Protein 3-nitrotyrosine formation during Trypanosoma cruzi infection in mice

Nitric oxide (·NO) is a diffusible messenger implicated in Trypanosoma cruzi resistance. Excess production of ·NO and oxidants leads to the generation of nitrogen dioxide (·NO2), a strong nitrating agent. Tyrosine nitration is a post-translational modification resulting from the addition of a nitro (-NO2) group to the ortho-position of tyrosine residues. Detection of protein 3-nitrotyrosine is regarded as a marker of nitro-oxidative stress and is observed in inflammatory processes. The formation and role of nitrating species in the control and myocardiopathy of T. cruzi infection remain to be studied. We investigated the levels of ·NO and protein 3-nitrotyrosine in the plasma of C3H and BALB/c mice and pharmacologically modulated their production during the acute phase of T. cruzi infection. We also looked for protein 3-nitrotyrosine in the hearts of infected animals. Our results demonstrated that C3H animals produced higher amounts of ·NO than BALB/c mice, but their generation of peroxynitrite was not proportionally enhanced and they had higher parasitemias. While N G-nitro-arginine methyl ester treatment abolished ·NO production and drastically augmented the parasitism, mercaptoethylguanidine and guanido-ethyl disulfide, at doses that moderately reduced the ·NO and 3-nitrotyrosine levels, paradoxically diminished the parasitemia in both strains. Nitrated proteins were also demonstrated in myocardial cells of infected mice. These data suggest that the control of T. cruzi infection depends not only on the capacity to produce ·NO, but also on its metabolic fate, including the generation of nitrating species that may constitute an important element in parasite resistance and collateral myocardial damage.

Contribution of matrix vesicles and alkaline phosphatase to ectopic bone formation

Endochondral calcification involves the participation of matrix vesicles (MVs), but it remains unclear whether calcification ectopically induced by implants of demineralized bone matrix also proceeds via MVs. Ectopic bone formation was induced by implanting rat demineralized diaphyseal bone matrix into the dorsal subcutaneous tissue of Wistar rats and was examined histologically and biochemically. Budding of MVs from chondrocytes was observed to serve as nucleation sites for mineralization during induced ectopic osteogenesis, presenting a diameter with Gaussian distribution with a median of 306 ± 103 nm. While the role of tissue-nonspecific alkaline phosphatase (TNAP) during mineralization involves hydrolysis of inorganic pyrophosphate (PPi), it is unclear how the microenvironment of MV may affect the ability of TNAP to hydrolyze the variety of substrates present at sites of mineralization. We show that the implants contain high levels of TNAP capable of hydrolyzing p-nitrophenylphosphate (pNPP), ATP and PPi. The catalytic properties of glycosyl phosphatidylinositol-anchored, polidocanol-solubilized and phosphatidylinositol-specific phospholipase C-released TNAP were compared using pNPP, ATP and PPi as substrates. While the enzymatic efficiency (k cat/Km) remained comparable between polidocanol-solubilized and membrane-bound TNAP for all three substrates, the k cat/Km for the phosphatidylinositol-specific phospholipase C-solubilized enzyme increased approximately 108-, 56-, and 556-fold for pNPP, ATP and PPi, respectively, compared to the membrane-bound enzyme. Our data are consistent with the involvement of MVs during ectopic calcification and also suggest that the location of TNAP on the membrane of MVs may play a role in determining substrate selectivity in this micro-compartment.

Expression of neuronal nitric oxide synthase in the hippocampal formation in affective disorders

Hippocampal output is increased in affective disorders and is mediated by increased glutamatergic input via N-methyl-D-aspartate (NMDA) receptor and moderated by antidepressant treatment. Activation of NMDA receptors by glutamate evokes the release of nitric oxide (NO) by the activation of neuronal nitric oxide synthase (nNOS). The human hippocampus contains a high density of NMDA receptors and nNOS-expressing neurons suggesting the existence of an NMDA-NO transduction pathway which can be involved in the pathogenesis of affective disorders. We tested the hypothesis that nNOS expression is increased in the human hippocampus from affectively ill patients. Immunocytochemistry was used to demonstrate nNOS-expressing neurons in sections obtained from the Stanley Consortium postmortem brain collection from patients with major depression (MD, N = 15), bipolar disorder (BD, N = 15), and schizophrenia (N = 15) and from controls (N = 15). nNOS-immunoreactive (nNOS-IR) and Nissl-stained neurons were counted in entorhinal cortex, hippocampal CA1, CA2, CA3, and CA4 subfields, and subiculum. The numbers of Nissl-stained neurons were very similar in different diagnostic groups and correlated significantly with the number of nNOS-IR neurons. Both the MD and the BD groups had greater number of nNOS-IR neurons/400 µm² in CA1 (mean ± SEM: MD = 9.2 ± 0.6 and BD = 8.4 ± 0.6) and subiculum (BD = 6.7 ± 0.4) when compared to control group (6.6 ± 0.5) and this was significantly more marked in samples from the right hemisphere. These changes were specific to affective disorders since no changes were seen in the schizophrenic group (6.7 ± 0.8). The results support the current view of the NMDA-NO pathway as a target for the pathophysiology of affective disorders and antidepressant drug development.

BMP-2 and titanium particles synergistically activate osteoclast formation

A previous study showed that BMP-2 (bone morphogenetic protein-2) and wear debris can separately support osteoclast formation induced by the receptor activator of NF-κB ligand (RANKL). However, the effect of BMP-2 on wear debris-induced osteoclast formation is unclear. In this study, we show that neither titanium particles nor BMP-2 can induce osteoclast formation in RAW 264.7 mouse leukemic monocyte macrophage cells but that BMP-2 synergizes with titanium particles to enhance osteoclast formation in the presence of RANKL, and that at a low concentration, BMP-2 has an optimal effect to stimulate the size and number of multinuclear osteoclasts, expression of osteoclast genes, and resorption area. Our data also clarify that the effects caused by the increase in BMP-2 on phosphorylated SMAD levels such as c-Fos expression increased throughout the early stages of osteoclastogenesis. BMP-2 and titanium particles stimulate the expression of p-JNK, p-P38, p-IkB, and P50 compared with the titanium group. These data suggested that BMP-2 may be a crucial factor in titanium particle-mediated osteoclast formation.

Studies on some precursors involved in meat flavour formation

The effect of some precursors on the formation of meat flavour during heating has been investigated. A comparison of the influence of three different precursors, inosine-5'-monophosphate (5'-IMP), cysteine and thiamine, added to the meat systems, showed that formation of certain heterocyclic compounds, like sulfur-containing furans, dithiolanones and thiophenes, was significantly affected by changes in the concentration of precursors. However, aliphatic compounds, such as hydrocarbons, alcohols and ketones were not changed by these additions. Inosine-5'-monophosphate was established to be more effective than cysteine or thiamine in the formation of some "meaty" volatiles, i.e. the furanthiols, when its concentration was increased 10 times in raw meat.

Composição, proteólise, capacidade de derretimento e formação de "blisters" do queijo mussarela obtido pelos métodos tradicional e de ultrafiltração: composition, proteolysis, melting capacity and blisters formation

O objetivo deste trabalho foi comparar a composição, a proteólise, a capacidade de derretimento e a formação de "blisters" (bolhas) em queijos tipo Mussarela fabricados com retentado de leite (MR) de fator de concentração volumétrica (FCV) de 2,34:1, com um queijo Mussarela padrão (MP) fabricado com leite não ultrafiltrado. Foi realizado um ensaio de produção com 3 lotes de MR e um lote de MP. Determinou-se a composição do leite, retentado, soro, água de filagem e queijos e a proteólise, a capacidade de derretimento e a formação de "blisters" nos queijos com 7, 15, 30 e 60 dias de armazenamento refrigerado. MRs apresentaram maiores valores de pH e de porcentagem de cinzas e de proteína total e menores porcentagens de acidez titulável, gordura, gordura no extrato seco e sal quando comparadas a MP. Durante o tempo de estocagem, as MRs apresentaram menor proteólise e capacidade de derretimento, em todas as datas analisadas. A porcentagem de área coberta por 'blisters" na pizza e o diâmetro médio dos mesmos foram maiores na MP durante o primeiro mês de estocagem e depois ambos os tipos de queijos apresentaram comportamentos similares para estes 2 parâmetros.

The best practices in the formation phase of Sino-Finnish joint ventures in China: For Finnish software companies

This study discusses the formation phase of Chinese-Finnish joint ventures in China. The purpose of this thesis is to create best practices for Finnish software companies in forming a joint venture with a local Chinese company in China. Therefore, the main research question, in what are the best practices for forming Sino-Finnish joint ventures in China for Finnish software firms, is examined through four different themes within the joint venture formation phase; the motives, the partner se- lection, the choice of a joint venture type and joint venture negotiations. The theoretical background of the study consists of literature relating to the establishment process of Sino-Western joint ventures in China. The empirical research conducted for this study is based on the expert interviews. The empirical data was gathered via nine semi-structured interviews with both Chinese and Finnish experts in software and technology industry, who have experience or knowledge in establishing Sino-Finnish joint ventures in China. Thematic analysis was used to cat- egorize and interpret the interview data. In addition, a thematic network was built to act as a basis of the analysis. According to the main findings, the main motives for Finnish software companies to establish a joint venture in China are lack of skills or experience, little resources to enter on their own, and China’s large market. The main motives for Chinese companies are to gain new technology or man- agerial skills, and expand internationally. The intellectual property rights (IPR) have recently im- proved a lot in China, but the Finnish companies’ knowledge on IPR is inadequate. The Finnish software companies should conduct a market and industry research in order to understand their po- sition in the market and to find a suitable location and potential joint venture partners. It is essential to define partner selection criteria and partner attributes. In addition, it is important to build the joint venture around complementary motives and a win-win situation between the joint venture partners. The Finnish companies should be prepared that the joint venture negotiations will be challenging and they will take a long time. The challenges can be overcome by gaining understanding about the Chinese culture and business environment. The findings of this study enhance understanding of the joint venture formation phase in China. This study provides guidelines for Finnish software companies to establish a joint venture in China. In addition, this study brings new insights to the Sino-Western joint venture literature with its soft- ware industry context. Future research is, however, necessary in order to gain an understanding of the advantages and disadvantages of a joint venture as an entry mode into China for Finnish soft- ware companies

Effects of grilling on cholesterol oxide formation and fatty acids alterations in fish

Due to the adverse effects of the cholesterol oxidation products for the human health, the search of the occurrence and the quantification of these compounds in foods are considered of great importance. In this paper the effect of grilling in hake and sardine on cholesterol oxides formation and fatty acids alterations was investigated. The main fatty acids determined in both fishes were docosahexaenoic (DHA), oleic, eicosapentaenoic (EPA) and palmitoleic. The total lipids, fatty acids and cholesterol contents were decreased significantly (p < 0.02) after thermal treatment, with simultaneous increase of the cholesterol oxides contents. The cholesterol oxides determined in both species in the present study were: 19-hydroxycholesterol, 24(S)-hydroxycholesterol, 22(S) hydroxycholesterol, 25-hydroxycholesterol, 25(R)-hydroxycholesterol and 7-ketocolesterol. Besides the presence of the cholesterol oxides in raw fishes, there were a greater number of products resulting from the oxidation of cholesterol side chain, a fact rarely observed in foods.

Tulevaisuuden lähtökohdista kansanvallan kolmiliittoon. Kansallinen Edistyspuolue ja kansallisen eheytymisen politiikka 1919–1939.

Kansallista Edistyspuoluetta ja sen toimijoita maailmansotien välisen Suomen sisäpolitiikassa tarkasteleva väitöstutkimus paneutuu puolueen kansallista eheytymistä ajaneen poliittisen linjan taustoihin, muodostumiseen ja toteutumiseen maailmansotien välisenä aikana vuosina 1919-1939. Vahvasti aineistopohjainen ja lähdekriittinen poliittisen historian tutkimus keskittyy parlamentaarisiin toimijoihin, poliittiseen kenttään ja näiden tuottamiin aineistoihin, kuten edistyspuolueen ja sen toimijoiden arkistoihin, lehdistöön ja valtiopäiväpöytäkirjoihin. Tutkimus selvittää, millainen oli edistyspuolueen kansallisen eheytymisen linja, mihin sillä pyrittiin, miten sitä toteutettiin ja miten se toteutui. Kansainvälisen vertailun kautta tutkimuksessa luodaan myös kuva suomalaisesta liberalismista ja liberalistista. Joulukuussa 1918 perustettu Kansallinen Edistyspuolue oli liberaali puolue, jonka politiikassa korostui erityisesti liberalismin sosiaalinen tulkinta. Puolueen sisäpoliittiseksi linjaksi vastaitsenäistyneessä ja sisällissodan runtelemassa valtiossa muodostui kansallisen eheytymisen edistäminen. Ajatuksen taustalla olivat K. J. Ståhlbergin tulevaisuuden lähtökohtia hahmotelleet artikkelit, jotka julkaistiin Helsingin Sanomissa huhtikuussa 1918 sisällissodan vielä riehuessa. Ståhlbergin mukaan kansalliseen eheytymiseen ei tullut pyrkiä sodan vuoksi vaan siitä huolimatta. Nuorsuomalaiselta puolueelta perityt liberaalit periaatteet täydentyivätkin edistyspuoluelaisessa ajattelussa sisällissodan ja tasavallan puolesta käydyn valtiomuototaistelun avainkokemuksilla. Itsenäisen Suomen ensimmäisiä vuosia hallinneissa keskustahallituksissa kansallista eheytymistä edistettiin sosiaalipoliittisin uudistuksin mm. oppivelvollisuus- ja asutuslakien muodossa. Myös sisällissodan vankien armahdukset olivat osa tätä ohjelmaa. Tutkimus osoittaa, että edistyspuolueen kansallisen eheytymisen politiikan keskeisenä tavoitteena oli poliittisen sovittelun kautta integroida vasemmisto osaksi parlamentaaris-demokraattista järjestelmää. Eheytyspolitiikan todellinen käyttöarvo ja edistyspuolueen poliittiset toimintamahdollisuudet alkoivat kuitenkin heiketä vuoden 1922 eduskuntavaalien jälkeen.Tutkimuksesta käy ilmi, että toteutettu eheytyspolitiikka ja sen osittainen epäonnistuminen näkyivät sekä kommunistien jatkuvana kannatuksena että sisäpoliittisen ilmapiirin oikeistolaistumisena. Tämä kehitys nosti myös edistyspuolueessa esille voimat, jotka suosivat porvariyhteistyötä ohi keskustavasemmistolaisen eheytyspoliittisen linjan. Alkuvuosien jälkeen valtiomuototaistelun koossapitävä voima heikkeni edistyspuolueen sisällä ja 1920-luvun puolivälissä käydyt linjakiistat osoittivat, että osalle puolueen jäsenistä vuoden 1918 puoluevalinnassa keskeisemmässä roolissa oli ollut tasavaltalaisuus kuin vasemmiston integrointi ja kansallinen eheytyminen. Edistyspuolueen johto ei kuitenkaan ollut valmis luopumaan eheytyspoliittisesta linjasta ja sen ympärille luodusta puolueidentiteetistä, joten porvariyhteistyötä kannattanut oikeisto-oppositio päätyi suurelta osin eroamaan puolueesta vuonna 1927. Tutkimus osoittaa, että parlamentarismin rapautuminen ja pienelle yleispuolueelle elintärkeiden yhteistyömahdollisuuksien heikkeneminen luokkapuolueiden puristuksessa johtivat edistyspuolueen kannatuksen alamäkeen sotien välisenä aikana. Se kutistui 26 kansanedustajan keskisuuresta puolueesta vain kuuden edustajan pienpuolueeksi. Puolueidentiteetin vahvuus ja keskeisten toimijoiden puolueen kokoa suurempi poliittinen painoarvo pitivät sen lakkauttamispohdinnoista huolimatta kuitenkin koossa ja kiinni politiikan ytimessä. Oikeistoradikalismin vuodet 1920–1930-lukujen taitteessa olivat edistyspuolueellesekä uhka että mahdollisuus. Tutkimuksessa käy ilmi, että vaikka kommunisminvastaisen kansanliikkeen vaatimukset olivat edistyspuoluelaisten mielestä oikeutettuja, oli kansanliikkeen niiden ajamiseksi omaksumia laittomia ja ulkoparlamentaarisia keinoja vaikea hyväksyä. Eheytyspolitiikan kannalta katsottuna melkotoivottamalta näyttänyt tilanne kääntyi kuitenkin lopulta voitoksi: äärivasemmisto eliminoitiin, äärioikeisto ajautui paitsioon ja tie maltillisen vasemmiston ja keskustan yhteistyölle aukesi jälleen. Tämä johti lopulta vuonna 1937 punamultahallitukseen ja kansanvallan kolmiliittoon Kansallisen Edistyspuolueen, SDP:n ja Maalaisliiton kesken. Kokemus siitä, että itsenäisyys oli alati uhattuna, toi suomalaiseen liberalismiin varsin nationalistisia piirteitä, joita eurooppalaisten veljespuolueiden ohjelmista ei löydy. Liberalismiin usein liitetty mielleyhtymä sen kosmopoliittisesta, kansallisvaltioita ylittävästä luonteesta jäi Suomessa sotien välisenä aikana nationalismin ja itäisen naapurin luoman uhan varjoon. Suomen sisäpoliittinen tilanne ja geopoliittinen asema loivat vaatimuksen vahvasta kansallisesta yhtenäisyydestä. Suomalainen liberalismi määrittyikin eurooppalaisia vastineitaan voimakkaammin nuorta valtiota hallinneen kansallisuusajattelun, itsesäilytysvaiston ja kansallisen eheyden vaatimusten kautta. Tutkimuksessa todetaan, että edistyspuolueen eheytyspoliittisen linjan muotoutumista ja toteutumista vuosien 1919‒1939 aikana voi pitää idealismin voittona realismista. Lukuun ottamatta reformipolitiikan vuosia edistyspuolueen pitäytyminen valitulla linjalla näyttäytyi poliittisten toimintamahdollisuuksien kannalta katsottuna ajoittain jopa epärealistiselta. Koko sotien välistä aikaa tarkastellessa voikin todeta, että se, minkä edistyspuolue poliittisten päämäärien saavuttamisen valossa voitti, sen se menetti kannatusluvuissa.

The Formation Of Internationalization Strategies Within The Construction Industry:Vision and Strategy

Internationalization represents a complex topic that has been researched for quite some time. However, since it continues to be extremely current a topic, its significance has not diminished, but maybe even increased in importance. Companies today face extreme pressure to enter new markets in the hope of growing, becoming more profitable, increasing market share, attracting new customers and meeting the requirements of its share- and stakeholders. In the increasingly global business environment of today, companies are facing both challenges and possible advantages of internationalization. Few companies are not operating internationally and it is becoming the question of ‘Why not?’ rather than ‘Why?’ to internationalize business operations. Internationalization and the importance of strategy are discussed in this research from the viewpoint of three case companies that were interviewed about internationalization strategies. This research project is a qualitative study that answers the research question of How is a business strategy constructed for entering a new market? The sub-questions are • How are goals set and what indicators are used to monitor the achievement of these goals? • What are the key characteristics of a strategy implementation process? The research method chosen for this study is a multiple-case study. Three case companies were chosen for the interviews in order to gain in-depth data of internationalization strategies within the construction industry.

Formation of the Employer Brand Image

The purpose of this study was to explore the employer brand image and its formation of a Finnish (yet international) service company in B2B sector. In the research qualitative case study method was used to explore the most preferred attributes in employer attraction, the employer brand perceptions towards the case company, and the effectors behind these brand perceptions among the prospective group of employees. The research was conducted through in-depth semistructured interviews among 23-30 undergraduate or graduate business students in Finnish universities close to their graduation. After deriving the attributes of an attractive employer, and exploring their relation to the case company, the employer brand image of the case company was determined and its attractiveness level evaluated. Moreover, the formation of the employer brand image was investigated and its sources detected. The most important factors for the target group in employer attractiveness were found to be company reputation and company culture/work atmosphere. Also career opportunities and international opportunities were seen important. The case company was found to hold a positive, attractive image on company culture and international opportunities, but failing to hold a good reputation as a fair employer. The main and most impactful source of employer brand image was former and current employees - directly or indirectly. Company’s own actions played only small part in employer brand formation as credibility is a critical factor in brand image formation and corporate communication found not to be perceived genuine. Based on the findings, suggestions for further employer branding were made.

Bacterial adhesion and biofilm formation on monolithic zirconia

Tutkimuksen tavoitteena oli selvittää bakteerien kiinnittymistä ja bakteeribiofilmin muodostumista implanttimateriaalien pinnalla. Monoliittisen zirkonian ja lasikeramien käyttö implanttikruunujen materiaaleina kasvaa jatkuvasti. Zirkoniaa käytetään myös abutmenttien materiaalina esteettisillä alueilla. Tällä hetkellä on vain vähän tutkimustietoa näiden implanttikruunumateriaalien sekä implanttikruunujen sementoimiseen käytetyn sementin pinnalla tapahtuvasta bakteeriadheesiosta ja biofilmin muodostumisesta. Bakteerien adheesiota ja biofilmin muodistumista tutkittiin neljän eri materiaalin pinnalla. Tutkimuksessa käytetyt materiaalit olivat: (1) Litiumdisilikaatti (LDS; IPS e.max CAD, Ivoclar Vivadent,kontrolli), (2) Kokonaan stabiloitu zirkonia (FSZ; Prettau Anterior, Zirkonzahn), (3) Osittain stabiloitu zirkonia (PSZ; Katana, Noritake), ja (4) Kaksoiskovetteinen sementti (DCC; Multilink hybrid abutment cement, Ivoclar Vivadent). Kaikki tutkimuksessa käytetyt materiaalit valmisteltiin ja kiillotettiin valmistajien ohjeiden mukaisesti Tutkittavat pinnat inkuboitiin Streptococcus mutans-suspensiossa +37°C:ssä asteessa. Bakteeriadheesiotestissä inkubointiaika oli 30 minuuttia ja biofilmitestissä vastaava aika oli 24 tuntia. Materiaalien pintoja tarkasteltiin myös elektronimikroskooppia käyttäen. Tutkimuksessa todettiin, että bakteeriadheesiossa oli eroja eri materiaalien välillä. Biofilmin. muodostumisessa ei todettu tilastollisesti merkittäviä eroja tutkittavien materiaalien välillä.