Tulevaisuuden yhteysalusliikenne: selvitys kehittämistarpeista

Saaristoliikenteen järjestämisestä säädellään laissa saariston kehityksen edistämisessä (494/1981). Lain 5 §:n mukaan valtion on pyrittävä huolehtimaan siitä, että saariston vakinaisella väestöllä on käytettävissään asumisen, toimeentulon ja välttämättömän asioinnin kannalta tarpeelliset liikenne- ja kuljetuspalvelut, sekä siitä, että nämä palvelut ovat mahdollisimman joustavat ja ilmaiset tai hinnaltaan kohtuulliset.Saaristoliikenteeseen, erityisesti yhteysalusliikenteeseen, kohdistuu monia kehittämistoiveita niin saaristolaisten, palvelun tarjoajien kuin palvelun tilaajan näkökulmasta. Yhteysalusliikenteen aluskanta on vanhaa, reitit eivät vastaa kaikilta osin käyttäjien tarpeita, ja myös saaristolaissa oleva kirjaus saaristoliikenteen järjestämisestä koetaan monin osin haasteelliseksi ja vaikeaksi toteuttaa. Saaristoasiain neuvottelukunnan tilaamassa Tulevaisuuden yhteysalusliikenne -selvityksessä keskitytään yhteysalusliikenteen tulevaisuuden näkymiin niin alustekniikan, -turvallisuuden kuin ympäristövaatimusten näkökulmasta. Lisäksi selvityksessä tarkastellaan digitalisaation tarjoamia mahdollisuuksia sekä yhteysalusliikenteen eri rahoitus- ja hallintomalleja.Selvityksessä luodaan myös näkymiä tulevaisuuden saaristoon yhteysalusliikenteen näkökulmasta.Selvitys antaa ajantasaista tietoa saariston yhteysalusliikenteen kehittämiseksi.</p

GluA4 Dependent Plasticity Mechanisms Contribute to Developmental Synchronization of the CA3-CA1 Circuitry in the Hippocampus

During the course of development, molecular mechanisms underlying activity-dependent synaptic plasticity change considerably. At immature CA3-CA1 synapses in the hippocampus, PKA-driven synaptic insertion of GluA4 AMPA receptors is the predominant mechanism for synaptic strengthening. However, the physiological significance of the developmentally restricted GluA4-dependent plasticity mechanisms is poorly understood. Here we have used microelectrode array (MEA) recordings in GluA4 deficient slice cultures to study the role of GluA4 in early development of the hippocampal circuit function. We find that during the first week in culture (DIV2-6) when GluA4 expression is restricted to pyramidal neurons, loss of GluA4 has no effect on the overall excitability of the immature network, but significantly impairs synchronization of the CA3 and CA1 neuronal populations. In the absence of GluA4, the temporal correlation of the population spiking activity between CA3-CA1 neurons was significantly lower as compared to wild-types at DIV6. Our data show that synapse-level defects in transmission and plasticity mechanisms are efficiently compensated for to normalize population firing rate at the immature hippocampal network. However, lack of the plasticity mechanisms typical for the immature synapses may perturb functional coupling between neuronal sub-populations, a defect frequently implicated in the context of developmentally originating neuropsychiatric disorders.Peer reviewe

Ecosystem responses to increased organic carbon concentration: comparing results based on longterm monitoring and whole-lake experimentation

Recent increases in terrestrial dissolved organic carbon (DOC) concentrations in northern inland waters have many ecological consequences. We examined available data on carbon cycles and food webs of 2 boreal headwater lakes in southern Finland. Basic limnology and catchment characteristics of a pristine lake, Valkea-Kotinen (VK), were monitored over the past 25 years while the lake has undergone browning and DOC increased from similar to 11 to 13 mg L-1. Pronounced changes in the early 2000s represent a regime shift in DOC concentration and color. Lake Alinen Mustajarvi (AM) was manipulated for 2 years by additions of labile DOC (cane sugar), raising the DOC concentration from similar to 10 to 12 mg L-1, but not changing light conditions. The 2 different approaches both revealed increased concentrations and efflux of carbon dioxide (CO2) from the lakes and thus net heterotrophy and changes in the pelagic community structure following an increase in DOC concentration. Long-term monitoring of VK revealed a decline in phytoplankton primary production (PP) along with browning, which was reflected in retarded growth of young (1-2-year-old) perch. In the experimentally manipulated lake (AM), PP was not affected, and the growth of young perch was more variable. The results suggested the importance of a pathway from labile DOC via benthic invertebrates to perch. Although provided with this extra resource, the food chain based on DOC proved inefficient. Long-term monitoring and whole-lake experimentation are complementary approaches for revealing how freshwater ecosystems respond to climate and/or atmospheric deposition-induced changes, such as browning.Peer reviewe

Comparative analysis of COVID-19 vaccine responses and third booster dose-induced neutralizing antibodies against Delta and Omicron variants

Vaccination shows efficacy in protecting from COVID-19, but regime and dosing optimization is still ongoing. Here the authors show that BNT162b2, mRNA-1273, or their combination with ChAdOx1 induces similar antibody responses, and those receiving three doses of BNT162b2 induce neutralizing antibodies against the Omicron variant. Two COVID-19 mRNA (of BNT162b2, mRNA-1273) and two adenovirus vector vaccines (ChAdOx1 and Janssen) are licensed in Europe, but optimization of regime and dosing is still ongoing. Here we show in health care workers (n = 328) that two doses of BNT162b2, mRNA-1273, or a combination of ChAdOx1 adenovirus vector and mRNA vaccines administrated with a long 12-week dose interval induce equally high levels of anti-SARS-CoV-2 spike antibodies and neutralizing antibodies against D614 and Delta variant. By contrast, two doses of BNT162b2 with a short 3-week interval induce 2-3-fold lower titers of neutralizing antibodies than those from the 12-week interval, yet a third BNT162b2 or mRNA-1273 booster dose increases the antibody levels 4-fold compared to the levels after the second dose, as well as induces neutralizing antibody against Omicron BA.1 variant. Our data thus indicates that a third COVID-19 mRNA vaccine may induce cross-protective neutralizing antibodies against multiple variants.Peer reviewe

No evidence of RET germline mutations in familial pituitary adenoma

Pituitary adenomas are common in the general population. Although most of them are sporadic, some occur in a familial setting. In familial pituitary adenoma patients it is common that no germline defects are found after screening of aryl hydrocarbon receptor interacting protein (AIP) and other genes known to underlie the condition, suggesting the existence of yet unknown predisposition genes. Recently, the RET proto-oncogene was found to be a novel in vivo interaction partner of AIP in the pituitary gland. Here, we have screened patients from 16 AIP mutation negative (AIPmut-) pituitary adenoma families for RET germline mutations to assess whether RET could play a role in pituitary adenoma predisposition, similar to AIP. We found five novel germline RET changes: one in RET Exon 4 and the rest in noncoding regions of RET. Two changes, c.1560*G&gt;A and -1285G&gt;A, were segregated in affected family members. We also analyzed the RET region with enhancer element locator (EEL) to identify RET regulatory elements, and to see whether the changes resided in these. None of the variants mapped to the regions predicted by EEL. Expression of RET was examined in ten AIPmut- and seven AIP mutation positive (AIPmut+) somatotropinomas by immunohistochemistry, with a trend showing reduced expression in the latter (P=0.05). We conclude that the RET variants are presumably not related to pituitary adenoma predisposition, although reduced RET expression may play a role in AIP-related genesis of somatotropinomas.</p

Candidate driver genes in microsatellite-unstable colorectal cancer

Defects in the mismatch repair system lead to microsatellite instability (MSI), a feature observed in similar to 15% of all colorectal cancers (CRCs). Microsatellite mutations that drive tumourigenesis, typically inactivation of tumour suppressors, are selected for and are frequently detected in MSI cancers. Here, we evaluated somatic mutations in microsatellite repeats of 790 genes chosen based on reduced expression in MSI CRC and existence of a coding mononucleotide repeat of 6 similar to 10 bp in length. All the repeats were initially sequenced in 30 primary MSI CRC samples and whenever frameshift mutations were identified in &gt;20%, additional 70 samples were sequenced. To distinguish driver mutations from passengers, we similarly analyzed the occurrence of frameshift mutations in 121 intronic control repeats and utilized a statistical regression model to determine cut-off mutation frequencies for repeats of all types (A/T and C/G, 610 bp). Along with several know target genes, including TGFBR2, ACVR2, and MSH3, six novel candidate driver genes emerged that harbored significantly more mutations than identical control repeats. The mutation frequencies in 100 MSI CRC samples were 51% in G8 of GLYR1, 47% in T9 of ABCC5, 43% in G8 of WDTC1, 33% in A8 of ROCK1, 30% in T8 of OR51E2, and 28% in A8 of TCEB3. Immunohistochemical staining of GLYR1 revealed defective protein expression in tumors carrying biallelic mutations, supporting a loss of function hypothesis. This is a large scale, unbiased effort to identify genes that when mutated are likely to contribute to MSI CRC development.</p