The hydrochemical state of Lake Peipsi-Pihkva

The distribution and time dependence of total phosphorus (TP), dissolved inorganic phosphate (PO₄P), total nitrogen (TN), chlorophyll a (Chl), dichromate oxidizability (CODCr), permanganate oxidizability (CODMn), water colour (Col) and transparency (SD), pH, dissolved oxygen (O₂) and oxygen saturation (O₂%) in the surface water of Lake Peipsi-Pihkva are studied by using 65-parameter regression models with the help of the SAS system. The yearly means, polarity and seasonal dependence of each investigated parameter during 1985–1994 are estimated from fitted models. The bulk of data consists of 456 to 1149 measurements per parameter. L. Peipsi-Pihkva appears to be polar with respect to the majority of the studied parameters. The content of TP, PO₄P, TN, Chl, CODCr, CODMn, and Col decrease from south to north, while SD has an opposite trend. pH, O₂, and O₂% are quite uniform all over the lake. L. Peipsi is eutrophic, L. Pihkva is hypertrophic. The lake is influenced by significant yearly and seasonal changes. It is concluded that the Velikaja River is the main source of pollution for L. Peipsi-Pihkva.     

Random search for shared chromosomal regions in four affected individuals: the assignment of a new hereditary ataxia locus.

Infantile-onset spinocerebellar ataxia (IOSCA) is an autosomal recessively inherited progressive neurological disorder of unknown etiology. This ataxia, identified so far only in the genetically isolated Finnish population, does not share gene locus with any of the previously identified hereditary ataxias, and a random mapping approach was adopted to assign the IOSCA locus. Based on the assumption of one founder mutation, a primary screening of the genome was performed using samples from just four affected individuals in two consanguineous pedigrees. The identification of a shared chromosomal region in these four patients provided the first evidence that the IOSCA gene locus is on chromosome 10q23.3-q24.1, which was confirmed by conventional linkage analysis in the complete family material. Strong linkage disequilibrium observed between IOSCA and the linked markers was utilized to define accurately the critical chromosomal region. The results showed the power of linkage disequilibrium in the locus assignment of diseases with very limited family materials.     

Antibodies against Toxoplasma gondii in Fennoscandian reindeer - association with the degree of domestication

To measure the prevalence of antibodies against Toxoplasma gondii in Fennoscandian reindeer, we examined 2577 serum samples collected between 1993 and 1996 from slaughtered reindeer from Finnmark county, Norway, and from several locations in Finland. The overall prevalence in this sample was 0.9%, and the titres of the seropositives in the Direct Agglutination Test (DAT) were between 1:40 and 1:162000. Logistic regression associated seropositivity with the age of the animal, the odds ratio (OR) of adults was four when compared with calves. Seropositivity was also positively associated with corral feeding, which was used in the analysis as an indicator of domestication. No significant association was found with sex, or the frost sum of the pasture area.     

Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey,van den Ende-Gupta,and Raine Syndromes

One to two percent of all children are born with a developmental disorder requiring pediatric hospital admissions. For many such syndromes, the molecular pathogenesis remains poorly characterized. Parallel developmental disorders in other species could provide complementary models for human rare diseases by uncovering new candidate genes, improving the understanding of the molecular mechanisms and opening possibilities for therapeutic trials. We performed various experiments, e.g. combined genome-wide association and next generation sequencing, to investigate the clinico-pathological features and genetic causes of three developmental syndromes in dogs, including craniomandibular osteopathy (CMO), a previously undescribed skeletal syndrome, and dental hypomineralization, for which we identified pathogenic variants in the canine SLC37A2 (truncating splicing enhancer variant), SCARF2 (truncating 2-bp deletion) and FAM20C (missense variant) genes, respectively. CMO is a clinical equivalent to an infantile cortical hyperostosis (Caffey disease), for which SLC37A2 is a new candidate gene. SLC37A2 is a poorly characterized member of a glucose-phosphate transporter family without previous disease associations. It is expressed in many tissues, including cells of the macrophage lineage, e.g. osteoclasts, and suggests a disease mechanism, in which an impaired glucose homeostasis in osteoclasts compromises their function in the developing bone, leading to hyperostosis. Mutations in SCARF2 and FAM20C have been associated with the human van den Ende-Gupta and Raine syndromes that include numerous features similar to the affected dogs. Given the growing interest in the molecular characterization and treatment of human rare diseases, our study presents three novel physiologically relevant models for further research and therapy approaches, while providing the molecular identity for the canine conditions.     

Familial early puberty: presentation and inheritance pattern in 139 families

Background

To describe common type 2 diabetes treatment intensification regimens, patients’ characteristics and changes in glycated hemoglobin (HbA1c) and body mass index (BMI).

Methods

We constructed a national retrospective cohort of veterans initially treated for diabetes with either metformin or sulfonylurea from 2001 through 2008, using Veterans Health Administration (VHA) and Medicare data. Patients were followed through September, 2011 to identify common diabetes treatment intensification regimens. We evaluated changes in HbA1c and BMI post-intensification for metformin-based regimens.

Results

We identified 323,857 veterans who initiated diabetes treatment. Of these, 55 % initiated metformin, 43 % sulfonylurea and 2 % other regimens. Fifty percent (N = 89,057) of metformin initiators remained on metformin monotherapy over a median follow-up 58 months (interquartile range [IQR] 35, 74). Among 80,725 patients who intensified metformin monotherapy, the four most common regimens were addition of sulfonylurea (79 %), thiazolidinedione [TZD] (6 %), or insulin (8 %), and switch to insulin monotherapy (2 %). Across these regimens, median HbA1c values declined from a range of 7.0–7.8 % (53–62 mmol/mol) at intensification to 6.6–7.0 % (49–53 mmol/mol) at 1 year, and remained stable up to 3 years afterwards. Median BMI ranged between 30.5 and 32 kg/m² at intensification and increased very modestly in those who intensified with oral regimens, but 1–2 kg/m² over 3 years among those who intensified with insulin-based regimens.

Conclusions

By 1 year post-intensification of metformin monotherapy, HbA1c declined in all four common intensification regimens, and remained close to 7 % in subsequent follow-up. BMI increased substantially for those on insulin-based regimens.

     

Chemical Analysis of Pottery Demonstrates Prehistoric Origin for High-Altitude Alpine Dairying

The European high Alps are internationally renowned for their dairy produce, which are of huge cultural and economic significance to the region. Although the recent history of alpine dairying has been well studied, virtually nothing is known regarding the origins of this practice. This is due to poor preservation of high altitude archaeological sites and the ephemeral nature of transhumance economic practices. Archaeologists have suggested that stone structures that appear around 3,000 years ago are associated with more intense seasonal occupation of the high Alps and perhaps the establishment of new economic strategies. Here, we report on organic residue analysis of small fragments of pottery sherds that are occasionally preserved both at these sites and earlier prehistoric rock-shelters. Based mainly on isotopic criteria, dairy lipids could only be identified on ceramics from the stone structures, which date to the Iron Age (ca. 3,000–2,500 BP), providing the earliest evidence of this practice in the high Alps. Dairy production in such a marginal environment implies a high degree of risk even by today’s standards. We postulate that this practice was driven by population increase and climate deterioration that put pressure on lowland agropastoral systems and the establishment of more extensive trade networks, leading to greater demand for highly nutritious and transportable dairy products.     

Co-migration and internalization of transferrin and its receptor on K562 cells

The incorporation of iron into human cells involves the binding of diferric transferrin to a specific cell surface receptor. We studied the process of endocytosis in K562, a human erythroid cell line, by using tetramethylrhodamine isothiocyanate-labeled transferrin (TRITC- transferrin) and fluorescein isothiocyanate-labeled Fab fragments of goat antireceptor IgG preparation (FITC-Fab-antitransferrin receptor antibody). Because the antireceptor antibody and transferrin bind to different sites on the transferrin receptor molecule it was possible to simultaneously and independently follow ligand and receptor. At 4 degrees C, the binding of TRITC-transferrin or FITC-Fab antitransferrin receptor antibody exhibited diffuse membrane fluorescence. At 20 degrees C, the binding of TRITC-transferrin was followed by the rapid formation of aggregates. However, the FITC-Fab antitransferrin receptor did not show similar aggregation at 20 degrees C unless transferrin was present. In the presence of transferrin, the FITC-Fab antitransferrin receptor antibody formed aggregates at the same sites and within the same time period as TRITC transferrin, indicating co-migration. Although the diffuse surface staining of either label was removed by proteolysis, the larger aggregates were not susceptible to enzyme degradation, indicating that they were intracellular. The internal location of the aggregates was also demonstrated using permeabilized cells that had been preincubated with transferrin and fixed with 4% paraformaldehyde. These cells showed aggregated receptor in the interior of the cell when reacted with fluorescein-labeled antibody to the receptor. This indicated that the transferrin and the transferrin receptor co-internalize and migrate to the same structures within the cell.     

Insecticide specific emulsifier production by hexachlorocyclohexane utilizingPseudomonas tralucida Ptm+ strain

The culture supernatant ofPseudomonas tralucida (Ptm⁺ strain) produces an agent which can emulsify the insecticide hexachlorocyclohexane (HCH), which was secreted by resting cells. Emulsifying agent is most active with -HCH, and has some activity towards other chlorinated and phosphatic insecticides. The emulsifier is a heat stable macromolecule and associated with growth of the organism on -HCH.