FGF signaling and cell state transitions during organogenesis

Organogenesis is a complex choreography of morphogenetic processes, patterns and dynamic shape changes as well as the specification of cell fates. Although several molecular actors and context-specific mechanisms have already been identified, our general understanding of the fundamental principles that govern the formation of organs is far from comprehensive. The application of the concept of ‘rebuild it to understand it’ from synthetic biology represents a promising alternative to the classical approach of ‘break it to understand it’ in order to distill biological understanding from complex developmental processes. According to this ‘rebuilding’ concept, in this study we sought to develop an experimental approach to induce the formation of organs from progenitor cells ‘on demand’ and to investigate the minimum requirements for such a process. The zebrafish lateral line chain cells are a powerful in vivo model for our study because they are a group of naïve multipotent progenitor cells that display mesenchyme-like features. In order to bring these cells to form organs, we used the well-known role of the FGF signaling pathway as a driver of organogenesis in the lateral line and developed an inducible and constitutively active form of the fibroblast growth factor receptor 1a (chemoFGFR). The cell-autonomous induction of this chemoFGFR in chain cells effectively triggered the formation of fully mature organs and thus enabled spatial and temporal control of the organogenesis process. Next, we asked what it takes to form an organ de novo. We used a combination of real-time microscopy, single cell tracking, polarity quantification, and mosaic analysis to study the cell behaviors that result from chemoFGFR induction. The picture that emerges from these analyses is that de novo organs form through a genetically encoded self-assembly process that is based on the pattern of chemoFGFR induction. In this scenario, cells expressing chemoFGFR aggregate into clusters and epithelialize as they sort out of non-expressing cells. We found that this sorting process occurs through cell rearrangement and slithering, which involves an extensive remodeling of the cell-cell contacts. Chain cells that do not express chemoFGFR can envelop these chemoFGFR expressing cell clusters and form a rim at the cluster periphery. This multi-stage process leads to the establishment of the inside-outside pattern of de novo organs, which is used as a blueprint for cell differentiation. In summary, in this study we provide insights into the mechanisms involved in the self-assembly of organs from a naïve population of progenitor cells

An image-based data-driven analysis of cellular architecture in a developing tissue

Quantitative microscopy is becoming increasingly crucial in efforts to disentangle the complexity of organogenesis, yet adoption of the potent new toolbox provided by modern data science has been slow, primarily because it is often not directly applicable to developmental imaging data. We tackle this issue with a newly developed algorithm that uses point cloud-based morphometry to unpack the rich information encoded in 3D image data into a straightforward numerical representation. This enabled us to employ data science tools, including machine learning, to analyze and integrate cell morphology, intracellular organization, gene expression and annotated contextual knowledge. We apply these techniques to construct and explore a quantitative atlas of cellular architecture for the zebrafish posterior lateral line primordium, an experimentally tractable model of complex self-organized organogenesis. In doing so, we are able to retrieve both previously established and novel biologically relevant patterns, demonstrating the potential of our data-driven approach

High flux solar simulators for concentrated solar thermal research: A review

When the availability of solar radiation is not enough to develop experimental investigation in the field of concentrating solar energy, solar simulators are a widely employed solution. They represent a source of artificial light, which can be comparable with concentrated sunlight. Besides, they provide advantages such as better parametric control of the process under study. In this work, it is presented an extensive review of the high flux solar simulators that are available in the different solar energy research centers around the world. Many of them are similarly designed and have common elements. Others are based on different concepts and their particular features are also pointed out. The main applications of solar simulators reported in literature are discussed along the work and remarked then in a specific section.The authors acknowledge the financial support provided by the FONDECYT project number 3150026 of CONICYT (Chile), the Education Ministry of Chile Grant PMI ANT 1201, as well as CONICYT/FONDAP/15110019 "Solar Energy Research Center" SERC-Chile. In addition, the first author wish to thank the University of Almeria and the Plataforma Solar de Almería for the collaboration and assistance devoted to the development of his Ph.D research

Expression of ID4 protein in breast cancer cells induces reprogramming of tumour-associated macrophages

Background: As crucial regulators of the immune response against pathogens, macrophages have been extensively shown also to be important players in several diseases, including cancer. Specifically, breast cancer macrophages tightly control the angiogenic switch and progression to malignancy. ID4, a member of the ID (inhibitors of differentiation) family of proteins, is associated with a stem-like phenotype and poor prognosis in basal-like breast cancer. Moreover, ID4 favours angiogenesis by enhancing the expression of pro-angiogenic cytokines interleukin-8, CXCL1 and vascular endothelial growth factor. In the present study, we investigated whether ID4 protein exerts its pro-angiogenic function while also modulating the activity of tumour-associated macrophages in breast cancer. Methods: We performed IHC analysis of ID4 protein and macrophage marker CD68 in a triple-negative breast cancer series. Next, we used cell migration assays to evaluate the effect of ID4 expression modulation in breast cancer cells on the motility of co-cultured macrophages. The analysis of breast cancer gene expression data repositories allowed us to evaluate the ability of ID4 to predict survival in subsets of tumours showing high or low macrophage infiltration. By culturing macrophages in conditioned media obtained from breast cancer cells in which ID4 expression was modulated by overexpression or depletion, we identified changes in the expression of ID4-dependent angiogenesis-related transcripts and microRNAs (miRNAs, miRs) in macrophages by RT-qPCR. Results: We determined that ID4 and macrophage marker CD68 protein expression were significantly associated in a series of triple-negative breast tumours. Interestingly, ID4 messenger RNA (mRNA) levels robustly predicted survival, specifically in the subset of tumours showing high macrophage infiltration. In vitro and in vivo migration assays demonstrated that expression of ID4 in breast cancer cells stimulates macrophage motility. At the molecular level, ID4 protein expression in breast cancer cells controls, through paracrine signalling, the activation of an angiogenic programme in macrophages. This programme includes both the increase of angiogenesis-related mRNAs and the decrease of members of the anti-angiogenic miR-15b/107 group. Intriguingly, these miRNAs control the expression of the cytokine granulin, whose enhanced expression in macrophages confers increased angiogenic potential. Conclusions: These results uncover a key role for ID4 in dictating the behaviour of tumour-associated macrophages in breast cancer

O Primeiro Atendimento Clinico no Imaginario de Estudantes de Psicologia

Considering the academic development of the psychologist as a complex process which articulates the transmission of scientific knowledge and changes in imaginative activity, we psychoanalytically investigate the collective imaginary of Psychology students regarding the first clinical consultation. We conducted a group interview with 52 undergraduate students, using the Thematic Story-Drawing Procedure as a way to open a dialogical field. The material obtained, through the psychoanalytical method, resulted in the creation/gathering of four affective-emotional meaning fields: “I came, I saw and I conquered”, “I know that I (do not) know”, “I survived and I will save” and “I am and I do”, from which we see an emotionally immature imaginary about the meeting with the patient, since students are more self-centered than concerned with the patient. The overall situation indicates the need for care regarding student academic development, in order to encourage a more mature approach toward the suffering of the other.Considerando la formación académica del psicólogo como un proceso complejo, que articula transmisión de conocimientos científicos con cambios en la actividad imaginativa, investigamos psicoanalíticamente el imaginario colectivo de estudiantes de Psicología sobre la primera experiencia de la práctica clínica. Realizamos una entrevista grupal, que incluyó 52 estudiantes universitarios, utilizando el Procedimiento Dibujos-Cuentos con Tema para favorecer la apertura de un campo dialógico. El material obtenido fue considerado a través del método psicoanalítico, resultando en la creación/encuentro de cuatro campos de sentido afectivo-emocional: “vino, vio, conquistó”, “Yo sé que (no) lo sé”, “sobreviví e salvaré” y “soy y hago”. Percibimos un imaginario emocionalmente inmaduro sobre el encuentro con el paciente, puesto que los alumnos están más centrados en sí mismo que preocupados por el paciente. El panorama general indica la necesidad de atención a la educación de los estudiantes, para facilitar un enfoque más maduro del sufrimiento de otro.Considerando a formação do psicólogo como um processo complexo, que articula transmissão de conhecimentos científicos e mudanças na atividade imaginativa, investigamos psicanaliticamente o imaginário coletivo de estudantes de Psicologia sobre o primeiro atendimento clínico. Realizamos entrevista grupal, da qual participaram 52 graduandos, usando o Procedimento de Desenho-Estória com Tema como favorecedor da abertura de um campo dialógico. O conjunto das produções foi considerado através do método psicanalítico, resultando na criação/encontro de quatro campos de sentido afetivo-emocional: “vim, vi e venci”, “sei que (não) sei”, “sobrevivi e salvarei” e “sou e faço”, a partir dos quais percebemos um imaginário emocionalmente imaturo sobre o encontro com o paciente, uma vez que os alunos se mostram mais centrados em si mesmos, do que preocupados com o paciente. O quadro geral indica a necessidade de cuidados em relação à formação do aluno, no sentido de facilitar uma aproximação mais amadurecida do sofrimento do outro

The multi-epoch X-ray tale of I Zwicky 1 outflows

The narrow-line Seyfert 1 galaxy I Zwicky 1 shows a unique and complex system of ionised gas in outflow, which consists of an ultra-fast wind and a two-component warm absorber. In the last two decades, XMM-Newton monitored the source multiple times enabling the study of the long-term variability of the various outflows. Plasma in photoionisation equilibrium with the ionising source responds and varies accordingly to any change of the ionising luminosity. However, detailed modelling of the past RGS data has shown no correlation between the plasma ionisation state and the ionising continuum, revealing a complex long-term variability of the multi-phase warm absorber. Here, we present a new observation of I Zwicky 1 by XMM-Newton taken in early 2020 characterised by a lower X-ray flux state. The soft X-ray spectrum from the RGS reveals the two components of the warm absorber with $\log \xi \sim -1.0$ and $\log \xi \sim 1.7$. Comparing our results with the previous observations, the ionisation state of the two absorbing gas components is continuously changing, following the same unpredictable behaviour. The new results strengthen the scenario in which the ionisation state of the warm absorber is driven by the density of the gas rather than the ionising luminosity. In particular, the presence of a radiation driven, inhomogeneous clumpy outflow may explain both the variability in ionisation throughout the years and the line-locked N V system observed in the UV band. Finally, the EPIC-pn spectrum reveals an ultra-fast wind with an outflow velocity of $\sim 0.26c$ and ionisation parameter of $\log \xi \sim 3.8$.Comment: 16 pages, 11 figures, 3 tables, accepted for publication in MNRA

A role for the centrosome in regulating the rate of neuronal efferocytosis by microglia in vivo

During brain development, many newborn neurons undergo apoptosis and are engulfed by microglia, the tissue-resident phagocytes of the brain, in a process known as efferocytosis. A hallmark of microglia is their highly branched morphology characterized by the presence of numerous dynamic extensions that these cells use for scanning the brain parenchyma and engulfing unwanted material. The mechanisms driving branch formation and apoptotic cell engulfment in microglia are unclear. By taking a live-imaging approach in zebrafish, we show that while microglia generate multiple microtubule-based branches, they only successfully engulf one apoptotic neuron at a time. Further investigation into the mechanism underlying this sequential engulfment revealed that targeted migration of the centrosome into one branch is predictive of phagosome formation and polarized vesicular trafficking. Moreover, experimentally doubling centrosomal numbers in microglia increases the rate of engulfment and even allows microglia to remove two neurons simultaneously, providing direct supporting evidence for a model where centrosomal migration is a rate-limiting step in branch-mediated efferocytosis. Conversely, light-mediated depolymerization of microtubules causes microglia to lose their typical branched morphology and switch to an alternative mode of engulfment, characterized by directed migration towards target neurons, revealing unexpected plasticity in their phagocytic ability. Finally, building on work focusing on the establishment of the immunological synapse, we identified a conserved signalling pathway underlying centrosomal movement in engulfing microglia

A lab-scale rotary kiln for thermal treatment of particulate materials under high concentrated solar radiation: Experimental assessment and transient numerical modeling

Rotary kilns are worldwide used for industrial processes that involve thermal treatments of particulate materials. However, a great amount of fossil fuels is employed in such processes. As alternative, solar rotary kilns are considered for this application due to their versatility and potential to substitute traditional fossil-fuel driven devices. In order to boost the development of this technology, efforts have to be focused on the control of the particle temperature during the treatment. In this context, a lab-scale rotary kiln was built and tested using a 7- kWe high-flux solar simulator at University of Antofagasta. It was conceived to treat particulate materials of different nature and it is able to reach temperatures higher than 800 °C under different operation strategies. Silicon carbide was selected for initial tests because it is inert, endures high temperatures (up to 1600 °C) and it has been proposed as thermal storage vector in several researches on concentrated solar power. In a first stage, the empty kiln was preheated up to about 800 °C, reaching a steady state in less than three hours and with a power of approximately 370 W entering the kiln cavity. Afterwards, 43 g of silicon carbide were introduced in the furnace and the system was heated again up to a second steady state above 800 °C. In this stage, particles showed a fast increment of their temperature and exceeded 700 °C in less than three minutes after loading. A one-dimensional transient numerical model was also developed to perform the thermal analysis of the kiln and the estimation of both the particle temperature and the system efficiency. Numerical results showed good agreement with experimental data and thermal losses could be quantified in detail. Therefore, the model was also used to predict the thermal behavior of a solar rotary kiln working in batch mode.The authors acknowledge the financial support provided by the FONDECYT project number 3150026 of CONICYT (Chile), the Education Ministry of Chile Grant PMI ANT 1201, as well as CONICYT/ FONDAP/15110019 “Solar Energy Research Center” SERC-Chile. The authors also gratefully acknowledge the financial support received from the Sectorial Fund CONACYT-SENER-Energy Sustainability, through grant 207450, Mexican Center for Innovation in Solar Energy (CeMIE-Sol), whithin strategic project P-10 “Solar Fuels and Industrial Processes” (COSOLpi). Special thanks go to the students Lou Cardinale, Rodrigo Méndez, and Daniel Vidal who gave a precious contribution during the experimental trials at LaCoSA of University of Antofagasta