The role of regional species diversity in large-scale species invasions has been largely controversial.On the one hand,it has been proposed that diversity may facilitate invasion(“diversity begets diversity”)because...The role of regional species diversity in large-scale species invasions has been largely controversial.On the one hand,it has been proposed that diversity may facilitate invasion(“diversity begets diversity”)because regions with higher diversity may indicate favorable conditions for many more species.On the other hand,high diversity may indicate high levels of niche occupation,thus making it more difficult for new species to invade.In the past,invasion biologists have evaluated how regional native and exotic richness are related.Here,we test whether the range size of exotic species may be constrained by regional native richness using plant data from three continental regions in the Northern Hemisphere,i.e.,Europe,Eastern Asia,and North America.We found that regional native plant diversity is inversely related to the range size of exotic species.This result may be due to stronger species interactions such as competition in species-rich habitats that limit the establishment and spread of exotic species.展开更多
运用连续颗粒物采样仪(URG Model 2000-01J)对贵阳市城区大气颗粒物PM2.5进行了连续3个月(9-11月)的采集与分析,探讨了PM2.5的浓度分布特征、气象条件的影响。结果显示,贵阳市大气颗粒物PM2.5的平均质量浓度为53±27μg/m^3,变...运用连续颗粒物采样仪(URG Model 2000-01J)对贵阳市城区大气颗粒物PM2.5进行了连续3个月(9-11月)的采集与分析,探讨了PM2.5的浓度分布特征、气象条件的影响。结果显示,贵阳市大气颗粒物PM2.5的平均质量浓度为53±27μg/m^3,变化范围为3.7-186μg/m^3;初步推断大气颗粒物PM2.5的污染来源主要是燃料燃烧、生物质燃烧、汽车尾气等人为源;相对湿度、风速、风向、温度等气象条件是影响大气颗粒物浓度及分布的重要因素。展开更多
Single-strand breaks (SSBs) can occur in cells either directly, or indirectly following initiation of base excision repair (BER). SSBs generally have blocked termini lacking the conventional 5'-phosphate and 3'-...Single-strand breaks (SSBs) can occur in cells either directly, or indirectly following initiation of base excision repair (BER). SSBs generally have blocked termini lacking the conventional 5'-phosphate and 3'-hydroxyl groups and require further processing prior to DNA synthesis and ligation. XRCC1 is devoid of any known enzymatic activity, but it can physically interact with other proteins involved in all stages of the overlapping SSB repair and BER pathways, including those that conduct the rate-limiting end-tailoring, and in many cases can stimulate their enzymatic activities. XRCC1^-/- mouse fibroblasts are most hypersensitive to agents that produce DNA lesions repaired by monofunctional glycosylase-initiated BER and that result in formation of indirect SSBs. A requirement for the deoxyribose phosphate lyase activity of DNA polymerase β (pol β) is specific to this pathway, whereas pol β is implicated in gap-filling during repair of many types of SSBs. Elevated levels of strand breaks, and diminished repair, have been demonstrated in MMS- treated XRCC1^-/-, and to a lesser extent in pol β^-/- cell lines, compared with wild-type cells. Thus a strong correlation is observed between cellular sensitivity to MMS and the ability of cells to repair MMS-induced damage. Exposure of wild-type and polβ^-/- cells to an inhibitor of PARP activity dramatically potentiates MMS-induced cytotoxicity. XRCC1^-/- cells are also sensitized by PARP inhibition demonstrating that PARP-mediated poly(ADP-ribosyl)ation plays a role in modulation of cytotoxicity beyond recruitment of XRCC 1 to sites of DNA damage.展开更多
Post-translational modification is central to protein stability and to the modulation of protein activity. Various types of protein modification, such as phosphorylation, methylation, acetylation, myristoylation, glyc...Post-translational modification is central to protein stability and to the modulation of protein activity. Various types of protein modification, such as phosphorylation, methylation, acetylation, myristoylation, glycosylation, and ubiquitination, have been reported. Among them, ubiquitination distinguishes itself from others in that most of the ubiquitinated proteins are targeted to the 26S proteasome for degradation. The ubiquitin/26S proteasome system constitutes the major protein degradation pathway in the cell. In recent years, the importance of the ubiquitination machinery in the control of numerous eukaryotic cellular functions has been increasingly appreciated. Increasing number of E3 ubiquitin ligases and their substrates, including a variety of essential cellular regulators have been identified. Studies in the past several years have revealed that the ubiquitination system is important for a broad range of plant developmental processes and responses to abiotic and biotic stresses. This review discusses recent advances in the functional analysis of ubiquitination-associated proteins from plants and pathogens that play important roles in plant-microbe interactions.展开更多
CONSORT声明被广泛用于提高随机对照临床试验的报告质量。Kenneth Schulz等对CONSORT声明的最新版本CONSORT2010作了详细说明,该版本基于新获得的方法学证据和经验的积累对报告指南作了更新。为了鼓励更多的人使用"CONSORT2010声明...CONSORT声明被广泛用于提高随机对照临床试验的报告质量。Kenneth Schulz等对CONSORT声明的最新版本CONSORT2010作了详细说明,该版本基于新获得的方法学证据和经验的积累对报告指南作了更新。为了鼓励更多的人使用"CONSORT2010声明",本文可从bmj.com免费获取,也将在Lancet,Obstetrics and Gynecology,PLoS Medicine,Annals of Internal Medicine,Open Medicine,Journal of Clinical Epidemiology,BMC Medicine和Trials等杂志发表。展开更多
The effect of sulfur dioxide (SO2) on the formation of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) has been studied in an entrained-flow reactor (EFR) under simulated wa...The effect of sulfur dioxide (SO2) on the formation of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) has been studied in an entrained-flow reactor (EFR) under simulated waste combustion conditions. A chlorination model based on conditional probability was employed to evaluate the homologue patterns of PCDDs and PCDFs. Results revealed that the presence of SO2 did not alter the formation pathway although SO2 suppressed PCDD/F formation. The prediction model of PCDF showed good agreement with the experimental data (R--0.95), whereas the prediction for PCDDs did not correlate well with the experimental data. This may be explained because potential chlorination pathways play a significant role in PCDF formation, whereas PCDDs are mainly formed through condensation reactions. Furthermore, the result indicated that the steric hindrance during formation has more effects on PCDD than on PCDF due to the symmetric molecular structures of PCDDs.展开更多
In this study,a new analytical technique was developed for the identification and quantification of multifunctional compounds containing simultaneously at least one hydroxyl or one carboxylic group,or both.This techni...In this study,a new analytical technique was developed for the identification and quantification of multifunctional compounds containing simultaneously at least one hydroxyl or one carboxylic group,or both.This technique is based on derivatizing first the carboxylic group(s) of the multifunctional compound using an alcohol (e.g.,methanol,1-butanol) in the presence of a relatively strong Lewisacid (BF3) as a catalyst.This esterification reaction quickly and quantitatively converts carboxylic acids to their ester forms.The second step is based on silylation of the ester compounds using bis(trimethylsilyl) trifluoroacetamide (BSTFA) as the derivatizing agent.For compounds bearing ketone groups in addition to carboxylic and hydroxyl groups,a third step was used based on PFBHA derivatizationof the carbonyls.Different parameters including temperature,reaction time,and effect due to artifacts were optimized.A GC/MS in EI and in methane-CI mode was used for the analysis of these compounds.The new approach was tested on a number of multifunctional compounds.The interpretation of their EI (70 eV) and CI mass spectra shows that critical information is gained leading to unambiguous identification of unknown compounds.For example,when derivatized only with BF3-methanol,their mass spectra comprise primary ions at m/z M ·+ +1,M ·+ +29,and M ·+ - 31 for compounds bearing only carboxylic groups and M ·+ +1,M ·+ +29,M ·+ -31,and M ·+ -17 for those bearing hydroxyl andcarboxylic groups.However,when a second derivatization (BSTFA) was used,compounds bearing hydroxyl and carboxylic groups simultaneously show,in addition to the ions observed before,ions at m/z M ·+ +73,M ·+ -15,M ·+ -59,M ·+ -75,M ·+ -89,and 73.To the best of our knowledge,this technique describes systematically for the first time a method for identifying multifunctional oxygenated compounds containing simultaneously one or more hydroxyl and carboxylic acid groups.展开更多
BCL2 is best known as a multifnnctional anti-apoptotic protein. However, little is known about its role in cell- adhesive and motility events. Here, we show that BCL2 may play a role in the regulation of cell adhesion...BCL2 is best known as a multifnnctional anti-apoptotic protein. However, little is known about its role in cell- adhesive and motility events. Here, we show that BCL2 may play a role in the regulation of cell adhesion, spreading, and motility. When BCL2 was overexpressed in cultured murine and human cell lines, cell spreading, adhesion, and motility were impaired. Consistent with these results, the loss of Bcl2 resulted in higher motility observed in Bcl2- null mouse embryonic fibroblast (MEF) cells compared to wild type. The mechanism of BCL2 regulation of cell adhesion and motility may involve formation of a complex containing BCL2, actin, and gelsolin, which appears to functionally decrease the severing activity of gelsolin. We have observed that the lysate from MCF-7 and NIH3T3 cells that overexpressed BCL2 enhanced actin polymerization in cell-free in vitro assays. Confocal immunofluorescent localization of BCL2 and F-actin during spreading consistently showed that increased expression of BCL2 resulted in increased F-actin polymerization. Thus, the formation of BCL2 and gelsolin complexes (which possibly contain other proteins) appears to play a critical role in the regulation of cell adhesion and migration. Given the established correlation of cell motility with cancer metastasis, this result may explain why the expression Of BCL2 in some tumor cell types reduces the potential for metastasis and is associated with improved patient prognosis.展开更多
In their seminal publication describing the structure of the DNA double helix , Watson and Crick wrote what may be one of the greatest understatements in the scientific literature, namely that "It has not escaped our...In their seminal publication describing the structure of the DNA double helix , Watson and Crick wrote what may be one of the greatest understatements in the scientific literature, namely that "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material." Half a century later, we more fully appreciate what a huge challenge it is to replicate six billion nucleotides with the accuracy needed to stably maintain the human genome over many generations. This challenge is perhaps greater than was realized 50 years ago, because subsequent studies have revealed that the genome can be destabilized not only by environmental stresses that generate a large number and variety of potentially cytotoxic and mutagenic lesions in DNA but also by various sequence motifs of normal DNA that present challenges to replication. Towards a better understanding of the many determinants of genome stability, this chapter reviews the fidelity with which undamaged and damaged DNA is copied, with a focus on the eukaryotic B- and Y-family DNA polymerases, and considers how this fidelity is achieved.展开更多
AIM To systematically review the literature on epidemiology,disease burden, and treatment outcomes for Crohn's disease(CD) patients with complex perianal fistulas.METHODS PubMed, Embase, and Cochrane were searched...AIM To systematically review the literature on epidemiology,disease burden, and treatment outcomes for Crohn's disease(CD) patients with complex perianal fistulas.METHODS PubMed, Embase, and Cochrane were searched for relevant articles(published 2000-November 2016) and congress abstracts(published 2011-November 2016).RESULTS Of 535 records reviewed, 62 relevant sources were identified(mostly small observational studies). The cumulative incidence of complex perianal fistulas in CD from two referral-centre studies was 12%-14%(follow-up time, 12 years in one study; not reported in the second study). Complex perianal fistulas result in greatly diminished quality of life; up to 59% of patients are at risk of faecal incontinence. Treatments include combinations of medical and surgical interventions and expanded allogeneic adipose-derived stem cells. High proportions of patients experience lack of or inadequate response to treatment(failure and relapse rates,respectively: medical, 12%-73% and 0%-41%; surgical:0%-100% and 11%.20%; combined medical/surgical:0%-80% and 0%-50%; stem cells: 29%-47% and not reported). Few studies(1 of infliximab; 3 of surgical interventions)have been conducted in treatment-refractory patients, a population with high unmet needs. Limited data exist on the clinical value of anti-tumour necrosis factor-α dose escalation in patients with complex perianal fistulas in CD.CONCLUSION Complex perianal fistulas in CD pose substantial clinical and humanistic burden. There is a need for effective treatments, especially for patients refractory to antitumour necrosis factor-α agents, as evidenced by high failure and relapse rates.展开更多
BACKGROUND: Sarcopenia and non-alcoholic fatty liver dis- ease (NAFLD) share similar pathophysiological mechanisms, and the relationship between sarcopenia and NAFLD has been recently investigated. The study invest...BACKGROUND: Sarcopenia and non-alcoholic fatty liver dis- ease (NAFLD) share similar pathophysiological mechanisms, and the relationship between sarcopenia and NAFLD has been recently investigated. The study investigated whether low skel- etal muscle mass is differentially associated with NAFLD by gender in Korean adults. METHODS: We conducted a cross-sectional analysis of the data from the Fifth Korea National Health and Nutrition Examination Survey. The skeletal muscle index (SMI) was obtained by the appendicular skeletal muscle mass divided by the weight. NAFLD was defined as a fatty liver index (FLI) 〉60 in the absence of other chronic liver disease. RESULTS: Among the included subjects, 18.3% (SE: 1.4%) in men and 7.0% (SE: 0.7%) in women were classified as having FLI-defined NAFLD. Most of the risk factors for FLI-defined NAFLD showed a significant negative correlation with the SMI in both genders. Multiple logistic regression analysis showed that low SMI was associated with FLI-defined NAFLD, inde- pendent of other metabolic and lifestyle parameters in both genders [males: odds ratio (OR)=1.35; 95% confidence inter- val (CI): 1.17-1.54; females: OR=1.36; 95% CI: 1.18-1.55]. The magnitude of the association between FLI-defined NAFLD and low SMI was higher in middle aged to elderly males (OR-1.50; 95% CI: 1.22-1.84) than in males less than 45 years of age (OR=1.25; 95% CI: 1.02-1.52) and in premenopausal females (OR=l.50; 95% CI: 1.12-2.03) than in postmenopausal females (OR-1.36; 95% CI: 1.20-1.54).CONCLUSIONS: Low SMI is associated with the risk of FLI- defined NAFLD independent of other well-known metabolic risk factors in both genders. This association may differ ac- cording to age group or menopausal status. Further studies are warranted to confirm this relationship.展开更多
文摘The role of regional species diversity in large-scale species invasions has been largely controversial.On the one hand,it has been proposed that diversity may facilitate invasion(“diversity begets diversity”)because regions with higher diversity may indicate favorable conditions for many more species.On the other hand,high diversity may indicate high levels of niche occupation,thus making it more difficult for new species to invade.In the past,invasion biologists have evaluated how regional native and exotic richness are related.Here,we test whether the range size of exotic species may be constrained by regional native richness using plant data from three continental regions in the Northern Hemisphere,i.e.,Europe,Eastern Asia,and North America.We found that regional native plant diversity is inversely related to the range size of exotic species.This result may be due to stronger species interactions such as competition in species-rich habitats that limit the establishment and spread of exotic species.
文摘运用连续颗粒物采样仪(URG Model 2000-01J)对贵阳市城区大气颗粒物PM2.5进行了连续3个月(9-11月)的采集与分析,探讨了PM2.5的浓度分布特征、气象条件的影响。结果显示,贵阳市大气颗粒物PM2.5的平均质量浓度为53±27μg/m^3,变化范围为3.7-186μg/m^3;初步推断大气颗粒物PM2.5的污染来源主要是燃料燃烧、生物质燃烧、汽车尾气等人为源;相对湿度、风速、风向、温度等气象条件是影响大气颗粒物浓度及分布的重要因素。
基金Financial support was provided by the following sources to convene a meeting of the CONSORT Group in Montebello Canada+9 种基金in January 2007:the American Society of Clinical OncologyBMJCanadian Institutes for Health ResearchJohnson & JohnsonThe LancetNordic Cochrane CentrePLoS Medicine UK Cochrane Centreand UK National Co-ordinating Centre for Research Methodology.DM is supported by a University of Ottawa Research Chair.国家重点基础研究发展计划(973计划)项目资助(No.2006CB504602)。
文摘背景:对于与随机对照试验(randomized controlled trial,RCT)有关的学术会议论文或期刊中发表的文章来说,清楚、明了、信息量充足的摘要是十分重要的,因为读者经常仅仅根据报告的摘要对一个临床试验作出评价。为此,我们需要对"临床试验报告的统一标准(Consolidated Standards of Reporting Trials,CONSORT)声明"进行扩充,制定一个期刊与学术会议论文摘要中报告RCT的必备条目清单。今后在任何期刊发表的论文或学术会议论文摘要中,作者对RCT结果的报告都要包含这些内容。方法与结果:我们根据现有的质量评价工具和基于经验的证据总结出一个条目清单。运用三轮修正式德尔菲法(modified-Delphi process)进行条目筛选。邀请共计109人参与电子网络调查,反馈率为61%。调查结果于2007年1月在加拿大蒙特贝罗举行的CONSORT小组会议中公布,与会的26人中有临床试验实施人员、统计学家、流行病学家以及生物医学编辑。经过讨论最终确定条目,随后对其进行修订以保证这些条目体现了会议期间以及会后的讨论思路。摘要CONSORT建议RCT报告的摘要需要有一个结构化的格式,其中应该包括具体的试验目的、试验设计(随机分配的方法、盲法或遮蔽等)、研究对象(对象描述、随机分组的样本量以及用于分析的样本量)、每组实施的干预、实施的干预对主要疗效结果的影响及其危害、试验结论、试验注册名称和编号以及资金来源。本文对每一条能够找到例子的纳入条目都配有良好报告范例、基本原理以及证据等,十分明了易懂,因此我们建议与清单同时使用。结论:摘要CONSORT旨在改善期刊与学术会议中发表的论文摘要的质量,这将有助于摘要提供详尽清晰的信息,这些信息能够帮助读者对试验的有效性和试验结果的适用性做出正确的评价。
文摘Single-strand breaks (SSBs) can occur in cells either directly, or indirectly following initiation of base excision repair (BER). SSBs generally have blocked termini lacking the conventional 5'-phosphate and 3'-hydroxyl groups and require further processing prior to DNA synthesis and ligation. XRCC1 is devoid of any known enzymatic activity, but it can physically interact with other proteins involved in all stages of the overlapping SSB repair and BER pathways, including those that conduct the rate-limiting end-tailoring, and in many cases can stimulate their enzymatic activities. XRCC1^-/- mouse fibroblasts are most hypersensitive to agents that produce DNA lesions repaired by monofunctional glycosylase-initiated BER and that result in formation of indirect SSBs. A requirement for the deoxyribose phosphate lyase activity of DNA polymerase β (pol β) is specific to this pathway, whereas pol β is implicated in gap-filling during repair of many types of SSBs. Elevated levels of strand breaks, and diminished repair, have been demonstrated in MMS- treated XRCC1^-/-, and to a lesser extent in pol β^-/- cell lines, compared with wild-type cells. Thus a strong correlation is observed between cellular sensitivity to MMS and the ability of cells to repair MMS-induced damage. Exposure of wild-type and polβ^-/- cells to an inhibitor of PARP activity dramatically potentiates MMS-induced cytotoxicity. XRCC1^-/- cells are also sensitized by PARP inhibition demonstrating that PARP-mediated poly(ADP-ribosyl)ation plays a role in modulation of cytotoxicity beyond recruitment of XRCC 1 to sites of DNA damage.
文摘Post-translational modification is central to protein stability and to the modulation of protein activity. Various types of protein modification, such as phosphorylation, methylation, acetylation, myristoylation, glycosylation, and ubiquitination, have been reported. Among them, ubiquitination distinguishes itself from others in that most of the ubiquitinated proteins are targeted to the 26S proteasome for degradation. The ubiquitin/26S proteasome system constitutes the major protein degradation pathway in the cell. In recent years, the importance of the ubiquitination machinery in the control of numerous eukaryotic cellular functions has been increasingly appreciated. Increasing number of E3 ubiquitin ligases and their substrates, including a variety of essential cellular regulators have been identified. Studies in the past several years have revealed that the ubiquitination system is important for a broad range of plant developmental processes and responses to abiotic and biotic stresses. This review discusses recent advances in the functional analysis of ubiquitination-associated proteins from plants and pathogens that play important roles in plant-microbe interactions.
文摘CONSORT声明被广泛用于提高随机对照临床试验的报告质量。Kenneth Schulz等对CONSORT声明的最新版本CONSORT2010作了详细说明,该版本基于新获得的方法学证据和经验的积累对报告指南作了更新。为了鼓励更多的人使用"CONSORT2010声明",本文可从bmj.com免费获取,也将在Lancet,Obstetrics and Gynecology,PLoS Medicine,Annals of Internal Medicine,Open Medicine,Journal of Clinical Epidemiology,BMC Medicine和Trials等杂志发表。
基金United Kingdom National Institute for Health ResearchCanadian Institutes of Health Research+4 种基金Presidents FundCanadian Institutes of Health ResearchJohnson & JohnsonBMJthe American Society for Clinical Oncology
文摘大量证据显示随机对照临床试验(randomised controlled trial,RCT)的报告质量不理想。报告不透明,则读者既不能评判试验结果是否真实可靠,也不能从中提取可用于系统综述的信息。最近的方法学分析表明,报告不充分和设计不合理与对治疗效果产生评价偏倚有关。这种系统误差对RCT损害严重,而RCT正是以其能减少或避免偏倚而被视为评价干预措施的金标准。为了提高RCT的报告质量,一个由专家和编辑组成的工作组制定了临床试验报告的统一标准(Consolidated Standards of Reporting Trials,CONSORT)声明。CONSORT声明于1996年首次发表,并于2001年更新。声明由对照检查清单和流程图组成,供作者在报告RCT时使用。许多核心医学期刊和主要国际性编辑组织都已认可CONSORT声明。该声明促进了对RCT的严格评价和解释。2001年,在对CONSORT进行修订时,人们就已经清楚地认识到,解释和说明制定CONSORT声明的原理,有助于研究人员等撰写或评价临床试验报告。一篇CONSORT说明与详述文章于2001年同2001版CONSORT声明一起发表。2007年1月的专家会议之后,对CONSORT声明作了进一步修订并已发表,即"CONSORT2010声明"。这次更新对原版对照检查清单作了文字上的修改,使其更为明晰,并收入了与一些新近才认识到的主题相关的建议,如选择性报告结局产生的偏倚。说明与详述文件旨在加强人们对CONSORT声明的理解、应用和传播,这次也作了大量修订,对每一项新增或更新的清单条目的含义和增改理由进行了解释,提供了优秀的报告实例,还尽可能地提供了相关的经验性研究的参考文献。文中收入了若干流程图实例。"CONSORT2010声明"、其说明与详述文件,以及相关网站(www.consort-statement.org),对于改进随机临床试验报告必将有所裨益。
基金Project supported by the China Scholarship Council Foundation (2003) the National Natural Science Foundation of China (No. 50576082).
文摘The effect of sulfur dioxide (SO2) on the formation of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) has been studied in an entrained-flow reactor (EFR) under simulated waste combustion conditions. A chlorination model based on conditional probability was employed to evaluate the homologue patterns of PCDDs and PCDFs. Results revealed that the presence of SO2 did not alter the formation pathway although SO2 suppressed PCDD/F formation. The prediction model of PCDF showed good agreement with the experimental data (R--0.95), whereas the prediction for PCDDs did not correlate well with the experimental data. This may be explained because potential chlorination pathways play a significant role in PCDF formation, whereas PCDDs are mainly formed through condensation reactions. Furthermore, the result indicated that the steric hindrance during formation has more effects on PCDD than on PCDF due to the symmetric molecular structures of PCDDs.
文摘In this study,a new analytical technique was developed for the identification and quantification of multifunctional compounds containing simultaneously at least one hydroxyl or one carboxylic group,or both.This technique is based on derivatizing first the carboxylic group(s) of the multifunctional compound using an alcohol (e.g.,methanol,1-butanol) in the presence of a relatively strong Lewisacid (BF3) as a catalyst.This esterification reaction quickly and quantitatively converts carboxylic acids to their ester forms.The second step is based on silylation of the ester compounds using bis(trimethylsilyl) trifluoroacetamide (BSTFA) as the derivatizing agent.For compounds bearing ketone groups in addition to carboxylic and hydroxyl groups,a third step was used based on PFBHA derivatizationof the carbonyls.Different parameters including temperature,reaction time,and effect due to artifacts were optimized.A GC/MS in EI and in methane-CI mode was used for the analysis of these compounds.The new approach was tested on a number of multifunctional compounds.The interpretation of their EI (70 eV) and CI mass spectra shows that critical information is gained leading to unambiguous identification of unknown compounds.For example,when derivatized only with BF3-methanol,their mass spectra comprise primary ions at m/z M ·+ +1,M ·+ +29,and M ·+ - 31 for compounds bearing only carboxylic groups and M ·+ +1,M ·+ +29,M ·+ -31,and M ·+ -17 for those bearing hydroxyl andcarboxylic groups.However,when a second derivatization (BSTFA) was used,compounds bearing hydroxyl and carboxylic groups simultaneously show,in addition to the ions observed before,ions at m/z M ·+ +73,M ·+ -15,M ·+ -59,M ·+ -75,M ·+ -89,and 73.To the best of our knowledge,this technique describes systematically for the first time a method for identifying multifunctional oxygenated compounds containing simultaneously one or more hydroxyl and carboxylic acid groups.
文摘BCL2 is best known as a multifnnctional anti-apoptotic protein. However, little is known about its role in cell- adhesive and motility events. Here, we show that BCL2 may play a role in the regulation of cell adhesion, spreading, and motility. When BCL2 was overexpressed in cultured murine and human cell lines, cell spreading, adhesion, and motility were impaired. Consistent with these results, the loss of Bcl2 resulted in higher motility observed in Bcl2- null mouse embryonic fibroblast (MEF) cells compared to wild type. The mechanism of BCL2 regulation of cell adhesion and motility may involve formation of a complex containing BCL2, actin, and gelsolin, which appears to functionally decrease the severing activity of gelsolin. We have observed that the lysate from MCF-7 and NIH3T3 cells that overexpressed BCL2 enhanced actin polymerization in cell-free in vitro assays. Confocal immunofluorescent localization of BCL2 and F-actin during spreading consistently showed that increased expression of BCL2 resulted in increased F-actin polymerization. Thus, the formation of BCL2 and gelsolin complexes (which possibly contain other proteins) appears to play a critical role in the regulation of cell adhesion and migration. Given the established correlation of cell motility with cancer metastasis, this result may explain why the expression Of BCL2 in some tumor cell types reduces the potential for metastasis and is associated with improved patient prognosis.
文摘In their seminal publication describing the structure of the DNA double helix , Watson and Crick wrote what may be one of the greatest understatements in the scientific literature, namely that "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material." Half a century later, we more fully appreciate what a huge challenge it is to replicate six billion nucleotides with the accuracy needed to stably maintain the human genome over many generations. This challenge is perhaps greater than was realized 50 years ago, because subsequent studies have revealed that the genome can be destabilized not only by environmental stresses that generate a large number and variety of potentially cytotoxic and mutagenic lesions in DNA but also by various sequence motifs of normal DNA that present challenges to replication. Towards a better understanding of the many determinants of genome stability, this chapter reviews the fidelity with which undamaged and damaged DNA is copied, with a focus on the eukaryotic B- and Y-family DNA polymerases, and considers how this fidelity is achieved.
基金Kate Lothman of RTI Health Solutions provided medical writing services,which were funded by Takeda
文摘AIM To systematically review the literature on epidemiology,disease burden, and treatment outcomes for Crohn's disease(CD) patients with complex perianal fistulas.METHODS PubMed, Embase, and Cochrane were searched for relevant articles(published 2000-November 2016) and congress abstracts(published 2011-November 2016).RESULTS Of 535 records reviewed, 62 relevant sources were identified(mostly small observational studies). The cumulative incidence of complex perianal fistulas in CD from two referral-centre studies was 12%-14%(follow-up time, 12 years in one study; not reported in the second study). Complex perianal fistulas result in greatly diminished quality of life; up to 59% of patients are at risk of faecal incontinence. Treatments include combinations of medical and surgical interventions and expanded allogeneic adipose-derived stem cells. High proportions of patients experience lack of or inadequate response to treatment(failure and relapse rates,respectively: medical, 12%-73% and 0%-41%; surgical:0%-100% and 11%.20%; combined medical/surgical:0%-80% and 0%-50%; stem cells: 29%-47% and not reported). Few studies(1 of infliximab; 3 of surgical interventions)have been conducted in treatment-refractory patients, a population with high unmet needs. Limited data exist on the clinical value of anti-tumour necrosis factor-α dose escalation in patients with complex perianal fistulas in CD.CONCLUSION Complex perianal fistulas in CD pose substantial clinical and humanistic burden. There is a need for effective treatments, especially for patients refractory to antitumour necrosis factor-α agents, as evidenced by high failure and relapse rates.
文摘BACKGROUND: Sarcopenia and non-alcoholic fatty liver dis- ease (NAFLD) share similar pathophysiological mechanisms, and the relationship between sarcopenia and NAFLD has been recently investigated. The study investigated whether low skel- etal muscle mass is differentially associated with NAFLD by gender in Korean adults. METHODS: We conducted a cross-sectional analysis of the data from the Fifth Korea National Health and Nutrition Examination Survey. The skeletal muscle index (SMI) was obtained by the appendicular skeletal muscle mass divided by the weight. NAFLD was defined as a fatty liver index (FLI) 〉60 in the absence of other chronic liver disease. RESULTS: Among the included subjects, 18.3% (SE: 1.4%) in men and 7.0% (SE: 0.7%) in women were classified as having FLI-defined NAFLD. Most of the risk factors for FLI-defined NAFLD showed a significant negative correlation with the SMI in both genders. Multiple logistic regression analysis showed that low SMI was associated with FLI-defined NAFLD, inde- pendent of other metabolic and lifestyle parameters in both genders [males: odds ratio (OR)=1.35; 95% confidence inter- val (CI): 1.17-1.54; females: OR=1.36; 95% CI: 1.18-1.55]. The magnitude of the association between FLI-defined NAFLD and low SMI was higher in middle aged to elderly males (OR-1.50; 95% CI: 1.22-1.84) than in males less than 45 years of age (OR=1.25; 95% CI: 1.02-1.52) and in premenopausal females (OR=l.50; 95% CI: 1.12-2.03) than in postmenopausal females (OR-1.36; 95% CI: 1.20-1.54).CONCLUSIONS: Low SMI is associated with the risk of FLI- defined NAFLD independent of other well-known metabolic risk factors in both genders. This association may differ ac- cording to age group or menopausal status. Further studies are warranted to confirm this relationship.