Germline-dependent gene expression in distant non-gonadal somatic tissues of Drosophila

<p>Abstract</p> <p>Background</p> <p><it>Drosophila </it>females commit tremendous resources to egg production and males produce some of the longest sperm in the animal kingdom. We know little about the coordinated regulation of gene expression patterns in distant somatic tissues that support the developmental cost of gamete production.</p> <p>Results</p> <p>We determined the non-gonadal gene expression patterns of <it>Drosophila </it>females and males with or without a germline. Our results show that germline-dependent expression in the non-gonadal soma is extensive. Interestingly, gene expression patterns and hormone titers are consistent with a hormone axis between the gonads and non-gonadal soma.</p> <p>Conclusions</p> <p>The germline has a long-range influence on gene expression in the <it>Drosophila </it>sexes. We suggest that this is the result of a germline/soma hormonal axis.</p

Cognitive dysfunction in naturally occurring canine idiopathic epilepsy

Globally, epilepsy is a common serious brain disorder. In addition to seizure activity, epilepsy is associated with cognitive impairments including static cognitive impairments present at onset, progressive seizure-induced impairments and co-morbid dementia. Epilepsy occurs naturally in domestic dogs but its impact on canine cognition has yet to be studied, despite canine cognitive dysfunction (CCD) recognised as a spontaneous model of dementia. Here we use data from a psychometrically validated tool, the canine cognitive dysfunction rating (CCDR) scale, to compare cognitive dysfunction in dogs diagnosed with idiopathic epilepsy (IE) with controls while accounting for age. An online cross-sectional study resulted in a sample of 4051 dogs, of which n = 286 had been diagnosed with IE. Four factors were significantly associated with a diagnosis of CCD (above the diagnostic cut-off of CCDR ≥50): (i) epilepsy diagnosis: dogs with epilepsy were at higher risk; (ii) age: older dogs were at higher risk; (iii) weight: lighter dogs (kg) were at higher risk; (iv) training history: dogs with more exposure to training activities were at lower risk. Impairments in memory were most common in dogs with IE, but progression of impairments was not observed compared to controls. A significant interaction between epilepsy and age was identified, with IE dogs exhibiting a higher risk of CCD at a young age, while control dogs followed the expected pattern of low-risk throughout middle age, with risk increasing exponentially in geriatric years. Within the IE sub-population, dogs with a history of cluster seizures and high seizure frequency had higher CCDR scores. The age of onset, nature and progression of cognitive impairment in the current IE dogs appear divergent from those classically seen in CCD. Longitudinal monitoring of cognitive function from seizure onset is required to further characterise these impairments

A Model-Based Analysis of Chemical and Temporal Patterns of Cuticular Hydrocarbons in Male Drosophila melanogaster

Drosophila Cuticular Hydrocarbons (CH) influence courtship behaviour, mating, aggregation, oviposition, and resistance to desiccation. We measured levels of 24 different CH compounds of individual male D. melanogaster hourly under a variety of environmental (LD/DD) conditions. Using a model-based analysis of CH variation, we developed an improved normalization method for CH data, and show that CH compounds have reproducible cyclic within-day temporal patterns of expression which differ between LD and DD conditions. Multivariate clustering of expression patterns identified 5 clusters of co-expressed compounds with common chemical characteristics. Turnover rate estimates suggest CH production may be a significant metabolic cost. Male cuticular hydrocarbon expression is a dynamic trait influenced by light and time of day; since abundant hydrocarbons affect male sexual behavior, males may present different pheromonal profiles at different times and under different conditions

Molecular Evolution and Functional Diversification of Fatty Acid Desaturases after Recurrent Gene Duplication in Drosophila

Frequent gene duplications in the genome incessantly supply new genetic materials for functional innovation presumably driven by positive Darwinian selection. This mechanism in the desaturase gene family has been proposed to be important in triggering the pheromonal diversification in insects. With the recent completion of a dozen Drosophila genomes, a genome-wide perspective is possible. In this study, we first identified homologs of desaturase genes in 12 Drosophila species and noted that while gene duplication events are relatively frequent, gene losses are not scarce, especially in the desat1–desat2–desatF clade. By reconciling the gene tree with species phylogeny and the chromosomal synteny of the sequenced Drosophila genomes, at least one gene loss in desat2 and a minimum of six gene gains (resulting in seven desatF homologs, α-η), three gene losses and one relocation in desatF were inferred. Upon branching off the ancestral desat1 lineage, both desat2 and desatF gained novel functions through accelerating protein evolution. The amino acid residues under positive selection located near the catalytic sites and the C-terminal region might be responsible for altered substrate selectivity between closely related species. The association between the expression pattern of desatF-α and the chemical composition of cuticular hydrocarbons implies that the ancestral function of desatF-α is the second desaturation at the four carbons after the first double bond in diene synthesis, and the shift from bisexual to female-specific expression in desatF-α occurred in the ancestral lineage of Drosophila melanogaster subgroup. A relationship between the number of expressed desatF homologs and the diene diversification has also been observed. These results suggest that the molecular diversification of fatty acid desaturases after recurrent gene duplication plays an important role in pheromonal diversity in Drosophila

Revealing a brain network endophenotype in families with idiopathic generalised epilepsy

Idiopathic generalised epilepsy (IGE) has a genetic basis. The mechanism of seizure expression is not fully known, but is assumed to involve large-scale brain networks. We hypothesised that abnormal brain network properties would be detected using EEG in patients with IGE, and would be manifest as a familial endophenotype in their unaffected first-degree relatives. We studied 117 participants: 35 patients with IGE, 42 unaffected first-degree relatives, and 40 normal controls, using scalp EEG. Graph theory was used to describe brain network topology in five frequency bands for each subject. Frequency bands were chosen based on a published Spectral Factor Analysis study which demonstrated these bands to be optimally robust and independent. Groups were compared, using Bonferroni correction to account for nonindependent measures and multiple groups. Degree distribution variance was greater in patients and relatives than controls in the 6-9 Hz band (p = 0.0005, p = 0.0009 respectively). Mean degree was greater in patients than healthy controls in the 6-9 Hz band (p = 0.0064). Clustering coefficient was higher in patients and relatives than controls in the 6-9 Hz band (p = 0.0025, p = 0.0013). Characteristic path length did not differ between groups. No differences were found between patients and unaffected relatives. These findings suggest brain network topology differs between patients with IGE and normal controls, and that some of these network measures show similar deviations in patients and in unaffected relatives who do not have epilepsy. This suggests brain network topology may be an inherited endophenotype of IGE, present in unaffected relatives who do not have epilepsy, as well as in affected patients. We propose that abnormal brain network topology may be an endophenotype of IGE, though not in itself sufficient to cause epilepsy

Rapid Evolution of Sex Pheromone-Producing Enzyme Expression in Drosophila

Rapid evolution of gene expression patterns responsible for pheromone production in 24 species of Drosophila was mapped to simple mutations within the regulatory domain of the desatF gene

Cerebellum Abnormalities in Idiopathic Generalized Epilepsy with Generalized Tonic-Clonic Seizures Revealed by Diffusion Tensor Imaging

Although there is increasing evidence suggesting that there may be subtle abnormalities in idiopathic generalized epilepsy (IGE) patients using modern neuroimaging techniques, most of these previous studies focused on the brain grey matter, leaving the underlying white matter abnormalities in IGE largely unknown, which baffles the treatment as well as the understanding of IGE. In this work, we adopted multiple methods from different levels based on diffusion tensor imaging (DTI) to analyze the white matter abnormalities in 14 young male IGE patients with generalized tonic-clonic seizures (GTCS) only, comparing with 29 age-matched male healthy controls. First, we performed a voxel-based analysis (VBA) of the fractional anisotropy (FA) images derived from DTI. Second, we used a tract-based spatial statistics (TBSS) method to explore the alterations within the white matter skeleton of the patients. Third, we adopted region-of-interest (ROI) analyses based on the findings of VBA and TBSS to further confirm abnormal brain regions in the patients. At last, considering the convergent evidences we found by VBA, TBSS and ROI analyses, a subsequent probabilistic fiber tractography study was performed to investigate the abnormal white matter connectivity in the patients. Significantly decreased FA values were consistently observed in the cerebellum of patients, providing fresh evidence and new clues for the important role of cerebellum in IGE with GTCS

Findings from the Peutz-Jeghers Syndrome Registry of Uruguay

Background: Peutz-Jeghers syndrome (PJS) is characterized by intestinal polyposis, mucocutaneous pigmentation and an increased cancer risk, usually caused by mutations of the STK11 gene. This study collected epidemiological, clinical and genetic data from all Uruguayan PJS patients. Methods: Clinical data were obtained from public and private medical centers and updated annually. Sequencing of the STK11 gene in one member of each family was performed. Results and discussion: 25 cases in 11 unrelated families were registered (15 males, 10 females). The average age of diagnosis and death was 18 and 41 years respectively. All patients had characteristic PJS pigmentation and gastrointestinal polyps. 72% required urgent surgery due to intestinal obstruction. 3 families had multiple cases of seizure disorder, representing 20% of cases. 28% developed cancer and two patients had more than one cancer. An STK11 mutation was found in 8 of the 9 families analyzed. A unique M136K missense mutation was noted in one family. Comparing annual live births and PJS birth records from 1970 to 2009 yielded an incidence of 1 in 155,000. Conclusion: The Uruguayan Registry for Peutz-Jeghers patients showed a high chance of emergent surgery, epilepsy, cancer and shortened life expectancy. The M136K missense mutation is a newly reported STK 11 mutation

Hierarchical chemosensory regulation of male-male social interactions in Drosophila

Pheromones regulate male social behaviors in Drosophila, but the identities and behavioral role(s) of these chemosensory signals, and how they interact, are incompletely understood. We found that (z)-7-tricosene, a male-enriched cuticular hydrocarbon that was previously shown to inhibit male-male courtship, was essential for normal levels of aggression. The mechanisms by which (z)-7-tricosene induced aggression and suppressed courtship were independent, but both required the gustatory receptor Gr32a. Sensitivity to (z)-7-tricosene was required for the aggression-promoting effect of 11-cis-vaccenyl acetate (cVA), an olfactory pheromone, but (z)-7-tricosene sensitivity was independent of cVA. (z)-7-tricosene and cVA therefore regulate aggression in a hierarchical manner. Furthermore, the increased courtship caused by depletion of male cuticular hydrocarbons was suppressed by a mutation in the olfactory receptor Or47b. Thus, male social behaviors are controlled by gustatory pheromones that promote aggression and suppress courtship, and whose influences are dominant to olfactory pheromones that enhance these behaviors

Mapping Neural Circuits with Activity-Dependent Nuclear Import of a Transcription Factor

Nuclear factor of activated T cells (NFAT) is a calcium-responsive transcription factor. We describe here an NFAT-based neural tracing method—CaLexA (calcium-dependent nuclear import of Lex A)—for labeling active neurons in behaving animals. In this system, sustained neural activity induces nuclear import of the chimeric transcription factor LexA-VP16-NFAT, which in turn drives green fluorescent protein (GFP) reporter expression only in active neurons. We tested this system in Drosophila and found that volatile sex pheromones excite specific neurons in the olfactory circuit. Furthermore, complex courtship behavior associated with multi-modal sensory inputs activated neurons in the ventral nerve cord. This method harnessing the mechanism of activity-dependent nuclear import of a transcription factor can be used to identify active neurons in specific neuronal population in behaving animals