The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms.Methylation of N6 adenosine(m^(6)A)and C5 cytosine(m^(5)C)bases occur on mRNA...The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms.Methylation of N6 adenosine(m^(6)A)and C5 cytosine(m^(5)C)bases occur on mRNAs,tRNA,mt-tRNA,and rRNA species as well as non-coding RNAs.With emerging knowledge of RNA binding proteins that act as writer,reader,and eraser effector proteins,comes a new understanding of physiological processes controlled by these systems.Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain,give rise to different forms of disease.In this review,we discuss accumulating evidence that changes in the m^(6)A and m^(5)C methylation systems contribute to neurocognitive disorders.Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m^(6)A RNA reader protein.Subsequently,familial mutations within the m^(6)A writer gene METTL5,m^(5)C writer genes NSUN2,NSUN3,NSUN5,and NSUN6,as well as THOC2 and THOC6 that form a protein complex with the m^(5)C reader protein ALYREF,were recognized to cause intellectual development disorders.Similarly,differences in expression of the m^(5)C writer and reader effector proteins,NSUN6,NSUN7,and ALYREF in brain tissue are indicated in individuals with Alzheimer's disease,individuals with a high neuropathological load or have suffered traumatic brain injury.Likewise,an abundance of m^(6)A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases,Alzheimer's disease,and individuals with high cognitive reserve.m^(6)A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson's disease tissue,whilst modified RNAs are misplaced within diseased cells,particularly where synapses are located.In parahippocampal brain tissue,m^(6)A modification is enriched in transcripts associated with psychiatric disorders including conditions with clear cognitive deficits.These findings indicate a diverse set of molecular mechanisms are influenced by RNA methylation systems that can cause neuronal and synaptic dysfunction underlying neurocognitive disorders.Targeting these RNA modification systems brings new prospects for neural regenerative therapies.展开更多
Annual forage legumes are important components of livestock production systems in East Texas and the southeastern US. Forage legumes contribute nitrogen (N) to cropping systems through biological N fixation, and their...Annual forage legumes are important components of livestock production systems in East Texas and the southeastern US. Forage legumes contribute nitrogen (N) to cropping systems through biological N fixation, and their seasonal biomass production can be managed to complement forage grasses. Our research objectives were to evaluate both warm- and cool-season annual forage legumes as green manure for biomass, N content, ability to enhance soil organic carbon (SOC) and soil N, and impact on post season forage grass crops. Nine warm-season forage legumes (WSL) were spring planted and incorporated as green manure in the fall. Forage rye (Secale cereale L.) was planted following the incorporation of WSL treatments. Eight cool-season forage legumes (CSL) were fall planted in previously fallow plots and incorporated as green manure in late spring. Sorghum-sudangrass (Sorghum bicolor x Sorghum bicolor var. sudanense) was planted over all treatments in early summer after forage rye harvest and incorporation of CSL treatments. Sorghum-sudangrass was harvested in June, August and September, and treatments were evaluated for dry matter and N concentration. Soil cores were taken from each plot, split into depths of 0 to 15, 15 to 30 and 30 to 60 cm, and soil C and N were measured using combustion analysis. Nylon mesh bags containing plant samples were buried at 15 cm and used to evaluate decomposition rate of above ground legume biomass, including change in C and N concentrations. Mungbean (Vigna radiata L. [Wilczek]) had the highest shoot biomass yield (6.24 t DM ha<sup>-1</sup>) and contributed the most total N (167 kg∙ha<sup>-1</sup>) and total C (3043 kg∙ha<sup>-1</sup>) of the WSL tested. Decomposition rate of WSL biomass was rapid in the first 10 weeks and very slow afterward. Winter pea (Pisum sativum L. spp. sativum), arrow leaf clover (Trifolium vesiculosum Savi.), and crimson clover (Trifolium incarnatum L.) were the most productive CSL in this trial. Austrian winter pea produced 8.41 t DM ha<sup>-1</sup> with a total N yield of 319 kg N ha<sup>-1</sup> and total C production of 3835 kg C ha<sup>-1</sup>. The WSL treatments had only small effects on rye forage yield and N concentration, possibly due to mineralization of N from a large SOC pool already in place. The CSL treatments also had only minimal effects on sorghum-sudangrass forage production. Winter pea, arrow leaf and crimson clover were productive cool season legumes and could be useful as green manure crops. Mungbean and cowpea (Vigna unguiculata [L.] Walp.) were highly productive warm season legumes but may include more production risk in green manure systems due to soil moisture competition.展开更多
Background:Nitrogen(N)deposition affects forest stoichiometric flexibility through changing soil nutrient availability to influence plant uptake.However,the effect of N deposition on the flexibility of carbon(C),N,and...Background:Nitrogen(N)deposition affects forest stoichiometric flexibility through changing soil nutrient availability to influence plant uptake.However,the effect of N deposition on the flexibility of carbon(C),N,and phosphorus(P)in forest plant-soil-microbe systems remains unclear.Methods:We conducted a meta-analysis based on 751 pairs of observations to evaluate the responses of plant,soil and microbial biomass C,N and P nutrients and stoichiometry to N addition in different N intensity(050,50–100,>100 kg·ha^(-1)·year^(-1)of N),duration(0–5,>5 year),method(understory,canopy),and matter(ammonium N,nitrate N,organic N,mixed N).Results:N addition significantly increased plant N:P(leaf:14.98%,root:13.29%),plant C:P(leaf:6.8%,root:25.44%),soil N:P(13.94%),soil C:P(10.86%),microbial biomass N:P(23.58%),microbial biomass C:P(12.62%),but reduced plant C:N(leaf:6.49%,root:9.02%).Furthermore,plant C:N:P stoichiometry changed significantly under short-term N inputs,while soil and microorganisms changed drastically under high N addition.Canopy N addition primarily affected plant C:N:P stoichiometry through altering plant N content,while understory N inputs altered more by influencing soil C and P content.Organic N significantly influenced plant and soil C:N and C:P,while ammonia N changed plant N:P.Plant C:P and soil C:N were strongly correlated with mean annual precipitation(MAT),and the C:N:P stoichiometric flexibility in soil and plant under N addition connected with soil depth.Besides,N addition decoupled the correlations between soil microorganisms and the plant.Conclusions:N addition significantly increased the C:P and N:P in soil,plant,and microbial biomass,reducing plant C:N,and aggravated forest P limitations.Significantly,these impacts were contingent on climate types,soil layers,and N input forms.The findings enhance our comprehension of the plant-soil system nutrient cycling mechanisms in forest ecosystems and plant strategy responses to N deposition.展开更多
H7N9 subtype avian influenza virus poses a great challenge for poultry industry.Newcastle disease virus(NDV)-vectored H7N9 avian influenza vaccines(NDV_(vec)H7N9)are effective in disease control because they are prote...H7N9 subtype avian influenza virus poses a great challenge for poultry industry.Newcastle disease virus(NDV)-vectored H7N9 avian influenza vaccines(NDV_(vec)H7N9)are effective in disease control because they are protective and allow mass administration.Of note,these vaccines elicit undetectable H7N9-specific hemagglutination-inhibition(HI)but high IgG antibodies in chickens.However,the molecular basis and protective mechanism underlying this particular antibody immunity remain unclear.Herein,immunization with an NDV_(vec)H7N9 induced low anti-H7N9 HI and virus neutralization titers but high levels of hemagglutinin(HA)-binding IgG antibodies in chickens.Three residues(S150,G151 and S152)in HA of H7N9 virus were identified as the dominant epitopes recognized by the NDV_(vec)H7N9 immune serum.Passively transferred NDV_(vec)H7N9 immune serum conferred complete protection against H7N9 virus infection in chickens.The NDV_(vec)H7N9 immune serum can mediate a potent lysis of HA-expressing and H7N9 virus-infected cells and significantly suppress H7N9 virus infectivity.These activities of the serum were significantly impaired after heat-inactivation or treatment with complement inhibitor,suggesting the engagement of the complement system.Moreover,mutations in the 150-SGS-152 sites in HA resulted in significant reductions in cell lysis and virus neutralization mediated by the NDV_(vec)H7N9 immune serum,indicating the requirement of antibody-antigen binding for complement activity.Therefore,antibodies induced by the NDV_(vec)H7N9 can activate antibody-dependent complement-mediated lysis of H7N9 virus-infected cells and complement-mediated neutralization of H7N9 virus.Our findings unveiled a novel role of the complement in protection conferred by the NDV_(vec)H7N9,highlighting a potential benefit of engaging the complement system in H7N9 vaccine design.展开更多
An operationally simple protocol was designed for the enantioselective silane reduction (ESR) of ketones using air- and moisture-stable [Ir(OMe)(cod)]<sub>2</sub> (cod = 1,5-cyclooctadiene) (3) as a metal ...An operationally simple protocol was designed for the enantioselective silane reduction (ESR) of ketones using air- and moisture-stable [Ir(OMe)(cod)]<sub>2</sub> (cod = 1,5-cyclooctadiene) (3) as a metal catalyst precursor. This reaction was driven by chiral hydroxyamide-functionalized azolium salt 2. The catalytic ESR reaction could be performed under benchtop conditions at room temperature. Treatment of 2 with 3 in THF yielded the monodentate IrCl(NHC)(cod) (NHC = N-heterocyclic carbene) complex 4 in 93% yield, herein the anionic methoxy ligand of 3 serves as an internal base that deprotonates the azolium ring of 2. The well-defined Ir complex 4 catalyzed the ESR reaction of propiophenone (6) with (EtO)<sub>2</sub>MeSiH using the pre-mixing reaction procedure. Based on this success, the catalytic ESR reaction was designed and implemented using an in situ-generated NHC/Ir catalyst derived from 2 and 3. Thus, a wide variety of aryl ketones could be reduced to the corresponding optically active alcohols in moderate to excellent stereoselectivities at room temperature without temperature control. Since the high catalytic activity of 3 was observed, we next evaluated several other transition metal catalyst precursors for the catalytic ESR reaction under the influence of 2. This evaluation revealed that Ir(acac)(cod) (acac = acetylacetonate) (28) and [IrCl(cod)]<sub>2</sub> (5) can be successfully used as metal catalyst precursors in the ESR reaction.展开更多
基金funded by Notingham University and the Neuroscience Support Group Charity,UK(to HMK)supported by a CONACYT PhD scholarshipMD?was supported by the Postdoctoral Research Fellowship Program of TUBITAK。
文摘The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms.Methylation of N6 adenosine(m^(6)A)and C5 cytosine(m^(5)C)bases occur on mRNAs,tRNA,mt-tRNA,and rRNA species as well as non-coding RNAs.With emerging knowledge of RNA binding proteins that act as writer,reader,and eraser effector proteins,comes a new understanding of physiological processes controlled by these systems.Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain,give rise to different forms of disease.In this review,we discuss accumulating evidence that changes in the m^(6)A and m^(5)C methylation systems contribute to neurocognitive disorders.Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m^(6)A RNA reader protein.Subsequently,familial mutations within the m^(6)A writer gene METTL5,m^(5)C writer genes NSUN2,NSUN3,NSUN5,and NSUN6,as well as THOC2 and THOC6 that form a protein complex with the m^(5)C reader protein ALYREF,were recognized to cause intellectual development disorders.Similarly,differences in expression of the m^(5)C writer and reader effector proteins,NSUN6,NSUN7,and ALYREF in brain tissue are indicated in individuals with Alzheimer's disease,individuals with a high neuropathological load or have suffered traumatic brain injury.Likewise,an abundance of m^(6)A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases,Alzheimer's disease,and individuals with high cognitive reserve.m^(6)A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson's disease tissue,whilst modified RNAs are misplaced within diseased cells,particularly where synapses are located.In parahippocampal brain tissue,m^(6)A modification is enriched in transcripts associated with psychiatric disorders including conditions with clear cognitive deficits.These findings indicate a diverse set of molecular mechanisms are influenced by RNA methylation systems that can cause neuronal and synaptic dysfunction underlying neurocognitive disorders.Targeting these RNA modification systems brings new prospects for neural regenerative therapies.
文摘Annual forage legumes are important components of livestock production systems in East Texas and the southeastern US. Forage legumes contribute nitrogen (N) to cropping systems through biological N fixation, and their seasonal biomass production can be managed to complement forage grasses. Our research objectives were to evaluate both warm- and cool-season annual forage legumes as green manure for biomass, N content, ability to enhance soil organic carbon (SOC) and soil N, and impact on post season forage grass crops. Nine warm-season forage legumes (WSL) were spring planted and incorporated as green manure in the fall. Forage rye (Secale cereale L.) was planted following the incorporation of WSL treatments. Eight cool-season forage legumes (CSL) were fall planted in previously fallow plots and incorporated as green manure in late spring. Sorghum-sudangrass (Sorghum bicolor x Sorghum bicolor var. sudanense) was planted over all treatments in early summer after forage rye harvest and incorporation of CSL treatments. Sorghum-sudangrass was harvested in June, August and September, and treatments were evaluated for dry matter and N concentration. Soil cores were taken from each plot, split into depths of 0 to 15, 15 to 30 and 30 to 60 cm, and soil C and N were measured using combustion analysis. Nylon mesh bags containing plant samples were buried at 15 cm and used to evaluate decomposition rate of above ground legume biomass, including change in C and N concentrations. Mungbean (Vigna radiata L. [Wilczek]) had the highest shoot biomass yield (6.24 t DM ha<sup>-1</sup>) and contributed the most total N (167 kg∙ha<sup>-1</sup>) and total C (3043 kg∙ha<sup>-1</sup>) of the WSL tested. Decomposition rate of WSL biomass was rapid in the first 10 weeks and very slow afterward. Winter pea (Pisum sativum L. spp. sativum), arrow leaf clover (Trifolium vesiculosum Savi.), and crimson clover (Trifolium incarnatum L.) were the most productive CSL in this trial. Austrian winter pea produced 8.41 t DM ha<sup>-1</sup> with a total N yield of 319 kg N ha<sup>-1</sup> and total C production of 3835 kg C ha<sup>-1</sup>. The WSL treatments had only small effects on rye forage yield and N concentration, possibly due to mineralization of N from a large SOC pool already in place. The CSL treatments also had only minimal effects on sorghum-sudangrass forage production. Winter pea, arrow leaf and crimson clover were productive cool season legumes and could be useful as green manure crops. Mungbean and cowpea (Vigna unguiculata [L.] Walp.) were highly productive warm season legumes but may include more production risk in green manure systems due to soil moisture competition.
基金supported by the National Natural Science Foundation of China(Nos.31800369,32271686,U1904204)the State Scholarship Fund of Chinathe Innovation Scientists and Technicians Troop Construction Projects of Henan Province(No.182101510005)。
文摘Background:Nitrogen(N)deposition affects forest stoichiometric flexibility through changing soil nutrient availability to influence plant uptake.However,the effect of N deposition on the flexibility of carbon(C),N,and phosphorus(P)in forest plant-soil-microbe systems remains unclear.Methods:We conducted a meta-analysis based on 751 pairs of observations to evaluate the responses of plant,soil and microbial biomass C,N and P nutrients and stoichiometry to N addition in different N intensity(050,50–100,>100 kg·ha^(-1)·year^(-1)of N),duration(0–5,>5 year),method(understory,canopy),and matter(ammonium N,nitrate N,organic N,mixed N).Results:N addition significantly increased plant N:P(leaf:14.98%,root:13.29%),plant C:P(leaf:6.8%,root:25.44%),soil N:P(13.94%),soil C:P(10.86%),microbial biomass N:P(23.58%),microbial biomass C:P(12.62%),but reduced plant C:N(leaf:6.49%,root:9.02%).Furthermore,plant C:N:P stoichiometry changed significantly under short-term N inputs,while soil and microorganisms changed drastically under high N addition.Canopy N addition primarily affected plant C:N:P stoichiometry through altering plant N content,while understory N inputs altered more by influencing soil C and P content.Organic N significantly influenced plant and soil C:N and C:P,while ammonia N changed plant N:P.Plant C:P and soil C:N were strongly correlated with mean annual precipitation(MAT),and the C:N:P stoichiometric flexibility in soil and plant under N addition connected with soil depth.Besides,N addition decoupled the correlations between soil microorganisms and the plant.Conclusions:N addition significantly increased the C:P and N:P in soil,plant,and microbial biomass,reducing plant C:N,and aggravated forest P limitations.Significantly,these impacts were contingent on climate types,soil layers,and N input forms.The findings enhance our comprehension of the plant-soil system nutrient cycling mechanisms in forest ecosystems and plant strategy responses to N deposition.
基金supported by the earmarked fund for China Agriculture Research System(CARS-40)the Key Research and Development Project of Yangzhou(Modern Agriculture),China(YZ2022052)the‘‘High-end Talent Support Program’’of Yangzhou University,China。
文摘H7N9 subtype avian influenza virus poses a great challenge for poultry industry.Newcastle disease virus(NDV)-vectored H7N9 avian influenza vaccines(NDV_(vec)H7N9)are effective in disease control because they are protective and allow mass administration.Of note,these vaccines elicit undetectable H7N9-specific hemagglutination-inhibition(HI)but high IgG antibodies in chickens.However,the molecular basis and protective mechanism underlying this particular antibody immunity remain unclear.Herein,immunization with an NDV_(vec)H7N9 induced low anti-H7N9 HI and virus neutralization titers but high levels of hemagglutinin(HA)-binding IgG antibodies in chickens.Three residues(S150,G151 and S152)in HA of H7N9 virus were identified as the dominant epitopes recognized by the NDV_(vec)H7N9 immune serum.Passively transferred NDV_(vec)H7N9 immune serum conferred complete protection against H7N9 virus infection in chickens.The NDV_(vec)H7N9 immune serum can mediate a potent lysis of HA-expressing and H7N9 virus-infected cells and significantly suppress H7N9 virus infectivity.These activities of the serum were significantly impaired after heat-inactivation or treatment with complement inhibitor,suggesting the engagement of the complement system.Moreover,mutations in the 150-SGS-152 sites in HA resulted in significant reductions in cell lysis and virus neutralization mediated by the NDV_(vec)H7N9 immune serum,indicating the requirement of antibody-antigen binding for complement activity.Therefore,antibodies induced by the NDV_(vec)H7N9 can activate antibody-dependent complement-mediated lysis of H7N9 virus-infected cells and complement-mediated neutralization of H7N9 virus.Our findings unveiled a novel role of the complement in protection conferred by the NDV_(vec)H7N9,highlighting a potential benefit of engaging the complement system in H7N9 vaccine design.
文摘An operationally simple protocol was designed for the enantioselective silane reduction (ESR) of ketones using air- and moisture-stable [Ir(OMe)(cod)]<sub>2</sub> (cod = 1,5-cyclooctadiene) (3) as a metal catalyst precursor. This reaction was driven by chiral hydroxyamide-functionalized azolium salt 2. The catalytic ESR reaction could be performed under benchtop conditions at room temperature. Treatment of 2 with 3 in THF yielded the monodentate IrCl(NHC)(cod) (NHC = N-heterocyclic carbene) complex 4 in 93% yield, herein the anionic methoxy ligand of 3 serves as an internal base that deprotonates the azolium ring of 2. The well-defined Ir complex 4 catalyzed the ESR reaction of propiophenone (6) with (EtO)<sub>2</sub>MeSiH using the pre-mixing reaction procedure. Based on this success, the catalytic ESR reaction was designed and implemented using an in situ-generated NHC/Ir catalyst derived from 2 and 3. Thus, a wide variety of aryl ketones could be reduced to the corresponding optically active alcohols in moderate to excellent stereoselectivities at room temperature without temperature control. Since the high catalytic activity of 3 was observed, we next evaluated several other transition metal catalyst precursors for the catalytic ESR reaction under the influence of 2. This evaluation revealed that Ir(acac)(cod) (acac = acetylacetonate) (28) and [IrCl(cod)]<sub>2</sub> (5) can be successfully used as metal catalyst precursors in the ESR reaction.
