Relationships among Body Condition,Insulin Resistance and Subcutaneous Adipose Tissue Gene Expression during the Grazing Season in Mares

Obesity and insulin resistance have been shown to be risk factors for laminitis in horses. The objective of the study was to determine the effect of changes in body condition during the grazing season on insulin resistance and the expression of genes associated with obesity and insulin resistance in subcutaneous adipose tissue (SAT). Sixteen Finnhorse mares were grazing either on cultivated high-yielding pasture (CG) or semi-natural grassland (NG) from the end of May to the beginning of September. Body measurements, intravenous glucose tolerance test (IVGTT), and neck and tailhead SAT gene expressions were measured in May and September. At the end of grazing, CG had higher median body condition score (7 vs. 5.4, interquartile range 0.25 vs. 0.43; P=0.05) and body weight (618 kg vs. 572 kg ± 10.21 (mean ± SEM); P=0.02), and larger waist circumference (P=0.03) than NG. Neck fat thickness was not different between treatments. However, tailhead fat thickness was smaller in CG compared to NG in May (P=0.04), but this difference disappeared in September. Greater basal and peak insulin concentrations, and faster glucose clearance rate (P=0.03) during IVGTT were observed in CG compared to NG in September. A greater decrease in plasma non-esterified fatty acids during IVGTT (P<0.05) was noticed in CG compared to NG after grazing. There was down-regulation of insulin receptor, retinol binding protein 4, leptin, and monocyte chemoattractant protein-1, and up-regulation of adiponectin (ADIPOQ), adiponectin receptor 1 and stearoyl-CoA desaturase (SCD) gene expressions in SAT of both groups during the grazing season (P<0.05). Positive correlations were observed between ADIPOQ and its receptors and between SCD and ADIPOQ in SAT (P<0.01). In conclusion, grazing on CG had a moderate effect on responses during IVGTT, but did not trigger insulin resistance. Significant temporal differences in gene expression profiles were observed during the grazing season.     

The Human Obesity Gene Map: The 2002 Update

This is the ninth update of the human obesity gene map, incorporating published results through October 2002 and continuing the previous format. Evidence from single‐gene mutation obesity cases, Mendelian disorders exhibiting obesity as a clinical feature, quantitative trait loci (QTLs) from human genome‐wide scans and various animal crossbreeding experiments, and association and linkage studies with candidate genes and other markers is reviewed. For the first time, transgenic and knockout murine models exhibiting obesity as a phenotype are incorporated (N = 38). As of October 2002, 33 Mendelian syndromes relevant to human obesity have been mapped to a genomic region, and the causal genes or strong candidates have been identified for 23 of these syndromes. QTLs reported from animal models currently number 168; there are 68 human QTLs for obesity phenotypes from genome‐wide scans. Additionally, significant linkage peaks with candidate genes have been identified in targeted studies. Seven genomic regions harbor QTLs replicated among two to five studies. Attempts to relate DNA sequence variation in specific genes to obesity phenotypes continue to grow, with 222 studies reporting positive associations with 71 candidate genes. Fifteen such candidate genes are supported by at least five positive studies. The obesity gene map shows putative loci on all chromosomes except Y. More than 300 genes, markers, and chromosomal regions have been associated or linked with human obesity phenotypes. The electronic version of the map with links to useful sites can be found at http:obesitygene.pbrc.edu .     

Flycatchers Copy Conspecifics in Nest-Site Selection but Neither Personal Experience nor Frequency of Tutors Have an Effect

Using the behavior of others in guiding one''s own behavior is a common strategy in animals. The prevailing theory predicts that young age and the inexperience of an individual are expected to increase the probability of adopting the behaviors of others. Also, the most common behavior in the population should be copied. Here, we tested the above predictions by examining social information use in the selection of nest-site features with a field experiment using a wild cavity nesting bird, the collared flycatcher (Ficedula albicollis). We used an experimental design in which geometric symbols depict nest-site features. By manipulating the apparent symbol choices of early settled individuals and monitoring the choices of later arriving birds, we can study social information use without bias from learned or innate preferences. Flycatchers were found to use social information in the selection of nest-site features, with about 60% of the population preferring the manipulated conspecific choices. However, age and experience as explanatory factors suggested by the social information use theory did not explain the choices. The present result, in concert with earlier similar experiments, implies that flycatchers may in some situations rely more on interspecific information in the selection of nest-site characteristics.     

Intra-annual tracheid formation of Norway spruce provenances in southern Finland

We studied the intra-annual wood formation in a Norway spruce provenance experiment in southern Finland from 2004–2008. Two Finnish provenances, northern and southern, as well as German and Hungarian provenances were included. Timing of tracheid formation and differentiation, and tracheid dimensions were determined from periodically extracted microcores. The aim was to determine the differences between the years and provenances in the timing of the xylogenesis and in the xylem characteristics. Year-to-year variation was high both in timing of tracheid formation and xylem characteristics, while between-provenance differences were small. The onset of tracheid formation varied from early May to late June in different trees in different years. The onset of tracheid formation was not closely related to the annual variations of temperature sum. In all the years, daily temperatures exceeded the threshold +5°C for several weeks before the onset of tracheid formation. The highest tracheid formation rate occurred after the summer solstice in all years and generally coincided with the highest daily temperatures during the growing season. Tracheid production ceased early in 2006 due to a mid-summer drought. Cell differentiation continued late in autumn as non-mature tracheids were still observed around mid-September. No clear differences between the provenances in the timing of tracheid formation were observed, although the Finnish provenances tended to initiate tracheid formation slightly earlier than the other provenances. The tree-ring widths of the Finnish provenances were also wider, while tracheid diameter of the German provenance was slightly smaller. Our results indicate that between-tree variation in the timing of wood formation is high compared with the latitude effect of seed source.     

Effects of novel C-methylated spermidine analogs on cell growth via hypusination of eukaryotic translation initiation factor 5A

The polyamines, putrescine, spermidine, and spermine, are ubiquitous multifunctional cations essential for cellular proliferation. One specific function of spermidine in cell growth is its role as a butylamine donor for hypusine synthesis in the eukaryotic initiation factor 5A (eIF5A). Here, we report the ability of novel mono-methylated spermidine analogs (α-MeSpd, β-MeSpd, γ-MeSpd, and ω-MeSpd) to function in the hypusination of eIF5A and in supporting the growth of DFMO-treated DU145 cells. We also tested them as substrates and inhibitors for deoxyhypusine synthase (DHS) in vitro. Of these compounds, α-MeSpd, β-MeSpd, and γ-MeSpd (but not ω-MeSpd) were substrates for DHS in vitro, while they all inhibited the enzyme reaction. As racemic mixtures, only α-MeSpd and β-MeSpd supported long-term growth (9-18 days) of spermidine-depleted DU145 cells, whereas γ-MeSpd and ω-MeSpd did not. The S-enantiomer of α-MeSpd, which supported long-term growth, was a good substrate for DHS in vitro, whereas the R-isomer was not. The long-term growth of DFMO-treated cells correlated with the hypusine modification of eIF5A by intracellular methylated spermidine analogs. These results underscore the critical requirement for hypusine modification in mammalian cell proliferation and provide new insights into the specificity of the deoxyhypusine synthase reaction.     

A potential estrogen mimetic effect of a bis(ethyl)polyamine analogue on estrogen receptor positive MCF-7 breast cancer cells

BE-3-3-3-3 (1,15-(ethylamino)4,8,12-triazapentadecane) is a bis(ethyl)polyamine analogue under investigation as a therapeutic agent for breast cancer. Since estradiol (E(2)) is a critical regulatory molecule in the growth of breast cancer, we examined the effect of BE-3-3-3-3 on estrogen receptor α (ERα) positive MCF-7 cells in the presence and absence of E(2). In the presence of E(2), a concentration-dependent decrease in DNA synthesis was observed using [(3)H]-thymidine incorporation assay. In the absence of E(2), low concentrations (2.5-10 μM) of BE-3-3-3-3 increased [(3)H]-thymidine incorporation at 24 and 48 h. BE-3-3-3-3 induced the expression of early response genes, c-myc and c-fos, in the absence of E(2), but not in its presence, as determined by real-time quantitative polymerase chain reaction (qPCR). BE-3-3-3-3 had no significant effect on these genes in an ERα-negative cell line, MDA-MB-231. Chromatin immunoprecipitation assay demonstrated enhanced promoter occupation by either E(2) or BE-3-3-3-3 of an estrogen-responsive gene pS2/Tff1 by ERα and its co-activator, steroid receptor co-activator 3 (SRC-3). Confocal microscopy of BE-3-3-3-3-treated cells revealed membrane localization of ERα, similar to that induced by E(2). The failure of BE-3-3-3-3 to inhibit cell proliferation was associated with autophagic vacuole formation, and the induction of Beclin 1 and MAP LC3 II. These results indicate a differential effect of BE-3-3-3-3 on MCF-7 cells in the absence and presence of E(2), and suggest that pre-clinical and clinical development of polyamine analogues might require special precautions and selection of sensitive subpopulation of patients.     

Tissue-specific alternative splicing of spermidine/spermine N 1-acetyltransferase

The polyamines, spermidine and spermine, are abundant organic cations participating in many important cellular processes. We have previously shown that the rate-limiting enzyme of polyamine catabolism, spermidine/spermine N ¹-acetyltransferase (SSAT), has an alternative mRNA splice variant (SSATX) which undergoes degradation via nonsense-mediated mRNA decay (NMD) pathway, and that the intracellular polyamine level regulates the ratio of the SSATX and SSAT splice variants. The aim of this study was to investigate the effect of SSATX level manipulation on SSAT activity in cell culture, and to examine the in vivo expression levels of SSATX and SSAT mRNA. Silencing SSATX expression with small interfering RNA led to increased SSAT activity. Furthermore, transfection of SSAT-deficient cells with mutated SSAT gene (which produced only trace amount of SSATX) yielded higher SSAT activity than transfection with natural SSAT gene (which produced both SSAT and SSATX). Blocking NMD in vivo by protein synthesis inhibitor cycloheximide resulted in accumulation of SSATX mRNA, and like in cell culture, the increase of SSATX mRNA was prevented by administration of polyamine analog N ¹ ,N ¹¹ -diethylnorspermine. Although SSATX/total SSAT mRNA ratio did not correlate with polyamine levels or SSAT activity between different tissues, increasing polyamine levels in a given tissue led to decreased SSATX/total SSAT mRNA ratio and vice versa. Taken together, the regulated unproductive splicing and translation of SSAT has a physiological relevance in modulating SSAT activity. However, in addition to polyamine level there seems to be additional factors regulating tissue-specific alternative splicing of SSAT.     

Patterns,Entropy, and Predictability of Human Mobility and Life

Cellular phones are now offering an ubiquitous means for scientists to observe life: how people act, move and respond to external influences. They can be utilized as measurement devices of individual persons and for groups of people of the social context and the related interactions. The picture of human life that emerges shows complexity, which is manifested in such data in properties of the spatiotemporal tracks of individuals. We extract from smartphone-based data for a set of persons important locations such as “home”, “work” and so forth over fixed length time-slots covering the days in the data-set (see also [1], [2]). This set of typical places is heavy-tailed, a power-law distribution with an exponent close to −1.7. To analyze the regularities and stochastic features present, the days are classified for each person into regular, personal patterns. To this are superimposed fluctuations for each day. This randomness is measured by “life” entropy, computed both before and after finding the clustering so as to subtract the contribution of a number of patterns. The main issue that we then address is how predictable individuals are in their mobility. The patterns and entropy are reflected in the predictability of the mobility of the life both individually and on average. We explore the simple approaches to guess the location from the typical behavior, and of exploiting the transition probabilities with time from location or activity A to B. The patterns allow an enhanced predictability, at least up to a few hours into the future from the current location. Such fixed habits are most clearly visible in the working-day length.