BioSig3D: High Content Screening of Three-Dimensional Cell Culture Models

BioSig3D is a computational platform for high-content screening of three-dimensional (3D) cell culture models that are imaged in full 3D volume. It provides an end-to-end solution for designing high content screening assays, based on colony organization that is derived from segmentation of nuclei in each colony. BioSig3D also enables visualization of raw and processed 3D volumetric data for quality control, and integrates advanced bioinformatics analysis. The system consists of multiple computational and annotation modules that are coupled together with a strong use of controlled vocabularies to reduce ambiguities between different users. It is a web-based system that allows users to: design an experiment by defining experimental variables, upload a large set of volumetric images into the system, analyze and visualize the dataset, and either display computed indices as a heatmap, or phenotypic subtypes for heterogeneity analysis, or download computed indices for statistical analysis or integrative biology. BioSig3D has been used to profile baseline colony formations with two experiments: (i) morphogenesis of a panel of human mammary epithelial cell lines (HMEC), and (ii) heterogeneity in colony formation using an immortalized non-transformed cell line. These experiments reveal intrinsic growth properties of well-characterized cell lines that are routinely used for biological studies. BioSig3D is being released with seed datasets and video-based documentation.     

Activation of brain steroidogenesis and neurogenesis during the gonadal differentiation in protandrous black porgy,Acanthopagrus schlegelii

The early brain development, at the time of gonadal differentiation was investigated using a protandrous teleost, black porgy. This natural model of monosex juvenile fish avoids the potential complexity of sexual dimorphism. Brain neurogenesis was evaluated by histological analyses of the diencephalon, at the time of testicular differentiation (in fish between 90 and 150 days after hatching). Increases in the number of both Nissl‐stained total brain cells, and Pcna‐immunostained proliferative brain cells were observed in specific area of the diencephalon, such as ventromedialis thalami and posterior preoptic area, revealing brain cell proliferation. qPCR analyses showed significantly higher expression of the radial glial cell marker blbp and neuron marker bdnf. Strong immunohistochemical staining of Blbp and extended cellular projections were observed. A peak expression of aromatase (cyp19a1b), as well as an increase in estradiol (E₂) content were also detected in the early brain. These data demonstrate that during gonadal differentiation, the early brain exhibits increased E₂ synthesis, cell proliferation, and neurogenesis. To investigate the role of E₂ in early brain, undifferentiated fish were treated with E₂ or aromatase inhibitor (AI). E₂ treatment upregulated brain cyp19a1b and blbp expression, and enhanced brain cell proliferation. Conversely, AI reduced brain cell proliferation. Castration experiment did not influence the brain gene expression patterns and the brain cell number. Our data clearly support E₂ biosynthesis in the early brain, and that brain E₂ induces neurogenesis. These peak activity patterns in the early brain occur at the time of gonad differentiation but are independent of the gonads. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 121–136, 2016     

Age- and Gender-Related Mean Hearing Threshold in a Highly-Screened Population: The Korean National Health and Nutrition Examination Survey 2010–2012

Background

In evaluating hearing disability in medicolegal work, the apportionment of age- and gender-related sensorineural hearing loss should be considered as a prior factor, especially for the elderly. However, in the literature written in the English language no studies have reported on the age- and gender-related mean hearing threshold for the South Korean population.

Objective

This study aimed to identify the mean hearing thresholds in the South Korean population to establish reference data and to identify the age- and gender-related characteristics.

Methods

This study is based on the Korea National Health and Nutrition Examination Survey (KNHANES) 2010–2012, which was conducted by the Korean government, the data of which was disclosed to the public. A total of 15,606 participants (unweighted) representing 33,011,778 Koreans (weighted) with normal tympanic membrane and no history of regular or occupational noise exposure were selected and analyzed in this study. The relationship between the hearing threshold level and frequency, age, and gender was investigated and analyzed in a highly-screened population by considering the sample weights of a complex survey design.

Results

A gender ratio difference was found between the unweighted and the weighted designs: male:female, 41.0%: 59.0% (unweighted, participants) vs. 47.2%:52.8% (weighted, representing population). As age increased, the hearing threshold increased for all frequencies. Hearing thresholds of 3 kHz, 4 kHz, and 6 kHz showed a statistical difference between both genders for people older than 30, with the 4 kHz frequency showing the largest difference. This paper presents details about the mean hearing threshold based on age and gender.

Conclusions

The data from KNHANES 2010–2012 showed gender differences at hearing thresholds of 3 kHz, 4 kHz, and 6 kHz in a highly-screened population. The most significant gender difference in relation to hearing threshold was observed at 4 kHz. The hearing thresholds at all of the tested frequencies worsened with increasing age. The mean hearing thresholds suggested in this study will be useful for the formulation of healthcare-related hearing policies and used as reference data for disability ratings for hearing loss due to various causes.     

The Influence of Perioperative Dexmedetomidine on Patients Undergoing Cardiac Surgery: A Meta-Analysis

BackgroundThe use of dexmedetomidine may have benefits on the clinical outcomes of cardiac surgery. We conducted a meta-analysis comparing the postoperative complications in patients undergoing cardiac surgery with dexmedetomidine versus other perioperative medications to determine the influence of perioperative dexmedetomidine on cardiac surgery patients.MethodsRandomized or quasi-randomized controlled trials comparing outcomes in patients who underwent cardiac surgery with dexmedetomidine, another medication, or a placebo were retrieved from EMBASE, PubMed, the Cochrane Library, and Science Citation Index.ResultsA total of 1702 patients in 14 studies met the selection criteria among 1,535 studies that fit the research strategy. Compared to other medications, dexmedetomidine has combined risk ratios of 0.28 (95% confidence interval [CI] 0.15, 0.55, P = 0.0002) for ventricular tachycardia, 0.35 (95% CI 0.20, 0.62, P = 0.0004) for postoperative delirium, 0.76 (95% CI 0.55, 1.06, P = 0.11) for atrial fibrillation, 1.08 (95% CI 0.74, 1.57, P = 0.69) for hypotension, and 2.23 (95% CI 1.36, 3.67, P = 0.001) for bradycardia. In addition, dexmedetomidine may reduce the length of intensive care unit (ICU) and hospital stay.ConclusionsThis meta-analysis revealed that the perioperative use of dexmedetomidine in patients undergoing cardiac surgery can reduce the risk of postoperative ventricular tachycardia and delirium, but may increase the risk of bradycardia. The estimates showed a decreased risk of atrial fibrillation, shorter length of ICU stay and hospitalization, and increased risk of hypotension with dexmedetomidine.     

Communication interference in sympatrically occurring moth species

In moth species, females emit a species‐specific sex pheromone that is perceived over long distance by conspecific males. The species‐specificity in the chemical communication channel is achieved by a combination of unique components in specific ratios and sometimes also by interspecific behavioural antagonists to deter sympatrically occurring heterospecific males. In this study, we determined possible antagonistic effects in Helicoverpa gelotopoeon Dyar (Lepidoptera: Noctuidae) males to the major sex pheromone component of sympatrically occurring heliothine moths, Z11‐16:Ald, as well as to the sex pheromone of the sympatrically occurring Heliothis virescens (Fabricius) (Lepidoptera: Noctuidae) (Z11‐16:Ald and Z9‐14:Ald). We also explored whether other co‐occurring species are attracted to these pheromone blends. Our field experiments showed that the addition of Z11‐16:Ald alone or in combination with Z9‐14:Ald inhibited trap catches of H. gelotopoeon males and that this inhibition depended on the concentration of these compounds. In addition, other moth species were attracted to the blends. Together, our results confirm the antagonistic effect of heterospecific sex pheromone compounds of H. virescens to H. gelotopoeon.     

Acoustic sequences in non‐human animals: a tutorial review and prospectus

Animal acoustic communication often takes the form of complex sequences, made up of multiple distinct acoustic units. Apart from the well‐known example of birdsong, other animals such as insects, amphibians, and mammals (including bats, rodents, primates, and cetaceans) also generate complex acoustic sequences. Occasionally, such as with birdsong, the adaptive role of these sequences seems clear (e.g. mate attraction and territorial defence). More often however, researchers have only begun to characterise – let alone understand – the significance and meaning of acoustic sequences. Hypotheses abound, but there is little agreement as to how sequences should be defined and analysed. Our review aims to outline suitable methods for testing these hypotheses, and to describe the major limitations to our current and near‐future knowledge on questions of acoustic sequences. This review and prospectus is the result of a collaborative effort between 43 scientists from the fields of animal behaviour, ecology and evolution, signal processing, machine learning, quantitative linguistics, and information theory, who gathered for a 2013 workshop entitled, ‘Analysing vocal sequences in animals’. Our goal is to present not just a review of the state of the art, but to propose a methodological framework that summarises what we suggest are the best practices for research in this field, across taxa and across disciplines. We also provide a tutorial‐style introduction to some of the most promising algorithmic approaches for analysing sequences. We divide our review into three sections: identifying the distinct units of an acoustic sequence, describing the different ways that information can be contained within a sequence, and analysing the structure of that sequence. Each of these sections is further subdivided to address the key questions and approaches in that area. We propose a uniform, systematic, and comprehensive approach to studying sequences, with the goal of clarifying research terms used in different fields, and facilitating collaboration and comparative studies. Allowing greater interdisciplinary collaboration will facilitate the investigation of many important questions in the evolution of communication and sociality.     

Sonic hedgehog is a regulator of extracellular glutamate levels and epilepsy

Sonic hedgehog (Shh), both as a mitogen and as a morphogen, plays an important role in cell proliferation and differentiation during early development. Here, we show that Shh inhibits glutamate transporter activities in neurons, rapidly enhances extracellular glutamate levels, and affects the development of epilepsy. Shh is quickly released in response to epileptic, but not physiological, stimuli. Inhibition of neuronal glutamate transporters by Shh depends on heterotrimeric G protein subunit Gα_i and enhances extracellular glutamate levels. Inhibiting Shh signaling greatly reduces epileptiform activities in both cell cultures and hippocampal slices. Moreover, pharmacological or genetic inhibition of Shh signaling markedly suppresses epileptic phenotypes in kindling or pilocarpine models. Our results suggest that Shh contributes to the development of epilepsy and suppression of its signaling prevents the development of the disease. Thus, Shh can act as a modulator of neuronal activity, rapidly regulating glutamate levels and promoting epilepsy.