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1.
Int J Mol Sci ; 25(12)2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38928426

RESUMEN

Thyroid cancer diagnosis primarily relies on imaging techniques and cytological analyses. In cases where the diagnosis is uncertain, the quantification of molecular markers has been incorporated after cytological examination. This approach helps physicians to make surgical decisions, estimate cancer aggressiveness, and monitor the response to treatments. Despite the availability of commercial molecular tests, their widespread use has been hindered in our experience due to cost constraints and variability between them. Thus, numerous groups are currently evaluating new molecular markers that ultimately will lead to improved diagnostic certainty, as well as better classification of prognosis and recurrence. In this review, we start reviewing the current preoperative testing methodologies, followed by a comprehensive review of emerging molecular markers. We focus on micro RNAs, long non-coding RNAs, and mitochondrial (mt) signatures, including mtDNA genes and circulating cell-free mtDNA. We envision that a robust set of molecular markers will complement the national and international clinical guides for proper assessment of the disease.


Asunto(s)
Biomarcadores de Tumor , ADN Mitocondrial , Mitocondrias , Neoplasias de la Tiroides , Humanos , Biomarcadores de Tumor/genética , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patología , ADN Mitocondrial/genética , Mitocondrias/metabolismo , Mitocondrias/genética , ARN no Traducido/genética , ARN Largo no Codificante/genética , MicroARNs/genética , Pronóstico
2.
Eur Phys J E Soft Matter ; 47(5): 32, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38735905

RESUMEN

The motion of droplets on solid surfaces in response to an external gradient is a fundamental problem with a broad range of applications, including water harvesting, heat exchange, mixing and printing. Here we study the motion of droplets driven by a humidity gradient, i.e. a variation in concentration of their own vapour in the surrounding gas phase. Using lattice-Boltzmann simulations of a diffuse-interface hydrodynamic model to account for the liquid and gas phases, we demonstrate that the droplet migrates towards the region of higher vapour concentration. This effect holds in situations where the ambient gradient drives either the evaporation or the condensation of the droplet, or both simultaneously. We identify two main mechanisms responsible for the observed motion: a difference in surface wettability, which we measure in terms of the Young stress, and a variation in surface tension, which drives a Marangoni flow. Our results are relevant in advancing our knowledge of the interplay between gas and liquid phases out of thermodynamic equilibrium, as well as for applications involving the control of droplet motion.

3.
bioRxiv ; 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38798556

RESUMEN

Background: Thrombosis is a major cause of myocardial infarction and ischemic stroke. The sodium/potassium ATPase (NKA), comprising α and ß subunits, is crucial in maintaining intracellular sodium and potassium gradients. However, the role of NKA in platelet function and thrombosis remains unclear. Methods: We utilized wild-type (WT, α1+/+) and NKA α1 heterozygous (α1+/-) mice, aged 8 to 16 weeks, of both sexes. An intravital microscopy-based, FeCl3-induced carotid artery injury thrombosis model was employed for in vivo thrombosis assessment. Platelet transfusion assays were used to evaluate platelet NKA α1 function on thrombosis. Human platelets isolated from healthy donors and heart failure patients treated with/without digoxin were used for platelet function and signaling assay. Complementary molecular approaches were used for mechanistic studies. Results: NKA α1 haplodeficiency significantly reduced its expression on platelets without affecting sodium homeostasis. It significantly inhibited 7.5% FeCl3-induced thrombosis in male but not female mice without disturbing hemostasis. Transfusion of α1+/-, but not α1+/+, platelets to thrombocytopenic WT mice substantially prolonged thrombosis. Treating WT mice with low-dose ouabain or marinobufagenin, both binding NKA α1 and inhibiting its ion-transporting function, markedly inhibited thrombosis in vivo. NKA α1 formed complexes with leucine-glycine-leucine (LGL)-containing platelet receptors, including P2Y12, PAR4, and thromboxane A2 receptor. This binding was significantly attenuated by LGL>SFT mutation or LGL peptide. Haplodeficiency of NKA α1 in mice or ouabain treatment of human platelets notably inhibited ADP-induced platelet aggregation. While not affecting 10% FeCl3-induced thrombosis, NKA α1 haplodeficiency significantly prolonged thrombosis time in mice treated with an ineffective dose of clopidogrel. Conclusion: NKA α1 plays an essential role in enhancing platelet activation through binding to LGL-containing platelet GPCRs. NKA α1 haplodeficiency or inhibition with low-dose ouabain and marinobufagenin significantly inhibited thrombosis and sensitized clopidogrel's anti-thrombotic effect. Targeting NKA α1 emerges as a promising antiplatelet and antithrombotic therapeutic strategy.

4.
Langmuir ; 39(44): 15676-15689, 2023 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-37874819

RESUMEN

Young's equation is fundamental to the concept of the wettability of a solid surface. It defines the contact angle for a droplet on a solid surface through a local equilibrium at the three-phase contact line. Recently, the concept of a liquid Young's law contact angle has been developed to describe the wettability of slippery liquid-infused porous surfaces (SLIPS) by droplets of an immiscible liquid. In this work, we present a new method to fabricate biphilic SLIP surfaces and show how the wettability of the composite SLIPS can be exploited with a macroscopic wedge-shaped pattern of two distinct lubricant liquids. In particular, we report the development of composite liquid surfaces on silicon substrates based on lithographically patterning a Teflon AF1600 coating and a superhydrophobic coating (Glaco Mirror Coat Zero), where the latter selectively dewets from the former. This creates a patterned base surface with preferential wetting to matched liquids: the fluoropolymer PTFE with a perfluorinated oil Krytox and the hydrophobic silica-based GLACO with olive oil (or other mineral oils or silicone oil). This allows us to successively imbibe our patterned solid substrates with two distinct oils and produce a composite liquid lubricant surface with the oils segregated as thin films into separate domains defined by the patterning. We illustrate that macroscopic wedge-shaped patterned SLIP surfaces enable low-friction droplet self-propulsion. Finally, we formulate an analytical model that captures the dependence of the droplet motion as a function of the wettability of the two liquid lubricant domains and the opening angle of the wedge. This allows us to derive scaling relationships between various physical and geometrical parameters. This work introduces a new approach to creating patterned liquid lubricant surfaces, demonstrates long-distance droplet self-propulsion on such surfaces, and sheds light on the interactions between liquid droplets and liquid surfaces.

5.
Front Cell Dev Biol ; 11: 1226604, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37645251

RESUMEN

Astrocytes play a critical role in the maintenance of a healthy central nervous system and astrocyte dysfunction has been implicated in various neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). There is compelling evidence that mouse and human ALS and ALS/FTD astrocytes can reduce the number of healthy wild-type motoneurons (MNs) in co-cultures or after treatment with astrocyte conditioned media (ACM), independently of their genotype. A growing number of studies have shown that soluble toxic factor(s) in the ACM cause non-cell autonomous MN death, including our recent identification of inorganic polyphosphate (polyP) that is excessively released from mouse primary astrocytes (SOD1, TARDBP, and C9ORF72) and human induced pluripotent stem cells (iPSC)-derived astrocytes (TARDBP) to kill MNs. However, others have reported that astrocytes carrying mutant TDP43 do not produce detectable MN toxicity. This controversy is likely to arise from the findings that human iPSC-derived astrocytes exhibit a rather immature and/or reactive phenotype in a number of studies. Here, we have succeeded in generating a highly homogenous population of functional quiescent mature astrocytes from control subject iPSCs. Using identical conditions, we also generated mature astrocytes from an ALS/FTD patient carrying the TDP43A90V mutation. These mutant TDP43 patient-derived astrocytes exhibit key pathological hallmarks, including enhanced cytoplasmic TDP-43 and polyP levels. Additionally, mutant TDP43 astrocytes displayed a mild reactive signature and an aberrant function as they were unable to promote synaptogenesis of hippocampal neurons. The polyP-dependent neurotoxic nature of the TDP43A90V mutation was further confirmed as neutralization of polyP in ACM derived from mutant TDP43 astrocytes prevented MN death. Our results establish that human astrocytes carrying the TDP43A90V mutation exhibit a cell-autonomous pathological signature, hence providing an experimental model to decipher the molecular mechanisms underlying the generation of the neurotoxic phenotype.

6.
Langmuir ; 39(31): 11028-11035, 2023 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-37487028

RESUMEN

In 1948, Cassie provided an equation describing the wetting of a smooth, heterogeneous surface. He proposed that the cosine of the contact angle, θc, for a droplet on a composite surface could be predicted from a weighted average using the fractional surface areas, fi, of the cosines of contact angles of a droplet on the individual component surfaces, i.e., cos θc = f1 cos θ1 + f2 cos θ2. This was a generalization of an earlier equation for porous materials, which has recently proven fundamental to underpinning the theoretical description of wetting of superhydrophobic and superoleophobic surfaces. However, there has been little attention paid to what happens when a liquid exhibits complete wetting on one of the surface components. Here, we show that Cassie's equation can be reformulated using spreading coefficients. This reformulated equation is capable of describing composite surfaces where the individual surface components have negative (droplet state/partial wetting) or positive (film-forming/complete wetting) spreading coefficients. The original Cassie equation is then a special case when the combination of interfacial tensions results in a droplet state on the composite surface for which a contact angle can be defined. In the case of a composite surface created from a partial wetting (droplet state) surface and a complete wetting (film-forming) surface, there is a threshold surface area fraction at which a liquid on the composite surface transitions from a droplet to a film state. The applicability of this equation is demonstrated from literature data including data on mixed self-assembled monolayers on copper, silver, and gold surfaces that was regarded as definitive in establishing the validity of the Cassie equation. Finally, we discuss the implications of these ideas for super-liquid repellent surfaces.

7.
Curr Issues Mol Biol ; 45(6): 4735-4748, 2023 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-37367050

RESUMEN

In cancer cells, the long non-coding RNA (lncRNA) MALAT1 has arisen as a key partner for the Polycomb Repressive Complex 2 (PRC2), an epigenetic modifier. However, it is unknown whether this partnership occurs genome-wide at the chromatin level, as most of the studies focus on single genes that are usually repressed. Due to the genomic binding properties of both macromolecules, we wondered whether there are binding sites shared by PRC2 and MALAT1. Using public genome-binding datasets for PRC2 and MALAT1 derived from independent ChIP- and CHART-seq experiments performed with the breast cancer cell line MCF7, we searched for regions containing PRC2 and MALAT1 overlapping peaks. Peak calls for each molecule were performed using MACS2 and then overlapping peaks were identified by bedtools intersect. Using this approach, we identified 1293 genomic sites where PRC2 and MALAT1 concur. Interestingly, 54.75% of those sites are within gene promoter regions (<3000 bases from the TSS). These analyses were also linked with the transcription profiles of MCF7 cells, obtained from public RNA-seq data. Hence, it is suggested that MALAT1 and PRC2 can concomitantly bind to promoters of actively-transcribed genes in MCF7 cells. Gene ontology analyses revealed an enrichment of genes related to categories including cancer malignancy and epigenetic regulation. Thus, by re-visiting occupancy and transcriptomic data, we identified a key gene subset controlled by the collaboration of MALAT1 and PRC2.

8.
Cell ; 186(12): 2593-2609.e18, 2023 06 08.
Artículo en Inglés | MEDLINE | ID: mdl-37209683

RESUMEN

Here, we describe an approach to correct the genetic defect in fragile X syndrome (FXS) via recruitment of endogenous repair mechanisms. A leading cause of autism spectrum disorders, FXS results from epigenetic silencing of FMR1 due to a congenital trinucleotide (CGG) repeat expansion. By investigating conditions favorable to FMR1 reactivation, we find MEK and BRAF inhibitors that induce a strong repeat contraction and full FMR1 reactivation in cellular models. We trace the mechanism to DNA demethylation and site-specific R-loops, which are necessary and sufficient for repeat contraction. A positive feedback cycle comprising demethylation, de novo FMR1 transcription, and R-loop formation results in the recruitment of endogenous DNA repair mechanisms that then drive excision of the long CGG repeat. Repeat contraction is specific to FMR1 and restores the production of FMRP protein. Our study therefore identifies a potential method of treating FXS in the future.


Asunto(s)
Síndrome del Cromosoma X Frágil , Expansión de Repetición de Trinucleótido , Humanos , Estructuras R-Loop , Metilación de ADN , Síndrome del Cromosoma X Frágil/genética , Epigénesis Genética , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/metabolismo
9.
J Chem Phys ; 158(12): 124708, 2023 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-37003735

RESUMEN

For sessile droplets of pure liquid on a surface, evaporation depends on surface wettability, the surrounding environment, contact angle hysteresis, and surface roughness. For non-pure liquids, the evaporation characteristics are further complicated by the constituents and impurities within the droplet. For saline solutions, this complication takes the form of a modified partial vapor pressure/water activity caused by the increasing salt concentration as the aqueous solvent evaporates. It is generally thought that droplets on surfaces will crystallize when the saturation concentration is reached, i.e., 26.3% for NaCl in water. This crystallization is initiated by contact with the surface and is thus due to surface roughness and heterogeneities. Recently, smooth, low contact angle hysteresis surfaces have been created by molecular grafting of polymer chains. In this work, we hypothesize that by using these very smooth surfaces to evaporate saline droplets, we can suppress the crystallization caused by the surface interactions and thus achieve constant volume droplets above the saturation concentration. In our experiments, we used several different surfaces to examine the possibility of crystallization suppression. We show that on polymer grafted surfaces, i.e., Slippery Omniphobic Covalently Attached Liquid-like (SOCAL) and polyethyleneglycol(PEGylated) surfaces, we can achieve stable droplets as low as 55% relative humidity at 25 °C with high reproducibility using NaCl in water solutions. We also show that it is possible to achieve stable droplets above the saturation concentration on other surfaces, including superhydrophobic surfaces. We present an analytical model, based on water activity, which accurately describes the final stable volume as a function of the initial salt concentration. These findings are important for heat and mass transfer in relatively low humidity environments.

10.
Langmuir ; 38(32): 10032-10042, 2022 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-35921631

RESUMEN

Slippery liquid-infused porous surfaces (SLIPS) are an innovation that reduces droplet-solid contact line pinning and interfacial friction. Recently, it has been shown that a liquid analogue of Young's law can be deduced for the apparent contact angle of a sessile droplet on SLIPS despite there never being contact by the droplet with the underlying solid. Since contact angles on solids are used to characterize solid-liquid interfacial interactions and the wetting of a solid by a liquid, it is our hypothesis that liquid-liquid interactions and the wetting of a liquid surface by a liquid can be characterized by apparent contact angles on SLIPS. Here, we first present a theory for deducing liquid-liquid interfacial tensions from apparent contact angles. This theory is valid irrespective of whether or not a film of the infusing liquid cloaks the droplet-vapor interface. We show experimentally that liquid-liquid interfacial tensions deduced from apparent contact angles of droplets on SLIPS are in excellent agreement with values from the traditional pendant drop technique. We then consider whether the Zisman method for characterizing the wettability of a solid surface can be applied to liquid surfaces created using SLIPS. We report apparent contact angles for a homologous series of alkanes on Krytox-infused SLIPS and for water-IPA mixtures on both the Krytox-infused SLIPS and a silicone oil-infused SLIPS. The alkanes on the Krytox-infused SLIPS follow a linear relationship in the liquid form of the Zisman plot provided that the effective droplet-vapor interfacial tension is used. All three systems follow a linear relationship on a modified Zisman plot. We interpret these results using the concept of the critical surface tension (CST) for the wettability of a solid surface introduced by Zisman. In our liquid surface case, the obtained critical surface tensions were found to be lower than the infusing liquid-vapor surface tensions.

11.
Langmuir ; 38(34): 10632-10641, 2022 08 30.
Artículo en Inglés | MEDLINE | ID: mdl-35977085

RESUMEN

A versatile method for the creation of multitier hierarchical structured surfaces is reported, which optimizes both antiviral and hydrophobic (easy-clean) properties. The methodology exploits the availability of surface-active chemical groups while also manipulating both the surface micro- and nanostructure to control the way the surface coating interacts with virus particles within a liquid droplet. This methodology has significant advantages over single-tier structured surfaces, including the ability to overcome the droplet-pinning effect and in delivering surfaces with high static contact angles (>130°) and good antiviral efficacy (log kill >2). In addition, the methodology highlights a valuable approach for the creation of mechanically robust, nanostructured surfaces which can be prepared by spray application using nonspecialized equipment.


Asunto(s)
Antivirales , Nanoestructuras , Antivirales/farmacología , Interacciones Hidrofóbicas e Hidrofílicas , Nanoestructuras/química , Propiedades de Superficie
12.
Neuron ; 110(10): 1656-1670.e12, 2022 05 18.
Artículo en Inglés | MEDLINE | ID: mdl-35276083

RESUMEN

Non-cell-autonomous mechanisms contribute to neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), in which astrocytes release unidentified factors that are toxic to motoneurons (MNs). We report here that mouse and patient iPSC-derived astrocytes with diverse ALS/FTD-linked mutations (SOD1, TARDBP, and C9ORF72) display elevated levels of intracellular inorganic polyphosphate (polyP), a ubiquitous, negatively charged biopolymer. PolyP levels are also increased in astrocyte-conditioned media (ACM) from ALS/FTD astrocytes. ACM-mediated MN death is prevented by degrading or neutralizing polyP in ALS/FTD astrocytes or ACM. Studies further reveal that postmortem familial and sporadic ALS spinal cord sections display enriched polyP staining signals and that ALS cerebrospinal fluid (CSF) exhibits increased polyP concentrations. Our in vitro results establish excessive astrocyte-derived polyP as a critical factor in non-cell-autonomous MN degeneration and a potential therapeutic target for ALS/FTD. The CSF data indicate that polyP might serve as a new biomarker for ALS/FTD.


Asunto(s)
Esclerosis Amiotrófica Lateral , Demencia Frontotemporal , Esclerosis Amiotrófica Lateral/genética , Animales , Astrocitos , Proteína C9orf72/genética , Medios de Cultivo Condicionados/farmacología , Demencia Frontotemporal/genética , Humanos , Ratones , Neuronas Motoras , Polifosfatos
13.
Nature ; 604(7904): 160-166, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35355011

RESUMEN

Although more than 98% of the human genome is non-coding1, nearly all of the drugs on the market target one of about 700 disease-related proteins. The historical reluctance to invest in non-coding RNA stems partly from requirements for drug targets to adopt a single stable conformation2. Most RNAs can adopt several conformations of similar stabilities. RNA structures also remain challenging to determine3. Nonetheless, an increasing number of diseases are now being attributed to non-coding RNA4 and the ability to target them would vastly expand the chemical space for drug development. Here we devise a screening strategy and identify small molecules that bind the non-coding RNA prototype Xist5. The X1 compound has drug-like properties and binds specifically the RepA motif6 of Xist in vitro and in vivo. Small-angle X-ray scattering analysis reveals that RepA can adopt multiple conformations but favours one structure in solution. X1 binding reduces the conformational space of RepA, displaces cognate interacting protein factors (PRC2 and SPEN), suppresses histone H3K27 trimethylation, and blocks initiation of X-chromosome inactivation. X1 inhibits cell differentiation and growth in a female-specific manner. Thus, RNA can be systematically targeted by drug-like compounds that disrupt RNA structure and epigenetic function.


Asunto(s)
Cromosomas Humanos X , ARN Largo no Codificante , Inactivación del Cromosoma X , Diferenciación Celular , Cromosomas Humanos X/genética , Femenino , Histonas/metabolismo , Humanos , ARN Largo no Codificante/genética , Inactivación del Cromosoma X/genética
14.
Langmuir ; 38(14): 4425-4433, 2022 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-35353534

RESUMEN

The empirical laws of dry friction between two solid bodies date back to the work of Amontons in 1699 and are pre-dated by the work of Leonardo da Vinci. Fundamental to those laws are the concepts of static and kinetic coefficients of friction relating the pinning and sliding friction forces along a surface to the normal load force. For liquids on solid surfaces, contact lines also experience pinning and the language of friction is used when droplets are in motion. However, it is only recently that the concept of coefficients of friction has been defined in this context and that droplet friction has been discussed as having a static and a kinetic regime. Here, we use surface free energy considerations to show that the frictional force per unit length of a contact line is directly proportional to the normal component of the surface tension force. We define coefficients of friction for both contact lines and droplets and provide a droplet analogy of Amontons' first and second laws but with the normal load force of a solid replaced by the normal surface tension force of a liquid. In the static regime, the coefficient of static friction, defined by the maximum pinning force of a droplet, is proportional to the contact angle hysteresis, whereas in the kinetic regime, the coefficient of kinetic friction is proportional to the difference in dynamic advancing and receding contact angles. We show the consistency between the droplet form of Amontons' first and second laws and an equation derived by Furmidge. We use these liquid-solid Amontons' laws to describe literature data and report friction coefficients for various liquid-solid systems. The conceptual framework reported here should provide insight into the design of superhydrophobic, slippery liquid-infused porous surfaces (SLIPS) and other surfaces designed to control droplet motion.

15.
Cureus ; 14(1): e21296, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35186558

RESUMEN

Acute ST-segment elevation (STE) on electrocardiogram (EKG) is very frequently associated with myocardial infarction, which requires prompt diagnosis and treatment. However, there are multiple other causes of acute STE, both cardiac and noncardiac. Here we describe a unique case of acute inferior and lateral STE caused by osteomyelitis and abscess of the lower cervical vertebrae.

16.
Int. j. cardiovasc. sci. (Impr.) ; 35(1): 127-134, Jan.-Feb. 2022. graf
Artículo en Inglés | LILACS | ID: biblio-1356306

RESUMEN

Abstract Cardiovascular diseases are the leading cause of death in the world. People living in vulnerable and poor places such as slums, rural areas and remote locations have difficulty in accessing medical care and diagnostic tests. In addition, given the COVID-19 pandemic, we are witnessing an increase in the use of telemedicine and non-invasive tools for monitoring vital signs. These questions motivate us to write this point of view and to describe some of the main innovations used for non-invasive screening of heart diseases. Smartphones are widely used by the population and are perfect tools for screening cardiovascular diseases. They are equipped with camera, flashlight, microphone, processor, and internet connection, which allow optical, electrical, and acoustic analysis of cardiovascular phenomena. Thus, when using signal processing and artificial intelligence approaches, smartphones may have predictive power for cardiovascular diseases. Here we present different smartphone approaches to analyze signals obtained from various methods including photoplethysmography, phonocardiograph, and electrocardiography to estimate heart rate, blood pressure, oxygen saturation (SpO2), heart murmurs and electrical conduction. Our objective is to present innovations in non-invasive diagnostics using the smartphone and to reflect on these trending approaches. These could help to improve health access and the screening of cardiovascular diseases for millions of people, particularly those living in needy areas.


Asunto(s)
Inteligencia Artificial/tendencias , Enfermedades Cardiovasculares/diagnóstico , Triaje/tendencias , Diagnóstico por Computador/métodos , Diagnóstico por Computador/tendencias , Teléfono Inteligente/tendencias , Triaje/métodos , Telemedicina/métodos , Telemedicina/tendencias , Aplicaciones Móviles/tendencias , Teléfono Inteligente/instrumentación , Telecardiología , COVID-19/diagnóstico
17.
Cell ; 184(25): 6157-6173.e24, 2021 12 09.
Artículo en Inglés | MEDLINE | ID: mdl-34856126

RESUMEN

Chromosome loops shift dynamically during development, homeostasis, and disease. CCCTC-binding factor (CTCF) is known to anchor loops and construct 3D genomes, but how anchor sites are selected is not yet understood. Here, we unveil Jpx RNA as a determinant of anchor selectivity. Jpx RNA targets thousands of genomic sites, preferentially binding promoters of active genes. Depleting Jpx RNA causes ectopic CTCF binding, massive shifts in chromosome looping, and downregulation of >700 Jpx target genes. Without Jpx, thousands of lost loops are replaced by de novo loops anchored by ectopic CTCF sites. Although Jpx controls CTCF binding on a genome-wide basis, it acts selectively at the subset of developmentally sensitive CTCF sites. Specifically, Jpx targets low-affinity CTCF motifs and displaces CTCF protein through competitive inhibition. We conclude that Jpx acts as a CTCF release factor and shapes the 3D genome by regulating anchor site usage.


Asunto(s)
Factor de Unión a CCCTC/metabolismo , Cromosomas/metabolismo , ARN Largo no Codificante/metabolismo , Animales , Sitios de Unión , Línea Celular , Células Madre Embrionarias , Ratones , Unión Proteica
18.
Polymers (Basel) ; 13(19)2021 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-34641074

RESUMEN

The manufacturing process of the aircraft cabin interior panels is expensive and time-consuming, and the resulting panel requires rework due to damages that occurred during their fabrication. The aircraft interior panels must meet structural requirements; hence sandwich composites of a honeycomb core covered with two layers of pre-impregnated fiberglass skin are used. Flat sandwich composites are transformed into panels with complex shapes or geometries using the compression molding process, leading to advanced manufacturing challenges. Some aircraft interior panels are required for non-structural applications; hence sandwich composites can be substituted by cheaper alternative materials and transformed using disruptive manufacturing techniques. This paper evaluates the feasibility of replacing the honeycomb and fiberglass skin layers core with rigid polyurethane foams and thermoplastic polymers. The results show that the structural composites have higher mechanical performances than the proposed sandwich composites, but they are compatible with non-structural applications. Sandwich composite fabrication using the vacuum forming process is feasible for developing non-structural panels. This manufacturing technique is fast, easy, economical, and ecological as it uses recyclable materials. The vacuum forming also covers the entire panel, thus eliminating tapestries, paints, or finishes to the aircraft interior panels. The conclusion of the article describes the focus of future research.

19.
Polymers (Basel) ; 13(19)2021 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-34641250

RESUMEN

In this work, henequen and ixlte plant fibers were carbonized in a horizontal quartz tube furnace. Several carbonized and non-carbonized fiber fabric configurations were impregnated with a bio-based epoxy resin through the infuseon process. The infrared spectra revealed characteristic bands of styrene instead of organic compounds, representing that the carbonization procedure was adequate to carbonize the plant fibers. The porosity volume ratio for the non-carbonized henequen laminates showed the highest number of voids >1.9%, and the rest of the composites had a similar void density between 1.2-1.7%. The storage modulus of the non-carbonized and carbonized henequen laminates resulted in 2268.5 MPa and 2092.1 MPa, respectively. The storage modulus of the carbonized ixtle laminates was 1541.4 MPa, which is 37.8% higher than the non-carbonized ixtle laminates and 12% higher than henequen composites. The laminates were subject to thermal shock cycling, and tomography scans revealed no alterations on the porosity level or in the cracks after the cycling procedure. Thermal shock cycling promoted the post-curing effect by increasing the glass transition temperature. The viscoelastic results showed a variation in the storage modulus when the carbonized fiber fabrics were located between natural fiber fabrics, which was attributed to more excellent compaction during the infusion process. Variations in the viscoelastic behavior were observed between the different types of natural fibers, which influenced the mechanical properties.

20.
Langmuir ; 37(24): 7328-7340, 2021 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-34101471

RESUMEN

The dynamic effect of an electric field on dielectric liquids is called liquid dielectrophoresis. It is widely used in several industrial and scientific applications, including inkjet printing, microfabrication, and optical devices. Numerical simulations of liquid-dielectrophoresis are necessary to understand the fundamental physics of the phenomenon, but also to explore situations that might be difficult or expensive to implement experimentally. However, such modeling is challenging, as one needs to solve the electrostatic and fluid dynamics equations simultaneously. Here, we formulate a new lattice-Boltzmann method capable of modeling the dynamics of immiscible dielectric fluids coupled with electric fields within a single framework, thus eliminating the need of using separate algorithms to solve the electrostatic and fluid dynamics equations. We validate the numerical method by comparing it with analytical solutions and previously reported experimental results. Beyond the benchmarking of the method, we study the spreading of a droplet using a dielectrowetting setup and quantify the mechanism driving the variation of the apparent contact angle of the droplet with the applied voltage. Our method provides a useful tool to study liquid-dielectrophoresis and can be used to model dielectric fluids in general, such as liquid-liquid and liquid-gas systems.

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