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1.
Chem Asian J ; : e202400308, 2024 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-38880773

RESUMEN

Hydrogen-driven energy is fascinating among the everlasting energy sources, particularly for stationary and onboard transportation applications. Efficient hydrogen storage presents a key challenge to accomplishing the sustainability goals of hydrogen economy. In this regard, solid-state hydrogen storage in nanomaterials, either physically or chemically adsorbed, has been considered a safe path to establishing sustainability goals. Though metal hydrides have been extensively explored, they fail to comply with the set targets for practical utilization. Recently, MXenes, both in bare form and hybrid state with metal hydrides, have proven their flair in ascertaining the hydrides' theoretical and experimental hydrogen storage capabilities far beyond the fancy materials and current state-of-the-art technologies. This review encompasses the significant accomplishments achieved by MXenes (primarily in 2019-2024) for enhancing the hydrogen storage performance of various metal hydride materials such as MgH2, AlH3, Mg(BH4)2, LiBH4, alanates, and composite hydrides. It also discusses the bottlenecks of metal hydrides for hydrogen storage, the potential use of MXenes hybrids, and their challenges, such as reversibility, H2 losses, slow kinetics, and thermodynamic barriers. Finally, it concludes with a detailed roadmap and recommendations for mechanistic-driven future studies propelling toward a breakthrough in solid material-driven hydrogen storage using cost-effective, efficient, and long-lasting solutions.

2.
Chem Asian J ; : e202400320, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38838273

RESUMEN

Hydrogen (H2) is being acknowledged as the future energy carrier due to its high energy density and potential to mitigate the intermittency of other renewable energy sources. H2 also ensures a clean, carbon-neutral, and sustainable environment for current and forthcoming generations by contributing to the global missions of decarbonization in the transportation, industrial, and building sectors. Several H2 storage technologies are available and have been employed for its secure and economical transport. The existing H2 storage and transportation technologies like liquid-state, cryogenic, or compressed hydrogen are in use but still suffer from significant challenges regarding successful realization at the commercial level. These factors affect the overall operational cost of technology. Therefore, H2 storage demands novel technologies that are safe for mobility, transportation, long-term storage, and yet it is cost-effective. This review article presents potential opportunities for H2 storage technologies, such as physical and chemical storage. The prime characteristics and requirements of H2 storage are briefly explained. A detailed discussion of chemical-based hydrogen storage systems such as metal hydrides, chemical hydrides (CH3OH, NH3, and HCOOH), and liquid organic hydrogen carriers (LOHCs) is presented. Furthermore, the recent developments and challenges regarding hydrogen storage, their real-world applications, and prospects have also been debated.

3.
Sci Rep ; 14(1): 13341, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38858506

RESUMEN

Accurate channel state information (CSI) is crucial for optimizing wireless communication systems. In scenarios with varying user-to-base station angles, the angle-dependent coherence time impacts conventional pilot strategies. Due to small angles, the coherence time of the user decreases dramatically because of doppler shift, which causes an increase in the number of pilots. We introduces an innovative sub-block design approach for systems with different user angles. This method harmonizes coherence time of high and low-angle users, while maintaining a constant pilot count. This not only improves spectral efficiency but also ensures accurate channel estimation. Through simulations, we demonstrate the effectiveness of our approach in enhancing both spectral efficiency upt to 10 % and CSI precision. This breakthrough contributes to the advancement of channel estimation techniques in scenarios with angle-dependent coherence time, offering practical benefits to wireless communication systems.

4.
J Egypt Natl Canc Inst ; 36(1): 22, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38910202

RESUMEN

BACKGROUND: Innovations in cancer treatment have contributed to the improved survival rate of cancer patients. The cancer survival rates have been growing and nearly two third of those survivors have been exposed to clinical radiation during their treatment. The study of long-term radiation effects, especially secondary cancer induction, has become increasingly important. An accurate assessment of out-of-field/peripheral dose (PDs) is necessary to estimate the risk of second cancer after radiotherapy and the damage to the organs at risk surrounding the planning target volume. This study was designed to measure the PDs as a function of dose, distances, and depths from Telecobalt-60 (Co-60) beam in water phantom using thermoluminescent dosimeter-100 (TLD-100). METHODS: The PDs were measured for Co-60 beam at specified depths of 0 cm (surface), 5 cm, 10 cm, and 15 cm outside the radiation beam at distances of 5, 10, and 13 cm away from the radiation field edge using TLD-100 (G1 cards) as detectors. These calibrated cards were placed on the acrylic disc in circular tracks. The radiation dose of 2000 mGy of Co-60 beam was applied inside 10 × 10 cm2 field size at constant source to surface distance (SSD) of 80 cm. RESULTS: The results showed maximum and minimum PDs at surface and 5 cm depth respectively at all distances from the radiation field edge. Dose distributions out of the field edge with respect to distance were isotropic. The decrease in PDs at 5 cm depth was due to dominant forward scattering of Co-60 gamma rays. The increase in PDs beyond 5 cm depth was due to increase in the irradiated volume, increase in penumbra, increase in source to axis distance (SAD), and increase in field size due to inverse square factor. CONCLUSION: It is concluded that the PDs depends upon depth and distance from the radiation field edge. All the measurements show PDs in the homogenous medium (water); therefore, it estimates absorbed dose to the organ at risk (OAR) adjacent to cancer tissues/planning target volume (PTV). It is suggested that PDs can be minimized by using the SAD technique, as this technique controls sources of scattered radiation like inverse square factor and effect of penumbra up-to some extent.


Asunto(s)
Radioisótopos de Cobalto , Fantasmas de Imagen , Dosificación Radioterapéutica , Dosimetría Termoluminiscente , Humanos , Dosimetría Termoluminiscente/métodos , Agua , Planificación de la Radioterapia Asistida por Computador/métodos , Neoplasias/radioterapia , Dosis de Radiación , Órganos en Riesgo/efectos de la radiación
5.
Chem Asian J ; : e202400365, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38705846

RESUMEN

Hydrogen energy heralded for its environmentally friendly, renewable, efficient, and cost-effective attributes, stands poised as the primary alternative to fossil fuels in the future. Despite its great potential, the low volumetric density presents a formidable challenge in hydrogen storage. Addressing this challenge necessitates exploring effective storage techniques for a sustainable hydrogen economy. Solid-state hydrogen storage in nanomaterials (physically or chemically) holds promise for achieving large-scale hydrogen storage applications. Such approaches offer benefits, including safety, compactness, lightness, reversibility, and efficient generation of pure hydrogen fuel under mild conditions. This article presents solid-state nanomaterials, specifically nanoporous carbons (activated carbon, carbon fibers), metal-organic frameworks, covalently connected frameworks, nanoporous organic polymers, and nanoscale metal hydrides. Furthermore, new developments in hydrogen fuel cell technology for stationary and mobile applications have been demonstrated. The review outlines significant advancements thus far, identifies key barriers to practical implementation, and presents a perspective for future sustainable energy research. It concludes with recommendations to enhance hydrogen storage performance for cost-effective and long-lasting utilization.

6.
Commun Biol ; 7(1): 613, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773248

RESUMEN

Understanding how to increase soybean yield is crucial for global food security. The genetic and epigenetic factors influencing seed size, a major crop yield determinant, are not fully understood. We explore the role of DNA demethylase GmDMEa in soybean seed size. Our research indicates that GmDMEa negatively correlates with soybean seed size. Using CRISPR-Cas9, we edited GmDMEa in the Dongnong soybean cultivar, known for small seeds. Modified plants had larger seeds and greater yields without altering plant architecture or seed nutrition. GmDMEa preferentially demethylates AT-rich transposable elements, thus activating genes and transcription factors associated with the abscisic acid pathway, which typically decreases seed size. Chromosomal substitution lines confirm that these modifications are inheritable, suggesting a stable epigenetic method to boost seed size in future breeding. Our findings provide insights into epigenetic seed size control and suggest a strategy for improving crop yields through the epigenetic regulation of crucial genes. This work implies that targeted epigenetic modification has practical agricultural applications, potentially enhancing food production without compromising crop quality.


Asunto(s)
Metilación de ADN , Elementos Transponibles de ADN , Glycine max , Semillas , Glycine max/genética , Semillas/genética , Semillas/crecimiento & desarrollo , Elementos Transponibles de ADN/genética , Epigénesis Genética , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/genética
7.
Mol Ecol ; : e17356, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38634782

RESUMEN

DNA methylation has been proposed to be an important mechanism that allows plants to respond to their environments sometimes entirely uncoupled from genetic variation. To understand the genetic basis, biological functions and climatic relationships of DNA methylation at a population scale in Arabidopsis thaliana, we performed a genome-wide association analysis with high-quality single nucleotide polymorphisms (SNPs), and found that ~56% on average, especially in the CHH sequence context (71%), of the differentially methylated regions (DMRs) are not tagged by SNPs. Among them, a total of 3235 DMRs are significantly associated with gene expressions and potentially heritable. 655 of the 3235 DMRs are associated with climatic variables, and we experimentally verified one of them, HEI10 (HUMAN ENHANCER OF CELL INVASION NO.10). Such epigenetic loci could be subjected to natural selection thereby affecting plant adaptation, and would be expected to be an indicator of accessions at risk. We therefore incorporated these climate-related DMRs into a gradient forest model, and found that the natural A. thaliana accessions in Southern Europe that may be most at risk under future climate change. Our findings highlight the importance of integrating DNA methylation that is independent of genetic variations, and climatic data to predict plants' vulnerability to future climate change.

10.
J Exp Zool B Mol Dev Evol ; 342(2): 85-100, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38369890

RESUMEN

TRPS1 serves as the causative gene for tricho-rhino phalangeal syndrome, known for its craniofacial and skeletal abnormalities. The Trps1 gene encodes a protein that represses Wnt signaling through strong interactions with Wnt signaling inhibitors. The identification of genomic cis-acting regulatory sequences governing Trps1 expression is crucial for understanding its role in embryogenesis. Nevertheless, to date, no investigations have been conducted concerning these aspects of Trps1. To identify deeply conserved noncoding elements (CNEs) within the Trps1 locus, we employed a comparative genomics approach, utilizing slowly evolving fish such as coelacanth and spotted gar. These analyses resulted in the identification of eight CNEs in the intronic region of the Trps1 gene. Functional characterization of these CNEs in zebrafish revealed their regulatory potential in various tissues, including pectoral fins, heart, and pharyngeal arches. RNA in-situ hybridization experiments revealed concordance between the reporter expression pattern induced by the identified set of CNEs and the spatial expression pattern of the trps1 gene in zebrafish. Comparative in vivo data from zebrafish and mice for CNE7/hs919 revealed conserved functions of these enhancers. Each of these eight CNEs was further investigated in cell line-based reporter assays, revealing their repressive potential. Taken together, in vivo and in vitro assays suggest a context-dependent dual functionality for the identified set of Trps1-associated CNE enhancers. This functionally characterized set of CNE-enhancers will contribute to a more comprehensive understanding of the developmental roles of Trps1 and can aid in the identification of noncoding DNA variants associated with human diseases.


Asunto(s)
Dedos/anomalías , Enfermedades del Cabello , Síndrome de Langer-Giedion , Nariz/anomalías , Secuencias Reguladoras de Ácidos Nucleicos , Pez Cebra , Animales , Ratones , Humanos , Pez Cebra/genética , Pez Cebra/metabolismo , Genoma , Secuencia de Bases , Expresión Génica , Mamíferos/genética , Proteínas Represoras/genética , Proteínas Represoras/metabolismo
11.
Pak J Med Sci ; 40(3Part-II): 526-533, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38356832

RESUMEN

Objectives: To review published clinical trials which assessed the effects of deep transverse friction massage on pain and range of motion in patients with adhesive capsulitis. Methods: A systematic review was conducted according to PRISMA guidelines. Literature search was performed in MEDLINE, AMED, EMBASE, HMIC, CINAHL, PEDRO, and SPORTDiscus. Two independent reviewers performed screening of the articles retrieved from different databases. Clinical trials published in English language from the earliest record to March 2022 that reported effects of deep transverse friction massage/Cyriax's friction massage on pain and/or range of motion in patients with diagnosis of adhesive capsulitis were included. The Critical Appraisal Skills Programme was used for quality assessment of the included studies. Results: A total of six studies reporting on 226 adhesive capsulitis patients were included in the systematic review. All the six studies were randomized controlled clinical trials. On the Critical Appraisal Skills Programme tool, four of the six studies had a score of 8/11, while the other two studies received a score of 7/11 and 6/11. Out of these six trials, four reported that pain was significantly (P<0.05) improved in the deep transverse friction massage group as compared to the control group. Regarding range of motion outcome, five studies showed that range of motion was significantly (P<0.05) improved in the deep transverse friction massage group while only one study showed non-significant results. Conclusion: It can be concluded that deep transverse friction massage significantly relieves pain and improves the range of motion in individuals with adhesive capsulitis.

12.
PLoS One ; 19(2): e0291309, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38324592

RESUMEN

This study investigates the impact of board governance mechanism on investment efficiency (IE) in PSX-listed firms. The study also examines the role of institutional ownership (IO) in board-IE relationships. In addition, we extend our analysis to re-examine this relationship by splitting the sample into two groups, i.e., the introductory phase of corporate governance (CG) i.e., 2004 to 2013, and revised codes of CG (2014 to 2018) to examine the impact of these separately on IE. The sample data comprises 155 non-financial PSX-listed firms from 2004 to 2018. IE is measured using firms' growth opportunities. The random effect model is used to test the study's hypotheses. A robustness test is also performed to validate the study's findings. The paired-sample t-test results show a significant improvement in IE after revising the CG codes in 2012. According to the regression results, board size has a significant direct, whereas board diversity has a significant inverse effect on IE. Regarding moderating effect, IO was found to moderate the relationship between board independence and IE significantly. Furthermore, it was discovered that following the issuance of revised CG codes-2012, the level of board independence and diversity increased in PSX-listed firms; however, only diversity positively impacted IE, and board independence had no impact on IE from 2014 to 2018. Despite the issuance of revised CG codes-2012, the level of CG among PSX-listed firms is low, which is a source of concern for regulators such as the Securities and Exchange Commission of Pakistan.


Asunto(s)
Instituciones de Salud , Propiedad , Inversiones en Salud , Pakistán
13.
Sci Rep ; 14(1): 4528, 2024 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-38402301

RESUMEN

The orthogonal frequency division multiplexing (OFDM) system applies coherent demodulation to achieve high spectral efficiency at a bandwidth cost by the pilot tones. Considering the statistical property of the down-link channels to the users, it can be found that there is an opportunity to reduce the pilot number in the conventional designs while maintaining the same signal demodulation performances. The design philosophy involves utilizing the difference of the channel coherent bandwidths (CCBs) by allocating data to appropriate positions upon the fact that different CCBs can tolerate different minimized pilot spacing. The proposed design allows each user's equipment's data not to exceed its CCB with the sparser pilots. The theoretical analysis is carried out based on the concept of channel frequency response using linear interpolation with channel estimation employing the least squares (LS) method. The gain of the proposed method is demonstrated in terms of the ergodic capacities and confirmed by the simulations.

14.
Phytomedicine ; 125: 155350, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38237512

RESUMEN

BACKGROUND: Myostatin (MSTN) inhibition has demonstrated promise for the treatment of diseases associated with muscle loss. In a previous study, we discovered that Glycyrrhiza uralensis (G. uralensis) crude water extract (CWE) inhibits MSTN expression while promoting myogenesis. Furthermore, three specific compounds of G. uralensis, namely liquiritigenin, tetrahydroxymethoxychalcone, and Licochalcone B (Lic B), were found to promote myoblast proliferation and differentiation, as well as accelerate the regeneration of injured muscle tissue. PURPOSE: The purpose of this study was to build on our previous findings on G. uralensis and demonstrate the potential of its two components, Licochalcone A (Lic A) and Lic B, in muscle mass regulation (by inhibiting MSTN), aging and muscle formation. METHODS: G. uralensis, Lic A, and Lic B were evaluated thoroughly using in silico, in vitro and in vivo approaches. In silico analyses included molecular docking, and dynamics simulations of these compounds with MSTN. Protein-protein docking was carried out for MSTN, as well as for the docked complex of MSTN-Lic with its receptor, activin type IIB receptor (ACVRIIB). Subsequent in vitro studies used C2C12 cell lines and primary mouse muscle stem cells to acess the cell proliferation and differentiation of normal and aged cells, levels of MSTN, Atrogin 1, and MuRF1, and plasma MSTN concentrations, employing techniques such as western blotting, immunohistochemistry, immunocytochemistry, cell proliferation and differentiation assays, and real-time RT-PCR. Furthermore, in vivo experiments using mouse models focused on measuring muscle fiber diameters. RESULTS: CWE of G. uralensis and two of its components, namely Lic A and B, promote myoblast proliferation and differentiation by inhibiting MSTN and reducing Atrogin1 and MuRF1 expressions and MSTN protein concentration in serum. In silico interaction analysis revealed that Lic A (binding energy -6.9 Kcal/mol) and B (binding energy -5.9 Kcal/mol) bind to MSTN and reduce binding between it and ACVRIIB, thereby inhibiting downstream signaling. The experimental analysis, which involved both in vitro and in vivo studies, demonstrated that the levels of MSTN, Atrogin 1, and MuRF1 were decreased when G. uralensis CWE, Lic A, or Lic B were administered into mice or treated in the mouse primary muscle satellite cells (MSCs) and C2C12 myoblasts. The diameters of muscle fibers increased in orally treated mice, and the differentiation and proliferation of C2C12 cells were enhanced. G. uralensis CWE, Lic A, and Lic B also promoted cell proliferation in aged cells, suggesting that they may have anti-muslce aging properties. They also reduced the expression and phosphorylation of SMAD2 and SMAD3 (MSTN downstream effectors), adding to the evidence that MSTN is inhibited. CONCLUSION: These findings suggest that CWE and its active constituents Lic A and Lic B have anti-mauscle aging potential. They also have the potential to be used as natural inhibitors of MSTN and as therapeutic options for disorders associated with muscle atrophy.


Asunto(s)
Chalconas , Fibras Musculares Esqueléticas , Miostatina , Ratones , Animales , Miostatina/metabolismo , Simulación del Acoplamiento Molecular , Diferenciación Celular , Fibras Musculares Esqueléticas/metabolismo , Proliferación Celular , Músculo Esquelético/metabolismo
15.
Small ; 20(23): e2310946, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38229536

RESUMEN

Owing to their extraordinary photophysical properties, organometal halide perovskites are emerging as a new material class for X-ray detection. However, the existence of toxic lead makes their commercialization questionable and should readily be replaced. Accordingly, several lead alternatives have been introduced into the framework of conventional perovskites, resulting in various new perovskite dimensionalities. Among these, Pb-free lower dimensional perovskites (LPVKs) not only show promising X-ray detecting properties due to their higher ionic migration energy, wider and tunable energy bandgap, smaller dark currents, and structural versatility but also exhibit extended environmental stability. Herein, first, the structural organization of the PVKs (including LPVKs) is summarized. In the context of X-ray detectors (XDs), the outstanding properties of the LPVKs and active layer synthesis routes are elaborated afterward. Subsequently, their applications in direct XDs are extensively discussed and the device performance, in terms of the synthesis method, device architecture, active layer size, figure of merits, and device stability are tabulated. Finally, the review is concluded with an in-depth outlook, thoroughly exploring the present challenges to LPVKs XDs, proposing innovative solutions, and future directions. This review provides valuable insights into optimizing non-toxic Pb-free perovskite XDs, paving the way for future advancements in the field.

16.
Sci Rep ; 14(1): 449, 2024 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-38172191

RESUMEN

The coronavirus (COVID-19) pandemic has not only had a severe impact on global health but also poses a threat to the environment. This research aims to explore an innovative approach to address the issue of increased waste generated by the pandemic. Specifically, the study investigates the utilization of discarded face masks in combination with recycled concrete aggregate (RCA) and Silica Fume (SFM) in civil construction projects. The disposable face masks were processed by removing the ear loops and nose strips, and then cutting them into small fibers measuring 20 mm in length, 5 mm in width, and 0.46 mm in thickness, resulting in an aspect ratio of 24. Various proportions of SFM and RCA were incorporated into the concrete mix, with a focus on evaluating the compressive strength, split tensile strength, and durability of the resulting material. The findings indicate that the addition of SFM led to improvements in both compressive and split tensile strength, while no significant impact on durability was observed.


Asunto(s)
Administración de Residuos , Administración de Residuos/métodos , Dióxido de Silicio , Máscaras , Materiales de Construcción , Residuos Industriales/análisis
17.
Chem Rec ; 24(1): e202300171, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37606899

RESUMEN

The global rapid transition from fossil fuels to renewable energy resources necessitates the implementation of long-duration energy storage technologies owing to the intermittent nature of renewable energy sources. Therefore, the deployment of grid-scale energy storage systems is inevitable. Sulfur-based batteries can be exploited as excellent energy storage devices owing to their intrinsic safety, low cost of raw materials, low risk of environmental hazards, and highest theoretical capacities (gravimetric: 2600 Wh/kg and volumetric: 2800 Wh/L). However, sulfur-based batteries exhibit certain scientific limitations, such as polysulfide crossover, which causes rapid capacity decay and low Coulombic efficiency, thereby hindering their implementation at a commercial scale. In this review article, we focus on the latest research developments between 2012-2023 to improve the separators/membranes and overcome the shuttle effect associated with them. Various categories of ion exchange membranes (IEMs) used in redox batteries, particularly polysulfide redox flow batteries and lithium-sulfur batteries, are discussed in detail. Furthermore, advances in IEM constituents are summarized to gain insights into different fundamental strategies for attaining targeted characteristics, and a critical analysis is proposed to highlight their efficiency in mitigating sulfur cross-shuttling issues. Finally, future prospects and recommendations are suggested for future research toward the fabrication of more effective membranes with desired properties.

18.
Chem Rec ; 24(1): e202300284, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38010347

RESUMEN

In recent years, aqueous organic redox flow batteries (AORFBs) have attracted considerable attention due to advancements in grid-level energy storage capacity research. These batteries offer remarkable benefits, including outstanding capacity retention, excellent cell performance, high energy density, and cost-effectiveness. The organic electrolytes in AORFBs exhibit adjustable redox potentials and tunable solubilities in water. Previously, various types of organic electrolytes, such as quinones, organometallic complexes, viologens, redox-active polymers, and organic salts, were extensively investigated for their electrochemical performance and stability. This study presents an overview of recently published novel organic electrolytes for AORFBs in acidic, alkaline, and neutral environments. Furthermore, it delves into the current status, challenges, and prospects of AORFBs, highlighting different strategies to overcome these challenges, with special emphasis placed on their design, composition, functionalities, and cost. A brief techno-economic analysis of various aqueous RFBs is also outlined, considering their potential scalability and integration with renewable energy systems.

19.
Chem Rec ; 24(1): e202300247, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37933973

RESUMEN

The high-temperature solid oxide fuel cells (SOFCs) are the most efficient and green conversion technology for electricity generation from hydrogen-based fuel as compared to conventional thermal power plants. Many efforts have been made to reduce the high operating temperature (>800 °C) to intermediate/low operating temperature (400 °C

20.
Dev Growth Differ ; 66(1): 75-88, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37925606

RESUMEN

Abnormal expression of the transcriptional regulator and hedgehog (Hh) signaling pathway effector Gli3 is known to trigger congenital disease, most frequently affecting the central nervous system (CNS) and the limbs. Accurate delineation of the genomic cis-regulatory landscape controlling Gli3 transcription during embryonic development is critical for the interpretation of noncoding variants associated with congenital defects. Here, we employed a comparative genomic analysis on fish species with a slow rate of molecular evolution to identify seven previously unknown conserved noncoding elements (CNEs) in Gli3 intronic intervals (CNE15-21). Transgenic assays in zebrafish revealed that most of these elements drive activities in Gli3 expressing tissues, predominantly the fins, CNS, and the heart. Intersection of these CNEs with human disease associated SNPs identified CNE15 as a putative mammalian craniofacial enhancer, with conserved activity in vertebrates and potentially affected by mutation associated with human craniofacial morphology. Finally, comparative functional dissection of an appendage-specific CNE conserved in slowly evolving fish (elephant shark), but not in teleost (CNE14/hs1586) indicates co-option of limb specificity from other tissues prior to the divergence of amniotes and lobe-finned fish. These results uncover a novel subset of intronic Gli3 enhancers that arose in the common ancestor of gnathostomes and whose sequence components were likely gradually modified in other species during the process of evolutionary diversification.


Asunto(s)
Elementos de Facilitación Genéticos , Pez Cebra , Animales , Humanos , Pez Cebra/genética , Pez Cebra/metabolismo , Elementos de Facilitación Genéticos/genética , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Animales Modificados Genéticamente , Mamíferos , Evolución Molecular , Secuencia Conservada/genética
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