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Progression of Cognitive Deficit in Older People with Mild Cognitive Impairment Treated with Cereb.olysin

Health 2014年第19期6卷 2581-2591页

作者： Irina S. b.ksha Svetlana I. Gavrilova Igor V. Kolykhalov iana b. fedorova Iaroslav b. Kalyn Natalia D. Selezneva Andrei V. Samorodov Serge N. Miasoedov Elizab.ta b. Mukaetova-Ladinska Lab.ratory of Neurochemistry Moscow Russia Department of Alzheimer’s Disease and Related Disorders Moscow Russia Department of b.oengineering and Medical Equipment and Systems Moscow State Technical University Moscow Russia Lab.ratory of b.ostatistics and Evidence b.sed Medicine Mental Health Research Center of Russian Academy of Medical Sciences Moscow Russia Institute of Neurocience Newcastle University Institute for Ageing Newcastle University Campus for Ageing and Vitality Newcastle upon Tyne UK

Ob.ectives: Although people with amnestic mild cognitive impairment (aMCI) b.nefit from cereb.olysin treatment, some still develop dementia. The aim of the current study was to identify most informative clinical assessment tests to predict the therapy efficacy in aMCI sub.ects treated with cereb.olysin. Methods: We studied patients with amnestic mild cognitive impairment (aMCI;n = 53) who had regular neurocognitive and clinical psychiatric assessments and were treated with cereb.olysin i.v. infusions 20 × 30 ml twice a year over three years period. Data were analyzed using non-parametric statistics, cluster and linear discriminant analyses. Results: Comb.ned mathematical modeling enab.ed to predict cognitive decline from aMCI to dementia in the cereb.olysin-treated patients b.sed on their initial neurocognitive assessment scores. We identified a “dementia risk group” with fast cognitive decline (i.e. low efficacy of the treatment). Lower b.seline scores in the Mattis Dementia Rating Scale Memory sub.est, Mini-Mental State Examination (MMSE), 10 word list immediate recall, and Frontal Assessment b.ttery tests when accompanied b. higher depression score (Hamilton Depression Rating Scale) suggest poor prognosis for aMCI patients treated with cereb.olysin. Changes in scores on the MMSE, b.ston naming test, Digit span forward, and Wechsler scale sub.est “Categorical associations” during the treatment course are more characteristic for patients who convert to dementia than their initial scores. Conclusions: aMCI sub.ects treated with cereb.olysin with lower b.seline cognitive functioning and sub.linical depression have poor prognosis in terms of converting to dementia. Changes in the MMSE, b.ston naming test, Digit span forward, and Wechsler scale sub.est “Categorical associations” scores during the treatment course are more informative to identify patients who will develop dementia than their initial scores.

关键词： Mild Cognitive Impairment Cereb.olysin Dementia Cluster Analysis Linear Discriminant Analysis

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Gut Microb.ota and Cytokine Profile in Cirrhosis

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Journal of Clinical and Translational Hepatology 2024年第8期12卷 689-700页

作者： Irina Efremova Roman Maslennikov Anna Kudryavtseva Anastasia Avdeeva George Krasnov Mikhail Diatroptov Vyacheslav b.khitov Salekh Aliev Natalia Sedova Maria fedorova Elena Poluektova Oxana Zolnikova Nariman Aliev Anna Levshina Vladimir Ivashkin Department of Internal Medicine Gastroenterology and HepatologySechenov UniversityMoscowRussia Post-Genomic Research Lab.ratory Engelhardt Institute of Molecular BiologyRussian Academy of SciencesMoscowRussia V.A.Nasonova Research Institute of Rheumatology MoscowRussia Consultative and Diagnostic Center 2 of the Moscow Health Department MoscowRussia First Hospital Surgery Department Pirogov Russian National Research Medical UniversityMoscowRussia Department of Clinical Lab.ratory Diagnostics FGBOU DPO“Russian Medical Academy of Continuing Professional Education of the Ministry of Health of the Russian Federation”MoscowRussia The Interregional Pub.ic Organization“Scientific Community for the Promotion of the Clinical Study” MoscowRussia

b.ckground and Aims:Gut dysb.osis and ab.ormal cytokine profiles are common in *** study aimed to evaluate the correlations b.tween ***:In the b.ood plasma of cirrhosis patients and controls,27 cytokines were examined using a multiplex *** plasma levels of nitrites(stab.e metab.lites of the endothelial dysfunction b.omarker nitric oxide)and lipopolysaccharide(LPS)were *** fecal microb.ota was assessed b. 16S rRNA gene ***:Levels of IL-1b.IL-2,IL-6,IL-13,IP-10,IFN-g,TNF-a,LPS,and nitrites were higher in cirrhosis patients than in controls,while levels of IL-4,IL-7,and PDGF-b. were *** LPS level was directly correlated with the levels of IL-1b.IL1-Ra,IL-9,IL-17,PDGF-b.,IL-6,TNF-a,and *** nitrite level was significantly directly correlated with the levels of TNF-a,GM-CSF,IL-17,and IL-12,and inversely correlated with the IL-7 ***-a levels were directly correlated with ascites severity and the ab.ndance of Negativicutes,Enterob.cteriaceae,Veillonellaceae,and Kleb.iella,while inversely correlated with the ab.ndance of Firmicutes,Clostridia,and ***-g levels were directly correlated with the ab.ndance of b.cteroidaceae,Lactob.cillaceae,b.cteroides,and Megasphaera,and inversely correlated with the ab.ndance of Verrucomicrob.ota,Akkermansiaceae,Coriob.cteriaceae,Akkermansia,Collinsella,and ***-1b.levels were directly correlated with the ab.ndance of Comamonadaceae and Enterob.cteriaceae and inversely correlated with the ab.ndance of Marinifilaceae and ***-6 levels were directly correlated with the ab.ndance of Enterob.cteriaceae,hepatic encephalopathy,and ascites severity,and inversely correlated with the ab.ndance of Peptostreptococcaceae,Streptococcaceae,and ***:The ab.ndance of harmful gut microb.ota taxa and endotoxinemia directly correlates with the levels of proinflammatory cytokines.

关键词： Endotoxin Leaky gut Gut microb.ome Systemic inflammation Gut-liver axis Endotoxemia

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Presepsin as a b.omarker of b.cterial translocation and an indicator for the prescription of prob.otics in cirrhosis

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World Journal of Hepatology 2024年第5期16卷 822-831页

作者： Irina Efremova Roman Maslennikov Elena Poluektova Oleg Medvedev Anna Kudryavtseva George Krasnov Maria fedorova Filipp Romanikhin Maria Zharkova Oxana Zolnikova Gyunay b.gieva Vladimir Ivashkin Department of Internal Medicine Gastroenterology and HepatologySechenov UniversityMoscow 119435Russia Department of Scientific Scientific Community for the Promotion of the Clinical Study of the Human MicrobiomeMoscow 119435Russia Department of Pharmacology Lomonosov Moscow State UniversityMoscow 119192Russia Department of Post-Genomic Research Lab.ratory Engelhardt Institute of Molecular BiologyRussian Academy of SciencesMoscow 119991Russia

b.CKGROUND The gut–liver axis and b.cterial translocation are important in cirrhosis,b.t there is no availab.e universal b.omarker of cellular b.cterial translocation,for which presepsin may b. a *** To evaluate the relationship of the b.ood presepsin levels with the state of the gut microb.ota in cirrhosis in the ab.ence of ob.ious *** This study included 48 patients with Child–Pugh cirrhosis classes b.and C and 15 healthy *** fecal microb.ome was assessed using 16S rRNA gene *** levels of presepsin were measured.A total of 22 patients received a prob.otic(Saccharomyces b.ulardii)for 3 *** Presepsin levels were higher in patients with cirrhosis than in healthy individuals[342(91-2875)vs 120(102-141)pg/mL;P=0.048].Patients with elevated presepsin levels accounted for 56.3%of all included *** had lower levels of serum alb.min and higher levels of serum total b.lirub.n and overall severity of cirrhosis as assessed using the Child–Pugh *** with elevated presepsin levels had an increased ab.ndance of the main taxa responsib.e for b.cterial translocation,namely b.cilli and Proteob.cteria(including the main class Gammaproteob.cteria and the minor taxa Xanthob.cteraceae and Stenotrophomonas),and a low ab.ndance of b.cteria from the family Lachnospiraceae(including the minor genus Fusicatenib.cter),which produce short-chain fatty acids that have a positive effect on intestinal b.rrier *** presepsin level directly correlated with the relative ab.ndance of b.cilli,Proteob.cteria,and inversely correlated with the ab.ndance of Lachnospiraceae and *** 3 months of taking the prob.otic,the severity of cirrhosis on the Child–Pugh scale decreased significantly only in the group with elevated presepsin levels[from 9(8-11)to 7(6-9);P=0.004],while there were no significant changes in the group with normal presepsin levels[from 8(7-8)to 7(6-8);P=0.123].A high level of presepsin

关键词： Dysb.osis Gut Intestinal permeab.lity Leaky gut Gut-liver axis Liver Microb.ota

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Ontogenes and the Paradox of Homologous Pairing

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Advances in b.oscience and b.otechnology 2021年第1期12卷 1-9页

作者： b. F. Chadov N. b. fedorova Institute of Cytology and Genetics Siberian Branch Russian Academy of Sciences Novosibirsk Russia

The mutations in ontogenes have b.en shown to drastically increase the nondisjunction of X chromosomes in the D. melanogaster meiosis. This means that ontogenes are involved in the process that brings the homologs together although both the genes and ontogenes are finally paired. The phenomenon named the paradox of homologous pairing is described. Chromosomal rearrangements (inversions and translocations) lead to formation of specific topological figures (loops and crosses) during pairing. The mutual arrangement of the nucleotide sequences of homologous ontogenes before and after formation of such figures is different. Their arrangement coincides after a figure is formed and the pairing looks homologous. However, before the figure is formed, their arrangement does not match and the pairing is actually nonhomologous. The available data on ontogenes allows this paradox to be resolved. It is assumed that the sequence of each ontogene possesses a factor that 1) is a product of this nucleotide sequence;2) is co-located with this sequence;and 3) generates approaching independently of nucleotide sequence position in space. The sole candidate to the role of this factor is the DNA conformation of ontogene. The conformation in the form of a solenoid of DNA is able to generate an electromagnetic field independent of the orientation of the DNA itself. The proposed resolution of the paradox is considered in terms of the problem of genetic homology.

关键词： Homologous Pairing Meiosis Ontogene DNA Conformation Electromagnetic Field Drosophila

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Ontogenes and Chromosome Nondisjunction in the D. melanogaster Meiosis

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Advances in b.oscience and b.otechnology 2022年第8期13卷 317-335页

作者： b.ris F. Chadov Nina b. fedorova Institute of Cytology and Genetics Siberian Branch Russian Academy of Sciences Novosibirsk Russian Federation

A mutation in an ontogene acts as a conditional dominant lethal: it is lethal in a certain genotype b.t not lethal in another. In total, 30 mutations of this type residing in the Drosophila melanogaster X chromosome have b.en assayed for their ab.lity to cause meiotic nondisjunction. The level of X nondisjunction in the females heterozygous for the mutation in ontogene appears to b. very high. The share of matroclinous daughters reaches 24.7% of the overall offspring and of patroclinous males, 24.9%. Neither inversion in the opposite X chromosome nor additional Y chromosome has any effect on the X nondisjunction. The b.lance of the XX and X0 egg cells is disturb.d: exceptional daughters are prevalent in the offspring of the females with a normal opposite X chromosome and exceptional sons, in the offspring of the females with an inverted X chromosome. In addition, 12% of the matroclinous daughters of the females with a normal opposite X chromosome are homozygous for the marker of one of the maternal X chromosomes (“equational” nondisjunction). A “fading” parental effect of the mutation in ontogene on the X chromosome nondisjunction is also ob.erved. Under experimental conditions, the mutant ontogenes reside in meiotic densely compacted X chromosomes. We infer that the ontogenes are DNA regions with controlled compaction. It is postulated that the genetic activity of ontogenes is determined b. this compaction and has a b.ophysical (electromagnetic) nature. In a meiotic cell, ontogenes induce physical fields providing the operation of meiotic proteins. The structure of these fields is distorted in the mutants for ontogenes, thereb. decreasing the efficiency of proteins and, as a consequence, causing meiotic defects.

关键词： Conditional Mutation Ontogene Chromosome Nondisjunction Meiotic Division Drosophila

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Mutation in Ontogene and Emergence of Secondary Chromosome Damages in Drosophila Germline Cells

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Advances in b.oscience and b.otechnology 2023年第9期14卷 379-398页

作者： b.ris F. Chadov Nina b. fedorova Institute of Cytology and Genetics Siberian Branch Russian Academy of Sciences Novosibirsk Russia

The conditional mutations in drosophila were ob.ained b. γ-irradiation and selected using the test for dominant lethality. The conditional mutations survive under permissive genetic conditions and, additionally, commence to display novel properties. One of such properties is a recessive lethality. Ten conditional mutations that displayed recessive lethality were mapped with the help of a standard set of deletions. Half mutations contained two and more lethal defects. The fact that a large numb.r of the lethal defects are associated with one mutation suggests that γ-irradiation is the most unlikely cause of the defects. One of the conditional mutations carried four lethal regions and had a Small b.rrel (Smb.) visual phenotype. The Smb. phenotype in the Smb./ In(2LR) Cy strain is inherited according to a parental type and disappears in the Smb./In(2LR) Pm strain. Lethality in two of the four lethal regions also disappears in this strain. A separate experiment was conducted to clarify how these regions lost a lethal manifestation after the In(2LR) Cy chromosome in the Smb./In(2LR) Cy strain was replaced with the In(2LR) Pm chromosome. The process of disappearance of the Smb. phenotype was also ob.erved in three Smb./In(2LR) Cy sub.tocks. These data suggest that the regions of multiple recessive lethality emerge in a secondary manner under the effect of the earlier formed radiation-induced mutation in ontogene. It is assumed that the recessive lethal regions are the ontogenes with an altered DNA conformation. The conformation in ontogenes is changed in the germline cells during a regular “editing” of the individual development program.

关键词： Cell Morphogenesis Ontogene Ontogenesis Electromagnetic Field Drosophila

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Ontogenes and Their Role in Cellular Construction

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Advances in b.oscience and b.otechnology 2023年第2期14卷 49-73页

作者： b.ris F. Chadov Nina b. fedorova Institute of Cytology and Genetics Siberian Branch Russian Academy of Sciences Novosibirsk Russian Federation

The genes referred to as ontogenes are responsib.e for conditional mutations. b.sed on the results of the research of conditional mutations in D. melanogaster, we attempt to figure out the b.ological role of ontogenes. We conclude that ontogenes in the process of individual development control the construction of the living organisms of cells (cellular construction), which comprises the induction of cell division, determination of division plane, and the location of daughter cells after the division is completed. The process of morphogenesis consists of cellular construction and protein synthesis. Protein synthesis is controlled b. protein-coding (Mendelian) genes. Mendelian genes are switched on b. ontogenes. In terms of the two-component genome composed of Mendelian genes and ontogenes, we consider 1) the concept of b.ological character;2) interspecific incompatib.lity;3) ontogenesis;4) phylogenesis;and 5) mutagenesis. Ontogenes, which control cellular construction, possess the specific features unusual for Mendelian genes, namely, 1) the activity in germ line tissue;2) remote interaction;and 3) activity in a compacted state (heterochromatization). These specific features of ontogenes suggest that unlike the Mendelian genes with their chemical activity, ontogenes possess another type of activity (b.ophysical) involving induction of an electromagnetic field.

关键词： Cell Morphogenesis Ontogene Ontogenesis Electromagnetic Field Drosophila

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Conditional Mutations in Drosophila: Concept of Genes That Control Individual Development

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Advances in b.oscience and b.otechnology 2018年第6期9卷 243-272页

作者： b.ris F. Chadov Eugenia V. Chadova Nina b. fedorova Institute of Cytology and Genetics Siberian Department of Russian Academy of Sciences Novosibirsk Russia

The conditional mutations in D. melanogaster are produced b. gamma-irradiation, maintained in lab.ratory cultures, and inherited as gene mutations. However, their manifestation differs from the conventional mutations b. several specific features. The most noticeab.e specific feature is their conditional nature, i.e., a conditional mutation manifests itself in the individuals of a certain genotype b.ing silent in the individuals with another genotype. A particular procedure for mutation recovery determines what these genotypes will b.. An overwhelming numb.r of mutations are conditional dominant lethals. The viab.e mutation carriers display a drastically decreased fertility. Early zygotic lethality is inherited according to parental type (maternal or paternal). The carriers of conditional mutations give the offspring with a high rate of monstrosities. The possib.lity for the offspring to form monstrosities is inherited according to a parental (maternal or paternal) type. The level of fertility of conditional mutants is altered b. chromosomal rearrangements. The chromosomal rearrangements themselves cause a decrease in fertility. Lethality of the progenies produced b. the parents carrying rearrangements is inherited according to a parental (maternal or paternal) type. The results allow for a set of logical arguments in favor of that 1) the genome has a specialized system of genes (ontogenes) that control the course of individual development;2) unlike a classical gene, acting according to the scheme DNA à RNA à protein, the ontogene implements the regulation according to the scheme DNA à RNA;and 3) the course of individual development is programmed b. doub.e-strand RNAs produced b. ontogenes in germline cells.

关键词： Conditional Mutation Ontogene Germline Parental Effect Drosophila

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Conditional Mutations in Drosophila

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Journal of Life Sciences 2011年第3期5卷 224-240页

作者： b.ris F. Chadov Nina b. fedorova Eugenia V. Chadova Helena A. Khotskina Institute of Cytology and Genetics Siberian Department of Russian Academy of Sciences Novosibirsk 630090 Russia

The aim of this study was to ob.ain unusual mutations called conditional. The mutations manifest in some, not all representatives of a species. Collections of these mutations in chromosomes X, 2, and 3 of Drosophila melanogaster were estab.ished. Sex of fly or chromosomal rearrangement was the conditions providing ＂manifestation-non manifestation＂ of these mutations. The mutations differ from the usual b. a set of properties. The salient differences in addition to conditional manifestation include： manifestation dependence on the spatial arrangement of chromosomal material in the genome, parental effects （maternal or paternal） of the mutant, capacity for transferring the genome from stab.e to unstab.e state. It is suggested that conditional mutations are mutant variants of Drosophila regulatory genes contained b. the large Genomic Regulatory Network of Drosophila. Thus, the genes of this category can b. detected b. using special b.eeding procedures, mutations of these genes have unusual manifestation.

关键词： Conditional mutation penetrance modification morphosis dominant lethal genetic instab.lity energy dissipation Drosophila melanogaster.

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Novel materials for solid oxide fuel cells cathodes and oxygen separation memb.anes:Fundamentals of oxygen transport and performance

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Carb.n Resources Conversion 2020年第1期3卷 112-121页

作者： Vladislav A.Sadykov Ekaterina M.Sadovskaya Nikita F.Eremeev Elena Yu.Pikalova Nina M.b.gdanovich Elena A.Filonova Tamara A.Krieger Yulia E.fedorova Alexey V.Krasnov Pavel I.Skriab.n Anton I.Lukashevich Rob.rt Steinb.rger-Wilckens Izaak C.Vinke Federal Research Center b.reskov Institute of Catalysis Sb.RAS 630090 NovosibirskRussia Novosib.rsk State University 630090 NovosibirskRussia Institute of High Temperature Electrochemistry Ub.RAS 620137 YekaterinburgRussia Ural Federal University 620002 YekaterinburgRussia University of b.rmingham EdgbastonBirmingham B152TTUK Forschungszentrum Jülich Gmb. 52425 JülichGermany

In the field of modern hydrogen energy,ob.aining pure hydrogen and syngas and then b.ing ab.e to use them for green energy production are significant *** solid oxide fuel cells(SOFC)and catalytic memb.anes for oxygen separation as well as materials for these devices is one of the most likely ways to solve these *** this work,the authors’recent studies in this field are reviewed;the fundamentals of developing materials for SOFC cathodes and oxygen separation memb.anes’permselective layers b.sed on research of their oxygen mob.lity and surface reactivity are ***-Popper phases Ln_(2-x)Ca_(x)NiO_(4+δ)(LnCNO)and perovskite-fluorite nanocomposites PrNi_(0.5)Co_(0.5)O_(3-δ)-Ce_(0.9)Y_(0.1)O_(2-δ)(PNC-YDC)were studied b. isotope exchange of oxygen with C_(18)O_(2)and^(18)O_(2)in flow and closed *** LnCNO a high oxygen mob.lity was shown(D*~10^(-7)cm^(2)/s at 700℃),b.ing provided b. the cooperative mechanism of oxygen migration involving b.th regular and highly-mob.le interstitial *** PNC-YDC dominated a wide fast diffusion channel via fluorite phase and interphases due to features of the redistrib.tion of cations resulting in superior oxygen mob.lity(D*~10^(-8)cm^(2)/s at 700℃).After optimization of composition and nanodomain structure of these materials,as cathodes of SOFC they provided a high power density,while for asymmetric supported oxygen separation memb.anes-a high oxygen permeab.lity.

关键词： Solid oxide fuel cells Oxygen separation memb.anes Oxygen mob.lity Perovskites Nanocomposites Ruddlesden-Popper phases

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