The plant genome possesses a large number of microRNAs （miRNAs） mainly 21-24 nucleotides in length. They play a vital role in regulation of target gene expression at various stages throughout the whole plant life cy...The plant genome possesses a large number of microRNAs （miRNAs） mainly 21-24 nucleotides in length. They play a vital role in regulation of target gene expression at various stages throughout the whole plant life cycle. Here we sequenced and analyzed ~ 10 million non-coding RNAs （ncRNAs） derived from fiber tissue of the allotetraploid cotton （Gossypium hirsutum） 7 days post-anthesis using ncRNA-seq technology. In terms of distinct reads, 24 nt ncRNA is by far the dominant species, followed by 21 nt and 23 nt ncRNAs. Using ab initio prediction, we identified and characterized a total of 562 candidate miRNA gene loci on the recently assembled D5 genome of the diploid cotton G. raimondii. Of all the 562 predicted miRNAs, 22 were previously discovered in cotton species and 187 had sequence conservation and homology to homologous miRNAs of other plant species. Nucleotide bias analysis showed that the 9th and 1st positions were significantly conserved among different types of miRNA genes. Among the 463 putative miRNA target genes, most significant up/down-regulation occurred in 10-20 days post-anthesis, indicating that miRNAs played an important role during the elongation and secondary cell wall synthesis stages of cotton fiber development. The discovery of new miRNA genes will help understand the mechanisms of miRNA generation and regulation in cotton.展开更多
We assembled a total of 297,239 Gossypium hirsutum （Gh, a tetraploid cotton, AADD） expressed sequence tag （EST） sequences that were available in the National Center for Biotechnology Information database, with ref...We assembled a total of 297,239 Gossypium hirsutum （Gh, a tetraploid cotton, AADD） expressed sequence tag （EST） sequences that were available in the National Center for Biotechnology Information database, with reference to the recently published G. raimondii （Gr, a diploid cotton, DD） genome, and obtained 49,125 UniGenes. The average lengths of the U niGenes were increased from 804 and 791 bp in two previous EST assemblies to 1,019 bp in the current analysis. The number of putative cotton UniGenes with lengths of 3 kb or more increased from 25 or 34 to 1,223. As a result, thousands of originally independent G. hirsutum ESTs were aligned to produce large contigs encoding transcripts with very long open reading frames, indicating that the G. raimondii genome sequence provided remarkable advantages to assemble the tetraploid cotton transcriptome. Significant different distribution patterns within several GO terms, including transcription factor activity, were observed between D- and A-derived assemblies. Tran- scriptome analysis showed that, in a tetraploid cotton cell, 29,547 UniGenes were possibly derived from the D subgenome while another 19,578 may come from the A subgenome. Finally, some of the in silico data were confirmed by reverse transcription polymerase chain reaction experiments to show the changes in transcript levels for several gene families known to play key role in cotton fiber development. We believe that our work provides a useful platform for functional and evolutionary genomic studies in cotton.展开更多
Peripheral nerve injury may trigger changes in mRNA levels in the spinal cord.Finding key mRNAs is important for improving repair after nerve injury.This study aimed to investigate changes in mRNAs in the spinal cord ...Peripheral nerve injury may trigger changes in mRNA levels in the spinal cord.Finding key mRNAs is important for improving repair after nerve injury.This study aimed to investigate changes in mRNAs in the spinal cord following sciatic nerve injury by transcriptomic analysis.The left sciatic nerve denervation model was established in C57 BL/6 mice.The left L4–6 spinal cord segment was obtained at 0,1,2,4 and 8 weeks after severing the sciatic nerve.mRNA expression profiles were generated by RNA sequencing.The sequencing results of spinal cord mRNA at 1,2,4,and 8 weeks after severing the sciatic nerve were compared with those at 0 weeks by bioinformatic analysis.We identified 1915 differentially expressed mRNAs in the spinal cord,of which 4,1909,and 2 were differentially expressed at 1,4,and 8 weeks after sciatic nerve injury,respectively.Sequencing results indicated that the number of differentially expressed mRNAs in the spinal cord was highest at 4 weeks after sciatic nerve injury.These mRNAs were associated with the cellular response to lipid,ATP metabolism,energy coupled proton transmembrane transport,nuclear transcription factor complex,vacuolar proton-transporting V-type ATPase complex,inner mitochondrial membrane protein complex,tau protein binding,NADH dehydrogenase activity and hydrogen ion transmembrane transporter activity.Of these mRNAs,Sgk1,Neurturin and Gpnmb took part in cell growth and development.Pathway analysis showed that these mRNAs were mainly involved in aldosterone-regulated sodium reabsorption,oxidative phosphorylation and collecting duct acid secretion.Functional assessment indicated that these mRNAs were associated with inflammation and cell morphology development.Our findings show that the number and type of spinal cord mRNAs involved in changes at different time points after peripheral nerve injury were different.The number of differentially expressed mRNAs in the spinal cord was highest at 4 weeks after sciatic nerve injury.These results provide reference data for finding new target展开更多
The diversity of antigen receptors and the specificity it underlies are the hallmarks of the cellular arm of the adaptive immune system. T and B lymphocytes are indeed truly unique in their ability to generate recepto...The diversity of antigen receptors and the specificity it underlies are the hallmarks of the cellular arm of the adaptive immune system. T and B lymphocytes are indeed truly unique in their ability to generate receptors capable of recognizing virtually any pathogen. It has been known for several decades that T lymphocytes recognize short peptides derived from degraded proteins presented by major histocompatibility complex （MHC） molecules at the cell surface. Interaction between peptide-MHC （pMHC） and the T cell receptor （TCR） is central to both thymic selection and peripheral antigen recognition. It is widely assumed that TCR diversity is required, or at least highly desirable, to provide sufficient immune coverage. However, a number of immune responses are associated with the selection of predictable, narrow, or skewed repertoires and public TCR chains. Here, we summarize the current knowledge on the formation of the TCR repertoire and its maintenance in health and disease. We also outline the various molecular mechanisms that govern the composition of the pre-selection, naive and antigen-specific TCR repertoires. Finally, we suggest that with the development of high-throughput sequencing, common TCR ＇signatures＇ raised against specific antigens could provide important diagnostic biomarkers and surrogate predictors of disease onset, progression and outcome.展开更多
Wang Shi Bao Chi Wan(WSBCW)is a traditional Chinese medicine with a recorded administration history of more than 180 years.In the present study,the preclinical safety of WSBCW was evaluated the preclinical safety of W...Wang Shi Bao Chi Wan(WSBCW)is a traditional Chinese medicine with a recorded administration history of more than 180 years.In the present study,the preclinical safety of WSBCW was evaluated the preclinical safety of WSBCW using a toxicity test,which consisted of an administration period of 28 d and a recovery period of 15 d.During the test,male and female SD rats were administered the medicine once a day by oral gavage,at a dose of 60 mg/kg/day,600 mg/kg/day,or 1500 mg/kg/day.As a reference medicine,mosapride citrate was administered at a dose of 37.5 mg/kg/day,which was clinically equivalent to the high-dosage treatment of WSBCW.With all the dosage groups,statistically,no adverse effect was observed in terms of clinical observation,food intake,body weights,organ coefficient,blood biochemistry,and histopathology examination.No intestinal melanosis was observed in the rats.When the data were examined animal by animal,test substance-related adverse effects were found with the high-dosage rats in hematology assay.The deranged,however,reversible changes suggested a compromised intestinal barrier,which was also observed with in mosapride citrate-treated rats.In addition to the histopathology assay,molecular toxicology was explored using high-throughput gene sequencing.No evident toxicity was revealed.In summary,administration of WSBCW was well tolerated within a treatment of 28 d.展开更多
Two traditional Chinese medicines(TCMs),namely WangshiBaochiwan and Panax Notoginseng Saponins(notoginsenoside),were chosen to study their effects on gut microbiota.Both of them have a long history of application in C...Two traditional Chinese medicines(TCMs),namely WangshiBaochiwan and Panax Notoginseng Saponins(notoginsenoside),were chosen to study their effects on gut microbiota.Both of them have a long history of application in China.During a test of 28 d,different doses of the medicines were administered to male Wistar rats daily.At the end of the administration,fresh fecal samples were collected and subjected to 16S rRNA sequencing to determine the profiles of gut microbiota.In relative to the controls,effects on gut microbiota were evaluated with medicine-treated rats.Consistent with its unique bidirectional effects on constipation and diarrhea,treatment of WangshiBaochiwan led to a balanced regulation of Lactobacillus and Bacteroides.The treatment also led to increased populations of Ruminiclostridium_9 and Eubacterium_ventriosum that are the major producer of short-chain fatty acid(SCFA),and decreased populations of genus Jeotgalicoccus and Bilophila that are associated with inflammation.These changes therefore resulted in a much healthier microbiota environment in WangshiBaochiwan-treated rates.For the treatment of notoginsenoside,effects were found with Enterobacteriaceae species that is associated with Parkinson's disease,Christensenellaceae family that is associated with aging,and hypertension-associated Rikenellaceae,Christensenellaceae,Lachnospiraceae and Bacteroidaceae species.In agreement with its major indications,the treatment further led to increased populations of SCFA-producing bacteria,such as Elusimicrobium,Anaerotruncus,Ruminococcaceae_NK4A214_group,and Intestinimonas.Taken together,treatment of the two TCMs led to active and distinguishable regulations of gut microbiota.Impressively,these changes were in agreement with their clinical efficacy,and suggested that they were involved in the treatment of these diseases.展开更多
Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage se...Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage sequencing technology, researchers have started to notice that genomic repeat regions, previously neglected in search of disease culprits, are active contributors to multiple neurodegenerative diseases. In this review, we describe the association between repeat element variants and multiple degenerative diseases through genome-wide association studies and targeted sequencing. We discuss the identification of disease-relevant repeat element variants, further powered by the advancement of long-read sequencing technologies and their related tools, and summarize recent findings in the molecular mechanisms of repeat element variants in brain degeneration, such as those causing transcriptional silencing or RNA-mediated gain of toxic function. Furthermore, we describe how in silico predictions using innovative computational models, such as deep learning language models, could enhance and accelerate our understanding of the functional impact of repeat element variants. Finally, we discuss future directions to advance current findings for a better understanding of neurodegenerative diseases and the clinical applications of genomic repeat elements.展开更多
文摘The plant genome possesses a large number of microRNAs （miRNAs） mainly 21-24 nucleotides in length. They play a vital role in regulation of target gene expression at various stages throughout the whole plant life cycle. Here we sequenced and analyzed ~ 10 million non-coding RNAs （ncRNAs） derived from fiber tissue of the allotetraploid cotton （Gossypium hirsutum） 7 days post-anthesis using ncRNA-seq technology. In terms of distinct reads, 24 nt ncRNA is by far the dominant species, followed by 21 nt and 23 nt ncRNAs. Using ab initio prediction, we identified and characterized a total of 562 candidate miRNA gene loci on the recently assembled D5 genome of the diploid cotton G. raimondii. Of all the 562 predicted miRNAs, 22 were previously discovered in cotton species and 187 had sequence conservation and homology to homologous miRNAs of other plant species. Nucleotide bias analysis showed that the 9th and 1st positions were significantly conserved among different types of miRNA genes. Among the 463 putative miRNA target genes, most significant up/down-regulation occurred in 10-20 days post-anthesis, indicating that miRNAs played an important role during the elongation and secondary cell wall synthesis stages of cotton fiber development. The discovery of new miRNA genes will help understand the mechanisms of miRNA generation and regulation in cotton.
基金supported by grants from the China National Basic Research Program(2010CB126002)the National Natural Science Foundation of China(90717009)the 111 Project funded by the Chinese Ministry of Education
文摘We assembled a total of 297,239 Gossypium hirsutum （Gh, a tetraploid cotton, AADD） expressed sequence tag （EST） sequences that were available in the National Center for Biotechnology Information database, with reference to the recently published G. raimondii （Gr, a diploid cotton, DD） genome, and obtained 49,125 UniGenes. The average lengths of the U niGenes were increased from 804 and 791 bp in two previous EST assemblies to 1,019 bp in the current analysis. The number of putative cotton UniGenes with lengths of 3 kb or more increased from 25 or 34 to 1,223. As a result, thousands of originally independent G. hirsutum ESTs were aligned to produce large contigs encoding transcripts with very long open reading frames, indicating that the G. raimondii genome sequence provided remarkable advantages to assemble the tetraploid cotton transcriptome. Significant different distribution patterns within several GO terms, including transcription factor activity, were observed between D- and A-derived assemblies. Tran- scriptome analysis showed that, in a tetraploid cotton cell, 29,547 UniGenes were possibly derived from the D subgenome while another 19,578 may come from the A subgenome. Finally, some of the in silico data were confirmed by reverse transcription polymerase chain reaction experiments to show the changes in transcript levels for several gene families known to play key role in cotton fiber development. We believe that our work provides a useful platform for functional and evolutionary genomic studies in cotton.
基金supported by the National Natural Science Foundation of China,No.81671215(to XFY),No.31571002(to BGJ)the Natural Science Foundation of Beijing of China,No.7192215(to XFY)
文摘Peripheral nerve injury may trigger changes in mRNA levels in the spinal cord.Finding key mRNAs is important for improving repair after nerve injury.This study aimed to investigate changes in mRNAs in the spinal cord following sciatic nerve injury by transcriptomic analysis.The left sciatic nerve denervation model was established in C57 BL/6 mice.The left L4–6 spinal cord segment was obtained at 0,1,2,4 and 8 weeks after severing the sciatic nerve.mRNA expression profiles were generated by RNA sequencing.The sequencing results of spinal cord mRNA at 1,2,4,and 8 weeks after severing the sciatic nerve were compared with those at 0 weeks by bioinformatic analysis.We identified 1915 differentially expressed mRNAs in the spinal cord,of which 4,1909,and 2 were differentially expressed at 1,4,and 8 weeks after sciatic nerve injury,respectively.Sequencing results indicated that the number of differentially expressed mRNAs in the spinal cord was highest at 4 weeks after sciatic nerve injury.These mRNAs were associated with the cellular response to lipid,ATP metabolism,energy coupled proton transmembrane transport,nuclear transcription factor complex,vacuolar proton-transporting V-type ATPase complex,inner mitochondrial membrane protein complex,tau protein binding,NADH dehydrogenase activity and hydrogen ion transmembrane transporter activity.Of these mRNAs,Sgk1,Neurturin and Gpnmb took part in cell growth and development.Pathway analysis showed that these mRNAs were mainly involved in aldosterone-regulated sodium reabsorption,oxidative phosphorylation and collecting duct acid secretion.Functional assessment indicated that these mRNAs were associated with inflammation and cell morphology development.Our findings show that the number and type of spinal cord mRNAs involved in changes at different time points after peripheral nerve injury were different.The number of differentially expressed mRNAs in the spinal cord was highest at 4 weeks after sciatic nerve injury.These results provide reference data for finding new target
文摘The diversity of antigen receptors and the specificity it underlies are the hallmarks of the cellular arm of the adaptive immune system. T and B lymphocytes are indeed truly unique in their ability to generate receptors capable of recognizing virtually any pathogen. It has been known for several decades that T lymphocytes recognize short peptides derived from degraded proteins presented by major histocompatibility complex （MHC） molecules at the cell surface. Interaction between peptide-MHC （pMHC） and the T cell receptor （TCR） is central to both thymic selection and peripheral antigen recognition. It is widely assumed that TCR diversity is required, or at least highly desirable, to provide sufficient immune coverage. However, a number of immune responses are associated with the selection of predictable, narrow, or skewed repertoires and public TCR chains. Here, we summarize the current knowledge on the formation of the TCR repertoire and its maintenance in health and disease. We also outline the various molecular mechanisms that govern the composition of the pre-selection, naive and antigen-specific TCR repertoires. Finally, we suggest that with the development of high-throughput sequencing, common TCR ＇signatures＇ raised against specific antigens could provide important diagnostic biomarkers and surrogate predictors of disease onset, progression and outcome.
基金Beijing Municipal science&Technology Commission(Grant No.2161100001816008)the National Natural Science Foundation of China(Grant No.31571403)Beijing Natural Science Foundation(Grant No.2171001)。
文摘Wang Shi Bao Chi Wan(WSBCW)is a traditional Chinese medicine with a recorded administration history of more than 180 years.In the present study,the preclinical safety of WSBCW was evaluated the preclinical safety of WSBCW using a toxicity test,which consisted of an administration period of 28 d and a recovery period of 15 d.During the test,male and female SD rats were administered the medicine once a day by oral gavage,at a dose of 60 mg/kg/day,600 mg/kg/day,or 1500 mg/kg/day.As a reference medicine,mosapride citrate was administered at a dose of 37.5 mg/kg/day,which was clinically equivalent to the high-dosage treatment of WSBCW.With all the dosage groups,statistically,no adverse effect was observed in terms of clinical observation,food intake,body weights,organ coefficient,blood biochemistry,and histopathology examination.No intestinal melanosis was observed in the rats.When the data were examined animal by animal,test substance-related adverse effects were found with the high-dosage rats in hematology assay.The deranged,however,reversible changes suggested a compromised intestinal barrier,which was also observed with in mosapride citrate-treated rats.In addition to the histopathology assay,molecular toxicology was explored using high-throughput gene sequencing.No evident toxicity was revealed.In summary,administration of WSBCW was well tolerated within a treatment of 28 d.
基金The National Natural Science Foundation of China(Grant No.31571403)Beijing Natural Science Foundation(Grant No.2171001).
文摘Two traditional Chinese medicines(TCMs),namely WangshiBaochiwan and Panax Notoginseng Saponins(notoginsenoside),were chosen to study their effects on gut microbiota.Both of them have a long history of application in China.During a test of 28 d,different doses of the medicines were administered to male Wistar rats daily.At the end of the administration,fresh fecal samples were collected and subjected to 16S rRNA sequencing to determine the profiles of gut microbiota.In relative to the controls,effects on gut microbiota were evaluated with medicine-treated rats.Consistent with its unique bidirectional effects on constipation and diarrhea,treatment of WangshiBaochiwan led to a balanced regulation of Lactobacillus and Bacteroides.The treatment also led to increased populations of Ruminiclostridium_9 and Eubacterium_ventriosum that are the major producer of short-chain fatty acid(SCFA),and decreased populations of genus Jeotgalicoccus and Bilophila that are associated with inflammation.These changes therefore resulted in a much healthier microbiota environment in WangshiBaochiwan-treated rates.For the treatment of notoginsenoside,effects were found with Enterobacteriaceae species that is associated with Parkinson's disease,Christensenellaceae family that is associated with aging,and hypertension-associated Rikenellaceae,Christensenellaceae,Lachnospiraceae and Bacteroidaceae species.In agreement with its major indications,the treatment further led to increased populations of SCFA-producing bacteria,such as Elusimicrobium,Anaerotruncus,Ruminococcaceae_NK4A214_group,and Intestinimonas.Taken together,treatment of the two TCMs led to active and distinguishable regulations of gut microbiota.Impressively,these changes were in agreement with their clinical efficacy,and suggested that they were involved in the treatment of these diseases.
基金supported by the National Natural Science Foundation of China, No.61932008Natural Science Foundation of Shanghai, No.21ZR1403200 (both to JC)。
文摘Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage sequencing technology, researchers have started to notice that genomic repeat regions, previously neglected in search of disease culprits, are active contributors to multiple neurodegenerative diseases. In this review, we describe the association between repeat element variants and multiple degenerative diseases through genome-wide association studies and targeted sequencing. We discuss the identification of disease-relevant repeat element variants, further powered by the advancement of long-read sequencing technologies and their related tools, and summarize recent findings in the molecular mechanisms of repeat element variants in brain degeneration, such as those causing transcriptional silencing or RNA-mediated gain of toxic function. Furthermore, we describe how in silico predictions using innovative computational models, such as deep learning language models, could enhance and accelerate our understanding of the functional impact of repeat element variants. Finally, we discuss future directions to advance current findings for a better understanding of neurodegenerative diseases and the clinical applications of genomic repeat elements.
