11 research outputs found
Identification of brain transcriptional variation reproduced in peripheral blood: an approach for mapping brain expression traits
Genome-wide gene expression studies may provide substantial insight into gene activities and biological pathways differing between tissues and individuals. We investigated such gene expression variation by analyzing expression profiles in brain tissues derived from eight different brain regions and from blood in 12 monkeys from a biomedically important non-human primate model, the vervet (Chlorocebus aethiops sabaeus). We characterized brain regional differences in gene expression, focusing on transcripts for which inter-individual variation of expression in brain correlates well with variation in blood from the same individuals. Using stringent criteria, we identified 29 transcripts whose expression is measurable, stable, replicable, variable between individuals, relevant to brain function and heritable. Polymorphisms identified in probe regions could, in a minority of transcripts, confound the interpretation of the observed inter-individual variation. The high heritability of levels of these transcripts in a large vervet pedigree validated our approach of focusing on transcripts that showed higher inter-individual compared with intra-individual variation. These selected transcripts are candidate expression Quantitative Trait Loci, differentially regulating transcript levels in the brain among individuals. Given the high degree of conservation of tissue expression profiles between vervets and humans, our findings may facilitate the understanding of regional and individual transcriptional variation and its genetic mechanisms in humans. The approach employed hereāutilizing higher quality tissue and more precise dissection of brain regions than is usually possible in humansāmay therefore provide a powerful means to investigate variation in gene expression relevant to complex brain related traits, including human neuropsychiatric diseases
The effects of testosterone and cortisol on the cognitive domain of empathy
FrĆ¼here Forschung hat gezeigt, dass Testosteron negativ mit empathischen FƤhigkeiten in Verbindung steht. Diese Beobachtung bezieht sich sowohl auf prƤnatale Testosteronbelastung als auch auf den basalen Testosteronspiegel. DarĆ¼ber hinaus haben pharmakologische Studien gezeigt, dass die Verabreichung von Testosteron zu einer BeeintrƤchtigung sozio-kognitiver FƤhigkeiten fĆ¼hrt, die mit Empathie in Verbindung gebracht werden. AuĆerdem hat sich gezeigt, dass auch Stress Auswirkungen auf Empathie und damit einhergehende soziale PhƤnomene haben kann. Die Annahme, dass Testosteron und Cortisol in Bezug auf Verhaltensweisen in sozialen Interaktionen miteinander interagieren, wird durch die Beobachtung gestĆ¼tzt, dass Cortisol und Testosteron intrinsisch ko-reguliert sind.
In der vorliegenden Arbeit wollten wir anhand einer doppelverblindeten, Placebo-kontrollierten between-subject Studie untersuchen, wie eine einzelne Dosis Testosteron kognitive Prozesse bei gesunden jungen MƤnnern (N = 120) beeinflusst, die im Zusammenhang mit kognitiver Empathie stehen. Kognitive Empathie wurde erhoben mittels des "Reading the mind in the eye" Tests, einer Aufgabe zur Emotionserkennung, einer Aufgabe zur PerspektivĆ¼bernahme und einer Aufgabe zur Inhibition imitierender Tendenzen. Weiterhin haben wir unter Verwendung des Cold Pressor Test (CPT) und dem Socially Evaluative Cold Pressor Test (SECPT) zur Stressinduktion, mƶgliche interaktive Effekte von Stress und Testosteronverabreichung untersucht. DarĆ¼ber hinaus haben wir untersucht, ob das VerhƤltnis des zweiten und vierten Fingers (2D:4D) - ein Mittel prƤnatale Testosteronbelastung zu erfassen - die Wirkung der Testosteronverabreichung auf kognitive Empathie mildert. SchlieĆlich untersuchten wir mƶgliche direkte ZusammenhƤnge zwischen 2D:4D-VerhƤltnis, basalem Testosteronspiegel und der Leistung in den Aufgaben.
Unsere Ergebnisse deuten darauf hin, dass die Testosteronverabreichung keinen negativen Einfluss auf die Leistung in den Aufgaben hatte. DarĆ¼ber hinaus lieferten unsere Daten keine Hinweise auf einen interaktiven Effekt zwischen Testosterongabe und Stress. Wir fanden jedoch partielle Beweise fĆ¼r einen Zusammenhang zwischen dem 2D:4D-VerhƤltnis und der Leistung in den Aufgaben. Im Einklang mit frĆ¼heren Forschungen fanden wir, dass in dem REMT und in der Aufgabe zur PerspektivĆ¼bernahme, kleinere 2D:4D-VerhƤltnisse mit einer schlechteren Leistung assoziiert waren. DarĆ¼ber hinaus prognostizierten hƶhere basale Testosteronwerte eine schlechtere Leistung bei der Aufgabe zur PerspektivĆ¼bernahme.
WƤhrend wir Beweise dafĆ¼r fanden, dass Testosteron das Verhalten von Erwachsenen durch prƤnatale organisatorische Effekte modulieren kƶnnte, wurden unsere Haupthypothesen zur Untersuchung der kausalen Effekte von Testosteron und Stress nicht bestƤtigt. Die vorliegende Studie liefert theoretische und methodische Erkenntnisse, die fĆ¼r die zukĆ¼nftige Forschung zum Thema neuroendokrinologische Mechanismen, die soziokognitiven Prozessen zugrunde liegen, von Nutzen sein kƶnnten.Previous research has suggested that testosterone is negatively associated with empathic abilities. This observation refers to both prenatal testosterone exposure as well as basal testosterone levels. Further, pharmacological treatment studies have shown that administration of testosterone leads to an impairment in socio-cognitive abilities related to empathy. Besides, stress has also been shown to have effects on empathy and related social phenomena. The assumption that testosterone and cortisol interact with each other in regard to behavioral outcome in social interactions is supported by the observation that cortisol and testosterone are intrinsically co-regulated.
Here, using a double-blind, placebo-controlled between-subject design, we aimed to assess how a single dose of testosterone impacts cognitive processes related to cognitive empathy in healthy young men (N = 120). Cognitive empathy was assessed by the use of the Reading the mind in the eyes task, an emotion recognition task, a perspective-taking task and an imitation-inhibition task. Further, using the Cold Pressor Test (CPT) and the Socially Evaluative Cold Pressor Test (SECPT) for stress induction, we looked into possible interactive effects of stress and testosterone administration. In addition, we investigated whether the second-to-fourth digit ratio (2D:4D) ā a proxy of fetal testosterone levels ā moderated the effect of testosterone administration on cognitive empathy. Lastly, we examined possible direct links between 2D:4D ratios, basal testosterone levels and performance in the tasks.
Our results indicate that testosterone administration did not have a negative impact on performance in the tasks. Further, our data did not provide any evidence for an interactive effect between testosterone administration and stress. We did however find partial evidence for a relationship between the 2D:4D ratio and performance in the task. In line with previous research, we found that in in the REMT and in the perspective-taking task, lower 2D:4D ratio, indicating higher fetal testosterone, was associated with poorer performance. Furthermore, higher basal levels of testosterone predicted poorer performance in the perspective-taking task.
While we did find evidence that testosterone might modulate adult behavior through prenatal organizational effects, our main hypotheses investigating causal effects of testosterone and stress were not confirmed. The study provides a theoretical and methodological insight that might be of value for future research on the topic of neuroendocrinological mechanisms underlying socio-cognitive processes
Identification and characterization of constrained non-exonic bases lacking predictive epigenomic and transcription factor binding annotations.
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Computational Methods for Processing and Analyzing Large Scale Genomics Datasets
This dissertation develops computational methods for analyzing large-scale genomic and epigenomic datasets. We developed a supervised machine learning approach to predict non-exonic evolutionarily conserved regions in the human genome based on vast amount of functional genomics data. The resulting probabilistic predictions provide a resource for prioritizing functionally important regulatory regions in the human genome. We also developed a method for identifying from large-scale gene expression datasets genes that are differentially expressed in both blood and brain from 12 vervet monkeys, which we used to identify 29 transcripts whose expression is variable between individuals and heritable. Additionally, we developed a method using a global search optimization algorithm to successfully improve a model of human thyroid hormone regulation dynamics leading to a better fit of data for thyrotoxicosis. Together, these three approaches have the potential to impact the understanding and eventual treatment of disease
Computational Methods for Processing and Analyzing Large Scale Genomics Datasets
This dissertation develops computational methods for analyzing large-scale genomic and epigenomic datasets. We developed a supervised machine learning approach to predict non-exonic evolutionarily conserved regions in the human genome based on vast amount of functional genomics data. The resulting probabilistic predictions provide a resource for prioritizing functionally important regulatory regions in the human genome. We also developed a method for identifying from large-scale gene expression datasets genes that are differentially expressed in both blood and brain from 12 vervet monkeys, which we used to identify 29 transcripts whose expression is variable between individuals and heritable. Additionally, we developed a method using a global search optimization algorithm to successfully improve a model of human thyroid hormone regulation dynamics leading to a better fit of data for thyrotoxicosis. Together, these three approaches have the potential to impact the understanding and eventual treatment of disease
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Identification and characterization of constrained non-exonic bases lacking predictive epigenomic and transcription factor binding annotations.
Annotations of evolutionary sequence constraint based on multi-species genome alignments and genome-wide maps of epigenomic marks and transcription factor binding provide important complementary information for understanding the human genome and genetic variation. Here we developed the Constrained Non-Exonic Predictor (CNEP) to quantify the evidence of each base in the genome being in an evolutionarily constrained non-exonic element from an input of over 60,000 epigenomic and transcription factor binding features. We find that the CNEP score outperforms baseline and related existing scores at predicting evolutionarily constrained non-exonic bases from such data. However, a subset of them are still not well predicted by CNEP. We developed a complementary Conservation Signature Score by CNEP (CSS-CNEP) that is predictive of those bases. We further characterize the nature of constrained non-exonic bases with low CNEP scores using additional types of information. CNEP and CSS-CNEP are resources for analyzing constrained non-exonic bases in the genome
Recommended from our members
Identification and characterization of constrained non-exonic bases lacking predictive epigenomic and transcription factor binding annotations.
Annotations of evolutionary sequence constraint based on multi-species genome alignments and genome-wide maps of epigenomic marks and transcription factor binding provide important complementary information for understanding the human genome and genetic variation. Here we developed the Constrained Non-Exonic Predictor (CNEP) to quantify the evidence of each base in the genome being in an evolutionarily constrained non-exonic element from an input of over 60,000 epigenomic and transcription factor binding features. We find that the CNEP score outperforms baseline and related existing scores at predicting evolutionarily constrained non-exonic bases from such data. However, a subset of them are still not well predicted by CNEP. We developed a complementary Conservation Signature Score by CNEP (CSS-CNEP) that is predictive of those bases. We further characterize the nature of constrained non-exonic bases with low CNEP scores using additional types of information. CNEP and CSS-CNEP are resources for analyzing constrained non-exonic bases in the genome
Recommended from our members
Identification of brain transcriptional variation reproduced in peripheral blood: an approach for mapping brain expression traits.
Genome-wide gene expression studies may provide substantial insight into gene activities and biological pathways differing between tissues and individuals. We investigated such gene expression variation by analyzing expression profiles in brain tissues derived from eight different brain regions and from blood in 12 monkeys from a biomedically important non-human primate model, the vervet (Chlorocebus aethiops sabaeus). We characterized brain regional differences in gene expression, focusing on transcripts for which inter-individual variation of expression in brain correlates well with variation in blood from the same individuals. Using stringent criteria, we identified 29 transcripts whose expression is measurable, stable, replicable, variable between individuals, relevant to brain function and heritable. Polymorphisms identified in probe regions could, in a minority of transcripts, confound the interpretation of the observed inter-individual variation. The high heritability of levels of these transcripts in a large vervet pedigree validated our approach of focusing on transcripts that showed higher inter-individual compared with intra-individual variation. These selected transcripts are candidate expression Quantitative Trait Loci, differentially regulating transcript levels in the brain among individuals. Given the high degree of conservation of tissue expression profiles between vervets and humans, our findings may facilitate the understanding of regional and individual transcriptional variation and its genetic mechanisms in humans. The approach employed here-utilizing higher quality tissue and more precise dissection of brain regions than is usually possible in humans-may therefore provide a powerful means to investigate variation in gene expression relevant to complex brain related traits, including human neuropsychiatric diseases
Formation of oxygen complexes in controlled atmosphere at surface of doped glassy carbon
The effects of boron and phosphorus incorporation in phenolic resin precursor to the oxidation resistance of glassy carbon have been studied. In order to reveal the nature and composition of the oxygen complexes formed at the surface of doped glassy carbon, under controlled atmosphere, the surface of the samples was cleaned under vacuum up to 1273 K. Specific functional groups, subsequently formed under dry CO2 or O-2 atmosphere on the surface of boron-doped and phosphorus-doped glassy carbon samples, were examined using the temperature-programmed desorption method combined with mass spectrometric analysis. Characterization of surface properties of undoped and doped samples has shown that in the presence of either boron or phosphorus heteroatoms, a lower amount of oxygen complexes formed after CO2 exposure, while, typically, higher amount of oxygen complexes formed after O-2 exposure. It has been concluded that the surface of undoped glassy carbon has a greater affinity towards CO2, while in the presence of either boron or phosphorus heteroatoms, the glassy carbon surface affinity becomes greater towards O-2, under experimental conditions