The extensive bloom of alternate-stage Prymnesium polylepis (Haptophyta) in the Baltic Sea during autumn–spring 2007–2008

During autumn 2007, an unusual increase in an algal species belonging to the order Prymnesiales was observed throughout the Baltic Sea Proper during routine national monitoring. Electron microscopical examination of the blooming species showed two types of flat scales – small and large – that resembled those of the alternate stage of Prymnesium polylepis. No spine-bearing scales were found. The 18S rDNA sequence data (n?=?20, c. 1500?bp) verified the species identification as P. polylepis. There was up to 0.5% (7?bp) variability in the P. polylepis partial 18?S rDNA sequences from the Baltic Sea. These environmental sequences differed by 0–0.35% (0–4?bp) from cultured P. polylepis (isolate UIO036), and by 1.0–3.7% from other available Prymnesium sequences. The number of cells assumed to be P. polylepis began to increase in October 2007 coincidently with significantly calm and dry weather, and at their maximum the cells accounted for over 80% of the total phytoplankton biovolume in December–January. During February–April 2008, 95% of the Prymnesiales cells were in the size class of P. polylepis (>6?µm). The species attained bloom concentrations (>1?×?10⁶?cells?l^–1) from March to May 2008. The species was observed throughout the Baltic Sea, except the Bothnian Bay, Gulf of Riga and the Kattegat. No toxic effects of the bloom were observed.     

An evaluation of the influence of water depth and river inflow on quantitative Cladocera-based temperature and lake level inferences in a shallow boreal lake

Hydrological parameters can potentially have an overwhelming influence on sedimentary assemblages of Cladocera at certain sampling sites that can cause problems for palaeoenvironmental reconstructions. We applied a previously developed Cladocera-based inference model of water depth and a mean July air temperature transfer function developed in this study to a surface sediment dataset of fossil Cladocera from a lake in eastern Finland aiming to investigate the influence of stream flow and water depth on reconstruction results. The developed temperature-inference model, using the weighted averaging-partial least squares technique, had relatively favourable performance statistics suggesting that it is valid in means of performing temperature estimations. When the temperature model was applied to the intralake samples, the lotic samples had inferred values mostly within the model??s prediction error and only one lotic sample showed an underestimated temperature. Samples taken from depths over ~3 m inferred generally underestimated temperatures, although most of the values were within the model??s prediction error. The water depth reconstructions correlated significantly with the measured water depth, but the shallowest samples and most of the lotic samples yielded overestimated inferred values and the samples taken from depths >5 m showed underestimated values. In both reconstruction sets, the inferred values were underestimated in samples taken from deeper sites. Based on the present results, it may be recommendable that downcore sediment samples should be taken from intermediate depths, where also the diversity is higher, and deepest sites and inflows should be avoided. However, more research is needed to validate these results in a larger geographical context.     

Metabolic Signatures of Adiposity in Young Adults: Mendelian Randomization Analysis and Effects of Weight Change

Background

Increased adiposity is linked with higher risk for cardiometabolic diseases. We aimed to determine to what extent elevated body mass index (BMI) within the normal weight range has causal effects on the detailed systemic metabolite profile in early adulthood.

Methods and Findings

We used Mendelian randomization to estimate causal effects of BMI on 82 metabolic measures in 12,664 adolescents and young adults from four population-based cohorts in Finland (mean age 26 y, range 16–39 y; 51% women; mean ± standard deviation BMI 24±4 kg/m²). Circulating metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics and biochemical assays. In cross-sectional analyses, elevated BMI was adversely associated with cardiometabolic risk markers throughout the systemic metabolite profile, including lipoprotein subclasses, fatty acid composition, amino acids, inflammatory markers, and various hormones (p<0.0005 for 68 measures). Metabolite associations with BMI were generally stronger for men than for women (median 136%, interquartile range 125%–183%). A gene score for predisposition to elevated BMI, composed of 32 established genetic correlates, was used as the instrument to assess causality. Causal effects of elevated BMI closely matched observational estimates (correspondence 87%±3%; R ² = 0.89), suggesting causative influences of adiposity on the levels of numerous metabolites (p<0.0005 for 24 measures), including lipoprotein lipid subclasses and particle size, branched-chain and aromatic amino acids, and inflammation-related glycoprotein acetyls. Causal analyses of certain metabolites and potential sex differences warrant stronger statistical power. Metabolite changes associated with change in BMI during 6 y of follow-up were examined for 1,488 individuals. Change in BMI was accompanied by widespread metabolite changes, which had an association pattern similar to that of the cross-sectional observations, yet with greater metabolic effects (correspondence 160%±2%; R ² = 0.92).

Conclusions

Mendelian randomization indicates causal adverse effects of increased adiposity with multiple cardiometabolic risk markers across the metabolite profile in adolescents and young adults within the non-obese weight range. Consistent with the causal influences of adiposity, weight changes were paralleled by extensive metabolic changes, suggesting a broadly modifiable systemic metabolite profile in early adulthood. Please see later in the article for the Editors'' Summary     

Scattered late‐glacial and early Holocene tree populations as dispersal nuclei for forest development in north‐eastern European Russia

Aim Concepts about patterns and rates of post‐glacial tree population migration are changing as a result of the increasing amount of palaeobotanical information being provided by macroscopic plant remains. Here we combine macrofossil, pollen and stomata records from five sites in north‐eastern European Russia and summarize the results for the late‐glacial–early Holocene transition. The late‐glacial–early Holocene transition encompasses the first indications of trees (tree‐type Betula, Picea abies, Abies sibirica and Larix sibirica) and subsequent forest development. Considerable time‐lags between the first macrobotanical and/or stomata finds of spruce (Picea abies) and the establishment of a closed forest are reconsidered. Location Pechora basin, north‐eastern European Russia. Methods We used plant macrofossil, stomata, pollen and radiocarbon analyses to reconstruct late‐glacial and early Holocene tree establishment and forest development. The data were derived from lake sediment and peat archives. Results Palaeobotanical data reveal an early Holocene presence (11,500–10,000 cal. yr bp ) of arboreal taxa at all five sites. One site presently located in the northernmost taiga zone, shows the presence of spruce and reproducing tree birch during the late‐glacial. Given the current view of post‐glacial population dynamics and migration rates, it seems likely that the source area of these early tree populations in north‐eastern European Russia was not located in southern Europe but that these populations had local origins. Results thus support the emerging view that the first post‐glacial population expansions in non‐glaciated regions at high latitudes do not reflect migration from the south but were a result of an increase in the size and density of small persisting outlying tree populations. Main conclusions Results suggest that the area east of the margin of the Scandinavian ice sheet to the Ural Mountains had isolated patches of trees during the late‐glacial and early Holocene and that these small populations acted as initial nuclei for population expansion and forest development in the early Holocene.     

Gas chromatographic analysis of therapeutic concentrations of maprotiline in serum, using flame-ionization detection

For the measurement of the tetracyclic antidepressant maprotiline in human serum, a gas chromatographic method with flame-ionization detection has been developed. The assay specifications obtained are as follows: a precision (C.V.) of 3.5–6.4%, and a relative recovery of 97–109% using amitriptyline as internal standard. The sensitivity of the assay from serum was 40 nmol/l. The applicability of the method has been shown by measuring steady-state serum levels of five inpatients. The steady-state serum levels of maprotiline given at a daily dosage of 75 mg varied from 272 to 570 nmol/l.     

Expression of Toll-like receptors in the developing brain

Toll-like receptors (TLR) are key players of the innate and adaptive immune response in vertebrates. The original protein Toll in Drosophila melanogaster regulates both host defense and morphogenesis during development. Making use of real-time PCR, in situ hybridization, and immunohistochemistry we systematically examined the expression of TLR1-9 and the intracellular adaptor molecules MyD88 and TRIF during development of the mouse brain. Expression of TLR7 and TLR9 in the brain was strongly regulated during different embryonic, postnatal, and adult stages. In contrast, expression of TLR1-6, TLR8, MyD88, and TRIF mRNA displayed no significant changes in the different phases of brain development. Neurons of various brain regions including the neocortex and the hippocampus were identified as the main cell type expressing both TLR7 and TLR9 in the developing brain. Taken together, our data reveal specific expression patterns of distinct TLRs in the developing mouse brain and lay the foundation for further investigation of the pathophysiological significance of these receptors for developmental processes in the central nervous system of vertebrates.     

Fine-scale estimation of location of birth from genome-wide single-nucleotide polymorphism data

Systematic nonrandom mating in populations results in genetic stratification and is predominantly caused by geographic separation, providing the opportunity to infer individuals' birthplace from genetic data. Such inference has been demonstrated for individuals' country of birth, but here we use data from the Northern Finland Birth Cohort 1966 (NFBC1966) to investigate the characteristics of genetic structure within a population and subsequently develop a method for inferring location to a finer scale. Principal component analysis (PCA) shows that while the first PCs are particularly informative for location, there is also location information in the higher-order PCs, but it cannot be captured by a linear model. We introduce a new method, pcLOCATE, which is able to exploit this information to improve the accuracy of location inference. pcLOCATE uses individuals' PC values to estimate the probability of birth in each town and then averages over all towns to give an estimated longitude and latitude of birth using a fully Bayesian model. We apply pcLOCATE to the NFBC1966 data to estimate parental birthplace, testing with successively more PCs and finding the model with the top 23 PCs most accurate, with a median distance of 23 km between the estimated and the true location. pcLOCATE predicts the most recent residence of NFBC1966 individuals to a median distance of 47 km. We also apply pcLOCATE to Indian individuals from the London Life Sciences Prospective Population Study (LOLIPOP) data, and find that birthplace is predicated to a median distance of 54 km from the true location. A method with such accuracy is potentially valuable in population genetics and forensics.     

Hearing impairment in patients with 3243A→G mtDNA mutation: phenotype and rate of progression

The relationship between the phenotype and the genotype is complex in diseases caused by mutations in mitochondrial DNA (mtDNA). The 3243A-->G mutation in mtDNA frequently leads to sensorineural hearing impairment (HI), a phenotype that can be assessed in severity by audiometry; hence, consecutive audiograms can give an estimate of the rate of HI progression.We examined the audiological phenotype of 38 patients (14 men, 24 women; mean age: 45+/-14 years) who possessed the 3243A-->G mutation and who belonged to a population-based cohort ascertained in the province of Northern Ostrobothnia, Finland. The subjects took part in an otorhinolaryngologic examination, including audiometry. Factors modulating the severity of HI were analyzed, and the rate of HI progression was calculated. The better ear hearing level (BEHL) at frequencies 0.5, 1, 2, and 4 kHz (BEHL0.5-4kHz) was greater than 20 dB suggesting HI in 28 patients (74%). A good correlation (r=0.428, P=0.009) was found between BEHL0.5-4kHz and the degree of the mutant heteroplasmy. BEHL0.5-4kHz was worse in men than in women, and women outnumbered men among patients with normal hearing or mild HI. In addition, 181 consecutive audiograms were reviewed from 24 patients with HI. The rate of HI progression was calculated to be 2.9 dB/year in men and 1.5 dB/year in women, being clearly faster than the rates that have been observed in the corresponding age group in the general population. A high degree of mutant heteroplasmy, male gender, and age were found to increase the severity of HI. Phenotypic difference by gender may thus be a more universal phenomenon in mitochondrial diseases, not only being associated with Leber's hereditary optic neuropathy. This study provides the first estimate of the rate of disease progression among patients with the 3243A-->G mutation.     

Inhibition of Src family kinases blocks epidermal growth factor (EGF)-induced activation of Akt, phosphorylation of c-Cbl, and ubiquitination of the EGF receptor

Stimulation of T47D cells with epidermal growth factor (EGF) results in the activation of the intrinsic tyrosine kinases of the receptor and the phosphorylation of multiple cellular proteins including the receptor, scaffold molecules such as c-Cbl, adapter molecules such as Shc, and the serine/threonine protein kinase Akt. We demonstrate that EGF stimulation of T47D cells results in the activation of the Src protein-tyrosine kinase and that the Src kinase inhibitor PP1 blocks the EGF-induced phosphorylation of c-Cbl but not the activation/phosphorylation of the EGF receptor itself. PP1 also blocks EGF-induced ubiquitination of the EGF receptor, which is presumably mediated by phosphorylated c-Cbl. Src is associated with c-Cbl, and we have previously demonstrated that the Src-like kinase Fyn can phosphorylate c-Cbl at a preferred binding site for the p85 subunit of phosphatidylinositol 3'-kinase. PP1 treatment blocks EGF-induced activation of the anti-apoptotic protein kinase Akt suggesting that Src may regulate activation of Akt, perhaps by a Src --> c-Cbl --> phosphatidylinositol 3'-kinase --> Akt pathway.