Analysis of Puumala hantavirus in a bank vole population in northern Finland: evidence for co-circulation of two genetic lineages and frequent reassortment between strains

"In this study, for the first time, two distinct genetic lineages of Puumala virus (PUUV) were found within a small sampling area and within a single host genetic lineage (Ural mtDNA) at Pallasjarvi, northern Finland. Lung tissue samples of 171 bank voles (Myodes glareolus) trapped in September 1998 were screened for the presence of PUUV nucleocapsid antigen and 25 were found to be positive. Partial sequences of the PUUV small (S), medium (M) and large (L) genome segments were recovered from these samples using RT-PCR. Phylogenetic analysis revealed two genetic groups of PUUV sequences that belonged to the Finnish and north Scandinavian lineages. This presented a unique opportunity to study inter-lineage reassortment in PUUV; indeed, 32% of the studied bank voles appeared to carry reassortant virus genomes. Thus, the frequency of inter-lineage reassortment in PUUV was comparable to that of intra-lineage reassortment observed previously (Razzauti, M., Plyusnina, A., Henttonen, H. & Plyusnin, A. (2008). J Gen Virol 89, 1649-1660). Of six possible reassortant S/M/L combinations, only two were found at Pallasjarvi and, notably, in all reassortants, both S and L segments originated from the same genetic lineage, suggesting a non-random pattern for the reassortment. These findings are discussed in connection to PUUV evolution in Fermoscandia."

Plexin B2 in mouse and zebrafish development

Plexins (plxn) are receptors of semaphorins (sema), which were originally characterized as axon guidance cues. Semaphorin-plexin signalling has now been implicated in many other developmental and pathological processes. In this thesis, my first aim was to study the expression of plexins during mouse development. My second aim was to study the function of Plexin B2 in the development of the kidney. Thirdly, my objective was to elucidate the evolutionary conservation of Plexin B2 by investigating its sequence, expression and function in developing zebrafish. I show by in situ hybridisation that plexins are widely expressed also in the non-neuronal tissues during mouse development. Plxnb1 and Plxnb2, for example, are expressed also in the ureteric epithelium, developing glomeruli and undifferentiated metanephric mesenchyme of the developing kidney. Plexin B2-deficient (Plxnb2-/-) mice die before birth and have severe defects in the nervous system. I demonstrate that they develop morphologically normal but hypoplastic kidneys. The ureteric epithelium of Plxnb2-/- kidneys has fewer branches and a lower rate of proliferating cells. 10% of the embryos show unilateral double ureters and kidneys. The defect in the branching is intrinsic to the epithelium as the isolated ureteric epithelium grown in vitro fails to respond to Glial-cell-line-derived neurotrophic factor (Gdnf). We prove by co-immunoprecipitation that Plexin B2 interacts with the Gdnf-receptor Ret. Sema4C, the Plexin B2 ligand, increases branching of the ureteric epithelium in controls but not in Plxnb2-/- kidney explants. These results suggest that Sema4C-Plexin B2 signalling modulates ureteric branching in a positive manner, possibly through directly regulating the activation of Ret. I cloned the zebrafish orthologs of Plexin B2, Plexin B2a and B2b. The corresponding proteins contain the conserved domains the B-subfamily plexins. Especially the expression pattern of plxnb2b recapitulates many aspects of the expression pattern of Plxnb2 in mouse. Plxnb2a and plxnb2b are expressed, for example, in the pectoral fins and at the midbrain-hindbrain region during zebrafish development. The nearly complete knockdown of Plexin B2a alone or together with the 45% knockdown of Plexin B2b did not interfere with the normal development of the zebrafish. In conclusion, my thesis reveals that plexins are broadly expressed during mouse embryogenesis. It also shows that Sema4C-Plexin B2 signalling modulates the branching of the ureteric epithelium during kidney development, perhaps through a direct interaction with Ret. Finally, I show that the sequence and expression of Plexin B2a and B2b are conserved in zebrafish. Their knockdown does not, however, result in the exencephaly phenotype of Plxnb2-/- mice.

Nature-based entrepreneurship in private forests – The preconditions for the sustainable co-operation between private forest owners and entrepreneurs

Nature-based tourism is one of the fastest growing tourism sectors at the moment. It is also the form of tourism that often benefits the economy of rural areas. In addition to state owned forests, nature-based tourism is in many countries situated in private forests, which are not owned by entrepreneurs themselves. Therefore, the ownership issues and property rights form central challenges for the business activities. The maintenance of good relationships between private forest owners and entrepreneurs, as well as combining their interests, becomes vital. These relationships are typically exceptionally asymmetrical, granting the forest owner unilateral rights regulating the business activities in their forests. Despite this, the co-operation is typically very informal and the existing economic compensation models do not necessarily cover all the forest owners’ costs. The ownership issues bring their own characteristics to the relationship. Therefore, we argue that different aspects of ownership, especially psychological ones, have to be more critically examined and taken into consideration in order to build truly successful relations between these parties. This is crucial for sustaining the business activities. The core of psychological ownership is the sense of possession. Psychological ownership can be defined as a state, in which individuals perceive the target of ownership, the object or idea, as “theirs”. The concept of psychological ownership has so far been mainly used in the context of professional organizations. In this research, it has been used to explain the relationships between private forest owners and nature-based entrepreneurs. The aim of this study is to provide new information concerning the effect of psychological ownership on the collaboration and to highlight the good practices. To address the complexity of the phenomenon, qualitative case study methods were adopted to understand the role of ownership at the level of subjective experience. The empirical data was based on 27 in-depth interviews with private forest owners and nature-based tourism entrepreneurs. The data was analysed by using the methods of qualitative analysis to construct different typologies to describe the essence of successful collaboration. As a result of the study, the special characteristics and the practical level expressions of the psychological ownership in the privately owned forest context were analysed. Four different strategies to perceive these ownership characteristics in co-operation relationships were found. By taking the psychological ownership into consideration via these strategies, the nature-based entrepreneurs aim to balance the co-operation relationship and minimise the risks in long term activities based on privately owned forests.

Ultrasonic degradation of poly (styrene-co-alkyl methacrylate) copolymers

The ultrasonic degradation of poly (styrene-co-methyl methacrylate) (SMMA), poly (styrene-co-ethyl methacrylate) (SEMA) and poly (styrene-co-butyl methacrylate) (SBMA) copolymers of different compositions was studied. The copolymers were synthesized and NMR spectroscopy was used to determine the composition, and the glass transition temperatures were determined by DSC. The reactivity ratios were determined by the Kelen-Tudos method and it indicated that the copolymers were random. The effect of solvent, temperature and copolymer composition on the ultrasonic degradation rate of these copolymers was investigated. A model based on continuous distribution kinetics was employed to study the degradation kinetics. The degradation rate coefficients of the copolymers decreased with an increase in the styrene content in the copolymer. At any particular copolymer composition the rate of degradation follows the order: SBMA >SEMA > SMMA. Thermogravimetric analysis (TGA) of the copolymers was carried in order to assess their thermal stability. The same order of degradation was observed for the thermal degradation of the copolymers as that observed for ultrasonic degradation. (C) 2010 Elsevier B.V. All rights reserved.

Depression and Cognition in Type 2 Diabetes from a Life Course Perspective

Background: Type 2 diabetes is linked to several complications which add to both physical and mental distress. Depression is a common co-morbidity of diabetes which can occur both as a cause and a consequence of type 2 diabetes. Depression has been shown to correlate with glucose regulation and treating depression might prove beneficial for glucose regulation as well as for mental well being. Another complication which might affect diabetes management is cognitive decline. Several risk factors and complications of diabetes might modify the risk for developing cognitive impairment, which is increased 1.5 times among subjects with type 2 diabetes. Type 2 diabetes, depression and impaired cognitive performance have all been linked to low birth weight. This thesis aimed to explore the effects and interactions of birth weight, depression and cognitive ability in relation to type 2 diabetes from a life course perspective. Subjects and methods: Studies I, II and V were part of the Helsinki Birth Cohort Study. 2003 subjects participated in an extensive clinical examination at an average age of 61 years. A standard glucose tolerance test (OGTT) was performed and depressive symptoms were assessed using the Beck Depression Inventory (BDI). In addition data was obtained from child welfare clinics and national registers. A subset of the cohort (n=1247) also performed a test on cognitive performance (CogState ®) at the average age of 64. Studies III and IV were randomised clinical trials where mildly depressed diabetic subjects were treated with paroxetine or placebo and the effect on metabolic parameters and quality of life was assessed. The first trial included 14 women and lasted 10 weeks, while the second trial included 43 subjects, both men and women, and lasted 6 months. Results: Type 2 diabetes was positively associated with the occurrence of depressive symptoms. Among diabetic subjects 23.6% had depressive symptoms, compared to 16.7% of subjects with normal glucose tolerance (OR = 1.77, p<0.001). Formal mediation analysis revealed that cardiovascular disease (CVD) is likely to act as a mediator in the association. Furthermore, low birth weight was found to modify the association between type 2 diabetes, CVD and depression. The association between BDI score and having type 2 diabetes or CVD was twice as strong in the subgroup with low birth weight (≤ 2500g) compared with the group with birth weight > 2500g (p for interaction 0.058). In the six months long randomised clinical trial (study IV) paroxetine had a transient beneficial effect on glycosylated haemoglobin A1c (GHbA1c) and quality of life when compared to placebo after three months of treatment. In study V we found that subjects with known diabetes had a consistently poorer level of cognitive performance than subjects with normal glucose tolerance in most of the tested cognitive domains. This effect was further amplified among those born with a small birth weight (p for interaction 0.002). Conclusions: Type 2 diabetes is associated with a higher occurrence of depressive symptoms compared to subjects with normal glucose tolerance. This association is especially strong among subjects with CVD and those born with a low birth weight. Treating depressed diabetic subjects with paroxetine has no long term effect on glucose regulation. Physicians should be aware of depression as an important co-morbidity of type 2 diabetes. Both depression and the cognitive decline often seen among diabetic subjects are increased if the subject is born with a low birth weight. Physicians should recognise low birth weight as an additional risk factor and modifier of diabetic complications.

Degradation Kinetics of Poly(HDDA-co-MMA)

1,6-hexanediol diacrylate (HDDA) and methyl methacrylate (MMA) were copolymerized in different weight ratios using UV light induced photo-polymerization to give poly(HDDA-co-MMA). Differential scanning calorimetry shows that copolymer was formed. The thermogravimetric and differential scanning calorimetric studies with different heating rates were carried out on these copolymers to understand the nature of degradation and to determine its kinetics. Different kinetic models were adopted to evaluate various parameters like the activation energy, the order, and the frequency factor. These analyses are important to study the binder removal from 3D-shaped ceramic objects made by techniques like Solid free form fabrication. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 117: 2444-2453, 2010.

Cascade PSI-BLAST web server: a remote homology search tool for relating protein domains

Owing to high evolutionary divergence, it is not always possible to identify distantly related protein domains by sequence search techniques. Intermediate sequences possess sequence features of more than one protein and facilitate detection of remotely related proteins. We have demonstrated recently the employment of Cascade PSI-BLAST where we perform PSI-BLAST for many 'generations', initiating searches from new homologues as well. Such a rigorous propagation through generations of PSI-BLAST employs effectively the role of intermediates in detecting distant similarities between proteins. This approach has been tested on a large number of folds and its performance in detecting superfamily level relationships is similar to 35% better than simple PSI-BLAST searches. We present a web server for this search method that permits users to perform Cascade PSI-BLAST searches against the Pfam, SCOP and SwissProt databases. The URL for this server is http://crick.mbu.iisc.ernet.in/similar to CASCADE/CascadeBlast.html.

Theoretical foundations for multiple rendezvous of glowworm-inspired mobile agents with variable local-decision domains

We present the theoretical foundations for the multiple rendezvous problem involving design of local control strategies that enable groups of visibility-limited mobile agents to split into subgroups, exhibit simultaneous taxis behavior towards, and eventually rendezvous at, multiple unknown locations of interest. The theoretical results are proved under certain restricted set of assumptions. The algorithm used to solve the above problem is based on a glowworm swarm optimization (GSO) technique, developed earlier, that finds multiple optima of multimodal objective functions. The significant difference between our work and most earlier approaches to agreement problems is the use of a virtual local-decision domain by the agents in order to compute their movements. The range of the virtual domain is adaptive in nature and is bounded above by the maximum sensor/visibility range of the agent. We introduce a new decision domain update rule that enhances the rate of convergence by a factor of approximately two. We use some illustrative simulations to support the algorithmic correctness and theoretical findings of the paper.

Towards Service Logic: The Unique Contribution of Value Co-Creation

The underpinning logic of value co-creation in service logic is analysed. It is observed that three of the ten foundational premises of the so-called service-dominant logic are problematic and do not support an understanding of value-co-creation and creation that is meaningful for theoretical development and decision making in business and marketing practice. Without a thorough understanding of the interaction concept, the locus and nature of value co-creation cannot be identified. Based on the analysis in the present article it is observed that a unique contribution of a service perspective on business (service logic) is not that customers always are co-creators of value, but that under certain circumstances the service provider gets opportunities to co-create value together with its customers. Finally, the three problematic premises are reformulated accordingly.

Effect of √-irradiation on the structure and dynamics of domains in triglycine selenate

A comparative study of the switching properties of pure and √-irradiated TGSe crystals has been carried out to see the effect of irradiation on the structure and dynamics of domains. The switching behaviour of √-irradiated TGSe has been found to be qualitatively similar to that of unirradiated crystal and this has been interpreted in terms of structural inhibition caused by the formation of radiolysis products as well as the difference between the domain structures of the unirradiated and irradiated samples. Confirmation of this has been obtained by studying the domain patterns using the etch method.

Evidence of ferromagnetic domains in the La0.67Ca0.33Mn0.9Fe0.1O3 perovskite

The nature of the low-temperature magnetic state of polycrystalline La0.67Ca0.33Mn0.9Fe0.1O3 has been studied by magnetization, neutron diffraction, and neutron depolarization measurements. Neutron depolarization measurements indicate the existence of ferromagnetic domains with low net magnetic moments below 108 K. The substitution of Mn3+ by Fe3+ reduces the number of available hopping sites for the Mn e(g) (up) electron and suppresses the double exchange, resulting in the reduction of ferromagnetic exchange. The competition between the ferromagnetic double-exchange interactions and the coexisting antiferromagnetic superexchange interactions and its randomness due to random substitutions of Mn3+ with Fe3+ drive the system into a randomly canted ferromagnetic state at low temperatures.

Characterization of poly(ADP-ribosyl)ated domains of rat pachytene chromatin

Poly(ADP-ribosyl)ation of nuclear proteins was several-fold higher in the pachytene spermatocytes than in the premeiotic germ cells of the rat. Among the histones of the pachytene nucleus, histone subtypes H2A, H1 and H3 were poly(ADP-ribosyl)ated. Based on the immunoaffinity fractionation procedure of Malik, Miwa, Sugimara & Smulson [(1983) Proc. Natl. Acad. Sci. U.S.A. 80, 2554-2558] we have fractionated DNAase-II-solubilized chromatin into poly(ADP-ribosyl)ated chromatin (PAC) and non-poly(ADP-ribosyl)ated chromatin (non-PAC) domains on an anti-[poly(ADP-ribose)] IgG affinity matrix. Approx. 2.5% of the pachytene chromatin represented the PAC domains. A significant amount of [alpha-32P]dATP-labelled pachytene chromatin (labelled in vitro) was bound to the affinity matrix. The DNA of pachytene PAC domains had internal strand breaks, significant length of gaps and ligatable ends, namely 5'-phosphoryl and 3'-hydroxyl termini. On the other hand, the PAC domains from 18 h regenerating liver had very few gaps, if any. The presence of gaps in the pachytene PAC DNA was also evident from thermal denaturation studies. Although many of the polypeptides were common to the PAC domains of both pachytene and regenerating liver, the DNA sequences associated with these domains were quite different. A 20 kDa protein and the testis-specific histone H1t were selectively enriched in the pachytene PAC domains. The pachytene PAC domains also contained approx. 10% of the messenger coding sequences present in the DNAase-II-solubilized chromatin. The pachytene PAC domains, therefore, may represent highly enriched DNA-repair domains of the pachytene nucleus.