Evolution of avian olfaction

The sense of smell enables animals to e.g. locate food, to navigate or to avoid predators. In vertebrates, odorants are detected by olfactory receptors (ORs) that are expressed in the olfactory epithelium on olfactory sensory neurons. In this study, I investigated OR gene repertoires in both closely and distantly related bird species. Using polymerase chain reaction (PCR) with degenerate primers designed to amplify OR genes, I showed that the majority of OR genes sequenced (~ 84%) were potentially functional in nine bird species from seven different orders. A nonparametric statistical technique was used to estimate the total number of OR genes in avian genomes. The total number of OR genes was surprisingly large and varied up to six fold between species (range: 106 – 667 OR genes). The total number of OR genes but not the proportion of potentially functional OR genes was positively correlated with the relative size of the olfactory bulb, which is considered an anatomical correlate of olfactory capability. A Southern Blot approach in combination with a PCR based approach revealed that two nocturnal bird species that heavily rely on olfactory cues, have evolved a larger OR gene repertoire than their diurnal, closest living relatives. Thus, it is likely that ecological niche adaptations (e.g. adaptations related to daily activity patterns) have shaped avian OR gene repertoires. Phylogenetic trees derived from predicted OR protein sequences revealed that a large, expanded OR gene clade, termed group-γ-c, is present in all bird genomes examined in this study. This clade seems to be a shared characteristic of all bird genomes. Further, I showed that positive selection has driven the molecular evolution of avian group-γ-c OR genes. Positively selected sites encoded residues within transmembrane regions that most likely interact with odour molecules and thus might influence OR receptor functioning. Interestingly, OR gene transcripts have been detected in testis and sperm of both mammals and fish, suggesting that OR genes are also involved in sperm-egg communication. Using reverse transcription (RT)-PCR with degenerate primers specific for OR genes, and subsequent cloning, I showed that several OR gene transcripts are present in chicken (Gallus gallus domesticus) testes and that they belong to the class-γ OR gene clade. Finally, a database search in the red jungle fowl (Gallus gallus) genome revealed that trace amine-associated receptors (TAARs) - a second family of chemosensory receptors primarily expressed in the olfactory epithelium that detect amine-based odour cues - are also encoded in avian genomes. The findings in this thesis contribute to our understanding of the evolution of avian OR genes. The estimated OR gene repertoire sizes, and the proportion of presumably functional OR genes, strongly suggest that avian olfactory ability is well developed and much more important than previously thought

Evidence for increased olfactory receptor gene repertoire size in two nocturnal bird species with well-developed olfactory ability

<p>Abstract</p> <p>Background</p> <p>In vertebrates, the molecular basis of the sense of smell is encoded by members of a large gene family, namely olfactory receptor (OR) genes. Both the total number of OR genes and the proportion of intact OR genes in a genome may indicate the importance of the sense of smell for an animal. There is behavioral, physiological, and anatomical evidence that some bird species, in particular nocturnal birds, have a well developed sense of smell. Therefore, we hypothesized that nocturnal birds with good olfactory abilities have evolved (i) more OR genes and (ii) more intact OR genes than closely related and presumably less 'olfaction-dependent' day-active avian taxa.</p> <p>Results</p> <p>We used both non-radioactive Southern hybridization and PCR with degenerate primers to investigate whether two nocturnal bird species that are known to rely on olfactory cues, the brown kiwi (<it>Apteryx australis</it>) and the kakapo (<it>Strigops habroptilus</it>), have evolved a larger OR gene repertoire than their day-active, closest living relatives (for kiwi the emu <it>Dromaius novaehollandiae</it>, rhea <it>Rhea americana</it>, and ostrich <it>Struthio camelus </it>and for kakapo the kaka <it>Nestor meridionalis </it>and kea <it>Nestor notabilis</it>). We show that the nocturnal birds did not have a significantly higher proportion of intact OR genes. However, the estimated total number of OR genes was larger in the two nocturnal birds than in their relatives.</p> <p>Conclusion</p> <p>Our results suggest that ecological niche adaptations such as daily activity patterns may have shaped avian OR gene repertoires.</p

Differential temporal profile of lowered blood glucose levels (3.5 to 6.5 mmol/l versus 5 to 8 mmol/l) in patients with severe traumatic brain injury

INTRODUCTION: Hyperglycaemia is detrimental, but maintaining low blood glucose levels within tight limits is controversial in patients with severe traumatic brain injury, because decreased blood glucose levels can induce and aggravate underlying brain injury. METHODS: In 228 propensity matched patients (age, sex and injury severity) treated in our intensive care unit (ICU) from 2000 to 2004, we retrospectively evaluated the influence of different predefined blood glucose targets (3.5 to 6.5 versus 5 to 8 mmol/l) on frequency of hypoglycaemic and hyperglycaemic episodes, insulin and norepinephrine requirement, changes in intracranial pressure and cerebral perfusion pressure, mortality and length of stay on the ICU. RESULTS: Mortality and length of ICU stay were similar in both blood glucose target groups. Blood glucose values below and above the predefined levels were significantly increased in the 3.5 to 6.5 mmol/l group, predominantly during the first week. Insulin and norepinephrine requirements were markedly increased in this group. During the second week, the incidences of intracranial pressure exceeding 20 mmHg and infectious complications were significantly decreased in the 3.5 to 6.5 mmol/l group. CONCLUSION: Maintaining blood glucose within 5 to 8 mmol/l appears to yield greater benefit during the first week. During the second week, 3.5 to 6.5 mmol/l is associated with beneficial effects in terms of reduced intracranial hypertension and decreased rate of pneumonia, bacteraemia and urinary tract infections. It remains to be determined whether patients might profit from temporally adapted blood glucose limits, inducing lower values during the second week, and whether concomitant glucose infusion to prevent hypoglycaemia is safe in patients with post-traumatic oedema

Neural Correlates of Behavioural Olfactory Sensitivity Changes Seasonally in European Starlings

Possibly due to the small size of the olfactory bulb (OB) as compared to rodents, it was generally believed that songbirds lack a well-developed sense of smell. This belief was recently revised by several studies showing that various bird species, including passerines, use olfaction in many respects of life. During courtship and nest building, male European starlings (Sturnus vulgaris) incorporate aromatic herbs that are rich in volatile compounds (e.g., milfoil, Achillea millefolium) into the nests and they use olfactory cues to identify these plants. Interestingly, European starlings show seasonal differences in their ability to respond to odour cues: odour sensitivity peaks during nest-building in the spring, but is almost non-existent during the non-breeding season.This study used repeated in vivo Manganese-enhanced MRI to quantify for the first time possible seasonal changes in the anatomy and activity of the OB in starling brains. We demonstrated that the OB of the starling exhibits a functional seasonal plasticity of certain plant odour specificity and that the OB is only able to detect milfoil odour during the breeding season. Volumetric analysis showed that this seasonal change in activity is not linked to a change in OB volume. By subsequently experimentally elevating testosterone (T) in half of the males during the non-breeding season we showed that the OB volume was increased compared to controls.By investigating the neural substrate of seasonal olfactory sensitivity changes we show that the starlings' OB loses its ability during the non-breeding season to detect a natural odour of a plant preferred as green nest material by male starlings. We found that testosterone, applied during the non-breeding season, does not restore the discriminatory ability of the OB but has an influence on its size

Aggressive PDACs show hypomethylation of repetitive elements and the execution of an intrinsic IFN program linked to a ductal cell of origin

Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive desmoplasia, which challenges the molecular analyses of bulk tumor samples. Here we FACS-purified epithelial cells from human PDAC and normal pancreas and derived their genome-wide transcriptome and DNA methylome landscapes. Clustering based on DNA methylation revealed two distinct PDAC groups displaying different methylation patterns at regions encoding repeat elements. Methylation(low) tumors are characterized by higher expression of endogenous retroviral (ERV) transcripts and dsRNA sensors which leads to a cell intrinsic activation of an interferon signature (IFNsign). This results in a pro-tumorigenic microenvironment and poor patient outcome. Methylation(low)/IFNsign(high) and Methylation(high)/IFNsign(low) PDAC cells preserve lineage traits, respective of normal ductal or acinar pancreatic cells. Moreover, ductal-derived Kras(G12D)/Trp53(−/−) mouse PDACs show higher expression of IFNsign compared to acinar-derived counterparts. Collectively, our data point to two different origins and etiologies of human PDACs, with the aggressive Methylation(low)/IFNsign(high) subtype potentially targetable by agents blocking intrinsic IFN-signaling

Sex, drugs and mating role: testosterone-induced phenotype-switching in Galapagos marine iguanas

Males of many vertebrate species have flexible reproductive phenotypes and must decide before each mating season whether to adopt sneaker, satellite, or territorial mating tactics. How do males gauge their abilities against others in the population? We tested experimentally whether hormone--behavior feedback loops allow Galapagos marine iguana males to activate their three behavioral phenotypes as predicted by the relative plasticity hypothesis. Territorial males defended small mating areas and had significantly higher plasma testosterone (T) levels (75 � 11 ng/ml) than did satellite males that roamed around territories (64 � 8 ng/ml) or sneaker males that behaved like females within territories (43 � 11ng/ml). In territorial males, temporary pharmacological blockade of T slowed head-bob patrolling, decreased territory size threefold, and reduced the number of females on territories 20-fold. This supports previous data that females may gauge male attractiveness by using head-bob patrolling, here shown to be a T-dependent trait. Control-treated neighbors reacted to the weakening of T-blocked males by increasing head-bob rate fivefold and territory size 1.6-fold, and female numbers increased 2.5-fold. Unmanipulated or control-injected males remained unchanged. Behavioral effects were partly reversed after 7 days. T injections induced satellite males to establish temporary territories, even at unconventional locations. Some T-boosted satellite males suffered serious fighting injuries. T-injected sneakers left female clusters and behaved like larger satellite males that roam around territories. Thus, territorial and mating tactics are activated by T, but experimental (de-) activation at the wrong ontogenetic stage is costly: manipulated males switched phenotype but thereby lowered their access to females. We hypothesize that T levels of males that are based on early-season behavioral interactions influence a males' subsequent phenotypic role. Copyright 2005.activation-organization of phenotypes; mating strategies; relative plasticity hypothesis; testosterone