Apoptoosi Alzheimerin taudin aiheuttajana

Tiivistelmä. Tämä kirjallisuustutkielma käsittelee apoptoosin roolia Alzheimerin taudin synnyssä ja kehityksessä. Ihmisen aivot ovat kompleksinen systeemi, jonka toimintaa ei täysin tunneta. Aivojen toiminnan keskiössä ovat kuitenkin hermosolut, neuronit, joita esiintyy aivojen lisäksi myös muualla kehossa. Hermosolujen tärkein tehtävä on viestien kuljettaminen solujen välillä. Niiden tai niiden toiminnan etenevä väheneminen eli hermostollinen rappeuma on keskeinen aivosairauksien, kuten muistisairauksien, aiheuttaja. Alzheimerin tauti on maailman yleisin muistisairaus. Alzheimerin tauti rappeuttaa aivoja edeten yleensä ohimolohkojen sisäosista aivokuorelle. Sen on todettu olevan dementian eli laaja-alaisen muistin ja muun kognitiivisen toimintakyvyn heikkenemisen yleisin aiheuttaja. Lukuisista tutkimuksista huolimatta taudin perimmäistä syytä ei täysin tunneta. Tauti ei itsessään ole yleensä perinnöllinen, mutta sairastumisalttius saattaa olla. Eräs teoria sairauden aiheuttajasta on hermostollinen apoptoosi. Liiallinen tai liian vähäinen apoptoosi voi aiheuttaa solu- ja kudostyypin mukaan muun muassa neurodegeneratiivisia sairauksia, autoimmuunisairauksia ja erilaisia syöpiä

The solution structure of the amino-terminal domain of human DNA polymerase ε subunit B is homologous to C-domains of AAA+ proteins

DNA polymerases α, δ and ε are large multisubunit complexes that replicate the bulk of the DNA in the eukaryotic cell. In addition to the homologous catalytic subunits, these enzymes possess structurally related B subunits, characterized by a carboxyterminal calcineurin-like and an aminoproximal oligonucleotide/oligosaccharide binding-fold domain. The B subunits also share homology with the exonuclease subunit of archaeal DNA polymerases D. Here, we describe a novel domain specific to the N-terminus of the B subunit of eukaryotic DNA polymerases ε. The N-terminal domain of human DNA polymerases ε (Dpoe2NT) expressed in Escherichia coli was characterized. Circular dichroism studies demonstrated that Dpoe2NT forms a stable, predominantly α-helical structure. The solution structure of Dpoe2NT revealed a domain that consists of a left-handed superhelical bundle. Four helices are arranged in two hairpins and the connecting loops contain short β-strand segments that form a short parallel sheet. DALI searches demonstrated a striking structural similarity of the Dpoe2NT with the α-helical subdomains of ATPase associated with various cellular activity (AAA+) proteins (the C-domain). Like C-domains, Dpoe2NT is rich in charged amino acids. The biased distribution of the charged residues is reflected by a polarization and a considerable dipole moment across the Dpoe2NT. Dpoe2NT represents the first C-domain fold not associated with an AAA+ protein

Gender- and age-stratified analyses of ADHD medication use in children and adolescents in Finland using population-based longitudinal data, 2008-2018

Aims: This study examined medication use for attention-deficit/hyperactivity disorder (ADHD) among children and adolescents by gender in Finland during 2008-2018. Methods: Aggregated data on medication use for ADHD from 2008 to 2018 were extracted from the nationwide register on reimbursed prescriptions. The annual prevalence of ADHD medication use was calculated as the number of children (6-12 years) and adolescents (13-17 years) per calendar year with at least one ADHD medication purchase divided by the number of children and adolescents in the population. Population prevalence for children was also examined by birth month. Results: In 2008, the prevalence rates for males were 1.26% in children and 0.93% in adolescents, and for females 0.21% and 0.14%, respectively. In 2018, the prevalence rates for males were 4.42% in children and 4.21% in adolescents, and for females 0.99% and 1.28%, respectively. Male-to-female ratios decreased during the study period from 6.0:1 to 4.5:1 (children) and from 6.6:1 to 3.3:1 (adolescents). ADHD medication use was more common among males and females (aged 6-12 years) born in May-August or September-December than among males and females born in January-April. Conclusions: The prevalence of ADHD medication use has continued to increase in Finland. Although use has increased more rapidly among females resulting in lower male-to-female ratios, medication use among females is considerably lower compared with males. Consequently, gender discrepancy in 2018 was relatively large, particularly among children. Future studies should also consider reporting annual prevalence by children's birth month

Children's Relative Age and ADHD Medication Use : A Finnish Population-Based Study

Using population-based register data, we examine the association between children's birth month and ADHD medication use in a single jurisdiction (Finland). OBJECTIVES: The youngest children in a classroom are at increased risk of being medicated for attention-deficit/hyperactivity disorder (ADHD). We examined the association between children's birth month and ADHD medication rates in Finland. METHODS: Using a population-based study, we analyzed ADHD medication use among children born in 2005 to 2007. Cases (n= 7054) were identified from the first purchase of medication for ADHD. Cox proportional hazard models and hazard ratios (HRs) were examined by birth month and sex. Finnish children start first grade in the year of their seventh birthday. The cutoff date is December 31. RESULTS: Risk of ADHD medication use increased throughout the year by birth month (ie, January through April to May through August to September through December). Among boys born in September to December, the association remained stable across cohorts (HR: 1.3; 95% confidence interval [CI]: 1.1-1.5). Among girls born in September to December, the HR in the 2005 cohort was 1.4 (95% CI: 1.1-1.8), whereas in the 2007 cohort it was 1.7 (95% CI: 1.3-2.2). In a restricted follow-up, which ended at the end of the year of the children's eighth birthday, the HRs for boys and girls born in September to December 2007 were 1.5 (95% CI: 1.3-1.7) and 2.0 (95% CI: 1.5-2.8), respectively. CONCLUSIONS: Relative immaturity increases the likelihood of ADHD medication use in Finland. The association was more pronounced during the first school years. Increased awareness of this association is needed among clinicians and teachers.Peer reviewe

Case report: bilateral Mooren ulcer in association with hepatitis C

Background: Mooren ulcer has been considered as an idiopathic autoimmune keratitis. However, it has been in some cases suggested to be associated with hepatitis C, although the evidence is very vague.Case presentation: We present a case of a man who was diagnosed with a primary Mooren ulcer in his right eye. The eye became blind despite of intensive treatment with local medications and extensive surgical procedures. After 10 years, the patient was diagnosed with the same disease, now in his left, previously healthy eye. There was no history that would suggest a secondary Mooren ulcer, but a chronic hepatitis C infection was detected. Treatment was targeted against hepatitis C (ribavirin and interferon) in addition to immunosuppressive medical and surgical treatment which resulted in a full and more than 6 years lasting remission of the disease.Conclusions: Whether the immunomodulatory and immunosuppressive medication against hepatitis C was the key reason for the good results in the treatment of the second eye, remains elusive. The causality of hepatitis C with respect to the pathogenesis of Mooren ulcer on this patient remains open, but should be considered as one of the possible etiological factors of the disease

The role of low volatile organics on secondary organic aerosol formation

Large-scale atmospheric models, which typically describe secondary organic aerosol (SOA) formation based on chamber experiments, tend to systematically underestimate observed organic aerosol burdens. Since SOA constitutes a significant fraction of atmospheric aerosol, this discrepancy translates into an underestimation of SOA contribution to radiative forcing of atmospheric aerosol. Here we show that the underestimation of SOA yields can be partly explained by wall losses of SOA forming compounds during chamber experiments. We present a chamber experiment where α-pinene and ozone are injected into a Teflon chamber. When these two compounds react, we observe rapid formation and growth of new particles. Theoretical analysis of this formation and growth event indicates rapid formation of oxidized volatile organic compounds (OVOC) of very low volatility in the chamber. If these oxidized organic compounds form in the gas phase, their wall losses will have significant implications on their partitioning between the gas and particle phase. Although these OVOCs of very low volatility contribute to the growth of new particles, their mass will almost completely be depleted to the chamber walls during the experiment, while the depletion of OVOCs of higher volatilities is less efficient. According to our model simulations, the volatilities of OVOC contributing to the new particle formation event can be of the order of 10−5 μg m−3

Laminin γ2 fragments are increased in the circulation of patients with early phase acute lung injury

Katayama, M., Ishizaka, A., Sakamoto, M. et al. Intensive Care Med (2010) 36: 479. https://doi.org/10.1007/s00134-009-1719-

Bounce behavior of freshly nucleated biogenic secondary organic aerosol particles

The assessment of the climatic impacts and adverse health effects of atmospheric aerosol particles requires detailed information on particle properties. However, very limited information is available on the morphology and phase state of secondary organic aerosol (SOA) particles. The physical state of particles greatly affects particulate-phase chemical reactions, and thus the growth rates of newly formed atmospheric aerosol. Thus verifying the physical phase state of SOA particles gives new and important insight into their formation, subsequent growth, and consequently potential atmospheric impacts. According to our recent study, biogenic SOA particles produced in laboratory chambers from the oxidation of real plant emissions as well as in ambient boreal forest atmospheres can exist in a solid phase in size range >30 nm. In this paper, we extend previously published results to diameters in the range of 17–30 nm. The physical phase of the particles is studied by investigating particle bounce properties utilizing electrical low pressure impactor (ELPI). We also investigate the effect of estimates of particle density on the interpretation of our bounce observations. According to the results presented in this paper, particle bounce clearly decreases with decreasing particle size in sub 30 nm size range. The comparison measurements by ammonium sulphate and investigation of the particle impaction velocities strongly suggest that the decreasing bounce is caused by the differences in composition and phase of large (diameters greater than 30 nm) and smaller (diameters between 17 and 30 nm) particles

Can pions created in high-energy heavy-ion collisions produce a Centauro-type effect?

We study a Centauro-type phenomenon in high-energy heavy-ion collisions by assuming that pions are produced semiclassically both directly and in pairs through the isovector channel. The leading-particle effect and the factorization property of the scattering amplitude in the impact-parameter space are used to define the classical pion field. By analyzing the joint probability function $P_{II_{3}}(n_{0},n_{\_})$ for producing $n_{0}$ neutral and $n_{-}$ negative pions from a definite isospin state $II_{3}$ of the incoming leading-particle system we show that only direct production of pions without isovector pairs favors Centauro-type behavior. The presence of isovector pairs seems to destroy the effect. Our conclusion is supported through the calculation of two pion correlation parameters, $f_{2}^{0-}$ and $f_{2}^{00}$, and the average number of neutral pions $(_{n_{\_}})$ as a function of negative pions $(n_{\_})$ produced.Comment: 12 pages, 3 pictures, late