyelination and neurodegeneration. Depending on the location of the demyelinated plaques and axonal loss, a variety of symptoms can be observed including deficits in vision, coordination, balance and movement. With a typical age of onset at 20-40 years, the social and economic impacts of MS on lives of the patients and their families are considerable. Unfortunately the current treatments are relatively inefficient and the development of more effective treatments has been impeded by our limited understanding of the causes and pathogenesis of MS. Risk of MS is higher in biological relatives of MS patients than in the general population. Twin and adoption studies have shown that familial clustering of MS is explained by shared genetic factors rather than by shared familial environment. While the involvement of the human leukocyte antigen (HLA) genes was first discovered four decades ago, additional genetic risk factors have only recently been identified through genome-wide association studies (GWAS). Current evidence suggests that MS is a highly polygenic disease with perhaps hundreds of common variants with relatively modest effects contributing to susceptibility. Despite extensive research, the majority of these risk factors still remain to be identified. In this thesis the aim was to identify novel genes and pathways involved in MS. Using genome-wide microarray technology, gene expression levels in peripheral blood mononuclear cells (PBMC) from 12 MS patients and 15 controls were profiled and more than 600 genes with altered expression in MS were identified. Three of five selected findings, DEFA1A3, LILRA4 and TNFRSF25, were successfully replicated in an independent sample. Increased expression of DEFA1A3 in MS is a particularly interesting observation, because its elevated levels have previously been reported also in several other autoimmune diseases. A systematic review of seven microarray studies was then performed leading to identification of 229 genes, in which either decreased or increased expression in MS had been reported in at least two studies. In general there was relatively little overlap across the experiments: 11 of the 229 genes had been reported in three studies and only HSPA1A in four studies. Nevertheless, these 229 genes were associated with several immunological pathways including interleukin pathways related to type 2 and type 17 helper T cells and regulatory T cells. However, whether these pathways are involved in causing MS or related to secondary processes activated after disease onset remains to be investigated. The 229 genes were also compared with loci identified in published MS GWASs. Single nucleotide polymorphisms (SNP) in 17 of the 229 loci had been reported to be associated with MS with P-value less than 0.0001 including variants in CXCR4 and SAPS2, which were the only loci where evidence for correlation between the associated variant and gene expression was found. The CXCR4 variant was further tested for association with MS in a large case-control sample and the previously reported suggestive association was replicated (P-value is 0.0004). Finally, common genetic variants in candidate genes, which had been selected on the basis of showing association with other autoimmune diseases (MYO9B) or showing differential expression in MS in our study (DEFA1A3, LILRA4 and TNFRSF25), were tested for association with MS, but no evidence of association was found. In conclusion, through a systematic review of genome-wide expression studies in MS we have identified several promising candidate genes and pathways for future studies. In addition, we have replicated a previously suggested association of a SNP variant upstream of CXCR4 with MS. Keywords: autoimmune disease, common variant, CXCR4, DEFA1A3, HSPA1A,gene expression, genetic association, GWAS, MS, multiple sclerosis, systematic review