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Recognizing individual faces is an important human ability that highly depends on experience. This is reflected in the so called other-race effect; adults are better at recognizing faces from their own ethnic group, while very young infants do not show this specialization yet. Two experiments examined whether 3-year-old children from two different cultural backgrounds show the other-race effect. In Experiment 1, German children (N = 41) were presented with a forced choice paradigm where they were asked to recognize female Caucasian or African faces. In Experiment 2, 3-year-olds from Cameroon (N = 66) participated in a similar task using the same stimulus material. In both cultures the other-race effect was present; children were better at recognizing individual faces from their own ethnic group. In addition, German children performed at a higher overall level of accuracy than Cameroonians. The results are discussed in relation to cultural aspects in particular.
The use of reporter gene fusions to assess cellular processes such as protein targeting and regulation of transcription or translation is established technology in archaeal, bacterial, and eukaryal genetics. Fluorescent proteins or enzymes resulting in chromogenic substrate turnover, like β -galactosidase, have been particularly useful for microscopic and screening purposes. However, application of such methodology is of limited use for strictly anaerobic organisms due to the requirement of molecular oxygen for chromophore formation or color development. We have developed β -lactamase from Escherichia coli (encoded by bla) in conjunction with the chromogenic substrate nitrocefin into a reporter system usable under anaerobic conditions for the methanogenic archaeon Methanosarcina acetivorans. By using a signal peptide of a putative flagellin from M. acetivorans and different catabolic promoters, we could demonstrate growth substrate-dependent secretion of β -lactamase, facilitating its use in colony screening on agar plates. Furthermore, a series of fusions comprised of a constitutive promoter and sequences encoding variants of the synthetic tetracycline-responsive riboswitch (tc-RS) was created to characterize its influence on translation initiation in M. acetivorans. One tc-RS variant resulted in more than 11-fold tetracycline-dependent regulation of bla expression, which is in the range of regulation by naturally occurring riboswitches. Thus, tc-RS fusions represent the first solely cis-active, that is, factor-independent system for controlled gene expression in Archaea.
Background: Cichlid fishes show considerable diversity in swim bladder morphology. In members of the subfamily Etroplinae, the connection between anterior swim bladder extensions and the inner ears enhances sound transmission and translates into an improved hearing ability. We tested the hypothesis that those swim bladder modifications coincide with differences in inner ear morphology and thus compared Steatocranus tinanti (vestigial swim bladder), Hemichromis guttatus (large swim bladder without extensions), and Etroplus maculatus (intimate connection between swim bladder and inner ears).
Methodology and results: We applied immunostaining together with confocal imaging and scanning electron microscopy for the investigation of sensory epithelia, and high-resolution, contrast-enhanced microCT imaging for characterizing inner ears in 3D, and evaluated otolith dimensions. Compared to S. tinanti and H. guttatus, inner ears of E. maculatus showed an enlargement of all three maculae, and a particularly large lacinia of the macula utriculi. While our analysis of orientation patterns of ciliary bundles on the three macula types using artificially flattened maculae uncovered rather similar orientation patterns of ciliary bundles, interspecific differences became apparent when illustrating the orientation patterns on the 3D models of the maculae: differences in the shape and curvature of the lacinia of the macula utriculi, and the anterior arm of the macula lagenae resulted in an altered arrangement of ciliary bundles.
Conclusions: Our results imply that improved audition in E. maculatus is associated not only with swim bladder modifications but also with altered inner ear morphology. However, not all modifications in E. maculatus could be connected to enhanced auditory abilities, and so a potential improvement of the vestibular sense, among others, also needs to be considered. Our study highlights the value of analyzing orientation patterns of ciliary bundles in their intact 3D context in studies of inner ear morphology and physiology.
Selection of higher order regression models in the analysis of multi-factorial transcription data
(2014)
Introduction: Many studies examine gene expression data that has been obtained under the influence of multiple factors, such as genetic background, environmental conditions, or exposure to diseases. The interplay of multiple factors may lead to effect modification and confounding. Higher order linear regression models can account for these effects. We present a new methodology for linear model selection and apply it to microarray data of bone marrow-derived macrophages. This experiment investigates the influence of three variable factors: the genetic background of the mice from which the macrophages were obtained, Yersinia enterocolitica infection (two strains, and a mock control), and treatment/non-treatment with interferon-γ.
Results: We set up four different linear regression models in a hierarchical order. We introduce the eruption plot as a new practical tool for model selection complementary to global testing. It visually compares the size and significance of effect estimates between two nested models. Using this methodology we were able to select the most appropriate model by keeping only relevant factors showing additional explanatory power. Application to experimental data allowed us to qualify the interaction of factors as either neutral (no interaction), alleviating (co-occurring effects are weaker than expected from the single effects), or aggravating (stronger than expected). We find a biologically meaningful gene cluster of putative C2TA target genes that appear to be co-regulated with MHC class II genes.
Conclusions: We introduced the eruption plot as a tool for visual model comparison to identify relevant higher order interactions in the analysis of expression data obtained under the influence of multiple factors. We conclude that model selection in higher order linear regression models should generally be performed for the analysis of multi-factorial microarray data.
Background: Endometriosis is characterized by the presence of functional endometrial tissue outside of the uterine cavity. It affects 1 in 10 women of reproductive age. This chronic condition commonly leads to consequences such as pelvic pain, dysmenorrhea, infertility and an elevated risk of epithelial ovarian cancer. Despite the prevalence of endometriosis and its impact on women's lives, there are relatively few in vitro and in vivo models available for studying the complex disease biology, pathophysiology, and for use in the preclinical development of novel therapies. The goal of this study was to develop a novel three-dimensional (3D) cell culture model of ovarian endometriosis and to test whether it is more reflective of endometriosis biology than traditional two dimensional (2D) monolayer cultures.
Methods: A novel ovarian endometriosis epithelial cell line (EEC16) was isolated from a 34-year old female with severe endometriosis. After characterization of cells using in vitro assays, western blotting and RNA-sequencing, this cell line and a second, already well characterized endometriosis cell line, EEC12Z, were established as in vitro 3D spheroid models. We compared biological features of 3D spheroids to 2D cultures and human endometriosis lesions using immunohistochemistry and real-time semi-quantitative PCR.
Results: In comparison to normal ovarian epithelial cells, EEC16 displayed features of neoplastic transformation in in vitro assays. When cultured in 3D, EEC16 and EEC12Z showed differential expression of endometriosis-associated genes compared to 2D monolayer cultures, and more closely mimicked the molecular and histological features of human endometriosis lesions.
Conclusions: To our knowledge, this represents the first report of an in vitro spheroid model of endometriosis. 3D endometriosis models represent valuable experimental tools for studying EEC biology and the development of novel therapeutic approaches.
The multifunctional molecule netrin-1 is upregulated in various malignancies and has recently been presented as a major general player in tumorigenesis leading to tumor progression and maintenance in various animal models. However, there is still a lack of clinico-epidemiological data related to netrin-1 expression. Therefore, the aim of our study was to elucidate the association of netrin-1 expression and patient survival in brain metastases since those constitute one of the most limiting factors for patient prognosis. We investigated 104 brain metastases cases for netrin-1 expression using in-situ hybridization and immunohistochemistry with regard to clinical parameters such as patient survival and MRI data. Our data show that netrin-1 is strongly upregulated in most cancer subtypes. Univariate analyses revealed netrin-1 expression as a significant factor associated with poor patient survival in the total cohort of brain metastasis patients and in sub-entities such as non-small cell lung carcinomas. Interestingly, many cancer samples showed a strong nuclear netrin-1 signal which was recently linked to a truncated netrin-1 variant that enhances tumor growth. Nuclear netrin-1 expression was associated with poor patient survival in univariate as well as in multivariate analyses. Our data indicate both total and nuclear netrin-1 expression as prognostic factors in brain metastases patients in contrast to other prognostic markers in oncology such as patient age, number of brain metastases or Ki67 proliferation index. Therefore, nuclear netrin-1 expression constitutes one of the first reported molecular biomarkers for patient survival in brain metastases. Furthermore, netrin-1 may constitute a promising target for future anti-cancer treatment approaches in brain metastases.
The haloarchaeon Haloferax volcanii was shown to contain 145 intergenic and 45 antisense sRNAs. In a comprehensive approach to unravel various biological roles of haloarchaeal sRNAs in vivo, 27 sRNA genes were selected and deletion mutants were generated. The phenotypes of these mutants were compared to that of the parent strain under ten different conditions, i.e. growth on four different carbon sources, growth at three different salt concentrations, and application of four different stress conditions. In addition, cell morphologies in exponential and stationary phase were observed. Furthermore, swarming of 17 mutants was analyzed. 24 of the 27 mutants exhibited a difference from the parent strain under at least one condition, revealing that haloarchaeal sRNAs are involved in metabolic regulation, growth under extreme conditions, regulation of morphology and behavior, and stress adaptation. Notably, 7 deletion mutants showed a gain of function phenotype, which has not yet been described for any other prokaryotic sRNA gene deletion mutant. Comparison of the transcriptomes of one sRNA gene deletion mutant and the parent strain led to the identification of differentially expressed genes. Genes for flagellins and chemotaxis were up-regulated in the mutant, in accordance with its gain of function swarming phenotype. While the deletion mutant analysis underscored that haloarchaeal sRNAs are involved in many biological functions, the degree of conservation is extremely low. Only 3 of the 27 genes are conserved in more than 10 haloarchaeal species. 22 of the 27 genes are confined to H. volcanii, indicating a fast evolution of haloarchaeal sRNA genes.
Genome-wide association studies are widely used to correlate phenotypic traits with genetic variants. These studies usually compare the genetic variation between two groups to single out certain Single Nucleotide Polymorphisms (SNPs) that are linked to a phenotypic variation in one of the groups. However, it is necessary to have a large enough sample size to find statistically significant correlations. Direct-To-Consumer (DTC) genetic testing can supply additional data: DTC-companies offer the analysis of a large amount of SNPs for an individual at low cost without the need to consult a physician or geneticist. Over 100,000 people have already been genotyped through Direct-To-Consumer genetic testing companies. However, this data is not public for a variety of reasons and thus cannot be used in research. It seems reasonable to create a central open data repository for such data. Here we present the web platform openSNP, an open database which allows participants of Direct-To-Consumer genetic testing to publish their genetic data at no cost along with phenotypic information. Through this crowdsourced effort of collecting genetic and phenotypic information, openSNP has become a resource for a wide area of studies, including Genome-Wide Association Studies. openSNP is hosted at http://www.opensnp.org, and the code is released under MIT-license at http://github.com/gedankenstuecke/snpr.
Three neonicotinoids, imidacloprid, clothianidin and thiacloprid, agonists of the nicotinic acetylcholine receptor in the central brain of insects, were applied at non-lethal doses in order to test their effects on honeybee navigation. A catch-and-release experimental design was applied in which feeder trained bees were caught when arriving at the feeder, treated with one of the neonicotinoids, and released 1.5 hours later at a remote site. The flight paths of individual bees were tracked with harmonic radar. The initial flight phase controlled by the recently acquired navigation memory (vector memory) was less compromised than the second phase that leads the animal back to the hive (homing flight). The rate of successful return was significantly lower in treated bees, the probability of a correct turn at a salient landscape structure was reduced, and less directed flights during homing flights were performed. Since the homing phase in catch-and-release experiments documents the ability of a foraging honeybee to activate a remote memory acquired during its exploratory orientation flights, we conclude that non-lethal doses of the three neonicotinoids tested either block the retrieval of exploratory navigation memory or alter this form of navigation memory. These findings are discussed in the context of the application of neonicotinoids in plant protection.
Objective: The objective of this study was to describe and analyze the effects of depression on health care utilization and costs in a sample of multimorbid elderly patients.
Method: This cross-sectional analysis used data of a prospective cohort study, consisting of 1,050 randomly selected multimorbid primary care patients aged 65 to 85 years. Depression was defined as a score of six points or more on the Geriatric Depression Scale (GDS-15). Subjects passed a geriatric assessment, including a questionnaire for health care utilization. The impact of depression on health care costs was analyzed using multiple linear regression models. A societal perspective was adopted.
Results: Prevalence of depression was 10.7%. Mean total costs per six-month period were €8,144 (95% CI: €6,199-€10,090) in patients with depression as compared to €3,137 (95% CI: €2,735-€3,538; p<0.001) in patients without depression. The positive association between depression and total costs persisted after controlling for socio-economic variables, functional status and level of multimorbidity. In particular, multiple regression analyses showed a significant positive association between depression and pharmaceutical costs.
Conclusion: Among multimorbid elderly patients, depression was associated with significantly higher health care utilization and costs. The effect of depression on costs was even greater than reported by previous studies conducted in less morbid patients.