Ascaroside Signaling Is Widely Conserved among Nematodes

Background: Nematodes are among the most successful animals on earth and include important human pathogens, yet little is known about nematode pheromone systems. A group of small molecules called ascarosides has been found to mediate mate finding, aggregation, and developmental diapause in Caenorhabditis elegans, but it is unknown whether ascaroside signaling exists outside of the genus Caenorhabditis. Results: To determine whether ascarosides are used as signaling molecules by other nematode species, we performed a mass spectrometry-based screen for ascarosides in secretions from a variety of both free-living and parasitic (plant, insect, and animal) nematodes. We found that most of the species analyzed, including nematodes from several different clades, produce species-specific ascaroside mixtures. In some cases, ascaroside biosynthesis patterns appear to correlate with phylogeny, whereas in other cases, biosynthesis seems to correlate with lifestyle and ecological niche. We further show that ascarosides mediate distinct nematode behaviors, such as retention, avoidance, and long-range attraction, and that different nematode species respond to distinct, but overlapping, sets of ascarosides. Conclusions: Our findings indicate that nematodes utilize a conserved family of signaling molecules despite having evolved to occupy diverse ecologies. Their structural features and level of conservation are evocative of bacterial quorum sensing, where acyl homoserine lactones (AHLs) are both produced and sensed by many species of gram-negative bacteria. The identification of species-specific ascaroside profiles may enable pheromone-based approaches to interfere with reproduction and survival of parasitic nematodes, which are responsible for significant agricultural losses and many human diseases worldwide

evaluating a novel online depression intervention for persons with epilepsy

Background Depression is common among persons with epilepsy (PwE), affecting roughly one in three individuals, and its presence is associated with personal suffering, impaired quality of life, and worse prognosis. Despite the availability of effective treatments, depression is often overlooked and treated inadequately in PwE, in part because of assumed concerns over drug interactions or proconvulsant effects of antidepressants. Internet- administered psychological interventions might complement antidepressant medication or psychotherapy, and preliminary evidence suggests that they can be effective. However, no trial has yet examined whether an Internet intervention designed to meet the needs of PwE can achieve sustained reductions in depression and related symptoms, such as anxiety, when offered as adjunct to treatment as usual. Methods/Design This randomized controlled trial will include 200 participants with epilepsy and a current depressive disorder, along with currently at least moderately elevated depression (Patient Health Questionnaire (PHQ-9) sum score of at least 10). Patients will be recruited via epilepsy treatment centers and other sources, including Internet forums, newspaper articles, flyers, posters, and media articles or advertisements, in German-speaking countries. Main inclusion criteria are: self-reported diagnosis of epilepsy and a depressive disorder, as assessed with a phone-administered structured diagnostic interview, none or stable antidepressant medication, no current psychotherapy, no other major psychiatric disorder, no acute suicidality. Participants will be randomly assigned to either (1) a care-as-usual/waitlist (CAU/WL) control group, in which they receive CAU and are given access to the Internet intervention after 3 months (that is, a CAU/WL control group), or (2) a treatment group that may also use CAU and in addition immediately receives six-month access to the novel, Internet-administered intervention. The primary outcome measure is the PHQ-9, collected at three months post-baseline; secondary measures include self-reported anxiety, work and social adjustment, epilepsy symptoms (including seizure frequency and severity), medication adherence, potential negative treatment effects and health-related quality of life. Measurements are collected online at pre-treatment (T0), three months (T1), six months (T2), and nine months (T3). Discussion Results of this trial are expected to extend the body of knowledge with regard to effective and efficient treatment options for PwE who experience elevated depression and anxiety. Trial registration ClinicalTrials.gov: NCT02791724. Registered 01 June 2016

Food Addiction and Its Relationship to Weight- and Addiction-Related Psychological Parameters in Individuals With Overweight and Obesity

Background and Aims: It is assumed that a relevant subgroup of individuals experiences an addiction-like eating behaviour (Food Addiction), characterized by an impaired control over eating behaviour, emotional eating and food craving. Individuals experiencing Food Addiction partially share common symptomatology with Binge-Eating-Disorder and Bulimia Nervosa. The aim of this study was to investigate the prevalence of Food Addiction, general psychopathology, and associations with weight- and addiction-related constructs in individuals with overweight and obesity, who did not suffer from Binge-Eating-Disorder or Bulimia Nervosa. Methods: N=213 (67.1% female; MBMI=33.35kg/m2, SDBMI=3.79kg/m2) participants who were included in a weight loss program (I-GENDO project) reported BMI and completed questionnaires before the start of the treatment. Food Addiction severity, depressive symptoms, alcohol use disorder, internet use disorder, psychological distress, impulsivity personality trait, impulsive and emotional eating behaviour, food related inhibitory control, weight bias internalization, and self-efficacy were assessed. Results: The prevalence of Food Addiction was 15% with higher, although not statistically significant, prevalence in female (18.2%) compared to male (8.6%) participants. Food Addiction was associated with higher BMI at baseline assessment, low self-esteem, impulsive and emotional eating behaviour, weight bias internalization, and deficits in food-related inhibitory control. In addition, correlations were found between Food Addiction and severity of depressive symptoms, internet use disorder, and psychological distress. Conclusion: A relevant subgroup of participants experiences Food Addiction even when controlling for Binge-Eating-Disorder and Bulimia Nervosa. Future studies are warranted that investigate whether Food Addiction affects treatment success

Saccadic modulation of neural excitability in auditory areas of the neocortex

In natural "active" vision, humans and other primates use eye movements (saccades) to sample bits of information from visual scenes. In the visual cortex, non-retinal signals linked to saccades shift visual cortical neurons into a high excitability state as each saccade ends. The extent of this saccadic modulation outside of the visual system is unknown. Here, we show that during natural viewing, saccades modulate excitability in numerous auditory cortical areas with a temporal pattern complementary to that seen in visual areas. Control somatosensory cortical recordings indicate that the temporal pattern is unique to auditory areas. Bidirectional functional connectivity patterns suggest that these effects may arise from regions involved in saccade generation. We propose that by using saccadic signals to yoke excitability states in auditory areas to those in visual areas, the brain can improve information processing in complex natural settings

Differential effects of the individualized gender-sensitive mHealth intervention I-GENDO on eating styles in individuals with overweight and obesity : a randomized controlled trial

Background: Addressing cognitive behavioral factors is associated with a favorable development of eating styles (i.e., increased levels of restrained eating, decreased levels of external and emotional eating) in individuals with overweight and obesity. Research suggests that the use of digital interventions that consider gender aspects regarding prevalence, comorbidities, and weight-related behaviors could enhance existing treatment options. This randomized controlled trial aimed to evaluate the effectiveness of the self-guided gender-sensitive mobile health intervention I-GENDO on restrained, emotional and external eating, body mass index, and physical activity at the end of the intervention, and at a 9- and 15-month follow-up. Methods: Two hundred thirteen individuals (67% female, body mass index: 33.35 ± 3.79 kg/m2) were randomly assigned to the intervention or control group. Multilevel models were calculated to investigate differences between groups. I-GENDO offered interactive modules addressing psychological content associated with obesity. Users were able to self-tailor intervention content based on their individual needs and life realities. Results: Restrained eating was higher in the intervention group after the intervention (95% CI: 0.20, 0.36) and at 9-months (95% CI: 0.07, 0.24). At 9-months, emotional eating among women was lower in the intervention group compared to the control group (95% CI: -0.44, -0,19). In the intervention group, external eating was lower after the intervention, which remained significant for women at 9 (95% CI: -0.40, -0.19) and 15-months (95% CI: -0.34, -0.13). Body mass index of men in the intervention group was 1.44 lower at 15-months than in the control group. No significant effects on physical activity were found. Conclusions: The I-GENDO intervention was effective in changing restrained eating of both women and men in the long-term, suggesting that a self-guided, gender-sensitive approach is promising. However, the differential effects on the outcome measures indicate that more research is warranted to examine distinct gender-sensitive mechanisms of digital psychological interventions (i.e., dose–response relationship, blended counselling). Trial registration: ClinicalTrials.gov identifier: NCT04080193, 06–09-2019

Comparative Metabolomics Reveals Biogenesis of Ascarosides, a Modular Library of Small-Molecule Signals in C. elegans

In the model organism Caenorhabditis elegans, a family of endogenous small molecules, the ascarosides function as key regulators of developmental timing and behavior that act upstream of conserved signaling pathways. The ascarosides are based on the dideoxysugar ascarylose, which is linked to fatty-acid-like side chains of varying lengths derived from peroxisomal β-oxidation. Despite the importance of ascarosides for many aspects of C. elegans biology, knowledge of their structures, biosynthesis, and homeostasis remains incomplete. We used an MS/MS-based screen to profile ascarosides in C. elegans wild-type and mutant metabolomes, which revealed a much greater structural diversity of ascaroside derivatives than previously reported. Comparison of the metabolomes from wild-type and a series of peroxisomal β-oxidation mutants showed that the enoyl CoA-hydratase MAOC-1 serves an important role in ascaroside biosynthesis and clarified the functions of two other enzymes, ACOX-1 and DHS-28. We show that, following peroxisomal β-oxidation, the ascarosides are selectively derivatized with moieties of varied biogenetic origin and that such modifications can dramatically affect biological activity, producing signaling molecules active at low femtomolar concentrations. Based on these results, the ascarosides appear as a modular library of small-molecule signals, integrating building blocks from three major metabolic pathways: carbohydrate metabolism, peroxisomal β-oxidation of fatty acids, and amino acid catabolism. Our screen further demonstrates that ascaroside biosynthesis is directly affected by nutritional status and that excretion of the final products is highly selective

Yang-Lee zeros for a nonequilibrium phase transition

Equilibrium systems which exhibit a phase transition can be studied by investigating the complex zeros of the partition function. This method, pioneered by Yang and Lee, has been widely used in equilibrium statistical physics. We show that an analogous treatment is possible for a nonequilibrium phase transition into an absorbing state. By investigating the complex zeros of the survival probability of directed percolation processes we demonstrate that the zeros provide information about universal properties. Moreover we identify certain non-trivial points where the survival probability for bond percolation can be computed exactly.Comment: LaTeX, IOP-style, 13 pages, 10 eps figure

On the ground states of the Bernasconi model

The ground states of the Bernasconi model are binary +1/-1 sequences of length N with low autocorrelations. We introduce the notion of perfect sequences, binary sequences with one-valued off-peak correlations of minimum amount. If they exist, they are ground states. Using results from the mathematical theory of cyclic difference sets, we specify all values of N for which perfect sequences do exist and how to construct them. For other values of N, we investigate almost perfect sequences, i.e. sequences with two-valued off-peak correlations of minimum amount. Numerical and analytical results support the conjecture that almost perfect sequences do exist for all values of N, but that they are not always ground states. We present a construction for low-energy configurations that works if N is the product of two odd primes.Comment: 12 pages, LaTeX2e; extended content, added references; submitted to J.Phys.

Calcium-calmodulin does not alter the anion permeability of the mouse TMEM16A calcium-activated chloride channel.

The transmembrane protein TMEM16A forms a Ca(2+)-activated Cl(-) channel that is permeable to many anions, including SCN(-), I(-), Br(-), Cl(-), and HCO3 (-), and has been implicated in various physiological functions. Indeed, controlling anion permeation through the TMEM16A channel pore may be critical in regulating the pH of exocrine fluids such as the pancreatic juice. The anion permeability of the TMEM16A channel pore has recently been reported to be modulated by Ca(2+)-calmodulin (CaCaM), such that the pore of the CaCaM-bound channel shows a reduced ability to discriminate between anions as measured by a shift of the reversal potential under bi-ionic conditions. Here, using a mouse TMEM16A clone that contains the two previously identified putative CaM-binding motifs, we were unable to demonstrate such CaCaM-dependent changes in the bi-ionic potential. We confirmed the activity of CaCaM used in our study by showing CaCaM modulation of the olfactory cyclic nucleotide-gated channel. We suspect that the different bi-ionic potentials that were obtained previously from whole-cell recordings in low and high intracellular [Ca(2+)] may result from different degrees of bi-ionic potential shift secondary to a series resistance problem, an ion accumulation effect, or both