The function of ATP binding cassette protein A1(ABCA1)is central to cholesterol mobilization.Reduced ABCA1 expression or activity is implicated in Alzheimer’s disease(AD)and other disorders.Therapeutic approaches to ...The function of ATP binding cassette protein A1(ABCA1)is central to cholesterol mobilization.Reduced ABCA1 expression or activity is implicated in Alzheimer’s disease(AD)and other disorders.Therapeutic approaches to boost ABCA1 activity have yet to be translated successfully to the clinic.The risk factors for AD development and progression,including comorbid disorders such as type2 diabetes and cardiovascular disease,highlight the intersection of cholesterol transport and inflammation.Upregulation of ABCA1 can positively impact APOE lipidation,insulin sensitivity,peripheral vascular and blood-brain barrier integrity,and anti-inflammatory signaling.Various strategies towards ABCA1-boosting compounds have been described,with a bias toward nuclear hormone receptor(NHR)agonists.These agonists display beneficial preclinical effects;however,important side effects have limited development.In particular,ligands that bind liver X receptor(LXR),the primary NHR that controls ABCA1 expression,have shown positive effects in AD mouse models;however,lipogenesis and unwanted increases in triglyceride production are often observed.The longstanding approach,focusing on LXRβvs.LXRa selectivity,is over-simplistic and has failed.Novel approaches such as phenotypic screening may lead to small molecule NHR modulators that elevate ABCA1 function without inducing lipogenesis and are clinically translatable.展开更多
Using the basic GenBank local alignment search tool program(BLAST)to identify fungi collected in a recently protected beech forest at Montricher(Switzerland),the number of ITS sequences associated to the wrong taxon n...Using the basic GenBank local alignment search tool program(BLAST)to identify fungi collected in a recently protected beech forest at Montricher(Switzerland),the number of ITS sequences associated to the wrong taxon name appears to be around 30%,even higher than previously estimated.Such results rely on the in-depth re-examination of BLAST results for the most interesting species that were collected,viz.first records for Switzerland,rare or patrimonial species and problematic species(when BLAST top scores were equally high for different species),all belonging to Agaricomycotina.This paper dissects for the first time a number of sequence-based identifications,thereby showing in every detail—particularly to the user community of taxonomic information—why sequence-based identification in the context of a fungal inventory can easily go wrong.Our first conclusion is that in-depth examination of BLAST results is too time consuming to be considered as a routine approach for future inventories:we spent two months on verification of approx.20 identifications.Apart from the fact that poor taxon coverage in public depositories remains the principal impediment for successful species identification,it can be deplored that even very recent fungal sequence deposits in GenBank involve an uncomfortably high number of misidentifications or errors with associated metadata.While checking the original publications associated with top score sequences for the few examples that were here re-examined,a positive consequence is that we uncovered over 80 type sequences that were not annotated as types in GenBank.Advantages and pitfalls of sequence-based identification are discussed,particularly in the light of undertaking fungal inventories.Recommendations are made to avoid or reduce some of the major problems with sequence-based identification.Nevertheless,the prospects for a more reliable sequence-based identification of fungi remain quite dim,unless authors are ready to check and update the metadata associated with previously deposit展开更多
Five novel vanadium substituted series of Dawson-type heteropoly acid H7 [As2Mo17VO62 ]·10H2O （1）, H8 [ As2Mo16 V2O62 ]· 7H2O（2）, Ha [ As2MO15 V3O62 ]·8H2O（3）, H8 [ As2Mo14 V4O62 H2 ]·7H2O（...Five novel vanadium substituted series of Dawson-type heteropoly acid H7 [As2Mo17VO62 ]·10H2O （1）, H8 [ As2Mo16 V2O62 ]· 7H2O（2）, Ha [ As2MO15 V3O62 ]·8H2O（3）, H8 [ As2Mo14 V4O62 H2 ]·7H2O（ 4 ）, H9[As2Mo13V5O62H2] ·10H2O（5） were prepared respectively in aqueous solution. When magnetic stirring and pH meter monitoring, all reactants mixed and controled different pH, then the mixture was refluxed for 10 h, later extracted by aether when it cooled, finally, it could be recrystaled by 0.5 % sulphuic acid solution, then yielded productions that we need. Compounds （ 1 ） - （5） were characterized by elemental analysis, thermogravimetic analysis （TGA）, infrared spectroscopy （IR）, ultraviolet and visible spectroscopy（UV-Vis）, X-ray powder diffraction analysis, ^51V nuclear magnetic resonance （SIV NMR） structure analysis. The study indicates that these compounds possess Dawson structures, ^51V NMR spectra reveals that V atom is polar-site substituted indeed.展开更多
BACKGROUND It is not uncommon to develop autoimmune encephalitis and paraneoplastic neurological syndromes(PNS).4 kinds of antibody-positive autoimmune paraneoplastic limbic encephalitis(PLE)have not been reported.CAS...BACKGROUND It is not uncommon to develop autoimmune encephalitis and paraneoplastic neurological syndromes(PNS).4 kinds of antibody-positive autoimmune paraneoplastic limbic encephalitis(PLE)have not been reported.CASE SUMMARY PNS are distant effects of cancer on the nervous system,rather than syndromes in which cancer directly invades and metastasizes to the nerves and/or muscle tissues.If the limbic lobe system of the brain is involved,this will result in PLE.The detection of patients with PNS is challenging since tumors that cause paraneoplastic neurologic disorders are often asymptomatic,obscure,and thus easily misdiagnosed or missed.Currently,single-or double-antibody-positive paraneoplastic marginal encephalitis has been reported.However,no cases of three or more-antibody-positive cases have been reported.Here,we report a case of PLE that is anti-collapsing response-mediator protein-5,anti-neuronal nuclear antibody-type 1,anti-aminobutyric acid B receptor,and anti-glutamate deglutase positive,and address relevant literature to improve our understanding of the disease.CONCLUSION This article reports on the management of a case of PLE with four positive antibodies,a review of the literature,in order to raise awareness among clinicians.展开更多
基金supported by NIH T32AG57468(USA)and American Heart Association 20PRE35150022(USA)and is a trainee in the University of Illinois Medical Scientist Training Program(USA)was provided through the UICentre for Drug Discovery as supported by the National Center for Advancing Translational Sciences,NIH UL1TR002003(USA)。
文摘The function of ATP binding cassette protein A1(ABCA1)is central to cholesterol mobilization.Reduced ABCA1 expression or activity is implicated in Alzheimer’s disease(AD)and other disorders.Therapeutic approaches to boost ABCA1 activity have yet to be translated successfully to the clinic.The risk factors for AD development and progression,including comorbid disorders such as type2 diabetes and cardiovascular disease,highlight the intersection of cholesterol transport and inflammation.Upregulation of ABCA1 can positively impact APOE lipidation,insulin sensitivity,peripheral vascular and blood-brain barrier integrity,and anti-inflammatory signaling.Various strategies towards ABCA1-boosting compounds have been described,with a bias toward nuclear hormone receptor(NHR)agonists.These agonists display beneficial preclinical effects;however,important side effects have limited development.In particular,ligands that bind liver X receptor(LXR),the primary NHR that controls ABCA1 expression,have shown positive effects in AD mouse models;however,lipogenesis and unwanted increases in triglyceride production are often observed.The longstanding approach,focusing on LXRβvs.LXRa selectivity,is over-simplistic and has failed.Novel approaches such as phenotypic screening may lead to small molecule NHR modulators that elevate ABCA1 function without inducing lipogenesis and are clinically translatable.
文摘Using the basic GenBank local alignment search tool program(BLAST)to identify fungi collected in a recently protected beech forest at Montricher(Switzerland),the number of ITS sequences associated to the wrong taxon name appears to be around 30%,even higher than previously estimated.Such results rely on the in-depth re-examination of BLAST results for the most interesting species that were collected,viz.first records for Switzerland,rare or patrimonial species and problematic species(when BLAST top scores were equally high for different species),all belonging to Agaricomycotina.This paper dissects for the first time a number of sequence-based identifications,thereby showing in every detail—particularly to the user community of taxonomic information—why sequence-based identification in the context of a fungal inventory can easily go wrong.Our first conclusion is that in-depth examination of BLAST results is too time consuming to be considered as a routine approach for future inventories:we spent two months on verification of approx.20 identifications.Apart from the fact that poor taxon coverage in public depositories remains the principal impediment for successful species identification,it can be deplored that even very recent fungal sequence deposits in GenBank involve an uncomfortably high number of misidentifications or errors with associated metadata.While checking the original publications associated with top score sequences for the few examples that were here re-examined,a positive consequence is that we uncovered over 80 type sequences that were not annotated as types in GenBank.Advantages and pitfalls of sequence-based identification are discussed,particularly in the light of undertaking fungal inventories.Recommendations are made to avoid or reduce some of the major problems with sequence-based identification.Nevertheless,the prospects for a more reliable sequence-based identification of fungi remain quite dim,unless authors are ready to check and update the metadata associated with previously deposit
文摘Five novel vanadium substituted series of Dawson-type heteropoly acid H7 [As2Mo17VO62 ]·10H2O （1）, H8 [ As2Mo16 V2O62 ]· 7H2O（2）, Ha [ As2MO15 V3O62 ]·8H2O（3）, H8 [ As2Mo14 V4O62 H2 ]·7H2O（ 4 ）, H9[As2Mo13V5O62H2] ·10H2O（5） were prepared respectively in aqueous solution. When magnetic stirring and pH meter monitoring, all reactants mixed and controled different pH, then the mixture was refluxed for 10 h, later extracted by aether when it cooled, finally, it could be recrystaled by 0.5 % sulphuic acid solution, then yielded productions that we need. Compounds （ 1 ） - （5） were characterized by elemental analysis, thermogravimetic analysis （TGA）, infrared spectroscopy （IR）, ultraviolet and visible spectroscopy（UV-Vis）, X-ray powder diffraction analysis, ^51V nuclear magnetic resonance （SIV NMR） structure analysis. The study indicates that these compounds possess Dawson structures, ^51V NMR spectra reveals that V atom is polar-site substituted indeed.
文摘BACKGROUND It is not uncommon to develop autoimmune encephalitis and paraneoplastic neurological syndromes(PNS).4 kinds of antibody-positive autoimmune paraneoplastic limbic encephalitis(PLE)have not been reported.CASE SUMMARY PNS are distant effects of cancer on the nervous system,rather than syndromes in which cancer directly invades and metastasizes to the nerves and/or muscle tissues.If the limbic lobe system of the brain is involved,this will result in PLE.The detection of patients with PNS is challenging since tumors that cause paraneoplastic neurologic disorders are often asymptomatic,obscure,and thus easily misdiagnosed or missed.Currently,single-or double-antibody-positive paraneoplastic marginal encephalitis has been reported.However,no cases of three or more-antibody-positive cases have been reported.Here,we report a case of PLE that is anti-collapsing response-mediator protein-5,anti-neuronal nuclear antibody-type 1,anti-aminobutyric acid B receptor,and anti-glutamate deglutase positive,and address relevant literature to improve our understanding of the disease.CONCLUSION This article reports on the management of a case of PLE with four positive antibodies,a review of the literature,in order to raise awareness among clinicians.
