Humoral factors released during trauma ofAplysia body wall

1. Preliminary, general chemical characteristics of substances in artificial sea water (ASW) washed through stimulated body wall (SBW) and in hemolymph taken from noxiously stimulated animals (SHL) were consistent with those of classical neurotransmitters, amino acids, and small- to medium-sized peptides. 2. 5-Hydroxytryptamine (5HT) and acetylcholine (ACh), unlike SBW and SHL, caused relaxation when perfused into isolated body wall. FMRFamide produced a biphasic response--brief contraction followed by prolonged relaxation. 3. Small cardioactive peptide (SCPB) caused body wall contractions similar to those produced by SBW and SHL, except that SCPB contractions displayed more desensitization and were completely blocked by 30 mM CoCl2. SCPB and SBW contractions were synergistic. 4. Dopamine caused persistent body wall contractions similar to those of SBW and SHL. Dopamine contractions were reduced but not blocked by 30 mM CoCl2. Unlike SBW activity, dopamine activity was reduced by alkalinization. 5. Glutamate and taurine produced strong but usually short-lasting body wall contractions. Adenosine, octopamine, arginine vasotocin, and cholecystokinin (CCK-8) caused weak or variable contractions. Met-enkephalin and somatostatin caused no obvious body wall responses. 6. When superfused over the fully sheathed abdominal ganglion, FMRFamide, met-enkephalin, glutamate, aspartate, and taurine reduced the magnitude of the gill-withdrawal reflex elicited by siphon nerve stimulation. 7. Taken together with earlier results, these data suggest a preliminary framework for trauma signal pathways. It is proposed that stress hormones (perhaps including FMRFamide, SCPs, 5HT, and dopamine) are released into hemolymph from neuroendocrine cells. Effective amounts of active intracellular solutes such as amino acids may also be released by extensive cellular rupture. Various humoral signals produce slow effects that contribute to hemostasis, balling up, increased cardiac output, and reflex suppression.     

Why are males more attractive after brood care? Proximate causes of enhanced sex pheromone emission in a burying beetle

Recent studies demonstrate that pheromones can be costly to produce and emit and, therefore, the types and quantities that they express are likely to covary with individual condition. Previous experiments reveal that, when given the opportunity to breed and care for young, male burying beetles Nicrophorus vespilloides go on to produce a higher amount of their sex pheromone and attract more females than control males that do not exhibit parental care. This finding is surprising because parental care is usually assumed to be energetically costly, reducing the future capacity to invest in sexual signalling. However, burying beetles reproduce on dead vertebrates and the carrion meal might enable males to acquire resources that can subsequently be allocated to pheromone signalling. Alternatively, males might accumulate pheromone precursors because they do not emit their sex pheromone during brood care. To shed light on the mechanisms of enhanced pheromone emission after brood care, in the present study, we test the effect of diet quality, social condition during care (biparental versus uniparental care) and an experimentally enforced calling pause on subsequent male pheromone emission, body weight and energy storage components. The experimentally enforced calling pause and social condition during brood care demonstrate no impact on pheromone quantity. However, the results of the present study suggest that the vertebrate carrion meal during brood care partly explains enhanced pheromone release after care. Unravelling the biosynthetic pathways of the pheromone components and analyzing the impact of potential microbial symbionts on pheromone production represents a fruitful avenue for future research.     

Fungal disease incidence along tree diversity gradients depends on latitude in European forests

European forests host a diversity of tree species that are increasingly threatened by fungal pathogens, which may have cascading consequences for forest ecosystems and their functioning. Previous experimental studies suggest that foliar and root pathogen abundance and disease severity decrease with increasing tree species diversity, but evidences from natural forests are rare. Here, we tested whether foliar fungal disease incidence was negatively affected by tree species diversity in different forest types across Europe. We measured the foliar fungal disease incidence on 16 different tree species in 209 plots in six European countries, representing a forest‐type gradient from the Mediterranean to boreal forests. Forest plots of single species (monoculture plots) and those with different combinations of two to five tree species (mixed species plots) were compared. Specifically, we analyzed the influence of tree species richness, functional type (conifer vs. broadleaved) and phylogenetic diversity on overall fungal disease incidence. The effect of tree species richness on disease incidence varied with latitude and functional type. Disease incidence tended to increase with tree diversity, in particular in northern latitudes. Disease incidence decreased with tree species richness in conifers, but not in broadleaved trees. However, for specific damage symptoms, no tree species richness effects were observed. Although the patterns were weak, susceptibility of forests to disease appears to depend on the forest site and tree type.     

Dietary nitrate supplementation enhances exercise performance in peripheral arterial disease

Peripheral arterial disease (PAD) results in a failure to adequately supply blood and oxygen (O(2)) to working tissues and presents as claudication pain during walking. Nitric oxide (NO) bioavailability is essential for vascular health and function. Plasma nitrite (NO(2)(-)) is a marker of vascular NO production but may also be a protected circulating "source" that can be converted to NO during hypoxic conditions, possibly aiding perfusion. We hypothesized that dietary supplementation of inorganic nitrate in the form of beetroot (BR) juice would increase plasma NO(2)(-) concentration, increase exercise tolerance, and decrease gastrocnemius fractional O(2) extraction, compared with placebo (PL). This was a randomized, open-label, crossover study. At each visit, subjects (n = 8) underwent resting blood draws, followed by consumption of 500 ml BR or PL and subsequent blood draws prior to, during, and following a maximal cardiopulmonary exercise (CPX) test. Gastrocnemius oxygenation during the CPX was measured by near-infrared spectroscopy. There were no changes from rest for [NO(2)(-)] (152 ± 72 nM) following PL. BR increased plasma [NO(2)(-)] after 3 h (943 ± 826 nM; P ≤ 0.01). Subjects walked 18% longer before the onset of claudication pain (183 ± 84 s vs. 215 ± 99 s; P ≤ 0.01) and had a 17% longer peak walking time (467 ± 223 s vs. 533 ± 233 s; P ≤ 0.05) following BR vs. PL. Gastrocnemius tissue fractional O(2) extraction was lower during exercise following BR (7.3 ± 6.2 vs. 10.4 ± 6.1 arbitrary units; P ≤ 0.01). Diastolic blood pressure was lower in the BR group at rest and during CPX testing (P ≤ 0.05). These findings support the hypothesis that NO(2)(-)-related NO signaling increases peripheral tissue oxygenation in areas of hypoxia and increases exercise tolerance in PAD.     

Molecular control of systemic bile acid homeostasis by the liver glucocorticoid receptor

Systemic bile acid (BA) homeostasis is a critical determinant of dietary fat digestion, enterohepatic function, and postprandial thermogenesis. However, major checkpoints for the dynamics and the molecular regulation of BA homeostasis remain unknown. Here we show that hypothalamic-pituitary-adrenal (HPA) axis impairment in humans and liver-specific deficiency of the glucocorticoid receptor (GR) in mice disrupts the normal changes in systemic BA distribution during the fasted-to-fed transition. Fasted mice with hepatocyte-specific GR knockdown had smaller gallbladder BA content and were more susceptible to developing cholesterol gallstones when fed a cholesterol-rich diet. Hepatic GR deficiency impaired liver BA uptake/transport via lower expression of the major hepatocyte basolateral BA transporter, Na(+)-taurocholate transport protein (Ntcp/Slc10a1), which affected dietary fat absorption and brown adipose tissue activation. Our results demonstrate a role of the HPA axis in the endocrine regulation of BA homeostasis through the liver GR control of enterohepatic BA recycling.     

Filopodia and adhesion in cancer cell motility

Slender bundled actin containing plasma membrane protrusions, called filopodia, are important for many essential cellular processes like cell adhesion, migration, angiogenesis and the formation of cell-cell contacts. In migrating cells, filopodia are the pioneers at the leading edge which probe the environment for cues. Integrins are cell surface adhesion receptors critically implicated in cell migration and they are transported actively to filopodia tips by an unconventional myosin, myosin-X. Integrin mediated adhesion stabilizes filopodia and promotes cell migration even though integrins are not essential for filopodia initiation. Myosin-X binds also PtdIns(3,4,5)P₃ and this regulates its activation and localization to filopodia. Filopodia stimulate cell migration in many cell types and increased filopodia density has been described in cancer. Furthermore, several proteins implicated in filopodia formation, like fascin, are also relevant for cancer progression. To investigate this further, we performed a meta-analysis of the expression profiles of 10 filopodia-linked genes in human breast cancer. These data implicated that several different filopodia-inducing genes may contribute in a collective manner to cancer progression and the high metastasis rates associated with basal-type breast carcinomas.Key words: filopodia, integrins, migration, cancer     

Borderline Personality and the Detection of Angry Faces

Background

Many studies have assessed emotion recognition in patients with Borderline Personality Disorder and considerable evidence has been accumulated on patients’ ability to categorize emotions. In contrast, their ability to detect emotions has been investigated sparsely. The only two studies that assessed emotion detection abilities found contradictory evidence on patients’ ability to detect angry faces.

Methods

To clarify whether patients with Borderline Personality Disorder show enhanced detection of angry faces, we conducted three experiments: a laboratory study (n = 53) with a clinical sample and two highly powered web studies that measured Borderline features (n₁ = 342, n₂ = 220). Participants in all studies completed a visual search paradigm, and the reaction times for the detection of angry vs. happy faces were measured.

Results

Consistently, data spoke against enhanced detection of angry faces in the Borderline groups, indicated by non-significant group (Borderline vs. healthy control) × target (angry vs. happy) interactions, despite highly satisfactory statistical power to detect even small effects.

Conclusions

In contrast to emotion categorization, emotion detection appears to be intact in patients with Borderline Personality Disorder and individuals high in Borderline features. The importance of distinguishing between these two processes in future studies is discussed.     

Phenotype-dependent mate choice and the influence of mixed-morph lineage on the reproductive success of a polymorphic and aposematic moth

Polymorphic warning signals in aposematic organisms are puzzling because efficient predator learning should select for the most efficient warning colouration. Yet, there are many examples of polymorphic and aposematic organisms in nature. Here, we investigated whether perceived trade-offs between natural and sexual selection, combined with different degrees of morph lineage admixture, can maintain polymorphic yellow and white hindwing colouration in aposematic wood tiger moth males (Arctia plantaginis). Prior research in the system suggests that yellow males have better warning colouration against predators, whereas white male morphs have higher mating success. We performed a mating experiment where females were offered four males: two white and two yellow. One male from each colour came from (purely) monomorphic lines (i.e. including the same paternal colour for multiple generations), whereas one male from each colour were from mixed-morph (or hybrid) lineages. We then assessed whether phenotype (colour), lineage, or an interaction between the two, best affected mating success. Our results showed that although white hindwing coloured males tended to have overall better reproductive success, this was mainly due to the significantly higher mating and hatching success of mixed-morph compared to pure-line individuals. Notably, this suggests the advantage of mixed-morph lineage is limited to white individuals, while on the contrary yellow mixed lineage moths have a disadvantage, i.e. the lowest mating success. The latter also suggests a cost to reproductive success in producing the more efficient against predators yellow warning colouration, even when those individuals recently descend from a white hindwing coloured lineage. Heterozygote, or hybrid advantage, even when confined to only one morph, has been shown to promote polymorphism in some systems, therefore, our results point at the need to further examine genetic architecture and the role of mixed-morph lineages in understanding the maintenance of polymorphisms in nature.     

Micronutrient Deficiency and Treatment Adherence in a Randomized Controlled Trial of Micronutrient Supplementation in ART-Na?ve Persons with HIV

Introduction

The MAINTAIN study is an on-going RCT comparing high-dose micronutrient and anti-oxidant supplementation versus recommended daily allowance (RDA) vitamins in slowing HIV immune deficiency progression in ART-naïve people with HIV infection.

Objective

We planned analysis of the first 127 participants to determine the baseline prevalence of serum micronutrient deficiencies and correlates, as well as tolerance and adherence to study interventions.

Methods

Participants receive eight capsules twice daily of 1) high-dose or 2) RDA supplements for two years and are followed-up quarterly for measures of immune deficiency progression, safety and tolerability. Regression analysis was used to identify correlates of micronutrient levels at baseline. Adherence was measured by residual pill count, self-report using the General Treatment Scale (GTS) and short-term recall HIV Adherence Treatment Scale (HATS).

Results

Prior micronutrient supplementation (within 30 days) was 27% at screening and 10% of study population, and was not correlated with baseline micronutrient levels. Low levels were frequent for carotene (24%<1 nmol/L), vitamin D (24%<40 nmol/L) and serum folate (20%<15 nmol/L). The proportion with B₁₂ deficiency (<133 pmol/L) was 2.4%. Lower baseline levels of B₁₂ correlated lower baseline CD4 count (r = 0.21, p = 0.02) with a 21 pmol/L reduction in B₁₂ per 100 cells/µL CD4. Vitamin D levels were higher in men (p<0.001). After a median follow-up of 1.63 years, there were 19 (15%) early withdrawals from the study treatment. Mean treatment adherence using pill count was 88%. Subjective adherence by the GTS was 81% and was moderately but significantly correlated with pill count (r = 0.29, p<0.001). Adherence based on short-term recall (HATS) was >80% in 75% of participants.

Conclusion

Micronutrient levels in asymptomatic HIV+ persons are in keeping with population norms, but micronutrient deficiencies are frequent. Adherence levels are high, and will permit a valid evaluation of treatment effects.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00798772","term_id":"NCT00798772"}}NCT00798772