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1.
Biosens Bioelectron ; 258: 116342, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38705071

RESUMO

In biological systems, nucleosides play crucial roles in various physiological processes. In this study, we designed and synthesized four achiral anthracene-based tetracationic nanotubes (1-4) as artificial hosts and chiroptical sensors for nucleosides in aqueous media. Notably, different nanotubes exhibit varied chirality sensing on circular dichroism (CD)/circularly polarized luminescence (CPL) spectra through the host-guest complexation, which prompted us to explore the factors influencing their chiroptical responses. Through systematic host-guest experiments, the structure-chirality sensing relationship between achiral anthracene-based tetracationic nanotubes and nucleosides in the host-guest complexation was unraveled. Firstly, the CD response originates from the anthracene rings situated at the side-wall position, resulting from the right-handed (P)- or left-handed (M)-twisted conformation of the macrocyclic structure. Secondly, the CPL signal is influenced by the presence of anthracene rings at the linking-wall position, which results from intermolecular chiral twisted stacking between these anthracene rings. Therefore, these nanotubes can serve as chiroptical sensor arrays to enhance the accuracy of nucleotide recognition through principal component analysis (PCA) analysis based on the diversified CD spectra. This study provides insights for the construction of adaptive chirality from achiral nanotubes with dynamic conformational nature and might facilitate further design of chiral functional materials for several applications.


Assuntos
Antracenos , Técnicas Biossensoriais , Dicroísmo Circular , Nanotubos , Nucleosídeos , Antracenos/química , Nanotubos/química , Técnicas Biossensoriais/métodos , Nucleosídeos/química , Água/química , Estereoisomerismo
2.
Bioinformatics ; 40(3)2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38426338

RESUMO

MOTIVATION: Retrosynthesis is a critical task in drug discovery, aimed at finding a viable pathway for synthesizing a given target molecule. Many existing approaches frame this task as a graph-generating problem. Specifically, these methods first identify the reaction center, and break a targeted molecule accordingly to generate the synthons. Reactants are generated by either adding atoms sequentially to synthon graphs or by directly adding appropriate leaving groups. However, both of these strategies have limitations. Adding atoms results in a long prediction sequence that increases the complexity of generation, while adding leaving groups only considers those in the training set, which leads to poor generalization. RESULTS: In this paper, we propose a novel end-to-end graph generation model for retrosynthesis prediction, which sequentially identifies the reaction center, generates the synthons, and adds motifs to the synthons to generate reactants. Given that chemically meaningful motifs fall between the size of atoms and leaving groups, our model achieves lower prediction complexity than adding atoms and demonstrates superior performance than adding leaving groups. We evaluate our proposed model on a benchmark dataset and show that it significantly outperforms previous state-of-the-art models. Furthermore, we conduct ablation studies to investigate the contribution of each component of our proposed model to the overall performance on benchmark datasets. Experiment results demonstrate the effectiveness of our model in predicting retrosynthesis pathways and suggest its potential as a valuable tool in drug discovery. AVAILABILITY AND IMPLEMENTATION: All code and data are available at https://github.com/szu-ljh2020/MARS.


Assuntos
Benchmarking , Descoberta de Drogas , Fases de Leitura
3.
Chem Sci ; 15(10): 3758-3766, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38455015

RESUMO

Chirality transfer for natural chiral biomolecules can reveal the indispensable role of chiral structures in life and can be used to develop the chirality-sensing biomolecular recognition. Here, we report the synthesis and characterization of a series of achiral supramolecular organic frameworks (SOF-1, SOF-2, and SOF-3), constructed from cucurbit[8]uril (CB[8]) and tetraphenylethene (TPE) derivatives (1, 2, and 3), respectively, as chirality-sensing platforms to explore their chirality transfer mechanism for peptides in water. Given the right-handed (P) and left-handed (M) rotational conformation of TPE units and the selective binding of CB[8] to aromatic amino acids, these achiral SOFs can be selectively triggered in water by peptides containing N-terminal tryptophan (W) and phenylalanine (F) residues into their P- or M-rotational conformation, exhibiting significantly different circular dichroism (CD) spectra. Although various peptides have the same l-type chiral configuration, they can induce positive CD signals of SOF-1 and negative CD signals of SOF-2 and SOF-3, respectively. Based on the structural analysis of the linkage units between CB[8] and TPE units in these SOFs, a "gear-driven"-type chirality transfer mechanism has been proposed to visually illustrate the multiple-step chirality transfer process from the recognition site in the CB[8]'s cavity to TPE units. Furthermore, by utilizing the characteristic CD signals generated through the "gear-driven"-type chirality transfer, these SOFs can serve as chiroptical sensor arrays to effectively recognize and distinguish various peptides based on their distinctive CD spectra.

4.
Zhongguo Gu Shang ; 36(10): 932-5, 2023 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-37881924

RESUMO

OBJECTIVE: To study the corretation between the cross-sectional area of hamstring tenden measured by MRI and gragt in anterior cruciate ligament rexonstruction. METHODS: MRI data of 50 patients who planned to undergo anterior cruciate ligament reconstruction from November 2021 to March 2022 were collected, including 32 males and 18 females, aged from 19 to 48 years old with an average of(31.1±8.7) years. Before the operation, the semitendinosus and gracilis tendons were measured and recorded by MRI, and then the anterior cruciate ligament was reconstructed under arthroscope. During the operation, gracilis and semitendinosus tendons were taken to prepare the final tendon to be transplanted, and the diameter of the prepared final graft was measured during the operation. Finally, the data were analyzed by statistical software. RESULTS: The cross sectional areas of semitendinosus tendon, gracilis tendon, semitendinosus tendon and gracilis tendon measured by MRI were significantly and positively correlated with the diameter of grafts required in anterior cruciate ligament surgery, the r values were 0.858, 0.728, 0.842(P<0.001), respectively. The area under curre (AUC), sensitivity, and specificity of the sum of the cross sectional areas of semitendinosus tendon and gracilis tendon were 0.925, 90.48%, and 85.71%, respectively. CONCLUSION: In patients undergoing anterior cruciate ligament reconstruction, preoperative MRI measurement has a strong statistical correlation with the diameter of hamstring muscle transplantation during operation. The sum of the cross sectional areas of semitendinosus tendon and gracilis tendon has a high predictive value for the diameter of grafts during anterior cruciate ligament reconstruction, and can predict the size of grafts during operation.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Tendões dos Músculos Isquiotibiais , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Tendões dos Músculos Isquiotibiais/cirurgia , Tendões dos Músculos Isquiotibiais/transplante , Lesões do Ligamento Cruzado Anterior/diagnóstico por imagem , Lesões do Ligamento Cruzado Anterior/cirurgia , Ligamento Cruzado Anterior/diagnóstico por imagem , Ligamento Cruzado Anterior/cirurgia , Imageamento por Ressonância Magnética
5.
Nat Commun ; 14(1): 5976, 2023 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-37749088

RESUMO

Chronic infection with the bacterial pathogen Pseudomonas aeruginosa often leads to coexistence of heterogeneous populations carrying diverse mutations. In particular, loss-of-function mutations affecting the quorum-sensing regulator LasR are often found in bacteria isolated from patients with lung chronic infection and cystic fibrosis. Here, we study the evolutionary dynamics of polymorphic P. aeruginosa populations using isolates longitudinally collected from patients with chronic obstructive pulmonary disease (COPD). We find that isolates deficient in production of different sharable extracellular products are sequentially selected in COPD airways, and lasR mutants appear to be selected first due to their quorum-sensing defects. Polymorphic populations including lasR mutants display survival advantages in animal models of infection and modulate immune responses. Our study sheds light on the multistage evolution of P. aeruginosa populations during their adaptation to host lungs.


Assuntos
Fibrose Cística , Doença Pulmonar Obstrutiva Crônica , Animais , Humanos , Pseudomonas aeruginosa/genética , Infecção Persistente , Pulmão
6.
Angew Chem Int Ed Engl ; 62(37): e202308029, 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37469108

RESUMO

Chiral induction by natural biomolecules can reveal the indispensable role of chiral structures in life and can be used to develop the chirality-sensing biomolecular recognition. Here, we present the synthesis and characterization of an achiral supramolecular organic framework (SOF-1) constructed from cucurbit[8]uril (CB[8]) and hexaphenylbenzene (HPB) derivative (1) in water. Due to the propeller-like rotational chiral conformation of HPB units and the specific recognition properties of CB[8], SOF-1 demonstrates chiral adaptive induction in water when interacting with the N-terminal Trp-/Phe-containing dipeptides including L-TrpX and L-PheX (X is an amino acid residue), respectively, exhibiting contrasting circular dichroism (CD) and circularly polarized luminescence (CPL) spectra. Consequently, SOF-1 has been developed as a supramolecular host and chiroptical sensor capable of recognizing and distinguishing the sequence-opposite Trp-/Phe-containing dipeptide pairs including L-TrpX/L-XTrp and L-PheX/L-XPhe based on the sequence-selective CD responses.

7.
Gait Posture ; 104: 58-69, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37321113

RESUMO

PURPOSE: This meta-analysis was performed to compare the spatiotemporal, kinematic, and kinetic gait characteristics during level walking between total knee arthroplasty (TKA) and unicompartmental knee arthroplasty (UKA). METHODS: An electronic database literature search was performed to screen clinical trials which were included the studies evaluating not only spatiotemporal, kinematic, and kinetic gait parameters, but also knee range of motion and knee score (Knee Society Score and Oxford Knee Score, i.e., KSS and OKS). The data analysis was performed using statistical software Stata 14.0 and Review Manager 5.4. RESULTS: Thirteen studies (369 knees) that met the criteria were eventually included in this meta-analysis. The results revealed significant differences between UKA and TKA with regard to walking speed (P = 0.04), stride length (P = 0.02), maximum knee flexion at loading (P = 0.001), the 1st peak of vert-GRF (P = 0.006), the 1st valley of vert-GRF (P = 0.007), knee internal rotational moment (P = 0.04), knee extension (P < 0.00001), and KSS Function score (P = 0.05). In contrast, there were no statistical differences in the remaining spatiotemporal, kinematic, and kinetic gait parameters. CONCLUSION: Medial UKA design is superior to TKA design with regard to walking speed, stride length, maximum knee flexion at loading, the 1st peak and the 1st valley of vert-GRF, knee internal rotational moment, knee extension, and KSS Function score. And it could provide a stronger basis for physicians to make clinical decisions.


Assuntos
Artroplastia do Joelho , Osteoartrite do Joelho , Humanos , Artroplastia do Joelho/métodos , Fenômenos Biomecânicos , Marcha , Caminhada , Articulação do Joelho , Amplitude de Movimento Articular , Osteoartrite do Joelho/cirurgia , Resultado do Tratamento
8.
Sci China Life Sci ; 66(10): 2399-2414, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37256419

RESUMO

Limb loss shows recurrent phenotypic evolution across squamate lineages. Here, based on three de novo-assembled genomes of limbless lizards from different lineages, we showed that divergence of conserved non-coding elements (CNEs) played an important role in limb development. These CNEs were associated with genes required for limb initiation and outgrowth, and with regulatory signals in the early stage of limb development. Importantly, we identified the extensive existence of insertions and deletions (InDels) in the CNEs, with the numbers ranging from 111 to 756. Most of these CNEs with InDels were lineage-specific in the limbless squamates. Nearby genes of these InDel CNEs were important to early limb formation, such as Tbx4, Fgf10, and Gli3. Based on functional experiments, we found that nucleotide mutations and InDels both affected the regulatory function of the CNEs. Our study provides molecular evidence underlying limb loss in squamate reptiles from a developmental perspective and sheds light on the importance of regulatory element InDels in phenotypic evolution.


Assuntos
Genoma , Répteis , Animais , Répteis/genética , Fatores de Transcrição/genética , Evolução Molecular , Sequência Conservada/genética , Evolução Biológica
9.
Genome Biol ; 24(1): 46, 2023 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-36895044

RESUMO

BACKGROUND: Reptiles exhibit a wide variety of skin colors, which serve essential roles in survival and reproduction. However, the molecular basis of these conspicuous colors remains unresolved. RESULTS: We investigate color morph-enriched Asian vine snakes (Ahaetulla prasina), to explore the mechanism underpinning color variations. Transmission electron microscopy imaging and metabolomics analysis indicates that chromatophore morphology (mainly iridophores) is the main basis for differences in skin color. Additionally, we assemble a 1.77-Gb high-quality chromosome-anchored genome of the snake. Genome-wide association study and RNA sequencing reveal a conservative amino acid substitution (p.P20S) in SMARCE1, which may be involved in the regulation of chromatophore development initiated from neural crest cells. SMARCE1 knockdown in zebrafish and immunofluorescence verify the interactions among SMARCE1, iridophores, and tfec, which may determine color variations in the Asian vine snake. CONCLUSIONS: This study reveals the genetic associations of color variation in Asian vine snakes, providing insights and important resources for a deeper understanding of the molecular and genetic mechanisms related to reptilian coloration.


Assuntos
Cromatóforos , Estudo de Associação Genômica Ampla , Animais , Peixe-Zebra/genética , Pigmentação da Pele , Serpentes/genética , Cor , Proteínas de Peixe-Zebra , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética
10.
Conserv Biol ; 37(4): e14069, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36751969

RESUMO

Over the past 40 years, the climate has been changing and human disturbance has increased in the vast Qinghai-Tibet Plateau (QTP). These 2 factors are expected to affect the distribution of a large number of endemic vertebrate species. However, quantitative relationships between range shifts and climate change and human disturbance of these species in the QTP have rarely been evaluated. We used occurrence records of 19 terrestrial vertebrate species (birds, mammals, amphibians, and reptiles) occurring in the QTP from 1980 to 2020 to quantify the effects of climate change and anthropogenic impacts on the distribution of these 4 taxonomic groups and estimated species range changes in each species. The trend in distribution changes differed among the taxonomic groups, although, generally, ranges shifted to central QTP. Climate change contributed more to range variation than human disturbance (the sum of the 4 climatic variables contributed more than the sum of the 4 human disturbance variables for all 4 taxonomic groups). Suitable geographic range increased for most mammals, amphibians, and reptiles (+27.6%, +18.4%, and +27.8% on average, respectively), whereas for birds range decreased on average by 0.9%. Quantitative evidence for climate change and human disturbance associations with range changes for endemic vertebrate species in the QTP can provide useful insights into biodiversity conservation under changing environments.


En los últimos 40 años, el clima ha cambiado y las perturbaciones humanas han aumentado en la vasta meseta Qinghai-Tíbet (MQT). Se espera que estos dos factores afecten la distribución de un gran número de especies de vertebrados endémicos. Sin embargo, las relaciones cuantitativas entre los cambios del área de distribución y el cambio climático y las perturbaciones humanas en estas especies de la MQT han sido poco evaluadas. Utilizamos los registros de presencia de 19 especies de vertebrados terrestres (aves, mamíferos, anfibios y reptiles) de la MQT tomados entre 1980 y 2020 para cuantificar los efectos del cambio climático y los impactos antropogénicos sobre la distribución de estos cuatro grupos taxonómicos y estimar los cambios en el área de distribución de cada especie. La tendencia en los cambios de distribución difirió entre los grupos taxonómicos, aunque, en general, las áreas de distribución se desplazaron hacia el centro de la MQT. El cambio climático contribuyó más a la variación del área de distribución que las perturbaciones humanas (la suma de las cuatro variables climáticas contribuyó más que la suma de las cuatro variables de perturbaciones humanas para los cuatro grupos taxonómicos). El área de distribución geográfica adecuada aumentó para la mayoría de los mamíferos, anfibios y reptiles (+27.6%, +18.4% y +27.8% en promedio, respectivamente), mientras que para las aves disminuyó en promedio un 0.9%. Las pruebas cuantitativas de la asociación del cambio climático y las perturbaciones humanas con los cambios en el área de distribución de las especies vertebradas endémicas de la MQT pueden aportar información útil para la conservación de la biodiversidad en entornos cambiantes.


Assuntos
Efeitos Antropogênicos , Mudança Climática , Animais , Humanos , Tibet , Conservação dos Recursos Naturais , Vertebrados , Mamíferos
11.
Mol Biol Evol ; 40(1)2023 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-36562771

RESUMO

Rare and geographically restricted species may be vulnerable to genetic effects from inbreeding depression in small populations or from genetic swamping through hybridization with common species, but a third possibility is that selective gene flow can restore fitness (genetic rescue). Climate-sensitive pikas (Ochotona spp.) of the Qinghai-Tibetan Plateau (QHTP) and its vicinity have been reduced to residual populations through the movement of climatic zones during the Pleistocene and recent anthropogenic disturbance, whereas the plateau pika (O. curzoniae) remains common. Population-level whole-genome sequencing (n = 142) of six closely related species in the subgenus Ochotona revealed several phases of ancient introgression, lineage replacement, and bidirectional introgression. The strength of gene flow was the greatest from the dominant O. curzoniae to ecologically distinct species in areas peripheral to the QHTP. Genetic analyses were consistent with environmental reconstructions of past population movements. Recurrent periods of introgression throughout the Pleistocene revealed an increase in genetic variation at first but subsequent loss of genetic variation in later phases. Enhanced dispersion of introgressed genomic regions apparently contributed to demographic recovery in three peripheral species that underwent range shifts following climate oscillations on the QHTP, although it failed to drive recovery of northeastern O. dauurica and geographically isolated O. sikimaria. Our findings highlight differences in timescale and environmental background to determine the consequence of hybridization and the unique role of the QHTP in conserving key evolutionary processes of sky island species.


Assuntos
Lagomorpha , Animais , Lagomorpha/genética , Evolução Biológica , Hibridização Genética , Genômica , Demografia
12.
Mol Ecol ; 32(6): 1335-1350, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36073004

RESUMO

Understanding how and why species evolve requires knowledge on intraspecific divergence. In this study, we examined intraspecific divergence in the endangered hot-spring snake (Thermophis baileyi), an endemic species on the Qinghai-Tibet Plateau (QTP). Whole-genome resequencing of 58 sampled individuals from 15 populations was performed to identify the drivers of intraspecific divergence and explore the potential roles of genes under selection. Our analyses resolved three groups, with major intergroup admixture occurring in regions of group contact. Divergence probably occurred during the Pleistocene as a result of glacial climatic oscillations, Yadong-Gulu rift, and geothermal fields differentiation, while complex gene flow between group pairs reflected a unique intraspecific divergence pattern on the QTP. Intergroup fixed loci involved selected genes functionally related to divergence and local adaptation, especially adaptation to hot spring microenvironments in different geothermal fields. Analysis of structural variants, genetic diversity, inbreeding, and genetic load indicated that the hot-spring snake population has declined to a low level with decreased diversity, which is important for the conservation management of this endangered species. Our study demonstrated that the integration of demographic history, gene flow, genomic divergence genes, and other information is necessary to distinguish the evolutionary processes involved in speciation.


Assuntos
Variação Genética , Fontes Termais , Humanos , Animais , Tibet , Variação Genética/genética , Filogenia , Uganda , Serpentes/genética , Genômica
13.
J Comput Biol ; 30(1): 82-94, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35972373

RESUMO

Molecule generation is the procedure to generate initial novel molecule proposals for molecule design. Molecules are first projected into continuous vectors in chemical latent space, and then, these embedding vectors are decoded into molecules under the variational autoencoder (VAE) framework. The continuous latent space of VAE can be utilized to generate novel molecules with desired chemical properties and further optimize the desired chemical properties of molecules. However, there is a posterior collapse problem with the conventional recurrent neural network-based VAEs for the molecule sequence generation, which deteriorates the generation performance. We investigate the posterior collapse problem and find that the underestimated reconstruction loss is the main factor in the posterior collapse problem in molecule sequence generation. To support our conclusion, we present both analytical and experimental evidence. What is more, we propose an efficient and effective solution to fix the problem and prevent posterior collapse. As a result, our method achieves competitive reconstruction accuracy and validity score on the benchmark data sets.


Assuntos
Benchmarking , Redes Neurais de Computação , Sulfadiazina
14.
Int J Mol Sci ; 23(17)2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36077479

RESUMO

Anan's rock agama (Laudakia sacra) is a lizard species endemic to the harsh high-altitude environment of the Qinghai-Tibet Plateau, a region characterized by low oxygen tension and high ultraviolet (UV) radiation. To better understand the genetic mechanisms underlying highland adaptation of ectotherms, we assembled a 1.80-Gb L. sacra genome, which contained 284 contigs with an N50 of 20.19 Mb and a BUSCO score of 93.54%. Comparative genomic analysis indicated that mutations in certain genes, including HIF1A, TIE2, and NFAT family members and genes in the respiratory chain, may be common adaptations to hypoxia among high-altitude animals. Compared with lowland reptiles, MLIP showed a convergent mutation in L. sacra and the Tibetan hot-spring snake (Thermophis baileyi), which may affect their hypoxia adaptation. In L. sacra, several genes related to cardiovascular remodeling, erythropoiesis, oxidative phosphorylation, and DNA repair may also be tailored for adaptation to UV radiation and hypoxia. Of note, ERCC6 and MSH2, two genes associated with adaptation to UV radiation in T. baileyi, exhibited L. sacra-specific mutations that may affect peptide function. Thus, this study provides new insights into the potential mechanisms underpinning high-altitude adaptation in ectotherms and reveals certain genetic generalities for animals' survival on the plateau.


Assuntos
Altitude , Lagartos , Adaptação Fisiológica/genética , Animais , Hipóxia/genética , Sacro , Seleção Genética , Serpentes , Tibet
15.
Biomolecules ; 12(9)2022 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-36139164

RESUMO

The main target of retrosynthesis is to recursively decompose desired molecules into available building blocks. Existing template-based retrosynthesis methods follow a template selection stereotype and suffer from limited training templates, which prevents them from discovering novel reactions. To overcome this limitation, we propose an innovative retrosynthesis prediction framework that can compose novel templates beyond training templates. As far as we know, this is the first method that uses machine learning to compose reaction templates for retrosynthesis prediction. Besides, we propose an effective reactant candidate scoring model that can capture atom-level transformations, which helps our method outperform previous methods on the USPTO-50K dataset. Experimental results show that our method can produce novel templates for 15 USPTO-50K test reactions that are not covered by training templates. We have released our source implementation.


Assuntos
Técnicas de Química Sintética , Aprendizado de Máquina , Técnicas de Química Sintética/métodos , Modelos Químicos
16.
Innovation (Camb) ; 3(5): 100295, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36032194

RESUMO

Animals have evolved sophisticated temperature-sensing systems and mechanisms to detect and respond to ambient temperature changes. As a relict species endemic to the Qinghai-Tibet Plateau, hot-spring snake (Thermophis baileyi) survived the dramatic changes in climate that occurred during plateau uplift and ice ages, providing an excellent opportunity to explore the evolution of temperature sensation in ectotherms. Based on distributional information and behavioral experiments, we found that T. baileyi prefer hot-spring habitats and respond more quickly to warmth than other two snakes, suggesting that T. baileyi may evolve an efficient thermal-sensing system. Using high-quality chromosome-level assembly and comparative genomic analysis, we identified cold acclimation genes experiencing convergent acceleration in high-altitude lineages. We also discovered significant evolutionary changes in thermosensation- and thermoregulation-related genes, including the transient receptor potential (TRP) channels. Among these genes, TRPA1 exhibited three species-specific amino acid replacements, which differed from those found in infrared imaging snakes, implying different temperature-sensing molecular strategies. Based on laser-heating experiments, the T. baileyi-specific mutations in TRPA1 resulted in an increase in heat-induced opening probability and thermal sensitivity of the ion channels under the same degree of temperature stimulation, which may help the organism respond to temperature changes more quickly. These results provide insight into the genetic mechanisms underpinning the evolution of temperature-sensing strategies in ectotherms as well as genetic evidence of temperature acclimation in this group.

17.
Cell Rep ; 40(2): 111079, 2022 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-35830808

RESUMO

Bungarus multicinctus is a widely distributed and medically important elapid snake that produces lethal neurotoxic venom. To study and enhance existing antivenom, we explore the complete repertoire of its toxin genes based on de novo chromosome-level assembly and multi-tissue transcriptome data. Comparative genomic analyses suggest that the three-finger toxin family (3FTX) may evolve through the neofunctionalization of flanking LY6E. A long-neglected 3FTX subfamily (i.e., MKA-3FTX) is also investigated. Only one MKA-3FTX gene, which evolves a different protein conformation, is under positive selection and actively transcribed in the venom gland, functioning as a major toxin effector together with MKT-3FTX subfamily homologs. Furthermore, this lethal snake may acquire self-resistance to its ß-bungarotoxin via amino acid replacements on fast-evolving KCNA2. This study provides valuable resources for further evolutionary and structure-function studies of snake toxins, which are fundamental for the development of effective antivenoms and drug candidates.


Assuntos
Venenos Elapídicos , Elapidae , Animais , Antivenenos/química , Antivenenos/metabolismo , Bungarus/metabolismo , Venenos Elapídicos/química , Venenos Elapídicos/metabolismo , Venenos Elapídicos/toxicidade , Elapidae/genética , Elapidae/metabolismo , Toxinas Três Dedos
18.
Front Plant Sci ; 13: 904178, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35720564

RESUMO

As an important economic and medicinal crop, Amomum tsao-ko is rich in volatile oils and widely used in food additives, essential oils, and traditional Chinese medicine. However, the lack of the genome remains a limiting factor for understanding its medicinal properties at the molecular level. Here, based on 288.72 Gb of PacBio long reads and 105.45 Gb of Illumina paired-end short reads, we assembled a draft genome for A. tsao-ko (2.70 Gb in size, contig N50 of 2.45 Mb). Approximately 90.07% of the predicted genes were annotated in public databases. Based on comparative genomic analysis, genes involved in secondary metabolite biosynthesis, flavonoid metabolism, and terpenoid biosynthesis showed significant expansion. Notably, the DXS, GGPPS, and CYP450 genes, which participate in rate-limiting steps for terpenoid backbone biosynthesis and modification, may form the genetic basis for essential oil formation in A. tsao-ko. The assembled A. tsao-ko draft genome provides a valuable genetic resource for understanding the unique features of this plant and for further evolutionary and agronomic studies of Zingiberaceae species.

19.
Mol Ecol Resour ; 22(4): 1582-1595, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34837470

RESUMO

The Hengduan Mountains region is an important hotspot of alpine plant diversity and endemism. Acanthochlamys bracteata is a species of a threatened monotypic genus endemic to the Hengduan Mountains. In this study, we present a high-quality, chromosome-level reference genome for A. bracteata, constructed using long reads, short reads and Hi-C technology. We characterized its genetic diversity, population structure, demographic history and gene flow by resequencing individuals collected across its distribution. Comparative genomics analyses based on sequence information from single-copy orthologous genes revealed that A. bracteata and Dioscorea rotundata diverged ~104.5 million years ago. Whole-genome resequencing based on population genetic analysis revealed that the division of the 14 populations into 10 distinct clusters reflected geographical divergence, and three separate high levels of gene flow occurred sequentially between isolated populations of the Hengduan Mountains, a finding which is consistent with the turnover between ice ages and interglacial periods. Our findings indicate that Quaternary climatic changes played an important role in shaping the genetic structure and demographic trajectories of A. bracteata, and provide critical insights into the genetic status and evolutionary history of this poorly understood species, and possibly other alpine plants with a similar distribution. This study demonstrates the usefulness of population genomics for evaluating the effects of past climatic changes and identifying conservation units for the conservation and management of threatened species. Our high-quality genome represents a valuable resource for future studies of the underlying molecular mechanisms of adaptive evolution and provides insight for further comparative genomic analysis with other Velloziaceae species.


Assuntos
Espécies em Perigo de Extinção , Genoma , Animais , Biodiversidade , Cromossomos , Humanos , Filogenia
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