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Abstract Neurogenins are proneural transcription factors required to specify neuronal identity. Their overexpression in human pluripotent stem cells rapidly produces cortical-like neurons with spiking activity and, because of this, they have been widely adopted for human neuron disease models. However, we do not fully understand the key downstream regulatory effectors responsible for driving neural differentiation. Here, using inducible expression of NEUROG1 and NEUROG2, we identify transcription factors (TFs) required for directed neuronal differentiation by combining expression and chromatin accessibility analyses with a pooled in vitro CRISPR-Cas9 screen targeting all ~1900 TFs in the human genome. The loss of one of these essential TFs (ZBTB18) yields few MAP2-positive neurons. Differentiated ZBTB18-null cells have radically altered gene expression, leading to cytoskeletal defects and stunted neurites and spines. In addition to identifying key downstream TFs for neuronal differentiation, our work develops an integrative multi-omics and TFome-wide perturbation platform to rapidly characterize essential TFs for the differentiation of any human cell type.

Adenomera is a genus of Neotropical leaf-litter frogs widely distributed in South America and regarded taxonomic-wise challenging. One of these is the open-habitat Adenomera diptyx from Paraguay, which may correspond to a species complex. An integrative analysis of morphological variation, in combination with acoustic and molecular data of several populations from Argentina, Paraguay, and Brazil resulted in the recharacterization of nominal A. diptyx and the description of a new, closely related species. Adenomera diptyx is recognized by its advertisement call given at a high repetition rate (176–299 per minute), and the dorsal color pattern consisting of a light mid-dorsal line and a dark brown interorbital bar with irregular black edges. In comparison with A. diptyx, the new species, Adenomera guarani sp. nov., produces its advertisement call at a lower repetition rate (73–147 per minute), and the dorsal color pattern consists of a light, broad, mid-dorsal stripe and a mask-like patch in the interorbital region. The redefinition of A. diptyx will contribute to future studies focusing on the taxonomic status of other genetic lineages tentatively assigned to this species complex, which could represent additional unnamed species in the open-habitat Adenomera clade.

Recognizing how populations fluctuate over time is a crucial factor in determining the environmental elements affecting population persistence. However, the limited information on wild bee populations complicates the estimation of the impact of anthropogenic threats leading to changes in population size. To address this, we conducted a study capturing and monitoring nine species of wild bees through monthly samplings over four years. Tray traps were placed in permanent plots, and capture records were used to determine population size (N) and density (D). A generalized linear model (GLM) was employed to determine how the use of traps affected bee species captures. The families Apidae and Halictidae represented the most captures. Apis mellifera, the Lasioglossum (Dialictus spp.) complex, and Macrotera sinaloana exhibited the largest number of captures and highest population density. Most species (77.7%) showed a tendency to remain constant over the years and to have a higher number of captures in the spring months. Moreover, yellow traps were the most effective in capturing bee individuals. We suggest that the availability of essential resources and the reduction in environmental stressors positively affected the capture of wild bee populations.

Abstract Background Transcription factor (TF) binding specificity is determined via a complex interplay between the transcription factor’s DNA binding preference and cell type-specific chromatin environments. The chromatin features that correlate with transcription factor binding in a given cell type have been well characterized. For instance, the binding sites for a majority of transcription factors display concurrent chromatin accessibility. However, concurrent chromatin features reflect the binding activities of the transcription factor itself and thus provide limited insight into how genome-wide TF-DNA binding patterns became established in the first place. To understand the determinants of transcription factor binding specificity, we therefore need to examine how newly activated transcription factors interact with sequence and preexisting chromatin landscapes. Results Here, we investigate the sequence and preexisting chromatin predictors of TF-DNA binding by examining the genome-wide occupancy of transcription factors that have been induced in well-characterized chromatin environments. We develop Bichrom, a bimodal neural network that jointly models sequence and preexisting chromatin data to interpret the genome-wide binding patterns of induced transcription factors. We find that the preexisting chromatin landscape is a differential global predictor of TF-DNA binding; incorporating preexisting chromatin features improves our ability to explain the binding specificity of some transcription factors substantially, but not others. Furthermore, by analyzing site-level predictors, we show that transcription factor binding in previously inaccessible chromatin tends to correspond to the presence of more favorable cognate DNA sequences. Conclusions Bichrom thus provides a framework for modeling, interpreting, and visualizing the joint sequence and chromatin landscapes that determine TF-DNA binding dynamics.

Neuronal programming by forced expression of transcription factors (TFs) holds promise for clinical applications of regenerative medicine. However, the mechanisms by which TFs coordinate their activities on the genome and control distinct neuronal fates remain obscure. Using direct neuronal programming of embryonic stem cells, we dissected the contribution of a series of TFs to specific neuronal regulatory programs. We deconstructed the Ascl1-Lmx1b-Foxa2-Pet1 TF combination that has been shown to generate serotonergic neurons and found that stepwise addition of TFs to Ascl1 canalizes the neuronal fate into a diffuse monoaminergic fate. The addition of pioneer factor Foxa2 represses Phox2b to induce serotonergic fate, similar to in vivo regulatory networks. Foxa2 and Pet1 appear to act synergistically to upregulate serotonergic fate. Foxa2 and Pet1 co-bind to a small fraction of genomic regions but mostly bind to different regulatory sites. In contrast to the combinatorial binding activities of other programming TFs, Pet1 does not strictly follow the Foxa2 pioneer. These findings highlight the challenges in formulating generalizable rules for describing the behavior of TF combinations that program distinct neuronal subtypes.

Este artículo estudia el caso de la empresa Uber Technologies Inc. y su oferta a nivel internacional, abordando cómo su incursión transforma la forma de transporte de personas y mercancías, a pesar de las brechas en las regulaciones nacionales (caso de Costa Rica) e internacionales. La investigación es exploratoria, descriptiva, transversal y cualitativa, con enfoque en el comercio transfronterizo de servicios y en la economía del transporte, provocada por este tipo de plataformas tecnológicas. El resultado es una propuesta de tres escenarios prospectivos, dos de tendencia (servicio público innovador y transporte privado colaborativo) y uno de ruptura (transporte multicarga) para vislumbrar la posibilidad de optimizar el modelo de negocio, a través de catorce variables identificadas y determinadas por cuatro factores: tiempo, costo, social y ambiental. This article examines the case of Uber Technologies Inc. and its international offering, addressing how its incursion transforms the way it provides the transportation of people and goods, despite gaps in national (Costa Rican case) and international regulations. The research is exploratory, descriptive, cross-cutting and qualitative, with a focus on cross-border trade in services and the transport economy, caused by such technological platforms. The result is a proposal of three prospective scenarios, two trend scenarios (innovative public service and collaborative private transport) and one rupture (multiload transport) to glimpse the possibility of optimizing the business model, through fourteen variables identified and determined by four factors: time, cost, social and environmental. Este artigo analisa o caso da Uber Technologies Inc. e da sua oferta internacional, abordando a forma como a sua incursão transforma a forma como fornece o transporte de pessoas e bens, apesar das lacunas nos regulamentos nacionais (caso costa-riquenho) e internacionais. A investigação é exploratória, descritiva, transversal e qualitativa, com foco no comércio transfronteiriço de serviços e na economia de transportes, causada por tais plataformas tecnológicas. O resultado é uma proposta de três cenários prospetivos, dois cenários de tendência (serviço público inovador e transporte privado colaborativo) e uma rutura (transporte multicarrego) para vislumbrar a possibilidade de otimizar o modelo de negócio, através de catorze variáveis identificadas e determinadas por quatro fatores: tempo, custo, social e ambiental.

Polycomb repressive complexes (PRCs) 1 and 2 maintain stable cellular memories of early fate decisions by establishing heritable patterns of gene repression. PRCs repress transcription through histone modifications and chromatin compaction, but their roles in neuronal subtype diversification are poorly defined. We found that PRC1 is essential for the specification of segmentally restricted spinal motor neuron (MN) subtypes, while PRC2 activity is dispensable to maintain MN positional identities during terminal differentiation. Mutation of the core PRC1 component Ring1 in mice leads to increased chromatin accessibility and ectopic expression of a broad variety of fates determinants, including Hox transcription factors, while neuronal class-specific features are maintained. Loss of MN subtype identities in Ring1 mutants is due to the suppression of Hox-dependent specification programs by derepressed Hox13 paralogs (Hoxa13, Hoxb13, Hoxc13, Hoxd13). These results indicate that PRC1 can function in the absence of de novo PRC2-dependent histone methylation to maintain chromatin topology and postmitotic neuronal fate.

Subcellular localization of RNAs and proteins is important for polarized cells such as neurons. Here the authors differentiate mouse embryonic stem cells into neurons, and analyze the local transcriptome, proteome, and translated transcriptome in their cell bodies and neurites, providing a unique resource for future studies on neuronal polarity.

Buscamos (re)construir una narrativa geocrítica para la esencia del paisaje al (re)escribir las especificidades de montaña que impriman atributos culturales en los paisajes andinos tropicales y templados, creando un trilema de identidad único para la gente de las tierras altas de América del Sur. Usamos la onomástica como un estudio de la individualidad errada con un enfoque post-estructuralista para definir “lo andino” dentro de la geoecología humanística; por lo tanto, incorporamos nociones relacionadas con los atributos fenotípicos de Andeanidad, junto con las propiedades crípticas emergentes de Andeancia y las condiciones místicas de espiritualidad de Andeanitud, para producir una nueva trifecta de construcción ecoregional, con una epistemología desafiante para el paisaje patrimonial biocultural basado en el conocimiento tradicional, apropiado dialécticamente de lo viejo a lo nuevo, de lo foráneo a lo nativo y de lo original a lo copiado. Por lo tanto, la dinámica identidad heterogénea imaginada de la gente andina está caracterizada por un flujo dinámico y evolutivo del paisaje montano. Argumentamos que la nomenclatura aún se adapta a marcos de cambio ambiental global; así, está aún sujeta a deterioro a no ser que ciertos microrefugios bioculturales puedan mantener la memoria del paisaje andino vivo. Con una revisión de la hermenéutica de Andes, debido a las variantes (c.f. grafiosis) que incorporaron palabras basadas en Kichwa, Kañary o Mapudungun en el léxico hegemónico del expansionismo colonial de los términos castellanos, apelamos a la inclusión de los descriptores vernáculos en vez del santoral romano y la efemérides patriótica utilizada para nombrar los atributos geográficos en la Sudamérica andina. Pedimos restaurar los descriptores vernáculos con el lenguaje usado por los pueblos originarios, su toponimia y onomatopeya, para atraer el reconocimiento político y para vigorizar el orgullo del patrimonio ancestral de las comunidades de montaña para refuerzo de su bienestar en los microrefugios bioculturales. Al cambiar los nombres impuestos por la geografía imperial colonial a las palabras vernáculas u otros locativos no hegemónicos de escolaridad decolonial, se ayudará a obtener un mejor ‘sentido del lugar’ en los Andes e incrementará la posibilidad de (super)vivencia y (re)generación de los paisajes productivos socioecológicos ancestrales andinos.

The motor neuron progenitor domain in the ventral spinal cord gives rise to multiple subtypes of motor neurons and glial cells. Here, we examine whether progenitors found in this domain are multipotent and which signals contribute to their cell-type-specific differentiation. Using an in vitro neural differentiation model, we demonstrate that motor neuron progenitor differentiation is iteratively controlled by Notch signaling. First, Notch controls the timing of motor neuron genesis by repressing Neurogenin 2 (Ngn2) and maintaining Olig2-positive progenitors in a proliferative state. Second, in an Ngn2-independent manner, Notch contributes to the specification of median versus hypaxial motor column identity and lateral versus medial divisional identity of limb-innervating motor neurons. Thus, motor neuron progenitors are multipotent, and their diversification is controlled by Notch signaling that iteratively increases cellular diversity arising from a single neural progenitor domain.

The ability to target Cas9 to specific genomic loci offers the potential for applications beyond genome editing. Here the authors use deactivated Cas9 and chimeric guide RNAs to visualise individual repetitive loci in living cells.

El TEC según la IBIA es la principal causa de convulsiones, muerte y discapacidad adquirida mundialmente. Las principales causas son las caídas en mayores de 65 años y los accidentes de tránsito en los menores. Los hematomas pos-TEC son una complicación muy frecuente, cuyas manifestaciones son variables, especialmente en los subdurales, presentando desde cefalea hasta síndromes demenciales o déficit neurológico focal, dentro de los cuales no es usual el reporte de casos con manifestaciones visuales. El presente artículo reporta un caso de discapacidad visual por déficit neurológico pos-TEC complicado con hematomas subdurales subcrónicos bilaterales parietooccipitales, y revisa la neuroanatomía funcional visual involucrada en ella.

RESUMEN Estudios acerca de la diversidad e historia natural de comunidades de anuros son elementales para distinguir entre fluctuaciones naturales de aquellas causadas por impactos antrópicos (herramienta clave en programas de conservación), evaluar el papel que juegan en la dinámica de los ecosistemas y permitir comparaciones de gradientes de diversidad. En este contexto, se analiza la diversidad, la distribución temporal y espacial, y los turnos de vocalización de anuros de tres sitios de reproducción en los Esteros del Iberá, en el nordeste de Argentina. Los muestreos fueron mensuales entre julio de 2008 y junio de 2010. Se registraron 26 especies pertenecientes a cinco familias: Bufonidae (2), Hylidae (11), Leptodactylidae (11), Microhylidae (1), y Odontophrynidae (1). Se encontraron variaciones en la riqueza de especies por sitio, en el periodo, frecuencia y turno de vocalización y en la abundancia de machos vocalizadores. La riqueza es similar al de otros humedales similares, incluyendo un importante dominio de leptodactílidos e hílidos, patrón frecuente en ensambles neotropicales. La concentración de las especies en actividad de vocalización en los meses más cálidos y lluviosos estuvo asociada con los cambios en la temperatura y en las precipitaciones, las cuales fueron señaladas como algunos de los factores que inician la actividad reproductiva en ambientes estacionales.

The rapidly evolving stem cell field puts much stress on developing educational resources. The ISSCR Education Committee has created a flexible stem cell syllabus rooted in core concepts to facilitate stem cell literacy. The free syllabus will be updated regularly to maintain accuracy and relevance.

Regulatory proteins can bind to different sets of genomic targets in various cell types or conditions. To reliably characterize such condition-specific regulatory binding we introduce MultiGPS, an integrated machine learning approach for the analysis of multiple related ChIP-seq experiments. MultiGPS is based on a generalized Expectation Maximization framework that shares information across multiple experiments for binding event discovery. We demonstrate that our framework enables the simultaneous modeling of sparse condition-specific binding changes, sequence dependence, and replicate-specific noise sources. MultiGPS encourages consistency in reported binding event locations across multiple-condition ChIP-seq datasets and provides accurate estimation of ChIP enrichment levels at each event. MultiGPS's multi-experiment modeling approach thus provides a reliable platform for detecting differential binding enrichment across experimental conditions. We demonstrate the advantages of MultiGPS with an analysis of Cdx2 binding in three distinct developmental contexts. By accurately characterizing condition-specific Cdx2 binding, MultiGPS enables novel insight into the mechanistic basis of Cdx2 site selectivity. Specifically, the condition-specific Cdx2 sites characterized by MultiGPS are highly associated with pre-existing genomic context, suggesting that such sites are pre-determined by cell-specific regulatory architecture. However, MultiGPS-defined condition-independent sites are not predicted by pre-existing regulatory signals, suggesting that Cdx2 can bind to a subset of locations regardless of genomic environment. A summary of this paper appears in the proceedings of the RECOMB 2014 conference, April 2-5.

El Código Internacional de Nomenclatura Zoológica (ICZN, 1961, y ediciones sucesivas) fijó el día 1 de enero de 1758 como el punto de partida de la nomenclatura zoológica. Si bien la elección de la fecha es arbitraria, las razones que llevaron a su establecimiento tienen bases objetivas, ya que en algún momento de ese año fue publicada la décima edición del Systema Naturae (Linnaeus, 1758), que fue la segunda obra que utilizó, de manera consistente, la nomenclatura binominal para designar a los animales (la primera, el Aranei Svecici, fue publicada por Clerck en 1757 y toma precedencia sobre Linnaeus en lo que respecta a arañas).

The Drosophila eye is a mosaic that results from the stochastic distribution of two ommatidial subtypes. Pale and yellow ommatidia can be distinguished by the expression of distinct rhodopsins and other pigments in their inner photoreceptors (R7 and R8), which are implicated in color vision. The pale subtype contains ultraviolet (UV)-absorbing Rh3 in R7 and blue-absorbing Rh5 in R8. The yellow subtype contains UV-absorbing Rh4 in R7 and green-absorbing Rh6 in R8. The exclusive expression of one rhodopsin per photoreceptor is a widespread phenomenon, although exceptions exist. The mechanisms leading to the exclusive expression or to co-expression of sensory receptors are currently not known. We describe a new class of ommatidia that co-express rh3 and rh4 in R7, but maintain normal exclusion between rh5 and rh6 in R8. These ommatidia, which are localized in the dorsal eye, result from the expansion of rh3 into the yellow-R7 subtype. Genes from the Iroquois Complex (Iro-C) are necessary and sufficient to induce co-expression in yR7. Iro-C genes allow photoreceptors to break the "one receptor-one neuron" rule, leading to a novel subtype of broad-spectrum UV- and green-sensitive ommatidia.

The study of developmentally regulated transcription factors by chromatin immunoprecipitation and deep sequencing (ChIP-seq) faces two major obstacles: availability of ChIP-grade antibodies and access to sufficient number of cells. We describe versatile genome-wide analysis of transcription-factor binding sites by combining directed differentiation of embryonic stem cells and inducible expression of tagged proteins. We demonstrate its utility by mapping DNA-binding sites of transcription factors involved in motor neuron specification.

Abstract Web-based pulmonary telerehabilitation (WBPTR) can serve as a valuable tool when access to conventional care is limited. This review assesses a series of studies that explore pulmonary telerehabilitation programmes delivered via web-based platforms. The studies involved participants with moderate to severe chronic obstructive pulmonary disease (COPD). Of the 3190 participants, 1697 engaged in WBPTR platforms, while the remaining 1493 comprised the control groups. Sixteen studies were included in the meta-analysis. Web-based pulmonary telerehabilitation led to an increase in daily step count (MD 446.66, 95% CI 96.47 to 796.86), though this did not meet the minimum clinically important difference. Additionally, WBPTR did not yield significant improvements in the six-minute walking test (MD 5.01, 95% CI − 5.19 to 15.21), health-related quality of life as measured by the St. George’s Respiratory Questionnaire (MD − 0.15, 95% CI − 2.24 to 1.95), or the Chronic Respiratory Disease Questionnaire (MD 0.17, 95% CI − 0.13 to 0.46). Moreover, there was no significant improvement in dyspnoea-related health status, as assessed by the Chronic Respiratory Disease Questionnaire (MD − 0.01, 95% CI − 0.29 to 0.27) or the modified Medical Research Council Dyspnoea Scale (MD − 0.14, 95% CI − 0.43 to 0.14). Based on these findings, this review concludes that WBPTR does not offer substantial advantages over traditional care. While slight improvements in exercise performance were observed, no meaningful enhancements were noted in dyspnoea or quality of life metrics. Overall, WBPTR remains a complementary and accessible option for managing and monitoring COPD patients. However, further research and innovation are required to improve its efficacy and adapt it to various clinical environments.

Background/Objectives: Physiotherapists face significant challenges in managing chronic pain; a complex condition best addressed through a biopsychosocial (BPS) approach. Although substantial evidence exists globally, research specific to Spain remains limited. This study explores the experiences and challenges Spanish physiotherapists encounter in integrating BPS elements across public and private healthcare settings. Methods: Semi-structured interviews with 12 experienced physiotherapists were conducted, using a qualitative approach with purposive sampling and reflexive thematic analysis. The analysis, grounded in a constructivist/interpretivist framework, allowed themes to emerge naturally from the data, supported by relevant quotes. Results: Three primary themes were identified: (1) challenges in implementing the BPS approach, including patient resistance and limited training; (2) facilitators for adopting the BPS model, such as multidisciplinary support and positive patient outcomes; and (3) emotional and psychological aspects of the physiotherapists. The findings highlight the complexities of chronic pain management in physiotherapy, emphasizing the need for enhanced psychological training, integrated multidisciplinary care, early diagnosis, and effective family involvement. These insights are critical for improving both patient care and physiotherapist well-being. Conclusions: This study provides valuable guidance for future strategies, focusing on educational enhancements, multidisciplinary collaboration, healthcare policy reform, and emotional support for physiotherapists within the Spanish healthcare context.