Evolution of associative learning in chemical networks

Organisms that can learn about their environment and modify their behaviour appropriately during their lifetime are more likely to survive and reproduce than organisms that do not. While associative learning – the ability to detect correlated features of the environment – has been studied extensively in nervous systems, where the underlying mechanisms are reasonably well understood, mechanisms within single cells that could allow associative learning have received little attention. Here, using in silico evolution of chemical networks, we show that there exists a diversity of remarkably simple and plausible chemical solutions to the associative learning problem, the simplest of which uses only one core chemical reaction. We then asked to what extent a linear combination of chemical concentrations in the network could approximate the ideal Bayesian posterior of an environment given the stimulus history so far? This Bayesian analysis revealed the ’memory traces’ of the chemical network. The implication of this paper is that there is little reason to believe that a lack of suitable phenotypic variation would prevent associative learning from evolving in cell signalling, metabolic, gene regulatory, or a mixture of these networks in cells

Herpes Simplex Virus 1 and 2 Infections during Differentiation of Human Cortical Neurons

Herpes simplex virus 1 (HSV-1) and 2 (HSV-2) can infect the central nervous system (CNS) with dire consequences; in children and adults, HSV-1 may cause focal encephalitis, while HSV-2 causes meningitis. In neonates, both viruses can cause severe, disseminated CNS infections with high mortality rates. Here, we differentiated human induced pluripotent stem cells (iPSCs) towards cortical neurons for infection with clinical CNS strains of HSV-1 or HSV-2. Progenies from both viruses were produced at equal quantities in iPSCs, neuroprogenitors and cortical neurons. HSV-1 and HSV-2 decreased viability of neuroprogenitors by 36.0% and 57.6% (p < 0.0001), respectively, 48 h post-infection, while cortical neurons were resilient to infection by both viruses. However, in these functional neurons, both HSV-1 and HSV-2 decreased gene expression of two markers of synaptic activity, CAMK2B and ARC, and affected synaptic activity negatively in multielectrode array experiments. However, unaltered secretion levels of the neurodegeneration markers tau and NfL suggested intact axonal integrity. Viral replication of both viruses was found after six days, coinciding with 6-fold and 22-fold increase in gene expression of cellular RNA polymerase II by HSV-1 and HSV-2, respectively. Our results suggest a resilience of human cortical neurons relative to the replication of HSV-1 and HSV-2

Reflections and Experiences of a Co-Researcher involved in a Renal Research Study

Background Patient and Public Involvement (PPI) is seen as a prerequisite for health research. However, current Patient and public involvement literature has noted a paucity of recording of patient and public involvement within research studies. There have been calls for more recordings and reflections, specifically on impact. Renal medicine has also had similar criticisms and any reflections on patient and public involvement has usually been from the viewpoint of the researcher. Roles of patient and public involvement can vary greatly from sitting on an Advisory Group to analysing data. Different PPI roles have been described within studies; one being a co-researcher. However, the role of the co-researcher is largely undefined and appears to vary from study to study. Methods The aims of this paper are to share one first time co-researcher's reflections on the impact of PPI within a mixed methods (non-clinical trial) renal research study. A retrospective, reflective approach was taken using data available to the co-researcher as part of the day-to-day research activity. Electronic correspondence and documents such as meeting notes, minutes, interview thematic analysis and comments on documents were re-examined. The co-researcher led on writing this paper. Results This paper offers a broad definition of the role of the co-researcher. The co-researcher reflects on undertaking and leading on the thematic analysis of interview transcripts, something she had not previously done before. The co-researcher identified a number of key themes; the differences in time and responsibility between being a coresearcher and an Advisory Group member; how the role evolved and involvement activities could match the co-researchers strengths (and the need for flexibility); the need for training and support and lastly, the time commitment. It was also noted that it is preferable that a co-researcher needs to be involved from the very beginning of the grant application. Conclusions The reflections, voices and views of those undertaking PPI has been largely underrepresented in the literature. The role of co-researcher was seen to be rewarding but demanding, requiring a large time commitment. It is hoped that the learning from sharing this experience will encourage others to undertake this role, and encourage researchers to reflect on the needs of those involved.Peer reviewedFinal Published versio

Brain immune cells undergo cGAS-STING-dependent apoptosis during herpes simplex virus type 1 infection

Protection of the brain from viral infections involves the type I interferon (IFN-I) system, defects in which renders humans susceptible to herpes simplex encephalitis (HSE). However, excessive cerebral IFN-I levels leads to pathologies, suggesting the need for tight regulation of responses. Based on data from mouse models, human HSE cases, and primary cell culture systems, we here show that microglia and other immune cells undergo apoptosis in the HSV-1-infected brain through a mechanism dependent on the cyclic GMP-AMP synthase (cGAS) - stimulator of interferon genes (STING) pathway, but independent of IFN-I. HSV-1 infection of microglia induced cGAS-dependent apoptosis at high viral doses, while lower viral doses led to IFN-I responses. Importantly, inhibition of caspase activity prevented microglial cell death and augmented IFN-I responses. Accordingly, HSV-1-infected organotypic brain slices, or mice treated with caspase inhibitor, exhibited lower viral load and improved outcome of infection. Collectively, we identify an activation-induced apoptosis program in brain immune cells which down-modulates local immune responses

Floral advertisement scent in a changing plant-pollinators market

Plant-pollinator systems may be considered as biological markets in which pollinators choose between different flowers that advertise their nectar/pollen rewards. Although expected to play a major role in structuring plant-pollinator interactions, community-wide patterns of flower scent signals remain largely unexplored. Here we show for the first time that scent advertisement is higher in plant species that bloom early in the flowering period when pollinators are scarce relative to flowers than in species blooming later in the season when there is a surplus of pollinators relative to flowers. We also show that less abundant flowering species that may compete with dominant species for pollinator visitation early in the flowering period emit much higher proportions of the generalist attractant β-ocimene. Overall, we provide a first community-wide description of the key role of seasonal dynamics of plant-specific flower scent emissions, and reveal the coexistence of contrasting plant signaling strategies in a plant-pollinator market

Evaluation of postural balance in postmenopausal women and its relationship with bone mineral density- a cross sectional study

Background: Low bone mineral density (BMD) and falls are common problems encountered in the postmenopausal women. The purpose was to evaluate the association between postural balance and BMD in postmenopausal women and its relation to risk for falls.Methods: In this cross-sectional study, 225 women in amenorrhea > 12 months and age >= 45 years were included and divided, according to BMD, in T-score values > -2.0 SD (n = 140) and <= -2 SD (n = 85). Those with neurological or musculoskeletal disorders, history of vestibulopathies, uncorrected visual deficit or drug use that could affect balance were excluded. History of falls (last 24 months), clinical and anthropometric characteristics were evaluated. Postural balance was assessed by stabilometry (force platform). For statistical analysis were used Wilcoxon's Test, Chi-Square Test and logistic regression method for fall risk (Odds Ratio-OR).Results: Patients with BMD > -2.0 SD were younger, with shorter time since menopause, and showed higher BMI as compared to those with low BMD (<= -2 SD) (p < 0.05). It was observed that 57.8% of the participants reported fall episodes without significant difference distribution between the groups (p = 0.055). No differences were found from the comparison between the groups (p > 0.05) for stabilometric parameters. Risk for falls increased with age (OR 1.07; CI 95% 1.01-1.13), current smoking (OR 2.19; CI 95% 1.22-3.21) and corrected visual deficit (OR 9.06; CI 95% 1.14-4.09). In contrast, hormone therapy (HT) use was significantly associated with reduced risk for falls (OR 0.48; CI 95% 0.26-0.88).Conclusions: In postmenopausal women, BMD did not show association with postural balance or risk for falls. Age, smoking and corrected visual deficit were clinical indicators of risk for falls whereas HT use showed to be a protective factor

Aging, working memory capacity and the proactive control of recollection:An event-related potential study

The present study investigated the role of working memory capacity (WMC) in the control of recollection in young and older adults. We used electroencephalographic event-related potentials (ERPs) to examine the effects of age and of individual differences in WMC on the ability to prioritize recollection according to current goals. Targets in a recognition exclusion task were words encoded using two alternative decisions. The left parietal ERP old/new effect was used as an electrophysiological index of recollection, and the selectivity of recollection measured in terms of the difference in its magnitude according to whether recognized items were targets or non-targets. Young adults with higher WMC showed greater recollection selectivity than those with lower WMC, while older adults showed nonselective recollection which did not vary with WMC. The data suggest that aging impairs the ability to engage cognitive control effectively to prioritize what will be recollected

Is organizational justice climate at the workplace associated with individual-level quality of care and organizational affective commitment?:A multi-level, cross-sectional study on dentistry in Sweden

Purpose The aim of this study is to investigate whether organizational justice climate at the workplace level is associated with individual staff members’ perceptions of carequality and affective commitment to the workplace.Methods The study adopts a cross-sectional multi-level design. Data were collected using an electronic survey and a response rate of 75% was obtained. Organizational justice climate and affective commitment to the workplace were measured by items from Copenhagen Psychosocial Questionnaire and quality of care by three self-developed items. Non-managerial staff working at dental clinics with at least five respondents (n = 900 from 68 units) was included in analyses. A set of Level-2 random intercept models were built to predict individual-level organizational affective commitment and perceived quality of care from unit-level organizational justice climate, controlling for potential confoundingby group size, gender, age, and occupation.Results The results of the empty model showed substantial between-unit variation for both affective commitment (ICC-1 = 0.17) and quality of care (ICC-1 = 0.12). The overall results showed that the shared perception of organizational justice climate at the clinical unit level was significantly associated with perceived quality of care and affective commitment to the organization (p < 0.001).Conclusions Organizational justice climate at work unit level explained all variation in affective commitment among dental clinics and was associated with both the individualstaff members’ affective commitment and perceived quality of care. These findings suggest a potential for that addressing organizational justice climate may be a way to promote quality of care and enhancing affective commitment. However, longitudinal studies are needed to support causality in the examined relationships. Intervention research is also recommended to probe the effectiveness of actions increasingunit-level organizational justice climate and test their impact on quality of care and affective commitment

Rhamnolipids: diversity of structures, microbial origins and roles

Rhamnolipids are glycolipidic biosurfactants produced by various bacterial species. They were initially found as exoproducts of the opportunistic pathogen Pseudomonas aeruginosa and described as a mixture of four congeners: α-L-rhamnopyranosyl-α-L-rhamnopyranosyl-β-hydroxydecanoyl-β-hydroxydecanoate (Rha-Rha-C10-C10), α-L-rhamnopyranosyl-α-L-rhamnopyranosyl-β-hydroxydecanoate (Rha-Rha-C10), as well as their mono-rhamnolipid congeners Rha-C10-C10 and Rha-C10. The development of more sensitive analytical techniques has lead to the further discovery of a wide diversity of rhamnolipid congeners and homologues (about 60) that are produced at different concentrations by various Pseudomonas species and by bacteria belonging to other families, classes, or even phyla. For example, various Burkholderia species have been shown to produce rhamnolipids that have longer alkyl chains than those produced by P. aeruginosa. In P. aeruginosa, three genes, carried on two distinct operons, code for the enzymes responsible for the final steps of rhamnolipid synthesis: one operon carries the rhlAB genes and the other rhlC. Genes highly similar to rhlA, rhlB, and rhlC have also been found in various Burkholderia species but grouped within one putative operon, and they have been shown to be required for rhamnolipid production as well. The exact physiological function of these secondary metabolites is still unclear. Most identified activities are derived from the surface activity, wetting ability, detergency, and other amphipathic-related properties of these molecules. Indeed, rhamnolipids promote the uptake and biodegradation of poorly soluble substrates, act as immune modulators and virulence factors, have antimicrobial activities, and are involved in surface motility and in bacterial biofilm development