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This document intends to auscultate the potential wind and mini-hydraulic energy in the lower basins of the rivers of the mountain ranges; given its topology, taking as an example the lower basin of the Ocoña river in Arequipa Peru, characterized by the canyoning of the mountain range, from the coast (0 masl) to the highlands (4,500 masl), and by the important flow hydraulic when descending from the highlands to the Pacific Ocean, in an area of 16,045 km2. For this, the wind speed has been recorded in anemometers placed at 6, 12, and 18 m above the surface. The section of the river and its speed have also been determined, the height of the river's water level has been recorded; all with an hourly periodicity. With this information we have determined the potential for wind and mini-hydro energy in this characteristic place. Wind speeds in the order of 10 m/s have been obtained, with a persistence of 8 h a day. As for the mini-hydraulic, with a minimum flow of 50 m3/s there is a persistence greater than 90 %. In conclusion, the potential of wind, mini-hydro, and combined energy of the place is sufficient to satisfy various energy demands, from very small to very large.
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BACKGROUND: Panic disorder (PD) is a common disabling condition characterized by recurrent panic attacks. Emotional and behavioral impairments are associated with functional connectivity (FC) and network abnormalities. We used the whole brain FC, modular networks, and graph-theory analysis to investigate extensive network profiles in PD. METHOD: The functional MRI data from 82 PD and 97 controls were included. Intrinsic FC between each pair of 160 regions, 6 intra-networks, and 15 inter-networks were analyzed. The topological properties were explored. RESULTS: PD patients showed altered FCs within the right insula, between frontal cortex-posterior cingulate cortex (PCC), frontal cortex-cerebellum, and PCC-occipital cortex (corrected P values < 0.001). Lower connections within the Sensorimotor Network (SMN) and SMN-Occipital Network (OCN) were detected (P values < 0.05). Various decreased global and local network features were found in PD (P values < 0.05). In addition, significant correlations were found between PD symptoms and nodal efficiency (Ne) in the insula (r = -0.273, P = 0.016), and the FC of the intra-insula (r = -0.226, P = 0.041). CONCLUSIONS: PD patients present with abnormal functional brain networks, especially the decreased FC and Ne within insula, suggesting that dysfunction of information integration plays an important role in PD.
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Three-dimensional structured illumination microscopy (3D-SIM) and fluorescence in situ hybridization on three-dimensional preserved cells (3D-FISH) have proven to be robust and efficient methodologies for analyzing nuclear architecture and profiling the genome's topological features. These methods have allowed the simultaneous visualization and evaluation of several target structures at super-resolution. In this chapter, we focus on the application of 3D-SIM for the visualization of 3D-FISH preparations of chromosomes in interphase, known as Chromosome Territories (CTs). We provide a workflow and detailed guidelines for sample preparation, image acquisition, and image analysis to obtain quantitative measurements for profiling chromosome topological features. In parallel, we address a practical example of these protocols in the profiling of CTs 9 and 22 involved in the translocation t(9;22) in Chronic Myeloid Leukemia (CML). The profiling of chromosome topological features described in this chapter allowed us to characterize a large-scale topological disruption of CTs 9 and 22 that correlates directly with patients' response to treatment and as a possible potential change in the inheritance systems. These findings open new insights into how the genome structure is associated with the response to cancer treatments, highlighting the importance of microscopy in analyzing the topological features of the genome.
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Imageamento Tridimensional , Hibridização in Situ Fluorescente , Humanos , Hibridização in Situ Fluorescente/métodos , Imageamento Tridimensional/métodos , Translocação Genética , Cromossomos/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Interfase/genética , Cromossomos Humanos/genética , Processamento de Imagem Assistida por Computador/métodosRESUMO
Protein-Protein Interaction Networks aim to model the interactome, providing a powerful tool for understanding the complex relationships governing cellular processes. These networks have numerous applications, including functional enrichment, discovering cancer driver genes, identifying drug targets, and more. Various databases make protein-protein networks available for many species, including Homo sapiens. This work topologically compares four Homo sapiens networks using a coarse-to-fine approach, comparing global characteristics, sub-network topology, specific nodes centrality, and interaction significance. Results show that the four human protein networks share many common protein-encoding genes and some global measures, but significantly differ in the interactions and neighbourhood. Small sub-networks from cancer pathways performed better than the whole networks, indicating an improved topological consistency in functional pathways. The centrality analysis shows that the same genes play different roles in different networks. We discuss how studies and analyses that rely on protein-protein networks for humans should consider their similarities and distinctions.
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One of the initial steps in the preprocessing of digital fundoscopy images is the identification of pixels containing relevant information. This can be achieved through different approaches, one of them is implementing background extraction, reducing the set of pixels to be analyzed later in the process. In this work, we present a background extraction method for digital fundoscopy images based on computational topology. By interpreting binarized images as cubical complexes and extracting their homological groups in 1 and 2 dimensions we identify a subset of luminescence values that can be used to binarize the original grayscale image, obtaining a mask to achieve background extraction. This method is robust to noise and suboptimal image quality, facilitating the analytical pipeline in the context of computer aided diagnosis approaches. This method facilitates the segmentation of the background of a digital fundoscopy image, which allows further methods to focus on pixels with relevant information (eye fundus). This tool is best suited to be implemented in the preprocessing stages of the analytical pipeline by computational ophthalmology specialists.â¢It is robust to noise and low-quality images.â¢Output provides an ideal scenario for down-the-line analysis by facilitating only relevant pixels in a digital fundoscopy.
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Teiid lizards possess an incomplete post-hepatic septum (PHS) separating the lungs and liver from the remaining viscera, and within this group, Salvator merianae has the most complete PHS. In this study, we explored the combined effects of the presence of the PHS and alterations in abdominal volume on the mechanics of the respiratory system. The PHS is believed to act as a mechanical barrier, mitigating the impact of the viscera on the lungs. Using established protocols, we determined static (Cstat) and dynamic (Cdyn) compliance, lung volume and work of breathing for the respiratory system in tegu lizards with intact (PHS+) or removed (PHS-) PHS, combined with (balloon+) or without (balloon-) increased abdominal volume. The removal of the PHS significantly reduced resting lung volume and Cdyn, as well as significantly increasing the work of breathing. An increase in abdominal volume significantly reduced Cstat, Cdyn, and resting and maximum lung volume. However, the work of breathing increased less in the PHS+/balloon+ treatment than in the PHS- treatments. These results highlight the barrier function of the PHS within the tegu lizard's body cavity. The septum effectively reduces the impact of the viscera on the respiratory system, enabling the lungs to be ventilated at a low work level, even when abdominal volume is increased. The presence of the PHS in teiid lizards underscores how extrapulmonary structures, such as septal divisions of the body cavity, can profoundly affect pulmonary breathing mechanics.
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Lagartos , Animais , Fígado , Pulmão , Respiração , Mecânica RespiratóriaRESUMO
The study of host-parasite interactions is essential to understand the role of each host species in the parasitic transmission cycles in a given community. The use of ecological network highlights the patterns of interactions between hosts and parasites, allowing us to evaluate the underlying structural features and epidemiological roles of different species within this context. Through network analysis, we aimed to understand the epidemiological roles of mammalian hosts species (n = 67) and their parasites (n = 257) in the Pantanal biome. Our analysis revealed a modular pattern within the network, characterized by 14 distinct modules, as well as nestedness patterns within these modules. Some key nodes, such as the multi-host parasites Trypanosoma cruzi and T. evansi, connect different modules and species. These central nodes showed us that various hosts species, including those with high local abundances, contribute to parasite maintenance. Ectoparasites, such as ticks and fleas, exhibit connections that reflect their roles as vectors of certain parasites. Overall, our findings contribute to a comprehensive understanding of the structure of host-parasite interactions in the Pantanal ecosystem, highlighting the importance of network analysis as a tool to identifying the main transmission routes and maintenance of parasites pathways. Such insights are valuable for parasitic disease control and prevention strategies and shed light on the broader complexities of ecological communities.
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Parasitos , Sifonápteros , Animais , Ecossistema , Interações Hospedeiro-Parasita , Mamíferos/parasitologiaRESUMO
Recently, many studies have addressed the performance of phylogenetic tree-building methods (maximum parsimony, maximum likelihood, and Bayesian inference), focusing primarily on simulated data. However, for discrete morphological data, there is no consensus yet on which methods recover the phylogeny with better performance. To address this lack of consensus, we investigate the performance of different methods using an empirical dataset for hexapods as a model. As an empirical test of performance, we applied normalized indices to effectively measure accuracy (normalized Robinson-Foulds metric, nRF) and precision, which are measured via resolution, one minus Colless' consensus fork index (1-CFI). Additionally, to further explore phylogenetic accuracy and support measures, we calculated other statistics, such as the true positive rate (statistical power) and the false positive rate (type I error), and constructed receiver operating characteristic plots to visualize the relationship between these statistics. We applied the normalized indices to the reconstructed trees from the reanalyses of an empirical discrete morphological dataset from extant Hexapoda using a well-supported phylogenomic tree as a reference. Maximum likelihood and Bayesian inference applying the k-state Markov (Mk) model (without or with a discrete gamma distribution) performed better, showing higher precision (resolution). Additionally, our results suggest that most available tree topology tests are reliable estimators of the performance measures applied in this study. Thus, we suggest that likelihood-based methods and tree topology tests should be used more often in phylogenetic tree studies based on discrete morphological characters. Our study provides a fair indication that morphological datasets have robust phylogenetic signal.
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Artrópodes , Animais , Filogenia , Funções Verossimilhança , Teorema de Bayes , InsetosRESUMO
Topological data analysis (TDA) is a recent approach for analyzing and interpreting complex data sets based on ideas a branch of mathematics called algebraic topology. TDA has proven useful to disentangle non-trivial data structures in a broad range of data analytics problems including the study of cardiovascular signals. Here, we aim to provide an overview of the application of TDA to cardiovascular signals and its potential to enhance the understanding of cardiovascular diseases and their treatment in the form of a literature or narrative review. We first introduce the concept of TDA and its key techniques, including persistent homology, Mapper, and multidimensional scaling. We then discuss the use of TDA in analyzing various cardiovascular signals, including electrocardiography, photoplethysmography, and arterial stiffness. We also discuss the potential of TDA to improve the diagnosis and prognosis of cardiovascular diseases, as well as its limitations and challenges. Finally, we outline future directions for the use of TDA in cardiovascular signal analysis and its potential impact on clinical practice. Overall, TDA shows great promise as a powerful tool for the analysis of complex cardiovascular signals and may offer significant insights into the understanding and management of cardiovascular diseases.
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Nanovesicles produced with lipids and polymers are promising devices for drug and bioactive delivery and are of great interest in pharmaceutical applications. These nanovesicles can be engineered for improvement in bioavailability, patient compliance or to provide modified release or enhanced delivery. However, their applicability strongly depends on the safety and low immunogenicity of the components. Despite this, the use of unsaturated lipids in nanovesicles, which degrade following oxidation processes during storage and especially during the proper routes of administration in the human body, may yield toxic degradation products. In this study, we used a biopolymer (chitosan) labeled with flavonoid (catechin) as a component over a lipid bilayer for micro- and nanovesicles and characterized the structure of these vesicles in oxidation media. The purpose of this was to evaluate the in situ effect of the antioxidant in three different vesicular systems of medium, low and high membrane curvature. Liposomes and giant vesicles were produced with the phospholipids DOPC and POPC, and crystalline cubic phase with monoolein/DOPC. Concentrations of chitosan-catechin (CHCa) were included in all the vesicles and they were challenged in oxidant media. The cytotoxicity analysis using the MTT assay (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) revealed that concentrations of CHCa below 6.67 µM are non-toxic to HeLa cells. The size and zeta potential of the liposomes evidenced the degradation of their structures, which was minimized by CHCa. Similarly, the membrane of the giant vesicle, which rapidly deteriorated in oxidative solution, was protected in the presence of CHCa. The production of a lipid/CHCa composite cubic phase revealed a specific cubic topology in small-angle X-ray scattering, which was preserved in strong oxidative media. This study demonstrates the specific physicochemical characteristics introduced in the vesicular systems related to the antioxidant CHCa biopolymer, representing a platform for the improvement of composite nanovesicle applicability.
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The discovery of new protein topologies with entanglements and loop-crossings have shown the impact of local amino acid arrangement and global three-dimensional structures. This phenomenon plays a crucial role in understanding how protein structure relates to folding and function, affecting the global stability, and biological activity. Protein entanglements encompassing knots and non-trivial topologies add complexity to their folding free energy landscapes. However, the initial native contacts driving the threading event for entangled proteins remains elusive. The Pierced Lasso Topology (PLT) represents an entangled topology where a covalent linker creates a loop in which the polypeptide backbone is threaded through. Compared to true knotted topologies, PLTs are simpler topologies where the covalent-loop persists in all conformations. In this work, the PLT protein leptin, is used to visualize and differentiate the preference for slipknotting over plugging transition pathways along the folding route. We utilize the Energy Landscape Visualization Method (ELViM), a multidimensional projection technique, to visualize and distinguish early threaded conformations that cannot be observed in an in vitro experiment. Critical contacts for the leptin threading mechanisms were identified where the competing pathways are determined by the formation of a hairpin loop in the unfolded basin. Thus, prohibiting the dominant slipknotting pathway. Furthermore, ELViM offers insights into distinct folding pathways associated with slipknotting and plugging providing a novel tool for de novo design and in vitro experiments with residue specific information of threading events in silico.
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Leptina , Dobramento de Proteína , Modelos Moleculares , Leptina/química , Software , Peptídeos , Conformação Proteica , TermodinâmicaRESUMO
This work investigates the use of Topology Optimization (TO) to support the design of femur prosthesis to obtain more efficient solutions from the point of view of material distribution and internal forces. Computational tests were performed by the Interior-Point OPTimizer (IPOPT) method, seeking to explore the elastic mechanical characteristics of three real scenarios of daily loads on the femur. Numerical examples are presented to verify the novelty of the proposed method. The results obtained indicate that it is possible to reduce the volume of material up to 30% of the customize human femoral prosthesis, respecting all the boundary conditions.
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Membros Artificiais , Implantação de Prótese , Humanos , Fêmur/cirurgia , Desenho de Prótese , Estresse Mecânico , Análise de Elementos FinitosRESUMO
The voltage-sensing domain (VSD) is a module capable of responding to changes in the membrane potential through conformational changes and facilitating electromechanical coupling to open a pore gate, activate proton permeation pathways, or promote enzymatic activity in some membrane-anchored phosphatases. To carry out these functions, this module acts cooperatively through conformational changes. The VSD is formed by four transmembrane segments (S1-S4) but the S4 segment is critical since it carries positively charged residues, mainly Arg or Lys, which require an aqueous environment for its proper function. The discovery of this module in voltage-gated ion channels (VGICs), proton channels (Hv1), and voltage sensor-containing phosphatases (VSPs) has expanded our understanding of the principle of modularity in the voltage-sensing mechanism of these proteins. Here, by sequence comparison and the evaluation of the relationship between sequence composition, intrinsic flexibility, and structural analysis in 14 selected representatives of these three major protein groups, we report five interesting differences in the folding patterns of the VSD both in prokaryotes and eukaryotes. Our main findings indicate that this module is highly conserved throughout the evolutionary scale, however: (1) segments S1 to S3 in eukaryotes are significantly more hydrophobic than those present in prokaryotes; (2) the S4 segment has retained its hydrophilic character; (3) in eukaryotes the extramembranous linkers are significantly larger and more flexible in comparison with those present in prokaryotes; (4) the sensors present in the kHv1 proton channel and the ciVSP phosphatase, both of eukaryotic origin, exhibit relationships of flexibility and folding patterns very close to the typical ones found in prokaryotic voltage sensors; and (5) archaeal channels KvAP and MVP have flexibility profiles which are clearly contrasting in the S3-S4 region, which could explain their divergent activation mechanisms. Finally, to elucidate the obscure origins of this module, we show further evidence for a possible connection between voltage sensors and TolQ proteins.
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Ativação do Canal Iônico , Prótons , Ativação do Canal Iônico/fisiologia , Monoéster Fosfórico Hidrolases/genéticaRESUMO
The subclass naphthoquinone represents a substance group containing several compounds with important activities against various pathogenic microorganisms. Accordingly, we evaluated O-allyl-lawsone (OAL) antiparasitic and antifungal activity free and encapsulated in 2-hydroxypropyl-ß-cyclodextrin (OAL MKN) against Trypanosoma cruzi and Sporothrix spp. OAL and OAL MKN were synthesized and characterized by physicochemical methods. The IC50 values of OAL against T. cruzi were 2.4 µM and 96.8 µM, considering epimastigotes and trypomastigotes, respectively. At the same time, OAL MKN exhibited a lower IC50 value (0.5 µM) for both trypanosome forms and low toxicity for mammalian cells. Additionally, the encapsulation showed a selectivity index approximately 240 times higher than that of benznidazole. Regarding antifungal activity, OAL and OAL MKN inhibited Sporothrix brasiliensis growth at 16 µM, while Sporothrix schenckii was inhibited at 32 µM. OAL MKN also exhibited higher selectivity toward fungus than mammalian cells. In conclusion, we described the encapsulation of O-allyl-lawsone in 2-hydroxypropyl-ß-cyclodextrin, increasing the antiparasitic activity compared with the free form and reducing the cytotoxicity and increasing the selectivity towardSporothrix yeasts and the T. cruzi trypomastigote form. This study highlights the potential development of this inclusion complex as an antiparasitic and antifungal agent to treat neglected diseases.
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Doença de Chagas , Naftoquinonas , Trypanosoma cruzi , Animais , 2-Hidroxipropil-beta-Ciclodextrina/farmacologia , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/uso terapêutico , Antiparasitários/uso terapêutico , Doença de Chagas/tratamento farmacológico , Mamíferos , Naftoquinonas/uso terapêuticoRESUMO
In this work, the problem of master-slave outer synchronization in different inner-outer network topologies is presented. Specifically, the studied inner-outer network topologies are coupled in master-slave configuration, where some particular scenarios concerning inner-outer topologies are addressed in order to disclose a suitable coupling strength to achieve outer synchronization. The novel MACM chaotic system is used as a node in the coupled networks, which presents robustness in its bifurcation parameters. Extensive numerical simulations are presented where the stability of the inner-outer network topologies is analyzed through a master stability function approach.
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Tree shape metrics can be computed fast for trees of any size, which makes them promising alternatives to intensive statistical methods and parameter-rich evolutionary models in the era of massive data availability. Previous studies have demonstrated their effectiveness in unveiling important parameters in viral evolutionary dynamics, although the impact of natural selection on the shape of tree topologies has not been thoroughly investigated. We carried out a forward-time and individual-based simulation to investigate whether tree shape metrics of several kinds could predict the selection regime employed to generate the data. To examine the impact of the genetic diversity of the founder viral population, simulations were run under two opposing starting configurations of the genetic diversity of the infecting viral population. We found that four evolutionary regimes, namely, negative, positive, and frequency-dependent selection, as well as neutral evolution, were successfully distinguished by tree topology shape metrics. Two metrics from the Laplacian spectral density profile (principal eigenvalue and peakedness) and the number of cherries were the most informative for indicating selection type. The genetic diversity of the founder population had an impact on differentiating evolutionary scenarios. Tree imbalance, which has been frequently associated with the action of natural selection on intrahost viral diversity, was also characteristic of neutrally evolving serially sampled data. Metrics calculated from empirical analysis of HIV datasets indicated that most tree topologies exhibited shapes closer to the frequency-dependent selection or neutral evolution regimes.
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Evolução Biológica , Árvores , Filogenia , Simulação por Computador , Seleção Genética , Modelos GenéticosRESUMO
Magnetic skyrmions are promising spin textures for building next-generation magnetic memories and spintronic devices. Nevertheless, one of the major challenges in realizing skyrmion-based devices is the stabilization of ordered arrays of these spin textures in different geometries. Here we numerically study the skyrmion-skyrmion interaction potential that arises due to the dynamics of itinerant electrons coupled to the magnetic texture in a ferromagnetic background with racetrack geometry. We consider different topological textures (ferromagnetic (FM) and antiferromagnetic (AFM)), namely: skyrmions, antiskyrmions and biskyrmions. We show that at low electron filling, for sufficiently short separation, the skyrmions strongly couple each other yielding a bound-state bound by electronic dynamics. However, when the filling is increased, the interaction potential energy presents local minima at specific values of the skyrmion-skyrmion distance. Each of these local minima corresponds to energetically stable positions of skyrmions which are 'protected' by well-defined energy barriers. By inspecting the local charge density, we find that in the case of AFM skyrmions, the local antiferromagnetic nature prevents electronic penetration into the core, allowing the AFM skyrmions to be seen as infinite potential barriers for electrons.
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Nestedness and modularity have been found in many species interaction networks. Despite being conceptually distinct, negatively correlated and having different causes, these patterns often co-occur. A realistic but seldom investigated alternative to these simple topologies is hierarchical compound networks, in which the entire network is modular, and modules are internally nested. In compound networks, nestedness is suppressed by modularity at higher network hierarchical levels, but prevails at lower levels, within modules. The aims of this study are (i) to evaluate the prevalence of simple and hierarchical compound topologies in binary and weighted networks describing different kinds of species interactions and (ii) to probe the relationships between modularity and nestedness at different network hierarchical levels. With a procedure that discriminates between simple and compound structures, we re-analysed the topology of 142 well-studied binary networks including seed dispersal, host-parasite, pollination and plant-herbivore interactions; 68 of these also had quantitative information. Additionally, we tested the relationship between robustness and topology of binary networks and compared the robustness of networks with compound topologies to different sequences of species removals. Compound topologies were detected in 34% of binary and 71% of weighted networks of all interaction kinds. These results establish the hierarchical compound topology as a widespread network architecture, often undetected without quantitative data. Furthermore, they disentangle an apparent paradox: despite conflicting with overall nestedness, modularity usually co-occurs with high values of low-level nestedness. Nestedness progressively decreased, while modularity increased, from seed dispersal to host-parasite, pollination and plant-herbivore networks. There were no consistent differences in the robustness of networks with nested and compound topologies. However, compound topologies were especially vulnerable to removal sequences that accelerate the exclusion of entire modules. Compound topologies improve the depiction of ecological networks and differentiate ecological and evolutionary processes that operate at different hierarchical levels, with the potential to advance our understanding of network dynamics, stability and response to species loss or change. Quantitative data often reveal specialization patterns that are indistinguishable in binary networks, strongly improving the detection of modular and compound topologies.
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Parasitos , Dispersão de Sementes , Animais , Ecossistema , Polinização/fisiologia , Herbivoria , Evolução BiológicaRESUMO
The possibility of analyzing chromatin topology in developing plant embryos is hampered by inaccessibility of the embryo sac, deeply embedded in the maternal seed tissue, following double fertilization. Here we describe a protocol to isolate, purify, and prepare developing Boechera stricta embryos for chromosome conformation capture-based methods as in situ Hi-C experiments. Early globular embryos can be isolated by air-pressure microaspiration, and subsequently washed to eliminate residual cells from the endosperm and maternal seed coat, allowing for pure sampling of selected stages of embryogenesis. This protocol allows for the possibility of comparing genome topology during plant embryonic differentiation since early until late embryo development stages.
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Brassicaceae , Brassicaceae/genética , Genoma , SementesRESUMO
Lamins are components of the nuclear lamina, a protein meshwork that underlies the nuclear membrane. Lamins interact with chromatin in transcriptionally silent regions defined as lamina-associated-domains (LADs). However, recent studies have shown that lamins regulate active transcription inside LADs. In addition, ChIP-seq analysis has shown that lamins interact with lamin-dependent promoters and enhancers located in the interior of the nucleus. Moreover, functional studies suggest that lamins regulate transcription at associated-promoters and long-range chromatin interactions of key developmental gene programs. This review will discuss emerging, non-canonical functions of lamins in controlling non-silent genes located both inside and outside of LADs, focusing on transcriptional regulation and chromatin organization in Drosophila and mammals as metazoan model organisms.