Does Human Body Odor Represent a Significant and Rewarding Social Signal to Individuals High in Social Openness?

Across a wide variety of domains, experts differ from novices in their response to stimuli linked to their respective field of expertise. It is currently unknown whether similar patterns can be observed with regard to social expertise. The current study therefore focuses on social openness, a central social skill necessary to initiate social contact. Human body odors were used as social cues, as they inherently signal the presence of another human being. Using functional MRI, hemodynamic brain responses to body odors of women reporting a high (n = 14) or a low (n = 12) level of social openness were compared. Greater activation within the inferior frontal gyrus and the caudate nucleus was observed in high socially open individuals compared to individuals low in social openness. With the inferior frontal gyrus being a crucial part of the human mirror neuron system, and the caudate nucleus being implicated in social reward, it is discussed whether human body odor might constitute more of a significant and rewarding social signal to individuals high in social openness compared to individuals low in social openness process.     

Essential Medicines in a High Income Country: Essential to Whom?

Objective

To explore the perspectives of a diverse group of stakeholders engaged in medicines decision making around what constitutes an “essential” medicine, and how the Essential Medicines List (EML) concept functions in a high income country context.

Methods

In-depth qualitative semi-structured interviews were conducted with 32 Australian stakeholders, recognised as decision makers, leaders or advisors in the area of medicines reimbursement or supply chain management. Participants were recruited from government, pharmaceutical industry, pharmaceutical wholesale/distribution companies, medicines non-profit organisations, academic health disciplines, hospitals, and consumer groups. Perspectives on the definition and application of the EML concept in a high income country context were thematically analysed using grounded theory approach.

Findings

Stakeholders found it challenging to describe the EML concept in the Australian context because many perceived it was generally used in resource scarce settings. Stakeholders were unable to distinguish whether nationally reimbursed medicines were essential medicines in Australia. Despite frequent generic drug shortages and high prices paid by consumers, many struggled to describe how the EML concept applied to Australia. Instead, broad inclusion of consumer needs, such as rare and high cost medicines, and consumer involvement in the decision making process, has led to expansive lists of nationally subsidised medicines. Therefore, improved communication and coordination is needed around shared interests between stakeholders regarding how medicines are prioritised and guaranteed in the supply chain.

Conclusions

This study showed that decision-making in Australia around reimbursement of medicines has strayed from the fundamental utilitarian concept of essential medicines. Many stakeholders involved in medicine reimbursement decisions and management of the supply chain did not consider the EML concept in their approach. The wide range of views of what stakeholders considered were essential medicines, challenges whether the EML concept is out-dated or underutilised in high income countries.     

Mitochondrial Cytochrome b mRNA Editing in Dinoflagellates: Possible Ecological and Evolutionary Associations?

To verify the hypothesis that mt mRNA editing is widespread in dinoflagellates, we analyzed cytochrome b (cob) mRNA editing for six species representing distinct ecotypes and taxonomic classes of Dinophyceae. Editing is detected in all, which is similar to the three other species studied previously in that edited sites appear to aggregate in four clusters and occur predominantly at first and second positions of codons (93%), overwhelmingly involving A --> G, U --> C, or C --> U substitutions with a smaller number of G --> C, G --> A changes. Comparative analyses on editing characteristics reveal interesting trends related to phylogenetic relatedness and ecological features. Editing density (percentage of nucleotide that is affected by editing) increases from early to derived lineages. Higher editing densities also map to red tide-forming lineages. Furthermore, similarity of location of edited codons (LOE) and the type of nucleotide changes (TOE) in different lineages mirror the taxonomic affinity of the lineages. Phylogenetic trees constructed from LOE and TOE resemble those inferred from cob sequences. The results bolster our earlier hypothesis that cob editing is widespread in dinoflagellates and suggest that density, location, and type of editing may bear yet-to-be-defined evolutionary and ecological significance.     

Bringing Back a Healthy Buzz? Invertebrate Parasites and Reintroductions: A Case Study in Bumblebees

Reintroductions can play a key role in the conservation of endangered species. Parasites may impact reintroductions, both positively and negatively, but few case studies of how to manage parasites during reintroductions exist. Bumblebees are in decline at regional and global scales, and reintroductions can be used to re-establish extinct local populations. Here we report on how the risks associated with parasites are being managed in an ongoing reintroduction of the short-haired bumblebee, Bombus subterraneus, to the UK. Disease risk analysis was conducted and disease risk management plans constructed to design a capture-quarantine-release system that minimised the impacts on both the bumblebees and on their natural parasites. Given that bumblebee parasites are (i) generalists, (ii) geographically ubiquitous, and (iii) show evidence of local adaptation, the disease risk management plan was designed to limit the co-introduction of parasites from the source population in Sweden to the destination site in the UK. Results suggest that this process at best eliminated, or at least severely curtailed the co-introduction of parasites, and ongoing updates of the plan enabled minimization of impacts on natural host-parasite dynamics in the Swedish source population. This study suggests that methods designed for reintroductions of vertebrate species can be successfully applied to invertebrates. Future reintroductions of invertebrates where the parasite fauna is less well known should take advantage of next-generation barcoding and multiple survey years prior to the start of reintroductions, to develop comprehensive disease risk management plans.     

Bringing Back a Healthy Buzz? Invertebrate Parasites and Reintroductions: A Case Study in Bumblebees

Reintroductions can play a key role in the conservation of endangered species. Parasites may impact reintroductions, both positively and negatively, but few case studies of how to manage parasites during reintroductions exist. Bumblebees are in decline at regional and global scales, and reintroductions can be used to re-establish extinct local populations. Here we report on how the risks associated with parasites are being managed in an ongoing reintroduction of the short-haired bumblebee, Bombus subterraneus, to the UK. Disease risk analysis was conducted and disease risk management plans constructed to design a capture-quarantine-release system that minimised the impacts on both the bumblebees and on their natural parasites. Given that bumblebee parasites are (i) generalists, (ii) geographically ubiquitous, and (iii) show evidence of local adaptation, the disease risk management plan was designed to limit the co-introduction of parasites from the source population in Sweden to the destination site in the UK. Results suggest that this process at best eliminated, or at least severely curtailed the co-introduction of parasites, and ongoing updates of the plan enabled minimization of impacts on natural host-parasite dynamics in the Swedish source population. This study suggests that methods designed for reintroductions of vertebrate species can be successfully applied to invertebrates. Future reintroductions of invertebrates where the parasite fauna is less well known should take advantage of next-generation barcoding and multiple survey years prior to the start of reintroductions, to develop comprehensive disease risk management plans.

     

Claudin expression in breast cancer: High or low, what to expect?

The evaluation of claudins (CLDNs) expression pattern in tumours can be important to understand breast carcinogenesis. The study of CLDNs became more appealing since it was found that CLDN3 and CLDN4 are putative therapeutic targets for Clostridium perfrigens enterotoxin (CPE), as well as for monoclonal antibody-based therapy. Moreover, the recently characterized CLDN-low molecular subgroup of breast tumours increased the interest in these molecules. Based on these facts, our aim was to explore the pattern of expression of CLDNs among a large series of invasive breast carcinomas. We also analysed the correlation between the combinatorial expression of CLDN3/CLDN4 and classical prognostic factors and biological markers. In addition, we also compared the characteristics of tumours with low expression of CLDN3, CLDN4 and CLDN7, assessed by immunohistochemistry (IHC), and the ones from CLDN-low subgroup of tumours previously defined by genomic assays. The combinatorial analysis of the expression of CLDN3/CLDN4 showed a significant association between high CLDN3/CLDN4 levels and triple-negative tumours, as well as with worse patient outcome. This combined analysis may provide useful information for breast carcinomas, since these two CLDN members are putative therapeutic targets. Comparing tumours with low expression of CLDN3, CLDN4 and CLDN7 with tumours previously referred to as CLDN-low by genomic assays, we demonstrated that the single IHC evaluation of these three specific CLDNs is insufficient to identify the CLDN-low molecular subtype of breast tumours. The analysis of several other molecular markers, such as EMT (epithelial-to-mesenchymal transition) and CSC (cancer stem cell) markers should probably be added to improve the identification of this subgroup of tumours by IHC, which probably are enriched in carcinomas with metaplastic differentiation.     

Overcoming Obstacles to Evolution Education: Why Bother Teaching Evolution in High School?

Evolution is a foundational organizing principle of the life sciences, and yet people still argue that it should be taught only in college, urging that it’s not necessary, too controversial, or too difficult to teach evolution in high school. Faced with such arguments, teachers and administrators need to have responses. Moreover, they need to teach evolution so that the coverage of evolution in the K-12 curriculum reflects its central place in biology.     

Cryptosporidium spp., Giardia duodenalis,Enterocytozoon bieneusi and Other Intestinal Parasites in Young Children in Lobata Province,Democratic Republic of S?o Tomé and Principe

Rare systemic studies concerning prevalence of intestinal parasites in children have been conducted in the second smallest country in Africa, the Democratic Republic of São Tomé and Príncipe. Fecal specimens from 348 children (214 in-hospital attending the Aires de Menezes Hospital and 134 from Agostinho Neto village) in São Tome Island were studied by parasitological and molecular methods. Of the 134 children from Agostinho Neto, 52.2% presented intestinal parasites. 32.1% and 20.2% of these children had monoparasitism and polyparasitism, respectively. Ascaris lumbricoides (27.6%), G. duodenalis (7.5%), T. trichiura (4.5%) and Entamoeba coli (10.5%) were the more frequent species identified in the children of this village. Giardia duodenalis (7.5%) and E. bieneusi (5.2%) were identified by PCR. Nested-PCR targeting G. duodenalis TPI identified Assemblage A (60%) and Assemblage B (40%). The E. bieneusi ITS-based sequence identified genotypes K (57.1%), KIN1 (28.6%) and KIN3 (14.3%). Among the 214 in-hospital children, 29.4% presented intestinal parasites. In 22.4% and 7.0% of the parasitized children, respectively, one or more species were concurrently detected. By microscopy, A. lumbricoides (10.3%) and Trichiuris trichiura (6.5%) were the most prevalent species among these children, and Cryptosporidium was detected by PCR in 8.9% of children. GP60 locus analysis identified 6.5% of C. hominis (subtypes IaA27R3 [35.7%], IaA23R3 [14.3%], IeA11G3T3 [28.6%] and IeA11G3T3R1 [21.4%]) and 2.3% of C. parvum (subtypes IIaA16G2R1 [20.0%], IIaA15G2R1 [20.0%], IIdA26G1 [40.0%] and IIdA21G1a [20.0%]). G. duodenalis and E. bieneusi were identified in 0.5% and 8.9% of the in-hospital children, respectively. G. duodenalis Assemblage B was characterized. The E. bieneusi genotypes K (52.6%), D (26.4%), A (10.5%) and KIN1 (10.5%) were identified. Although further studies are required to clarify the epidemiology of these infectious diseases in this endemic region the significance of the present results highlights that it is crucial to strength surveillance on intestinal pathogens.     

Associations between anticipated reactions to genetic test results and interest in genetic testing: will self-selection reduce the potential for harm?

The proliferation of genetic susceptibility tests for complex diseases away from clinic settings increases the potential for harm. This study assessed whether people are likely to self-select themselves into or out of genetic testing depending on whether they believe they could cope with the results. Associations between anticipated reactions to adverse genetic test results and interest in taking genetic tests for cancer and heart disease were examined in a community sample of English adults (n = 1,024). Interest in genetic testing overall was 78% for cancer risk and 80% for heart disease risk. As predicted, there were differences by anticipated reactions. People who anticipated regret about having taken a genetic test for cancer risk expressed lower interest than those who did not anticipate regret (46% vs. 89%), and people who anticipated being glad to know of increased risk status (i.e., reduced uncertainty) were more interested than those who did not look forward to reduced uncertainty (91% vs. 22%). Patterns were similar for heart disease ("regret" 66% vs. 87%; "reduced uncertainty" 87% vs. 38%). The potential for harm from future genetic susceptibility tests may be less than feared if people who anticipate adverse reactions self-select themselves out of testing. However, given that a significant proportion of people who anticipated adverse reactions also expressed interest in testing, there is still a concern about safety. It remains to be seen whether the same patterns emerge in studies that actually offer genetic tests for common gene variants in community settings.     

Actinomycetes biosynthetic potential: how to bridge in silico and in vivo?

Actinomycetes genome sequencing and bioinformatic analyses revealed a large number of “cryptic” gene clusters coding for secondary metabolism. These gene clusters have the potential to increase the chemical diversity of natural products. Indeed, reexamination of well-characterized actinomycetes strains revealed a variety of hidden treasures. Growing information about this metabolic diversity has promoted further development of strategies to discover novel biologically active compounds produced by actinomycetes. This new task for actinomycetes genetics requires the development and use of new approaches and tools. Application of synthetic biology approaches led to the development of a set of strategies and tools to satisfy these new requirements. In this review, we discuss strategies and methods to discover small molecules produced by these fascinating bacteria and also discuss a variety of genetic instruments and regulatory elements used to activate secondary metabolism cryptic genes for the overproduction of these metabolites.     

How Hot Are Drosophila Hotspots? Examining Recombination Rate Variation and Associations with Nucleotide Diversity,Divergence, and Maternal Age in Drosophila pseudoobscura

Fine scale meiotic recombination maps have uncovered a large amount of variation in crossover rate across the genomes of many species, and such variation in mammalian and yeast genomes is concentrated to <5kb regions of highly elevated recombination rates (10–100x the background rate) called “hotspots.” Drosophila exhibit substantial recombination rate heterogeneity across their genome, but evidence for these highly-localized hotspots is lacking. We assayed recombination across a 40Kb region of Drosophila pseudoobscura chromosome 2, with one 20kb interval assayed every 5Kb and the adjacent 20kb interval bisected into 10kb pieces. We found that recombination events across the 40kb stretch were relatively evenly distributed across each of the 5kb and 10kb intervals, rather than concentrated in a single 5kb region. This, in combination with other recent work, indicates that the recombination landscape of Drosophila may differ from the punctate recombination pattern observed in many mammals and yeast. Additionally, we found no correlation of average pairwise nucleotide diversity and divergence with recombination rate across the 20kb intervals, nor any effect of maternal age in weeks on recombination rate in our sample.     

Are the same Compounds in Microcystis responsible for Toxicity to Daphnia and Inhibition of its Filtering Rate?

Three strains of Microcystis when supplied to Daphnia in mixtures with Scenedesmus differed in their power to inhibit filtering rates. The axenic strain PCC 7806 had the strongest effect (93% inhibition with 50% Microcystis in the food). This strain was toxic to daphnids since Daphnia died faster under these conditions than without any food. Strain PCC 7806 also exhibited strong toxicity against mice (LD₅₀ 22 mg/kg). When the toxicity against Daphnia and mice was tested with cells of Microcystis PCC 7806 which has been subjected to various extraction procedures, the extraction of freeze-thawed cells with water slightly reduced the mouse toxicity, eliminated Daphnia toxicity and reduced the inhibition of the filtering rate. After treatment with a lipophilic solvent, the cells of PCC 7806 still showed low mouse toxicity, but no longer inhibition of the filtering rate and no toxicity to Daphnia. Thus, our data suggest that Daphnia toxicity and inhibition of the filtering rate are caused by different compounds, but we cannot rule out the possibility that the factors toxic to mice and inhibitory to the filtering rate are identical.     

Left and right in the amphibian world: which way to develop and where to turn?

The last decade has seen a dramatic increase in studies on the development, function and evolution of asymmetries in vertebrates, including amphibians. Here we discuss current knowledge of behavioral and anatomical asymmetries in amphibians. Behavioral laterality in the response of both adult and larval anurans to presumed predators and competitors is strong and may be related, respectively, to laterality in the telencephalon of adults and the Mauthner neurons of tadpoles. These behavior lateralities, however, do not seem to correlate with visceral asymmetries in the same animals. We briefly compare what is known about the evolution and development of asymmetry in the structure and function of amphibians with what is known about asymmetries in other chordate and non-chordate groups. Available data suggest that the majority of asymmetries in amphibians fall into two independent groups: (1) related to situs viscerum and (2) of a neurobehavioral nature. We find little evidence linking these two groups, which implies different developmental regulatory pathways and independent evolutionary histories for visceral and telencephalic lateralizations. Studies of animals other than standard model species are essential to test hypotheses about the evolution of laterality in amphibians and other chordates.     

Metabolic and Kidney Disorders Correlate with High Atazanavir Concentrations in HIV-Infected Patients: Is It Time to Revise Atazanavir Dosages?

Introduction

Ritonavir-boosted atazanavir (ATV/r) is a relatively well tolerated antiretroviral drug. However, side effects including hyperbilirubinemia, dyslipidemia, nephrolithiasis and cholelithiasis have been reported in the medium and long term. Unboosted ATV may be selected for some patients because it has fewer gastrointestinal adverse effects, less hyperbilirubinemia and less impact on lipid profiles.

Methods

We investigated the distribution of ATV plasma trough concentrations according to drug dosage and the potential relationship between ATV plasma trough concentrations and drug-related adverse events in a consecutive series of 240 HIV-infected patients treated with ATV/r 300/100 mg (68%) or ATV 400 mg (32%).

Results

43.9% of patients treated with ATV/r 300/100 mg had ATV concentrations exceeding the upper therapeutic threshold. A significant and direct association has been observed between the severity of hyperbilirubinemia and ATV plasma trough concentrations (ATV concentrations: 271 [77–555], 548 [206–902], 793 [440–1164], 768 [494–1527] and 1491 [1122–1798] ng/mL in patients with grade 0, 1, 2, 3 and 4 hyperbilirubinemia, respectively). In an exploratory analysis we found that patients with dyslipidemia or nephrolitiasis had ATV concentrations significantly higher (582 [266–1148], and 1098 [631–1238] ng/mL, respectively) (p<0.001), as compared with patients with no ATV-related complications (218 [77–541] ng/mL).

Conclusions

A significant proportion of patients treated with the conventional dosage of ATV (300/100) had plasma concentrations exceeding the upper therapeutic threshold. These patients that are at high risk to experience ATV-related complications may benefit from TDM-driven adjustments in ATV dosage with potential advantages in terms of costs and toxicity.     

Associations between the FAS ?670?A/G and ?1,377?G/A polymorphisms and susceptibility to autoimmune rheumatic diseases: a meta-analysis

The aim of this study was to explore whether FAS ?670?A/G and ?1,377?G/A polymorphisms confer susceptibility to autoimmune rheumatic diseases. A meta-analysis was conducted on the associations between the FAS ?670?A/G and ?1,377?G/A polymorphisms and autoimmune rheumatic diseases using allele contrast, a recessive model, a dominant model, and an additive model. Thirteen articles with 21 comparison studies (16 on FAS ?670?A/G and 5 on ?1,377?G/A polymorphisms) including systemic lupus erythematosus (SLE), four systemic sclerosis, four Sjogren’s syndrome, three rheumatoid arthritis (RA), one juvenile idiopathic arthritis, and one spondyloarthropathy were available for the meta-analysis. Meta-analysis revealed an association between rheumatic diseases and the FAS ?670?A/G polymorphism in the dominant model (odds ratio [OR]?=?0.761, 95?% confidence interval [CI]?=?0.621–0.932, p?=?0.008]. Stratification by ethnicity indicated an association between the FAS ?670?G allele carrier and rheumatic diseases in Asian (OR?=?0.569, 95?% CI?=?0.409–0.791, p?=?0.001). Furthermore, stratification by disease indicated an association between the FAS ?670?G allele carrier and SLE and RA (OR?=?0.578, 95?% CI?=?0.358–0.934, p?=?0.025; OR?=?0.609, 95?% CI?=?0.398–0.934, p?=?0.023, respectively). The FAS ?670?G allele was negatively associated with SLE susceptibility. Meta-analysis of the FAS ?1,377?G/A polymorphism stratified by disease showed an association between the FAS ?1,377 A allele and SLE (OR?=?0.783, 95?% CI?=?0.613–0.997, p?=?0.047). Meta-analyses using the dominant model also showed a significant association in SLE (OR?=?0.712, 95?% CI?=?0.528–0.961, p?=?0.027). This meta-analysis demonstrates that the FAS ?670?A/G polymorphism confers susceptibility to rheumatic diseases in Asians and SLE and RA, and the FAS ?1,377?G/A polymorphism is associated with SLE susceptibility.     

High Discrepancy in Abdominal Obesity Prevalence According to Different Waist Circumference Cut-Offs and Measurement Methods in Children: Need for Age-Risk-Weighted Standardized Cut-Offs?

Background

Waist circumference (WC) is a good proxy measure of central adiposity. Due to the multiplicity of existing WC cut-offs and different measurement methods, the decision to use one rather than another WC chart may lead to different prevalence estimates of abdominal obesity in the same population. Aim of our study was to assess how much the prevalence of abdominal obesity varies in Italian schoolchildren using the different available WC cut-offs.

Methods

We measured WC at just above the uppermost lateral border of the right ilium in 1062 Italian schoolchildren aged 7–14 years, 499 living in Northern Italy and 563 in Southern Italy. Abdominal obesity was defined as WC ≥90^th percentile for gender and age according to nine WC charts.

Results

We found an extremely high variability in the prevalence of abdominal obesity detected in our study-populations according to the different WC charts, ranging in the overall group from 9.1% to 61.4%. In Northern Italy children it varied from 2.4% to 35.7%, and in Southern ones from 15.1% to 84.2%.

Conclusions

On the basis of the chosen WC cut-offs the prevalence of abdominal obesity varies widely, because percentile-charts are strongly influenced by the population status in a particular moment. A further rate of variability may lay on the site of WC measurement and on the statistical method used to calculate WC cut-offs. Risk-weighted WC cut-offs measured in a standardized anatomic site and calculated by the appropriate method are needed to simply identify by WC measurement those children at high risk of cardio-metabolic complications to whom specific and prompt health interventions should be addressed.     

p53 and TGF-beta in development: prelude to tumor suppression?

Recent work in Xenopus embryos reveals an unexpected developmental role for the tumor suppressor gene p53. This finding may have implications for the evolution of p53, its interaction with Smads in TGF-beta dependent mesoderm specification, and the cooperation among p53 family members.     

Schistosomiasis in African infants and preschool children: to treat or not to treat?

The occurrence of schistosomiasis in African infants and preschool children has been largely overlooked, with preventive chemotherapy usually focused on school-aged children instead. Two recent surveys by Bosompem et al. and Odogwu et al. have shown that schistosomiasis in younger children is much more common than previously thought. This article highlights the importance of the disease in this age group and discusses the future prospects for schistosomiasis control.