Ketjukyyn (Daboia russelii) myrkyn hyödyntäminen syöpätutkimuksessa

Tiivistelmä. Rintasyöpä on naisten yleisin syöpätyyppi. Vuonna 2018 siihen sairastui 2,1 miljoonaa naista ja maailmanlaajuisesti raportoitiin 627 000 rintasyövästä johtuvaa kuolemaa. Rintasyöpiä luokitellaan useisiin eri tyyppeihin ja sitä voidaan hoitaa leikkauksilla sekä säde- ja lääkehoidoilla. Nykyisissä rintasyöpähoidoissa on paljon haitallisia sivuvaikutuksia ja rintasyöpätutkimus pyrkiikin minimoimaan näiden haitallisten vaikutusten määrää kehittämällä jatkuvasti uusia hoitokeinoja. Nykyinen syöpätutkimus on kartoittanut luonnosta löytyvien aineiden, kuten käärmeenmyrkkyjen mahdollisuuksia syövän hoidossa. Nykyaikaiset menetelmät mahdollistavat mielenkiintoisten ja mahdollisesti lääketieteellistä potentiaalia omaavien aineiden eristämisen myrkyistä sekä niiden kokonaisvaltaisen ja yksityiskohtaisen tarkastelun. Muun muassa munuaisten toimintahäiriötä ja neuromuskulaarista halvausta puremallaan aiheuttavan Etelä-Aasian ketjukyyn (Daboia russelii) myrkystä on eristetty kaksi syövän hoidon kannalta mielenkiintoista ainetta, rusvinoksidaasi ja ruvipraasi. Molemmat näistä aineista osoittivat tutkimuksissa vaikuttavansa MCF-7 rintasyöpäsolulinjan soluihin indusoimalla apoptoosia, joka on syöpäsoluissa tyypillisesti estettynä. Indusointi tapahtui apoptoosin reittejä, kuten sisäistä ja ulkoista, sekä p52- ja p21-välitteistä reittiä pitkin. Tutkimuksissa on havaittu, että kyseiset aineet vaikuttavat apoptoosin indusointiin säätelemällä solussa esiintyvien apoptoottisten proteiinien määrää ja suhteita. Rusvinoksidaasi ja ruvipraasi aiheuttivat MCF-7 soluihin esimerkiksi pro-apoptoottisten proteiinien, kuten Bax:n ilmentämisen tehostumista. Rusvinoksidaasilla käsitellyissä MCF-7 soluissa havaittiin anti-apoptoottisen Bcl-xl-proteiinin ilmentämisen laskua ja ruvipraasilla käsitellyissä soluissa anti-apoptoottisen Bcl2-proteiinin ekspression laskua. Tämänkaltaiset apoptoosia säätelevien proteiinien määrien muutokset indusoivat soluissa apoptoosia, joka tunnistettiin esimerkiksi fragmentoituneesta ja tiivistyneestä DNA:sta. Tutkimusten perusteella rusvinoksidaasia ja ruvipraasia pidetään potentiaalisina aineina syöpähoidoille niiden apoptoosia indusoivan luonteen takia, mutta aineiden tarkempi prekliininen arviointi on vielä tarpeen ennen ihmistestaukseen siirtymistä. Esimerkiksi laajemmat in vivo -testaukset, joissa selvitetään aineiden farmakokineettisiä sekä farmakodynaamisia ominaisuuksia, ovat tarpeellisia. Erityisesti yksityiskohtaisten vaikutuskohteiden, kuten solukalvon reseptorien, paikantaminen on kriittistä, kun halutaan saada syöpälääkkeistä aiempaa spesifimpiä. Rusvinoksidaasin, ruvipraasin sekä muiden käärmeenmyrkyistä löydettyjen farmakologisten aineiden laaja-alaista tutkimusta lähitulevaisuudessa tukevat poikkitieteelliset tutkimusryhmät sekä jatkuvasti uudistuva tieteellinen data aihepiiriin liittyen

Embracing complexity in international forest governance: a way forward; Policy Brief

This Policy Brief summarizes the findings of a comprehensive assessment of scientific information about international forest governance carried out by an Expert Panel of over 30 of the world's leading scientists working in the areas of environmental governance and international forest law. It aims to provide policy and decision makers with essential knowledge and building blocks required for a more effective and inclusive governance of the world's forest

Precise determination of the hyperfine parameters of europium in multifluorite perovskites by 151Eu Mössbauer spectroscopy

The hyperfine interactions at the europium lattice sites in samples of the homologous (Fe,Cu)Sr2(Eu,Ce)nCu2O4+2n+z (n=2,3) series were studied by Eu151 Mössbauer spectroscopy. The work was motivated by the search for new superconducting phases. This homologous series is based on the YBa2Cu3O7−δ (1:2:3) structure. The samples used in the Mössbauer measurements consisted of crystallites with random orientation and grain oriented crystallites. The texture of oriented samples was analyzed by x-ray diffraction. The complete quadrupole Hamiltonian of the 21.5-keV γ-transition of Eu151 was successfully applied in the analyses of all the Mössbauer spectra. In samples having n≤2 the europium atoms occupy a single lattice site, whereas the spectra of the n=3 samples exhibit hyperfine interactions of the two different europium sites. Analyzing the hyperfine parameters of the latter samples was made possible by simultaneous fitting of three spectra, corresponding to three different crystal orientations of the same specimen. This fitting scheme also enables more precise determination of the hyperfine parameters in the n=2 samples. In these samples an electric field gradient (EFG), with a large negative-valued main component (Vzz) parallel with the crystal c axis, was found. In the n=3 samples, the two EFG’s of the europium sites were found to have Vzz components of opposite signs. The negative Vzz value was attributed to the rare-earth site adjacent to the CuO layer. This site, found in all samples of the series, corresponds to the rare-earth site of the 1:2:3 system.Peer reviewe

Regional brain morphometry in patients with traumatic brain injury based on acute- and chronic-phase magnetic resonance imaging.

Traumatic brain injury (TBI) is caused by a sudden external force and can be very heterogeneous in its manifestation. In this work, we analyse T1-weighted magnetic resonance (MR) brain images that were prospectively acquired from patients who sustained mild to severe TBI. We investigate the potential of a recently proposed automatic segmentation method to support the outcome prediction of TBI. Specifically, we extract meaningful cross-sectional and longitudinal measurements from acute- and chronic-phase MR images. We calculate regional volume and asymmetry features at the acute/subacute stage of the injury (median: 19 days after injury), to predict the disability outcome of 67 patients at the chronic disease stage (median: 229 days after injury). Our results indicate that small structural volumes in the acute stage (e.g. of the hippocampus, accumbens, amygdala) can be strong predictors for unfavourable disease outcome. Further, group differences in atrophy are investigated. We find that patients with unfavourable outcome show increased atrophy. Among patients with severe disability outcome we observed a significantly higher mean reduction of cerebral white matter (3.1%) as compared to patients with low disability outcome (0.7%)

Integrating databases for research on health and performance in small animals and horses in the Nordic countries

In a world of limited resources, using existing databases in research is a potentially cost-effective way to increase knowledge, given that correct and meaningful results are gained

Potential of heart fatty-acid binding protein, neurofilament light, interleukin-10 and S100 calcium-binding protein B in the acute diagnostics and severity assessment of traumatic brain injury

Background: There is substantial interest in blood biomarkers as fast and objective diagnostic tools for traumatic brain injury (TBI) in the acute setting. Methods: Adult patients (≥18) with TBI of any severity and indications for CT scanning and orthopaedic injury controls were prospectively recruited during 2011–2013 at Turku University Hospital, Finland. The severity of TBI was classified with GCS: GCS 13–15 was classified as mild (mTBI); GCS 9–12 as moderate (moTBI) and GCS 3–8 as severe (sTBI). Serum samples were collected within 24 hours of admission and biomarker levels analysed with high-performance kits. The ability of biomarkers to distinguish between severity of TBI and CT-positive and CT-negative patients was assessed. Results: Among 189 patients recruited, neurofilament light (NF-L) was obtained from 175 patients with TBI and 40 controls. S100 calcium-binding protein B (S100B), heart fatty-acid binding protein (H-FABP) and interleukin-10 (IL-10) were analysed for 184 patients with TBI and 39 controls. There were statistically significant differences between levels of all biomarkers between the severity classes, but none of the biomarkers distinguished patients with moTBI from patients with sTBI. Patients with mTBI discharged from the ED had lower levels of IL-10 (0.26, IQR=0.21, 0.39 pg/mL), H-FABP (4.15, IQR=2.72, 5.83 ng/mL) and NF-L (8.6, IQR=6.35, 15.98 pg/mL) compared with those admitted to the neurosurgical ward, IL-10 (0.55, IQR=0.31, 1.42 pg/mL), H-FABP (6.022, IQR=4.19, 20.72 ng/mL) and NF-L (13.95, IQR=8.33, 19.93 pg/mL). We observed higher levels of H-FABP and NF-L in older patients with mTBI. None of the biomarkers or their combinations was able to distinguish CT-positive (n=36) or CT-negative (n=58) patients with mTBI from controls. Conclusions: S100B, H-FABP, NF-L and IL-10 levels in patients with mTBI were significantly lower than in patients with moTBI and sTBI but alone or in combination, were unable to distinguish patients with mTBI from orthopaedic controls. This suggests these biomarkers cannot be used alone to diagnose mTBI in trauma patients in the acute setting. Data availability statement: Data are available on reasonable request. De-identified clinical, imaging and biochemical data not published within the article can be shared with a qualified investigator by request

What Determines the Innovation Capability of Firm Founders?

Innovative start-ups, not start-ups in general, seem to be important drivers of economic growth. However, little is known about how such firms look like. As activities of start-ups are strongly related to firm founders, we investigate this question focusing on the innovation capability of firm founders. We find that the combination of different founder characteristics such as university education (at best a combination of technical and commercial education), prior experience in R&D, and strong motivation to realize own innovative ideas increases innovative activities of start-ups by more than 40%

Mitigation of Moral Hazard and Adverse Selection in Venture Capital Financing: The Influence of the Country’s Institutional Setting

A venture capitalist (VC) needs to trade off benefits and costs when attempting to mitigate agency problems in their investor-investee relationship. We argue that signals of ventures complement the VC’s capacity to screen and conduct a due diligence during the pre-investment phase, but its attractiveness may diminish in institutional settings supporting greater transparency. Similarly, whereas a VC may opt for contractual covenants to curb potential opportunism by ventures in the post-investment phase, this may only be effective in settings supportive of shareholder rights enforcement. Using an international sample of VC contracts, our study finds broad support for these conjectures. It delineates theoretical and practical implications for how investors can best deploy their capital in different institutional settings whilst nurturing their relationships with entrepreneurs