Osbpl8 Deficiency in Mouse Causes an Elevation of High-Density Lipoproteins and Gender-Specific Alterations of Lipid Metabolism

OSBP-related protein 8 (ORP8) encoded by Osbpl8 is an endoplasmic reticulum sterol sensor implicated in cellular lipid metabolism. We generated an Osbpl8^−/− (KO) C57Bl/6 mouse strain. Wild-type and Osbpl8KO animals at the age of 13-weeks were fed for 5 weeks either chow or high-fat diet, and their plasma lipids/lipoproteins and hepatic lipids were analyzed. The chow-fed Osbpl8KO male mice showed a marked elevation of high-density lipoprotein (HDL) cholesterol (+79%) and phospholipids (+35%), while only minor increase of apolipoprotein A-I (apoA-I) was detected. In chow-fed female KO mice a less prominent increase of HDL cholesterol (+27%) was observed, while on western diet the HDL increment was prominent in both genders. The HDL increase was accompanied by an elevated level of HDL-associated apolipoprotein E in male, but not female KO animals. No differences between genotypes were observed in lecithin:cholesterol acyltransferase (LCAT) or hepatic lipase (HL) activity, or in the fractional catabolic rate of fluorescently labeled mouse HDL injected in chow-diet fed animals. The Osbpl8KO mice of both genders displayed reduced phospholipid transfer protein (PLTP) activity, but only on chow diet. These findings are consistent with a model in which Osbpl8 deficiency results in altered biosynthesis of HDL. Consistent with this hypothesis, ORP8 depleted mouse hepatocytes secreted an increased amount of nascent HDL into the culture medium. In addition to the HDL phenotype, distinct gender-specific alterations in lipid metabolism were detected: Female KO animals on chow diet showed reduced lipoprotein lipase (LPL) activity and increased plasma triglycerides, while the male KO mice displayed elevated plasma cholesterol biosynthetic markers cholestenol, desmosterol, and lathosterol. Moreover, modest gender-specific alterations in the hepatic expression of lipid homeostatic genes were observed. In conclusion, we report the first viable OsbplKO mouse model, demonstrating a HDL elevating effect of Osbpl8 knock-out and additional gender- and/or diet-dependent impacts on lipid metabolism.     

Do anuran larvae respond behaviourally to chemical cues from an invasive crayfish predator? A community-wide study

Antipredator behaviour is an important fitness component in most animals. A co-evolutionary history between predator and prey is important for prey to respond adaptively to predation threats. When non-native predator species invade new areas, native prey may not recognise them or may lack effective antipredator defences. However, responses to novel predators can be facilitated by chemical cues from the predators’ diet. The red swamp crayfish Procambarus clarkii is a widespread invasive predator in the Southwest of the Iberian Peninsula, where it preys upon native anuran tadpoles. In a laboratory experiment we studied behavioural antipredator defences (alterations in activity level and spatial avoidance of predator) of nine anurans in response to P. clarkii chemical cues, and compared them with the defences towards a native predator, the larval dragonfly Aeshna sp. To investigate how chemical cues from consumed conspecifics shape the responses, we raised tadpoles with either a tadpole-fed or starved crayfish, or dragonfly larva, or in the absence of a predator. Five species significantly altered their behaviour in the presence of crayfish, and this was largely mediated by chemical cues from consumed conspecifics. In the presence of dragonflies, most species exhibited behavioural defences and often these did not require the presence of cues from predation events. Responding to cues from consumed conspecifics seems to be a critical factor in facilitating certain behavioural responses to novel exotic predators. This finding can be useful for predicting antipredator responses to invasive predators and help directing conservation efforts to the species at highest risk.     

Salivary flow rate and risk of malnutrition – a study among dentate,community‐dwelling older people

doi: 10.1111/j.1741‐2358.2012.00679.x Salivary flow rate and risk of malnutrition – a study among dentate, community‐dwelling older people Objective: To analyse the relation between unstimulated and stimulated salivary secretion and the risk of malnutrition among home‐dwelling elderly people. Background: Saliva has an important role in eating. Despite this, there are only a few studies on the role of salivary secretion in the development of malnutrition among elderly people. Materials and methods: The study population consisted of 157 subjects aged 75 or older. This was a part of GeMS study carried out in Kuopio, in eastern Finland. The data used in this study were collected by means of interviews and geriatric and oral clinical examinations. The risk of malnutrition was measured using the Mini Nutritional Assessment Short‐Form. Logistic regression models were used to estimate odds ratios (OR) and their 95% Confidence Intervals (CI). Results: Subjects with a low unstimulated salivary flow rate (<0.1 ml/min) or stimulated salivary flow rate (<1.0 ml/min) had no statistically significant increase in risk of malnutrition, OR: 1.3, CI: 0.5–3.9, OR: 1.5, CI: 0.5–4.2, respectively, when compared with those with a normal unstimulated and stimulated salivary flow rate. Conclusion: Our results do not support the concept that low salivary secretion is an important risk factor for malnutrition among community‐dwelling elders.     

Fine‐grained adaptive divergence in an amphibian: genetic basis of phenotypic divergence and the role of nonrandom gene flow in restricting effective migration among wetlands

Adaptive ecological differentiation among sympatric populations is promoted by environmental heterogeneity, strong local selection and restricted gene flow. High gene flow, on the other hand, is expected to homogenize genetic variation among populations and therefore prevent local adaptation. Understanding how local adaptation can persist at the spatial scale at which gene flow occurs has remained an elusive goal, especially for wild vertebrate populations. Here, we explore the roles of natural selection and nonrandom gene flow (isolation by breeding time and habitat choice) in restricting effective migration among local populations and promoting generalized genetic barriers to neutral gene flow. We examined these processes in a network of 17 breeding ponds of the moor frog Rana arvalis, by combining environmental field data, a common garden experiment and data on variation in neutral microsatellite loci and in a thyroid hormone receptor (TRβ) gene putatively under selection. We illustrate the connection between genotype, phenotype and habitat variation and demonstrate that the strong differences in larval life history traits observed in the common garden experiment can result from adaptation to local pond characteristics. Remarkably, we found that haplotype variation in the TRβ gene contributes to variation in larval development time and growth rate, indicating that polymorphism in the TRβ gene is linked with the phenotypic variation among the environments. Genetic distance in neutral markers was correlated with differences in breeding time and environmental differences among the ponds, but not with geographical distance. These results demonstrate that while our study area did not exceed the scale of gene flow, ecological barriers constrained gene flow among contrasting habitats. Our results highlight the roles of strong selection and nonrandom gene flow created by phenological variation and, possibly, habitat preferences, which together maintain genetic and phenotypic divergence at a fine‐grained spatial scale.     

3-[(Imidazolidin-2-yl)imino]indazole ligands with selectivity for the α(2)-adrenoceptor compared to the imidazoline I(1) receptor

A series of 3-[(4,5-dihydroimidazolidin-2-yl)imino]indazoles has been synthesized as positional analogues of marsanidine, a highly selective ??₂-adrenoceptor ligand. Parent compound 4a and its 4-chloro (4c) and 4-methyl (4d) derivatives display ??₂-adrenoceptor affinity at nanomolar concentrations (K_i = 39.4, 15.9 and 22.6 nM, respectively) and relatively high ??₂/I₁ selectivity ratios of 82, 115 and 690, respectively. Evidence was obtained that these compounds act as partial agonists at ??_2A-adrenoceptors. Compound 4d with intrinsic activity comparable with that of marsanidine, but lower than that of clonidine, elicited pronounced cardiovascular effects in anesthetized rats at doses as low as 0.01 mg/kg iv     

Mice Lacking NCF1 Exhibit Reduced Growth of Implanted Melanoma and Carcinoma Tumors

The NADPH oxidase 2 (NOX2) complex is a professional producer of reactive oxygen species (ROS) and is mainly expressed in phagocytes. While the activity of the NOX2 complex is essential for immunity against pathogens and protection against autoimmunity, its role in the development of malignant tumors remains unclear. We compared wild type and Ncf1 ^m1J mutated mice, which lack functional NOX2 complex, in four different tumor models. Ncf1 ^m1J mutated mice developed significantly smaller tumors in two melanoma models in which B16 melanoma cells expressing a hematopoietic growth factor FLT3L or luciferase reporter were used. Ncf1 ^m1J mutated mice developed significantly fewer Lewis Lung Carcinoma (LLC) tumors, but the tumors that did develop, grew at a pace that was similar to the wild type mice. In the spontaneously arising prostate carcinoma model (TRAMP), tumor growth was not affected. The lack of ROS-mediated protection against tumor growth was associated with increased production of immunity-associated cytokines. A significant increase in Th2 associated cytokines was observed in the LLC model. Our present data show that ROS regulate rejection of the antigenic B16-luc and LLC tumors, whereas the data do not support a role for ROS in growth of intrinsically generated tumors.     

Sex differences in age structure, growth rate and body size of common frogs Rana temporaria in the subarctic

The thermal environment and length of the activity season are important factors in shaping life-history trait variation in ectotherms. Many ectothermic vertebrates living at high latitudes or altitudes tend to be larger and older than their conspecifics living at lower latitudes or altitudes. However, detailed data on age, body size and growth variation—and how they may differ between males and females—are still scarce, especially from extreme high-latitude environments. We studied growth (body length increment), age and size structure of common frogs (Rana temporaria) in subarctic Finland (69°04′N) by applying skeletochronological methods to individually marked adults (n?=?169) captured and recaptured between 1999 and 2003. We found that breeding males were on average younger (mean?=?8.5?years) than females (11.9?years) and that males started reproducing earlier (≥3–4?years of age) than females (>4–5?years). The oldest encountered individual was an 18-year-old female, which to our knowledge is the oldest wild common frog ever reported. Females were on average larger (mean body length?=?76.6?mm) than males (70.7?mm), and this appeared to be mainly due to their older age as compared to males. While body length increased and growth rate decreased with age in both sexes, growth rate declined significantly faster with age in males than in females. The latter finding provides a proximate explanation for the observation that even after accounting for age differences among sexes (females?>?males), females were longer than males.     

Dementia and oral health among subjects aged 75 years or older

doi: 10.1111/j.1741‐2358.2010.00396.x Dementia and oral health among subjects aged 75 years or older Objective: To study the association between diagnosed dementia and oral health, focusing on the type of dementia, among an elderly population aged 75 years or older. Background: Elderly people with dementia are at risk from oral diseases, but to date, only a few studies have analysed the association between type of dementia and oral health, and their results are inconclusive. Materials and methods: This cross‐sectional study is based on the Geriatric multi‐disciplinary strategy (Gems) study that included 76 demented and 278 non‐demented subjects. The data were collected by means of an interview and an oral clinical examination. The type of dementia was diagnosed according to DSM‐IV criteria. Poisson’s and logistic regression models were used to determine relative risks (RR), odds ratios (OR) and 95% confidence limits (CI). Results: Our results showed that patients with Alzheimer’s disease and those with other types of dementia had an increased likelihood of having carious teeth, teeth with deep periodontal pockets, and poor oral and denture hygiene, compared with non‐demented persons. The results showed that the type of dementia does not seem to be an essential determinant of oral health. Conclusions: Among the elderly aged 75 years or older, patients with Alzheimer’s disease or other types of dementia are at increased risk of poor oral health and poor oral hygiene.     

The quantitative genetic basis of adaptive divergence in the moor frog (Rana arvalis) and its implications for gene flow

Knowledge on the relative contribution of direct genetic, maternal and environmental effects to adaptive divergence is important for understanding the drivers of biological diversification. The moor frog (Rana arvalis) shows adaptive divergence in embryonic and larval fitness traits along an acidification gradient in south-western Sweden. To understand the quantitative genetic basis of this divergence, we performed reciprocal crosses between three divergent population pairs and reared embryos and larvae at acid and neutral pH in the laboratory. Divergence in embryonic acid tolerance (survival) was mainly determined by maternal effects, whereas the relative contributions of maternal, additive and nonadditive genetic effects in larval life-history traits differed between traits, population pairs and rearing environments. These results emphasize the need to investigate the quantitative genetic basis of adaptive divergence in multiple populations and traits, as well as different environments. We discuss the implications of our findings for maintenance of local adaptation in the context of migrant and hybrid fitness.     

Seasonality determines patterns of growth and age structure over a geographic gradient in an ectothermic vertebrate

Environmental variation connected with seasonality is likely to affect the evolution of life-history strategies in ectotherms, but there is no consensus as to how important life-history traits like body size are influenced by environmental variation along seasonal gradients. We compared adult body size, skeletal growth, mean age, age at first reproduction and longevity among 11 common frog (Rana temporaria) populations sampled along a 1,600-km-long latitudinal gradient across Scandinavia. Mean age, age at first reproduction and longevity increased linearly with decreasing growth season length. Lifetime activity (i.e. the estimated number of active days during life-time) was highest at mid-latitudes and females had on average more active days throughout their lives than males. Variation in body size was due to differences in lifetime activity among populations??individuals (especially females) were largest where they had the longest cumulative activity period??as well as to differences between populations in skeletal growth rate as determined by skeletochronological analyses. Especially, males grew faster at intermediate latitudes. While life-history trait variation was strongly associated with latitude, the direction and shape of these relationships were sex- and trait-specific. These context-dependent relationships may be the result of life-history trade-offs enforced by differences in future reproductive opportunities and time constraints among the populations. Thus, seasonality appears to be an important environmental factor shaping life-history trait variation in common frogs.