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In the efforts to develop effective therapeutic strategies limiting post-ischemic injury, mitochondria emerge as key element in determining the fate of the neurons. Mitochondrial damage can be alleviated by various mechanisms including mitochondrial network remodelling, mitochondrial elimination and mitochondrial protein biogenesis. However, the mechanisms regulating the relationship between these phenomena are poorly understood. Here we hypothesize that mitofusin 2 (Mfn2), a mitochondrial GTPase, involved in mitochondrial fusion, mitochondria trafficking and mitochondria and endoplasmic reticulum (ER) tethering, may act as a linking and regulatory factor in neurons following ischemic insult. To verify this assumption, we performed a temporal oxygen and glucose deprivation (OGD) on rat cortical primary culture to determine whether Mfn2 protein reduction may affect the onset of mitophagy, subsequent mitochondrial biogenesis and thus neuronal survival. In our study we found that Mfn2 knock-down increased the susceptibility of the neurons to the OGD. Mfn2 protein reduction prevented mitochondrial network remodelling and resulted in the prolonged mitophagosomes formation in response to the insult. Further on, Mfn2 protein reduction was accompanied by a reduced level of Parkin protein and an increased Parkin accumulation with mitochondria. As for Mfn2-expressing neurons, the OGD insult was followed by an elevated mtDNA content and an increase in the respiratory chain proteins. Neither of this phenomena were observed for Mfn2-reduced neurons. Collectively, our findings show that Mfn2 in neurons is involved in their response to mild and transient OGD stress, balancing the extent of elimination of defective mitochondria and positively influencing mitochondrial respiratory proteins levels. Our study confirms that Mfn2 is an essential element of the neuronal response to ischemic insult, necessary for the neuronal survival.

Additional file 5: Movie S4. Exemplary results of RUSH assay in MCF7 cells treated with INK128

The aim of this paper is to identify factors influencing the capital structure of Polish food manufacturing companies. In the first part of the paper, the most probable determinants of the capital structure have been identified on the basis of literature review and the current research conducted in this field. The second part of the paper presents an empirical verification of the relationship between capital structure and its fundamental determinants. The study was made using panel models. The scope of the survey covered Polish food companies between 2012 and 2015. Key determinants of total debt in the food manufacturing companies include: share of fixed assets in total assets, liquidity, profitability and non-debt tax shield with negative relationship. These factors also include: business size and growth with a positive relationship. For the long-term debt, the following factors are important: share of fixed assets in total assets, size of the business and liquidity (positive relationship). A negative relationship has been diagnosed for profitability and non-debt tax shield. The identified factors and the direction of dependence are similar to those previously diagnosed in the Czech Republic and Italy. However, they differ significantly from those of the US and Turkey. The capital structure of Polish food enterprises, measured by the total debt ratio, is best explained by the pecking order theory, while the share of long-term debt in the capital structure can be explained by static trade-off theory.

In neurons, the polarized distribution of vesicles and other cellular materials is established through molecular motors that steer selective transport between axons and dendrites. It is currently unclear whether interactions between kinesin motors and microtubule-binding proteins can steer polarized transport. By screening all 45 kinesin family members, we systematically addressed which kinesin motors can translocate cargo in living cells and drive polarized transport in hippocampal neurons. While the majority of kinesin motors transport cargo selectively into axons, we identified five members of the kinesin-3 (KIF1) and kinesin-4 (KIF21) subfamily that can also target dendrites. We found that microtubule-binding protein doublecortin-like kinase 1 (DCLK1) labels a subset of dendritic microtubules and is required for KIF1-dependent dense-core vesicles (DCVs) trafficking into dendrites and dendrite development. Our study demonstrates that microtubule-binding proteins can provide local signals for specific kinesin motors to drive polarized cargo transport.

Celem badań było rozpoznanie relacji między rentownością a płynnością finansową przedsiębiorstw sektora przetwórstwa spożywczego. Materiał badawczy stanowiły dane sprawozdawcze 1046 przedsiębiorstw z lat 2012-2015. Do identyfikacji poszukiwanej zależności użyto modelu panelowego opartego na klasycznej metodzie najmniejszych kwadratów. Nie wykryto istotnej statystycznie zależności dla całej próby badawczej. Zależność dodatnią stwierdzono dla podpróby, na którą złożyły się dane finansowe przedsiębiorstw o współczynniku płynności bieżącej (CR) mniejszym od 2,0.

In neurons, the polarized distribution of vesicles and other cellular materials is established through molecular motors that steer selective transport between axons and dendrites. It is currently unclear whether interactions between kinesin motors and microtubule-binding proteins can steer polarized transport. By screening all 45 kinesin family members, we systematically addressed which kinesin motors can translocate cargo in living cells and drive polarized transport in hippocampal neurons. While the majority of kinesin motors transport cargo selectively into axons, we identified five members of the kinesin-3 (KIF1) and kinesin-4 (KIF21) subfamily that can also target dendrites. We found that microtubule-binding protein doublecortin-like kinase 1 (DCLK1) labels a subset of dendritic microtubules and is required for KIF1-dependent dense-core vesicles (DCVs) trafficking into dendrites and dendrite development. Our study demonstrates that microtubule-binding proteins can provide local signals for specific kinesin motors to drive polarized cargo transport.

Current technologies have become a source of omnipresent electromagnetic pollution from generated electromagnetic fields and resulting electromagnetic radiation. In many cases this pollution is much stronger than any natural sources of electromagnetic fields or radiation. The harm caused by this pollution is still open to question since there is no clear and definitive evidence of its negative influence on humans. This is despite the fact that extremely low frequency electromagnetic fields were classified as potentially carcinogenic. For these reasons, in recent decades a significant growth can be observed in scientific research in order to understand the influence of electromagnetic radiation on living organisms. However, for this type of research the appropriate selection of relevant model organisms is of great importance. It should be noted here that the great majority of scientific research papers published in this field concerned various tests performed on mammals, practically neglecting lower organisms. In that context the objective of this paper is to systematise our knowledge in this area, in which the influence of electromagnetic radiation on lower organisms was investigated, including bacteria, E. coli and B. subtilis, nematode, Caenorhabditis elegans, land snail, Helix pomatia, common fruit fly, Drosophila melanogaster, and clawed frog, Xenopus laevis.

The objetive of this paper is to present the results of empirical research on the assessment of the significance of strategic information for decision-making in Polish farms. The survey covered 338 managers of farms from all over the country. Analysis of central tendency measures proved that the information referred in the research, significantly shape the strategic decisions of farmers. The most important information is on the financial situation of the farm and on the demand side of its business. Managers assess information on competitors’ activity and on the situation on the labor market as the least important.

Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that was identified as one of the important regulators of dendritogenesis. mTOR forms two functionally separate complexes (mTORC) in mammalian cells. The complexes are defined by unique mTOR binding partners, Raptor for the mTORC1, and Rictor for the mTORC2. These two complexes control different cellular processes and their roles seem non-overlapping. mTORC1 was initially characterized as a protein translation regulator while mTORC2 was shown to affect cytoskeleton. Both processes are known to be essential for neuron development, but until now the role of particular mTORCs in dendritogenesis was not studied. Therefore, in our study we precisely characterized mTOR involvement in dendrite development. Using RNA interference in developing rat hippocampal neurons in culture we targeted either Raptor or Rictor to separate activities of mTORC1 and mTORC2, respectively. Dendritic arbors of neurons, depleted of either one of these proteins were reduced. However, no obvious differences were observed in context of dendrite number, length, dendritic arbor complexity and dynamics of dendritic growth and retraction between cells with either Raptor or Rictor knockdown. Yet on the molecular level we were able to pin-point differences between cells lacking Rictor and Raptor. For example, Rictor, but not Raptor knockdown phenotype could be rescued by overexpression of a constitutively active mutant of Akt (myr-Akt), a kinase known to be mTORC2 effector. Besides of being mTORC2 effector, Akt is the most important positive regulator of mTORC1. Since, Rictor and Raptor knockdown have similar and not additive dendritic phenotypes, we hypothesized that mTORC1 acts downstream of mTORC2 during dendritic growth. Therefore, we tested the effects of Rictor knockdown in neurons on phosphorylation of S6 (Ser-235/236) and eIF4B (Ser-422), canonical targets for mTORC1. Indeed, downregulation of Rictor, significantly inhibited phosphorylation of these proteins. Because p70S6K is a kinase responsible for the phosphorylation of S6 and eiF4B in response to Akt-mTORC1 activation, we tested if mTORC2 controls dendritic arbor growth, at least partially, via the Akt-mTOR-p70S6K pathway. In fact, the overexpression of a p70S6KT389E mutant that mimics the phosphorylation of p70S6K1 induced by mTOR, not only restored P-S6 to control levels but also, to some extent, rescued dendritic arbors of cells transfected with shRNAs against Rictor. Together, our research indicates that 1) both mTOR complexes are crucial for the proper dendritic arbor morphology, and 2) mTORC2 is upstream of mTORC1 in hippocampal neurons in culture.

Zipcode Binding Protein 1 (ZBP1) is one of proteins involved in local translation, a mechanism present in polarized cells, enabling rapid, localized protein synthesis in response to extracellular stimuli. It was previously shown that in neurons, processes coordinated by ZBP1 are indispensable for proper axonal growth cone and spine formation. We recently showed that developing neurons with overexpressed or knockdown ZBP1 cannot obtain proper morphology. We also proved that phosphorylation of ZBP1 by Src kinase is needed for proper dendritic branching [1]. Subsequently, we asked a question about other regulators of ZBP1 during dendritogenesis. Now, we demonstrate that ZBP1 is effectively phosphorylated in vitro by mTOR kinase. We took advantage of recently published data regarding potential mTOR-dependent phosphorylation sites in ZBP1 i.e. Ser181 [2] and examined role of this phosphorylation in (i) dendritic arborization and (ii) cellular distribution of ZBP1. To address these questions, we constructed non-phosphorable (S181A) and phosphomimicking (S181E) mutants of ZBP1 fused to GFP. We observed that S181E but not S181A reversed morphological deficits caused by ZBP1 knockdown. Another observation was that distribution along the dendrites of non-phosphorable mutant was more even than distribution of wild type ZBP1, which is denser at the dendritic branching points. Thus, we concluded that Ser181 phosphorylation is involved in ZBP1 functions during dendritic growth.

Glycogen synthase kinase-3 (GSK-3) is expressed as two isozymes α and β. They share high similarity in their catalytic domains but differ in their N- and C-terminal regions, with GSK-3α having an extended glycine-rich N terminus. Here, we undertook live cell imaging combined with molecular and bioinformatic studies to understand the distinct functions of the GSK-3 isozymes focusing on GSK-3α N-terminal region. We found that unlike GSK-3β, which shuttles between the nucleus and cytoplasm, GSK-3α was excluded from the nucleus. Deletion of the N-terminal region of GSK-3α resulted in nuclear localization, and treatment with leptomycin B resulted in GSK-3α accumulation in the nucleus. GSK-3α rapidly accumulated in the nucleus in response to calcium or serum deprivation, and accumulation was strongly inhibited by the calpain inhibitor calpeptin. This nuclear accumulation was not mediated by cleavage of the N-terminal region or phosphorylation of GSK-3α. Rather, we show that calcium-induced GSK-3α nuclear accumulation was governed by GSK-3α binding with as yet unknown calpain-sensitive protein or proteins; this binding was mediated by the N-terminal region. Bioinformatic and experimental analyses indicated that nuclear exclusion of GSK-3α was likely an exclusive characteristic of mammalian GSK-3α. Finally, we show that nuclear localization of GSK-3α reduced the nuclear pool of β-catenin and its target cyclin D1. Taken together, these data suggest that the N-terminal region of GSK-3α is responsible for its nuclear exclusion and that binding with a calcium/calpain-sensitive product enables GSK-3α nuclear retention. We further uncovered a novel link between calcium and nuclear GSK-3α-mediated inhibition of the canonical Wnt/β-catenin pathway.

Hihm notat nr 2, 2011 Norsk: Den finansielle styringen av et moderne foretak er i noen grad sammensatt. I bidraget har en et fokus på grunnleggende utfordringer, og tilnærminger til disse, som leder i retning av at mål blir nådd på en effektiv og rasjonell måte. Bidraget innledes med noen perspektiver på den finansielle styringen, og sett i forhold til elementer og områder. I tillegg har vi spørsmålet om hva de finansielle målene bør gå ut på. Mer konkret ser en på hva oppstillinger i finansregnskapet har å bidra med som kilde til informasjon om den finansielle situasjon. Det er klart at et foretak må arbeide med en sammensetning av eiendeler og forpliktelser (egenkapital og gjeld) som er formålstjenelig. Dette innbefatter styringen av omløpsmidler, som blir fokusert avslutningsvis. English: The main goal of the paper is to present the fundamental rules and problems of corporate financial management in the context of proficient and effective achievement of financial objectives. The first part of the paper explains the concept of corporate finance, describes its components and defines the main areas of financial management. The second part is devoted to the financial objectives of the company. The next section provides a brief description of the financial statements as a source of information about the company’s financial condition. The last two parts include issues related to shaping the structure of assets and liabilities and to working capital management. Gdansk School of Banking

Głównym celem rozdziału jest prezentacja użyteczności analitycznej funkcji sprawozdania finansowego w pomiarze i kształtowaniu nośników wartości przedsiębiorstwa. Na początku zdefiniowano wartość przedsiębiorstwa oraz wskazano na czynniki ją kreujące. Następnie zaprezentowano pojemność informacyjną sprawozdania finansowego, a także omówiono jego wykorzystanie w ocenie kondycji finansowej przedsiębiorstwa. Ostatnia część rozdziału zawiera studium przypadku, w którym zweryfikowano przydatność metod analizy finansowej w ocenie bieżącej wartości przedsiębiorstwa oraz jego perspektyw rozwojowych. Publikacja dofinansowana przez STOWARZYSZENIE KSIĘGOWYCH W POLSCE ZARZĄD GŁÓWNY W WARSZAWIE ODDZIAŁ OKRĘGOWY W ŁODZI, ul. Narutowicza 35, 90-125 Łódź; tel. 042-631-95-23, 042-631-95-29, fax 042-630-26-37; www.skwp-lodz.pl, biuro@skwp-lodz.pl.

Diamentopodobne powłoki weglowe sa obecnie intensywnie badane jako materiały o wielorakich potencjalnych zastosowaniach w elektronice, optyce i trybologii. W raporcie przedstawiamy pierwsze warstwy amorficznego wegla uformowane metoda PLD w IFJ PAN. Powłoki deponowane były na podłozach krzemowych w komorze prózniowej pod cisnieniem 5x10¡5 mbar przez ablacje laserowa tarczy grafitowej. W eksperymencie uzyto lasera Nd:YAG o długosci fali 1064 nm i gestosci energii w zakresie 10-50 J/cm2. Mikrostruktura uzyskanych powłok została przebadana przy uzyciu spektroskopii Ramana.