Phylogenetic Codivergence Supports Coevolution of Mimetic Heliconius Butterflies

The unpalatable and warning-patterned butterflies _Heliconius erato_ and _Heliconius melpomene_ provide the best studied example of mutualistic Müllerian mimicry, thought – but rarely demonstrated – to promote coevolution. Some of the strongest available evidence for coevolution comes from phylogenetic codivergence, the parallel divergence of ecologically associated lineages. Early evolutionary reconstructions suggested codivergence between mimetic populations of _H. erato_ and _H. melpomene_, and this was initially hailed as the most striking known case of coevolution. However, subsequent molecular phylogenetic analyses found discrepancies in phylogenetic branching patterns and timing (topological and temporal incongruence) that argued against codivergence. We present the first explicit cophylogenetic test of codivergence between mimetic populations of _H. erato_ and _H. melpomene_, and re-examine the timing of these radiations. We find statistically significant topological congruence between multilocus coalescent population phylogenies of _H. erato_ and _H. melpomene_, supporting repeated codivergence of mimetic populations. Divergence time estimates, based on a Bayesian coalescent model, suggest that the evolutionary radiations of _H. erato_ and _H. melpomene_ occurred over the same time period, and are compatible with a series of temporally congruent codivergence events. This evidence supports a history of reciprocal coevolution between Müllerian co-mimics characterised by phylogenetic codivergence and parallel phenotypic change

Gating at the Mouth of the Acetylcholine Receptor Channel: Energetic Consequences of Mutations in the αM2-Cap

Gating of nicotinic acetylcholine receptors from a C(losed) to an O(pen) conformation is the initial event in the postsynaptic signaling cascade at the vertebrate nerve-muscle junction. Studies of receptor structure and function show that many residues in this large, five-subunit membrane protein contribute to the energy difference between C and O. Of special interest are amino acids located at the two transmitter binding sites and in the narrow region of the channel, where C↔O gating motions generate a low↔high change in the affinity for agonists and in the ionic conductance, respectively. We have measured the energy changes and relative timing of gating movements for residues that lie between these two locations, in the C-terminus of the pore-lining M2 helix of the α subunit (‘αM2-cap’). This region contains a binding site for non-competitive inhibitors and a charged ring that influences the conductance of the open pore. αM2-cap mutations have large effects on gating but much smaller effects on agonist binding, channel conductance, channel block and desensitization. Three αM2-cap residues (αI260, αP265 and αS268) appear to move at the outset of channel-opening, about at the same time as those at the transmitter binding site. The results suggest that the αM2-cap changes its secondary structure to link gating motions in the extracellular domain with those in the channel that regulate ionic conductance

Geminin-Deficient Neural Stem Cells Exhibit Normal Cell Division and Normal Neurogenesis

Neural stem cells (NSCs) are the progenitors of neurons and glial cells during both embryonic development and adult life. The unstable regulatory protein Geminin (Gmnn) is thought to maintain neural stem cells in an undifferentiated state while they proliferate. Geminin inhibits neuronal differentiation in cultured cells by antagonizing interactions between the chromatin remodeling protein Brg1 and the neural-specific transcription factors Neurogenin and NeuroD. Geminin is widely expressed in the CNS during throughout embryonic development, and Geminin expression is down-regulated when neuronal precursor cells undergo terminal differentiation. Over-expression of Geminin in gastrula-stage Xenopus embryos can expand the size of the neural plate. The role of Geminin in regulating vertebrate neurogenesis in vivo has not been rigorously examined. To address this question, we created a strain of Nestin-Cre/Gmnnfl/fl mice in which the Geminin gene was specifically deleted from NSCs. Interestingly, we found no major defects in the development or function of the central nervous system. Neural-specific GmnnΔ/Δ mice are viable and fertile and display no obvious neurological or neuroanatomical abnormalities. They have normal numbers of BrdU+ NSCs in the subgranular zone of the dentate gyrus, and GmnnΔ/Δ NSCs give rise to normal numbers of mature neurons in pulse-chase experiments. GmnnΔ/Δ neurosphere cells differentiate normally into both neurons and glial cells when grown in growth factor-deficient medium. Both the growth rate and the cell cycle distribution of cultured GmnnΔ/Δ neurosphere cells are indistinguishable from controls. We conclude that Geminin is largely dispensable for most of embryonic and adult mammalian neurogenesis

Using participatory design methodologies to co-design and culturally adapt the Spanish version of the Mental Health eClinic: Qualitative study

Background: The Mental Health eClinic (MHeC) aims to deliver best-practice clinical services to young people experiencing mental health problems by making clinical care accessible, affordable, and available to young people whenever and wherever they need it most. The original MHeC consists of home page with a visible triage system for those requiring urgent help; a online physical and mental health self-report assessment; a results dashboard; a booking and videoconferencing system; and the generation of a personalized well-being plan. Populations who do not speak English and reside in English-speaking countries are less likely to receive mental health care. In Australia, international students have been identified as disadvantaged compared with their peers; have weaker social support networks; and have higher rates of psychological distress. This scenario is acquiring significant relevance as Spanish-speaking migration is rapidly growing in Australia, and the mental health services for culturally and linguistically diverse populations are limited. Having a Spanish version (MHeC-S) of the Mental Health eClinic would greatly benefit these students. Objective: We used participatory design methodologies with users (young people aged 16-30 years, supportive others, and health professionals) to (1) conduct workshops with users to co-design and culturally adapt the MHeC; (2) inform the development of the MHeC-S alpha prototype; (3) test the usability of the MHeC-S alpha prototype; (4) translate, culturally adapt, and face-validate the MHeC-S self-report assessment; and (5) collect information to inform its beta prototype. Methods: A research and development cycle included several participatory design phases: co-design workshops; knowledge translation; language translation and cultural adaptation; and rapid prototyping and user testing of the MHeC-S alpha prototype. Results: We held 2 co-design workshops with 17 users (10 young people, 7 health professionals). A total of 15 participated in the one-on-one user testing sessions (7 young people, 5 health professionals, 3 supportive others). We collected 225 source documents, and thematic analysis resulted in 5 main themes (help-seeking barriers, technology platform, functionality, content, and user interface). A random sample of 106 source documents analyzed by 2 independent raters revealed almost perfect agreement for functionality (kappa=.86; P\u3c.001) and content (kappa=.92; P\u3c.001) and substantial agreement for the user interface (kappa=.785; P\u3c.001). In this random sample, no annotations were coded for help-seeking barriers or the technology platform. Language was identified as the main barrier to getting medical or psychological services, and smartphones were the most-used device to access the internet. Acceptability was adequate for the prototype’s 5 main elements: home page and triage system, self-report assessment, dashboard of results, booking and video visit system, and personalized well-being plan. The data also revealed gaps in the alpha prototype, such as the need for tailored assessment tools and a greater integration with Spanish-speaking services and communities. Spanish-language apps and e-tools, as well as online mental health information, were lacking. Conclusions: Through a research and development process, we co-designed and culturally adapted, developed and user tested, and evaluated the MHeC-S. By translating and culturally adapting the MHeC to Spanish, we aimed to increase accessibility and availability of e-mental health care in the developing world, and assist vulnerable populations that have migrated to English-speaking countries

Basal ganglia correlates of fatigue in young adults

Although the prevalence of chronic fatigue is approximately 20% in healthy individuals, there are no studies of brain structure that elucidate the neural correlates of fatigue outside of clinical subjects. We hypothesized that fatigue without evidence of disease might be related to changes in the basal ganglia and prefrontal cortex and be implicated in fatigue with disease. We aimed to identify the white matter structures of fatigue in young subjects without disease using magnetic resonance imaging (MRI). Healthy young adults (n = 883; 489 males and 394 females) were recruited. As expected, the degrees of fatigue and motivation were associated with larger mean diffusivity (MD) in the right putamen, pallidus and caudate. Furthermore, the degree of physical activity was associated with a larger MD only in the right putamen. Accordingly, motivation was the best candidate for widespread basal ganglia, whereas physical activity might be the best candidate for the putamen. A plausible mechanism of fatigue may involve abnormal function of the motor system, as well as areas of the dopaminergic system in the basal ganglia that are associated with motivation and reward

Integrated sensory motor system in prematurely born children

Objetivo: Investigar a existência de sistema sensório motor integrado em recém-nascidos (RNs) prematuros submetidos à estimulação gustativa. Métodos: Estudo experimental analítico e duplo-cego. Participaram 90 RNs prematuros, divididos em dois grupos (água e sacarose para análise (PA) 12%), filmados durante 15 minutos (primeiro e último momentos, sem estimulação; e segundo momento com estimulação gustativa). Três juízes independentes analisaram os comportamentos mão na boca direita e esquerda e sucção da mão direita e esquerda durante os diversos estados comportamentais, inseridos no banco de dados do Statistical Package for Social Science, sendo considerados em concordância os eventos observados por pelo menos dois deles. Empregou-se teste de correlação de Spearman com nível de significância valor de p<0,05. Resultados: Tanto ao serem considerados os grupos separadamente quanto juntos, mão na boca direita e esquerda tiveram inicialmente correlação moderada, sendo que mão na boca direita manteve-se forte no final e mão na boca esquerda finalizou com correlação moderada e forte, de acordo com cada estado comportamental. Sucção de mão direita na totalidade e em sacarose apresentou-se inicialmente com correlação forte no estado sonolento, passando para moderada ao final. No estado alerta houve inicialmente correlação fraca em ambos os estímulos, finalizando com correlação moderada em sacarose e forte em água. Sucção de mão esquerda apresentou-se inicialmente correlação moderada em alerta, finalizando com correlação fraca no grupo sacarose, o que não ocorreu na água, que iniciou e finalizou forte. Conclusão: A estimulação oral influenciou na coordenação mão-boca, independente do estímulo, evidenciando integração sensório motora precoce, mas não inferindo sobre capacidade de discriminação gustativa nos prematuros. _________________________________________________________________________________________ ABSTRACT: Purpose: To investigate about an integrated sensory motor system existence in premature newborns, submitted to gustatory stimulation. Methods: Analytical and experimental study of contents, double-blind. Being participants 90 premature newborns, divided into two groups (water or sucrose analysis 12%). Recorded by 15 minutes (first and last moments, without stimulation; and second time with gustatory stimulation). Three independent judges analyzed the behaviors in the right hand and left hand in the mouth and suction in the left and right and hand during the various behavioral states, those being inserted in the database of Statistical Package for Social Science, being then considered that the events observed by at least two of them. It was made use of Spearman’s rank correlation test on a significance level by p<0.05. Results: Considering the groups both separately and together, right and left had initially moderate correlation, being right hand in the mouth remained strong at the end and left hand in the mouth finished on moderate and strong correlation, according to each behavioral state. Right hand suction in its total and sucrose showed a strong correlation initially in drowsy state, becoming moderate at the end. In alertness state there was initially a weak correlation in both stimuli ending in moderate correlation in sucrose and strong in water. Left hand suction presented initially moderate correlation on the alert state, ending in weak correlation in sucrose stimuli, which did not occur in the water that started and finished strong. Conclusion: The oral stimulation influenced the hand-mouth coordination, showing early motor sensory integration. However, there was no discrimination about the gustatory capacity on the newborns

Guiding principles for the development and application of solid-phase phosphorus adsorbents for freshwater ecosystems

While a diverse array of phosphorus (P)-adsorbent materials is currently available for application to freshwater aquatic systems, selection of the most appropriate P-adsorbents remains problematic. In particular, there has to be a close correspondence between attributes of the P-adsorbent, its field performance, and the management goals for treatment. These management goals may vary from a rapid reduction in dissolved P to address seasonal enrichments from internal loading, targeting external fluxes due to anthropogenic sources, or long term inactivation of internal P inventories contained within bottom sediments. It also remains a challenge to develop new methods and materials that are ecologically benign and cost-effective. We draw on evidence in the literature and the authors’ personal experiences in the field, to summarise the attributes of a range of P-adsorbent materials. We offer 'guiding principles' to support practical use of existing materials and outline key development needs for new materials