| 1. |
- Alizadehheidari, Mohammadreza, 1987, et al.
(författare)
-
Nanoconfined Circular and Linear DNA: Equilibrium Conformations and Unfolding Kinetics
- 2015
-
Ingår i: Macromolecules. - : American Chemical Society (ACS). - 0024-9297 .- 1520-5835. ; 48:3, s. 871-878
-
Tidskriftsartikel (refereegranskat)abstract
- Studies of circular DNA confined to nanofluidic channels are relevant both from a fundamental polymer-physics perspective and due to the importance of circular DNA molecules in vivo. We here observe the unfolding of confined DNA from the circular to linear configuration as a light-induced double-strand break occurs, characterize the dynamics, and compare the equilibrium conformational statistics of linear and circular configurations. This is important because it allows us to determine to what extent existing statistical theories describe the extension of confined circular DNA. We find that the ratio of the extensions of confined linear and circular DNA configurations increases as the buffer concentration decreases. The experimental results fall between theoretical predictions for the extended de Gennes regime at weaker confinement and the Odijk regime at stronger confinement. We show that it is possible to directly distinguish between circular and linear DNA molecules by measuring the emission intensity from the DNA. Finally, we determine the rate of unfolding and show that this rate is larger for more confined DNA, possibly reflecting the corresponding larger difference in entropy between the circular and linear configurations.
|
|
| 2. |
- Alizadehheidari, Mohammadreza, 1987, et al.
(författare)
-
Unfolding of nanoconfined circular DNA
- 2015
-
Ingår i: BIOPHYSICAL JOURNAL. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 108:2 Supplement 1, s. 231A-231A
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 3. |
- Asp, Michaela, et al.
(författare)
-
Spatial detection of fetal marker genes expressed at low level in adult human heart tissue
- 2017
-
Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Heart failure is a major health problem linked to poor quality of life and high mortality rates. Hence, novel biomarkers, such as fetal marker genes with low expression levels, could potentially differentiate disease states in order to improve therapy. In many studies on heart failure, cardiac biopsies have been analyzed as uniform pieces of tissue with bulk techniques, but this homogenization approach can mask medically relevant phenotypes occurring only in isolated parts of the tissue. This study examines such spatial variations within and between regions of cardiac biopsies. In contrast to standard RNA sequencing, this approach provides a spatially resolved transcriptome- and tissue-wide perspective of the adult human heart, and enables detection of fetal marker genes expressed by minor subpopulations of cells within the tissue. Analysis of patients with heart failure, with preserved ejection fraction, demonstrated spatially divergent expression of fetal genes in cardiac biopsies.
|
|
| 4. |
- Fornander, Louise, 1984, et al.
(författare)
-
Visualizing the Nonhomogeneous Structure of RAD51 Filaments Using Nanofluidic Channels
- 2016
-
Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 32:33, s. 8403-8412
-
Tidskriftsartikel (refereegranskat)abstract
- RAD51 is the key component of the homologous recombination pathway in eukaryotic cells and performs its task by forming filaments on DNA. In this study we investigate the physical properties of RAD51 filaments formed on DNA using nanofluidic channels and fluorescence microscopy. Contrary to the bacterial ortholog RecA, RAD51 forms inhomogeneous filaments on long DNA in vitro, consisting of several protein patches. We demonstrate that a permanent "kink" in the filament is formed where two patches meet if the stretch of naked DNA between the patches is short. The kinks are readily seen in the present microscopy approach but would be hard to identify using conventional single DNA molecule techniques where the DNA is more stretched. We also demonstrate that protein patches separated by longer stretches of bare DNA roll up on each other and this is visualized as transiently overlapping filaments. RAD51 filaments can be formed at several different conditions, varying the cation (Mg2+ or Ca2+), the DNA substrate (single-stranded or double-stranded), and the RAD51 concentration during filament nucleation, and we compare the properties of the different filaments formed. The results provide important information regarding the physical properties of RAD51 filaments but also demonstrate that nanofluidic channels are perfectly suited to study protein-DNA complexes.
|
|
| 5. |
- Gebert Persson, Sabine, et al.
(författare)
-
Public and private networks in tourism – : barriers to network identity construction and commitmen
- 2019
-
Konferensbidrag (refereegranskat)abstract
- IntroductionDestinations all over the world encompass a broad range of stakeholders who all aspire to increase the tourism industry to accomplish regional development. At these destinations, there are many different stakeholders, who have mutual interest in a specific region, and there are different attempts to promote cooperation for joint efforts to attract visitors. Moreover, there is an increasing drive for municipalities to influence the tourism business as part of their regional development (Tillväxtverket, 2017).However, the aforementioned development of destinations has proven to involve competing interests between local, national and international stakeholders. Although private enterprises, the municipalities and on-governmental organizations, and residents have a common, or at least partly overlapping, interest in the development of a specific destination, competing interests will occasionally occur (c.f. Elbe et al., 2018). For instance, private businesses, like small local entrepreneurs, could be in direct competition with national or international corporations, despite the fact that they may have much to gain from joint marketing efforts (c.f. investment in a common brand). Similarly, public1organizations have a shared interest in the development of the tourism industry to increase tax revenues and job creation. However, municipalities have a greater responsibility for communities and its residents.As in many other sectors, public and private interactions are common within the tourism industry due to an overall reduction in public sector funding (Valente et al., 2015). Relationships between public and private actors are also set up to conjointly pool resources, share risks in the process of building, maintaining and developing public services (Keränen, 2017). Interactions between public-private actors have been acknowledged as important since these relationships enable firms to influence decisions within areas such as the public sector, rules and actions that can affect how the firm is perceived as legitimate or not (Hadjikhani, Lee, & Ghauri, 2008; Jansson, Saqib, & Sharma, 1995) but also as ways to develop new and existing resources. However, research has shown that uncertainty tends to be rather high in these relationships and the roles that the actors play are consequently dynamic and unclear. This in turn also affects how the actors perceive the cooperation between public and private actors (Keränen, 2017) and their commitment to these types of networks (Elbe et al., 2018). The sought after commitment would be enhanced if a mutual identity could be constituted; still the identity is established from how the stakeholders perceive their roles and relations to each other. So how could the identity of public actors merge with the identity of private actors to establish a mutual and common identity?Despite the apparent advantage to create a network to coordinate mutual, or at least overlapping, interests, it has proven to entail a number of difficult issues of which some will be addressed below. The combination of private and public stakeholders in one organization may have implications for its role and commitments (c.f. Elbe et al. 2009; 2018) i.e. it could influence the perceived identity construction of its constituents. The combination of public and private interests in the same organization could create tension; one perspective could have precedence over the other. For instance, if a publicly funded organization considers it to be its mission to only enhance businesses, there are stakeholder who could be overlooked, such as permanent residents, community services, and other lines of industry. Although the established networks are intended to work towards common goals, there may still be implicit and ambiguous goals, roles and identity formations.2The organizing of public and private interests in order to transform a place and its characteristics into a destination has proven to be a complex process. More research is needed in order to bring further clarity into factors affecting these types of relationships in terms of activities and resources (de Araujo and Bramwell, 2002) as well as how this affects the actors. Although there is a growing scholarly interest in public-private relationships, additional knowledge is needed on how the processes of these types of cooperation evolve (de Araujo and Bramwell, 2002). This is especially so in the context of created networks where the network is constructed rather than emerging and where the aim is to foster and manage activities, resource interactions and actor bonds.This paper sets out to further the understanding of interaction processes where public and private actors attempt to find ways to cooperate on a common issue. This is done by analyzing how the identity of a created network, consisting of public and private actors, develops over time. This paper focuses on explaining how a created network develops over time and why it evolves in the way it does. The purpose is to identify possible barriers to identity construction in a created network consisting of public and private actors. This is done through a case taking its point of departure in the decision of a major infrastructural investment in a destination in Sweden: the building of a new cruise quay on Gotland.Created public-private cooperation – previous research.Interactions between public-private actors have been acknowledged as important since these relationships enable firms to influence decisions within different areas such as the public sector, rules and actions (Keränen, 2017; Elbe et al., 2018) but also as ways to develop new and existing resources. These co-operations are encouraged by governments in many countries as interactions can facilitate the discussions and decisions related to how different activities evolve and are coordinated as well as how public resources are distributed. Moral responsibility and a way to recover citizens’ trust for politicians’ abilities to deliver on electoral pledge when resources are scarce has been emphasized as a reason for cooperation between public and private actors (Velotti, Botti & Vesci, 2012). In a tourism context, private-public cooperation can also increase the competitive advantage of destinations (Kotler et al., 1993).Over the last decades, a growing number of designated organizations for the coordination of tourist actors have been established using the concept of: Destination Management Organizations, DMO (c.f. Elbe et al. 2009). According to UNWTO (2018), the DMO’s3role should, “be to lead and coordinate activities under a coherent strategy in pursuit of this common goal.” The argument in research, and in practice, has been that these destination organizations can manage marketing and coordinate different actors from varying sectors in the society. Through this, it is assumed that the destination through facilitation of interactions among local actors and creation of networks can stimulate economic growth (Elbe et al., 2018). Hence, specific organizations are politically created to facilitate regional development. In addition, DMOs are proposed as a coalition of many organizations and interest although in practice, these organizations have proven to be composed in different ways, with varying performance (Tillväxtverket 2017). In order to understand the accomplishment the sought-after coordination of diverse stakeholder interests, a network approach has been suggested that encompasses inter-organizational relations (Elbe et al. 2018). The proposed network approach could take into account relations between organizations, not only limited to intra-organizational management models that do not encompass all stakeholders.Despite the numerous potential advantages of public-private interactions, they can be time- consuming and difficult as the participants come from different sectors and with deviating interests. Therefore, actors can perceive a risk that their power and influence may decrease. This can also lead to a lack of trust between the actors (de Araujo & Bramwell, 2002).Tensions and paradoxesInteraction between business actors are built around an economic rational. An assumption is that without economic incentives, interactions between business actors in networks will not come about (Håkansson, 1982; Finke et al., 2017). Different types of resources such as financial resources (capital), physical resources (time, technologies, people) and informational resources (knowledge) are exchanged and combined in new and unique ways through the interactions. Resources are through inherently dynamic and can always be used in new combinations within one relationship or in other relationships (Baraldi et al., 2012). An important condition and a factor influencing the interaction processes are the norms and perceptions of what constitutes the rules of the game. Through the interactions new norms for exchange can form and influence the continuation of the exchange. Whether to engage in the cooperation or not will be affected by previous experiences and expectations as expressed by Mousas and Ford (2009, p. 497): “Recurrent episodes are affected by the perceptions of the participants of their previous interactions and by their expectations of the future.” These exchange relationships, constitute the context in which interaction4processes between actors takes place (Easton & Håkansson, 1996; Håkansson & Ford, 2002; Håkansson & Waluszewski, 2002, 2007; Ritter, 2000).In tourist destinations, many of the resources used to attract tourists are public and common goods. The question of who owns these common goods is not always clear. Beaches, lakes, museums, culture heritage buildings are all resources that can attract tourists but that are public. Exchange relationships and agreement on how these public resources are exploited becomes essential for the survival of those organizations involved in developing act
|
|
| 6. |
|
|
| 7. |
- Persson, Patrik, et al.
(författare)
-
Adenosine A(2)a receptor stimulation prevents proteinuria in diabetic rats by promoting an anti-inflammatory phenotype without affecting oxidative stress
- 2015
-
Ingår i: Acta Physiologica. - : Wiley: 12 months. - 1748-1708 .- 1748-1716. ; 214:3, s. 311-318
-
Tidskriftsartikel (refereegranskat)abstract
- AimDiabetic patients are at increased risk for kidney disease. There is presently no clinical treatment available that effectively protects kidney function in diabetics. This study investigates whether chronic stimulation of the adenosine A(2a) receptor (A(2a)AR) protects kidney function in insulinopenic diabetic rats. MethodsStreptozotocin-induced diabetic rats and corresponding controls were chronically treated with the adenosine A(2a)AR agonist CGS21680 throughout the four-week diabetes duration. Kidney function was thereafter investigated, and urine and plasma samples were collected for analysis of protein, oxidative stress and inflammatory markers. ResultsGlomerular filtration rate, renal blood flow, filtration fraction and diabetes-induced kidney hypoxia were all unaffected by chronic A(2a)AR stimulation. Furthermore, diabetic rats had increased oxidative stress, which was further increased by chronic A(2a)AR stimulation. However, the 10-fold increased urinary protein excretion observed in the diabetic rats was completely prevented by chronic A(2a)AR stimulation. These beneficial effects were accompanied by reduced levels of the pro-inflammatory TNF- and increased levels of the anti-inflammatory IL-10 as well as decreased infiltration of macrophages, glomerular damage and basement membrane thickness. ConclusionChronic A(2a)AR stimulation prevents proteinuria and glomerular damage in experimental diabetes via an anti-inflammatory mechanism independent of oxidative stress and kidney hypoxia.
|
|
| 8. |
|
|
| 9. |
- Bolin, Sara, 1988-, et al.
(författare)
-
Combined BET bromodomain and CDK2 inhibition in MYC-driven medulloblastoma
- 2018
-
Ingår i: Oncogene. - : Nature Publishing Group. - 0950-9232 .- 1476-5594. ; 37:21, s. 2850-2862
-
Tidskriftsartikel (refereegranskat)abstract
- Medulloblastoma (MB) is the most common malignant brain tumor in children. MYC genes are frequently amplified and correlate with poor prognosis in MB. BET bromodomains recognize acetylated lysine residues and often promote and maintain MYC transcription. Certain cyclin-dependent kinases (CDKs) are further known to support MYC stabilization in tumor cells. In this report, MB cells were suppressed by combined targeting of MYC expression and MYC stabilization using BET bromodomain inhibition and CDK2 inhibition, respectively. Such combination treatment worked synergistically and caused cell cycle arrest as well as massive apoptosis. Immediate transcriptional changes from this combined MYC blockade were found using RNA-Seq profiling and showed remarkable similarities to changes in MYC target gene expression when MYCN was turned off with doxycycline in our MYCN-inducible animal model for Group 3 MB. In addition, the combination treatment significantly prolonged survival as compared to single-agent therapy in orthotopically transplanted human Group 3 MB with MYC amplifications. Our data suggest that dual inhibition of CDK2 and BET bromodomains can be a novel treatment approach for suppressing MYC-driven cancer.
|
|
| 10. |
- Elbe, Jörgen, 1960-, et al.
(författare)
-
Network approach to public-private organizing of destinations
- 2018
-
Ingår i: The IMP Journal. - : Emerald Group Publishing Limited. - 2059-1403 .- 0809-7259. ; 12:2, s. 313-332
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose – This paper explores a type of organizing that can be found in tourist destinations that areadministratively bound to a specific geographic area in the intersection of public and private context.The purpose of this paper is to contribute to the understanding of the organizing of activities withindestinations and also to contribute theoretically and conceptually to how place dependency and public/private can be understood from an industrial marketing and purchasing (IMP) network perspective.Design/methodology/approach – The research approach has its origin in an ongoing multi-disciplinaryand longitudinal case study.Findings – By applying a network approach to the organizing of destinations, where interaction ofrelationships, resources, actors and activities play an essential role, a number of propositions have been putforth so as to provide for a better understanding of place-specific organizing, in the intersection betweenpublic and private interests.Research limitations/implications – The paper is conceptual and more empirical studies are needed totest the findings. One implication to consider in future empirical studies is the tensions between created andorganic networks that exist in public and private place partnerships.Practical implications – The paper provides insights into factors affecting destination management.Social implications – With an emphasis on a socio-political context, the opportunities and limitations thatexist between public and private sectors are discussed.Originality/value – The paper sheds light on a neglected aspect of a contemporary phenomenon where theIMP network approach could contribute to the understanding of destination marketing or managementorganization that are bound to a specific place in the intersection between the public and private context.The area of public-private organizing is a topic that may also add new aspects to the IMP community.
|
|
