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1.
Plant J ; 107(3): 801-816, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33993566

RESUMO

The NDC80 complex is a conserved eukaryotic complex composed of four subunits (NUF2, SPC25, NDC80, and SPC24). In yeast and animal cells, the complex is located at the outer layer of the kinetochore, connecting the inner layer of the kinetochore and spindle microtubules (MTs) during cell division. In higher plants, the relationship of the NDC80 complex with MTs is still unclear. In this study, we characterized the biological function of AtNUF2, a subunit of the Arabidopsis NDC80 complex. We found that AtNUF2 is widely expressed in various organs, especially in different stages of embryonic development. It was verified that AtNUF2 co-localized with α-tubulin on MTs during mitosis by immunohistochemical assays. Mutation of AtNUF2 led to severe mitotic defects, not only in the embryo and endosperm, but also in seedlings, resulting in seed abortion and stagnating seedling growth. Furthermore, the biological function of AtNUF2 was studied using partially complemented nuf2-3/-DD45;ABI3pro::AtNUF2 (nuf2-3/-DA ) seedlings. The chromosome bridge and lagging chromatids occurred in nuf2-3/-DA root apical meristem cells, along with aberration of spindle MTs, resulting in blocked root growth. Meanwhile, the direct binding of AtNUF2 and AtSPC25 to MTs was determined by an MT co-sedimentation assay in vitro. This study revealed the function of AtNUF2 in mitosis and the underlying mechanisms, modulating spindle MT organization and ensuring chromosome segregation during embryo, endosperm, and root development, laying the foundation for subsequent research of the NDC80 complex.


Assuntos
Proteínas de Arabidopsis/metabolismo , Proteínas de Ciclo Celular/metabolismo , Regulação da Expressão Gênica de Plantas/fisiologia , Proteínas de Arabidopsis/genética , Proteínas de Ciclo Celular/genética , Segregação de Cromossomos , Cromossomos de Plantas , Sequência Conservada , Genótipo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Mitose/fisiologia , Plantas Geneticamente Modificadas , Conformação Proteica , Transporte Proteico , Plântula/citologia , Plântula/crescimento & desenvolvimento , Sementes/genética , Sementes/metabolismo
2.
J Integr Plant Biol ; 64(8): 1575-1595, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35603832

RESUMO

Vitamin B1 (VB1), including thiamin, thiamin monophosphate (TMP), and thiamin pyrophosphate (TPP), is an essential micronutrient for all living organisms. Nevertheless, the precise function of VB1 in rice remains unclear. Here, we described a VB1 auxotrophic mutant, chlorotic lethal seedling (cles) from the mutation of OsTH1, which displayed collapsed chloroplast membrane system and decreased pigment content. OsTH1 encoded a phosphomethylpyrimidine kinase/thiamin-phosphate pyrophosphorylase, and was expressed in various tissues, especially in seedlings, leaves, and young panicles. The VB1 content in cles was markedly reduced, despite an increase in the expression of VB1 synthesis genes. The decreased TPP content affected the tricarboxylic acid cycle, pentose phosphate pathway, and de novo fatty acid synthesis, leading to a reduction in fatty acids (C16:0 and C18:0) and sugars (sucrose and glucose) of cles. Additionally, irregular expression of chloroplast membrane synthesis genes led to membrane collapse. We also found that alternative splicing and translation allowed OsTH1 to be localized to both chloroplast and cytosol. Our study revealed that OsTH1 was an essential enzyme in VB1 biosynthesis and played crucial roles in seedling growth and development by participating in fatty acid and sugar metabolism, providing new perspectives on VB1 function in rice.


Assuntos
Oryza , Tiamina , Cloroplastos/metabolismo , Ácidos Graxos , Oryza/genética , Oryza/metabolismo , Plântula/genética , Plântula/metabolismo , Açúcares , Tiamina/metabolismo , Vitaminas
3.
J Exp Bot ; 72(13): 4871-4887, 2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-33909904

RESUMO

Reproductive development is a crucial process during plant growth. The structural maintenance of chromosome (SMC) 5/6 complex has been studied in various species. However, there are few studies on the biological function of SMC6 in plant development, especially during reproduction. In this study, knocking out of both AtSMC6A and AtSMC6B led to severe defects in Arabidopsis seed development, and expression of AtSMC6A or AtSMC6B could completely restore seed abortion in the smc6a-/-smc6b-/-double mutant. Knocking down AtSMC6A in the smc6b-/- mutant led to defects in female and male development and decreased fertility. The double mutation also resulted in loss of cell viability, and caused embryo and endosperm cell death through vacuolar cell death and necrosis. Furthermore, the expression of genes involved in embryo patterning, endosperm cellularisation, DNA damage repair, cell cycle regulation, and DNA replication were significantly changed in the albino seeds of the double mutant. Moreover, we found that the SMC5/6 complex may participate in the SOG1 (SUPPRESSOR OF GAMMA RESPONSE1)-dependent DNA damage repair pathway. These findings suggest that both AtSMC6A and AtSMC6B are functionally redundant and play important roles in seed and gametophyte development through maintaining chromosome stability in Arabidopsis.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Endosperma/metabolismo , Regulação da Expressão Gênica de Plantas , Células Germinativas Vegetais/metabolismo , Mutação , Sementes/genética , Sementes/metabolismo
4.
PLoS Genet ; 13(9): e1007036, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28961247

RESUMO

Chaperonins are a class of molecular chaperones that assist in the folding and assembly of a wide range of substrates. In plants, chloroplast chaperonins are composed of two different types of subunits, Cpn60α and Cpn60ß, and duplication of Cpn60α and Cpn60ß genes occurs in a high proportion of plants. However, the importance of multiple Cpn60α and Cpn60ß genes in plants is poorly understood. In this study, we found that loss-of-function of CPNA2 (AtCpn60α2), a gene encoding the minor Cpn60α subunit in Arabidopsis thaliana, resulted in arrested embryo development at the globular stage, whereas the other AtCpn60α gene encoding the dominant Cpn60α subunit, CPNA1 (AtCpn60α1), mainly affected embryonic cotyledon development at the torpedo stage and thereafter. Further studies demonstrated that CPNA2 can form a functional chaperonin with CPNB2 (AtCpn60ß2) and CPNB3 (AtCpn60ß3), while the functional partners of CPNA1 are CPNB1 (AtCpn60ß1) and CPNB2. We also revealed that the functional chaperonin containing CPNA2 could assist the folding of a specific substrate, KASI (ß-ketoacyl-[acyl carrier protein] synthase I), and that the KASI protein level was remarkably reduced due to loss-of-function of CPNA2. Furthermore, the reduction in the KASI protein level was shown to be the possible cause for the arrest of cpna2 embryos. Our findings indicate that the two Cpn60α subunits in Arabidopsis play different roles during embryo development through forming distinct chaperonins with specific AtCpn60ß to assist the folding of particular substrates, thus providing novel insights into functional divergence of Cpn60α subunits in plants.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Chaperoninas/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/genética , 3-Oxoacil-(Proteína de Transporte de Acila) Sintase/metabolismo , Proteína de Transporte de Acila/genética , Proteína de Transporte de Acila/metabolismo , Sequência de Aminoácidos , Arabidopsis/embriologia , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Chaperoninas/genética , Cloroplastos/genética , Cloroplastos/metabolismo , Clonagem Molecular , Cotilédone/embriologia , Cotilédone/genética , Duplicação Gênica , Conformação Proteica , Plântula/embriologia , Espectrometria de Massas em Tandem
5.
Plant J ; 94(2): 288-303, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29406597

RESUMO

Replication factor C (RFC) is a conserved eukaryotic complex consisting of RFC1/2/3/4/5. It plays important roles in DNA replication and the cell cycle in yeast and fruit fly. However, it is not very clear how RFC subunits function in higher plants, except for the Arabidopsis (At) subunits AtRFC1 and AtRFC3. In this study, we investigated the functions of AtRFC4 and found that loss of function of AtRFC4 led to an early sporophyte lethality that initiated as early as the elongated zygote stage, all defective embryos arrested at the two- to four-cell embryo proper stage, and the endosperm possessed six to eight free nuclei. Complementation of rfc4-1/+ with AtRFC4 expression driven through the embryo-specific DD45pro and ABI3pro or the endosperm-specific FIS2pro could not completely restore the defective embryo or endosperm, whereas a combination of these three promoters in rfc4-1/+ enabled the aborted ovules to develop into viable seeds. This suggests that AtRFC4 functions simultaneously in endosperm and embryo and that the proliferation of endosperm is critical for embryo maturation. Assays of DNA content in rfc4-1/+ verified that DNA replication was disrupted in endosperm and embryo, resulting in blocked mitosis. Moreover, we observed a decreased proportion of late S-phase and M-phase cells in the rfc4-1/-FIS2;DD45;ABI3pro::AtRFC4 seedlings, suggesting that incomplete DNA replication triggered cell cycle arrest in cells of the root apical meristem. Therefore, we conclude that AtRFC4 is a crucial gene for DNA replication.


Assuntos
Proteínas de Arabidopsis/fisiologia , Arabidopsis , Replicação do DNA , Mitose , Proteína de Replicação C/fisiologia , Arabidopsis/fisiologia , Núcleo Celular/metabolismo , Replicação do DNA/fisiologia , Endosperma/metabolismo , Técnicas de Silenciamento de Genes , Genes de Plantas , Mitose/fisiologia , Plântula/fisiologia , Sementes/crescimento & desenvolvimento
6.
J Exp Bot ; 70(21): 6229-6244, 2019 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-31408172

RESUMO

Embryogenesis is an essential process during seed development in higher plants. It has previously been shown that mutation of the Arabidopsis non-SMC element genes AtNSE1 or AtNSE3 leads to early embryo abortion, and their proteins can interact with each other directly. However, the crucial regions of these proteins in this interaction and how the proteins are cytologically involved in Arabidopsis embryo development are unknown. In this study, we found that the C-terminal including the Ring-like motif of AtNSE1 can interact with the N-terminal of AtNSE3, and only the Ring-like motif is essential for binding with three α motifs of AtNSE2 (homologous to AtMMS21). Using genetic assays and by analysing molecular markers of cell fate decisions (STM, WOX5, and WOX8) in mutant nse1 and nse3 embryos, we found that AtNSE1 and AtNSE3 work non-redundantly in early embryo development, and that differentiation of the apical meristem and the hypophysis fails in the mutants, which have disrupted auxin transportation and responses. However, the upper cells of the suspensor in the mutants seem to have proper embryo cell identity. Cytological examination showed that cell death occurred from the early embryo stage, and that vacuolar programmed cell death and necrosis in the nse1 and nse3 mutant embryos led to ovule abortion. Thus, AtNSE1 and AtNSE3 are essential for maintaining cell viability and growth during early embryogenesis. Our results improve our understanding of the functions of SMC5/6 complex in early embryogenesis in Arabidopsis.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/embriologia , Arabidopsis/metabolismo , Padronização Corporal , Proteínas Nucleares/metabolismo , Sementes/citologia , Sementes/embriologia , Ubiquitina-Proteína Ligases/metabolismo , Apoptose , Arabidopsis/citologia , Arabidopsis/genética , Proteínas de Arabidopsis/química , Transporte Biológico , Sobrevivência Celular , Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos/metabolismo , Meristema/metabolismo , Proteínas Mutantes/metabolismo , Mutação/genética , Proteínas Nucleares/química , Fenótipo , Ligação Proteica , Domínios Proteicos , Estrutura Secundária de Proteína , Sementes/ultraestrutura , Ubiquitina-Proteína Ligases/química
7.
Plant Cell Physiol ; 59(10): 2113-2128, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30020502

RESUMO

The endosperm and embryo originate from the fertilized central cell and egg cell through a programmed series of cell division and differentiation events. Characterization of more vital genes involved in endosperm and embryo development can help us to understand the regulatory mechanism in more depth. In this study, we found that loss of NAA10 and NAA15, the catalytic and auxiliary subunits of Arabidopsis thaliana N-terminal acetyltransferase A (AtNatA), respectively, led to severely delayed and incomplete endosperm cellularization, accompanied by disordered cell division in the early embryo. Studies on the marker genes/lines of the endosperm (AGL62-GFP, pDD19::GFP, pDD22::NLS-GFP and N9185) and embryo (STM, FIL, SCR and WOX5) in naa10/naa15 mutants showed that expression patterns of these markers were significantly affected, which were tightly associated with the defective feature of endosperm cellularization and embryo cell differentiation. Subsequently, embryonic complementation rescued the abortive embryos, but failed to initiate endosperm cellularization properly, further confirming the essential role of AtNatA in both endosperm and embryo development. Moreover, repression of AGL62 in naa10 and naa15 restored the endosperm cellularization, suggesting that NAA10/NAA15 functions in initiation of endosperm cellularization by inhibiting the expression of AGL62 in Arabidopsis. Therefore, NAA10 and NAA15 could be considered as crucial factors involved in promoting endosperm cellularization in Arabidopsis.


Assuntos
Acetiltransferases/metabolismo , Arabidopsis/metabolismo , Endosperma/metabolismo , Acetiltransferases/genética , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Endosperma/genética , Regulação da Expressão Gênica de Plantas
8.
J Exp Bot ; 68(5): 1039-1054, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28207059

RESUMO

Early embryo development from the zygote is an essential stage in the formation of the seed, while seedling development is the beginning of the formation of an individual plant. AtNSE1 and AtNSE3 are subunits of the structural maintenance of chromosomes (SMC) 5/6 complex and have been identified as non-SMC elements, but their functions in Arabidopsis growth and development remain as yet unknown. In this study, we found that loss of function of AtNSE1 and AtNSE3 led to severe defects in early embryo development. Partially complemented mutants showed that the development of mutant seedlings was inhibited, that chromosome fragments occurred during anaphase, and that the cell cycle was delayed at G2/M, which led to the occurrence of endoreduplication. Further, a large number of DNA double-strand breaks (DSBs) occurred in the nse1 and nse3 mutants, and the expression of AtNSE1 and AtNSE3 was up-regulated following treatment of the plants with DSB inducer compounds, suggesting that AtNSE1 and AtNSE3 have a role in DNA damage repair. Therefore, we conclude that AtNSE1 and AtNSE3 facilitate DSB repair and contribute to maintaining genome stability and cell division in mitotic cells. Thus, we think that AtNSE1 and AtNSE3 may be crucial factors for maintaining proper early embryonic and post-embryonic development.


Assuntos
Arabidopsis/crescimento & desenvolvimento , Arabidopsis/genética , Plântula/crescimento & desenvolvimento , Sementes/crescimento & desenvolvimento , Arabidopsis/metabolismo , Proteínas de Arabidopsis , Ligases
9.
J Surg Res ; 220: 261-267, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29180190

RESUMO

BACKGROUND: Most of the literature concerning the neurocutaneous flap is related to its anatomic investigation and clinical application, and the more in-depth physiological problem such as whether the cutaneous nerve contains sympathetic fibers that innervate its accompanying vessels has never been explored. MATERIALS AND METHODS: Dissection was first performed on three rabbits. In another 22 rabbits, two rabbits undergoing no surgery were used as the normal control group. In the remaining 20 rabbits, the 40 sides of hind limbs were divided into a nerve severance group, where the sural nerve was transected at its origin after creation of the proximally based sural neurocutaneous flap, and a nerve preservation group, in which the continuation of the sural nerve was preserved. The sural neurovascular bundles at four time points were harvested for immunohistochemical and Western blotting analyses of the expression of tyrosine hydroxylase (TH). An infrared thermal imager was used for measurement of the average flap temperature within the first 24 h. RESULTS: The sural neurovascular bundle entered the skin at 4.5 ± 1.2 cm above the lateral malleolus. The TH in the sural nerve and tunica adventitia of the sural artery showed a synchronized abated expression in the nerve severance group. The TH expression showed no decline in the nerve preservation group. The average flap temperature in the nerve severance group was higher than that in the nerve preservation group starting from 2 h after flap harvest (P = 0.05). CONCLUSIONS: The cutaneous nerve has meted out sympathetic fibers to the accompanying artery, regulating its vascular tone.


Assuntos
Nervo Sural/anatomia & histologia , Retalhos Cirúrgicos/irrigação sanguínea , Retalhos Cirúrgicos/inervação , Animais , Artérias/inervação , Western Blotting , Imuno-Histoquímica , Coelhos , Retalhos Cirúrgicos/cirurgia , Temperatura , Tirosina 3-Mono-Oxigenase/análise
10.
Plant Physiol ; 166(2): 853-68, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25104724

RESUMO

In the life cycle of flowering plants, the sporophytic generation takes up most of the time and plays a dominant role in influencing plant growth and development. The embryo cell and endosperm free nucleus divisions establish the critical initiation phase of early sporophyte development, which forms mature seeds through a series of cell growth and differentiation events. Here, we report on the biological functions of two Arabidopsis (Arabidopsis thaliana) mitochondrial proteins, TRANSLOCASE OF THE INNER MEMBRANE9 (TIM9) and TIM10. We found that dysfunction of either AtTIM9 or AtTIM10 led to an early sporophyte-lethal phenotype; the embryo and endosperm both arrest division when the embryo proper developed to 16 to 32 cells. The abortion of tim9-1 and tim10 embryos at the 16/32-cell stage was caused by the loss of cell viability and the cessation of division in the embryo proper region, and this inactivation was due to the collapse of the mitochondrial structure and activity. Our characterization of tim9-1 and tim10 showed that mitochondrial membrane permeability increased and that cytochrome c was released from mitochondria into the cytoplasm in the 16/32-cell embryo proper, indicating that mitochondrial dysfunction occurred in the early sporophytic cells, and thus caused the initiation of a necrosis-like programmed cell death, which was further proved by the evidence of reactive oxygen species and DNA fragmentation tests. Consequently, we verified that AtTIM9 and AtTIM10 are nonredundantly essential for maintaining the mitochondrial function of early embryo proper cells and endosperm-free nuclei; these proteins play critically important roles during sporophyte initiation and development in Arabidopsis.


Assuntos
Proteínas de Arabidopsis/fisiologia , Arabidopsis/fisiologia , Divisão Celular/fisiologia , Endosperma/citologia , Sementes/citologia , Arabidopsis/embriologia , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Potencial da Membrana Mitocondrial , Mutação , Espécies Reativas de Oxigênio/metabolismo
11.
J Exp Bot ; 66(7): 2079-91, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25871650

RESUMO

Chloroplasts perform many essential metabolic functions and their proper development is critically important in embryogenesis. However, little is known about how chloroplasts function in embryogenesis and more relevant components need to be characterized. In this study, we show that Arabidopsis Ribonuclease J (RNase J) is required for chloroplast and embryo development. Mutation of AtRNJ led to albino ovules containing aborted embryos; the morphological development of rnj embryos was disturbed after the globular stage. Observation of ultrastructures indicated that these aborted embryos may result from impaired chloroplast development. Furthermore, by analyzing the molecular markers of cell fate decisions (STM, FIL, ML1, SCR, and WOX5) in rnj embryos, we found that this impairment of chloroplast development may lead to aberrant embryo patterning along the apical-basal axis, indicating that AtRNJ is important in initiating and maintaining the organization of shoot apical meristems (SAMs), cotyledons, and hypocotyls. Moreover, the transport and response of auxin in rnj embryos was found to be disrupted, suggesting that AtRNJ may be involved in auxin-mediated pathways during embryogenesis. Therefore, we speculate that RNJ plays a vital role in embryo morphogenesis and apical-basal pattern formation by regulating chloroplast development.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/enzimologia , Cloroplastos/metabolismo , Ácidos Indolacéticos/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Ribonucleases/genética , Arabidopsis/citologia , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/metabolismo , Cotilédone/citologia , Cotilédone/enzimologia , Cotilédone/genética , Cotilédone/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Hipocótilo/citologia , Hipocótilo/enzimologia , Hipocótilo/genética , Hipocótilo/crescimento & desenvolvimento , Meristema/citologia , Meristema/enzimologia , Meristema/genética , Meristema/crescimento & desenvolvimento , Mutagênese Insercional , Ribonucleases/metabolismo
12.
IEEE J Biomed Health Inform ; 28(7): 4170-4183, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38954557

RESUMO

Efficient medical image segmentation aims to provide accurate pixel-wise predictions with a lightweight implementation framework. However, existing lightweight networks generally overlook the generalizability of the cross-domain medical segmentation tasks. In this paper, we propose Generalizable Knowledge Distillation (GKD), a novel framework for enhancing the performance of lightweight networks on cross-domain medical segmentation by generalizable knowledge distillation from powerful teacher networks. Considering the domain gaps between different medical datasets, we propose the Model-Specific Alignment Networks (MSAN) to obtain the domain-invariant representations. Meanwhile, a customized Alignment Consistency Training (ACT) strategy is designed to promote the MSAN training. Based on the domain-invariant vectors in MSAN, we propose two generalizable distillation schemes, Dual Contrastive Graph Distillation (DCGD) and Domain-Invariant Cross Distillation (DICD). In DCGD, two implicit contrastive graphs are designed to model the intra-coupling and inter-coupling semantic correlations. Then, in DICD, the domain-invariant semantic vectors are reconstructed from two networks (i.e., teacher and student) with a crossover manner to achieve simultaneous generalization of lightweight networks, hierarchically. Moreover, a metric named Fréchet Semantic Distance (FSD) is tailored to verify the effectiveness of the regularized domain-invariant features. Extensive experiments conducted on the Liver, Retinal Vessel and Colonoscopy segmentation datasets demonstrate the superiority of our method, in terms of performance and generalization ability on lightweight networks.


Assuntos
Processamento de Imagem Assistida por Computador , Humanos , Processamento de Imagem Assistida por Computador/métodos , Algoritmos , Redes Neurais de Computação , Bases de Dados Factuais , Aprendizado Profundo
13.
Org Lett ; 26(27): 5811-5816, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38940397

RESUMO

A practical strategy for the construction of diverse phosphonyl and thiofunctionalized sulfoxonium ylides via controllable monofunctionalization of hybrid I(III)/S(VI) ylides is presented. This process allows efficient P-H insertion of I(III)/S(VI) ylides under Cu catalysis, enabling the synthesis of phosphonyl sulfoxonium ylides, whereas reaction with sulfur-containing reagents including AgSCF3, KSC(S)OR, and KSCN under mild conditions resulted in α-trifluoromethylthiolation, dithiocarbanation, and thiocyanation of sulfoxonium ylides accordingly. Of note, wide substrate compatibility (108 examples), excellent efficiency (up to 99% yield), gram-scale experiments, and various product derivatizations highlight the synthetic utility of this protocol.

14.
Org Lett ; 26(29): 6263-6268, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-38995695

RESUMO

A metal-free cascade of α-acyloxylation/carboxamidation of I(III)/S(VI)-ylides, carboxylic acids, and isonitriles via a Passerini-like multicomponent reaction is reported. Unexpectedly, [3 + 1+1] cyclization involving I(III)/S(VI)-ylides and two molecules of ethyl isocyanoacetate was observed. The strategy allows for the synthesis of unsymmetrical α,α-disubstituted ketones and functionalized pyrroles with up to 99% yield and wide substrate compatibility. Notably, the procedure has been extended to the late-stage modification of drugs and natural products, offering an elegant complement to the classic Passerini reaction.

15.
Phys Rev E ; 107(2-1): 024307, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36932505

RESUMO

Recurrent neural networks are widely used for modeling spatiotemporal sequences in both nature language processing and neural population dynamics. However, understanding the temporal credit assignment is hard. Here, we propose that each individual connection in the recurrent computation is modeled by a spike and slab distribution, rather than a precise weight value. We then derive the mean-field algorithm to train the network at the ensemble level. The method is then applied to classify handwritten digits when pixels are read in sequence, and to the multisensory integration task that is a fundamental cognitive function of animals. Our model reveals important connections that determine the overall performance of the network. The model also shows how spatiotemporal information is processed through the hyperparameters of the distribution, and moreover reveals distinct types of emergent neural selectivity. To provide a mechanistic analysis of the ensemble learning, we first derive an analytic solution of the learning at the infinitely large network limit. We then carry out a low-dimensional projection of both neural and synaptic dynamics, analyze symmetry breaking in the parameter space, and finally demonstrate the role of stochastic plasticity in the recurrent computation. Therefore, our study sheds light on mechanisms of how weight uncertainty impacts the temporal credit assignment in recurrent neural networks from the ensemble perspective.

16.
Phys Rev E ; 108(1-1): 014309, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37583230

RESUMO

An obstacle to artificial general intelligence is set by continual learning of multiple tasks of a different nature. Recently, various heuristic tricks, both from machine learning and from neuroscience angles, were proposed, but they lack a unified theory foundation. Here, we focus on continual learning in single-layered and multilayered neural networks of binary weights. A variational Bayesian learning setting is thus proposed in which the neural networks are trained in a field-space, rather than a gradient-ill-defined discrete-weight space, and furthermore, weight uncertainty is naturally incorporated, and it modulates synaptic resources among tasks. From a physics perspective, we translate variational continual learning into a Franz-Parisi thermodynamic potential framework, where previous task knowledge serves as a prior probability and a reference as well. We thus interpret the continual learning of the binary perceptron in a teacher-student setting as a Franz-Parisi potential computation. The learning performance can then be analytically studied with mean-field order parameters, whose predictions coincide with numerical experiments using stochastic gradient descent methods. Based on the variational principle and Gaussian field approximation of internal preactivations in hidden layers, we also derive the learning algorithm considering weight uncertainty, which solves the continual learning with binary weights using multilayered neural networks, and performs better than the currently available metaplasticity algorithm in which binary synapses bear hidden continuous states and the synaptic plasticity is modulated by a heuristic regularization function. Our proposed principled frameworks also connect to elastic weight consolidation, weight-uncertainty modulated learning, and neuroscience-inspired metaplasticity, providing a theoretically grounded method for real-world multitask learning with deep networks.

17.
IEEE Trans Med Imaging ; 42(4): 1159-1171, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36423314

RESUMO

With the development of deep convolutional neural networks, medical image segmentation has achieved a series of breakthroughs in recent years. However, high-performance convolutional neural networks always mean numerous parameters and high computation costs, which will hinder the applications in resource-limited medical scenarios. Meanwhile, the scarceness of large-scale annotated medical image datasets further impedes the application of high-performance networks. To tackle these problems, we propose Graph Flow, a comprehensive knowledge distillation framework, for both network-efficiency and annotation-efficiency medical image segmentation. Specifically, the Graph Flow Distillation transfers the essence of cross-layer variations from a well-trained cumbersome teacher network to a non-trained compact student network. In addition, an unsupervised Paraphraser Module is integrated to purify the knowledge of the teacher, which is also beneficial for the training stabilization. Furthermore, we build a unified distillation framework by integrating the adversarial distillation and the vanilla logits distillation, which can further refine the final predictions of the compact network. With different teacher networks (traditional convolutional architecture or prevalent transformer architecture) and student networks, we conduct extensive experiments on four medical image datasets with different modalities (Gastric Cancer, Synapse, BUSI, and CVC-ClinicDB). We demonstrate the prominent ability of our method on these datasets, which achieves competitive performances. Moreover, we demonstrate the effectiveness of our Graph Flow through a novel semi-supervised paradigm for dual efficient medical image segmentation. Our code will be available at Graph Flow.


Assuntos
Processamento de Imagem Assistida por Computador , Redes Neurais de Computação
18.
Artigo em Inglês | MEDLINE | ID: mdl-37018302

RESUMO

Clinical management and accurate disease diagnosis are evolving from qualitative stage to the quantitative stage, particularly at the cellular level. However, the manual process of histopathological analysis is lab-intensive and time-consuming. Meanwhile, the accuracy is limited by the experience of the pathologist. Therefore, deep learning-empowered computer-aided diagnosis (CAD) is emerging as an important topic in digital pathology to streamline the standard process of automatic tissue analysis. Automated accurate nucleus segmentation can not only help pathologists make more accurate diagnosis, save time and labor, but also achieve consistent and efficient diagnosis results. However, nucleus segmentation is susceptible to staining variation, uneven nucleus intensity, background noises, and nucleus tissue differences in biopsy specimens. To solve these problems, we propose Deep Attention Integrated Networks (DAINets), which mainly built on self-attention based spatial attention module and channel attention module. In addition, we also introduce a feature fusion branch to fuse high-level representations with low-level features for multi-scale perception, and employ the mark-based watershed algorithm to refine the predicted segmentation maps. Furthermore, in the testing phase, we design Individual Color Normalization (ICN) to settle the dyeing variation problem in specimens. Quantitative evaluations on the multi-organ nucleus dataset indicate the priority of our automated nucleus segmentation framework.

19.
iScience ; 26(10): 107825, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37736036

RESUMO

Dysregulated cardiac function after sepsis in intensive care unit is known to predict poor long-term outcome and increase mortality. Their pathological feature and molecular mechanism remain unclear. We observed that septic patients with depressed left ventricular ejection fraction (LVEF) have the highest in-hospital and 28 days mortality comparing to patients with hyperdynamic LVEF or with heart failure with preserved LVEF. Echocardiograms reveal that survivors post cecum ligation and puncture (CLP) on rodents have stable LVEF and non-survivors have fluctuated LVEF at CLP early phase. CLP-induced mice fall into three groups based on LVEF 24 h post-surgery: high-, low-, and normal-LVEF. Transcriptomic and proteomic analyses identify jointly and distinctively changed genes, proteins and biologically essential pathways in left ventricles from three CLP groups. Notably, transmission electron microscopy shows different mitochondrial and sarcomere defects associated with LVEF variances. Together, this study systematically characterizes the molecular, morphological, and functional alterations in CLP-induced cardiac injury.

20.
Org Lett ; 25(23): 4286-4291, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37265108

RESUMO

Two categories of tetrasubstituted phenols were prepared via the cycloaddition reaction of vinyl sulfoxonnium ylides with cyclopropenones in a switchable manner. Copper carbenoid was proposed as the active intermediate in the process of 2,3,4,5-tetrasubstituted phenols formation, while 2,3,5,6-tetrasubstituted phenols were generated via the direct [3 + 3] annulation of vinyl sulfoxonnium ylides with cyclopropenones under metal-free conditions. Further synthetic applications were also demonstrated.


Assuntos
Cobre , Metais , Catálise , Reação de Cicloadição
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