Salamander limb regeneration involves the activation of a multipotent skeletal muscle satellite cell population

In contrast to mammals, salamanders can regenerate complex structures after injury, including entire limbs. A central question is whether the generation of progenitor cells during limb regeneration and mammalian tissue repair occur via separate or overlapping mechanisms. Limb regeneration depends on the formation of a blastema, from which the new appendage develops. Dedifferentiation of stump tissues, such as skeletal muscle, precedes blastema formation, but it was not known whether dedifferentiation involves stem cell activation. We describe a multipotent Pax7+ satellite cell population located within the skeletal muscle of the salamander limb. We demonstrate that skeletal muscle dedifferentiation involves satellite cell activation and that these cells can contribute to new limb tissues. Activation of salamander satellite cells occurs in an analogous manner to how the mammalian myofiber mobilizes stem cells during skeletal muscle tissue repair. Thus, limb regeneration and mammalian tissue repair share common cellular and molecular programs. Our findings also identify satellite cells as potential targets in promoting mammalian blastema formation

CETSA-based target engagement of taxanes as biomarkers for efficacy and resistance

The use of taxanes has for decades been crucial for treatment of several cancers. A major limitation of these therapies is inherent or acquired drug resistance. A key to improved outcome of taxane-based therapies is to develop tools to predict and monitor drug efficacy and resistance in the clinical setting allowing for treatment and dose stratification for individual patients. To assess treatment efficacy up to the level of drug target engagement, we have established several formats of tubulin-specific Cellular Thermal Shift Assays (CETSAs). This technique was evaluated in breast and prostate cancer models and in a cohort of breast cancer patients. Here we show that taxanes induce significant CETSA shifts in cell lines as well as in animal models including patient-derived xenograft (PDX) models. Furthermore, isothermal dose response CETSA measurements allowed for drugs to be rapidly ranked according to their reported potency. Using multidrug resistant cancer cell lines and taxane-resistant PDX models we demonstrate that CETSA can identify taxane resistance up to the level of target engagement. An imaging-based CETSA format was also established, which in principle allows for taxane target engagement to be accessed in specific cell types in complex cell mixtures. Using a highly sensitive implementation of CETSA, we measured target engagement in fine needle aspirates from breast cancer patients, revealing a range of different sensitivities. Together, our data support that CETSA is a robust tool for assessing taxane target engagement in preclinical models and clinical material and therefore should be evaluated as a prognostic tool during taxane-based therapies

Contracting muscle for regeneration : Myogenic dedifferentiation in limb progenitor cell formation

The urodele amphibians, such as newts and axolotls, are unique among vertebrates since they regenerate their limbs, tail, jaws and part of their heart and CNS as adults. After amputation of a newt limb, regeneration proceeds by the reversal of differentiation of tissues in the limb stump. In this process, termed dedifferentiation, tissue characteristics are lost and cells with a more stem cell-like morphology appear. Such cells migrate distally and proliferate to form the blastema, a structure that gives rise to the tissues of the new limb. In this thesis, I have studied cellular and molecular mechanisms of how progenitor cells are formed from skeletal muscle during newt limb regeneration. It is not established to what extent skeletal muscle tissue dedifferentiation, seen after amputation, involves cellularization of myofibres, and to what extent it involves activation of resident reserve cells. In paper I we identified a Pax7+ satellite cell population in newt skeletal muscle, which is mitotically activated after limb amputation. We established a method to isolate and cultivate newt single muscle fibres, in which activation of satellite cells as well as cellularization of the myofibre can be studied. Newt single fibres produced proliferating progeny that we showed to be satellite cell derived. When implanted into a newt limb before its amputation, the satellite cell progeny appeared to contribute to the blastema and to cartilage and epidermis of the regenerate. In paper II we developed a way of expressing genes exclusively in terminally differentiated muscle cells by cytoplasmic injection of expression vectors. This method enables the study of the effect of various molecules on dedifferentiation without interfering with the differentiation process. In addition, injecting plasmids expressing fluorescent markers provides a tool for tracing of individual cells derived by cellular dedifferentiation, a method used in paper IV. Newt myotubes reenter S-phase in response to a thrombin-activated serum component. Thrombin is activated after both amputation and lentectomy in the newt, and might provide a link between tissue injury and dedifferentiation. Mouse myotubes do not respond to serum by S-phase reentry, a feature that might be an aspect of the relatively poor regenerative ability in mammals. In paper III we used quantitative RT-PCR to study the responsiveness of mouse myotubes to various serum components in comparison to their newt counterparts. We show that mouse myotubes respond to the thrombin-activated factor by increased expression of Id1, c-fos and c-jun, indicating that mouse myotubes retain responsiveness to this factor as well as the ability to leave G0 and reenter the cell cycle. Furthermore, we found that in newt myotubes global methylation of H3K9 is reversed after serum stimulation, while this classical repressor mark is retained in serum stimulated mouse myotubes, which might reflect their block to S-phase reentry. The molecular pathways inducing cellularization of myofibres are not known. However, in addition to major tissue damage, myofibre fragmentation requires direct injury to the fibre. This fact led us to hypothesize that inducing a programmed cell death (PCD) response in the fibre can lead to its dedifferentiation. In paper IV we tested this hypothesis, by lineage tracing of individual myotubes, and showed that a previously identified inducer of cellularization evokes a PCD response in myotubes. Furthermore, we showed that the pro-apoptotic drugs, STS and TSA, induce myotube cellularization, an effect that can be blocked by the anti-apoptotic drug DIDS. In summary, the major findings of this thesis are the following. Similarly to mammals, newt skeletal muscle harbours a Pax7+ satellite cell population, which is activated during newt limb regeneration. Furthermore, cellular dedifferentiation and PCD share molecular pathways in both newt and mammalian myotubes. In addition, mammalian myotubes retain responsiveness to the thrombin activated serum factor. Our data pinpoint several features that characterize both newt and mammalian skeletal muscle and indicate that further understanding of skeletal muscle plasticity after injury may reveal ways to promote blastema formation in mammals

Aktiv vs passiv fondförvaltning : En studie som jämför aktiv och passiv förvaltning i Sverige, Storbritanien och USA i relation till varderas marknadsutveckling under perioden 2008-20017

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Hur agerar aktiebolag, i dagsläget, inför ett möjligt val av frivillig revision? Vilka faktorer påverkar agerandet?

Sammanfattning Titel: Hur agerar aktiebolag, i dagsläget, inför ett möjligt val av frivillig revision? Ämne/kurs:  Företagsekonomi 61-90, inriktning externredovisning Författare:  Sofia Lorentzon &amp; Anna-Sara Lööf Handledare: Sven-Olof Yrjö Collin. Nyckelord: revisionspliktens avskaffande, ekonomiförändring, relationsförändring Bakgrund: I Mars 2010 beslutade regeringen om tre gränser, var ett företag måste uppfylla minst två för att få lov till att avskaffa sin revisor. Lagförslaget som än så länge ligger som en proposition säger att från och med den 1 november 2010 ska företagen få välja om de vill ha avskaffa sin revisor eller inte. Syfte: Vårt syfte är att förklara hur aktiebolagen agerar i dagsläget, inför ett möjligt val till frivillig revision. Empirisk metod: För att undersöka hur företagen agerar i dagsläget inför valet om frivillig revision har vi utfört en enkätundersökning. Slutsatser: Genom vår undersökning har vi kommit fram till att ju mer företag agerar mot att satsa på relationsförändring desto mer tenderar de att slopa sin revisor. De variabler som påverkar företagens relationsförändring är; storlek, bransch, kassalikviditet, lönsamhet, ägare och omgivningens åsikter

TRADE FIRM PERFORMANCE AND INTERNATIONAL TRADE : evidence from a small open economy

This paper presents a comprehensive description and analysis of the international trading activities of firms based on novel detailed Swedish data. As a small open economy with a limited domestic market, Sweden constitutes an interesting contrast to existing evidence. We show that much of the stylized facts from large countries (specifically the US) about firms’ participation in international trade also pertain to a small open economy. We provide robust evidence of selection operating from market to market which is consistent with that low productive firms are confined to markets with low productivity thresholds. We further show that selection also applies to number of products traded. Both export and import productivity premiums increase in number of markets and number of products traded, respectively. There is a substantial heterogeneity among exporters and importers in terms of the number of markets they trade with and in terms of the number of products they trade.QC 2012020

Librarian Ethics in Action

Bakalaura darba temats – „Bibliotekāra ētika darbībā” , kas ir plaša pētījums par bibliotekāra ētikas kodeksa un darbību Latvijas un pasaules valstu lielākajās bibliotēkās. Problēmsituācija un pētījuma problēma ir bibliotekāra ētikas nozīme bibliotēku darbā. Pētījuma problēmsituāciju noteica tas, ka informācija par šo tēmu presē un profesionālajā literatūrā ir samēra neliela. Pētījuma mērķis ir apkopot, izpētīt un analizēt bibliotekāra ētikas darbību, nozīmi bibliotekārajā apkalpošana Latvijas bibliotēku sistēmā. Paradīt, cik svarīga un vajadzīga ir bibliotekāra ētika darbā ar lasītājiem un saskarsmē ar kolēģiem. Rezultātā var secināt, ka bibliotekāra ētika ir svarīga, nozīmīga un neatņemama bibliotēkas darba sastāvdaļa, tāpēc bibliotēku praksē ir nepieciešams bibliotekārais ētikas kodekss, kas palīdzēs kvalitatīvāk apkalpot bibliotēkas apmeklētājus un komunicēt ar tiem. Veicot aptauju, var secināt, ka ētikas kodekss joprojām nezaudē savu aktualitātiThe theme of this bachelor's work-"Librarian ethics in action", which is a spacious research work of the ethics code and work of a librarian in the largest Latvian and world state libraries. The problem of this situation and the problem of the research is the importance of the librarian ethics code in the work of a librarian. The problem situation of the research is determined by the lack of information on this theme in a press and in the professional literature. The purpose of this research is to summarize, explore and analyze the librarian ethics work, the importance of library service in the system of the Latvian libraries. It shows the importance and necessity of librarian ethics at work with readers and in contiguity with colleagues. To sum up we can make a conclusion that the librarian ethic is a very important, significant and integral part of librarian's work, so the librarian ethics code is necessary in the library practice and it can help to serve visitors more qualitative and communicate with them

Normkritik och samarbeten inom fastighetsautomation

Norms, gender and collaboration in proptech Here, an engineering approach to norm criticism is used to study a male-dominated interdisciplinary digitization project in the area of prop tech. In property automation (prop tech) the participants are in principle exclusively men, and thus the platforms and program development that will be the basis for all prop tech development are coded in a male context. There are also major challenges, as in most interdisciplinary groups, where the balance of power is often skewed through different norms. The project has mainly addressed challenges due to the interdisciplinary groups, while the gender perspective has been given less focus. The focus on norms has been assigned a full work package, with a similar budget as the other work packages focused on other areas and the norm work package has interacted very closely with all parts of the project, including the more technical ones. In this way, the norm critics has created a platform of its own in the project, based on how a norm critical analysis could be offered to help other work packages in their tasks. Based on the work on norms; discussions, workshops and surveys have been supplemented with interviews, in close collaboration with other work packages. Through the norm-critical analysis, different groups, both within the project and in the industry around prop tech, have been identified. Differences between these groups relate to understanding of different types of technology, priorities, communication and balance of power. Norm criticism has been a way of supporting the entire project in both the expansion of business models and interaction between the various scientific areas that are part of the project. The norm criticism has been well received by the project group and many are aware that the industry is facing a change that requires new ways of thinking, new business models and new collaboration models. There is a new awareness in both the conversations within the project and the surveys and interviews based on the understanded need to see multiple perspectives. This awareness has also been used to broaden the business model. The understanding that it is more difficult to see the order of power for those who belong to the prioritized group has also increased. At the same time, we see a large effect of personal, or corporate, interest in norm criticism, which strongly influences how respondents react to the questions about norm criticism. The project shows that the method of using norm criticism in collaborative processes between different groups has been successful

Productivity and International Trade - firm-level evidence from a small open economy

This paper presents a comprehensive description and analysis of the international trading activities of firms based on novel detailed Swedish data. As a small open economy with a limited domestic market, Sweden constitutes an interesting contrast to existing evidence. We show that much of the stylized facts from large countries (specifically the US) about firms’ participation in international trade also pertain to a small open economy. We provide robust evidence of selection operating from market to market which is consistent with that low productive firms are confined to markets with low productivity thresholds. We further show that selection also applies to number of products traded. Both export and import productivity premiums increase in number of markets and number of products traded, respectively. There is a substantial heterogeneity among exporters and importers in terms of the number of markets they trade with and in terms of the number of products they trade.international trade; exports; imports; firm heterogeneity; productivity; import premium; export premium