3D Cultures of Prostate Cancer Cells Cultured in a Novel High-Throughput Culture Platform Are More Resistant to Chemotherapeutics Compared to Cells Cultured in Monolayer

Despite monolayer cultures being widely used for cancer drug development and testing, 2D cultures tend to be hypersensitive to chemotherapy and are relatively poor predictors of whether a drug will provide clinical benefit. Whilst generally more complicated, three dimensional (3D) culture systems often better recapitulate true cancer architecture and provide a more accurate drug response. As a step towards making 3D cancer cultures more accessible, we have developed a microwell platform and surface modification protocol to enable high throughput manufacture of 3D cancer aggregates. Herein we use this novel system to characterize prostate cancer cell microaggregates, including growth kinetics and drug sensitivity. Our results indicate that prostate cancer cells are viable in this system, however some non-cancerous prostate cell lines are not. This system allows us to consistently control for the presence or absence of an apoptotic core in the 3D cancer microaggregates. Similar to tumor tissues, the 3D microaggregates display poor polarity. Critically the response of 3D microaggregates to the chemotherapeutic drug, docetaxel, is more consistent with in vivo results than the equivalent 2D controls. Cumulatively, our results demonstrate that these prostate cancer microaggregates better recapitulate the morphology of prostate tumors compared to 2D and can be used for high-throughput drug testing.     

How Willing Are You to Accept Sexual Requests from Slightly Unattractive to Exceptionally Attractive Imagined Requestors?

In their classic study of differences in mating strategies, Clark and Hatfield (1989, Journal of Psychology and Human Sexuality, 2, 39–54) found that men and women demonstrated a striking difference in interest in casual sex. The current study examined the role of an imagined requestor’s physical attractiveness (slightly unattractive, moderately attractive, and exceptionally attractive) on men’s and women’s willingness to accept three different requests (go out, come to apartment, go to bed) as reflected in answers to a questionnaire. We tested two hypotheses with a sample of 427 men and 443 women from three countries. Hypothesis 1 states that men, relative to women, will demonstrate a greater willingness to accept the “come to apartment” and “go to bed” requests but not the “go out” request for all three levels of requestor attractiveness. This hypothesis reflects Clark and Hatfield’s main findings. Hypothesis 2 states that the physical attractiveness of a potential partner will have a greater effect on women’s than on men’s willingness to accept all three requests, and particularly for the explicit request for casual sex. The results partially supported Hypothesis 1 and fully supported Hypothesis 2. The discussion highlights limitations of the current research and presents directions for future research.     

Helpful Female Subordinate Cichlids Are More Likely to Reproduce

Background

In many cooperatively breeding vertebrates, subordinates assist a dominant pair to raise the dominants'' offspring. Previously, it has been suggested that subordinates may help in payment for continued residency on the territory (the ‘pay-to-stay hypothesis’), but payment might also be reciprocated or might allow subordinates access to reproductive opportunities.

Methodology/Principal Findings

We measured dominant and subordinate female alloparental brood care and reproductive success in four separate experiments and show that unrelated female dominant and subordinate cichlid fish care for each other''s broods (alloparental brood care), but that there is no evidence for reciprocal ‘altruism’ (no correlation between alloparental care received and given). Instead, subordinate females appear to pay with alloparental care for own direct reproduction.

Conclusions/Significance

Our results suggest subordinate females pay with alloparental care to ensure access to the breeding substrate and thereby increase their opportunities to lay their own clutches. Subordinates'' eggs are laid, on average, five days after the dominant female has produced her first brood. We suggest that immediate reproductive benefits need to be considered in tests of the pay-to-stay hypothesis.     

Why Amphibians Are More Sensitive than Mammals to Xenobiotics

Dramatic declines in amphibian populations have been described all over the world since the 1980s. The evidence that the sensitivity to environmental threats is greater in amphibians than in mammals has been generally linked to the observation that amphibians are characterized by a rather permeable skin. Nevertheless, a numerical comparison of data of percutaneous (through the skin) passage between amphibians and mammals is lacking. Therefore, in this investigation we have measured the percutaneous passage of two test molecules (mannitol and antipyrine) and three heavily used herbicides (atrazine, paraquat and glyphosate) in the skin of the frog Rana esculenta (amphibians) and of the pig ear (mammals), by using the same experimental protocol and a simple apparatus which minimizes the edge effect, occurring when the tissue is clamped in the usually used experimental device.The percutaneous passage (P) of each substance is much greater in frog than in pig. LogP is linearly related to logK_ow (logarithm of the octanol-water partition coefficient). The measured P value of atrazine was about 134 times larger than that of glyphosate in frog skin, but only 12 times in pig ear skin. The FoD value (P_frog/P_pig) was 302 for atrazine, 120 for antipyrine, 66 for mannitol, 29 for paraquat, and 26 for glyphosate.The differences in structure and composition of the skin between amphibians and mammals are discussed.     

Fructose Levels Are Markedly Elevated in Cerebrospinal Fluid Compared to Plasma in Pregnant Women

Background

Fructose, unlike glucose, promotes feeding behavior in rodents and its ingestion exerts differential effects in the human brain. However, plasma fructose is typically 1/1000th of glucose levels and it is unclear to what extent fructose crosses the blood-brain barrier. We investigated whether local endogenous central nervous system (CNS) fructose production from glucose via the polyol pathway (glucose→sorbitol→fructose) contributes to brain exposure to fructose.

Methods

In this observational study, fasting glucose, sorbitol and fructose concentrations were measured using gas-chromatography-liquid mass spectroscopy in cerebrospinal fluid (CSF), maternal plasma, and venous cord blood collected from 25 pregnant women (6 lean, 10 overweight/obese, and 9 T2DM/gestational DM) undergoing spinal anesthesia and elective cesarean section.

Results

As expected, CSF glucose was ~60% of plasma glucose levels. In contrast, fructose was nearly 20-fold higher in CSF than in plasma (p < 0.001), and CSF sorbitol was ~9-times higher than plasma levels (p < 0.001). Moreover, CSF fructose correlated positively with CSF glucose (ρ 0.45, p = 0.02) and sorbitol levels (ρ 0.75, p < 0.001). Cord blood sorbitol was also ~7-fold higher than maternal plasma sorbitol levels (p = 0.001). There were no differences in plasma, CSF, and cord blood glucose, fructose, or sorbitol levels between groups.

Conclusions

These data raise the possibility that fructose may be produced endogenously in the human brain and that the effects of fructose in the human brain and placenta may extend beyond its dietary consumption.     

Xerotolerant Cladosporium sphaerospermum Are Predominant on Indoor Surfaces Compared to Other Cladosporium Species

Indoor fungi are a major cause of cosmetic and structural damage of buildings worldwide and prolonged exposure of these fungi poses a health risk. Aspergillus, Penicillium and Cladosporium species are the most predominant fungi in indoor environments. Cladosporium species predominate under ambient conditions. A total of 123 Cladosporium isolates originating from indoor air and indoor surfaces of archives, industrial factories, laboratories, and other buildings from four continents were identified by sequencing the internal transcribed spacer (ITS), and a part of the translation elongation factor 1α gene (TEF) and actin gene (ACT). Species from the Cladosporium sphaerospermum species complex were most predominant representing 44.7% of all isolates, while the Cladosporium cladosporioides and Cladosporium herbarum species complexes represented 33.3% and 22.0%, respectively. The contribution of the C. sphaerospermum species complex was 23.1% and 58.2% in the indoor air and isolates from indoor surfaces, respectively. Isolates from this species complex showed growth at lower water activity (≥ 0.82) when compared to species from the C. cladosporioides and C. herbarum species complexes (≥ 0.85). Together, these data indicate that xerotolerance provide the C. sphaerospermum species complex advantage in colonizing indoor surfaces. As a consequence, C. sphaerospermum are proposed to be the most predominant fungus at these locations under ambient conditions. Findings are discussed in relation to the specificity of allergy test, as the current species of Cladosporium used to develop these tests are not the predominant indoor species.     

Receptive Fields in Primate Retina Are Coordinated to Sample Visual Space More Uniformly

In the visual system, large ensembles of neurons collectively sample visual space with receptive fields (RFs). A puzzling problem is how neural ensembles provide a uniform, high-resolution visual representation in spite of irregularities in the RFs of individual cells. This problem was approached by simultaneously mapping the RFs of hundreds of primate retinal ganglion cells. As observed in previous studies, RFs exhibited irregular shapes that deviated from standard Gaussian models. Surprisingly, these irregularities were coordinated at a fine spatial scale: RFs interlocked with their neighbors, filling in gaps and avoiding large variations in overlap. RF shapes were coordinated with high spatial precision: the observed uniformity was degraded by angular perturbations as small as 15°, and the observed populations sampled visual space with more than 50% of the theoretical ideal uniformity. These results show that the primate retina encodes light with an exquisitely coordinated array of RF shapes, illustrating a higher degree of functional precision in the neural circuitry than previously appreciated.     

Atheists and Agnostics Are More Reflective than Religious Believers: Four Empirical Studies and a Meta-Analysis

Individual differences in the mere willingness to think analytically has been shown to predict religious disbelief. Recently, however, it has been argued that analytic thinkers are not actually less religious; rather, the putative association may be a result of religiosity typically being measured after analytic thinking (an order effect). In light of this possibility, we report four studies in which a negative correlation between religious belief and performance on analytic thinking measures is found when religious belief is measured in a separate session. We also performed a meta-analysis on all previously published studies on the topic along with our four new studies (N = 15,078, k = 31), focusing specifically on the association between performance on the Cognitive Reflection Test (the most widely used individual difference measure of analytic thinking) and religious belief. This meta-analysis revealed an overall negative correlation (r) of -.18, 95% CI [-.21, -.16]. Although this correlation is modest, self-identified atheists (N = 133) scored 18.7% higher than religiously affiliated individuals (N = 597) on a composite measure of analytic thinking administered across our four new studies (d = .72). Our results indicate that the association between analytic thinking and religious disbelief is not caused by a simple order effect. There is good evidence that atheists and agnostics are more reflective than religious believers.     

Women Are Seen More than Heard in Online Newspapers

Feminist news media researchers have long contended that masculine news values shape journalists’ quotidian decisions about what is newsworthy. As a result, it is argued, topics and issues traditionally regarded as primarily of interest and relevance to women are routinely marginalised in the news, while men’s views and voices are given privileged space. When women do show up in the news, it is often as “eye candy,” thus reinforcing women’s value as sources of visual pleasure rather than residing in the content of their views. To date, evidence to support such claims has tended to be based on small-scale, manual analyses of news content. In this article, we report on findings from our large-scale, data-driven study of gender representation in online English language news media. We analysed both words and images so as to give a broader picture of how gender is represented in online news. The corpus of news content examined consists of 2,353,652 articles collected over a period of six months from more than 950 different news outlets. From this initial dataset, we extracted 2,171,239 references to named persons and 1,376,824 images resolving the gender of names and faces using automated computational methods. We found that males were represented more often than females in both images and text, but in proportions that changed across topics, news outlets and mode. Moreover, the proportion of females was consistently higher in images than in text, for virtually all topics and news outlets; women were more likely to be represented visually than they were mentioned as a news actor or source. Our large-scale, data-driven analysis offers important empirical evidence of macroscopic patterns in news content concerning the way men and women are represented.     

Sweet/Dessert Foods Are More Appealing to Adolescents after Sleep Restriction

DesignRandomized cross-over sleep restriction-extension paradigm.SettingSleep was obtained and monitored at home. Outcome measures were gathered during office visits.Participants31 typically-developing adolescents aged 14–17 years.InterventionsThe three-week protocol consisted of a baseline week, followed randomly by five consecutive nights of SR (6.5 hours in bed) versus healthy sleep duration (HS; 10 hours in bed), a 2-night wash-out period, and a 5-night cross-over.MeasurementsSleep was monitored via actigraphy. The morning after each experimental condition, teens rated their hunger, underwent a 24-hour diet recall interview, and rated the appeal of a series of pictures of sweet/dessert foods (e.g., ice cream, candy) and non-sweets (meat, eggs, fruits, vegetables).ResultsTeens rated pictures of sweet/dessert foods to be more appealing after SR than after HS (Cohen’s d = .41, t = 2.07, p = .045). The sleep manipulation did not affect self-reported hunger or the appeal of non-sweet foods (p >.10). Consistent with our prior work, intake of overall calories was 11% higher and consumption of sweet/dessert servings was 52% greater during SR than HS.ConclusionsAdolescent SR appears to increase the subjective appeal of sweet/dessert foods, indicating a potential mechanism by which SR might contribute to weight gain and the risk for obesity and chronic illness.     

Herbaceous Angiosperms Are Not More Vulnerable to Drought-Induced Embolism Than Angiosperm Trees

The water transport pipeline in herbs is assumed to be more vulnerable to drought than in trees due to the formation of frequent embolisms (gas bubbles), which could be removed by the occurrence of root pressure, especially in grasses. Here, we studied hydraulic failure in herbaceous angiosperms by measuring the pressure inducing 50% loss of hydraulic conductance (P₅₀) in stems of 26 species, mainly European grasses (Poaceae). Our measurements show a large range in P₅₀ from −0.5 to −7.5 MPa, which overlaps with 94% of the woody angiosperm species in a worldwide, published data set and which strongly correlates with an aridity index. Moreover, the P₅₀ values obtained were substantially more negative than the midday water potentials for five grass species monitored throughout the entire growing season, suggesting that embolism formation and repair are not routine and mainly occur under water deficits. These results show that both herbs and trees share the ability to withstand very negative water potentials without considerable embolism formation in their xylem conduits during drought stress. In addition, structure-function trade-offs in grass stems reveal that more resistant species are more lignified, which was confirmed for herbaceous and closely related woody species of the daisy group (Asteraceae). Our findings could imply that herbs with more lignified stems will become more abundant in future grasslands under more frequent and severe droughts, potentially resulting in lower forage digestibility.Terrestrial biomes provide numerous ecosystem services to humans, such as biodiversity refuges, forage supply, carbon sequestration, and associated atmospheric feedback (Bonan, 2008). Drought frequency and severity are predicted to increase across various ecosystems (Dai, 2013), and its impact on the fate of terrestrial biomes has aroused great concern for stakeholders over the past decade. For instance, worldwide forest declines have been associated with drought events (Allen et al., 2010), and the sustainability of grasslands, one of the most important agro-ecosystems representing 26% of the world land area, is threatened due to increasing aridity in the light of climate change (Tubiello et al., 2007; Brookshire and Weaver, 2015). Since the maintenance of grasslands is of prime importance for livestock, and several of the most valuable crops are grasses, herbaceous species deserve more attention from a hydraulic point of view to understand how they will cope with shifts in precipitation and temperature patterns.During water deficit, hydraulic failure in trees has been put forward as one of the primary causes of forest decline (Anderegg et al., 2015, 2016). Drought exacerbates the negative pressure inside the water conducting cells, making the liquid xylem sap more metastable, and thus more vulnerable, to air entry (i.e. gas embolism; Lens et al., 2013a). Extensive levels of embolisms may lead to desiccation, leaf mortality, branch sacrifice, and ultimately plant death (Barigah et al., 2013; Urli et al., 2013). Plant resistance to embolism is therefore assumed to represent a key parameter in determining the drought tolerance of trees and is estimated using so-called vulnerability curves (VCs), from which the P₅₀, i.e. the sap pressure inducing 50% loss of hydraulic conductivity, can be estimated (Cochard et al., 2013). P₅₀ values are therefore good proxies for drought stress tolerance in woody plants and have been published for hundreds of angiosperm and gymnosperm tree species (Delzon et al., 2010; Choat et al., 2012), illustrating a wide range from −0.5 to −19 MPa (Larter et al., 2015).Studies focusing on P₅₀ values of herbs are limited to stems of ∼14 angiosperm species (see Supplemental Table S1 and references cited therein). Half of the herbaceous angiosperms studied so far (Supplemental Table S1) have a stem P₅₀ between 0 and −2 MPa, indicating that many herbs are highly vulnerable to embolism. Moreover, positive root pressure has been reported in various herbs, including many grasses (Poaceae) with hydathodes in their leaves (Evert, 2006), and root pressure is hypothesized to refill embolized conduits overnight when transpiration is low (Miller, 1985; Neufeld et al., 1992; Cochard et al., 1994; Macduff and Bakken, 2003; Saha et al., 2009; Cao et al., 2012). This could suggest that embolism formation and repair follow a daily cycle in herbs. In other words, the midday water potential that herbs experience in the field may often be more negative than P₅₀, which would result in an extremely vulnerable hydraulic pipeline characterized by a negative hydraulic safety margin (expressed as the minimum midday water potential minus P₅₀). In contrast to herbs, most trees operate at a slightly positive hydraulic safety margin (Choat et al., 2012), and woody plants are often too tall to allow refilling by positive root and/or stem pressure in the upper stems (Ewers et al., 1997; Fisher et al., 1997). Therefore, it could be postulated that herbaceous species possess a hydraulic system that is more vulnerable to embolism than that of woody species. In this study, we want to underpin possible differences in embolism resistance between stems of herbaceous and woody angiosperms.The scarcity of P₅₀ measures in herbaceous angiosperms, including grasses and herbaceous eudicots, is mainly due to their fragile stems and low hydraulic conductivity, making VCs technically more challenging. Using minor adaptations to existing centrifuge techniques (Supplemental Text S1), we obtained a P₅₀ stem data set of 26 herbaceous angiosperm species (mainly grasses) from various collection sites in France and Switzerland. In addition, we compared our data set with published data from woody (gymnosperm and angiosperm) species, confronted some of our herbaceous eudicot measurements with original P₅₀ data from derived, woody relatives, and performed anatomical observations in grasses to investigate a possible link between stem anatomical characters and differences in P₅₀ among the species studied. Three main research questions are central in our article: (1) Are stems of herbaceous angiosperms more vulnerable to embolism than those of woody angiosperms? (2) Do grasses operate with highly vulnerable, negative hydraulic safety margins? (3) Do grasses show structure-function trade-offs in their stems with respect to embolism resistance?     

Tree-Related Microhabitats Follow Similar Patterns but are More Diverse in Primary Compared to Managed Temperate Mountain Forests

Ecosystems - The impact of forest management on biodiversity is difficult to scrutinize along gradients of management. A step towards analyzing the impact of forest management on biodiversity is...     

Ethnicity and Child Health in Northern Tanzania: Maasai Pastoralists Are Disadvantaged Compared to Neighbouring Ethnic Groups

The Maasai of northern Tanzania, a semi-nomadic ethnic group predominantly reliant on pastoralism, face a number of challenges anticipated to have negative impacts on child health, including marginalisation, vulnerabilities to drought, substandard service provision and on-going land grabbing conflicts. Yet, stemming from a lack of appropriate national survey data, no large-scale comparative study of Maasai child health has been conducted. Savannas Forever Tanzania surveyed the health of over 3500 children from 56 villages in northern Tanzania between 2009 and 2011. The major ethnic groups sampled were the Maasai, Sukuma, Rangi, and the Meru. Using multilevel regression we compare each ethnic group on the basis of (i) measurements of child health, including anthropometric indicators of nutritional status and self-reported incidence of disease; and (ii) important proximate determinants of child health, including food insecurity, diet, breastfeeding behaviour and vaccination coverage. We then (iii) contrast households among the Maasai by the extent to which subsistence is reliant on livestock herding. Measures of both child nutritional status and disease confirm that the Maasai are substantially disadvantaged compared to neighbouring ethnic groups, Meru are relatively advantaged, and Rangi and Sukuma intermediate in most comparisons. However, Maasai children were less likely to report malaria and worm infections. Food insecurity was high throughout the study site, but particularly severe for the Maasai, and reflected in lower dietary intake of carbohydrate-rich staple foods, and fruits and vegetables. Breastfeeding was extended in the Maasai, despite higher reported consumption of cow''s milk, a potential weaning food. Vaccination coverage was lowest in Maasai and Sukuma. Maasai who rely primarily on livestock herding showed signs of further disadvantage compared to Maasai relying primarily on agriculture. We discuss the potential ecological, socioeconomic, demographic and cultural factors responsible for these differences and the implications for population health research and policy.     

Trait-Associated SNPs Are More Likely to Be eQTLs: Annotation to Enhance Discovery from GWAS

Although genome-wide association studies (GWAS) of complex traits have yielded more reproducible associations than had been discovered using any other approach, the loci characterized to date do not account for much of the heritability to such traits and, in general, have not led to improved understanding of the biology underlying complex phenotypes. Using a web site we developed to serve results of expression quantitative trait locus (eQTL) studies in lymphoblastoid cell lines from HapMap samples (http://www.scandb.org), we show that single nucleotide polymorphisms (SNPs) associated with complex traits (from http://www.genome.gov/gwastudies/) are significantly more likely to be eQTLs than minor-allele-frequency–matched SNPs chosen from high-throughput GWAS platforms. These findings are robust across a range of thresholds for establishing eQTLs (p-values from 10⁻⁴–10⁻⁸), and a broad spectrum of human complex traits. Analyses of GWAS data from the Wellcome Trust studies confirm that annotating SNPs with a score reflecting the strength of the evidence that the SNP is an eQTL can improve the ability to discover true associations and clarify the nature of the mechanism driving the associations. Our results showing that trait-associated SNPs are more likely to be eQTLs and that application of this information can enhance discovery of trait-associated SNPs for complex phenotypes raise the possibility that we can utilize this information both to increase the heritability explained by identifiable genetic factors and to gain a better understanding of the biology underlying complex traits.     

Fanconi Anemia Patients Are More Susceptible to Infection with Tumor Virus SV40

Fanconi anemia (FA) is a recessive DNA repair disease characterized by a high predisposition to developing neoplasms. DNA tumor polyomavirus simian virus 40 (SV40) transforms FA fibroblasts at high efficiency suggesting that FA patients could be highly susceptible to SV40 infection. To test this hypothesis, the large tumor (LT) antigen of SV40, BKV, JCV and Merkel Cell (MC) polyomaviruses were tested in blood samples from 89 FA patients and from 82 of their parents. Two control groups consisting of 47 no-FA patients affected by other genetic bone marrow failure diseases and 91 healthy subjects were also evaluated. Although JCV, BKV and MC were not found in any of the FA samples, the prevalence and viral load of SV40 were higher in FA patients (25%; mean viral load: 1.1×10² copies/10⁵cells) as compared with healthy individuals (4.3%; mean viral load: 0.8×10¹ copies/10⁵cells) and genetic controls (0%) (p<0.005). A marked age-dependent frequency of SV40 was found in FA with respect to healthy subjects suggesting that, although acquired early in life, the virus can widespread more easily in specific groups of population. From the analysis of family pedigrees, 60% of the parents of SV40-positive probands were positive for the virus compared to 2% of the parents of the SV40-negative probands (p<0.005). It is worthy of note that the relative frequency of SV40-positive relatives detected in this study was the highest ever reported, showing that asymptomatic FA carriers are also more susceptible to SV40. In conclusion, we favor the hypothesis that SV40 spread could be facilitated by individuals who are genetically more susceptible to infection, such as FA patients. The increased susceptibility to SV40 infection seems to be associated with a specific defect of the immune system which supports a potential interplay of SV40 with an underlying genetic alteration that increases the risk of malignancies.