Iin vanhan Haminan hautausmaan naisvainaja CH36 ja hänen kasvorekonstruktionsa

Tiivistelmä. Pro gradu -tutkielmani otsikko on ”Iin vanhan Haminan naisvainaja CH36 ja hänen kasvorekonstruktionsa”. Tutkielmassani tarkastelen Iin vanhan Haminan vuoden 2009 arkeologisissa kaivauksissa löydettyä naisvainajaa CH36 ja toteutan työssäni myös hänen kasvorekonstruktionsa. Alueen ihmisistä ei ole aikaisemmin tehty kasvorekonstruktioita ja tekemäni rekonstruktio on kolmas, joka on tehty suomalaisesta aineistosta. Ensimmäisen kasvorekonstruktion suomalaisesta aineistosta on tehnyt pro gradu ohjaajani Sirpa Niinimäki. Hän toteutti rekonstruktion osana oma pro gradu -työtään vuonna 2004. Toinen suomalaisesta aineistosta tehty kasvorekonstruktio on Heidi Kuivaniemi-Smithin tietokoneella toteuttama kasvorekonstruktio vuodelta 2018. Pro gradussani tutkimuskysymyksiä ovat muun muassa seuraavat: Miten rekonstruktion eri vaiheissa tehdyt valinnat vaikuttavat lopputulokseen? Tämä kysymys jakautuu alakysymyksiin: Miten vainajan CH36 kasvorekonstruktio voidaan toteuttaa? Miten kasvorekonstruktion teko onnistui? Tutkimusongelmani käsittelee eniten kasvorekonstruktion tekoon liittyviä seikkoja, kuten menetelmien valintaa. Työssäni kerron myös jonkin verran kasvorekonstruktioiden historiasta, Iin vanhan Haminan kaivauksista ja vainajan CH36 tutkimushistoriasta. Vainaja CH36 on todennäköisesti tunnetuin ja tutkituin kaivauksilta löytynyt vainaja, koska hänet oli haudattu harvinaisen pronssisen ristin kanssa. Vainajan CH36 luut ovat erittäin huonossa kunnossa ja niiden kunto huononee koko ajan, siksi olikin tärkeää tehdä kasvorekonstruktio juuri nyt. Kasvorekonstruktioiden historia alkoi tuhansia vuosia sitten. Modernien kasvorekonstruktioiden historia alkoi kuitenkin vain parisataa vuotta sitten. Kasvorekonstruktioista on olemassa kolme koulukuntaa, joista nykyisin eniten käytetään Manchesterin metodia, joka yhdistelee kahden muun koulukunnan käyttämiä menetelmiä. Toteutin vainaja CH36:n rekonstruktion kuitenkin hyödyntäen amerikkalaisen koulukunnan metodia. Siinä keskitytään kudosten paksuuksiin ja jätetään lihasten yksittäinen rekonstruointi tekemättä. Valitsin amerikkalaisen metodin, koska toteutin rekonstruktion piirtämällä ja yksittäisiä lihaksia on piirroksessa vaikea lisätä rekonstruktioon. Kasvorekonstruktioiden tekoon liittyen on olemassa kolme eri metodia. Näistä metodeista yleisin nykyään on kasvorekonstruktion teko tietokoneella. Itse kuitenkin toteutin rekonstruktion piirtämällä, suurimmaksi osaksi budjettisyistä. Osasyy oli kuitenkin myös luiden erittäin huono kunto. Kasvorekonstruktion tekoon liittyy monta eri vaihetta. Tärkeä vaihe ennen itse rekonstruktion aloitusta on luiden osteologinen analyysi. Vainajan CH36 osteologinen analyysi oli kuitenkin jo tehty, joten en tehnyt sitä osana omaa työtäni. Rekonstruktion aloitin kuvaamalla kallon. Tämän jälkeen muokkasin ottamani kuvat oikeaan kokoon ja tulostin ne. Näiden kuvien perusteella pystyin piirtämään vainajan CH36 kallon piirtopaperille. Tämän jälkeen lisäsin 13 eri kudospaksuuspistettä kallon piirroksen päälle, käyttäen apuna Niinimäen ja Karttusen mittaamia kudosten paksuuksia suomalaisille naisille. Seuraava vaihe oli kasvojen tärkeimpien piirteiden viimeistely, näihin kuuluu silmät, nenä ja suu. Kasvorekonstruktion viimeistelyyn kuuluu muun muassa hiusten, ripsien, kulmakarvojen ja ihon pinnan piirtäminen. Rekonstruktioni on kaksiulotteinen, joka hieman vaikeutti ihon kudospisteiden merkitsemistä ja ihon viimeistelemistä. Lopuksi piirsin henkilön kaulaan hänen kanssaan haudatun pronssiristin. Tekemäni kasvorekonstruktio on arkeologinen kasvorekonstruktio, eli aineistona on arkeologisilla kaivauksilla löydetty, noin 600 vuotta vanha aineisto. Tämän takia on lähes mahdotonta päätellä, onko piirrokseni vainajan CH36 näköinen vai ei. Käytin kuitenkin avuksi minulle saataville olevat tiedot kasvorekonstruktion teosta, joten uskon, että suoriuduin työstä hyvin. Yksi kasvorekonstruktioiden ongelma on myös se, että jokainen tekijä toteuttaa rekonstruktion hieman eri tavalla. Kasvorekonstruktiot ovatkin oikeastaan popularisoinnin keino, jonka tarkoitukseni on mielestäni saada tavalliset ihmiset kiinnostumaan historiasta. Tavalliset ihmiset ehkä kuvittelevat pääsevänsä kurkistamaan 600 vuotta sitten eläneen ihmisen elämään kasvorekonstruktioni avulla

Isolation of Intact and Functional Melanosomes from the Retinal Pigment Epithelium

Melanosomes of retinal pigment epithelium (RPE) have many vision supporting functions. Melanosome research would benefit from a method to isolate pure and characterized melanosomes. Sucrose gradient centrifugation is the most commonly used method for isolation of RPE melanosomes, but the isolated products are insufficiently characterized and their quality is unclear. Here we introduce a new gentle method for fractionation of porcine RPE that produces intact functional melanosomes with minimal cross-contamination from other cell organelles. The characterization of isolated organelles was conducted with several methods confirming the purity of the isolated melanosomal fraction (transmission electron microscopy, immunoblotting) and presence of the melanosomal membrane (fluorescence staining of melanosomal membrane, zeta potential measurement). We demonstrate that our isolation method produces RPE melanosomes with the ability to generate free phosphate (Pi) from ATP thereby proving that many membrane proteins remain functional after isolation. The isolated porcine RPE melanosomes represented V-type H(+)ATPase activity that was demonstrated with bafilomycin A1, a specific V-ATPase inhibitor. We anticipate that the isolation method described here can easily be optimized for the isolation of stage IV melanosomes from other pigmented cell types and tissues.Peer reviewe

A modular brain-on-a-chip for modelling epileptic seizures with functionally connected human neuronal networks

Epilepsies are a group of neurological disorders characterised by recurrent epileptic seizures. Seizures, defined as abnormal transient discharges of neuronal activity, can affect the entire brain circuitry or remain more focal in the specific brain regions and neuronal networks. Human pluripotent stem cell (hPSC)-derived neurons are a promising option for modelling epilepsies, but as such, they do not model groups of connected neuronal networks or focal seizures. Our solution is a Modular Platform for Epilepsy Modelling In Vitro (MEMO), a lab-on-chip device, in which three hPSC-derived networks are separated by a novel microfluidic cell culture device that allows controlled network-to-network axonal connections through microtunnels. In this study, we show that the neuronal networks formed a functional circuitry that was successfully cultured in MEMO for up to 98 days. The spontaneous neuronal network activities were monitored with an integrated custom-made microelectrode array (MEA). The networks developed spontaneous burst activity that was synchronous both within and between the axonally connected networks, i.e. mimicking both local and circuitry functionality of the brain. A convulsant, kainic acid, increased bursts only in the specifically treated networks. The activity reduction by an anticonvulsant, phenytoin, was also localised to treated networks. Therefore, modelling focal seizures in human neuronal networks is now possible with the developed chip.acceptedVersionPeer reviewe

Sequelae due to bacterial meningitis among African children: a systematic literature review

<p>Abstract</p> <p>Background</p> <p>African children have some of the highest rates of bacterial meningitis in the world. Bacterial meningitis in Africa is associated with high case fatality and frequent neuropsychological sequelae. The objective of this study is to present a comprehensive review of data on bacterial meningitis sequelae in children from the African continent.</p> <p>Methods</p> <p>We conducted a systematic literature search to identify studies from Africa focusing on children aged between 1 month to 15 years with laboratory-confirmed bacterial meningitis. We extracted data on neuropsychological sequelae (hearing loss, vision loss, cognitive delay, speech/language disorder, behavioural problems, motor delay/impairment, and seizures) and mortality, by pathogen.</p> <p>Results</p> <p>A total of 37 articles were included in the final analysis representing 21 African countries and 6,029 children with confirmed meningitis. In these studies, nearly one fifth of bacterial meningitis survivors experienced in-hospital sequelae (median = 18%, interquartile range (IQR) = 13% to 27%). About a quarter of children surviving pneumococcal meningitis and <it>Haemophilus influenzae </it>type b (Hib) meningitis had neuropsychological sequelae by the time of hospital discharge, a risk higher than in meningococcal meningitis cases (median = 7%). The highest in-hospital case fatality ratios observed were for pneumococcal meningitis (median = 35%) and Hib meningitis (median = 25%) compared to meningococcal meningitis (median = 4%). The 10 post-discharge studies of children surviving bacterial meningitis were of varying quality. In these studies, 10% of children followed-up post discharge died (range = 0% to 18%) and a quarter of survivors had neuropsychological sequelae (range = 3% to 47%) during an average follow-up period of 3 to 60 months.</p> <p>Conclusion</p> <p>Bacterial meningitis in Africa is associated with high mortality and risk of neuropsychological sequelae. Pneumococcal and Hib meningitis kill approximately one third of affected children and cause clinically evident sequelae in a quarter of survivors prior to hospital discharge. The three leading causes of bacterial meningitis are vaccine preventable, and routine use of conjugate vaccines could provide substantial health and economic benefits through the prevention of childhood meningitis cases, deaths and disability.</p

A pan-European epidemiological study reveals honey bee colony survival depends on beekeeper education and disease control

Reports of honey bee population decline has spurred many national efforts to understand the extent of the problem and to identify causative or associated factors. However, our collective understanding of the factors has been hampered by a lack of joined up trans-national effort. Moreover, the impacts of beekeeper knowledge and beekeeping management practices have often been overlooked, despite honey bees being a managed pollinator. Here, we established a standardised active monitoring network for 5 798 apiaries over two consecutive years to quantify honey bee colony mortality across 17 European countries. Our data demonstrate that overwinter losses ranged between 2% and 32%, and that high summer losses were likely to follow high winter losses. Multivariate Poisson regression models revealed that hobbyist beekeepers with small apiaries and little experience in beekeeping had double the winter mortality rate when compared to professional beekeepers. Furthermore, honey bees kept by professional beekeepers never showed signs of disease, unlike apiaries from hobbyist beekeepers that had symptoms of bacterial infection and heavy Varroa infestation. Our data highlight beekeeper background and apicultural practices as major drivers of honey bee colony losses. The benefits of conducting trans-national monitoring schemes and improving beekeeper training are discussed

Pharmacokinetic aspects of retinal drug delivery

Drug delivery to the posterior eye segment is an important challenge in ophthalmology, because many diseases affect the retina and choroid leading to impaired vision or blindness. Currently, intravitreal injections are the method of choice to administer drugs to the retina, but this approach is applicable only in selected cases (e.g. anti-VEGF antibodies and soluble receptors). There are two basic approaches that can be adopted to improve retinal drug delivery: prolonged and/or retina targeted delivery of intravitreal drugs and use of other routes of drug administration, such as periocular, suprachoroidal, sub-retinal, systemic, or topical. Properties of the administration route, drug and delivery system determine the efficacy and safety of these approaches. Pharmacokinetic and pharmacodynamic factors determine the required dosing rates and doses that are needed for drug action. In addition, tolerability factors limit the use of many materials in ocular drug delivery. This review article provides a critical discussion of retinal drug delivery, particularly from the pharmacokinetic point of view. This article does not include an extensive review of drug delivery technologies, because they have already been reviewed several times recently. Instead, we aim to provide a systematic and quantitative view on the pharmacokinetic factors in drug delivery to the posterior eye segment. This review is based on the literature and unpublished data from the authors' laboratory.Peer reviewe

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe