Host cell-specific folding of the neuronal nicotinic acetylcholine receptor α7 and α8 subunits

The α7 and α8 nicotinic acetylcholine receptor (nAChR) subunits when expressed in Xenopus oocytes, form functional homo-oligomeric ion channels which are potently inhibited by the nicotinic antagonist α-bungarotoxin (αBTX). However, expression of the rat α7 and chick α8 subunits in several mammalian cell lines demonstrates that the folding of α7 and α8 into a conformation able to bind αBTX or conformation- sensitive antibodies, is critically dependent on the host cell type. In all cell lines, production of α7 (~58 kDa) or α8 (~57 kDa) subunit protein was verified by metabolic labelling and immunoprecipitation using subunit-specific antibodies which recognise linear epitopes. In contrast, for both α7 and α8 subunits, antibodies which recognise conformation-dependent extracellular epitopes fail to detect subunit protein in cell lines which fail to produce nicotinic radioligand binding, implying that these subunits are misfolded. The α7 subunit was expressed in a panel of nine mammalian cell lines from neuronal (N1E-115, NCB-20, Neuro2A, NG108-15, PC12, SH-SY5Y) and non-neuronal (HEK293, CHO, COS-7) origins. However, elevated levels of αBTX-binding could be detected in only two (PC12 and SH-SY5Y) of the nine cell lines examined. The α8 subunit was expressed in three cell lines (HEK293, GH4C1, SH-SY5Y) and readily formed αBTX-binding sites in a polyclonal SH-SY5Y-α8 cell line and when transiently expressed in GH4C1 cells. Saturation binding revealed that α8 nAChRs expressed in transfected GH4C1-α8 cells bind epibatidine with high affinity (KD=0.24 ± 0.4 nM) although no specific αBTX or epibatidine binding could be detected in transfected HEK293-α8 cells. HEK293 cells which fail to correctly fold the α7 and α8 nAChR subunits form functional cell surface rat muscle nAChRs and homo-oligomeric 5-HT3 receptors. In addition, chimaeric subunits encoding the N-terminal region of α7 or α8 and the C-terminal domain of the 5-HT3 receptor were expressed very efficiently in all cell lines examined. These results implicate the C-terminal domain of α7 and α8 in the cell-type specific folding and further chimeras need to be generated to more precisely determine which region mediates this effect

Examining student achievement and curriculum in a nursing program at a Midwestern community college

ABSTRACT The purpose of this study was to examine the pathway model of a nursing curriculum and evaluate the relationship and predictive ability of demographic and academic variables on the success or failure of those taking the National Council Licensure Examination for Registered Nurses (NCLEX-RN®) and to determine the impact of noncognitive role variables to student outcomes. A retrospective exploratory study was conducted using a purposive sample of 225 students admitted between 2007 and 2009 to an associate degree nursing program at a large Midwestern community college. Demographic and academic variables of age, prior degrees, Test of Essential Academic Skills (TEAS®) nursing entrance assessment score, science and nursing course grades, ATI RN Comprehensive Predictor Assessment exit score and cumulative grade point averages were analyzed for predictive value of first-attempt pass on the NCLEX-RN. In a separate analysis, the program database was explored to determine the impact of the noncognitive role variables of employment, and caregiving responsibilities on student academic outcomes in the first year of the program. Descriptive analyses supported the relationship of the TEAS entrance assessment with early nursing program success. Students with prior degrees were more likely to persist in the program and graduate. Descriptive analysis of the cumulative grade point average showed implications for transfer and completion of a 4-year degree. The results of the chi-square analysis revealed statistical significance in associations between passing or failing the NCLEX-RN in the cumulative GPA and the RN Comprehensive Assessment score and first nursing course in the first and second years of the program: PNN139 and ADN577, respectively. The independent t test determined there were no significant differences in academic outcomes related to students\u27 noncognitive roles. An exploratory forward stepwise regression was employed to test the theoretical pathway model that examines the factors that predict the results of NCLEX-RN exam. The pathway model was not significant due to the limited variability number of observations in the dependent variable. Implications for nursing education and recommendations for further study are addressed

Tributes to Professor Robert Berkley Harper

In 1977, I began teaching at The University of Pittsburgh Law School and in short order one of my closest friends during my tenure there was Professor Robert “Bob” Harper. I wondered when I was hired whether I was selected because I looked strikingly similar to Bob, and perhaps the faculty thought my favoring Professor Harper would make my assimilation into the law school faculty that much easier. Students constantly called me Professor Harper and, indeed, many on the faculty called me Bob for several years; I never bothered to correct them. I thought if they paid that little attention to detail in law school, I would just let them go through life missing some of the finer points their education, and life for that matter, has to offer

The Late Iron Age in Switzerland: a review of anthropological, funerary, and isotopic studies

The Iron Age in continental Europe is a period of profound cultural and biological importance with heterogeneous trends through space and time. Regional overviews are therefore useful for better understanding the main cultural and biological patterns characterizing this period across the European regions. For the area of modern Switzerland, a rich archeological and anthropological record represents the Late Iron Age. However, no review of the main anthropological and funerary patterns for this period is available to date. Here we assess the available demographic, paleopathological, funerary, and isotopic data for the Late Iron Age in the Swiss territory, and summarize the cultural and biological patterns emerging from the available literature. Finally, we highlight a series of research avenues for future studies

Restructuring and hospital care: Sub-national trends, differentials, and their impacts; New Zealand from 1981

An analysis of the "nation's health" is the central concern of this study. Its genesis was a detailed, technical, time-series research on regional and ethnic differentials in health in New Zealand. But as this work progressed it became increasingly evident that the results of this more narrow analysis could make a wider contribution to the development of a knowledge-base on health trends and on the impacts of policy on these. In a sense, the analysis provides a demographic audit of health trends over the last two decades. The focus here is different from that in most other studies on restructuring of the New Zealand health system as their concern was either to review in detail the rewriting of policy per se, and attendant structural and institutional changes (Fougere 2001), or to identify how these changes relate to changes in mortality (Blakely et al. 2008). The research question reported here was, instead, to analyse the most crucial of health outcomes, „how long we live and how often we end up in hospital‟, identified in the earlier quotation, to report patterns and trends in hospital use nationally and sub-nationally over the period under review, and to determine the degrees to which various sub-populations benefited, or did not benefit, from these changes. The analysis focuses on the hospital sector in the system, but it will also show relations between this and other sectors, formal (e.g. primary health) and less formal (notably the healthcare afforded sickness and invalid beneficiaries). Thus two questions are addressed: 1. whether or not the nation‟s population health improved over the period and; 2. whether or not there was a convergence in patterns of health gain across its constituent sub-populations defined geographically and ethnically. This monograph deals with sub-national differences in health in New Zealand over a period of substantial socio-economic restructuring and associated radical changes in health policy, health systems and their related information systems (see also, Text Appendix A). It complements the recently published analysis of national ethnic trends in mortality (Blakely et al. 2004), but differs in several critical respects. That study reviewed health status by emphasising aetiologies and causes of death. In contrast, the present analysis focuses on actuarial dimensions of both mortality and morbidity and on health as measured by functional capacity rather than the disease orientated „burden of disease‟. It goes beyond health status issues to look at the system itself, to assess whether health policy outcomes were generated more through efficiency-gain (economic or service delivery, such as those resulting in a convergence sub-nationally of supply and demand effects), or through health gains, or ideally, by both. To do this, and as a by-product to analyse changes in health status and the system in an era of restructuring, innovative methodologies and composite time-series indices combining the two dimensions of a „nation‟s health‟, needing hospital care and longevity, have had to be custom-designed. To achieve this objective, the ensuing analysis is often technical, and may introduce concepts that are unfamiliar to some readers. In order to look at possible inequalities of outcome, comparisons were made between regions and ethnic groups, as well as age-groups and genders, and as a result, in places the analysis becomes rather complex

Conhecimento e ação no desenvolvimento cognitivo do adulto : o caso da educação econômico-financeira

Orientadora: Profª Drª Tania StoltzTese (doutorado) - Universidade Federal do Paraná, Setor de Educação, Programa de Pós-Graduação em Educação. Defesa: Curitiba, 30/03/2017Inclui referências : p. 225-239Resumo: Este estudo tem, como questão central, a relação entre conhecimento e ação. Como objetivo geral, investiga a prática pedagógica em educação econômico-financeira de adultos, inspirada nas teorias do conhecimento de Jean Piaget e de Rudolf Steiner, voltada ao uso consciente de cartão de crédito. A revisão de literatura aponta para a importância da educação econômico-financeira que oportunize o uso consciente do crédito ofertado via cartão. Contudo, é frequente constatar que a educação econômico-financeira tende a enfocar a transmissão de informação, refutando o papel ativo do sujeito do conhecimento, bem como da afetividade e das emoções na construção do conhecimento. Consumir, de forma crítica e consciente, não implica ser avesso ao uso de cartão de crédito, baseado em uma racionalidade anticonsumo e sim, fazer escolhas a partir da tomada de consciência de suas ações e apoiadas em sua vontade que, por sua vez, também não deve ser puramente regida pelas emoções e impulsos, e sim por uma liberdade de escolha, fundamentada em um individualismo ético. Trata-se de estudo qualitativo na modalidade pesquisa-ação. A metodologia deste estudo envolve prática pedagógica que visa integrar o conhecimento (vivenciado) e a ação (transformada). A prática pedagógica, desenvolvida como curso de extensão da UFPR, foi ofertada aos estudantes de um Centro Estadual de Educação Básica de Jovens e Adultos, em Curitiba. Participaram deste estudo 23 estudantes adultos, sendo 14 mulheres e 9 homens com idades entre 19 e 50 anos. Inspirada no método clínico de Piaget e contando com produções artístico-criativas, a prática pedagógica oportunizou momentos de reflexão e troca de saberes entre os participantes, destacando a importância do trabalho em grupo e do self-government no processo de tomada de consciência dos fatores pessoais e sociais envolvidos no uso de cartão de crédito. A coleta de dados contou com observação e registro em diário de campo, produções criativo-artísticas dos participantes, gravações das práticas pedagógicas. A análise de dados buscou regularidades no conjunto de dados coletados, estabelecendo categorias explicativas do movimento em cada encontro com os estudantes e no conjunto de encontros. Foram encontradas três categorias representativas das representações dos participantes em relação ao uso de cartão de crédito, a saber: visão positivoextremista, visão negativo-extremista e visão flutuante. Nos casos extremos, os participantes tendem a considerar apenas os pontos negativos ou positivos do uso de cartão de crédito e, na categoria flutuante, oscilam, considerando ora os pontos positivos, ora os negativos. Os resultados destacam a necessidade de equilíbrio entre esses modos de visão, a partir da tomada de consciência das próprias ações e do processo de crédito. Conclui-se que a prática pedagógica deve oportunizar a integração entre o querer, o sentir e o pensar dos participantes, para que possam utilizar o crédito ofertado por meio de cartão de forma consciente, aliando conhecimento e ação, agindo, assim, a partir de um individualismo ético. Palavras-chave: Educação econômico-financeira. Piaget. Rudolf Steiner. Prática pedagógica.Abstract: This study has, as central question, the relation between knowledge and action. As a general objective, he investigates the pedagogical practice in adult economic and financial education, inspired by the theories of knowledge of Jean Piaget and Rudolf Steiner, aimed at the conscious use of credit card. The literature review points to the importance of economic-financial education that allows the conscious use of credit offered through the card. However, it is common to see that economic-financial education tends to focus on the transmission of information, refuting the active role of the subject of knowledge as well as the affectivity and emotions in the construction of knowledge. Consumption, in a critical and conscious way, does not imply being averse to using a credit card, based on an anti-consumption rationality, but making choices based on the awareness of your actions and supported by your will, which, in turn, also It should not be purely governed by emotions and impulses, but by a freedom of choice, based on an ethical individualism. This is a qualitative study in the research-action modality. The methodology of this study involves pedagogical practice that aims to integrate knowledge (lived) and (transformed) action. The pedagogical practice, developed as a UFPR extension course, was offered to students of a State Center for Basic Education of Young and Adult, in Curitiba. Twenty-three adult students participated in this study, of which 14 were women and 9 were men aged 19-50. Inspired by Piaget's clinical method and with artistic-creative productions, the pedagogical practice provided opportunities for reflection and exchange of knowledge among participants, highlighting the importance of group work and self-government in the process of becoming aware of personal factors and social networks involved in the use of credit card. Data collection included observation and recording in field diary, creative-artistic productions of the participants, recordings of pedagogical practices. The data analysis sought regularities in the set of data collected, establishing explanatory categories of movement in each encounter with the students and in the set of encounters. Three representative categories of participants' representations regarding credit card use were found: positive-extremist view, negative-extremist view, and floating view. In extreme cases, participants tend to consider only the negative or positive points of credit card use, and fluctuate in the floating category, considering both the positive and negative points. The results highlight the need for a balance between these modes of vision, from the awareness of one's actions and the credit process. It is concluded that the pedagogical practice should allow the integration between the participants' will, feeling and thinking, so that they can use the credit offered by means of a card in a conscious way, combining knowledge and action, thus acting from an ethical individualism. Keywords: Economic-financial education. Piaget. Rudolf Steiner. Pedagogical practice.Resumen: Este estudio tiene como cuestión central la relación entre conocimiento y acción. Como objetivo general, se investiga la práctica pedagógica en educación económico-financiera de adultos, con inspiración en las teorías del conocimiento de Jean Piaget y de Rudolf Steiner, volcada al uso consciente de la tarjeta de crédito. La revisión de literatura apunta hacia a la importancia de la educación económicofinanciera que ofrezca el uso consciente del crédito ofrecido por la tarjeta. Sin embargo, es frecuente constatar que la educación económico-financiera tiende a enfocar la transmisión de información, y se acaba por preterir el papel activo del sujeto del conocimiento, bien como la afectividad y las emociones en la construcción del conocimiento. Consumir, de forma crítica y consciente, no implica en ser avieso al uso de la tarjeta, basándose en una racionalidad anti-consumo pero hacer elecciones a partir de la tomada de consciencia de sus acciones y estas apoyadas en su voluntad que, por su vez, tampoco debe ser puramente regida por las emociones e impulsos, pero sí por una libertad de escoja, fundamentada en un individualismo ético. Es un estudio cualitativo en la modalidad investigación acción. La metodología de este estudio involucra una práctica pedagógica que visa a integrar el conocimiento (vivido) y la acción (transformada). La práctica pedagógica, desarrollada como curso de extensión de la UFPR, fue ofrecida a los estudiantes de un Centro Estadual de Educación Básica de Jóvenes y Adultos, en Curitiba. Participaron de este estudio 23 estudiantes adultos, 14 mujeres y 9 hombres con edades entre 19 y 50 años. Inspirada en el método clínico de Piaget y contando con producciones artístico-creativas, la práctica pedagógica ofreció momentos de reflexión e intercambio de saberes entre los participantes, con relieve a la importancia del trabajo en grupo y al self-government en el proceso de tomada de consciencia de los factores personales y sociales involucrados en el uso de la tarjeta de crédito. Para la recolección de datos se utilizó la observación, el registro en apuntes de producciones creativo-artísticas de los participantes, y grabaciones de las prácticas pedagógicas. El análisis de datos buscó las regularidades en un conjunto de datos recogidos, estableciendo categorías explicativas del movimiento en cada encuentro con los estudiantes y en el conjunto de encuentros. Se encontraron tres categorías representativas de las representaciones de los participantes en relación al uso de la tarjeta de crédito: visión positivo-extremista, visión negativo-extremista y visión flotante. En los casos extremos, los participantes tienden a considerar solamente los puntos negativos o los positivos del uso de la tarjeta de crédito, ya en la categoría flotante, oscilan, o sea, en ciertos momentos presentan puntos positivos, en otros los negativos. Los resultados ponen en relieve la necesidad de equilibrio entre eses modos de ver, a partir de la tomada de consciencia de las propias acciones y del proceso de crédito. Se concluye que la práctica pedagógica debe provocar la integración entre la voluntad, el sentir y el pensar de los participantes, para que puedan utilizar el crédito ofrecido por medio de tarjeta de manera consciente, asociando conocimiento y acción, para así actuar a partir de un individualismo ético. Palabras-clave: Educación económico-financiera. Piaget. Rudolf Steiner. Práctica pedagógica

Cartão de crédito : salvação ou perdição? Representações de adultos jovens sobre instituições financeiras e utilização de cartão de crédito

Orientadora: Profª Drª Tania StoltzDissertação (mestrado) - Universidade Federal do Paraná, Setor de Educação, Programa de Pós-Graduação em Educação. Defesa: Curitiba, 31/03/2011Bibliografia: fls. 159-169Resumo: Trata-se de um estudo de abordagem piagetiana, inserido no campo dos estudos sobre o conhecimento social, que teve como objetivo identificar as representações de adultos jovens de Curitiba/PR, referentes aos processos de obtenção de lucro das instituições financeiras, a partir da utilização do cartão de crédito. A revisão da literatura evidencia a escassez dos estudos referentes à compreensão dos sujeitos em relação ao mundo econômico, principalmente no que se refere aos jovens e adultos. Uma vez que as ações dos sujeitos são regidas por suas representações, é importante conhecer como estes constroem e organizam suas representações sobre o mundo econômico, mais especificamente sobre os processos que envolvem a utilização do cartão de crédito, e assim contribuir para a elaboração de propostas educacionais que vislumbrem o entendimento destas questões de ordem socioeconômicas. Os dados foram coletados por meio de entrevistas individuais, realizadas a partir de um roteiro de perguntas semiestruturado, elaborado segundo o método clínico de Piaget (1926), baseado na perspectiva do pesquisador Delval (2002). Todas as entrevistas foram transcritas e distribuídas em planilhas descritivas a partir das quais foram determinadas dez categorias que descrevem as representações dos participantes, a saber: 1) quantidade de cartões de crédito, 2) forma de obtenção do cartão de crédito, 3) forma de pagamento com cartão, 4) controle de gastos com cartão de crédito, 5) forma de pagamento das faturas, 6) vantagens e desvantagens das financiadoras conforme a forma de pagamento das faturas, 7) limite de crédito, 8) prejuízos e benefícios na utilização do cartão de crédito, 9) recomendações para a utilização do cartão de crédito e, 10) representações referentes aos processos de obtenção de lucro das instituições. Os resultados deste estudo revelaram formas distintas de conceber os processos de obtenção de lucro das instituições financeiras. Embora apontem a cobrança de juros como principal fonte de obtenção de lucro das financiadoras, a maioria dos participantes desconhece os múltiplos fatores que permeiam esse tipo de negociação. Concluiu-se que os adultos jovens, participantes deste estudo, que em tese, estão no estádio formal do desenvolvimento cognitivo, em sua maioria, apresentam um pensamento muito elementar, muitas vezes fantasioso, sobre as questões que envolvem a utilização do cartão de crédito e em relação aos processos de obtenção de lucro das financeiras, assemelhando-se ao pensamento infantil, com características dos estádios pré-operatório e operatório concreto. O que evidencia o importante papel da educação na construção de noções econômicas. Entende-se que, para que ocorra a construção do conhecimento é necessário que haja uma interiorização reflexiva dos sujeitos para além da ação prática. Deste modo, conclui-se que a aprendizagem resulta das próprias ações (reflexivas) do sujeito sobre o objeto de aprendizagem e que, se a estrutura é desenvolvida espontaneamente e alcançado o estado de equilíbrio, o aprendizado será duradouro (PIAGET, 1973/1970). Assim, propõe-se que as práticas pedagógicas, voltadas para o ensino de jovens e adultos, enfatizem a atividade do próprio indivíduo, uma vez que "sem essa atividade não há didática ou pedagogia que significativamente transforme o sujeito" (PIAGET, 1964, p.2).Abstract: This is a study of Piaget's approach, inserted in the field of social studies knowledge, which aimed to identify the representations of young adults, in Curitiba / Pr, regarding the procedures of the financial institutions for obtaining profits, from the use of credit card. The literature review makes evident the scarcity of studies about the understanding of the subject in relation to the economic world, especially reporting to youth and adults. Once the actions of this subjects are governed by their representations, it is important to know how they construct and organize their representations of the world economy, more specifically, about the processes that involves the use of credit card, and thus contribute to the development of proposals education that envisage the understanding of these issues of socioeconomic order. Data were collected through individual interviews, conducted from a script of questions semi-structured, prepared according to the clinical method of Piaget (1926), based on the researcher's perspective Delval (2002). All interviews were transcribed and distributed in worksheets, from which were determined ten categories that describe the representations of the participants, namely: 1) amount of credit cards, 2) how to obtain credit card, 3) form of card payment, 4) control of expenses with credit cards, 5) payment of invoices 6) advantages and disadvantages of financing as the payment of invoices, 7) credit limit, 8) losses and benefits of using credit card, 9) recommendations for the use of credit cards, and 10) representations regarding the procedures for obtaining profit institutions.The results of this study revealed different ways of conceiving the process of making a profit from financial institutions. While pointing out the charging of interest as the main source of funding make a profit, most participants are unaware of the multiple factors involved in such trading. It was concluded that young adults participants in this study, which in theory are in the formal stage of cognitive development, have very basic thoughts, often fanciful, on issues involving the use of credit card and regarding procedures for obtaining profit from financial, resembling the children's thought, with features of pre-operative stage and concrete operational. This shows the important role of education in building economic notions. It is understood that, for the occurrence of construction of knowledge is necessary to have a reflective internalization of the subjects in addition to the practical action. In this way, is concluded that learning is the result of the actions themselves (reflexive) of the subject on the object of learning and that if the structure is developed spontaneously reached steady state, the learning will be sustained (Piaget, 1973/1970) . Thus, it is proposed that the pedagogical practices, aimed at teaching young people and adults, emphasizing the activity of the subject, and that "without this activity there is no teaching or pedagogy that significantly transform the subject" (Piaget, 1964, p .2)

Do age-associated changes of voltage-gated sodium channel isoforms expressed in the mammalian heart predispose the elderly to atrial fibrillation?

© The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved. Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. The prevalence of the disease increases with age, strongly implying an age-related process underlying the pathology. At a time when people are living longer than ever before, an exponential increase in disease prevalence is predicted worldwide. Hence unraveling the underlying mechanics of the disease is paramount for the development of innovative treatment and prevention strategies. The role of voltage-gated sodium channels is fundamental in cardiac electrophysiology and may provide novel insights into the arrhythmogenesis of AF. Nav1.5 is the predominant cardiac isoform, responsible for the action potential upstroke. Recent studies have demonstrated that Nav1.8 (an isoform predominantly expressed within the peripheral nervous system) is responsible for cellular arrhythmogenesis through the enhancement of pro-arrhythmogenic currents. Animal studies have shown a decline in Nav1.5 leading to a diminished action potential upstroke during phase 0. Furthermore, the study of human tissue demonstrates an inverse expression of sodium channel isoforms; reduction of Nav1.5 and increase of Nav1.8 in both heart failure and ventricular hypertrophy. This strongly suggests that the expression of voltage-gated sodium channels play a crucial role in the development of arrhythmias in the diseased heart. Targeting aberrant sodium currents has led to novel therapeutic approaches in tackling AF and continues to be an area of emerging research. This review will explore how voltage-gated sodium channels may predispose the elderly heart to AF through the examination of laboratory and clinical based evidence

Phylogenetic analysis of ferlin genes reveals ancient eukaryotic origins

<p>Abstract</p> <p>Background</p> <p>The ferlin gene family possesses a rare and identifying feature consisting of multiple tandem C2 domains and a C-terminal transmembrane domain. Much currently remains unknown about the fundamental function of this gene family, however, mutations in its two most well-characterised members, dysferlin and otoferlin, have been implicated in human disease. The availability of genome sequences from a wide range of species makes it possible to explore the evolution of the ferlin family, providing contextual insight into characteristic features that define the ferlin gene family in its present form in humans.</p> <p>Results</p> <p>Ferlin genes were detected from all species of representative phyla, with two ferlin subgroups partitioned within the ferlin phylogenetic tree based on the presence or absence of a DysF domain. Invertebrates generally possessed two ferlin genes (one with DysF and one without), with six ferlin genes in most vertebrates (three DysF, three non-DysF). Expansion of the ferlin gene family is evident between the divergence of lamprey (jawless vertebrates) and shark (cartilaginous fish). Common to almost all ferlins is an N-terminal C2-FerI-C2 sandwich, a FerB motif, and two C-terminal C2 domains (C2E and C2F) adjacent to the transmembrane domain. Preservation of these structural elements throughout eukaryotic evolution suggests a fundamental role of these motifs for ferlin function. In contrast, DysF, C2DE, and FerA are optional, giving rise to subtle differences in domain topologies of ferlin genes. Despite conservation of multiple C2 domains in all ferlins, the C-terminal C2 domains (C2E and C2F) displayed higher sequence conservation and greater conservation of putative calcium binding residues across paralogs and orthologs. Interestingly, the two most studied non-mammalian ferlins (Fer-1 and Misfire) in model organisms <it>C. elegans </it>and <it>D. melanogaster</it>, present as outgroups in the phylogenetic analysis, with results suggesting reproduction-related divergence and specialization of species-specific functions within their genus.</p> <p>Conclusions</p> <p>Our phylogenetic studies provide evolutionary insight into the ferlin gene family. We highlight the existence of ferlin-like proteins throughout eukaryotic evolution, from unicellular phytoplankton and apicomplexan parasites, through to humans. We characterise the preservation of ferlin structural motifs, not only of C2 domains, but also the more poorly characterised ferlin-specific motifs representing the DysF, FerA and FerB domains. Our data suggest an ancient role of ferlin proteins, with lessons from vertebrate biology and human disease suggesting a role relating to vesicle fusion and plasma membrane specialization.</p