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Abstract Current therapeutics of endometriosis focus on hormonal disruption of endometriotic lesions (ectopic endometrium, EcE). Recent findings show higher glycolysis utilization in EcE, suggesting non-hormonal strategy for disease treatment that addresses cellular metabolism. Identifying metabolically altered cell types in EcE is important for targeted metabolic drug therapy without affecting eutopic endometrium (EuE). Here, using single-cell RNA-sequencing, we examine twelve metabolic pathways in paired samples of EuE and EcE from women with confirmed endometriosis. We detect nine major cell types in both EuE and EcE. Metabolic pathways are most differentially regulated in perivascular, stromal, and endothelial cells, with the highest changes in AMPK signaling, HIF-1 signaling, glutathione metabolism, oxidative phosphorylation, and glycolysis. We identify transcriptomic co-activation of glycolytic and oxidative metabolism in perivascular and stromal cells of EcE, indicating a critical role of metabolic reprogramming in maintaining endometriotic lesion growth. Perivascular cells, involved in endometrial stroma repair and angiogenesis, may be potential targets for non-hormonal treatment of endometriosis.

Kliimamuutused koos loodusliku mitmekesisuse vähenemisega on inimkonna käekäiku määravad globaalprobleemid ning kliimakriisi süvenemise aeglustamisel ja peatamisel on kliimamuutuste haridusel võtmetähtsus. Kliimamuutuste haridus nõuab terviklikku ja teaduspõhist käsitlust, sealhulgas sotsiaalteaduslike teemade käsitlemist kliimamuutuste kontekstis. Mitmed rahvusvahelised organisatsioonid, sh UNESCO, on algatanud kliimamuutuste hariduse edendamiseks erinevaid tegevusi, kuid paraku ei edene muutused hariduses soovitud tempos. Rahvusvahelisest teaduskirjandusest ilmneb, et õppekavad ei hõlma globaalmuutusi ning õpetajate ettevalmistus ei ole piisav, õpetamaks kliimamuutuste keerulisi ja läbipõimunud teemasid, nende inimtekkelisi põhjuseid, samuti kliimamuutustega kohanemise ja nende leevendamise strateegiaid. Sama kehtib ka Eesti kohta: kliimateadlikkuse projekti eri haridusastmete töörühmade koostatud analüüsidest selgus, et kliima- ja keskkonnaharidus ei ole kooskõlas Eesti ambitsioonikate keskkonnaeesmärkidega ning Eestis puudub lõimitud haridus- ja keskkonnapoliitika. Õpetajate professionaalses arengus ja täienduskoolituses on vaja pöörata kliimamuutuste haridusele senisest rohkem tähelepanu, sest vaatamata õpetajate huvile ja valmisolekule õpetada kliimamuutuste teemasid ei ole õpetajaid nende käsitlemiseks hästi ette valmistatud. Õppekavade ja koolipraktika uuendamine, tehnoloogiate lõimimine, projektide läbiviimine ning koolide keskkonnasõbralikkuse suurendamine on võtmetähtsusega, pakkumaks õpilastele kvaliteetset ja kaasahaaravat kliimamuutuste haridust. Summary

Eri õppeastmete õpetajate teadmised jätkusuutlikkusest ja kliimamuutusest ei ole kuigi süsteemsed, mis võib takistada kliimateadlikkuse kasvu ühiskonnas. Uuringu esimene eesmärk oli kirjeldada interdistsiplinaarsel kliimamuutuste teemalisel koolitusel osalenud õpetajate teadmisi kliimamuutuste olemuse ning nendega kohanemise kohta. Samuti uuriti õpetajate kliimamuutusega seotud pseudo-, sünteetilisi ja väärmõisteid. Õpetajatele (N = 221) esitati kaks kliimateemalist vabavastuselist küsimust, mille vastuste analüüsimiseks kasutati kontentanalüüsi. Tulemustest ilmnes, et kuigi kliimamuutustest tervikuna on teatud arusaam olemas, mainivad õpetajad mõningaid olulisi aspekte vähe või üldse mitte. Samuti esineb selgitustes mõningaid väärmõisteid. Uuringu teine eesmärk oli seotud kliimateadlikkuse teemalise koolituse mõjuga. Arvestades lühikeste koolituste tavapärasust, nendele kulutatavat ressurssi ning teadmiste illusiooni tekkimise ohtu, on põhjendatud, et uuritakse ka koolitustegevuse efektiivsust. Seepärast hinnati, milline muutus koolitatute kliimamuutusega seotud teadmistes koolituse mõjul tekib. Kui kliimamuutuste olemuse mõistmist peegeldavates vastustes muutust ei ilmnenud, siis nendega kohanemise teemal oli märgata eelkõige sagedasemat kohanemise mõiste kasutust ja kohanemise probleemi äratundmist. Summary

Kliimamuutus ja selle mõjud on nüüdisaja üks kesksemaid ja pakilisemaid küsimusi, kuna see puudutab kõiki inimesi ja eluvaldkondi. Tuleb tõdeda, et ehkki kestliku arengu haridust ning kliimamuutuste haridust on peetud maailmas tähtsaks juba 1990. aastate algusest alates, on kliimamuutustega seotud haridus keskendunud pigem reaalteadustele ja sotsiaalseid aspekte ei ole käsitletud või on seda tehtud pealiskaudselt. Kliimamuutuste teemade käsitlemine hariduses on oluline samm, et kasvatada uut põlvkonda, kes mõistab ja suudab lahendada kliimakriisist tulenevaid probleeme. Siinne Eesti Haridusteaduste Ajakirja erinumber toetab seda protsessi, pakkudes uudseid teadmisi ja metoodikaid, mis toetavad kliimateadlikkuse kasvu ja ühiskonna valmisolekut astuda vastu muutustele.

Sustainable natural resource management is a high priority in the 21st century as it plays a crucial role in mitigating climate change and preventing some of its consequences like loss of biodiversity, land degradation, desertification, and the exhaustion of natural resources. This concern is reflected in the United Nations Sustainable Development Goals (SDGs), which emphasize, among other factors, sustainable cities and communities, responsible production and consumption, and climate action. Achieving sustainable natural resource management begins with raising awareness and educating the next generation. Therefore, it is essential to develop educational initiatives that prepare young people to become responsible and proactive adults in promoting environmental sustainability across industries and communities. Additionally, these initiatives should develop critical and analytical thinking skills, nurture innovative mindsets for creating environmentally sound solutions, and enhance the ability to collaborate within multidisciplinary teams. The NATURE project addressed these needs by designing and developing a serious educational game that fosters this set of skills. The results of the pilot testing show that the game is an effective tool and contributes to the education and awareness of the younger generation.

Sustainable natural resource management is a high priority in the 21st century as it plays a crucial role in mitigating climate change and preventing some of its consequences like loss of biodiversity, land degradation, desertification, and the exhaustion of natural resources. This concern is reflected in the United Nations Sustainable Development Goals (SDGs), which emphasize, among other factors, sustainable cities and communities, responsible production and consumption, and climate action. Achieving sustainable natural resource management begins with raising awareness and educating the next generation. Therefore, it is essential to develop educational initiatives that prepare young people to become responsible and proactive adults in promoting environmental sustainability across industries and communities. Additionally, these initiatives should develop critical and analytical thinking skills, nurture innovative mindsets for creating environmentally sound solutions, and enhance the ability to collaborate within multidisciplinary teams. The NATURE project addressed these needs by designing and developing a serious educational game that fosters this set of skills. The results of the pilot testing show that the game is an effective tool and contributes to the education and awareness of the younger generation. [ABSTRACT FROM AUTHOR]

The protein wolframin is localized in the membrane of the endoplasmic reticulum (ER), influencing Ca2+ metabolism and ER interaction with mitochondria, but the exact role of the protein remains unclear. Mutations in Wfs1 gene cause autosomal recessive disorder Wolfram syndrome (WS). The first symptom of the WS is diabetes mellitus, so accurate diagnosis of the disease as WS is often delayed. In this study we aimed to characterize the role of the Wfs1 deficiency on bioenergetics of muscles. Alterations in the bioenergetic profiles of Wfs1-exon-5-knock-out (Wfs1KO) male rats in comparison with their wild-type male littermates were investigated using high-resolution respirometry, and enzyme activity measurements. The changes were followed in oxidative (cardiac and soleus) and glycolytic (rectus femoris and gastrocnemius) muscles. There were substrate-dependent alterations in the oxygen consumption rate in Wfs1KO rat muscles. In soleus muscle, decrease in respiration rate was significant in all the followed pathways. The relatively small alterations in muscle during development of WS, such as increased mitochondrial content and/or increase in the OxPhos-related enzymatic activity could be an adaptive response to changes in the metabolic environment. The significant decrease in the OxPhos capacity is substrate dependent indicating metabolic inflexibility when multiple substrates are available.

Abstract Wolfram syndrome (WS) is a monogenic progressive neurodegenerative disease and is characterized by various neurological symptoms, such as optic nerve atrophy, loss of vision, cognitive decline, memory impairment, and learning difficulties. GLP1 receptor agonist liraglutide and BDNF mimetic 7,8-dihydroxyflavone (7,8-DHF) have had protective effect to visual pathway and to learning and memory in different rat models of neurodegenerative disorders. Although synergistic co-treatment effect has not been reported before and therefore the aim of the current study was to investigate liraglutide, 7,8-DHF and most importantly for the first time their co-treatment effect on degenerative processes in WS rat model. We took 9 months old WS rats and their wild-type (WT) control animals and treated them daily with liraglutide, 7,8-DHF or with the combination of liraglutide and 7,8-DHF up to the age of 12.5 months (n = 47, 5–8 per group). We found that liraglutide, 7,8-DHF and their co-treatment all prevented lateral ventricle enlargement, improved learning in Morris Water maze, reduced neuronal inflammation, delayed the progression of optic nerve atrophy, had remyelinating effect on optic nerve and thereby improved visual acuity in WS rats compared to WT controls. Thus, the use of the liraglutide, 7,8-DHF and their co-treatment could potentially be used as a therapeutic intervention to induce neuroprotection or even neuronal regeneration.

Higher Education engineering students need to be prepared to address sustainable solutions to the complex problems faced in this century. They should become proficient problem solvers, able to work in multidisciplinary teams, ready to adapt to new technologies, and able to acquire new knowledge and skills when needed. Usually known as soft skills, these competences play a key role in Engineering and have being taught in the last two decades, to a greater or lesser extent, using different methodologies and tools. This study reviews the promotion and teaching of soft skills in Higher Education across 5 European countries: Greece, Estonia, Denmark, Portugal and Spain. It provides an overview of best practices on these countries, focusing also on technological solutions to actually enable the development of soft skills. The purpose of this research is to shed some light about how soft skills are being taught presently and the difficulties involved in that process.

The COVID-19 pandemic challenged the sustainability of higher education as millions of students were forced out of school, shifting to online learning instead of in-class education. In the Erasmus+ project, Virtual Presence in Higher Education Hybrid Learning Delivery (VIE), we were concerned with the level of readiness and the ability of higher-education students and teachers to face this changing situation. This paper reports the results of a survey which assessed the experiences that students and teachers had during the pandemic and, in particular, the development of soft skills through active learning methodologies. The project results show that there are still some unmet needs, but existing digital technologies, tools, and platforms already provide valuable solutions both for students and teachers that ensure a continuation of high-quality learning experiences.

Metabolic plasticity is the ability of the cell to adjust its metabolism to changes in environmental conditions. Increased metabolic plasticity is a defining characteristic of cancer cells, which gives them the advantage of survival and a higher proliferative capacity. Here we review some functional features of metabolic plasticity of colorectal cancer cells (CRC). Metabolic plasticity is characterized by changes in adenine nucleotide transport across the outer mitochondrial membrane. Voltage-dependent anion channel (VDAC) is the main protein involved in the transport of adenine nucleotides, and its regulation is impaired in CRC cells. Apparent affinity for ADP is a functional parameter that characterizes VDAC permeability and provides an integrated assessment of cell metabolic state. VDAC permeability can be adjusted via its interactions with other proteins, such as hexokinase and tubulin. Also, the redox conditions inside a cancer cell may alter VDAC function, resulting in enhanced metabolic plasticity. In addition, a cancer cell shows reprogrammed energy transfer circuits such as adenylate kinase (AK) and creatine kinase (CK) pathway. Knowledge of the mechanism of metabolic plasticity will improve our understanding of colorectal carcinogenesis.

In France, in the last few years, a lot of ponds have been removed during operations of river restoration, remobilizing the sediments that had been deposited behind the dam over the years. Pond sediments are complicated mixtures predominantly consisting of rocks and soils particles from the watershed, atmospheric dust brought by winds, algae and organic remains or particles that were produced by processes in the water column, such as amorphous silica or calcite. Sediments “can be dressed” with chemical elements of various kinds, including pollutants that settle on the bottom of the ponds. It is therefore important to understand what types of substances can be found in pond and to understand the effect of operations of river restoration on water quality. We applied the X-ray fluorescence spectrometry (XRF), where sample is irradiated with X-rays from a radioactive source, which excites the elements in the sample and generates secondary fluorescent X-rays. Elements emit energy of unique wavelengths, which allows their qualitative and quantitative determination. Commonly, elements from atomic number 11 (Na) to 92 (U) can be detected. Using this methodology, analyses were made on sediments samples from a pond located in the centre of France: results show that the pond is relatively free of pollutants. Starting from this reference, we will think which substances can be remobilized after operations of rivers restoration.

Radiocarbon-dated peat cores collected from an ombrotrophic bog in southern Estonia record shifting environmental conditions and carbon accumulation rates in northern Europe during the late Holocene. Modern observations indicate that the water balance of the peatland is highly influenced by changes in relative humidity, followed by temperature and precipitation. The modern δ18O and δ2H values of surface water suggest that the groundwater is an integration of several months of precipitation. There also appears to be little or no direct influence of surface evaporation on the water within the bog, suggesting that water loss is preferentially through transpiration and sub-surface flow. Bulk peat δ13C values exhibit a trend of higher values through the late Holocene, suggesting a pattern of overall increased surface wetness. The δ15N values were low from ~4130 to 3645 cal yr BP, suggesting drier conditions, followed by intermediate values until ~2995 cal yr BP. The δ15N values decrease again from ~2995 to 2470 cal yr BP, suggesting a return to drier conditions, followed by intermediate values until ~955 cal yr BP. The δ15N values were high, suggesting wetter conditions from ~955 to 250 cal yr BP, followed by intermediate values through the modern. Carbon accumulation rates were low to intermediate from ~4200 to 2470 cal yr BP, followed by intermediate-to-high values until ~1645 cal yr BP. Carbon accumulation rates were then low until ~585 cal yr BP, followed by intermediate values through the modern. The geochemical data, combined with observed changes in peat composition and regional proxies of temperature and water table fluctuations through the late Holocene, suggest that carbon accumulation rates were relatively low under dry and warm conditions, whereas accumulation was generally higher (up to ~80 g C m−2 yr−1) when the climate was wetter and/or colder. These findings further suggest that future environmental changes affecting the regional water balance and temperature will impact the potential for northern peatlands to capture and store carbon.

Wolfram syndrome (WS), also known as a DIDMOAD (diabetes insipidus, early-onset diabetes mellitus, optic nerve atrophy and deafness) is a rare autosomal disorder caused by mutations in the Wolframin1 (WFS1) gene. Previous studies have revealed that glucagon-like peptide-1 receptor agonist (GLP1 RA) are effective in delaying and restoring blood glucose control in WS animal models and patients. The GLP1 RA liraglutide has also been shown to have neuroprotective properties in aged WS rats. WS is an early-onset, chronic condition. Therefore, early diagnosis and lifelong pharmacological treatment is the best solution to control disease progression. Hence, the aim of this study was to evaluate the efficacy of the long-term liraglutide treatment on the progression of WS symptoms. For this purpose, 2-month-old WS rats were treated with liraglutide up to the age of 18 months and changes in diabetes markers, visual acuity, and hearing sensitivity were monitored over the course of the treatment period. We found that treatment with liraglutide delayed the onset of diabetes and protected against vision loss in a rat model of WS. Therefore, early diagnosis and prophylactic treatment with the liraglutide may also prove to be a promising treatment option for WS patients by increasing the quality of life.

An intravenously injectable illicit drug made by mixing pseudoephedrine, potassium permanganate, vinegar and water, yielding methcathinone (Mcat) and manganese (Mn), induces an extrapyramidal syndrome with parkinsonism, dystonia, gait and balance disorders similar to manganism. Although the cause of the syndrome is largely attributed to Mn, the interaction of the drug's individual components is not known and the role of Mcat is possibly underestimated. Aim of the present study was to analyze dose-dependent behavioral effects of the mixture and its two main active components Mcat and Mn in an acute setting and determine the lethal doses of each substance.Three groups of C57BL/6 mice were injected intraperitoneally with (1) the drug mixture containing 10, 25, 50, 100 or 150 mg of Mcat and respectively 1.6, 3.8, 6.9, 17.1 and 22.6 mg of Mn per kilogram of body weight; (2) 10, 25, 50, 100, 150, 200 or 300 mg of racemic Mcat/kg of body weight; (3) MnCl2 10, 25 or 50 mg/kg of body weight. Locomotor activity of the animals, various signs and time of death were recorded.Lower doses (10 and 25 mg/kg) of Mcat had a clear motor activity stimulating effect and this was clearly dose-dependent. High doses of Mcat produced epileptic seizures in 74% of the animals and became lethal with the highest doses. Similarly, the mixture had a clear dose-dependent stimulating effect and the higher doses became lethal. The LD50 of the pseudoephedrine mixture was 110.2 mg of Mcat/kg and for pure Mcat 201.7 mg/kg. Mn did not prove to be lethal in doses up to 50 mg/kg, but had a strong dose dependent inhibitory effect on the animals’ behavior. Our data reveal that both Mn and Mcat have a significant role in the toxicity of the mixture.

The abundance and properties of small standing water bodies (SSWB) is globally not well known for their ecological importance is undervalued and their detection suffers from technical limitations. In the current study, we used a combination of GIS-based methods (satellite, orthophoto, ground validation) to evaluate regional estimates of standing water body (SWB) inventories in two geographically different parts of Europe – France, and Estonia. In our study the SWBs surface area threshold limit was 0.00001 km2, exceeding the limits of previous studies (>0.002 km2). The total number of SWBs in Estonia is 111 552 (2.5 per km2) and in France 598 371 (1.1 per km2). Our estimates show that the median size of SWBs in Estonia and France is 0.0003 km2 and 0.0007 km2 respectively, meaning that most of the SSWBs are not included in the global inventories, and their number is therefore underestimated. SSWBs (area below 0.01 km2) form a significant share of the total shoreline length of SWBs, 70.3% in Estonia and 58.8% in France. As nearshore areas are often very productive with diverse habitats, the SSWBs hold a crucial role in maintaining biodiversity. Our results provide quantitative evidence that SSWBs are vital and abundant landscape elements, freshwater resources, and habitats that should not be ignored in global inventories.

Having reliable estimates of the number of water bodies on different geographical scales is of great importance to better understand biogeochemical cycles and to tackle the social issues related to the economic and cultural use of water bodies. However, limnological research suffers from a lack of reliable inventories; the available scientific references are predominately based on water bodies of natural origin, large in size and preferentially located in previously glaciated areas. Artificial, small and randomly distributed water bodies, especially ponds, are usually not inventoried. Following Wetzel’s theory (1990), some authors included them in global inventories by using remote sensing or mathematical extrapolation, but fieldwork on the ground has been done on a very limited amount of territory. These studies have resulted in an explosive increase in the estimated number of water bodies, going from 8.44 million lakes (Meybeck 1995) to 3.5 billion water bodies (Downing 2010). These numbers raise several questions, especially about the methodology used for counting small-sized water bodies and the methodological treatment of spatial variables. In this study, we use inventories of water bodies for Sweden, Finland, Estonia and France to show incoherencies generated by the “global to local” approach. We demonstrate that one universal relationship does not suffice for generating the regional or global inventories of water bodies because local conditions vary greatly from one region to another and cannot be offset adequately by each other. The current paradigm for global estimates of water bodies in limnology, which is based on one representative model applied to different territories, does not produce sufficiently exact global inventories. The step-wise progression from the local to the global scale requires the development of many regional equations based on fieldwork; a specific equation that adequately reflects the actual relationship between distribution and abundance of water bodies in a given area must be produced for each geographical region.

As karst aquifers are often characterised by non-linear behaviour, ascertaining the turning points in their hydraulic regime may provide essential information on the functioning of the aquifer. These characteristics also apply to the Silurian-Ordovician aquifer system, composed of diverse carbonate rocks, in Estonia. The aquifer system is an important source of drinking water in northern Estonia. It also comprises the Nabala- Rakvere aquifer, a locally important groundwater resource that underlies the Tuhala karst area famous for an intermittently overflowing karst spring known as the Witch's Well. The water rich in humic substances of the Tuhala River recharges the Tuhala karst system, which is drained by two spring groups. In order to develop measures for the sustainable management of the aquifer in the future, the aim of this study was to enhance understanding of the hydraulic behaviour and hydrodynamic properties of the Tuhala karst system. From October 2014 to December 2016 an extensive field campaign was carried out comprising the observation of 22 surface- and groundwater monitoring points for water level and physico-chemical parameters and the performance of four quantitative tracer tests. The data obtained were evaluated in accordance with the input– output water level relation curves and a conceptual model of the system was set up. The results show that a strong hydraulic link exists, primarily through well-developed conduits between the recharge and discharge area of the karst system. Depending on the hydrological conditions, groundwater flow direc tions vary and maximum linear flow velocities range between ~225 and 800 m/h. A threshold-controlled throughput capacity and interaction with the adjacent aquifer cause imbalances between the input and output discharges of the karst system. Tracer tests coupled with surface and groundwater level relation curve analysis allowed the specification of flow threshold conditions for the Witch's Well spring group and the overflow threshold for the Witch's Well, among other key hydrological events. The hydraulic regime of the karst system was divided into three stages, each with differing threshold controls and hydrodynamic characteristics. Key words: karst system, shallow carbonate aquifer, monitoring, tracer test, water level relation curve, threshold, overflow. Določanje mejnih vrednosti tristopenjskega hidravljičnega obnašanja pokritega plitvega karbonatnega vodonosnika (Tuhalski kras, severna Estonija) Kraški vodonosniki se pogosto obnašajo nelinearno, zato lahko z ugotavljanjem mejnih vrednosti v hidravličnem režimu zagotovimo bistvene informacije o delovanju vodonosnika. To velja tudi za silurijsko-ordovicijski vodonosni sistem v Estoniji, ki ga sestavljajo različne karbonatne kamnine in je pomemben vir pitne vode na severu države. Vključuje tudi vodonosnik Nabala- Rakvere, ki je lokalno pomemben vodni vir. Na tem območju se nahaja Tuhalski kras, ki je znan po občasno bruhajočem kraškem izviru Witch's Well (Čarovničin vodnjak). Tuhalski vodonosnik napaja reka Tuhala, bogata z huminskimi snovmi, prazni pa se skozi dve skupini izvirov. Da bi v prihodnje razvili ukrepe za trajnostno upravljanje vodonosnika, je bil namen te raziskave izboljšati razumevanje hidravličnega obnašanja in hidrodinamičnih lastnosti kraškega sistema. Od oktobra 2014 do decembra 2016 smo opravili obsežno terensko delo, ki je obsegalo spremljanje vodostajev in fizikalno-kemijskih parametrov v 23 površinskih in podzemnih točkah ter izvedbo štirih kvantitativnih sledilnih poskusov. Pridobljene podatke smo ovrednotili na podlagi krivulje odvisnosti vhodnih in izhodnih vodnih nivojev. Vzpostavili smo konceptualni model sistema. Rezultati kažejo na obstoj močne hidravlične povezave predvsem z dobro razvitimi kanali med območji napajanja in praznjenja kraškega sistema. Odvisno od hidroloških razmer se spreminjajo smeri in hitrosti toka podzemne vode, ki znašajo od ~225 do 800 m/h. Kapaciteta prepustnosti, ki jo uravnavajo določene mejne vrednosti, in posledične in terakcije s sosednjimi vodonosniki povzročajo neravnovesja med vhodnimi in izhodnimi pretočnimi vrednostmi kraškega sistema. Združevanje rezultatov sledilnih poskusov z analizo krivulje odvisnosti površinskih in podzemnih vodostajev nam je omogočilo, da smo določili mejne pretočne vrednosti izvira Witch's Well in druge ključne hidrološke dogodke. Hidravlični režim kraškega sistema smo razdelili na tri faze, od katerih ima vsaka določene mejne vrednosti in hidrodinamične lastnosti. Ključne besede: kraški sistem, plitvi karbonatni vodonosnik, monitoring, sledilni poskus, krivulja odvisnosti vodnih nivojev, prag, preliv.

During amniote evolution, the construction of the forebrain has diverged across different lineages, and accompanying the structural changes, functional diversification of the homologous brain regions has occurred. This can be assessed by studying the expression patterns of marker genes that are relevant in particular functional circuits. In all vertebrates, the dopaminergic system is responsible for the behavioral responses to environmental stimuli. Here we show that the brain regions that receive dopaminergic input through dopamine receptor D1 are relatively conserved, but with some important variations between three evolutionarily distant vertebrate lines-house mouse (Mus musculus), domestic chick (Gallus gallus domesticus) / common quail (Coturnix coturnix) and red-eared slider turtle (Trachemys scripta). Moreover, we find that in almost all instances, those brain regions expressing D1-like dopamine receptor genes also express Wfs1. Wfs1 has been studied primarily in the pancreas, where it regulates the endoplasmic reticulum (ER) stress response, cellular Ca2+ homeostasis, and insulin production and secretion. Using radioligand binding assays in wild type and Wfs1-/- mouse brains, we show that the number of binding sites of D1-like dopamine receptors is increased in the hippocampus of the mutant mice. We propose that the functional link between Wfs1 and D1-like dopamine receptors is evolutionarily conserved and plays an important role in adjusting behavioral reactions to environmental stimuli.

Numerous lakes in the world serve as sensitive indicators of climate change. Water levels for lakes Ahnejärv and Martiska, two vulnerable oligotrophic closed-basin lakes on sandy plains in northeastern Estonia, fell more than 3 m in 1946–1987 and rose up to 2 m by 2009. Earlier studies indicated that changes in rates of groundwater abstraction were primarily responsible for the changes, but scientifically sound explanations for water-level fluctuations were still lacking. Despite the inconsistent water-level dataset, we were able to assess the importance of changing climate, catchment vegetation and hydrogeology in water-level fluctuations in these lakes. Our results from water-balance simulations indicate that before the initiation of ground­water abstraction in 1972 a change in the vegetation composition on the catchments triggered the lake-level decrease. The water-level rise in 1990–2009 was caused, in addition to the reduction of groundwater abstraction rates, by increased precipitation and decreased evaporation. The results stress that climate, catchment vegetation and hydrogeology must all be considered while evaluating the causes of modern water-level changes in lakes.

Small lakes and their sediments are widely used for palaeolimnological reconstructions. Often only one core from the deepest part of the lake is used for reconstructing the lake catchment development, water-level changes and climate. To interpret palaeoinformation correctly, it is necessary to understand the spatio-temporal dynamics and the essence of lake basin evolution (topography, sedimentation zones, etc.) during the selected time period. The current study focuses on reconstructing the development of Lake Väike Juusa (southern Estonia) during the Holocene with the help of 3D digital elevation models compiled for the palaeolake stages at 9000 BP, 8000 BP, 4000 BP, 2000 BP and the present. The results suggest that we have to consider lake stages as completely different lakes with different sedimentation patterns – the hypsocraphic curve of Lake Väike Juusa was convex at the beginning of the Holocene and is concave nowadays. The proportion of the accumulation areas varied from 6% to 60% at the beginning of the Holocene and is around 30% nowadays. In order to understand lake basin development and water-level changes, the sampling sites should be selected close to the transitional zone and more than one core from a lake is needed. Commonly the sites located spatially rather close to each other have significantly different sedimentation patterns. Three-dimensional digital elevation models of palaeolake basins are useful tools for visualizing data and for hypothesizing about possible effects of lake-level fluctuations on the lake and its sedimentation regime.

Sediment samples from an outcrop in the near-shore area of Lake Ķūži (Vidzeme Heights, Central Latvia) were investigated using palaeobotanical (pollen and macrofossil analysis) and lithological (grain-size analysis) methods and accelerator mass spectrometry 14C dating. A dark, organic-rich sediment layer was found below 1.7 m of sandy layers approximately 30 cm above the present lake level. Radiocarbon dating of a wood sample from the lowermost layer (11 050 ± 60 14C BP, 13 107–12 721 cal BP) shows that the layer is of late glacial age. The composition of the pollen spectra is characterized by Betula nana, Cyperaceae pollen and spores of Equisetum, confirming that the lowermost sediments were formed during the late glacial. Fossils of obligate aquatic organisms in the upper layer, which include oospores of Characeae and seeds of Potamogeton, indicate an open water environment. Pollen of Myriophyllum and Potamogeton and non-pollen palynomorphs, such as algal Botryococcus and Pediastrum cf. boryanum, confirm this conclusion. The pollen assemblage from the greyish loam layer following this lacustrine phase shows a pattern characteristic of the Younger Dryas vegetation before the start of the real expansion of birch forests at the beginning of the Holocene.

Valproic acid (VPA) is a widely used anticonvulsant and mood-stabilizing drug whose use is often associated with drug-induced weight gain. Treatment with VPA has been shown to upregulate Wfs1 expression in vitro. Aim of the present study was to compare the effect of chronic VPA treatment in wild type (WT) and Wfs1 knockout (KO) mice on hepatic gene expression profile. Wild type, Wfs1 heterozygous, and homozygous mice were treated with VPA for three months (300 mg/kg i.p. daily) and gene expression profiles in liver were evaluated using Affymetrix Mouse GeneChip 1.0 ST array. We identified 42 genes affected by Wfs1 genotype, 10 genes regulated by VPA treatment, and 9 genes whose regulation by VPA was dependent on genotype. Among the genes that were regulated differentially by VPA depending on genotype was peroxisome proliferator-activated receptor delta (Ppard), whose expression was upregulated in response to VPA treatment in WT, but not in Wfs1 KO mice. Thus, regulation of Ppard by VPA is dependent on Wfs1 genotype.