Fluorescence Behavioral Imaging (FBI) Tracks Identity in Heterogeneous Groups of Drosophila

Distinguishing subpopulations in group behavioral experiments can reveal the impact of differences in genetic, pharmacological and life-histories on social interactions and decision-making. Here we describe Fluorescence Behavioral Imaging (FBI), a toolkit that uses transgenic fluorescence to discriminate subpopulations, imaging hardware that simultaneously records behavior and fluorescence expression, and open-source software for automated, high-accuracy determination of genetic identity. Using FBI, we measure courtship partner choice in genetically mixed groups of Drosophila.     

Assessing Social Engagement in Heterogeneous Groups of Zebrafish: A New Paradigm for Autism-Like Behavioral Responses

Because of its highly developed social character, zebrafish is a promising model system for the study of the genetic and neurochemical basis of altered social engagement such as is common in autism and schizophrenia. The traditional shoaling paradigm investigates social cohesion in homogeneous groups of zebrafish. However, the social dynamics of mixed groups is gaining interest from a therapeutic point of view and thus warrants animal modeling. Furthermore, mutant zebrafish are not always available in large numbers. Therefore, we developed a new paradigm that allows exploring shoaling in heterogeneous groups. The effects of MK-801, a non-competitive antagonist of the glutamate N-methyl-D-aspartate (NMDA) receptor, on social cohesion were studied to evaluate the paradigm. The drug has previously been shown to mimic aspects of autism and schizophrenia. Our results show that a single MK-801-treated zebrafish reduced social cohesion of the entire shoal drastically. Preliminary observations suggest that the social dynamics of the shoal as a whole was altered.     

Impact of Obesity on Pregnancy Outcome in Different Ethnic Groups: Calculating Population Attributable Fractions

Objectives

To quantify the proportion of adverse pregnancy outcome attributable to maternal obesity.

Design

Cross sectional analysis of routine obstetric dataset.

Setting

Guy’s and St Thomas’s NHS Foundation Trust (GSTFT).

Population

23,668 women who had singleton deliveries at GSTFT between 2004 and 2008.

Methods

Logistic regression was used to estimate the association between BMI and outcome in different ethnic groups. Adjusted odds ratios, and the proportions of obese women, were used to calculate population attributable risk fractions (PAFs).

Main Outcome Measures

(i) Maternal outcomes: diabetes, type of delivery, post-partum haemorrhage, and preterm delivery. (ii) Perinatal outcomes: macrosomia, low birth weight, admission to neonatal intensive care/special care baby unit, and perinatal death.

Results

The prevalence of maternal obesity was 14%. Increasing BMI was independently associated with increasing risk of adverse obstetric and neonatal outcome. At the individual level, the effect of obesity on diabetes was highest in Asian women compared to white women (p for interaction = 0.03). Calculation of population attributable risk fractions demonstrated that one third of diabetes cases and one in six Caesarean sections could be avoided in this population if all obese women were of normal BMI. At the population level, the contribution of obesity to diabetes was highest for Black women (42%), and lowest for oriental women (8%). Seven percent of neonatal macrosomia in all the population, and 13% in Black mothers, were attributable to obesity.

Conclusions

Preventing obesity prior to pregnancy will substantially reduce the burden of obstetric and neonatal morbidity in this population. This reduction will be higher in Black women.     

内蒙古7个群体优势眼的调查

1987～1991年间4次调查了内蒙古7个群体3 247例优势眼的分布特征。研究结果显示：（1）7个群体中右优势眼出现率约为70%～80%。呼和浩特回族、阿拉善蒙古族右优势眼出现率明显低于其他5个群体;（2）右优势眼出现率无性别间差异;（3）优势眼与惯用手这两个性状间存在一定的联系。 Abstract：　A survey on distribution of eye preference of 3247 cases among seven groups in Inner Mongolia were carried out from 1987 to 1991. The results showed that：（1）The right-eye preference showed a frequency of 70%～80% in seven groups. The Hui ethinc group of Huhhot city and Mongols of Alashan League had a obviously lower frequency of this trait than the other five groups.（2）The frequency of this trait showed no sexual signi-ficant difference.（3）There were cor-relations between the eye preference and handedness.     

内蒙古7个群体优势眼的调查

1987～1991年间4次调查了内蒙古7个群体3 247例优势眼的分布特征。研究结果显示：（1）7个群体中右优势眼出现率约为70%～80%。呼和浩特回族、阿拉善蒙古族右优势眼出现率明显低于其他5个群体;（2）右优势眼出现率无性别间差异;（3）优势眼与惯用手这两个性状间存在一定的联系。 Abstract：　A survey on distribution of eye preference of 3247 cases among seven groups in Inner Mongolia were carried out from 1987 to 1991. The results showed that：（1）The right-eye preference showed a frequency of 70%～80% in seven groups. The Hui ethinc group of Huhhot city and Mongols of Alashan League had a obviously lower frequency of this trait than the other five groups.（2）The frequency of this trait showed no sexual signi-ficant difference.（3）There were cor-relations between the eye preference and handedness.     

The Impact of Heterogeneous Thresholds on Social Contagion with Multiple Initiators

The threshold model is a simple but classic model of contagion spreading in complex social systems. To capture the complex nature of social influencing we investigate numerically and analytically the transition in the behavior of threshold-limited cascades in the presence of multiple initiators as the distribution of thresholds is varied between the two extreme cases of identical thresholds and a uniform distribution. We accomplish this by employing a truncated normal distribution of the nodes’ thresholds and observe a non-monotonic change in the cascade size as we vary the standard deviation. Further, for a sufficiently large spread in the threshold distribution, the tipping-point behavior of the social influencing process disappears and is replaced by a smooth crossover governed by the size of initiator set. We demonstrate that for a given size of the initiator set, there is a specific variance of the threshold distribution for which an opinion spreads optimally. Furthermore, in the case of synthetic graphs we show that the spread asymptotically becomes independent of the system size, and that global cascades can arise just by the addition of a single node to the initiator set.     

Behavioral Aspects of Rodent Population Biology

Five approaches to the study of behavior as a factor in thepopulation biology of rodents are outlined. These approachesare: (1) genetics, (2) physiology, (3) chronobiology,(4) behavioralecology and sociobiology, and (5) the use of intra- and inter-specificcomparisons. For each approach selected examples from the recentliterature, from this symposium and from my own work are usedto illustrate the new directions that are emerging for analyzingbehavior as a factor affecting natality, mortality and emigration/immigrationin rodents. Areas where additional investigations are neededare noted including some questions to be tested by future experiments.A variety of new techniques that have been developed or areinnovative applications of existing techniques are incorporatedinto the examples. Most of the material presented concerns fourgenera of rodents, Microtus, Mus, Peromyscus, and Rattus. Thefollowing major conclusions emerge from an overview of theseapproaches: Most recent research on behavior as a factor inrodent population biology has been concerned primarily withnatality. Few investigators have dealt with mortality and onlya limited number have explored emigration/immigration. Fieldand laboratory studies on behavioral aspects of rodent populationbiology have become more integrated than they were several decadesago. Both proximate and ultimate questions about behavior andpopulation dynamics are now being tested by both laboratoryand field methods. In contrast to some earlier approaches thatoften viewed population control as involving a single factor,most emerging conceptual frameworks have, as a major assumption,that population regulation is a multi-factorial process includingmany behavioral components.     

Modeling the Potential Impact of Host Population Survival on the Evolution of M. tuberculosis Latency

Tuberculosis (TB) is an infectious disease with a peculiar feature: Upon infection with the causative agent, Mycobacterium Tuberculosis (MTB), most hosts enter a latent state during which no transmission of MTB to new hosts occurs. Only a fraction of latently infected hosts develop TB disease and can potentially infect new hosts. At first glance, this seems like a waste of transmission potential and therefore an evolutionary suboptimal strategy for MTB. It might be that the human immune response keeps MTB in check in most hosts, thereby preventing it from achieving its evolutionary optimum. Another possible explanation is that long latency and progression to disease in only a fraction of hosts are evolutionary beneficial to MTB by allowing it to persist better in small host populations. Given that MTB has co-evolved with human hosts for millenia or longer, it likely encountered small host populations for a large share of its evolutionary history and had to evolve strategies of persistence. Here, we use a mathematical model to show that indeed, MTB persistence is optimal for an intermediate duration of latency and level of activation. The predicted optimal level of activation is above the observed value, suggesting that human co-evolution has lead to host immunity, which keeps MTB below its evolutionary optimum.     

Diurnal and Seasonal Changes in Thermal Preference of Single,Isolated Bees and Small Groups of Bees (Apis mellifera L.)

The aim of the present study was: to compare thermoregulatory behaviour of single honeybee workers and groups of 3–15 bees over their annual activity period and to check out whether the annual fluctuations of ambient temperature selection are correlated with phases of the colony development. Thermal behaviour of both single workers and groups of bees was recorded, using a video camera, in a thermal gradient system. Thermal preferences of the insects were tested seasonally in spring (May/June), summer (July/August) and autumn (September–November). Both single bees and small groups of bees changed their thermal behaviour in daily cycle. The season of the year had distinct effect on temperature preferences of both single honeybee workers or small groups of bees. In single honeybee workers the lowest ambient temperatures were preferred in late spring (the swarming phase) while the highest temperatures were selected during the summer (the colony growing phase). There were significant seasonal changes in ambient temperature selected by groups of honeybee workers. Groups of honeybee workers tended to prefer the lowest temperatures in late spring and the highest temperatures were selected during the summer. The day-night differences exhibited by small groups of bees in our experiments are likely to represent behavioural responses of the honeybee colony. In our experiments we proved an influence of the season of the year on the honeybees’ thermal behaviour, which might be connected with seasonal shifts of temperature regulated by the honeybee colony.     

不同青枯病抗性的番茄品种内生细菌生理群数量研究

本论文对青枯病抗性不同的番茄品种其内生细菌生理群数量变化进行了研究,结果表明,番茄内生细菌生理群数量的变化随品种抗性、生育期和季节的不同而变化.在7大类生理群细菌中,氨化细菌的数量最多,且在幼苗期以后,高抗青枯病番茄品种中数量明显高于高感品种,初步认为,氨化细菌可能是影响青枯病发生的关键性微生物.番茄抗病品种在不同生育期,其内生细菌的总体数量要比感病品种多,呈交替波动变化.氨化细菌、硝化细菌、固氮细菌和反硫化细菌平均数量均表现为在夏季高于冬季,硫化细菌的数量则冬季高于夏季,厌气性细菌数量最少.     

Evolution under Spatially Heterogeneous Selection in Solid Tumors

Spatial genetic and phenotypic diversity within solid tumors has been well documented. Nevertheless, how this heterogeneity affects temporal dynamics of tumorigenesis has not been rigorously examined because solid tumors do not evolve as the standard population genetic model due to the spatial constraint. We therefore, propose a neutral spatial (NS) model whereby the mutation accumulation increases toward the periphery; the genealogical relationship is spatially determined and the selection efficacy is blunted (due to kin competition). In this model, neutral mutations are accrued and spatially distributed in manners different from those of advantageous mutations. Importantly, the distinctions could be blurred in the conventional model. To test the NS model, we performed a three-dimensional multiple microsampling of two hepatocellular carcinomas. Whole-genome sequencing (WGS) revealed a 2-fold increase in mutations going from the center to the periphery. The operation of natural selection can then be tested by examining the spatially determined clonal relationships and the clonal sizes. Due to limited migration, only the expansion of highly advantageous clones can sweep through a large part of the tumor to reveal the selective advantages. Hence, even multiregional sampling can only reveal a fraction of fitness differences in solid tumors. Our results suggest that the NS patterns are crucial for testing the influence of natural selection during tumorigenesis, especially for small solid tumors.     

Laboratory Research on Behavioral Interactions as Generators of Population Phenomena in Rodents

Many population phenomena are driven by the behavior of individualanimals. The effects of behavior on differential reproductionvary with the mating system and with ecological factors; understandingof the complex interactions requires both laboratory and fieldresearch. Ecologically-relevant laboratory research should bedesigned using generalizable behavioral patterns with animalsof appropriate species, meaningful genotypes, and known earlyexperience that are studied in carefully-designed situations.Three exemplars of research of potential relevance to populationphenomena are discussed. Studies of dominance and differentialreproduction in deer mice in seminatural enclosures suggestthat dominant males make disproportionately large contributionsto gene pools and that dominance may be heritable. Laboratorystudies of reproductive function in individuals bearing differentalleles, determined electrophoretically, appear relevant topopulation processes reported correlated with changes in genefrequencies at these loci. Patterns of mate choice in two speciesof Microtus may be important in generating their contrastingmating systems in the field. Well-designed laboratory researchcan help reveal behavioral processes critical to populationphenomena.     

Effects of Voluntary Alcohol Intake on Risk Preference and Behavioral Flexibility during Rat Adolescence

Alcohol use is common in adolescence, with a large portion of intake occurring during episodes of binging. This pattern of alcohol consumption coincides with a critical period for neurocognitive development and may impact decision-making and reward processing. Prior studies have demonstrated alterations in adult decision-making following adolescent usage, but it remains to be seen if these alterations exist in adolescence, or are latent until adulthood. Here, using a translational model of voluntary binge alcohol consumption in adolescents, we assess the impact of alcohol intake on risk preference and behavioral flexibility during adolescence. During adolescence (postnatal day 30–50), rats were given 1-hour access to either a 10% alcohol gelatin mixture (EtOH) or a calorie equivalent gelatin (Control) at the onset of the dark cycle. EtOH consuming rats were classified as either High or Low consumers based on intake levels. Adolescent rats underwent behavioral testing once a day, with one group performing a risk preference task, and a second group performing a reversal-learning task during the 20-day period of gelatin access. EtOH-High rats showed increases in risk preference compared to Control rats, but not EtOH-Low animals. However, adolescent rats did a poor job of matching their behavior to optimize outcomes, suggesting that adolescents may adopt a response bias. In addition, adolescent ethanol exposure did not affect the animals'' ability to flexibly adapt behavior to changing reward contingencies during reversal learning. These data support the view that adolescent alcohol consumption can have short-term detrimental effects on risk-taking when examined during adolescence, which does not seem to be attributable to an inability to flexibly encode reward contingencies on behavioral responses.     

Behavioral Trait of Morningness-Eveningness in Association with Articular and Spinal Diseases in a Population

Earlier studies have revealed that the more the preference to schedule daily activities towards the evening hours is, the higher the odds for a range of health hazards are. Therefore, we wanted to analyze, whether the behavioral trait of morningness-eveningness is associated with articular and spinal diseases or those with musculoskeletal disorders. Participants (n = 6089), as part of the National FINRISK 2007 Study, were derived from the general population, aged 25 to 74 years, living in Finland. Chronotype was assessed based on six items from the original Horne-Östberg Morningness-Eveningness Questionnaire. Information about risk factors and the diagnoses of articular and spinal diseases were based on the self-reported information. Our results suggest that Evening-types have higher odds for articular and spinal diseases as compared with Morning-types, and this risk is heightened especially regarding spinal disease and backache (odds ratios of 1.8 to 2.1, and 1.6 to 1.8, respectively) and remains significant after controlling for the sex, age, education, civil status, physical activity, alcohol use, and smoking, and additionally for the body-mass index, insufficient sleep, or depressive symptoms.     

Testing for Associations of Opposite Directionality in a Heterogeneous Population

In gene networks, it is possible that the patterns of gene co-expression may exist only in a subset of the sample. In studies of relationships between genotypes and expressions of genes over multiple tissues, there may be associations in some tissues but not in the others. Despite the importance of the problem in genomic applications, it is challenging to identify relationships between two variables when the correlation may only exist in a subset of the sample. The situation becomes even less tractable when there exist two subsets in which correlations are in opposite directions. By ranking subset relationships according to Kendall’s tau, a tau-path can be derived to facilitate the identification of correlated subsets, if such subsets exist. However, the current tau-path methodology only considers the situation in which there is association in a subsample; the more complex scenario depicting the existence of two subsets with opposite directionality of associations was not addressed. Further, existing algorithms for finding tau-paths may be suboptimal given their greedy nature. In this paper, we extend the tau-path methodology to accommodate the situation in which the sample may be drawn from a heterogeneous population composed of subpopulations portraying positive and negative associations. We also propose the use of a cross entropy Monte Carlo procedure to obtain an optimal tau-path, CEMC\(_{tp}\). The algorithm not only can provide simultaneous detection of positive and negative correlations in the same sample, but also can lead to the identification of subsamples that provide evidence for the detected associations. An extensive simulation study shows the aptness of CEMC\(_{tp}\) for detecting associations under various scenarios. Compared with two standard tests for detecting associations, CEMC\(_{tp}\) is seen to be more powerful when there are indeed complex subset associations with well-controlled type-I error rates. We applied CEMC\(_{tp}\) to the NCI-60 gene expression data to illustrate its utility for uncovering network relationships that were missed with standard methods.