Highly Differentiated Human Fetal RPE Cultures Are Resistant to the Accumulation and Toxicity of Lipofuscin-Like Material

PURPOSE. The accumulation of undigestible autofluorescent material (UAM), termed lipofuscin in vivo, is a hallmark of aged RPE. Lipofuscin derives, in part, from the incomplete degradation of phagocytized photoreceptor outer segments (OS). Whether this accumulated waste is toxic is unclear. We therefore investigated the effects of UAM in highly differentiated human fetal RPE (hfRPE) cultures. METHODS. Unmodified and photo-oxidized OS were fed daily to confluent cultures of ARPE-19 RPE or hfRPE. The emission spectrum, composition, and morphology of resulting UAM were measured and compared to in vivo lipofuscin. Effects of UAM on multiple RPE phenotypes were assessed. RESULTS. Compared to ARPE-19, hfRPE were markedly less susceptible to UAM buildup. Accumulated UAM in hfRPE initially resembled the morphology of lipofuscin from AMD eyes, but compacted and shifted spectrum over time to resemble lipofuscin from healthy aged human RPE. UAM accumulation mildly reduced transepithelial electrical resistance, ketogenesis, certain RPE differentiation markers, and phagocytosis efficiency, while inducing senescence and rare, focal pockets of epithelial-mesenchymal transition. However, it had no effects on mitochondrial oxygen consumption rate, certain other RPE differentiation markers, secretion of drusen components or polarity markers, nor cell death. CONCLUSIONS. hfRPE demonstrates a remarkable resistance to UAM accumulation, suggesting mechanisms for efficient OS processing that may be lost in other RPE culture models. Furthermore, while UAM alters hfRPE phenotype, the effects are modest, consistent with conflicting reports in the literature on the toxicity of lipofuscin. Our results suggest that healthy RPE may adequately adapt to and tolerate lipofuscin accumulation

Current cosmological constraints on the curvature, dark energy and modified gravity

We apply the Union2 compilation of 557 supernova Ia data, the baryon acoustic oscillation measurement of distance, the cosmic microwave background radiation data from the seven year Wilkinson Microwave Anisotropy Probe, and the Hubble parameter data to study the geometry of the Universe and the property of dark energy by using models and parametrizations with different high redshift behaviours of $w(z)$. We find that $\Lambda$CDM model is consistent with current data, that the Dvali-Gabadadze-Porrati model is excluded by the data at more than $3\sigma$ level, that the Universe is almost flat, and that the current data is unable to distinguish models with different behaviours of $w(z)$ at high redshift. We also add the growth factor data to constrain the growth index of Dvali-Gabadadze-Porrati model and find that it is more than $1\sigma$ away from its theoretical value.Comment: v3: 7 pages, 5 figures, correct typos on the citation of wmap7 dat

Asthma Phenotypes in Childhood

INTRODUCTION: Asthma is no longer thought of as a single disease, but rather a collection of varying symptoms expressing different disease patterns. One of the ongoing challenges is understanding the underlying pathophysiological mechanisms that may be responsible for the varying responses to treatment. Areas Covered: This review provides an overview of our current understanding of the asthma phenotype concept in childhood and describes key findings from both conventional and data-driven methods. Expert Commentary: With the vast amounts of data generated from cohorts, there is hope that we can elucidate distinct pathophysiological mechanisms, or endotypes. In return, this would lead to better patient stratification and disease management, thereby providing true personalised medicine

Clinical implications

Funding: GC was funded by Fundaçao para a Ciência e Tecnologia (FCT; Portugal) through a PhD Scholarship (SFRH/BD/130210/2017). AJOM was funded by FCT (Portugal) through a Junior Research and Career Development Award from the Harvard Medical School e Portugal Program (HMSP-ICJ/0020/2011). GC and AJO-M were supported by grant PTDC/MED-NEU/31331/2017, and AJO-M by grant PTDC/MED-NEU/30302/2017, funded by national funds from FCT/MCTES and co-funded by FEDER, under the Partnership Agreement Lisboa 2020 - Programa Operacional Regional de Lisboa. The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of the Fundaçao para a Ciência e Tecnologia, Harvard University or its affiliated academic health care centers. AJO-M was national coordinator for Portugal of a noninterventional study (EDMS-ERI-143085581, 4.0) to characterize a Treatment-Resistant Depression Cohort in Europe, sponsored by Janssen-Cilag, Ltd (2019e2020), is recipient of a grant from Schuhfried GmBH for norming and validation of cognitive tests, and is national coordinator for Portugal of trials of psilocybin therapy for treatment-resistant depression, sponsored by Compass Pathways, Ltd (EudraCT number 2017-003288-36 and 2020-001348- 25), and of esketamine for treatment-resistant depression, sponsored by Janssen-Cilag, Ltd (EudraCT NUMBER: 2019-002992-33). AP-L is a co-founder of Linus Health and TI Solutions AG; serves on the scientific advisory boards for Starlab Neuroscience, Neuroelectrics, Magstim Inc., Nexstim, Cognito, and MedRhythms; and is listed as an inventor on several issued and pending patents on the real-time integration of noninvasive brain stimulation with electroencephalography and magnetic resonance imaging. None of the aforementioned agencies had a role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, in the preparation, review, or approval of the manuscript, nor in the decision to submit the manuscript for publication. The remaining authors have declared that they have no potential conflicts of interest involving this work, including relevant financial activities outside the submitted work and any other relationships or activities that readers could perceive to have influenced, or that give the appearance of potentially influencing what is written.Background: When repetitive transcranial magnetic stimulation (rTMS) is used to treat medication refractory depression, the treatment pulse intensity is individualized according to motor threshold (MT). This measure is often acquired only on the first day of treatment, as per the protocol currently approved by Food and Drug Administration. Objective: Here, we aimed to assess daily MT variability across an rTMS treatment course and simulate the effects of different schedules of MT assessment on treatment intensity. Methods: We conducted a naturalistic retrospective study with 374 patients from a therapeutic rTMS program for depression that measures MT daily. Results: For each patient, in almost half the TMS sessions, MT varied on average more than 5% as compared to the baseline MT acquired in the first treatment day. Such variability was only minimally impacted by having different TMS technicians acquiring MT in different days. In a smaller cohort of healthy individuals, we confirmed that the motor hotspot localization method, a critical step for accurate MT assessment, was stable in different days, arguing that daily MT variability reflects physiological variability, rather than an artifact of measurement error. Finally, in simulations of the effect of one-time MT measurement, we found that half of sessions would have been 5% or more above or below target intensity, with almost 5% of sessions 25% above target intensity. The simulated effects of weekly MT measurements were significantly improved. Conclusions: In conclusion, MT varies significantly across days, not fully dependent on methods of MT acquisition. This finding may have important implications for therapeutic rTMS practice regarding safety and suggests that regular MT assessments, daily or at least weekly, would ameliorate the effect.publishersversionpublishe

Variability in motor threshold

Funding Information: GC was funded by Funda??o para a Ci?ncia e Tecnologia (FCT; Portugal) through a PhD Scholarship (SFRH/BD/130210/2017). AJO-M was funded by FCT (Portugal) through a Junior Research and Career Development Award from the Harvard Medical School ? Portugal Program (HMSP-ICJ/0020/2011). GC and AJO-M were supported by grant PTDC/MED-NEU/31331/2017, and AJO-M by grant PTDC/MED-NEU/30302/2017, funded by national funds from FCT/MCTES and co-funded by FEDER, under the Partnership Agreement Lisboa 2020 - Programa Operacional Regional de Lisboa. The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of the Funda??o para a Ci?ncia e Tecnologia, Harvard University or its affiliated academic health care centers. Funding Information: GC was funded by Fundação para a Ciência e Tecnologia (FCT; Portugal) through a PhD Scholarship ( SFRH/BD/130210/2017 ). AJO-M was funded by FCT (Portugal) through a Junior Research and Career Development Award from the Harvard Medical School – Portugal Program ( HMSP-ICJ/0020/2011 ). GC and AJO-M were supported by grant PTDC/MED-NEU/31331/2017, and AJO-M by grant PTDC/MED-NEU/30302/2017, funded by national funds from FCT/MCTES and co-funded by FEDER , under the Partnership Agreement Lisboa 2020 - Programa Operacional Regional de Lisboa. The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of the Fundação para a Ciência e Tecnologia, Harvard University or its affiliated academic health care centers. Funding Information: AJO-M was national coordinator for Portugal of a non-interventional study (EDMS-ERI-143085581, 4.0) to characterize a Treatment-Resistant Depression Cohort in Europe, sponsored by Janssen-Cilag, Ltd (2019–2020), is recipient of a grant from Schuhfried GmBH for norming and validation of cognitive tests, and is national coordinator for Portugal of trials of psilocybin therapy for treatment-resistant depression, sponsored by Compass Pathways, Ltd (EudraCT number 2017-003288-36 and 2020-001348-25), and of esketamine for treatment-resistant depression, sponsored by Janssen-Cilag, Ltd (EudraCT NUMBER: 2019-002992-33). AP-L is a co-founder of Linus Health and TI Solutions AG; serves on the scientific advisory boards for Starlab Neuroscience, Magstim Inc., Radiant Hearts, and MedRhythms; and is listed as an inventor on several issued and pending patents on the real-time integration of noninvasive brain stimulation with electroencephalography and magnetic resonance imaging. None of the aforementioned agencies or companies had a role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, in the preparation, review, or approval of the manuscript, nor in the decision to submit the manuscript for publication. The remaining authors have declared that they have no potential conflicts of interest involving this work, including relevant financial activities outside the submitted work and any other relationships or activities that readers could perceive to have influenced, or that give the appearance of potentially influencing what is written.publishersversionpublishe

ETNOBOTÂNICA APOIANDO AÇÕES EM EDUCAÇÃO NA FORMAÇÃO DE PROFESSORES DO ENSINO BÁSICO: UM ESTUDO DE CASO COM LICENCIANDOS EM CABO FRIO, RIO DE JANEIRO (BRASIL)

As mudanças ambientais têm gerado impactos na biodiversidade e no conhecimento ecológico tradicional (CET) associado em diversas regiões do mundo. No Brasil, a região costeira vem sofrendo com a intensa pressão antrópica, a supressão da vegetação nativa (restinga) e consequentes perdas e/ou modificações do CET de comunidades de pesca artesanal, entre outras. Além disso, o processo de globalização e padronização dos sistemas educacionais estão transformando e empobrecendo o CET intergeracional. Nesse contexto, a educação pode subsidiar processos de registro e salvaguarda de conhecimentos bioculturais através da problematização e contextualização no ensino, ultrapassando as barreiras da sala de aula e tocando as questões socioambientais regionais. Essa contextualização pode ser realizada através do diálogo entre os conhecimentos tradicionais e científicos, sendo a Etnobotânica uma possível mediadora de saberes no campo da educação. Neste sentido, aqui descrevemos uma experiência de aproximação realizada com um grupo de licenciandos em Ciências da Natureza do Instituto Federal de Educação, Ciência e Tecnologia Fluminense – Campus Cabo Frio, futuros professores da rede básica de ensino na região de Cabo Frio, litoral sudeste do Brasil. Para tal, foi elaborado um jogo da memória, com informações etnobotânicas de espécies vegetais nativas da Restinga de Massambaba (RJ). A partir deste jogo foram realizadas trocas de informações e uma visita técnica de campo à Restinga de Massambaba, com estudantes dos cursos de Licenciatura em Biologia, em Química e em Física durante o Estágio Curricular Supervisionado III e Currículo e Avaliação da Aprendizagem. Estas atividades foram bem-sucedidas, pois os licenciandos se mostraram interessados em reaplicar futuramente o jogo na educação básica, além de em ampliar o conhecimento sobre a diversidade cultural e biológica da região em que atuarão

Non-Abelian statistics and topological quantum information processing in 1D wire networks

Topological quantum computation provides an elegant way around decoherence, as one encodes quantum information in a non-local fashion that the environment finds difficult to corrupt. Here we establish that one of the key operations---braiding of non-Abelian anyons---can be implemented in one-dimensional semiconductor wire networks. Previous work [Lutchyn et al., arXiv:1002.4033 and Oreg et al., arXiv:1003.1145] provided a recipe for driving semiconducting wires into a topological phase supporting long-sought particles known as Majorana fermions that can store topologically protected quantum information. Majorana fermions in this setting can be transported, created, and fused by applying locally tunable gates to the wire. More importantly, we show that networks of such wires allow braiding of Majorana fermions and that they exhibit non-Abelian statistics like vortices in a p+ip superconductor. We propose experimental setups that enable the Majorana fusion rules to be probed, along with networks that allow for efficient exchange of arbitrary numbers of Majorana fermions. This work paves a new path forward in topological quantum computation that benefits from physical transparency and experimental realism.Comment: 6 pages + 17 pages of Supp. Mat.; 10 figures. Supp. Mat. has doubled in size to establish results more rigorously; many other improvements as wel

Constraining noncommutative field theories with holography

An important window to quantum gravity phenomena in low energy noncommutative (NC) quantum field theories (QFTs) gets represented by a specific form of UV/IR mixing. Yet another important window to quantum gravity, a holography, manifests itself in effective QFTs as a distinct UV/IR connection. In matching these two principles, a useful relationship connecting the UV cutoff $\Lambda_{\rm UV}$, the IR cutoff $\Lambda_{\rm IR}$ and the scale of noncommutativity $\Lambda_{\rm NC}$, can be obtained. We show that an effective QFT endowed with both principles may not be capable to fit disparate experimental bounds simultaneously, like the muon $g-2$ and the masslessness of the photon. Also, the constraints from the muon $g-2$ preclude any possibility to observe the birefringence of the vacuum coming from objects at cosmological distances. On the other hand, in NC theories without the UV completion, where the perturbative aspect of the theory (obtained by truncating a power series in $\Lambda_{\rm NC}^{-2}$) becomes important, a heuristic estimate of the region where the perturbative expansion is well-defined $E/ \Lambda_{\rm NC} \lesssim 1$, gets affected when holography is applied by providing the energy of the system $E$ a $\Lambda_{\rm NC}$-dependent lower limit. This may affect models which try to infer the scale $\Lambda_{\rm NC}$ by using data from low-energy experiments.Comment: 4 pages, version to be published in JHE

MULHERES E A PESCA ARTESANAL: SALVAGUARDANDO CONHECIMENTOS TRADICIONAIS SOBRE PLANTAS DA RESTINGA EM ARRAIAL DO CABO, BRASIL

A pesca artesanal é o principal meio de sobrevivência para cerca de 39 milhões de pessoas no mundo. As mulheres representam 50% da força de trabalho nos setores de pré e pós-captura, no entanto, seguem na invisibilidade. Tal espaço de labor ainda é majoritariamente masculino, tanto que no Brasil meio milhão de trabalhadoras da pesca continuam marginalizadas devido ao preconceito de gênero, ainda que sejam detentoras de conhecimentos que garantem a sobrevivência de suas famílias, como em Arraial do Cabo (RJ). O estudo, nesse contexto, objetivou investigar o papel delas nas atividades pesqueiras realizadas pela comunidade tradicional do município – uma das mais antigas e importantes do estado do Rio de Janeiro –, assim como seus conhecimentos sobre as plantas da restinga utilizadas na pesca, especialmente entre os períodos compreendidos entre 1940-1960 e a partir de 1990 até hoje. Para tal, foram realizados levantamentos bibliográficos sobre a história da região e entrevistas com duas nativas, cujos dados demonstraram que em décadas passadas elas eram responsáveis pelo beneficiamento do pescado através da salga, serviço remunerado por donos de paióis e tido como secundário. Hoje em dia elas atuam na captura, no beneficiamento e na confecção de diversos produtos – à base de peixe – para comercialização. Tais tarefas indicam que o papel da mulher na atividade pesqueira vem sofrendo mudanças. Ademais, elas detêm conhecimentos importantes quanto à segurança alimentar, os recursos pesqueiros e a flora da restinga, bem como sobre frutos nativos e o preparo de alimentos locais

Apresentação

As dificuldades enfrentadas por mulheres no universo acadêmico, na carreira enquanto cientistas, na gestão de recursos naturais ou na salvaguarda do conhecimento sobre a biodiversidade são expressas pelos vieses de gênero na pesquisa etnobiológica e em diferentes áreas do conhecimento, considerando a persistência histórica de uma lógica que privilegia os homens em diversas atividades. A fim de levantar discussões sobre essa temática e com o objetivo central de valorizar o trabalho de mulheres na etnobiologia e na salvaguarda do conhecimento tradicional na América Latina, a Revista Ethnoscientia lança o número especial intitulado: “Olhares femininos na Etnobiologia”. Nesta edição especial apresentamos trabalhos que versam sobre o histórico da participação feminina na pesquisa etnobiológica e suas respectivas contribuições, trabalhos sobre vieses de gênero em relação ao conhecimento e uso de recursos naturais, bem como trabalhos que trazem uma reflexão sobre as dificuldades e/ou potencialidades femininas na etnobiologia por pesquisadoras e pesquisadas. Os trabalhos aceitos têm primeiras e/ou últimas autoras mulheres do Brasil e de alguns países da América Latina, foram submetidos em diferentes formatos, de acordo com as sessões indicadas na revista e foram revisados e editorados exclusivamente por pesquisadoras mulheres. Dessa forma, convidamos vocês a desfrutarem das leituras dos artigos, bem como divulgá-los entre outras pesquisadoras e pesquisadores. Seguimos avançando no necessário caminho para diminuir a disparidade de gênero na pesquisa etnobiológica e em todos os setores da sociedade