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1.
Cell ; 185(26): 4954-4970.e20, 2022 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-36493774

RESUMO

Nuclear pore complexes (NPCs) are channels for nucleocytoplasmic transport of proteins and RNAs. However, it remains unclear whether composition, structure, and permeability of NPCs dynamically change during the cleavage period of vertebrate embryos and affect embryonic development. Here, we report that the comprehensive NPC maturity (CNM) controls the onset of zygotic genome activation (ZGA) during zebrafish early embryogenesis. We show that more nucleoporin proteins are recruited to and assembled into NPCs with development, resulting in progressive increase of NPCs in size and complexity. Maternal transcription factors (TFs) transport into nuclei more efficiently with increasing CNM. Deficiency or dysfunction of Nup133 or Ahctf1/Elys impairs NPC assembly, maternal TFs nuclear transport, and ZGA onset, while nup133 overexpression promotes these processes. Therefore, CNM may act as a molecular timer for ZGA by controlling nuclear transport of maternal TFs that reach nuclear concentration thresholds at a given time to initiate ZGA.


Assuntos
Poro Nuclear , Peixe-Zebra , Animais , Desenvolvimento Embrionário/genética , Regulação da Expressão Gênica no Desenvolvimento , Poro Nuclear/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Peixe-Zebra/metabolismo , Zigoto/metabolismo , Genoma
2.
Trends Biochem Sci ; 48(8): 673-688, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37221124

RESUMO

Spatiotemporal regulation of cell type-specific gene expression is essential to convert a zygote into a complex organism that contains hundreds of distinct cell types. A class of cis-regulatory elements called enhancers, which have the potential to enhance target gene transcription, are crucial for precise gene expression programs during development. Following decades of research, many enhancers have been discovered and how enhancers become activated has been extensively studied. However, the mechanisms underlying enhancer silencing are less well understood. We review current understanding of enhancer decommissioning and dememorization, both of which enable enhancer silencing. We highlight recent progress from genome-wide perspectives that have revealed the life cycle of enhancers and how its dynamic regulation underlies cell fate transition, development, cell regeneration, and epigenetic reprogramming.


Assuntos
Elementos Facilitadores Genéticos , Estágios do Ciclo de Vida , Animais , Diferenciação Celular
3.
Mol Cell ; 72(4): 673-686.e6, 2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-30444999

RESUMO

The epigenome plays critical roles in controlling gene expression and development. However, how the parental epigenomes transit to the zygotic epigenome in early development remains elusive. Here we show that parental-to-zygotic transition in zebrafish involves extensive erasure of parental epigenetic memory, starting with methylating gametic enhancers. Surprisingly, this occurs even prior to fertilization for sperm. Both parental enhancers lose histone marks by the 4-cell stage, and zygotic enhancers are not activated until around zygotic genome activation (ZGA). By contrast, many promoters remain hypomethylated and, unexpectedly, acquire histone acetylation before ZGA at as early as the 4-cell stage. They then resolve into either activated or repressed promoters upon ZGA. Maternal depletion of histone acetyltransferases results in aberrant ZGA and early embryonic lethality. Finally, such reprogramming is largely driven by maternal factors, with zygotic products mainly contributing to embryonic enhancer activation. These data reveal widespread enhancer dememorization and promoter priming during parental-to-zygotic transition.


Assuntos
Código das Histonas/genética , Código das Histonas/fisiologia , Peixe-Zebra/embriologia , Acetilação , Animais , Metilação de DNA/genética , Epigênese Genética/genética , Epigênese Genética/fisiologia , Epigenômica , Regulação da Expressão Gênica no Desenvolvimento/genética , Genoma/genética , Histonas/genética , Masculino , Oócitos , Regiões Promotoras Genéticas/genética , Processamento de Proteína Pós-Traducional , Sequências Reguladoras de Ácido Nucleico/genética , Espermatozoides , Transcrição Gênica/genética , Peixe-Zebra/genética , Proteínas de Peixe-Zebra , Zigoto/fisiologia
4.
Proc Natl Acad Sci U S A ; 120(10): e2201504120, 2023 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-36867684

RESUMO

The slow-evolving invertebrate amphioxus has an irreplaceable role in advancing our understanding of the vertebrate origin and innovations. Here we resolve the nearly complete chromosomal genomes of three amphioxus species, one of which best recapitulates the 17 chordate ancestor linkage groups. We reconstruct the fusions, retention, or rearrangements between descendants of whole-genome duplications, which gave rise to the extant microchromosomes likely existed in the vertebrate ancestor. Similar to vertebrates, the amphioxus genome gradually establishes its three-dimensional chromatin architecture at the onset of zygotic activation and forms two topologically associated domains at the Hox gene cluster. We find that all three amphioxus species have ZW sex chromosomes with little sequence differentiation, and their putative sex-determining regions are nonhomologous to each other. Our results illuminate the unappreciated interspecific diversity and developmental dynamics of amphioxus genomes and provide high-quality references for understanding the mechanisms of chordate functional genome evolution.


Assuntos
Anfioxos , Animais , Cromatina , Cromossomos Sexuais , Rearranjo Gênico , Família Multigênica
5.
FASEB J ; 38(4): e23492, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38363564

RESUMO

Lineage specification and X chromosome dosage compensation are two crucial biological processes that occur during preimplantation embryonic development. Although extensively studied in mice, the timing and regulation of these processes remain elusive in other species, including humans. Previous studies have suggested conserved principles of human and bovine early development. This study aims to provide fundamental insights into these programs and the regulation using a bovine embryo model by employing single-cell transcriptomics and genome editing approaches. The study analyzes the transcriptomes of 286 individual cells and reveals that bovine trophectoderm/inner cell mass transcriptomes diverge at the early blastocyst stage, after cavitation but before blastocyst expansion. The study also identifies transcriptomic markers and provides the timing of lineage specification events in the bovine embryo. Importantly, we find that SOX2 is required for the first cell decision program in bovine embryos. Moreover, the study shows the occurrence of X chromosome dosage compensation from morula to late blastocyst and reveals that this compensation results from downregulation of X-linked genes in female embryonic cells. The transcriptional atlas generated by this study is expected to be widely useful in improving our understanding of mammalian early embryo development.


Assuntos
Blastocisto , Análise da Expressão Gênica de Célula Única , Gravidez , Bovinos , Animais , Feminino , Humanos , Camundongos , Embrião de Mamíferos , Desenvolvimento Embrionário/genética , Cromossomo X/genética , Regulação da Expressão Gênica no Desenvolvimento , Linhagem da Célula/genética , Mamíferos
6.
Neuroimage ; 300: 120861, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39326769

RESUMO

Significant changes in brain morphology occur during the third trimester of gestation. The capability of deep learning in leveraging these morphological features has enhanced the accuracy of brain age predictions for this critical period. Yet, the opaque nature of deep learning techniques, often described as "black box" approaches, limits their interpretability, posing challenges in clinical applications. Traditional interpretable methods developed for computer vision and natural language processing may not directly translate to the distinct demands of neuroimaging. In response, our research evaluates the effectiveness and adaptability of two interpretative methods-regional age prediction and the perturbation-based saliency map approach-for predicting the brain age of neonates. Analyzing 664 T1 MRI scans with the NEOCIVET pipeline to extract brain surface and cortical features, we assess how these methods illuminate key brain regions for age prediction, focusing on technical analysis with clinical insight. Through a comparative analysis of the saliency index (SI) with relative brain age (RBA) and the examination of structural covariance networks, we uncover the saliency index's enhanced ability to pinpoint regions vital for accurate indication of clinical factors. Our results highlight the advantages of perturbation techniques in addressing the complexities of medical data, steering clinical interventions for premature neonates towards more personalized and interpretable approaches. This study not only reveals the promise of these methods in complex medical scenarios but also offers a blueprint for implementing more interpretable and clinically relevant deep learning models in healthcare settings.


Assuntos
Encéfalo , Aprendizado Profundo , Imageamento por Ressonância Magnética , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Feminino , Masculino , Interpretação de Imagem Assistida por Computador/métodos , Neuroimagem/métodos , Neuroimagem/normas
7.
J Am Chem Soc ; 146(22): 15428-15437, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38795044

RESUMO

Chemical recycling to monomers (CRM) offers a promising closed-loop approach to transition from current linear plastic economy toward a more sustainable circular paradigm. Typically, this approach has focused on modulating the ceiling temperature (Tc) of monomers. Despite considerable advancements, polymers with low Tc often face challenges such as inadequate thermal stability, exemplified by poly(γ-butyrolactone) (PGBL) with a decomposition temperature of ∼200 °C. In contrast, floor temperature (Tf)-regulated polymers, particularly those synthesized via the ring-opening polymerization (ROP) of macrolactones, inherently exhibit enhanced thermodynamic stability as the temperature increases. However, the development of those Tf regulated chemically recyclable polymers remains relatively underexplored. In this context, by judicious design and efficient synthesis of a biobased macrocyclic diester monomer (HOD), we developed a type of Tf -regulated closed-loop chemically recyclable poly(ketal-ester) (PHOD). First, the entropy-driven ROP of HOD generated high-molar mass PHOD with exceptional thermal stability with a Td,5% reaching up to 353 °C. Notably, it maintains a high Td,5% of 345 °C even without removing the polymerization catalyst. This contrasts markedly with PGBL, which spontaneously depolymerizes back to the monomer above its Tc in the presence of catalyst. Second, PHOD displays outstanding closed-loop chemical recyclability at room temperature within just 1 min with tBuOK. Finally, copolymerization of pentadecanolide (PDL) with HOD generated high-performance copolymers (PHOD-co-PPDL) with tunable mechanical properties and chemical recyclability of both components.

8.
Mol Biol Evol ; 40(12)2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38061001

RESUMO

Parasitoids introduce various virulence factors when parasitism occurs, and some taxa generate teratocytes to manipulate the host immune system and metabolic homeostasis for the survival and development of their progeny. Host-parasitoid interactions are extremely diverse and complex, yet the evolutionary dynamics are still poorly understood. A category of serpin genes, named CvT-serpins, was discovered to be specifically expressed and secreted by the teratocytes of Cotesia vestalis, an endoparasitoid of the diamondback moth Plutella xylostella. Genomic and phylogenetic analysis indicated that the C. vestalis serpin genes are duplicated and most of them are clustered into 1 monophyletic clade. Intense positive selection was detected at the residues around the P1-P1' cleavage sites of the Cv-serpin reactive center loop domain. Functional analyses revealed that, in addition to the conserved function of melanization inhibition (CvT-serpins 1, 16, 18, and 21), CvT-serpins exhibited novel functions, i.e. bacteriostasis (CvT-serpins 3 and 5) and nutrient metabolism regulation (CvT-serpins 8 and 10). When the host-parasitoid system is challenged with foreign bacteria, CvT-serpins act as an immune regulator to reprogram the host immune system through sustained inhibition of host melanization while simultaneously functioning as immune effectors to compensate for this suppression. In addition, we provided evidence that CvT-serpin8 and 10 participate in the regulation of host trehalose and lipid levels by affecting genes involved in these metabolic pathways. These findings illustrate an exquisite tactic by which parasitoids win out in the parasite-host evolutionary arms race by manipulating host immune and nutrition homeostasis via adaptive gene evolution and neofunctionalization.


Assuntos
Mariposas , Parasitos , Serpinas , Vespas , Animais , Serpinas/genética , Filogenia , Mariposas/genética , Homeostase , Larva/metabolismo , Vespas/genética
9.
Small ; 20(11): e2305459, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37922532

RESUMO

Electrocatalyst engineering from the atomic to macroscopic level of electrocatalysts is one of the most powerful routes to boost the performance of electrochemical devices. However, multi-scale structure engineering mainly focuses on the range of atomic-to-particle scale such as hierarchical porosity engineering, while catalyst engineering at the macroscopic level, such as the arrangement configuration of nanoparticles, is often overlooked. Here, a 2D carbon polyhedron array with a multi-scale engineered structure via facile chemical etching, ice-templating induced self-assembly, and high-temperature pyrolysis processes is reported. Controlled phytic acid etching of the carbon precursor introduces homogeneous atomic phosphorous and nitrogen doping, as well as a well-defined mesoporous structure. Subsequent ice-templated self-assembly triggers the formation of a 2D particle array superstructure. The atomic-level doping gives rise to high intrinsic activity, while the well-engineered porous structure and particle arrangement addresses the mass transport limitations at the microscopic particle level and macroscopic electrode level. As a result, the as-prepared electrocatalyst delivers outstanding performance toward oxygen reduction reaction in both acidic and alkaline media, which is better than recently reported state-of-the-art metal-free electrocatalysts. Molecular dynamics simulation together with extensive characterizations indicate that the performance enhancement originates from multi-scale structural synergy.

10.
Planta ; 259(5): 119, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594473

RESUMO

MAIN CONCLUSION: S. plumbizincicola genetic transformation was optimized using a self-excision molecular-assisted transformation system by integrating the SpGRF4/SpGIF1 gene with XVE and Cre/loxP. Sedum plumbizincicola, despite being an excellent hyperaccumulator of cadmium and zinc with significant potential for soil pollution phytoremediation on farmland, has nonetheless trailed behind other major model plants in genetic transformation technology. In this study, different explants and SpGRF4-SpGIF1 genes were used to optimize the genetic transformation of S. plumbizincicola. We found that petiole and stem segments had higher genetic transformation efficiency than cluster buds. Overexpression of SpGRF4-SpGIF1 could significantly improve the genetic transformation efficiency and shorten the period of obtaining regenerated buds. However, molecular assistance with overexpression of SpGRF4-SpGIF1 leads to abnormal morphology, resulting in plant tissue enlargement and abnormal growth. Therefore, we combined SpGRF4-SpGIF1 with XVE and Cre/loxP to obtain DNA autocleavage transgenic plants induced by estradiol, thereby ensuring normal growth in transgenic plants. This study optimized the S. plumbizincicola genetic transformation system, improved the efficiency of genetic transformation, and established a self-excision molecular-assisted transformation system. This work also established the basis for studying S. plumbizincicola gene function, and for S. plumbizincicola breeding and germplasm innovation.


Assuntos
Sedum , Poluentes do Solo , Melhoramento Vegetal , Cádmio , Biodegradação Ambiental , Transformação Genética , Solo
11.
Reproduction ; 167(3)2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38206180

RESUMO

In brief: Lineage specification plays a vital role in preimplantation development. TEAD4 is an essential transcription factor for trophectoderm lineage specification in mice but not in cattle. Abstract: Tead4, a critical transcription factor expressed during preimplantation development, is essential for the expression of trophectoderm-specific genes in mice. However, the functional mechanism of TEAD4 in mouse preimplantation development and its conservation across mammals remain unclear. Here, we report that Tead4 is a crucial transcription factor necessary for blastocyst formation in mice. Disruption of Tead4 through base editing results in developmental arrest at the morula stage. Additionally, RNA-seq analysis reveals dysregulation of 670 genes in Tead4 knockout embryos. As anticipated, Tead4 knockout led to a decrease in trophectoderm genes Cdx2 and Gata3. Intriguingly, we observed a reduction in Krt8, suggesting that Tead4 influences the integrity of the trophectoderm epithelium in mice. More importantly, we noted a dramatic decrease in nuclear Yap in outside cells for Tead4-deficient morula, indicating that Tead4 directly regulates Hippo signaling. In contrast, bovine embryos with TEAD4 depletion could still develop to blastocysts with normal expression of CDX2, GATA3, and SOX2, albeit with a decrease in total cell number and ICM cell number. In conclusion, we propose that Tead4 regulates mouse blastocyst formation via Krt8 and Yap, both of which are critical regulators of mouse preimplantation development.


Assuntos
Proteínas de Ligação a DNA , Fatores de Transcrição , Animais , Bovinos , Camundongos , Blastocisto/metabolismo , Fator de Transcrição CDX2/genética , Fator de Transcrição CDX2/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Desenvolvimento Embrionário/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Via de Sinalização Hippo , Mamíferos/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
12.
Int Urogynecol J ; 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39373911

RESUMO

INTRODUCTION AND HYPOTHESIS: Vaginal delivery and resulting pelvic floor muscle (PFM) dysfunction are significant risk factors for pelvic floor dysfunction (PFD). Despite this, the biological basis underlying PFD after childbirth remain unclear. This study was aimed at assessing the early response of the vaginal wall and PFM to simulated birth injury (SBI) in rats. METHODS: Forty female Sprague-Dawley rats were divided into four groups: control (sham operation), and 1, 4, and 14 days post-injury. In the SBI groups, a catheter was inserted into the vagina with 130 g of weight attached to the end, and the balloon was inflated to 5 ml for 2 h. Evaluation of vaginal tissues and PFMs included histological, immunohistochemical, Western blot, and uniaxial biomechanical testing. RESULTS: In the vaginal wall, the SBI group showed significantly lower COL1A1 expression and higher MMP-2 and MMP-9 expression. At 4 and 14 days post-injury, there was a significant decrease in PFM fiber area and increased collagen content. The SBI group also exhibited significant increases in the expression of Nrf2, NQO1, HO-1, and SOD-2, indicating involvement of oxidative stress in both the vaginal wall and PFMs. Protein expression of Pax7 and MyoG, as well as the number of fibers with centralized nuclei, continued to increase significantly after SBI. Additionally, the vaginal wall of the SBI group showed a decreasing trend in tensile strength and elastic modulus, with a greater ultimate strain. CONCLUSION: Extracellular matrix remodeling, oxidative stress, decreased biomechanical properties, and muscle dysmyogenesis may collectively contribute to increased susceptibility to PFD development.

13.
PLoS Genet ; 17(9): e1009751, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34492000

RESUMO

Some DNA viruses infect host animals usually by integrating their DNAs into the host genome. However, the mechanisms for integration remain largely unknown. Here, we find that Cotesia vestalis bracovirus (CvBV), a polydnavirus of the parasitic wasp C. vestalis (Haliday), integrates its DNA circles into host Plutella xylostella (L.) genome by two distinct strategies, conservatively and randomly, through high-throughput sequencing analysis. We confirmed that the conservatively integrating circles contain an essential "8+5" nucleotides motif which is required for integration. Then we find CvBV circles are integrated into the caterpillar's genome in three temporal patterns, the early, mid and late stage-integration. We further identify that three CvBV-encoded integrases are responsible for some, but not all of the virus circle integrations, indeed they mainly participate in the processes of early stage-integration. Strikingly, we find two P. xylostella retroviral integrases (PxIN1 and PxIN2) are highly induced upon wasp parasitism, and PxIN1 is crucial for integration of some other early-integrated CvBV circles, such as CvBV_04, CvBV_12 and CvBV_24, while PxIN2 is important for integration of a late-integrated CvBV circle, CvBV_21. Our data uncover a novel mechanism in which CvBV integrates into the infected host genome, not only by utilizing its own integrases, but also by recruiting host enzymes. These findings will strongly deepen our understanding of how bracoviruses regulate and integrate into their hosts.


Assuntos
DNA Viral/genética , Integrases/metabolismo , Mariposas/genética , Polydnaviridae/fisiologia , Animais , Interações Hospedeiro-Parasita/genética , Mariposas/enzimologia , Mariposas/parasitologia , Polydnaviridae/genética , Vespas/genética , Vespas/fisiologia
14.
Nano Lett ; 23(4): 1435-1444, 2023 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-36752657

RESUMO

A light-activated chemically reactive fibrous patch (ChemPatch) with tissue adhesion and wound healing activity was developed for preventing postoperative peritoneal adhesion. ChemPatch was constructed by an integrative electrospinning fabrication strategy, generating multifunctional PCL-NHS fibers encapsulating antioxidant curcumin and MnO2 nanoparticles. ChemPatch exhibited excellent photothermal conversion, which not only reformed the physical state to match the tissue but also improved conjugation between ChemPatch and tissues, allowing for strong attachment. Importantly, ChemPatch possessed good antioxidant and radical scavenging activity, which protected cells in an oxidative microenvironment and improved tissue regeneration. Particularly, ChemPatch acted as a multifunctional barrier and could not only promote reepithelialization and revascularization in wound defect model but simultaneously ameliorate inflammation and prevent postoperative peritoneal adhesion in a mouse cecal defect model. Thus, ChemPatch represents a dual-active bioadhesive barrier for reducing the incidence and severity of peritoneal adhesions.


Assuntos
Cirurgia Geral , Complicações Pós-Operatórias , Telas Cirúrgicas , Aderências Teciduais , Cicatrização , Cavidade Peritoneal/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Aderências Teciduais/prevenção & controle , Luz , Telas Cirúrgicas/normas , Cirurgia Geral/instrumentação , Cirurgia Geral/métodos , Curcumina/uso terapêutico , Nanopartículas/química , Nanopartículas/uso terapêutico , Óxido de Magnésio/uso terapêutico , Resultado do Tratamento , Camundongos Endogâmicos ICR , Animais , Camundongos , Linhagem Celular
15.
Angew Chem Int Ed Engl ; 63(22): e202404179, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38488293

RESUMO

Chemical recycling of polymers to monomers presents a promising solution to the escalating crisis associated with plastic waste. Despite considerable progress made in this field, the primary efforts have been focused on redesigning new monomers to produce readily recyclable polymers. In contrast, limited research into the potential of seemingly "non-polymerizable" monomers has been conducted. Herein, we propose a paradigm that leverages a "chaperone"-assisted strategy to establish closed-loop circularity for a "non-polymerizable" α, ß-conjugated lactone, 5,6-dihydro-2H-pyran-2-one (DPO). The resulting PDPO, a structural analogue of poly(δ-valerolactone) (PVL), exhibits enhanced thermal properties with a melting point (Tm) of 114 °C and a decomposition temperature (Td,5%) of 305 °C. Notably, owing to the structural similarity between DPO and δ-VL, the copolymerization generates semi-crystalline P(DPO-co-VL)s irrespective of the DPO incorporation ratio. Intriguingly, the inherent C=C bonds in P(DPO-co-VL)s enable their convenient post-functionalization via Michael-addition reaction. Lastly, PDPO was demonstrated to be chemically recyclable via ring-closing metathesis (RCM), representing a significant step towards the pursuit of enabling the closed-loop circularity of "non-polymerizable" lactones without altering the ultimate polymer structure.

16.
Angew Chem Int Ed Engl ; : e202414075, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39313469

RESUMO

Metal-free covalent organic frameworks (COFs) are employed in oxygen reduction reactions (ORR) because of their diverse structural units and controllable catalytic sites, and the edge sites have high catalytic activity than the basal sites. However, it is still challenge to modulate the edge sites in COFs, because the extended frameworks in two- or three-dimensional topologies resulted in limited edge parts. In this study, we have demonstrated the edge site modulation engineering based on one dimensional (1D) COFs to catalyze the ORR, which featured distinct edge groups-carbonyl, diaminopyrazine, phenylimidazole, and benzaldehyde imidazole units. The synthesized COFs had same ordered frameworks, similar pore structure, but had different electronic states of the carbons along the edge sites, which results in tailored catalytic properties. Notably, the COF functionalized with a phenylimidazole edge group exhibited superior catalytic performance compared to the other synthesized COFs. And the theoretical calculation further revealed the different edge sites have tunable binding ability of the intermediates OOH*, which contributed modulated activity. Our findings introduce a novel way for designing COFs optimized for ORR applications through molecular level control of edge sites.

17.
Development ; 147(1)2020 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-31826864

RESUMO

Cilia rotation-driven nodal flow is crucial for the left-right (L-R) break in symmetry in most vertebrates. However, the mechanism by which the flow signal is translated to asymmetric gene expression has been insufficiently addressed. Here, we show that Hedgehog (Hh) signalling is asymmetrically activated (L

Assuntos
Cílios/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Proteínas Hedgehog/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Anfioxos/embriologia , Animais , Evolução Biológica , Padronização Corporal , Embrião não Mamífero/fisiologia , Embrião não Mamífero/ultraestrutura , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Anfioxos/genética , Anfioxos/metabolismo , Anfioxos/ultraestrutura
18.
PLoS Pathog ; 17(3): e1009365, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33647060

RESUMO

Parasites alter host energy homeostasis for their own development, but the mechanisms underlying this phenomenon remain largely unknown. Here, we show that Cotesia vestalis, an endoparasitic wasp of Plutella xylostella larvae, stimulates a reduction of host lipid levels. This process requires excess secretion of P. xylostella tachykinin (PxTK) peptides from enteroendocrine cells (EEs) in the midgut of the parasitized host larvae. We found that parasitization upregulates PxTK signaling to suppress lipogenesis in midgut enterocytes (ECs) in a non-cell-autonomous manner, and the reduced host lipid level benefits the development of wasp offspring and their subsequent parasitic ability. We further found that a C. vestalis bracovirus (CvBV) gene, CvBV 9-2, is responsible for PxTK induction, which in turn reduces the systemic lipid level of the host. Taken together, these findings illustrate a novel mechanism for parasite manipulation of host energy homeostasis by a symbiotic bracovirus gene to promote the development and increase the parasitic efficiency of an agriculturally important wasp species.


Assuntos
Interações Hospedeiro-Parasita/imunologia , Metabolismo dos Lipídeos/fisiologia , Parasitos/virologia , Polydnaviridae/genética , Animais , Sistema Digestório/metabolismo , Interações Hospedeiro-Parasita/genética , Larva/metabolismo , Larva/virologia , Metabolismo dos Lipídeos/imunologia , Parasitos/patogenicidade , Polydnaviridae/patogenicidade , Transdução de Sinais/imunologia , Transdução de Sinais/fisiologia , Vespas/fisiologia , Vespas/virologia
19.
Opt Express ; 31(25): 42524-42538, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38087624

RESUMO

X-ray microspectroscopic techniques are essential for studying morphological and chemical changes in materials, providing high-resolution structural and spectroscopic information. However, its practical data analysis for reliably retrieving the chemical states remains a major obstacle to accelerating the fundamental understanding of materials in many research fields. In this work, we propose a novel data formulation model for X-ray microspectroscopy and develop a dedicated unmixing framework to solve this problem, which is robust to noise and spectral variability. Moreover, this framework is not limited to analyzing two-state material chemistry, making it an effective alternative to conventional and widely used methods. In addition, an alternative directional multiplier method with explicit or implicit regularization is applied to obtain the solution efficiently. Our framework can accurately identify and characterize chemical states in complex and heterogeneous samples, even under challenging conditions such as low signal-to-noise ratios and overlapping spectral features. By testing six simulated datasets, our method improves the existing methods by up to 151.84% and 136.33% in terms of the peak signal-to-noise ratio (PSNR) and the structural similarity index (SSIM) for the chemical phase map. Extensive experimental results on simulated and real datasets demonstrate its effectiveness and reliability.

20.
Reproduction ; 165(3): 325-333, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36630554

RESUMO

In brief: The lineage specification during early embryonic development in cattle remains largely elusive. The present study determines the effects of trophectoderm-associated factors GATA3 and CDX2 on lineage specification during bovine early embryonic development. Abstract: Current understandings of the initiation of the trophectoderm (TE) program during mammalian embryonic development lack evidence of how TE-associated factors such as GATA3 and CDX2 participate in bovine lineage specification. In this study, we describe the effects of TE-associated factors on the expression of lineage specification marker genes such as SOX2, OCT4, NANOG, GATA6, and SOX17, by using cytosine base editor system. We successfully knockout GATA3 or CDX2 in bovine embryos with a robust efficiency. However, GATA3 or CDX2 deletion does not affect the developmental potential of embryos to reach the blastocyst stage. Interestingly, GATA3 deletion downregulates the NANOG expression in bovine blastocysts. Further analysis of the mosaic embryos shows that GATA3 is required for NANOG in the TE of bovine blastocysts. Single blastocyst RNA-seq analysis reveals that GATA3 deletion disrupts the transcriptome in bovine blastocysts. Altogether, we propose that GATA3 plays an important role in maintaining TE lineage program in bovine embryos and the functional role of GATA3 is species-specific.


Assuntos
Blastocisto , Desenvolvimento Embrionário , Animais , Bovinos , Feminino , Gravidez , Fator de Transcrição CDX2/genética , Fator de Transcrição CDX2/metabolismo , Linhagem da Célula/genética , Desenvolvimento Embrionário/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Mamíferos/genética , Transcriptoma , Fator de Transcrição GATA3/metabolismo
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