Negative feedback regulation of calcineurin-dependent Prz1 transcription factor by the CaMKK-CaMK1 axis in fission yeast

Calcium signals trigger the translocation of the Prz1 transcription factor from the cytoplasm to the nucleus. The process is regulated by the calciumactivated phosphatase calcineurin, which activates Prz1 thereby maintaining active transcription during calcium signalling. When calcium signalling ceases, Prz1 is inactivated by phosphorylation and exported to the cytoplasm. In budding yeast and mammalian cells, different kinases have been reported to counter calcineurin activity and regulate nuclear export. Here, we show that the Ca2+/calmodulin-dependent kinase Cmk1 is first phosphorylated and activated by the newly identified kinase CaMKK2 homologue, Ckk2, in response to Ca2+. Then, active Cmk1 binds, phosphorylates and inactivates Prz1 transcription activity whilst at the same time cmk1 expression is enhanced by Prz1 in response to Ca2+. Furthermore, Cdc25 phosphatase is also phosphorylated by Cmk1, inducing cell cycle arrest in response to an increase in Ca2+. Moreover, cmk1 deletion shows a high tolerance to chronic exposure to Ca2+, due to the lack of cell cycle inhibition and elevated Prz1 activity. This work reveals that Cmk1 kinase activated by the newly identified Ckk2 counteracts calcineurin function by negatively regulating Prz1 activity which in turn is involved in activating cmk1 gene transcription. These results are the first insights into Cmk1 and Ckk2 function in Schizosaccharomyces pombe.

Dominant-Negative Effects of Adult-Onset Huntingtin Mutations Alter the Division of Human Embryonic Stem Cells-Derived Neural Cells.

Mutations of the huntingtin protein (HTT) gene underlie both adult-onset and juvenile forms of Huntington's disease (HD). HTT modulates mitotic spindle orientation and cell fate in mouse cortical progenitors from the ventricular zone. Using human embryonic stem cells (hESC) characterized as carrying mutations associated with adult-onset disease during pre-implantation genetic diagnosis, we investigated the influence of human HTT and of an adult-onset HD mutation on mitotic spindle orientation in human neural stem cells (NSCs) derived from hESCs. The RNAi-mediated silencing of both HTT alleles in neural stem cells derived from hESCs disrupted spindle orientation and led to the mislocalization of dynein, the p150Glued subunit of dynactin and the large nuclear mitotic apparatus (NuMA) protein. We also investigated the effect of the adult-onset HD mutation on the role of HTT during spindle orientation in NSCs derived from HD-hESCs. By combining SNP-targeting allele-specific silencing and gain-of-function approaches, we showed that a 46-glutamine expansion in human HTT was sufficient for a dominant-negative effect on spindle orientation and changes in the distribution within the spindle pole and the cell cortex of dynein, p150Glued and NuMA in neural cells. Thus, neural derivatives of disease-specific human pluripotent stem cells constitute a relevant biological resource for exploring the impact of adult-onset HD mutations of the HTT gene on the division of neural progenitors, with potential applications in HD drug discovery targeting HTT-dynein-p150Glued complex interactions.

Presence of Chlamydiales DNA in samples negative by broad-range bacterial 16S rRNA PCRs: new insights into chlamydial pathogenic role.

Since routine eubacterial 16S rRNA PCR does not amplify members of the Chlamydiales order, we tested all samples received in our laboratory during a 10 months period using a pan-Chlamydiales real-time PCR. 3 of 107 samples (2.8%) revealed to be positive, suggesting a role of some Chlamydiales in the pathogenesis of chronic bronchial stenosis or bronchial stenosis superinfection and as agents of orthopaedic prosthesis infections.

Gram-negative flagella glycosylation

Protein glycosylation had been considered as an eccentricity of a few bacteria. However, through advances in analytical methods and genome sequencing, it is now established that bacteria possess both N-linked and O-linked glycosylation pathways. Both glycosylation pathways can modify multiple proteins, flagellins from Archaea and Eubacteria being one of these. Flagella O-glycosylation has been demonstrated in many polar flagellins from Gram-negative bacteria and in only the Gram-positive genera Clostridium and Listeria. Furthermore, O-glycosylation has also been demonstrated in a limited number of lateral flagellins. In this work, we revised the current advances in flagellar glycosylation from Gram-negative bacteria, focusing on the structural diversity of glycans, the O-linked pathway and the biological function of flagella glycosylation.

Yllätys yritysjohdon ennusteissa: Vaikutus osakekurssiin

Tutkielman tavoitteena oli selvittää Suomen osakemarkkinoiden hinnoittamistehokkuutta johdon ennustepoikkeamien tapauksessa. Tarkastelu-ajanjakso on 1.1.2000–31.12.2006. Kiinnostuneita oltiin erityisesti keski-pitkän ja pitkän aikavälin (10 kaupankäyntivuorokautta ja 40 kaupankäyntivuorokautta) epänormaaleista tuotoista. Työn empiriaosuus suoritettiin tapahtumatutkimusmenetelmää hyväksikäyttäen. Empiriaosuudessa laskettiin ennustepoikkeaman aiheuttamat epänormaalit tuotot pienimmän neliösumman regressiota hyväksikäyttäen. Positiivisten poikkeamien aiheuttamat epänormaalit tuotot eivät poikenneet tilastollisesti markkinatuotoista millään tarkasteluvälillä. Negatiivisten epänormaalien tuottojen poikkeamaa havaittiin 10 kaupankäyntivuorokautta ennustepoikkeaman julkaisun jälkeen. Toimialakohtaisessa tarkastelussa parillisten otosten t-testissä havaittiin, että terveydenhuollon, rahoituksen ja informaatioteknologian epänormaalit tuotot poikkesivat markkinatuotoista. Yrityskohtaisia tekijöitä tutkittiin yksinkertaisella t-testillä. Näistä velkaisuusasteella, beetalla, päivätuottojen keskihajonnalla, päivittäisellä liikevaihdolla sekä P/E-luvulla havaittiin voi-tavan ennustaa mahdollisten ennustepoikkeamien esiintymistiheyttä. Sen sijaan markkina-arvolla ja P/B-luvulla ei havaittu yhteyttä ennustepoikkeamien esiintymistiheyteen. Tutkittaessa käyttäytymistieteellisen rahoituksen olettamaa kaupankäyntivolyymin kasvusta ennustepoikkeamaa ympäröivänä aikana ei tilastollista merkittävyyttä löydetty.

Negative Regulation of Receptor Tyrosine Kinases by T-cell Protein Tyrosine Phosphatase

Protein tyrosine phosphorylation controls a wide array of cellular responses such as growth, migration, proliferation, differentiation, metabolism and cytoskeletal organisation. Tyrosine phosphorylation is a dynamic process involving the competing activities of protein tyrosine kinases and protein tyrosine phosphatases. The protein tyrosine kinases are further divided into non-receptor- and receptor tyrosine kinases. The latter are transmembrane glycoproteins activated by the binding of specific ligands, mostly growth factors, to their extracellular domain, transmitting different signals to the cell. Growth factor receptors such as the epidermal growth factor receptor, vascular endothelial growth factor receptor 2 and platelet-derived growth factor receptor β, belong to the receptor tyrosine kinases, the signalling of which is often disturbed in various diseases, including cancer. This has led to the development of receptor tyrosine kinase antagonists for use as anti-cancer drugs. As the receptor tyrosine kinases, also the protein tyrosine phosphatases can be divided into receptor- and non-receptor types. The protein tyrosine phosphatases have attained much less attention than the receptor tyrosine kinases partly because they were identified later. However, accumulating evidence shows that the protein tyrosine phosphatases have important roles as specific and active regulators of tyrosine phosphorylation in cells and of physiological processes. Consequently, the protein tyrosine phosphatases are receiving arising interest as novel drug targets. The aim of this work was to elucidate the negative regulation of receptor tyrosine kinases by one non-receptor protein tyrosine phosphatase, T-cell protein tyrosine phosphatase TCPTP. The results show that TCPTP activated by cell adhesion receptor integrin α1 functions as a negative regulator of the epidermal growth factor receptor. It was also found that TCPTP affects vascular endothelial growth factor receptor 2 signalling and angiogenesis. Lastly, a High-throughput screen with 64,280 compounds was performed to identify novel TCPTP activators, resulting in identification of one small molecule compound capable of exerting similar effects on TCPTP signalling as integrin α1. This compound is shown to downregulate signalling of epidermal growth factor receptor and platelet-derived growth factor receptor β, as well as to inhibit cell proliferation and angiogenesis. Our results suggest that a suitable small-molecule TCPTP activator could be utilized in the development of novel anti-cancer drugs.

Public-private sector wage differentials by type of contract: evidence from Spain

The article examines public-private sector wage differentials in Spain using microdata from the Structure of Earnings Survey (Encuesta de Estructura Salarial). When applying various decomposition techniques, we find that it is important to distinguish by gender and type of contract. Our results also highlight the presence of a positive wage premium for public sector workers that can be partially explained by their better endowment of characteristics, in particular by the characteristics of the establishment where they work. The wage premium is greater for female and fixed-term employees and falls across the wage distribution, being negative for more highly skilled workers.

Osakekurssin reagointi tulosvaroitukseen nousu- ja laskumarkkinoilla

Tutkimuksen tavoitteena on selvittää tapahtuuko tulosvaroituksen yhteydessä yli- tai alireagointia nousu- ja laskumarkkinoiden aikana. Tutkimus tehdään tapahtumatutkimuksena, jossa tarkoituksena on tutkia osakkeiden epänormaaleja tuottoja tulosvaroituspäivän ympärillä. Tapahtumaikkunan pituus on yhteensä 11 päivää [-5, +5]. Aineisto koostuu Helsingin pörssin OMXH25 indeksin yritysten julkaisemista tulosvaroituksista vuosien 1997–2009 välillä. Tälle aikavälille osuu 200 päivän liukuvalla keskiarvolla mitattuna kaksi nousu- ja kaksi laskumarkkinaa. Tutkimuksessa ei havaittu selvää yli- tai alireagointia nousu- tai laskumarkkinoilla. Sen sijaan tietty säännöllisyys reagoinnissa tulosvaroituksiin löydettiin: Nousumarkkinoilla, tulosvaroituspäivän jälkeen näkyy selvä positiivinen tuotto kahden päivän ajalta tulosvaroituksen jälkeen, riippumatta siitä onko kyseessä positiivinen vai negatiivinen tulosvaroitus. Vastaavasti laskumarkkinoilla löydettiin selvä negatiivinen epänormaali tuotto kahden päivän ajalta tulosvaroituksen jälkeen.

Earnings quality and performance in the banking industry: a profit frontier approach

The analysis of efficiency and productivity in banking has received a great deal of attention for almost three decades now. However, most of the literature to date has not explicitly accounted for risk when measuring efficiency. We propose an analysis of profit efficiency taking into account how the inclusion of a variety of bank risk measures might bias efficiency scores. Our measures of risk are partly inspired by the literature on earnings management and earnings quality, keeping in mind that loan loss provisions, as a generally accepted proxy for risk, can be adjusted to manage earnings and regulatory capital. We also consider some variants of traditional models of profit efficiency where different regimes are stipulated so that financial institutions can be evaluated in different dimensions—i.e., prices, quantities, or prices and quantities simultaneously. We perform this analysis on the Spanish banking industry, whose institutions have been deeply affected by the current international financial crisis, and where re-regulation is taking place. Our results can be explored in multiple dimensions but, in general, they indicate that the impact of earnings management on profit efficiency is of less magnitude than what might a priori be expected, and that on the whole, savings banks have performed less well than commercial banks. However, savings banks are adapting to the new regulatory scenario and rapidly catching up with commercial banks, especially in some dimensions of performance.

Earnings Management Shareholders point of view

This paper studies the relationship of earnings management and investors. Analysis of incentives reveals that most of them are opportunistic in nature. Unfortunately the investor would need insider information to distinguish between different forms of earnings management. Investors in some countries seem to devalue earnings when government body has signaled that earnings management might be involved, unfortunately without a clear signal the behavior seems reverse among non-institutional investors.

Puolustusteollisuusalan yrityksen strategisen verkoston hallinta ja tuloksellisuus vastakauppatoiminnan näkökulmasta

Valtiot soveltavat yleisesti puolustusvälinehankintojensa yhteydessä vastakauppamenettelyä, jota kutsutaan offsetiksi. Tämän laadullisen tapaustutkimuksen tavoitteena on selvittää minkälaista verkottumista suora offset edellyttää myyjäyritykseltä ja mitä vaikutuksia verkottumisella on myyjäyritykseen. Offsetvaatimusten ja paikallisyhteistyön vuoksi tapahtuvalla verkottumisella on monia vaikutuksia myyjäyritykseen, joista pääosan voidaan sanoa olevan liiketaloudellisessa mielessä negatiivisia. Huomioitavaa kuitenkin on, että ilman offsetia ei voida voittaa hankkeita ja näin generoida liiketoimintaa. Suoran offsetin verkostoituminen perustuu ratkaisuliiketoiminnan eli arvopajan kautta tuotettuun lisäarvoon loppuasiakkaalle. Tällaista verkostotoimintaa harjoittavaa yritystä voidaan kutsua asiakaskeskeisen verkoston ansaitsijaksi joka kasvattaa ansaintaansa tuottamansa korkeamman lisäarvon kautta. Offsetin luonteesta johtuen erilaisten mittausjärjestelmien rakentaminen voi nousta haasteeksi.

Earnings management in the process of preparing corporate financial reports

Earnings management (EM) literature examines managers’ use of judgment in financial reporting and in structuring transactions to alter financial reports for a specific reason. Mainstream EM literature strongly concentrates on statistical research methodologies and it is driven by positive accounting theory. Although EM occurs in the process of preparing corporate financial reports, that process has so far largely remained a “black box” in prior literature. The purpose of this study is to analyze what EM is, how and why it unfolds and how it is intertwined in the process of preparing corporate financial reports. In order to meet the needs of the study, a qualitative case study method will be used. The contribution of this study is threefold. First, it indicates that the concept of EM is not as unam-biguous as the prior literature has assumed. I find that EM is socially constructed and more open to interpretation than absolutely dichotomous conception given by previous studies. Second, this study contributes to our knowledge of the role and the importance of actors involved in conducting EM, indicating that EM is much more actor-dependent than the prior literature has assumed. Third, this study broadens our knowledge base with regard to the processes and potential for EM in academic research.

Pricing anomalies in the Finnish stock market

The aim of this thesis is to examine whether the pricing anomalies exists in the Finnish stock markets by comparing the performance of quantile portfolios that are formed on the basis of either individual valuation ratios, composite value measures or combined value and momentum indicators. All the research papers included in the thesis show evidence of value anomalies in the Finnish stock markets. In the first paper, the sample of stocks over the 1991-2006 period is divided into quintile portfolios based on four individual valuation ratios (i.e., E/P, EBITDA/EV, B/P, and S/P) and three hybrids of them (i.e. composite value measures). The results show the superiority of composite value measures as selection criterion for value stocks, particularly when EBITDA/EV is employed as earnings multiple. The main focus of the second paper is on the impact of the holding period length on performance of value strategies. As an extension to the first paper, two more individual ratios (i.e. CF/P and D/P) are included in the comparative analysis. The sample of stocks over 1993- 2008 period is divided into tercile portfolios based on six individual valuation ratios and three hybrids of them. The use of either dividend yield criterion or one of three composite value measures being examined results in best value portfolio performance according to all performance metrics used. Parallel to the findings of many international studies, our results from performance comparisons indicate that for the sample data employed, the yearly reformation of portfolios is not necessarily optimal in order to maximally gain from the value premium. Instead, the value investor may extend his holding period up to 5 years without any decrease in long-term portfolio performance. The same holds also for the results of the third paper that examines the applicability of data envelopment analysis (DEA) method in discriminating the undervalued stocks from overvalued ones. The fourth paper examines the added value of combining price momentum with various value strategies. Taking account of the price momentum improves the performance of value portfolios in most cases. The performance improvement is greatest for value portfolios that are formed on the basis of the 3-composite value measure which consists of D/P, B/P and EBITDA/EV ratios. The risk-adjusted performance can be enhanced further by following 130/30 long-short strategy in which the long position of value winner stocks is leveraged by 30 percentages while simultaneously selling short glamour loser stocks by the same amount. Average return of the long-short position proved to be more than double stock market average coupled with the volatility decrease. The fifth paper offers a new approach to combine value and momentum indicators into a single portfolio-formation criterion using different variants of DEA models. The results throughout the 1994-2010 sample period shows that the top-tercile portfolios outperform both the market portfolio and the corresponding bottom-tercile portfolios. In addition, the middle-tercile portfolios also outperform the comparable bottom-tercile portfolios when DEA models are used as a basis for stock classification criteria. To my knowledge, such strong performance differences have not been reported in earlier peer-reviewed studies that have employed the comparable quantile approach of dividing stocks into portfolios. Consistently with the previous literature, the division of the full sample period into bullish and bearish periods reveals that the top-quantile DEA portfolios lose far less of their value during the bearish conditions than do the corresponding bottom portfolios. The sixth paper extends the sample period employed in the fourth paper by one year (i.e. 1993- 2009) covering also the first years of the recent financial crisis. It contributes to the fourth paper by examining the impact of the stock market conditions on the main results. Consistently with the fifth paper, value portfolios lose much less of their value during bearish conditions than do stocks on average. The inclusion of a momentum criterion somewhat adds value to an investor during bullish conditions, but this added value turns to negative during bearish conditions. During bear market periods some of the value loser portfolios perform even better than their value winner counterparts. Furthermore, the results show that the recent financial crisis has reduced the added value of using combinations of momentum and value indicators as portfolio formation criteria. However, since the stock markets have historically been bullish more often than bearish, the combination of the value and momentum criteria has paid off to the investor despite the fact that its added value during bearish periods is negative, on an average.