Every year, around the world, between 250,000 and 500,000 people suffer a spinal cord injury(SCI). SCI is a devastating medical condition that arises from trauma or disease-induced damage to the spinal cord, disruptin...Every year, around the world, between 250,000 and 500,000 people suffer a spinal cord injury(SCI). SCI is a devastating medical condition that arises from trauma or disease-induced damage to the spinal cord, disrupting the neural connections that allow communication between the brain and the rest of the body, which results in varying degrees of motor and sensory impairment. Disconnection in the spinal tracts is an irreversible condition owing to the poor capacity for spontaneous axonal regeneration in the affected neurons.展开更多
COVID-19 has devastated numerous nations around the world and has overburdened numerous healthcare systems,which has also caused the loss of livelihoods due to prolonged shutdowns and further led to a cascading effect...COVID-19 has devastated numerous nations around the world and has overburdened numerous healthcare systems,which has also caused the loss of livelihoods due to prolonged shutdowns and further led to a cascading effect on the global economy.COVID-19 infections have an incubation period of 2–7 days,but 40 to 45%of cases are asymptomatic or show mild to moderate respiratory symptoms after the period due to subclinical lung abnormalities,making it more likely to spread the pandemic disease.To restrict the spread of the virus,on-site diagnosis methods that are quicker,more precise,and easily accessible are required.Rapid Antigen Detection Tests and Polymerase Chain Reaction tests are currently the primary methods used to determine the presence of COVID-19 viruses.These tests are typically time-consuming,not accurate,and,more importantly,not available to everyone.Hence,in this review and hypothesis,we proposed equipment that employs the properties of photonics to improve the detection of COVID-19 viruses by taking the advantage of typical binding of coronavirus with angiotensin-converting enzyme 2(ACE2)receptors.This hypothetical model would combine Surface-Enhanced Raman Scattering(SERS)and Fluorescence Resonance Energy Transfer(FRET)to provide great flexibility,high sensitivities,and enhanced accessibility.展开更多
The coronavirus(COVID-19)pandemic has caused severe medical emergencies,economic depression,inflation,social distress,and research burden worldwide.Despite the severity of the spreading COVID-19,individual governments...The coronavirus(COVID-19)pandemic has caused severe medical emergencies,economic depression,inflation,social distress,and research burden worldwide.Despite the severity of the spreading COVID-19,individual governments and the World Health Organization have mandated several safety protocols including quarantine,physical distancing,advanced research in decoding the disease mechanism to build an effective vaccine,and promoting mental health to achieve the aim of coping through this infectious pandemic.Around the globe,mental health research emphasizes how social isolation impacts anxiety and depression,however,the cause of mental health depletion due to the type of individual's living accommodation(apartment and house)during a pandemic remains unexplored.The apartments have high elevation and high population density while the houses have low elevation and low population density as they are more spaced apart.This paper presents a novel hypothesis to maintain/enhance individuals’mental health during the pandemic,known as“Modi’s Pandemic Infrastructure Hypothesis”,which suggests that individuals residing in varying living accommodations(i.e.apartment or house)would exhibit a significant difference in the experienced pandemic(i.e.COVID-19)anxiety due to varying amount of experienced“silent stress”.Hence,any type of infrastructure(medical,residential,educational,or corporate)should be designed following the public survey of that geographic area based on hypotheses laid in this paper,to minimize the magnitude of“silent stress”.“Silent stress”can be defined as the stress that is unknowingly experienced in the assimilated living accommodation,which is responsible for depleting individuals’mental health and affecting the ability to cope with the pandemic.In support of this novel hypothesis,previous research has demonstrated that the number of coronavirus per unit area has a positive association with elevation above the ground level while a negative association with the population density.Although the scientific data supports the idea that there would be an equal trade-off in the quantity of coronavirus around an individual in both types of accommodation,however,psychologically the public would perceive it differently.Along with the two key variables(i.e.elevation and population density),other influencing factors would be taken into account while determining the magnitude of silent stress,pandemic anxiety,and the best type of infrastructure.In conclusion,this promising hypothesis will not only help the government to build anxiety-free infrastructure for pandemic times but also increase the effectiveness of medical treatments as mental health and strength is the best medicine to defeat severe diseases.展开更多
Dear Editor,The passage of DNA replication forks during eukaryotic cell division disrupts the nucleosomes they encounter,and de novo assembly of nucleosomes onto replicated DNA must take place to restore chromatin str...Dear Editor,The passage of DNA replication forks during eukaryotic cell division disrupts the nucleosomes they encounter,and de novo assembly of nucleosomes onto replicated DNA must take place to restore chromatin structure.There are two sources of histones for the replicationcoupled nucleosome assembly.展开更多
Promoter silencing by ectopic?de novo?methylation of tumor suppressor genes has been proposed as comparable or equivalent to inactivating mutations as a factor in carcinogenesis. However, this hypotheses had not previ...Promoter silencing by ectopic?de novo?methylation of tumor suppressor genes has been proposed as comparable or equivalent to inactivating mutations as a factor in carcinogenesis. However, this hypotheses had not previously been tested by high resolution,?high-coverage whole-genome methylation profiling in primary carcinomas. We have determined the genomic methylation status of a series of primary mammary carcinomas and matched control tissues by examination of more than 2.7 billion CpG dinucleotides. Most of the tumors showed variable losses of DNA methylation?from all sequence compartments, but increases in promoter methylation were infrequent, very small in extent, and were observed largely at CpG-poor promoters. De novo methylation at the promoters?of proto-oncogenes and tumor suppressor genes occurred at approximately the same frequency. The findings indicate that tumor suppressor silencing by?de novo?methylation is much less common than currently believed. We put forward a hypothesis under which the demethylation commonly observed in carcinomas is a manifestation of a defensive system that kills incipient cancer cells.展开更多
Obesity is characterized by chronic,low-grade inflammation,which is driven by macrophage infiltration of adipose tissue.PPARγ is well established to have an anti-inflammatory function in macrophages,but the mechanism...Obesity is characterized by chronic,low-grade inflammation,which is driven by macrophage infiltration of adipose tissue.PPARγ is well established to have an anti-inflammatory function in macrophages,but the mechanism that regulates its function in these cells remains to be fully elucidated.PPARγundergoes post-translational modifications(PTMs),including acetylation,to mediate ligand responses,including on metabolic functions.Here,we report that PPARγacetylation in macrophages promotes their infiltration into adipose tissue,exacerbating metabolic dysregulation.We generated a mouse line that expresses a macrophage-specific,constitutive acetylation-mimetic form of PPARγ(K293Q^(flox/flox):LysM-cre,mK293Q)to dissect the role of PPARγacetylation in macrophages.Upon highfat diet feeding to stimulate macrophage infiltration into adipose tissue,we assessed the overall metabolic profile and tissue-specific phenotype of the mutant mice,including responses to the PPARγagonist Rosiglitazone.Macrophage-specific PPARγK293Q expression promotes proinflammatory macrophage infiltration and fibrosis in epididymal white adipose tissue,but not in subcutaneous or brown adipose tissue,leading to decreased energy expenditure,insulin sensitivity,glucose tolerance,and adipose tissue function.Furthermore,mK293Q mice are resistant to Rosiglitazone-induced improvements in adipose tissue remodeling.Our study reveals that acetylation is a new layer of PPARγregulation in macrophage activation,and highlights the importance and potential therapeutic implications of such PTMs in regulating metabolism.展开更多
JMJD3(KDM6B)is an H3K27me3 demethylase and counteracts polycomb-mediated transcription repression.However,the function of JMJD3 in vivo is not well understood.Here we show that JMJD3 is highly expressed in cells of th...JMJD3(KDM6B)is an H3K27me3 demethylase and counteracts polycomb-mediated transcription repression.However,the function of JMJD3 in vivo is not well understood.Here we show that JMJD3 is highly expressed in cells of the chondrocyte lineage,especially in prehypertrophic and hypertrophic chondrocytes,during endochondral ossification.Homozygous deletion of Jmjd3 results in severely decreased proliferation and delayed hypertrophy of chondrocytes,and thereby marked retardation of endochondral ossification in mice.Genetically,JMJD3 associates with RUNX2 to promote proliferation and hypertrophy of chondrocytes.Biochemically,JMJD3 associates with and enhances RUNX2 activity by derepression of Runx2 and Ihh transcription throughits H3K27me3 demethylase activity.These results demonstrate that JMJD3 is a key epigenetic regulator in the process of cartilage maturation during endochondral bone formation.展开更多
Epigenetic research focuses on heritable changes beyond the DNA sequence, which has led to a revolution in biologicalstudies and benefits in many other fields. The well-known model ciliate, Tetrahymena thermophila off...Epigenetic research focuses on heritable changes beyond the DNA sequence, which has led to a revolution in biologicalstudies and benefits in many other fields. The well-known model ciliate, Tetrahymena thermophila offers a unique system forepigenetic studies due to its nuclear dimorphism and special mode of sexual reproduction (conjugation), as well as abundantgenomic resources and genetic tools. In this paper, we summarize recent progress made by our research team and collaboratorsin understanding epigenetic mechanisms using Tetrahymena. This includes: (1) providing the first genome-wide basepair-resolution map of DNA N6-methyladenine (6mA) and revealed it as an integral part of the chromatin landscape;(2)dissecting the relative contribution of cis・ and trans- elements to nucleosome distribution by exploring the unique nucleardimorphism of Tetrahymena, (3) demonstrating the epigenetic controls of RNAi-dependent Polycomb repression pathwayson transposable elements, and (4) identifying a new histone monomethyltransferase, TXR1 (Tetrahymena Trithorax 1), thatfacilitates replication elongation through 让s substrate histone H3 lysine 27 monomethylation (H3K27mel).展开更多
基金financially supported by Ministerio de Ciencia e Innovación projects SAF2017-82736-C2-1-R to MTMFin Universidad Autónoma de Madrid and by Fundación Universidad Francisco de Vitoria to JS+2 种基金a predoctoral scholarship from Fundación Universidad Francisco de Vitoriafinancial support from a 6-month contract from Universidad Autónoma de Madrida 3-month contract from the School of Medicine of Universidad Francisco de Vitoria。
文摘Every year, around the world, between 250,000 and 500,000 people suffer a spinal cord injury(SCI). SCI is a devastating medical condition that arises from trauma or disease-induced damage to the spinal cord, disrupting the neural connections that allow communication between the brain and the rest of the body, which results in varying degrees of motor and sensory impairment. Disconnection in the spinal tracts is an irreversible condition owing to the poor capacity for spontaneous axonal regeneration in the affected neurons.
文摘COVID-19 has devastated numerous nations around the world and has overburdened numerous healthcare systems,which has also caused the loss of livelihoods due to prolonged shutdowns and further led to a cascading effect on the global economy.COVID-19 infections have an incubation period of 2–7 days,but 40 to 45%of cases are asymptomatic or show mild to moderate respiratory symptoms after the period due to subclinical lung abnormalities,making it more likely to spread the pandemic disease.To restrict the spread of the virus,on-site diagnosis methods that are quicker,more precise,and easily accessible are required.Rapid Antigen Detection Tests and Polymerase Chain Reaction tests are currently the primary methods used to determine the presence of COVID-19 viruses.These tests are typically time-consuming,not accurate,and,more importantly,not available to everyone.Hence,in this review and hypothesis,we proposed equipment that employs the properties of photonics to improve the detection of COVID-19 viruses by taking the advantage of typical binding of coronavirus with angiotensin-converting enzyme 2(ACE2)receptors.This hypothetical model would combine Surface-Enhanced Raman Scattering(SERS)and Fluorescence Resonance Energy Transfer(FRET)to provide great flexibility,high sensitivities,and enhanced accessibility.
文摘The coronavirus(COVID-19)pandemic has caused severe medical emergencies,economic depression,inflation,social distress,and research burden worldwide.Despite the severity of the spreading COVID-19,individual governments and the World Health Organization have mandated several safety protocols including quarantine,physical distancing,advanced research in decoding the disease mechanism to build an effective vaccine,and promoting mental health to achieve the aim of coping through this infectious pandemic.Around the globe,mental health research emphasizes how social isolation impacts anxiety and depression,however,the cause of mental health depletion due to the type of individual's living accommodation(apartment and house)during a pandemic remains unexplored.The apartments have high elevation and high population density while the houses have low elevation and low population density as they are more spaced apart.This paper presents a novel hypothesis to maintain/enhance individuals’mental health during the pandemic,known as“Modi’s Pandemic Infrastructure Hypothesis”,which suggests that individuals residing in varying living accommodations(i.e.apartment or house)would exhibit a significant difference in the experienced pandemic(i.e.COVID-19)anxiety due to varying amount of experienced“silent stress”.Hence,any type of infrastructure(medical,residential,educational,or corporate)should be designed following the public survey of that geographic area based on hypotheses laid in this paper,to minimize the magnitude of“silent stress”.“Silent stress”can be defined as the stress that is unknowingly experienced in the assimilated living accommodation,which is responsible for depleting individuals’mental health and affecting the ability to cope with the pandemic.In support of this novel hypothesis,previous research has demonstrated that the number of coronavirus per unit area has a positive association with elevation above the ground level while a negative association with the population density.Although the scientific data supports the idea that there would be an equal trade-off in the quantity of coronavirus around an individual in both types of accommodation,however,psychologically the public would perceive it differently.Along with the two key variables(i.e.elevation and population density),other influencing factors would be taken into account while determining the magnitude of silent stress,pandemic anxiety,and the best type of infrastructure.In conclusion,this promising hypothesis will not only help the government to build anxiety-free infrastructure for pandemic times but also increase the effectiveness of medical treatments as mental health and strength is the best medicine to defeat severe diseases.
基金supported by the National Key Research and Development Program of China(2019YFA0508900)the National Natural Science Foundation of China(32330021,31991162,32200477)the Strategic Priority Research Program of Chinese Academy of Sciences(XDB37010100)。
文摘Dear Editor,The passage of DNA replication forks during eukaryotic cell division disrupts the nucleosomes they encounter,and de novo assembly of nucleosomes onto replicated DNA must take place to restore chromatin structure.There are two sources of histones for the replicationcoupled nucleosome assembly.
文摘Promoter silencing by ectopic?de novo?methylation of tumor suppressor genes has been proposed as comparable or equivalent to inactivating mutations as a factor in carcinogenesis. However, this hypotheses had not previously been tested by high resolution,?high-coverage whole-genome methylation profiling in primary carcinomas. We have determined the genomic methylation status of a series of primary mammary carcinomas and matched control tissues by examination of more than 2.7 billion CpG dinucleotides. Most of the tumors showed variable losses of DNA methylation?from all sequence compartments, but increases in promoter methylation were infrequent, very small in extent, and were observed largely at CpG-poor promoters. De novo methylation at the promoters?of proto-oncogenes and tumor suppressor genes occurred at approximately the same frequency. The findings indicate that tumor suppressor silencing by?de novo?methylation is much less common than currently believed. We put forward a hypothesis under which the demethylation commonly observed in carcinomas is a manifestation of a defensive system that kills incipient cancer cells.
基金This work was supported by the National Institutes of Health F31DK124926(N.A.),T32DK007328(N.A.),R01DK112943(L.Q.),R01DK128848(L.Q.),R01DK131169(U.B.P.and L.Q.),and P01 HL087123(L.Q.).
文摘Obesity is characterized by chronic,low-grade inflammation,which is driven by macrophage infiltration of adipose tissue.PPARγ is well established to have an anti-inflammatory function in macrophages,but the mechanism that regulates its function in these cells remains to be fully elucidated.PPARγundergoes post-translational modifications(PTMs),including acetylation,to mediate ligand responses,including on metabolic functions.Here,we report that PPARγacetylation in macrophages promotes their infiltration into adipose tissue,exacerbating metabolic dysregulation.We generated a mouse line that expresses a macrophage-specific,constitutive acetylation-mimetic form of PPARγ(K293Q^(flox/flox):LysM-cre,mK293Q)to dissect the role of PPARγacetylation in macrophages.Upon highfat diet feeding to stimulate macrophage infiltration into adipose tissue,we assessed the overall metabolic profile and tissue-specific phenotype of the mutant mice,including responses to the PPARγagonist Rosiglitazone.Macrophage-specific PPARγK293Q expression promotes proinflammatory macrophage infiltration and fibrosis in epididymal white adipose tissue,but not in subcutaneous or brown adipose tissue,leading to decreased energy expenditure,insulin sensitivity,glucose tolerance,and adipose tissue function.Furthermore,mK293Q mice are resistant to Rosiglitazone-induced improvements in adipose tissue remodeling.Our study reveals that acetylation is a new layer of PPARγregulation in macrophage activation,and highlights the importance and potential therapeutic implications of such PTMs in regulating metabolism.
基金This work was supported by the National Natural Science Foundation of China(91219304)National Basic Research Program of China(2010CB529705,2011CB510103,2014CB943100)the Council of Shanghai Municipal Government for Science and Technology.
文摘JMJD3(KDM6B)is an H3K27me3 demethylase and counteracts polycomb-mediated transcription repression.However,the function of JMJD3 in vivo is not well understood.Here we show that JMJD3 is highly expressed in cells of the chondrocyte lineage,especially in prehypertrophic and hypertrophic chondrocytes,during endochondral ossification.Homozygous deletion of Jmjd3 results in severely decreased proliferation and delayed hypertrophy of chondrocytes,and thereby marked retardation of endochondral ossification in mice.Genetically,JMJD3 associates with RUNX2 to promote proliferation and hypertrophy of chondrocytes.Biochemically,JMJD3 associates with and enhances RUNX2 activity by derepression of Runx2 and Ihh transcription throughits H3K27me3 demethylase activity.These results demonstrate that JMJD3 is a key epigenetic regulator in the process of cartilage maturation during endochondral bone formation.
基金supported by Natural Science Foundation ofShandong Province (JQ201706)The Marine S&T Fund of ShandongProvince for Pilot National Laboratory for Marine Science and Technology(Qingdao) (2018SDKJ0406-2)+1 种基金Fundamental Research Fundsfor the Central Universities (201841005)the Blue Life BreakthroughProgram of LMBB of Qingdao National Laboratory for MarineScience and Technology (MS2018N004).
文摘Epigenetic research focuses on heritable changes beyond the DNA sequence, which has led to a revolution in biologicalstudies and benefits in many other fields. The well-known model ciliate, Tetrahymena thermophila offers a unique system forepigenetic studies due to its nuclear dimorphism and special mode of sexual reproduction (conjugation), as well as abundantgenomic resources and genetic tools. In this paper, we summarize recent progress made by our research team and collaboratorsin understanding epigenetic mechanisms using Tetrahymena. This includes: (1) providing the first genome-wide basepair-resolution map of DNA N6-methyladenine (6mA) and revealed it as an integral part of the chromatin landscape;(2)dissecting the relative contribution of cis・ and trans- elements to nucleosome distribution by exploring the unique nucleardimorphism of Tetrahymena, (3) demonstrating the epigenetic controls of RNAi-dependent Polycomb repression pathwayson transposable elements, and (4) identifying a new histone monomethyltransferase, TXR1 (Tetrahymena Trithorax 1), thatfacilitates replication elongation through 让s substrate histone H3 lysine 27 monomethylation (H3K27mel).
