Haplotypic information in diploid organisms provides valuable information on human evolutionary history and plays an important role in identifying a candidate gene in the etiology of complex genetic diseases. However,...Haplotypic information in diploid organisms provides valuable information on human evolutionary history and plays an important role in identifying a candidate gene in the etiology of complex genetic diseases. However, haplotypes of diploid individuals cannot be acquired easily. Molecular haplotyping methods are very costly and have low throughput, and current genotyping and sequenc- ing methods do not provide information on the linkage phase in diploid organisms. The application of statistical methods to infer the haplotype phase in samples of diploid sequences is a very cost-effective approach.展开更多
In multiloci-based genetic association studies of complex diseases, a powerful and high efficient tool for analyses oflinkage disequilibrium (LD) between markers, haplotype distributions and many chi-square/p values w...In multiloci-based genetic association studies of complex diseases, a powerful and high efficient tool for analyses oflinkage disequilibrium (LD) between markers, haplotype distributions and many chi-square/p values with a large numberof samples has been sought for long. In order to achieve the goal of obtaining meaningful results directly from raw data,we developed a robust and user-friendly software platform with a series of tools for analysis in association study withhigh efficiency. The platform has been well evaluated by several sets of real data.展开更多
Activating transcription factor 4 （ATF4） has been shown to play key roles in many physiological processes. There are no reports, however, demonstrating a direct link between ATF4 and lipid metabolism. We noticed tha...Activating transcription factor 4 （ATF4） has been shown to play key roles in many physiological processes. There are no reports, however, demonstrating a direct link between ATF4 and lipid metabolism. We noticed that Atf4- deficient mice are lean, suggesting a possible role for ATF4 in regulating lipid metabolism. The goal of our current study is to investigate the involvement of ATF4 in lipid metabolism and elucidate the underlying mechanisms. Studies using Atf4-deficient mice revealed increased energy expenditure, as measured by oxygen consumption. These mice also showed increases in lipolysis, expression of uncoupling protein 2 （UCP2） and p-oxidation genes and decreases in expression of lipogenic genes in white adipose tissue （WAT）, suggesting increased utilization and decreased synthesis of fatty acids, respectively. Expression of UCP1, 2 and 3 was also increased in brown adipose tissue （BAT）, suggesting increased thermogenesis. The effect of ATF4 deletion on expression of UCPs in BAT suggests that increased thermogenesis may underlie increased energy expenditure. Thus, our study identifies a possible new function for ATF4 in regulating lipid metabolism and thermogenesis.展开更多
SIRT1 plays an important role in adipogenesis, but how SIRT1 is regulated in adipogenesis is largely unknown. In this study, we show that both SIRT1 protein and mRNA levels were increased along with CCAAT/enhancer-bin...SIRT1 plays an important role in adipogenesis, but how SIRT1 is regulated in adipogenesis is largely unknown. In this study, we show that both SIRT1 protein and mRNA levels were increased along with CCAAT/enhancer-binding protein a （C/EBPa） during adipocyte differentiation. C/EBPa, but not C/EBPap30, activated SIRT1 promoter in both HeLa cells and 3T3-L1 preadipocytes. Furthermore, C/EBPa upregulated SIRT1 mRNA and protein levels in HeLa cells and increased SIRT1 expression in a p53-independent manner in Soas2 cells. In preadipocytes, ectopic expression of C/EBPa upregulated SIRT1 protein level and knockdown of C/EBPa led to the decrease of SIRTI pro- tein level. Moreover, by promoter deletion analysis, gel shift assay and chromatin immunoprecipitation, we found that C/EBPa bound to the SIRT1 promoter at a consensus C/EBPα binding site. These data demonstrate that C/ EBPα regulates SIRT1 expression during adipogenesis by directly binding to the SIRT1 promoter.展开更多
The Hedgehog （Hh） family of secreted signaling proteins plays a critical role in regulating the development of several tissues and organ systems. The ability of Hh proteins to exert their biological effects is regul...The Hedgehog （Hh） family of secreted signaling proteins plays a critical role in regulating the development of several tissues and organ systems. The ability of Hh proteins to exert their biological effects is regulated by a series of post-translational processes. These processes include an intramolecular cleavage, covalent addition of cholesterol and/or palmitate, and conversion into a multimeric freely diffusible form. The processing of Hh proteins affects their trafficking, potency, and ability to signal over several cell diameters. Here we review the current understanding of the Hh signaling mechanisms that govern the establishment of the Hh gradient and the transduction of the Hh signal in the light of recent data.展开更多
Single-nucleotide polymorphisms （SNPs） of ADIPOQ, ADIPOR1, and ADIPOR2 have been associated with type 2 diabetes mellitus （T2DM）, but there are many conflicting results especially in Chinese populations. To invest...Single-nucleotide polymorphisms （SNPs） of ADIPOQ, ADIPOR1, and ADIPOR2 have been associated with type 2 diabetes mellitus （T2DM）, but there are many conflicting results especially in Chinese populations. To investigate the contribution of the adiponectin genes and their receptors to T2DM, a case-control study was performed and 11 SNPs ofADIPOQ, ADIPOR1, and ADIPOR2 were genotyped in 985 T2DM and 1,050 control subjects, rs 16861194 （-11426 A〉G） in the putative promoter of ADIPOQ was associated with T2DM （P = 0.007; OR = 1.29, 95% CI 1.08-1.55）. None of the other 10 SNPs were associated with T2DM in this study, although rs2241766 and rs1501299 were reported to be associated with T2DM in previous Chinese studies. There was also no significant difference found from the ADIPOQ haplotype analysis, which contains rs 16861194. In addition, we also assessed potential gene-gene interactions in three genes and no interactions were found. In conclusion, our results supported the ADIPOQ gene as a possible risk factor for type 2 diabetes in Han Chinese population.展开更多
Dear Editor, We developed a GPU-based analytical method, named as SHEsisEpi, which purely focuses on risk epistasis in a genome-wide association study （GWAS） of complex traits, excluding the contamination of margin...Dear Editor, We developed a GPU-based analytical method, named as SHEsisEpi, which purely focuses on risk epistasis in a genome-wide association study （GWAS） of complex traits, excluding the contamination of marginal effects caused by single-locus association. We analyzed the Wellcome Trust Case Control Consortium＇s （WTCCC） GWAS data of bipolar disorder （BPD） with 500K SNPs.展开更多
In eukaryotic cells, receptor endocytosis is a key event regulating signaling transduction. Adiponectin receptors belong to a new receptor family that is distinct from G-protein-coupled receptors and has critical role...In eukaryotic cells, receptor endocytosis is a key event regulating signaling transduction. Adiponectin receptors belong to a new receptor family that is distinct from G-protein-coupled receptors and has critical roles in the pathogenesis of diabetes and metabolic syndrome. Here, we analyzed the endocytosis of adiponectin and adiponectin receptor 1 （AdipoR1） and found that they are both internalized into transferrin-positive compartments that follow similar traffic routes. Blocking clathrin-mediated endocytosis by expressing Eps15 mutants or depleting K^＋ trapped AdipoR1 at the plasma membrane, and K^＋ depletion abolished adiponectin internalization, indicating that the endocytosis of AdipoR1 and adiponectin is clathrin-dependent. Depletion of K^＋ and overexpression of Eps15 mutants enhance adiponectin- stimulated AMP-activated protein kinase phosphorylation, suggesting that the endocytosis of AdipoR1 might down-regulate adiponectin signaling. In addition, AdipoR1 colocalizes with the small GTPase Rab5, and a dominant negative Rab5 abrogates AdipoR1 endocytosis. These data indicate that AdipoR1 is internalized through a clathrin- and Rab5- dependent pathway and that endocytosis may play a role in the regulation of adiponectin signaling.展开更多
Objective： To study the anti-fatigue effects of salidroside in mice. Methods： Totally 120 normal male Kunming mice were randomized into 5 groups （4 salidroside intervention groups and the control group） based on b...Objective： To study the anti-fatigue effects of salidroside in mice. Methods： Totally 120 normal male Kunming mice were randomized into 5 groups （4 salidroside intervention groups and the control group） based on body weight. The control group was given distilled water and the 4 intervention groups were given various doses of salidroside （60, 180, 360, 720 mg/kg） for 15 consecutive days, respectively. The levels of lactate, serum urea nitrogen, muscle and liver glycogen, the longest swimming time and hemoglobin were determined before and after swimming test. Results： Different doses of salidroside significantly lengthened the swimming time and increased the contents of hemoglobin and muscle and liver glycogen, while reducing that of lactate in blood significantly compared with control group, especially in the 180 mg/kg salidroside group. Conclusion： Salidroside has noticeable anti-fatigue effect on mice. These effects were dose-dependent, and the strongest effect on most biomarkers was seen with an intermediate dose.展开更多
Vertebrate digits are essential structures for movement, feeding and communication. Specialized regions of the developing limb bud including the zone of polarizing activity （ZPA）, the apical ectodermal ridge （AER）...Vertebrate digits are essential structures for movement, feeding and communication. Specialized regions of the developing limb bud including the zone of polarizing activity （ZPA）, the apical ectodermal ridge （AER）, and the non-ridge ectoderm regulate the patterning of digits. Although a series of signaling molecules have been characterized as patterning signals from the organizing centers, the delicate cellular and molecular mechanisms that interpret how these patterning signals control the detailed digit anatomy remain unclear, Recent studies from model organisms and human hand malformations provide new insights into the mechanisms regulating this process. Here, we review the current understanding of the genetic networks governing digit morphogenesis展开更多
Objective To investigate the roles of the cyclin D1/CDK4 and E2F-1/4 pathways and compare their work patterns in cell cycle changes induced by different doses of B[a]E Methods Human embryo lung fibroblasts （HELFs） w...Objective To investigate the roles of the cyclin D1/CDK4 and E2F-1/4 pathways and compare their work patterns in cell cycle changes induced by different doses of B[a]E Methods Human embryo lung fibroblasts （HELFs） were treated with 2 μmol/L or 100 μmol/L B[a]P which were provided with some characteristics of transformed cells （T-HELFs）. Cyclin D l, CDK4 and E2F-1/4 expressions were determined by Western blotting. Flow cytometry was used to detect the distribution of cell cycle. Results After B[a]P treatment, the proportion of the first gap （G 1） phase cells decreased. CDK4 and E2F-4 expression did not change significantly. In 2 μmol/L treated cells, a marked overexpression of cyclin D1 and E2F-1 was observed. However, in T-HELFs overexpression was limited to cyclin D1 only, and no overexpression of E2F-1 was observed. The decreases of G1 phase in response to B[a]P treatment were blocked in antisense cyclin D1 and antisense CDK4 transfected HELFs （A-D1 and A-K4） and T-HELFs （T-A-D1 and T-A-K4）. After 2 μmol/L B[a]P treatment, overexpression of E2F-1 was attenuated in A-D1, and E2F-4 expression was decreased significantly in A-K4. In T-A-D1 and T-A-K4, E2F-4 expression was increased significantly, compared with T-HELFs. The E2F-1 expression remained unchanged in T-A-D1 and T-A-K4. Condusions Cyclin DI/CDK4-E2F-1/4 pathways work in different patterns in response to low dose and high dose B[a]P treatment. In HELFs treated with 2 μmol/L B[a]P, cyclin D1 positively regulates the E2F-1 expression while CDK4 negatively regulates the E2F-4 expression; however, in HELFs treated with 100 μmol/L B[a]P, both cyclin D1 and CDK4 negatively regulate the E2F-4 expression.展开更多
Glatiramer acetate （GA） is an immunomodulatory peptide drug used to treat multiple sclerosis. Its treatment effect has been expanded to other autoimmune conditions such as uveoretinitis, inflammatory bowel disease, ...Glatiramer acetate （GA） is an immunomodulatory peptide drug used to treat multiple sclerosis. Its treatment effect has been expanded to other autoimmune conditions such as uveoretinitis, inflammatory bowel disease, graft re- jection and hepatic fibrosis. Here, we report that GA was effective in altering the clinical course of diabetes in cyclo- phosphamide （CY）-potentiated non-obese diabetic （CY-NOD） mice. Treatment with GA significantly reduced the dia- betic rate in the mice and ameliorated insulitis, which coincided with increased CD4＋CD25＋Foxp3＋ T cell response in treated mice. GA treatment led to increased expression of transcription factor Foxp3 and elevated production of interleukin-4 （IL-4） both in vivo and in vitro. It was evident that the effect of GA on up-regulation of Foxp3 was me- diated partially through IL-4. IL-4 was found to maintain Foxp3 expression and regulatory function of CD4＋CD25＋ regulatory T cells （Tregs）. This study provides new evidence that GA has treatment potential for type 1 diabetes through the induction of Tregs and that increased IL-4 production is partially responsible for the enhanced Treg＇s function in GA treatment.展开更多
All eukaryotic mRNAs are capped at their 5＇ end. Capping of mRNAs takes place co-transcriptionally and involves three steps. The intermediates of the capping process, as well as the uncapped 5＇ tri-phosphate RNA, ar...All eukaryotic mRNAs are capped at their 5＇ end. Capping of mRNAs takes place co-transcriptionally and involves three steps. The intermediates of the capping process, as well as the uncapped 5＇ tri-phosphate RNA, are resistant to decapping and degradation by known factors, leading to the assumption that the capping process always proceeds to completion. This view was recently drastically changed. A novel family of enzymes, including the yeast proteins Rail, Dxo1/Ydr370C, and the mammalian protein DXO/Dom3Z, has been identified. These enzymes catalyze the conversion of the improperly capped mRNAs to 5＇ mono-phosphate RNA, allowing them to be degraded by 5＇-3＇ exoribonucleases. Several of these enzymes also possess 5＇-3＇ exoribonuclease activities themselves, and can single-handedly clear the improperly capped mRNAs. Studying of these enzymes has led to the realization that mRNA capping does not always proceed to completion, and the identification of an mRNA capping quality control mechanism in eukaryotes. In this paper, we briefly review recent advances in this area.展开更多
Nanomaterials and nanotechnology have great potential in the biological and biomedical field. Recent studies reveal that many nanomaterials possess antibacterial activities. While most of these studies focus on the ab...Nanomaterials and nanotechnology have great potential in the biological and biomedical field. Recent studies reveal that many nanomaterials possess antibacterial activities. While most of these studies focus on the ability of nanomaterials to inhibit the growth of pathogenic bacteria in vitro, few of them test the effects of nanomaterials on intestinal commensal bacteria. Here, we report that Ti O_2nanoparticles(10, 50 and 100 nm in size) can inhibit the growth of Drosophila intestinal commensal bacteria in vitro. This activity depends on the dosage or size, but is independent of the photocatalytic activity of Ti O_2 nanoparticles. Surprisingly, dietary Ti O_2 nanoparticles of the same dosage fail to display similar effects in Drosophila larvae or adults. These flies show a normal amount of intestinal commensal bacteria, as well as a normal developmental cycle, energy store, and locomotor activity. These results imply that the antibacterial effect of Ti O_2 nanoparticles differs in vitro and in vivo.展开更多
Protein phosphorylation, one of the most important protein post-translational modifications, is involved in various biological processes, and the identification of phosphorylation peptides （phosphopeptides） and thei...Protein phosphorylation, one of the most important protein post-translational modifications, is involved in various biological processes, and the identification of phosphorylation peptides （phosphopeptides） and their corresponding phosphorylation sites （phosphosites） will facilitate the understanding of the molecular mechanism and function of phosphorylation. Mass spectrometry （MS） provides a high- throughput technology that enables the identification of large numbers of phosphosites. PhoPepMass is designed to assist human phosphopeptide identification from MS data based on a specific database of phophopeptide masses and a multivariate hypergeometric matching algorithm. It contains 244,915 phosphosites from several public sources. Moreover, the accurate masses of peptides and fragments with phosphosites were calculated. It is the first database that provides a systematic resource for the query of phosphosites on peptides and their corresponding masses. This allows researchers to search certain proteins of which phosphosites have been reported, to browse detailed phosphopeptide and fragment information, to match masses from MS analyses with defined threshold to the corresponding phos- phopeptide, and to compare proprietary phosphopeptide discovery results with results from previous studies. Additionally, a database search software is created and a ＂two-stage search strategy＂ is suggested to identify phosphopeptides from tandem mass spectra of proteomics data. We expect PhoPepMass to be a useful tool and a source of reference for proteomics researchers.展开更多
Telomeres are protein--DNA complex structure at the ends of chromosomes, which are involved in genomic stability （Blackburn, 2010）. In most human cells, telomere erosion with each round of cell division eventually l...Telomeres are protein--DNA complex structure at the ends of chromosomes, which are involved in genomic stability （Blackburn, 2010）. In most human cells, telomere erosion with each round of cell division eventually limits cell proliferation and tissue renewal, thereby impacting age-dependent pathol- ogies （Lundblad, 2012）. Leukocyte telomere length （LTL） undertakes a slow loss throughout life across human pop- ulations in general （Blackburn, 2010）. Telomerase is a ribo- nucleoprotein that adds telomeric DNA to chromosomal ends and contains two essential components：展开更多
Precision medicine emerges as a new approach that takes into account individual variability. Successful realization of precision medicine requires disease models that are able to incorporate personalized dis- ease inf...Precision medicine emerges as a new approach that takes into account individual variability. Successful realization of precision medicine requires disease models that are able to incorporate personalized dis- ease information and recapitulate disease development processes at the molecular, cellular and organ levels. With recent development in stem cell field, a variety of tissue organoids can be derived from patient specific pluripotent stem cells and adult stem cells. In combi- nation with the state-of-the-art genome editing tools, organoids can be further engineered to mimic disease- relevant genetic and epigenetic status of a patient. This has therefore enabled a rapid expansion of sophisticated in vitro disease models, offering a unique system for fundamental and biomedical research as well as the development of personalized medicine. Here we summarize some of the latest advances and future perspectives in engineering stem cell organoids for human disease modeling.展开更多
Amygdala plays a critical role in the regulation of emotional behavior and food intake.Neuropeptides are short chains of amino acids secreted by neurons as intercellular messengers,which regulate different functions s...Amygdala plays a critical role in the regulation of emotional behavior and food intake.Neuropeptides are short chains of amino acids secreted by neurons as intercellular messengers,which regulate different functions such as emotion,food intake,learning and memory.In this review,we summarize the recent progress on the regulation of food intake by amygadala,which is mediated by those neuropeptides known to be critical in the regulation of this process.展开更多
文摘Haplotypic information in diploid organisms provides valuable information on human evolutionary history and plays an important role in identifying a candidate gene in the etiology of complex genetic diseases. However, haplotypes of diploid individuals cannot be acquired easily. Molecular haplotyping methods are very costly and have low throughput, and current genotyping and sequenc- ing methods do not provide information on the linkage phase in diploid organisms. The application of statistical methods to infer the haplotype phase in samples of diploid sequences is a very cost-effective approach.
基金This work was supported by the Major State Basic Research Development program of Chinathe National High Technology Research and Development Program of China.
文摘In multiloci-based genetic association studies of complex diseases, a powerful and high efficient tool for analyses oflinkage disequilibrium (LD) between markers, haplotype distributions and many chi-square/p values with a large numberof samples has been sought for long. In order to achieve the goal of obtaining meaningful results directly from raw data,we developed a robust and user-friendly software platform with a series of tools for analysis in association study withhigh efficiency. The platform has been well evaluated by several sets of real data.
文摘Activating transcription factor 4 （ATF4） has been shown to play key roles in many physiological processes. There are no reports, however, demonstrating a direct link between ATF4 and lipid metabolism. We noticed that Atf4- deficient mice are lean, suggesting a possible role for ATF4 in regulating lipid metabolism. The goal of our current study is to investigate the involvement of ATF4 in lipid metabolism and elucidate the underlying mechanisms. Studies using Atf4-deficient mice revealed increased energy expenditure, as measured by oxygen consumption. These mice also showed increases in lipolysis, expression of uncoupling protein 2 （UCP2） and p-oxidation genes and decreases in expression of lipogenic genes in white adipose tissue （WAT）, suggesting increased utilization and decreased synthesis of fatty acids, respectively. Expression of UCP1, 2 and 3 was also increased in brown adipose tissue （BAT）, suggesting increased thermogenesis. The effect of ATF4 deletion on expression of UCPs in BAT suggests that increased thermogenesis may underlie increased energy expenditure. Thus, our study identifies a possible new function for ATF4 in regulating lipid metabolism and thermogenesis.
文摘SIRT1 plays an important role in adipogenesis, but how SIRT1 is regulated in adipogenesis is largely unknown. In this study, we show that both SIRT1 protein and mRNA levels were increased along with CCAAT/enhancer-binding protein a （C/EBPa） during adipocyte differentiation. C/EBPa, but not C/EBPap30, activated SIRT1 promoter in both HeLa cells and 3T3-L1 preadipocytes. Furthermore, C/EBPa upregulated SIRT1 mRNA and protein levels in HeLa cells and increased SIRT1 expression in a p53-independent manner in Soas2 cells. In preadipocytes, ectopic expression of C/EBPa upregulated SIRT1 protein level and knockdown of C/EBPa led to the decrease of SIRTI pro- tein level. Moreover, by promoter deletion analysis, gel shift assay and chromatin immunoprecipitation, we found that C/EBPa bound to the SIRT1 promoter at a consensus C/EBPα binding site. These data demonstrate that C/ EBPα regulates SIRT1 expression during adipogenesis by directly binding to the SIRT1 promoter.
文摘The Hedgehog （Hh） family of secreted signaling proteins plays a critical role in regulating the development of several tissues and organ systems. The ability of Hh proteins to exert their biological effects is regulated by a series of post-translational processes. These processes include an intramolecular cleavage, covalent addition of cholesterol and/or palmitate, and conversion into a multimeric freely diffusible form. The processing of Hh proteins affects their trafficking, potency, and ability to signal over several cell diameters. Here we review the current understanding of the Hh signaling mechanisms that govern the establishment of the Hh gradient and the transduction of the Hh signal in the light of recent data.
基金supported by the National Natural Science Foundation of ChinaNational Basic Research Pro-gram of China (973 Program)+5 种基金National High-tech R&D Program (863 Program)the Chinese Nutrition Soci-ety (No. 05015)the Dannon Institute, the Shanghai-Unilever Research and Development Fund (No. 06SU07007)the Shanghai Municipality Science & Tech-nology Commission (No. 05JC14090)the Shanghai Leading Academic Discipline Project (No. B205)the Knowledge Innovation Program of the Chinese Academy of Sciences (No. KSCX2-YW-R-01)
文摘Single-nucleotide polymorphisms （SNPs） of ADIPOQ, ADIPOR1, and ADIPOR2 have been associated with type 2 diabetes mellitus （T2DM）, but there are many conflicting results especially in Chinese populations. To investigate the contribution of the adiponectin genes and their receptors to T2DM, a case-control study was performed and 11 SNPs ofADIPOQ, ADIPOR1, and ADIPOR2 were genotyped in 985 T2DM and 1,050 control subjects, rs 16861194 （-11426 A〉G） in the putative promoter of ADIPOQ was associated with T2DM （P = 0.007; OR = 1.29, 95% CI 1.08-1.55）. None of the other 10 SNPs were associated with T2DM in this study, although rs2241766 and rs1501299 were reported to be associated with T2DM in previous Chinese studies. There was also no significant difference found from the ADIPOQ haplotype analysis, which contains rs 16861194. In addition, we also assessed potential gene-gene interactions in three genes and no interactions were found. In conclusion, our results supported the ADIPOQ gene as a possible risk factor for type 2 diabetes in Han Chinese population.
文摘Dear Editor, We developed a GPU-based analytical method, named as SHEsisEpi, which purely focuses on risk epistasis in a genome-wide association study （GWAS） of complex traits, excluding the contamination of marginal effects caused by single-locus association. We analyzed the Wellcome Trust Case Control Consortium＇s （WTCCC） GWAS data of bipolar disorder （BPD） with 500K SNPs.
文摘In eukaryotic cells, receptor endocytosis is a key event regulating signaling transduction. Adiponectin receptors belong to a new receptor family that is distinct from G-protein-coupled receptors and has critical roles in the pathogenesis of diabetes and metabolic syndrome. Here, we analyzed the endocytosis of adiponectin and adiponectin receptor 1 （AdipoR1） and found that they are both internalized into transferrin-positive compartments that follow similar traffic routes. Blocking clathrin-mediated endocytosis by expressing Eps15 mutants or depleting K^＋ trapped AdipoR1 at the plasma membrane, and K^＋ depletion abolished adiponectin internalization, indicating that the endocytosis of AdipoR1 and adiponectin is clathrin-dependent. Depletion of K^＋ and overexpression of Eps15 mutants enhance adiponectin- stimulated AMP-activated protein kinase phosphorylation, suggesting that the endocytosis of AdipoR1 might down-regulate adiponectin signaling. In addition, AdipoR1 colocalizes with the small GTPase Rab5, and a dominant negative Rab5 abrogates AdipoR1 endocytosis. These data indicate that AdipoR1 is internalized through a clathrin- and Rab5- dependent pathway and that endocytosis may play a role in the regulation of adiponectin signaling.
基金the Foundation of the Gym Sport Bureau of Shanghai (04JT017)
文摘Objective： To study the anti-fatigue effects of salidroside in mice. Methods： Totally 120 normal male Kunming mice were randomized into 5 groups （4 salidroside intervention groups and the control group） based on body weight. The control group was given distilled water and the 4 intervention groups were given various doses of salidroside （60, 180, 360, 720 mg/kg） for 15 consecutive days, respectively. The levels of lactate, serum urea nitrogen, muscle and liver glycogen, the longest swimming time and hemoglobin were determined before and after swimming test. Results： Different doses of salidroside significantly lengthened the swimming time and increased the contents of hemoglobin and muscle and liver glycogen, while reducing that of lactate in blood significantly compared with control group, especially in the 180 mg/kg salidroside group. Conclusion： Salidroside has noticeable anti-fatigue effect on mice. These effects were dose-dependent, and the strongest effect on most biomarkers was seen with an intermediate dose.
基金the National Basic Research Program of China (973 Program) (No. 2007CB947301).
文摘Vertebrate digits are essential structures for movement, feeding and communication. Specialized regions of the developing limb bud including the zone of polarizing activity （ZPA）, the apical ectodermal ridge （AER）, and the non-ridge ectoderm regulate the patterning of digits. Although a series of signaling molecules have been characterized as patterning signals from the organizing centers, the delicate cellular and molecular mechanisms that interpret how these patterning signals control the detailed digit anatomy remain unclear, Recent studies from model organisms and human hand malformations provide new insights into the mechanisms regulating this process. Here, we review the current understanding of the genetic networks governing digit morphogenesis
基金Grants of National Natural Science Foundation of China (30371206, 30028019)973 National Key Basic Research and Development Program (2002 CB 512905)
文摘Objective To investigate the roles of the cyclin D1/CDK4 and E2F-1/4 pathways and compare their work patterns in cell cycle changes induced by different doses of B[a]E Methods Human embryo lung fibroblasts （HELFs） were treated with 2 μmol/L or 100 μmol/L B[a]P which were provided with some characteristics of transformed cells （T-HELFs）. Cyclin D l, CDK4 and E2F-1/4 expressions were determined by Western blotting. Flow cytometry was used to detect the distribution of cell cycle. Results After B[a]P treatment, the proportion of the first gap （G 1） phase cells decreased. CDK4 and E2F-4 expression did not change significantly. In 2 μmol/L treated cells, a marked overexpression of cyclin D1 and E2F-1 was observed. However, in T-HELFs overexpression was limited to cyclin D1 only, and no overexpression of E2F-1 was observed. The decreases of G1 phase in response to B[a]P treatment were blocked in antisense cyclin D1 and antisense CDK4 transfected HELFs （A-D1 and A-K4） and T-HELFs （T-A-D1 and T-A-K4）. After 2 μmol/L B[a]P treatment, overexpression of E2F-1 was attenuated in A-D1, and E2F-4 expression was decreased significantly in A-K4. In T-A-D1 and T-A-K4, E2F-4 expression was increased significantly, compared with T-HELFs. The E2F-1 expression remained unchanged in T-A-D1 and T-A-K4. Condusions Cyclin DI/CDK4-E2F-1/4 pathways work in different patterns in response to low dose and high dose B[a]P treatment. In HELFs treated with 2 μmol/L B[a]P, cyclin D1 positively regulates the E2F-1 expression while CDK4 negatively regulates the E2F-4 expression; however, in HELFs treated with 100 μmol/L B[a]P, both cyclin D1 and CDK4 negatively regulate the E2F-4 expression.
文摘Glatiramer acetate （GA） is an immunomodulatory peptide drug used to treat multiple sclerosis. Its treatment effect has been expanded to other autoimmune conditions such as uveoretinitis, inflammatory bowel disease, graft re- jection and hepatic fibrosis. Here, we report that GA was effective in altering the clinical course of diabetes in cyclo- phosphamide （CY）-potentiated non-obese diabetic （CY-NOD） mice. Treatment with GA significantly reduced the dia- betic rate in the mice and ameliorated insulitis, which coincided with increased CD4＋CD25＋Foxp3＋ T cell response in treated mice. GA treatment led to increased expression of transcription factor Foxp3 and elevated production of interleukin-4 （IL-4） both in vivo and in vitro. It was evident that the effect of GA on up-regulation of Foxp3 was me- diated partially through IL-4. IL-4 was found to maintain Foxp3 expression and regulatory function of CD4＋CD25＋ regulatory T cells （Tregs）. This study provides new evidence that GA has treatment potential for type 1 diabetes through the induction of Tregs and that increased IL-4 production is partially responsible for the enhanced Treg＇s function in GA treatment.
基金Project supported by the National Basic Research Program (973) of China (Nos.2011CB910500 and 2010CB912502)the One Hundred Talent Program of the Chinese Academy of Sciences,China
文摘All eukaryotic mRNAs are capped at their 5＇ end. Capping of mRNAs takes place co-transcriptionally and involves three steps. The intermediates of the capping process, as well as the uncapped 5＇ tri-phosphate RNA, are resistant to decapping and degradation by known factors, leading to the assumption that the capping process always proceeds to completion. This view was recently drastically changed. A novel family of enzymes, including the yeast proteins Rail, Dxo1/Ydr370C, and the mammalian protein DXO/Dom3Z, has been identified. These enzymes catalyze the conversion of the improperly capped mRNAs to 5＇ mono-phosphate RNA, allowing them to be degraded by 5＇-3＇ exoribonucleases. Several of these enzymes also possess 5＇-3＇ exoribonuclease activities themselves, and can single-handedly clear the improperly capped mRNAs. Studying of these enzymes has led to the realization that mRNA capping does not always proceed to completion, and the identification of an mRNA capping quality control mechanism in eukaryotes. In this paper, we briefly review recent advances in this area.
基金Supported by National Natural Science Foundation of China (Nos. 31322039 and 31371493)STS program from Chinese Academy of Sciences (No. KFJ-EW-STS-099)
文摘Nanomaterials and nanotechnology have great potential in the biological and biomedical field. Recent studies reveal that many nanomaterials possess antibacterial activities. While most of these studies focus on the ability of nanomaterials to inhibit the growth of pathogenic bacteria in vitro, few of them test the effects of nanomaterials on intestinal commensal bacteria. Here, we report that Ti O_2nanoparticles(10, 50 and 100 nm in size) can inhibit the growth of Drosophila intestinal commensal bacteria in vitro. This activity depends on the dosage or size, but is independent of the photocatalytic activity of Ti O_2 nanoparticles. Surprisingly, dietary Ti O_2 nanoparticles of the same dosage fail to display similar effects in Drosophila larvae or adults. These flies show a normal amount of intestinal commensal bacteria, as well as a normal developmental cycle, energy store, and locomotor activity. These results imply that the antibacterial effect of Ti O_2 nanoparticles differs in vitro and in vivo.
基金supported by National Key Research and Development Program of China (2016YFC0904101)Chinese Human Proteome Projects (CNHPP: 2014DFB30020, 2014DFB30030)+1 种基金Shanghai Municipal Science and Technology Commission of China (No. 17ZR1420300)National Hi-Tech Program (2015AA020101)
文摘Protein phosphorylation, one of the most important protein post-translational modifications, is involved in various biological processes, and the identification of phosphorylation peptides （phosphopeptides） and their corresponding phosphorylation sites （phosphosites） will facilitate the understanding of the molecular mechanism and function of phosphorylation. Mass spectrometry （MS） provides a high- throughput technology that enables the identification of large numbers of phosphosites. PhoPepMass is designed to assist human phosphopeptide identification from MS data based on a specific database of phophopeptide masses and a multivariate hypergeometric matching algorithm. It contains 244,915 phosphosites from several public sources. Moreover, the accurate masses of peptides and fragments with phosphosites were calculated. It is the first database that provides a systematic resource for the query of phosphosites on peptides and their corresponding masses. This allows researchers to search certain proteins of which phosphosites have been reported, to browse detailed phosphopeptide and fragment information, to match masses from MS analyses with defined threshold to the corresponding phos- phopeptide, and to compare proprietary phosphopeptide discovery results with results from previous studies. Additionally, a database search software is created and a ＂two-stage search strategy＂ is suggested to identify phosphopeptides from tandem mass spectra of proteomics data. We expect PhoPepMass to be a useful tool and a source of reference for proteomics researchers.
基金supported by the grants from the National Basic Research Program of China(No.2011CB504000)the National Key Technology R&D Program(No.2012BAI01B09)+1 种基金the Wu Jieping Medical Foundation(No.320.67001118)the National Natural Science Foundation of China(No.81121001)
文摘Telomeres are protein--DNA complex structure at the ends of chromosomes, which are involved in genomic stability （Blackburn, 2010）. In most human cells, telomere erosion with each round of cell division eventually limits cell proliferation and tissue renewal, thereby impacting age-dependent pathol- ogies （Lundblad, 2012）. Leukocyte telomere length （LTL） undertakes a slow loss throughout life across human pop- ulations in general （Blackburn, 2010）. Telomerase is a ribo- nucleoprotein that adds telomeric DNA to chromosomal ends and contains two essential components：
文摘Precision medicine emerges as a new approach that takes into account individual variability. Successful realization of precision medicine requires disease models that are able to incorporate personalized dis- ease information and recapitulate disease development processes at the molecular, cellular and organ levels. With recent development in stem cell field, a variety of tissue organoids can be derived from patient specific pluripotent stem cells and adult stem cells. In combi- nation with the state-of-the-art genome editing tools, organoids can be further engineered to mimic disease- relevant genetic and epigenetic status of a patient. This has therefore enabled a rapid expansion of sophisticated in vitro disease models, offering a unique system for fundamental and biomedical research as well as the development of personalized medicine. Here we summarize some of the latest advances and future perspectives in engineering stem cell organoids for human disease modeling.
文摘Amygdala plays a critical role in the regulation of emotional behavior and food intake.Neuropeptides are short chains of amino acids secreted by neurons as intercellular messengers,which regulate different functions such as emotion,food intake,learning and memory.In this review,we summarize the recent progress on the regulation of food intake by amygadala,which is mediated by those neuropeptides known to be critical in the regulation of this process.
