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1.
Nature ; 551(7679): 198-203, 2017 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-29120414

RESUMO

The rate of behavioural decline in the ageing population is remarkably variable among individuals. Despite the considerable interest in studying natural variation in ageing rate to identify factors that control healthy ageing, no such factor has yet been found. Here we report a genetic basis for variation in ageing rates in Caenorhabditis elegans. We find that C. elegans isolates show diverse lifespan and age-related declines in virility, pharyngeal pumping, and locomotion. DNA polymorphisms in a novel peptide-coding gene, named regulatory-gene-for-behavioural-ageing-1 (rgba-1), and the neuropeptide receptor gene npr-28 influence the rate of age-related decline of worm mating behaviour; these two genes might have been subjected to recent selective sweeps. Glia-derived RGBA-1 activates NPR-28 signalling, which acts in serotonergic and dopaminergic neurons to accelerate behavioural deterioration. This signalling involves the SIR-2.1-dependent activation of the mitochondrial unfolded protein response, a pathway that modulates ageing. Thus, natural variation in neuropeptide-mediated glia-neuron signalling modulates the rate of ageing in C. elegans.


Assuntos
Envelhecimento/genética , Envelhecimento/fisiologia , Caenorhabditis elegans/genética , Caenorhabditis elegans/fisiologia , Variação Genética , Neuroglia/metabolismo , Neurônios/metabolismo , Transdução de Sinais/genética , Alelos , Animais , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Neurônios Dopaminérgicos/metabolismo , Feminino , Genética Populacional , Locomoção/genética , Locomoção/fisiologia , Longevidade/genética , Longevidade/fisiologia , Masculino , Faringe/fisiologia , Polimorfismo de Nucleotídeo Único/genética , Receptores Acoplados a Proteínas G/metabolismo , Neurônios Serotoninérgicos/metabolismo , Comportamento Sexual Animal/fisiologia , Sirtuínas/metabolismo , Resposta a Proteínas não Dobradas/genética , Resposta a Proteínas não Dobradas/fisiologia
2.
Angew Chem Int Ed Engl ; 62(10): e202217839, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36631412

RESUMO

An ideal adsorbent for separation requires optimizing both storage capacity and selectivity, but maximizing both or achieving a desired balance remain challenging. Herein, a de-linker strategy is proposed to address this issue for metal-organic frameworks (MOFs). Broadly speaking, the de-linker idea targets a class of materials that may be viewed as being intermediate between zeolites and MOFs. Its feasibility is shown here by a series of ultra-microporous MOFs (SNNU-98-M, M=Mn, Co, Ni, Zn). SNNU-98 exhibit high volumetric C2 H2 uptake capacity under low and ambient pressures (175.3 cm3 cm-3 @ 0.1 bar, 222.9 cm3 cm-3 @ 1 bar, 298 K), as well as extraordinary selectivity (2405.7 for C2 H2 /C2 H4 , 22.7 for C2 H2 /CO2 ). Remarkably, SNNU-98-Mn can efficiently separate C2 H2 from C2 H2 /CO2 and C2 H2 /C2 H4 mixtures with a benchmark C2 H2 /C2 H4 (1/99) breakthrough time of 2325 min g-1 , and produce 99.9999 % C2 H4 with a productivity up to 64.6 mmol g-1 , surpassing values of reported MOF adsorbents.

3.
Appl Environ Microbiol ; 88(9): e0034122, 2022 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-35442081

RESUMO

Isopropanol dehydrogenase (IPADH) is one of the most attractive options for nicotinamide cofactor regeneration due to its low cost and simple downstream processing. However, poor thermostability and strict cofactor dependency hinder its practical application for bioconversions. In this study, we simultaneously improved the thermostability (433-fold) and catalytic activity (3.3-fold) of IPADH from Brucella suis via a flexible segment engineering strategy. Meanwhile, the cofactor preference of IPADH was successfully switched from NAD(H) to NADP(H) by 1.23 × 106-fold. When these variants were employed in three typical bioredox reactions to drive the synthesis of important chiral pharmaceutical building blocks, they outperformed the commonly used cofactor regeneration systems (glucose dehydrogenase [GDH], formate dehydrogenase [FDH], and lactate dehydrogenase [LDH]) with respect to efficiency of cofactor regeneration. Overall, our study provides two promising IPADH variants with complementary cofactor specificities that have great potential for wide applications. IMPORTANCE Oxidoreductases represent one group of the most important biocatalysts for synthesis of various chiral synthons. However, their practical application was hindered by the expensive nicotinamide cofactors used. Isopropanol dehydrogenase (IPADH) is one of the most attractive biocatalysts for nicotinamide cofactor regeneration. However, poor thermostability and strict cofactor dependency hinder its practical application. In this work, the thermostability and catalytic activity of an IPADH were simultaneously improved via a flexible segment engineering strategy. Meanwhile, the cofactor preference of IPADH was successfully switched from NAD(H) to NADP(H). The resultant variants show great potential for regeneration of nicotinamide cofactors, and the engineering strategy might serve as a useful approach for future engineering of other oxidoreductases.


Assuntos
NAD , Niacinamida , 2-Propanol , Formiato Desidrogenases/genética , NADP , Regeneração
4.
Inorg Chem ; 60(23): 18473-18482, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34797628

RESUMO

Acetylene (C2H2) purification is of great importance for many chemical synthesis and processes. Metal-organic frameworks (MOFs) are widely used for gas adsorption and separation due to their variable structure and porosity. However, the exploitation of ideal MOF adsorbents for C2H2 keeps a challenging task. Herein, a combination of open metal sites (OMSs) and Lewis basic sites (LBSs) in robust MOFs is demonstrated to effectively promote the C2H2 purification performance. Accordingly, SNNU-37(Fe/Sc), two isostructural MOFs constituted by [Fe3O(COO)6] or [Sc3O(COO)6] trinuclear clusters and amide-functionalized tricarboxylate linkers, were designed with extra-stable 3,6-connected new architectures. Derived from the coexistence of high-density OMSs and LBSs, the C2H2 adsorption amounts of SNNU-37(Fe/Sc) are much higher than those values for C2H4 and CO2. Theoretical IAST selectivity values of SNNU-37(Fe) are 2.4 for C2H2/C2H4 (50/50, v/v) and 9.9 for C2H2/CO2 (50/50, v/v) at 298 K and 1 bar, indicating an excellent C2H2 separation ability. Experimental breakthrough curves also revealed that SNNU-37(Fe) could effectively separate C2H2/C2H4 and C2H2/CO2 under ambient conditions. GCMC simulations further indicate that open Fe or Sc sites and amide groups mainly contribute to stronger adsorption sites for C2H2 molecules.

5.
Sensors (Basel) ; 21(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34640891

RESUMO

To construct circular barrier coverage (CBC) with multistatic radars, a deployment optimization method based on equipartition strategy is proposed in this paper. In the method, the whole circular area is divided into several sub-circles with equal width, and each sub-circle is blanketed by a sub-CBC that is built based on the multistatic radar deployment patterns. To determine the optimal deployment patterns for each sub-CBC, the optimization conditions are firstly studied. Then, to optimize the deployment of the whole circular area, a model based on minimum deployment cost is proposed, and the proposed model is divided into two sub-models to solve the optimization issue. In the inner model, it is assumed that the width of a sub-circle is given. Based on the optimization conditions of the deployment pattern, integer linear programming (ILP) and exhaustive method (EM) are jointly adopted to determine the types and numbers of deployment patterns. Moreover, a modified formula is introduced to calculate the maximum valid number of receivers in a pattern, thus narrowing the search scope of the EM. In the outer model, the width of a sub-circle is assumed to be a variable, and the EM is adopted to determine the minimum total deployment cost and the optimal deployment patterns on each sub-circle. Moreover, the improved formula is exploited to determine the range of width for a sub-circle barrier and reduce the search scope of the EM. Finally, simulations are conducted in different conditions to verify the effectiveness of the proposed method. The simulation results indicate that the proposed method can spend less deployment cost and deploy fewer transmitters than the state-of-the-artwork.

6.
Mol Biol Evol ; 36(3): 487-499, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30481341

RESUMO

The origin and population history of the endangered golden snub-nosed monkey (Rhinopithecus roxellana) remain largely unavailable and/or controversial. We here integrate analyses of multiple genomic markers, including mitochondrial (mt) genomes, Y-chromosomes, and autosomes of 54 golden monkey individuals from all three geographic populations (SG, QL, and SNJ). Our results reveal contrasting population structures. Mt analyses suggest a division of golden monkeys into five lineages: one in SNJ, two in SG, and two in QL. One of the SG lineages (a mixed SG/QL lineage) is basal to all other lineages. In contrast, autosomal analyses place SNJ as the most basal lineage and identify one QL and three SG lineages. Notably, Y-chromosome analyses bear features similar to mt analyses in placing the SG/QL-mixed lineage as the first diverging lineage and dividing SG into two lineages, while resembling autosomal analyses in identifying one QL lineage. We further find bidirectional gene flow among all three populations at autosomal loci, while asymmetric gene flow is suggested at mt genomes and Y-chromosomes. We propose that different population structures and gene flow scenarios are the result of sex-linked differences in the dispersal pattern of R. roxellana. Moreover, our demographic simulation analyses support an origin hypothesis suggesting that the ancestral R. roxellana population was once widespread and then divided into SNJ and non-SNJ (SG and QL) populations. This differs from previous mt-based "mono-origin (SG is the source population)" and "multiorigin (SG is a fusion of QL and SNJ)" hypotheses. We provide a detailed and refined scenario for the origin and population history of this endangered primate species, which has a broader significance for Chinese biogeography. In addition, this study highlights the importance to investigate multiple genomic markers with different modes of inheritance to trace the complete evolutionary history of a species, especially for those exhibiting differential or mixed patterns of sex dispersal.


Assuntos
Distribuição Animal , Cercopithecidae/genética , Espécies em Perigo de Extinção , Fluxo Gênico , Animais , China , Genoma Mitocondrial , Desequilíbrio de Ligação , Masculino , Filogenia , Filogeografia , Polimorfismo de Nucleotídeo Único , Cromossomo Y
7.
Inorg Chem ; 59(22): 16725-16736, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33152248

RESUMO

Both methane (CH4) and acetylene (C2H2) are important energy source and raw chemicals in many industrial processes. The development of an energy-efficient and environmentally friendly separation and purification strategy for CH4 and C2H2 is necessary. Ultramicroporous metal-organic framework (MOF) materials have shown great success in the separation and purification of small-molecule gases. Herein, the synergy effect of tritopic polytetrazolate and ditopic terephthalate ligands successfully generates a series of isoreticular ultramicroporous cadmium tetrazolate-carboxylate MOF materials (SNNU-13-16) with excellent CH4 and C2H2 purification performance. Except for the uncoordinated tetrazolate N atoms serving as Lewis base sites, the pore size and pore surface of MOFs are systematically engineered by regulating dicarboxylic acid ligands varying from OH-BDC (SNNU-13) to Br-BDC (SNNU-14) to NH2-BDC (SNNU-15) to 1,4-NDC (SNNU-16). Benefiting from the ultramicroporous character (3.8-5.9 Å), rich Lewis base N sites, and tunable pore environments, all of these ultramicroporous MOFs exhibit a prominent separation capacity for carbon dioxide (CO2) or C2 hydrocarbons from CH4 and C2H2. Remarkably, SNNU-16 built by 1,4-NDC shows the highest ideal adsorbed solution theory CO2/CH4, ethylene (C2H4)/CH4, and C2H2/CH4 separation selectivity values, which are higher than those of most famous MOFs with or without open metal sites. Dynamic breakthrough experiments show that SNNU-16 can also efficiently separate the C2H2/CO2 mixtures with a gas flow rate of 4 mL min-1 under 1 bar and 298 K. The breakthrough time (18 min g-1) surpasses most best-gas-separation MOFs and nearly all other metal azolate-carboxylate MOF materials under the same conditions. The above prominently CH4 and C2H2 purification abilities of SNNU-13-16 materials were further confirmed by the Grand Canonical Monte Carlo (GCMC) simulations.

8.
Exp Cell Res ; 376(1): 77-85, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30690026

RESUMO

Cyclic stretch regulates proliferation of vascular smooth muscle cells (VSMCs) during hypertension-induced vascular remodeling, but the underlying mechanisms remain to be studied. Connective tissue growth factor (CTGF) has been reported associated with several cellular function such as proliferation,migration and adhesion. Herein, the role of CTGF in VSMCs was investigated in response to mechanical cyclic stretch. Here we show that CTGF is up-regulated both in vivo and in vitro during hypertension. Overexpression of CTGF markedly promoted VSMC proliferation, whereas CTGF knockdown attenuated cyclic stretch-induced proliferation. Furthermore, 3'UTR reporter assays revealed that microRNA-19b-3p (miR-19b-3p) directly regulates CTGF expression. Under pathological condition (e.g. 15% cyclic stretch), miR-19b-3p expression was significantly down-regulated; conversely miR-19b-3p overexpression blocked VSMC proliferation. Taken together, these findings indicate that pathological cyclic stretch induces vascular remodeling by promoting VSMC proliferation via miR-19b-3p/CTGF pathway, and point to CTGF as a potential therapeutic target for hypertension.


Assuntos
Proliferação de Células/genética , Fator de Crescimento do Tecido Conjuntivo/genética , Hipertensão/genética , MicroRNAs/genética , Músculo Liso Vascular/crescimento & desenvolvimento , Regiões 3' não Traduzidas/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/patologia , Músculo Liso Vascular/metabolismo , Transdução de Sinais/genética
9.
Sheng Li Xue Bao ; 72(4): 506-512, 2020 Aug 25.
Artigo em Zh | MEDLINE | ID: mdl-32820313

RESUMO

Alzheimer's disease (AD) is currently the most prevalent neurodegenerative disease in the aging population. It is characterized by massive deposition of extracellular ß-amyloid peptide and formation of intracellular neurofibrillary tangles. Cancer is also an age-related disease. Some epidemiological studies have shown an inverse relationship between AD and the onset of various types of cancers, that is, the risk of cancer in patients with AD is reduced, and vice versa. Epigenetic mechanisms play important roles in the development of AD and cancer. In this article, we will review the recent research advances on the epigenetic mechanisms of AD and cancer onset, and provide new ideas for rethinking the relevance of AD and cancer with a "holistic concept".


Assuntos
Doença de Alzheimer , Neoplasias , Doenças Neurodegenerativas , Idoso , Epigênese Genética , Humanos , Emaranhados Neurofibrilares
10.
Mol Biol Evol ; 35(1): 149-158, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29087519

RESUMO

The geographic origin and migration of the brown rat (Rattus norvegicus) remain subjects of considerable debate. In this study, we sequenced whole genomes of 110 wild brown rats with a diverse world-wide representation. We reveal that brown rats migrated out of southern East Asia, rather than northern Asia as formerly suggested, into the Middle East and then to Europe and Africa, thousands of years ago. Comparison of genomes from different geographical populations reveals that many genes involved in the immune system experienced positive selection in the wild brown rat.


Assuntos
Filogeografia/métodos , Ratos/genética , África , Animais , Sudeste Asiático/epidemiologia , Evolução Biológica , Europa (Continente) , Evolução Molecular , Variação Genética/genética , Genética Populacional , Genoma/genética , Oriente Médio , Filogenia , Sequenciamento Completo do Genoma/métodos
11.
Inorg Chem ; 58(16): 11220-11230, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31368311

RESUMO

The detection of nitro compounds and removal of organic dyes remain urgent issues because they are poisonous to humans. Taking advantage of metal-organic framework (MOF) materials, we demonstrate herein an indium-organic framework (InOF) exhibiting sensitive fluorescence sensing of nitro compounds, prominent dye capture, and excellent photodegradation of dyes. By using 4,4',4″-s-triazine-1,3,5-triyltri-p-aminobenzoate (TATAB), an amino-functionalized BTB-like linker, the 3D SNNU-110 structure ({[In3OCl(H2O)2(TATAB)2]}n) is formed. SNNU-110 shows a 3,6-connected 3,6T22 topology with TATAB and [In3O(CO2)6] tricapped trigonal-prismatic clusters as 3- and 6-connected nodes. Thanks to the fluorescence properties and amine recognition sites of TATAB, SNNU-110 exhibits excellent performance of fluorescence quenching for six electron-deficient nitroaromatics. The intercrossing 1D channels in SNNU-110 formed from the a- and b-axis directions with dimensions of about 18 Å × 11 Å can capture diverse cationic, anionic, or neutral dyes effectively. What is more, the existence of an inorganic [In3O] cluster enable SNNU-110 to be a good photocatalyst. Upon irradiation with a 300 W xenon lamp, SNNU-110 shows outstanding photocatalytic activity toward rhodamine B (RhB) and methylene blue (MB), and there was almost no degradation. The catalytic activity can retain about 94.6% (RhB) and 93.1% (MB), respectively. Overall, SNNU-110 fully demonstrates the power of multicomponent MOFs, which provide a feasible route for the design of functional materials toward to pollutant identification and removal applications.

12.
Proc Natl Acad Sci U S A ; 113(19): 5293-8, 2016 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-27114541

RESUMO

Cyclic stretch is an important inducer of vascular smooth muscle cell (VSMC) proliferation, which is crucial in vascular remodeling during hypertension. However, the molecular mechanism remains unclear. We studied the effects of emerin and lamin A/C, two important nuclear envelope proteins, on VSMC proliferation in hypertension and the underlying mechano-mechanisms. In common carotid artery of hypertensive rats in vivo and in cultured cells subjected to high (15%) cyclic stretch in vitro, VSMC proliferation was increased significantly, and the expression of emerin and lamin A/C was repressed compared with normotensive or normal (5%) cyclic stretch controls. Using targeted siRNA to mimic the repressed expression of emerin or lamin A/C induced by 15% stretch, we found that VSMC proliferation was enhanced under static and 5%-stretch conditions. Overexpression of emerin or lamin A/C reversed VSMC proliferation induced by 15% stretch. Hence, emerin and lamin A/C play critical roles in suppressing VSMC hyperproliferation induced by hyperstretch. ChIP-on-chip and MOTIF analyses showed that the DNAs binding with emerin contain three transcription factor motifs: CCNGGA, CCMGCC, and ABTTCCG; DNAs binding with lamin A/C contain the motifs CVGGAA, GCCGCYGC, and DAAGAAA. Protein/DNA array proved that altered emerin or lamin A/C expression modulated the activation of various transcription factors. Furthermore, accelerating local expression of emerin or lamin A/C reversed cell proliferation in the carotid artery of hypertensive rats in vivo. Our findings establish the pathogenetic role of emerin and lamin A/C repression in stretch-induced VSMC proliferation and suggest mechanobiological mechanism underlying this process that involves the sequence-specific binding of emerin and lamin A/C to specific transcription factor motifs.


Assuntos
Proliferação de Células/fisiologia , Lamina Tipo A/metabolismo , Mecanotransdução Celular/fisiologia , Proteínas de Membrana/metabolismo , Miócitos de Músculo Liso/fisiologia , Membrana Nuclear/metabolismo , Proteínas Nucleares/metabolismo , Animais , Células Cultivadas , Masculino , Músculo Liso Vascular/citologia , Músculo Liso Vascular/fisiologia , Miócitos de Músculo Liso/citologia , Ratos , Ratos Sprague-Dawley , Estresse Mecânico , Resistência à Tração/fisiologia
13.
Angew Chem Int Ed Engl ; 58(38): 13590-13595, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31407503

RESUMO

A strategy called ultramicroporous building unit (UBU) is introduced. It allows the creation of hierarchical bi-porous features that work in tandem to enhance gas uptake capacity and separation. Smaller pores from UBUs promote selectivity, while larger inter-UBU packing pores increase uptake capacity. The effectiveness of this UBU strategy is shown with a cobalt MOF (denoted SNNU-45) in which octahedral cages with 4.5 Špore size serve as UBUs. The C2 H2 uptake capacity at 1 atm reaches 193.0 cm3 g-1 (8.6 mmol g-1 ) at 273 K and 134.0 cm3 g-1 (6.0 mmol g-1 ) at 298 K. Such high uptake capacity is accompanied by a high C2 H2 /CO2 selectivity of up to 8.5 at 298 K. Dynamic breakthrough studies at room temperature and 1 atm show a C2 H2 /CO2 breakthrough time up to 79 min g-1 , among top-performing MOFs. Grand canonical Monte Carlo simulations agree that ultrahigh C2 H2 /CO2 selectivity is mainly from UBU ultramicropores, while packing pores promote C2 H2 uptake capacity.

14.
Mol Biol Evol ; 34(12): 3148-3153, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28961982

RESUMO

The laboratory rat, widely used in biomedical research, is domesticated from wild brown rat. The origin and genetic mechanism underlying domestication of the laboratory rat remain largely elusive. In the present study, large scale genomes supported a single origin for the laboratory rat, possibly from a sister group to wild rats from Europe/Africa/Middle East. Genomic and transcriptomic analyses uncovered many artificially selected genes (e.g., FOXP2, B3GAT1, and CLOCK) involved in the nervous system. These genes associate with learning ability and regulation of circadian rhythm, which likely enabled the successful domestication of the laboratory rat. Particularly, many genes, including mitochondrial genes responsible for energy metabolism, displayed a substantially increased expression in the brain of laboratory rats compared with wild rats. Our findings demystify the origin and evolution of this model animal, and provide insight into the process of its domestication.


Assuntos
Animais Domésticos/genética , Ratos/genética , Animais , Evolução Biológica , Proteínas CLOCK/genética , Domesticação , Metabolismo Energético/genética , Evolução Molecular , Fatores de Transcrição Forkhead/genética , Genoma/genética , Genômica/métodos , Aprendizagem/fisiologia , Filogenia , Seleção Genética/genética
15.
Knee Surg Sports Traumatol Arthrosc ; 24(9): 2806-2810, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25583655

RESUMO

The discoid medial meniscus is an extremely rare anomaly. Bilateral discoid medial menisci are much more rare but intermittently reported. We report the first case of bilateral discoid medial menisci with positive double PCL sign, which typically indicates a bucket-handle tear of medial meniscus. A literature review was also conducted on bilateral discoid medial menisci.


Assuntos
Doenças das Cartilagens/congênito , Deformidades Congênitas das Extremidades Inferiores/diagnóstico por imagem , Imageamento por Ressonância Magnética , Meniscos Tibiais/anormalidades , Ligamento Cruzado Posterior/diagnóstico por imagem , Lesões do Menisco Tibial/diagnóstico por imagem , Adolescente , Artroscopia , Doenças das Cartilagens/diagnóstico por imagem , Diagnóstico Diferencial , Humanos , Masculino , Meniscos Tibiais/diagnóstico por imagem
16.
Yi Chuan ; 38(8): 707-17, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27531609

RESUMO

The genomes of more and more organisms have been sequenced due to the advances in next-generation sequencing technologies. As a powerful tool, computer simulators play a critical role in studying the genome-wide DNA polymorphism pattern. Simulations can be performed both forwards-in-time and backwards-in-time, which complement each other and are suitable for meeting different needs, such as studying the effect of evolutionary dynamics, the estimation of parameters, and the validation of evolutionary hypotheses as well as new methods. In this review, we briefly introduced population genetics related theoretical framework and provided a detailed comparison of 32 simulators published over the last ten years. The future development of new simulators was also discussed.


Assuntos
Simulação por Computador , Genética Populacional/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Evolução Molecular
17.
ChemSusChem ; : e202400704, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38860330

RESUMO

The biosynthesis of valuable plant-derived monoterpene (-)-menthol from readily available feedstocks (e.g., (-)-limonene) is of great significance because of the high market demand for this product. However, biotransforming (+)-pulegone into (-)-menthone, the (-)-menthol precursor, through (+)-pulegone reductase (PGR) catalysis is inefficient because of the poor protein expression or catalytic efficiency (kcat/Km) of plant origin PGRs. In this study, a novel bacterial PGR from Pseudomonas resinovorans (PrPGR) was identified, and the most successful variant, PrPGRM2-1 (A50V/G53W), was obtained, showing respective 20-fold and 204-fold improvements in specific activity and catalytic efficiency. PrPGRM2-1 was employed to bioreduce (+)-pulegone, resulting in 4.4-fold and 35-fold enhancements in (-)-menthone titers compared with the bioreductions catalyzed by wild-type (WT) PrPGR and MpPGR, respectively. Furthermore, a whole-cell biocatalyst containing PrPGRM2-1, MpMMR, and BstFDH was constructed and achieved the highest (-)-menthol titer reported to date without externally supplemented NADPH/NADP+. Overall, this study details an efficient PGR with high catalytic efficiency that possesses great potential for (-)-menthol biosynthesis.

18.
Lancet Infect Dis ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38878787

RESUMO

Avian influenza virus continues to pose zoonotic, epizootic, and pandemic threats worldwide, as exemplified by the 2020-23 epizootics of re-emerging H5 genotype avian influenza viruses among birds and mammals and the fatal jump to humans of emerging A(H3N8) in early 2023. Future influenza pandemic threats are driven by extensive mutations and reassortments of avian influenza viruses rooted in frequent interspecies transmission and genetic mixing and underscore the urgent need for more effective actions. We examine the changing global epidemiology of human infections caused by avian influenza viruses over the past decade, including dramatic increases in both the number of reported infections in humans and the spectrum of avian influenza virus subtypes that have jumped to humans. We also discuss the use of advanced surveillance, diagnostic technologies, and state-of-the-art analysis methods for tracking emerging avian influenza viruses. We outline an avian influenza virus-specific application of the One Health approach, integrating enhanced surveillance, tightened biosecurity, targeted vaccination, timely precautions, and timely clinical management, and fostering global collaboration to control the threats of avian influenza viruses.

19.
Nanoscale ; 14(48): 18200-18208, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36465000

RESUMO

It is well known that the introduction of exposed fluorine (F) sites into metal-organic frameworks (MOFs) can effectively promote acetylene (C2H2) adsorption via C-H⋯F hydrogen bonds. However, such super strong hydrogen bonding interactions usually lead to very high acetylene adsorption enthalpy and thus require more energy during the adsorbent regeneration process. As the same group elements, chlorine (Cl), bromine (Br) and iodine (I) also can act as hydrogen bond acceptors but with relatively weak forces. So, it is speculated that the decoration of Cl, Br or I sites on the pore surface of MOF adsorbents may enhance acetylene adsorption but with lower energy consumption. Herein, ultra-microporous MOFs constructed by Cu4X4 (X = Cl, Br, I) motifs and 1,2,4-triazolate linkers, namely, [Cu8X4(TRZ)4]n (TRZ = 3,5-diethyl-1,2,4-triazole or detrz for SNNU-313-X, and 3,5-dipropyl-1,2,4-triazole or dptrz for SNNU-314-X), provide an ideal platform to investigate the effect of C-H⋯X (X = Cl, Br, I) hydrogen bonding on C2H2 adsorption and purification performance. Benefiting from the small pore size and pore environment, the C2H2 uptake and separation properties of this series of MOFs are systematically regulated. Detailed gas adsorption results show that with the same organic linker, the C2H2 uptake and separation (C2H2/C2H4 and C2H2/CO2) performance decrease clearly with the electronegativity of halogen ions (SNNU-313-Cl > SNNU-313-Br > SNNU-313-I). With the same halogen ion, the gas adsorption decreases with the bulk of decorated alkyl groups (SNNU-313-Cl > SNNU-314-Cl). Remarkably, SNNU-313/314 series MOF adsorbents exhibit moderate C2H2 uptake capacity and high separation ability, but the C2H2 adsorption enthalpies are much lower than those of MOF materials with exposed F sites. Dynamic fixed-bed column breakthrough experiments and Grand Canonical Monte Carlo (GCMC) simulations further indicate the critical effects of halogen hydrogen bonds on acetylene adsorption and separation. Overall, this work demonstrated an effective regulation of acetylene adsorption and separation by rational C-H⋯X hydrogen bonding, which may provide a new route for the exploration of energy-efficient acetylene adsorbent materials.

20.
Zool Res ; 43(1): 52-63, 2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-34821086

RESUMO

The ability to sense temperature changes is crucial for mammalian survival. Mammalian thermal sensing is primarily carried out by thermosensitive transient receptor potential channels (Thermo-TRPs). Some mammals hibernate to survive cold winter conditions, during which time their body temperature fluctuates dramatically. However, the underlying mechanisms by which these mammals regulate thermal responses remain unclear. Using quantitative real-time polymerase chain reaction (qRT-PCR) and the Western blotting, we found that Myotis ricketti bats had high levels of heat-activated TRPs (e.g., TRPV1 and TRPV4) during torpor in winter and cold-activated TRPs (e.g., TRPM8 and TRPC5) during active states in summer. We also found that laboratory mice had high mRNA levels of cold-activated TRPs (e.g., Trpm8 and Trpc5) under relatively hot conditions (i.e., 40 °C). These data suggest that small mammals up-regulate the expression of cold-activated TRPs even under warm or hot conditions. Binding site analysis showed that some homeobox (HOX) transcription factors (TFs) regulate the expression of hot- and cold-activated TRP genes and that some TFs of the Pit-Oct-Unc (POU) family regulate warm-sensitive and cold-activated TRP genes. The dual-luciferase reporter assay results demonstrated that TFs HOXA9, POU3F1, and POU5F1 regulate TRPC5 expression, suggesting that Thermo-TRP genes are regulated by multiple TFs of the HOX and POU families at different levels. This study provides insights into the adaptive mechanisms underlying thermal sensing used by bats to survive hibernation.


Assuntos
Quirópteros , Temperatura Alta , Estações do Ano , Canais de Cátion TRPC , Animais , Quirópteros/genética , Feminino , Hibernação/genética , Masculino , Camundongos , Canais de Cátion TRPC/genética , Canais de Cátion TRPV/genética
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