Association of the LINGO2-related SNP rs10968576 with body mass in a cohort of elderly Swedes

Genome-wide association studies (GWAS) have identified common genetic factors influencing body mass as well as body adiposity. The functional implications of these loci are currently under investigation. Intense scrutiny of the body mass-associated FTO locus revealed age-specific effects, or a weakened effect in elderly populations. In this study, we aimed to determine the effects of single nucleotide polymorphisms (SNPs) representing 35 GWAS-identified body mass- and adiposity-associated genetic loci. In our analysis, 949 participants of the Prospective Investigation of the Vasculature in Uppsala Seniors cohort were included. All participants were born between 1920 and 1924. Data were available for 474 male and 475 female participants at age 70 and 380 male and 390 female participants at age 75. Genetic associations with BMI and change in BMI from age 70 to 75 were analyzed. In our analysis, rs10968576, an intronic SNP within the LINGO2 (LERN3, LRRN6C) gene, was associated with body mass in a cross section of elderly Swedes at age 70. This is the first study to replicate the association of a LINGO2-related genetic variant with body mass in an independent cohort of elderly citizens.     

Subarachnoidal Neurocysticercosis non-responsive to cysticidal drugs: a case series

Background  

Neurocysticercosis (NC) is one of the most frequent parasitic diseases of the central nervous system. Cysticidal drugs, albendazole and praziquantel, are generally effective when parasites localize in the parenchyma. In contrast, parasites lodged in the subarachnoid basal cisterns are less responsive to treatment.     

Independent HHsearch, Needleman--Wunsch-based, and motif analyses reveal the overall hierarchy for most of the G protein-coupled receptor families

Several families of G protein-coupled receptors (GPCRs) show no significant sequence similarities to each other, and it has been debated which of them share a common origin. We developed and performed integrated and independent HHsearch, Needleman--Wunsch-based and motif analyses on more than 6,600 unique GPCRs from 12 species. Moreover, we mined the evolutionary important Trichoplax adhaerens, Nematostella vectensis, Thalassiosira pseudonana, and Strongylocentrotus purpuratus genomes, revealing remarkably rich vertebrate-like GPCR repertoires already in the early Metazoan species. We found strong evidence that the Adhesion and Frizzled families are children to the cyclic AMP (cAMP) family with HHsearch homology probabilities of 99.8% and 99.4%, respectively, also supported by the Needleman--Wunsch analysis and several motifs. We also found that the large Rhodopsin family is likely a child of the cAMP family with an HHsearch homology probability of 99.4% and conserved motifs. Therefore, we suggest that the Adhesion and Frizzled families originated from the cAMP family in an event close to that which gave rise to the Rhodopsin family. We also found convincing evidence that the Rhodopsin family is parent to the important sensory families; Taste 2 and Vomeronasal type 1 as well as the Nematode chemoreceptor families. The insect odorant, gustatory, and Trehalose receptors, frequently referred to as GPCRs, form a separate cluster without relationship to the other families, and we propose, based on these and others' results, that these families are ligand-gated ion channels rather than GPCRs. Overall, we suggest common descent of at least 97% of the GPCRs sequences found in humans.     

Differential neural responses to food images in women with bulimia versus anorexia nervosa

Background

Previous fMRI studies show that women with eating disorders (ED) have differential neural activation to viewing food images. However, despite clinical differences in their responses to food, differential neural activation to thinking about eating food, between women with anorexia nervosa (AN) and bulimia nervosa (BN) is not known.

Methods

We compare 50 women (8 with BN, 18 with AN and 24 age-matched healthy controls [HC]) while they view food images during functional Magnetic Resonance Imaging (fMRI).

Results

In response to food (vs non-food) images, women with BN showed greater neural activation in the visual cortex, right dorsolateral prefrontal cortex, right insular cortex and precentral gyrus, women with AN showed greater activation in the right dorsolateral prefrontal cortex, cerebellum and right precuneus. HC women activated the cerebellum, right insular cortex, right medial temporal lobe and left caudate. Direct comparisons revealed that compared to HC, the BN group showed relative deactivation in the bilateral superior temporal gyrus/insula, and visual cortex, and compared to AN had relative deactivation in the parietal lobe and dorsal posterior cingulate cortex, but greater activation in the caudate, superior temporal gyrus, right insula and supplementary motor area.

Conclusions

Women with AN and BN activate top-down cognitive control in response to food images, yet women with BN have increased activation in reward and somatosensory regions, which might impinge on cognitive control over food consumption and binge eating.     

Acute ghrelin administration reverses depressive-like behavior induced by bilateral olfactory bulbectomy in mice

This study aims to examine the antidepressant-like action of Ghrelin (Ghr), a hormone synthesized predominantly by gastrointestinal endocrine cells and released during periods of negative energy balance, in two behavioral models: tail suspension test (TST), a predictive model of antidepressant activity, and the olfactory bulbectomy (OB), an established animal model of depression. The reduction in the immobility time in the TST was the parameter used to assess antidepressant-like effect of Ghr. The depressive-like behavior in olfactory bulbectomized mice was inferred through the increase in the immobility time in the TST and the hyperlocomotor activity in the open-field test. Ghr produced antidepressant-like effect in TST (0.3 nmol/μl, i.c.v.), and reversed OB-induced depressive-like behavior. In conclusion, these results provide clear evidence that an acute administration of ghrelin produce antidepressant-like effect in the TST and OB.     

Characterisation and expression of the paired box protein 7 (Pax7) gene in polymorphic Arctic charr (Salvelinus alpinus)

Arctic charr (Salvelinus alpinus L.) from Lake Thingvallavatn, Iceland occur as four distinct morphs: large benthivorous (LB), dwarf benthivorous (DB), piscivorous (PI) and planktonivorous (PL). The morphs differ with respect to body size, head morphology, growth rate, and life history. The aim of this study was to investigate the paired box protein 7 (Pax7) gene as a candidate for such polymorphisms due to its importance in cranio-facial, skeletal muscle, and central nervous system development. No variation in coding and intronic sequences was found between morphs. We identified 10 alternate Pax7 isoforms with insertions/deletions: a four-residue (GNRT) deletion, a GEASS insertion truncated by the first serine residue (GEAS), and a thirteen-residue insertion (GQYA/TGPEYVYCGT). The latter insertion with a threonine (T) contains a putative casein kinase II (CK-2) phosphorylation site. Pax7 spatial expression patterns were identical in embryos of DB-, LB-, and PL-morphs, and were similar to those described for zebrafish Pax7c, but a difference in temporal expression for segmentation was observed between DB and LB morphs. At the end of segmentation, novel expression was observed in the mandibular region as two bilateral domains. The potential role of multiple alternative splicing of the Pax7 gene for the generation of different Arctic charr morphs is briefly discussed.     

Further evidence for ancient role of ACTH peptides at melanocortin (MC) receptors; pharmacology of dogfish and lamprey peptides at dogfish MC receptors

The cloning of melanocortin (MC) receptors in distant species has provided us tools to get insight in how the ligand-receptors interactions in the MC system have evolved. We have however lacked studies on pharmacology of native ancient melanocortin peptides at the ancient MC receptors. In this paper we synthesized melanocortin peptides from both the sea lamprey (Petromyzon marinus) and spiny dogfish (Squalus acanthias) and tested them on the MC3 and MC4 receptors from spiny dogfish. The results show that both the dogfish and lamprey ACTH peptides have similar or higher affinity than the dogfish alpha-, beta- and gamma-MSH peptides to the dogfish MC3 and MC4 receptors. Moreover, both the dogfish and lamprey ACTH peptides have more than 10-fold higher affinity than alpha-MSH to the dogfish MC4 receptor. We also show that dogfish delta-MSH is able to bind to MC receptors and its potency is higher than of dogfish beta-MSH, which is considered to be its precursor. Our results provide the first evidence that native ACTH ligands from dogfish and lamprey have a preference above native MSH peptides to ancient version of the MC3 and MC4 receptors. This further strengthens the hypotheses that the ligand contributing to the first version of the melanocortin ligand-receptor system resembled ACTH.     

Variability of bio-optical parameters in two North-European large lakes

The bio-optical properties of some North-European large lakes were examined during 1995–2005 using field data and laboratory measurements. The key variables were optically active substances (OAS: chlorophyll, total suspended matter and dissolved organic matter), Secchi depth, and the “spectrometric” and diffuse light attenuation coefficients. Our main study sites were Lake Peipsi and Lake Võrtsjärv in Estonia, both eutrophic with mean Secchi depth below 3 m. The measured water parameters were compared with those obtained from two clear-water Swedish lakes, Lake Vänern and Lake Vättern. This comparison describes the bio-optical differences of the water in eutrophic and oligotrophic lakes. The variability of water parameters in the turbid Estonian lakes was rather high, e.g. the chlorophyll content varied from 1.8 to 102 mg m^?3 and the diffuse light attenuation coefficient from 0.92 to 6.5 m^?1. The change in water properties depends on the season and the biological activity of phytoplankton. We found no apparent long-time trend in water properties. Regression analysis showed that in the turbid Estonian lakes the optical properties were well correlated with chlorophyll and suspended matter, but not with dissolved organic matter. The highest determination coefficients (between 0.73 and 0.89) were obtained when the optical parameters were correlated with all three OAS together (multiple regressions). Our results concerning the variability and interconnections among bio-optical parameters in two Estonian large lakes illustrate the effect of OAS and light field on the ecological conditions of lakes in general.