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1.
J Mol Evol ; 92(1): 21-29, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38158403

RESUMO

The Praja family is an E3 ubiquitin ligase, promoting polyubiquitination and subsequent degradation of substrates. It comprises two paralogs, praja1 and praja2. Prior research suggests these paralogs have undergone functional divergence, with examples, such as their distinct roles in neurite outgrowth. However, the specific evolutionary trajectories of each paralog remain largely unexplored preventing mechanistic understanding of functional differences between paralogs. Here, we investigated the phylogeny and divergence of the vertebrate Praja family through molecular evolutionary analysis. Phylogenetic examination of the vertebrate praja revealed that praja1 and praja2 originated from the common ancestor of placentals via gene duplication, with praja1 evolving at twice the rate of praja2 shortly after the duplication. Moreover, a unique evolutionary trajectory for praja1 relative to other vertebrate Praja was indicated, as evidenced by principal component analysis on GC content, codon usage frequency, and amino acid composition. Subsequent motif/domain comparison revealed conserved N terminus and C terminus in praja1 and praja2, together with praja1-specific motifs, including nuclear localization signal and Ala-Gly-Ser repeats. The nuclear localization signal was demonstrated to be functional in human neuroblastoma SH-SY5Y cells using deletion mutant, while praja2 was exclusively expressed in the nucleus. These discoveries contribute to a more comprehensive understanding of the Praja family's phylogeny and suggest a functional divergence between praja1 and praja2. Specifically, the shift of praja1 into the nucleus implies the degradation of novel substrates located in the nucleus as an evolutionary consequence.


Assuntos
Neuroblastoma , Sinais de Localização Nuclear , Animais , Humanos , Filogenia , Sinais de Localização Nuclear/genética , Vertebrados/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Evolução Molecular
2.
Chemistry ; : e202401590, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38749912

RESUMO

Photo-triggered phase transition is a new type of phase transition in which a photochromic crystal with a thermal phase transition transforms into an identical high-temperature phase in a temperature region lower than the thermal phase transition temperature upon light irradiation. Here, we report a second crystal that exhibits a photo-triggered phase transition, thereby demonstrating that the photo-triggered phase transition is a general phenomenon that occurs in crystals. When the chiral salicylidenephenylethylamine crystal was irradiated with ultraviolet (UV) light, the photo-triggered phase transition occurred in the temperature range -30 to -10 °C. The photo-triggered phase transition is induced by local stress due to trans-keto molecules produced by photoisomerization near the irradiated surface. Crystal cantilevers exhibited stepwise bending by the combination of the photo-triggered phase transition and photoisomerization. Alternate irradiation with UV and visible light achieved locomotion of single crystals driven by repeated stepwise bending. Finally, a detailed comparison of photo-triggered and non-photo-triggered phase transition crystals revealed that a sufficient molecular conformation change in affordable crystal voids, smooth photoisomerization, and most likely a chiral molecular arrangement are required for inducing the photo-triggered phase transition.

3.
BMC Biol ; 21(1): 245, 2023 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-37940920

RESUMO

BACKGROUND: Cerebral organoids are three-dimensional in vitro cultured brains that mimic the function and structure of the human brain. One of the major challenges for cerebral organoids is the lack of functional vasculature. Without perfusable vessels, oxygen and nutrient supplies may be insufficient for long-term culture, hindering the investigation of the neurovascular interactions. Recently, several strategies for the vascularization of human cerebral organoids have been reported. However, the generalizable trends and variability among different strategies are unclear due to the lack of a comprehensive characterization and comparison of these vascularization strategies. In this study, we aimed to explore the effect of different vascularization strategies on the nervous system and vasculature in human cerebral organoids. RESULTS: We integrated single-cell RNA sequencing data of multiple vascularized and vascular organoids and fetal brains from publicly available datasets and assessed the protocol-dependent and culture-day-dependent effects on the cell composition and transcriptomic profiles in neuronal and vascular cells. We revealed the similarities and uniqueness of multiple vascularization strategies and demonstrated the transcriptomic effects of vascular induction on neuronal and mesodermal-like cell populations. Moreover, our data suggested that the interaction between neurons and mesodermal-like cell populations is important for the cerebrovascular-specific profile of endothelial-like cells. CONCLUSIONS: This study highlights the current challenges to vascularization strategies in human cerebral organoids and offers a benchmark for the future fabrication of vascularized organoids.


Assuntos
Organoides , Análise da Expressão Gênica de Célula Única , Humanos , Células Endoteliais , Encéfalo
4.
Sci Technol Adv Mater ; 25(1): 2292485, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38259326

RESUMO

Among various metal-organic frameworks (MOFs), the zeolitic imidazole framework (ZIF), constructed by the regular arrangement of 2-methylimidazole and metal ions, has garnered significant attention due to its distinctive crystals and pore structures. Variations in the sizes and shapes of ZIF crystals have been reported by changing the synthesis parameters, such as the molar ratios of organic ligands to metal ions, choice of solvents, and temperatures. Nonetheless, the giant ZIF-8 single crystals beyond the typical range have rarely been reported. Herein, we present the synthesis of millimeter-scale single crystal ZIF-8 using the solvothermal method in N,N-diethylformamide. The resulting 1-mm single crystal is carefully characterized through N2 adsorption-desorption isotherms, scanning electron microscopy, and other analytical techniques. Additionally, single-crystal X-ray diffraction is employed to comprehensively investigate the framework's mobility at various temperatures.


Millimeter-sized ZIF-8 single crystals were synthesized using the solvothermal method. These crystals exhibit a notable BET surface area of 1681 m2∙g−1 and demonstrate a reversible change in their crystal structure.

5.
Angew Chem Int Ed Engl ; : e202405571, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38757486

RESUMO

The rational design of efficient catalysts for uric acid (UA) electrooxidation, as well as the establishment of structure-activity relationships, remains a critical bottleneck in the field of electrochemical sensing. To address these challenges, herein, a hybrid catalyst that integrates carbon-supported Pt nanoparticles and nitrogen-coordinated Mn single atoms (PtNPs/MnNC) is developed. The metal-metal interaction during annealing affords the construction of metallic-bonded Pt-Mn pairs between PtNPs and Mn single atoms, facilitating the electron transfer from PtNPs to the support and thereby optimizing the electronic structure of catalysts. More importantly, experiments and theoretical calculations provide visual proof for the 'incipient hydrous oxide adatom mediator' mechanism for UA oxidation. The Pt-Mn pairs first adsorb OH* to construct the bridged Pt-OH-Mn mediators to serve as a highly active intermediate for N-H bond dissociation and proton transfer. Benefiting from the unique electronic and geometric structure of the catalytic center and reactive intermediates, PtNPs/MnNC exhibits superior electrooxidation performance. The electrochemical sensor based on PtNPs/MnNC enables sensitive detection and discrimination of UA and dopamine in serum samples. This work offers new insights into the construction of novel electrocatalysts for sensitive sensing platforms.

6.
Biochem Biophys Res Commun ; 682: 316-324, 2023 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-37837752

RESUMO

Muscle cell cultivation, specifically the culture of artificial meat from livestock-derived cells in serum-free media is an emerging technology and has attracted much attention. However, till now, the high cost of production and environmental load have been significant deterrents. This study aims to provide an alternate growth-promoting substance that is free from animal derivatives and lowers nitrogen pollution. We have extracted water-soluble compounds from the filamentous nitrogen-fixing cyanobacteria Anabaena sp. PCC 7120 by the ultrasonication method. The heat-inactivated and molecular weight separation experiments were conducted to identify the bioactive compound present in the extract. Finally, the compounds soluble in water (CW) containing the water-soluble pigment protein, phycocyanin as a bioactive compound, was added as a growth supplement to cultivate muscle cells such as C2C12 muscle cells and quail muscle clone 7 (QM7) cells to analyze the effectiveness of the extract. The results indicated that CW had a positive role in muscle cell proliferation. A three-dimensional (3-D) cell-dense structure was fabricated by culturing QM7 cells using the extract. Furthermore, the nitrogen-fixing cyanobacterial extract has vast potential for cultured meat production without animal sera in the near future.


Assuntos
Anabaena , Cianobactérias , Nitrogênio/metabolismo , Proteínas de Bactérias/metabolismo , Cianobactérias/metabolismo , Anabaena/metabolismo , Músculos/metabolismo , Proliferação de Células , Regulação Bacteriana da Expressão Gênica
7.
Small ; 19(48): e2304450, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37518827

RESUMO

Although hollow carbon structures have been extensively studied in recent years, their interior surfaces are not fully utilized due to the lack of fluent porous channels in the closed shell walls. This study presents a tailored design of open-mouthed particles hollow cobalt/nitrogen-doped carbon with mesoporous shells (OMH-Co/NC), which exhibits sufficient accessibility and electroactivity on both the inner and outer surfaces. By leveraging the self-conglobation effect of metal sulfate in methanol, a raspberry-structured Zn/Co-ZIF (R-Zn/Co-ZIF) precursor is obtained, which is further carbonized to fabricate the OMH-Co/NC. In-depth electrochemical investigations demonstrate that the introduction of open pores can enhance mass transfer and improve the utilization of the inner active sites. Benefiting from its unique structure, the resulting OMH-Co/NC exhibits exceptional electrocatalytic oxygen reduction performance, achieving a half-wave potential of 0.865 V and demonstrating excellent durability.

8.
Mol Phylogenet Evol ; 178: 107636, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36208695

RESUMO

Phylogenetic trees are essential tools in evolutionary biology that present information on evolutionary events among organisms and molecules. From a dataset of n sequences, a phylogenetic tree of (2n-5)!! possible topologies exists, and determining the optimum topology using brute force is infeasible. Recently, a recursive graph cut on a graph-represented-similarity matrix has proven accurate in reconstructing a phylogenetic tree containing distantly related sequences. However, identifying the optimum graph cut is challenging, and approximate solutions are currently utilized. Here, a phylogenetic tree was reconstructed with an improved graph cut using a quantum-inspired computer, the Fujitsu Digital Annealer (DA), and the algorithm was named the "Normalized-Minimum cut by Digital Annealer (NMcutDA) method". First, a criterion for the graph cut, the normalized cut value, was compared with existing clustering methods. Based on the cut, we verified that the simulated phylogenetic tree could be reconstructed with the highest accuracy when sequences were diverged. Moreover, for some actual data from the structure-based protein classification database, only NMcutDA could cluster sequences into correct superfamilies. Conclusively, NMcutDA reconstructed better phylogenetic trees than those using other methods by optimizing the graph cut. We anticipate that when the diversity of sequences is sufficiently high, NMcutDA can be utilized with high efficiency.


Assuntos
Algoritmos , Computadores , Filogenia , Análise por Conglomerados , Bases de Dados de Proteínas
9.
Biomacromolecules ; 24(11): 5035-5045, 2023 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-37800307

RESUMO

Surface modification of polydimethylsiloxane (PDMS) with an extracellular matrix (ECM) is useful for enhancing stable cell attachment. However, few studies have investigated the correlation between the stability of deposited ECM and cell behavior on the PDMS surfaces in external stretched cell culture systems. Herein, covalent collagen type I (Col)-immobilized PDMS surfaces were fabricated using 3-aminopropyl-trimethoxysilane, glutaraldehyde, and Col molecules. The immobilized collagen molecules on the PDMS surface were more stable and uniform than the physisorbed collagen. The cells stably adhered to the Col-immobilized surface and proliferated even under uniaxial cyclic mechanical stretching stress (UnCyMSt), whereas the cells gradually detached from the Col-physisorbed PDMS surface, accompanied by a decrease in the number of deposited collagen molecules. Moreover, the immobilization of collagen molecules enhanced cell alignment under the UnCyMSt. This study reveals that cell adhesion, proliferation, and alignment under the UnCyMSt can be attributed to the retention of collagen molecules on the PDMS surface.


Assuntos
Colágeno Tipo I , Colágeno , Propriedades de Superfície , Colágeno/metabolismo , Adesão Celular , Dimetilpolisiloxanos , Proliferação de Células
10.
Microb Ecol ; 86(4): 2627-2641, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37479827

RESUMO

The insect gut is colonized by microbes that confer a myriad of beneficial services to the host, including nutritional support, immune enhancement, and even influence behavior. Insect gut microbes show dynamic changes due to the gut compartments, sex, and seasonal and geographic influences. Crickets are omnivorous hemimetabolous insects that have sex-specific roles, such as males producing chirping sounds for communication and exhibiting fighting behavior. However, limited information is available on their gut bacterial communities, hampering studies on functional compartmentalization of the gut and sex-specific roles of the gut microbiota in omnivorous insects. Here, we report a metagenomic analysis of the gut bacteriome of the field cricket Teleogryllus occipitalis using 16S rRNA V3-V4 amplicon sequencing to identify sex- and compartment-dependent influences on its diversity and function. The structure of the gut microbiota is strongly influenced by their gut compartments rather than sex. The species richness and diversity analyses revealed large difference in the bacterial communities between the gut compartments while minor differences were observed between the sexes. Analysis of relative abundance and predicted functions revealed that nitrogen- and oxygen-dependent metabolism and amino acid turnover were subjected to functional compartmentalization in the gut. Comparisons between the sexes revealed differences in the gut microbiota, reflecting efficiency in energy use, including glycolytic and carbohydrate metabolism, suggesting a possible involvement in egg production in females. This study provides insights into the gut compartment dependent and sex-specific roles of host-gut symbiont interactions in crickets and the industrial production of crickets.


Assuntos
Críquete , Microbioma Gastrointestinal , Gryllidae , Animais , Feminino , Masculino , RNA Ribossômico 16S/genética , Bactérias/genética
11.
J Am Chem Soc ; 144(21): 9280-9291, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35604393

RESUMO

This study demonstrates a special ultrathin N-doped graphene nanomesh (NGM) as a robust scaffold for highly exposed Fe-N4 active sites. Significantly, the pore sizes of the NGM can be elaborately regulated by adjusting the thermal exfoliation conditions to simultaneously disperse and anchor Fe-N4 moieties, ultimately leading to highly loaded Fe single-atom catalysts (SA-Fe-NGM) and a highly exposed morphology. The SA-Fe-NGM is found to deliver a superior oxygen reduction reaction (ORR) activity in acidic media (half-wave potential = 0.83 V vs RHE) and a high power density of 634 mW cm-2 in the H2/O2 fuel cell test. First-principles calculations further elucidate the possible catalytic mechanism for ORR based on the identified Fe-N4 active sites and the pore size distribution analysis. This work provides a novel strategy for constructing highly exposed transition metals and nitrogen co-doped carbon materials (M-N-C) catalysts for extended electrocatalytic and energy storage applications.

12.
Small ; 18(25): e2107182, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35570326

RESUMO

This article reviews recent fabrication methods for surface-enhanced Raman spectroscopy (SERS) substrates with a focus on advanced nanoarchitecture based on noble metals with special nanospaces (round tips, gaps, and porous spaces), nanolayered 2D materials, including hybridization with metallic nanostructures (NSs), and the contemporary repertoire of nanoarchitecturing with organic molecules. The use of SERS for multidisciplinary applications has been extensively investigated because the considerably enhanced signal intensity enables the detection of a very small number of molecules with molecular fingerprints. Nanoarchitecture strategies for the design of new NSs play a vital role in developing SERS substrates. In this review, recent achievements with respect to the special morphology of metallic NSs are discussed, and future directions are outlined for the development of available NSs with reproducible preparation and well-controlled nanoarchitecture. Nanolayered 2D materials are proposed for SERS applications as an alternative to the noble metals. The modern solutions to existing limitations for their applications are described together with the state-of-the-art in bio/environmental SERS sensing using 2D materials-based composites. To complement the existing toolbox of plasmonic inorganic NSs, hybridization with organic molecules is proposed to improve the stability of NSs and selectivity of SERS sensing by hybridizing with small or large organic molecules.


Assuntos
Nanoestruturas , Análise Espectral Raman , Nanoestruturas/química , Análise Espectral Raman/métodos
13.
Small ; 18(33): e2203411, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35863911

RESUMO

Controlling the morphology, composition, and crystalline phase of mesoporous nonnoble metal catalysts is essential for improving their performance. Herein, well-defined P- and B-codoped NiFe alloy mesoporous nanospheres (NiFeB-P MNs) with an adjustable Ni/Fe ratio and large mesopores (11 nm) are synthesized via soft-template-based chemical reduction and a subsequent phosphine-vapor-based phosphidation process. Earth-abundant NiFe-based materials are considered promising electrocatalysts for the oxygen evolution reaction (OER) because of their low cost and high intrinsic catalytic activity. The resulting NiFeB-P MNs exhibit a low OER overpotential of 252 mV at 10 mA cm-2 , which is significantly smaller than that of B-doped NiFe MNs (274 mV) and commercial RuO2 (269 mV) in alkaline electrolytes. Thus, this work highlights the practicality of designing mesoporous nonnoble metal structures and the importance of incorporating P in metallic-B-based alloys to modify their electronic structure for enhancing their intrinsic activity.

14.
Photochem Photobiol Sci ; 21(12): 2169-2177, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36058993

RESUMO

In this study, the conversion of self-assembled structures into continuous polymeric structures by linking the self-assembled molecules using the [2 + 2]-cycloaddition reaction was investigated. Synthesized bio-inspired thymine-based bolaamphiphilic molecules were designed to force the interactions between two molecules to engage two thymines in their self-assembled structure to undergo a cycloaddition reaction. Thymine-based bolaamphiphilic molecules were designed and synthesized using different phenylene spacers based on aromatic substituents (ortho-) (meta-) (para-). The formed self-assembled structures from these molecules were characterized and compared using molecular mechanical simulations. Simulations were performed to discuss the relationship between the inter- and intramolecular cycloaddition sensitivity to different substituents. This study provides a strategy for creating higher molecular weight linear polymers by controlling the photocyclization sites within the self-assembly by spacers between thymines. An intermolecular [2 + 2] cycloaddition reaction of thymine-based bolaamphiphilic molecules proceeded within the self-assembled nano-ribbon-like structure to form the continuous covalent structure.


Assuntos
Timina , Reação de Cicloadição
15.
J Am Chem Soc ; 143(23): 8866-8877, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34096298

RESUMO

Mechanically responsive crystals have been increasingly explored, mainly based on photoisomerization. However, photoisomerization has some disadvantages for crystal actuation, such as a slow actuation speed, no actuation of thick crystals, and a narrow wavelength range. Here we report photothermally driven fast-bending actuation and simulation of a salicylideneaniline derivative crystal with an o-amino substituent in enol form. Under ultraviolet (UV) light irradiation, these thin (<20 µm) crystals bent but the thick (>40 µm) crystals did not due to photoisomerization; in contrast, thick crystals bent very quickly (in several milliseconds) due to the photothermal effect, even by visible light. Finally, 500 Hz high-frequency bending was achieved by pulsed UV laser irradiation. The generated photothermal energy was estimated based on the photodynamics using femtosecond transient absorption. Photothermal bending is caused by a nonsteady temperature gradient in the thickness direction due to the heat conduction of photothermal energy generated near the crystal surface. The temperature gradient was calculated based on the one-dimensional nonsteady heat conduction equation to simulate photothermally driven crystal bending successfully. Most crystals that absorb light have their own photothermal effects. It is expected that the creation and design of actuation of almost all crystals will be possible via the photothermal effect, which cannot be realized by photoisomerization, and the potential and versatility of crystals as actuation materials will expand in the near future.

16.
Biochem Biophys Res Commun ; 524(1): 236-241, 2020 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-31983437

RESUMO

Cereblon (CRBN) was identified as a gene that causes intellectual disabilities. The encoded CRBN protein, containing 442 amino acids, is located in several organs. Cytosolic CRBN was reported to mainly act as a component of the E3 ubiquitin ligase complex. CRBN is one of the substrate receptors of the E3 ubiquitin ligase complex and promotes the degradation of targeted proteins. Studies have reported that CRBN recognizes the C-terminal region of the amyloid precursor protein (APP), a protein known for its involvement in the development of Alzheimer's disease. Although CRBN may interact with the C-terminal region of APP in mice, the CRBN-mediated degradation mechanism of human APP remains unclear. Here, we analyzed the CRBN-mediated degradation mechanism of human APP via the ubiquitin-proteasome system. Immunoprecipitation experiments showed that CRBN interacts with human full-length APP via its C-terminal region. Next, we examined CRBN-mediated degradation of APP in the ubiquitin-proteasome system. CRBN recognizes Lys751 in human APP and ubiquitinates it in SH-SY5Y cells. Overexpression of CRBN decreased wild-type APP expression levels. In contrast, the expression level of K751R APP remained unchanged by CRBN overexpression, while knockdown of endogenous CRBN increased APP levels. As such, our results suggest that CRBN ubiquitinates Lys751 of human APP thereby degrading it via the ubiquitin-proteasome system.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Ubiquitina/metabolismo , Sequência de Aminoácidos , Precursor de Proteína beta-Amiloide/química , Animais , Células CHO , Linhagem Celular Tumoral , Cricetinae , Cricetulus , Humanos , Lisina/metabolismo , Inibidores de Proteassoma/farmacologia , Agregados Proteicos/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Ubiquitina-Proteína Ligases , Ubiquitinação/efeitos dos fármacos
17.
Small ; 16(10): e1906707, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32022431

RESUMO

Selective hydrogenation of nitriles is an industrially relevant synthetic route for the preparation of primary amines. Amorphous metal-boron alloys have a tunable, glass-like structure that generates a high concentration of unsaturated metal surface atoms that serve as active sites in hydrogenation reactions. Here, a method to create nanoparticles composed of mesoporous 3D networks of amorphous nickel-boron (Ni-B) alloy is reported. The hydrogenation of benzyl cyanide to ß-phenylethylamine is used as a model reaction to assess catalytic performance. The mesoporous Ni-B alloy spheres have a turnover frequency value of 11.6 h-1 , which outperforms non-porous Ni-B spheres with the same composition. The bottom-up synthesis of mesoporous transition metal-metalloid alloys expands the possible reactions that these metal architectures can perform while simultaneously incorporating more Earth-abundant catalysts.

18.
Mol Phylogenet Evol ; 135: 78-85, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30836149

RESUMO

Cereblon (CRBN) is a substrate receptor for an E3 ubiquitin ligase that directly binds to target proteins resulting in cellular activities, such as energy metabolism, membrane potential regulation, and transcription factor degradation. Genetic mutations in human CRBN lead to intellectual disabilities. In addition, it draws pathological attention because direct binding with immunomodulatory drugs can cure multiple myeloma (MM) and lymphocytic leukemia. To further explore the function of CRBN, we focused on its molecular evolution. Since CRBN interacts directly with its substrates and is widely conserved in vertebrates, evolutionary study to identify the selective pressure on CRBN that occur during CRBN-substrate interaction is an effective approach to search for a novel active site. Using mammalian CRBN sequences, dN/dS analysis was conducted to detect positive selection. By multiple sequence alignment we found that the residue at position 366 was under positive selection. This residue is present in the substrate-binding domain of CRBN. Most mammals harbor cysteine at position 366, whereas rodents and chiroptera have serine at this site. Subsequently, we constructed a C366S human CRBN to confirm the potential of positive selection. Auto-ubiquitination activity occurs in E3 ubiquitin ligases, including CRBN, and increased in C366S CRBN, which lead to the conclusion that E3 ubiquitin ligase activity may have changed over the course of mammalian evolution. Furthermore, binding with AMP-activated protein kinase was augmented when the substitution was present, which is supported by coevolution analysis. These results suggest that the molecular evolution of CRBN occurred through codon-based positive selection, providing a new approach to investigate CRBN function.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Peptídeo Hidrolases/genética , Peptídeo Hidrolases/metabolismo , Seleção Genética , Ubiquitina-Proteína Ligases/metabolismo , Animais , Linhagem Celular Tumoral , Códon/genética , Evolução Molecular , Humanos , Mamíferos/metabolismo , Mutação/genética , Filogenia , Ligação Proteica , Ubiquitinação
19.
Org Biomol Chem ; 17(17): 4200-4203, 2019 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-30932119

RESUMO

Chiral crystals of the only achiral proteinogenic α-amino acid, glycine induced the asymmetric autocatalysis with amplification of enantiomeric excess (ee). The P31 crystals of γ-glycine, which display positive Cotton effect (CD) at around 215 nm, mediate the asymmetric autocatalysis to yield (R)-pyrimidyl alkanol with high ee. In contrast, the enantiomorphic P32 crystals, which display negative Cotton effect, afford (S)-alkanol after the significant amplification of ee by asymmetric autocatalysis.

20.
BMC Genomics ; 19(1): 330, 2018 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-29728068

RESUMO

BACKGROUND: Allopolyploidy is a genomic structure wherein two or more sets of chromosomes derived from divergent parental species coexist within an organism. It is a prevalent genomic configuration in plants, as an important source of genetic variation, and also frequently confers environmental adaptability and increased crop productivity. We previously reported the oleaginous marine diatom Fistulifera solaris JPCC DA0580 to be a promising host for biofuel production and that its genome is allopolyploid, which had never previously been reported in eukaryotic microalgae. However, the study of allopolyploidy in F. solaris was hindered by the difficulty in classifying the homoeologous genes based on their progenitor origins, owing to the shortage of diatom genomic references. RESULTS: In this study, the allopolyploid genome of F. solaris was tentatively classified into two pseudo-parental subgenomes using sequence analysis based on GC content and codon frequency in each homoeologous gene pair. This approach clearly separated the genome into two distinct fractions, subgenome Fso_h and Fso_l, which also showed the potency of codon usage analysis to differentiate the allopolyploid subgenome. Subsequent homoeolog expression bias analysis revealed that, although both subgenomes appear to contribute to global transcription, there were subgenomic preferences in approximately 61% of homoeologous gene pairs, and the majority of these genes showed continuous bias towards a specific subgenome during lipid accumulation. Additional promoter analysis indicated the possibility of promoter motifs involved in biased transcription of homoeologous genes. Among these subgenomic preferences, genes involved in lipid metabolic pathways showed interesting patterns in that biosynthetic and degradative pathways showed opposite subgenomic preferences, suggesting the possibility that the oleaginous characteristics of F. solaris derived from one of its progenitors. CONCLUSIONS: We report the detailed genomic structure and expression patterns in the allopolyploid eukaryotic microalga F. solaris. The allele-specific patterns reported may contribute to the oleaginous characteristics of F. solaris and also suggest the robust oleaginous characteristics of one of its progenitors. Our data reveal novel aspects of allopolyploidy in a diatom that is not only important for evolutionary studies but may also be advantageous for biofuel production in microalgae.


Assuntos
Diatomáceas/genética , Expressão Gênica , Composição de Bases , Biocombustíveis , Códon , Diatomáceas/metabolismo , Genoma , Metabolismo dos Lipídeos/genética , Redes e Vias Metabólicas/genética , Microalgas/genética , Microalgas/metabolismo , Poliploidia , Transcriptoma
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