Alexander Ivanov - Academia.edu (original) (raw)

Papers by Alexander Ivanov

Research paper thumbnail of Screening of Potential HIV-1 Inhibitors/ Replication Blockers Using Secure Lentiviral in Vitro System

Acta Naturae, 2011

The development and usage of safe cell systems for testing agents which possess anti-HIV activity... more The development and usage of safe cell systems for testing agents which possess anti-HIV activity is a very important factor in the design of new drugs. We have described in detail a system we designed that is based on lentiviral vectors (Prokofjeva et. al., Antiviral Therapy, in print) for swift and completely safe screening of potential HIV-1 replication inhibitors. The system enables one to test the efficiency of the inhibitory activity of compounds whose action is directed towards either wild-type HIV-1 reverse transcriptase or integrase, or mutant enzymes corresponding to the drug-resistant virus form. Testing results of a number of already known drugs, which correlate well with published data as well as data on newly synthesized compounds, were obtained. Application of this system substantially broadens the possibilities of preclinical anti-HIV drugs testing. KEYWORDS HIV; lentiviral vectors; pseudo-HIV-1 particles; nucleoside reverse transcriptase inhibitors; nonnucleoside reverse transcriptase inhibitors; integrase inhibitors. ABBREVIATIONS HIV-human immunodeficiency virus; RT-reverse transcriptase; VSV-vesicular stomatitis virus; eGFP-enhanced green fluorescent protein; AZT-3-azido-3-deoxythymidine; IC 50-half maximal (50%) inhibitory concentration (IC) of a substance.

Research paper thumbnail of Purification of phospholipase-C from Bacillus cereus by affinity chromatography on 2-(4-aminophenylsulphonyl)ethyl-cellulose

Journal of Chromatography B: Biomedical Sciences and Applications, 1990

A new method for the purification of phospholipase-C (phosphatidylcholine chohnephosphohydrolase,... more A new method for the purification of phospholipase-C (phosphatidylcholine chohnephosphohydrolase, EC 3.1.4.3) from Bacillus cereus has been developed, based on its affinity to 2-(4ammophenylsulphonyl)ethyl derivative of beaded cellulose. The enzyme was adsorbed on the affinity sorbent through a site(s) that was clearly distinct from its catalytically active site, because it was still active in the immobilized state. A possible role of enzyme-inhibitor interaction in enzyme binding to the ligand used is discussed.

Research paper thumbnail of Late Devonian - Early Permian chondrichthyans of the Russian Arctic

Acta geologica Polonica

New chondrichthyan material is reported from the Upper Devonian - Lower Permian of the various re... more New chondrichthyan material is reported from the Upper Devonian - Lower Permian of the various regions of the Russian Arctic. Shark remains are recorded from the Novaya Zemlya Archipelago for the first time. Ten species are described, two of which are new, Denaea? decora sp.n. and Adamantina foliacea sp.n. Upper Devonian - Lower Permian shark assemblages are discussed.

Research paper thumbnail of Structure-functional analysis of interactions of terminal deoxynucleotidyl transferase with new non-nucleoside substrates

Russian Journal of Bioorganic Chemistry, 2009

New non-nucleoside esters of phosphoric acid containing various hydrophobic groups, namely (1) N-... more New non-nucleoside esters of phosphoric acid containing various hydrophobic groups, namely (1) N-(2-tripticencarbonyl)-4-aminobutyl; (2) 5-phenylsubstituted N-(2,4-dinitrophenyl)-4-aminobutyl; (3) N-(4-phenylbenzoyl)- and N-(4-(N-benzylamino)benzoyl)-2-aminoethyl groups, as well as (4) diphenylmethyl and fluorenyl groups were synthesized and studied as substrates of terminal deoxynucleotidyl transferase. With the exception of the two latter derivatives, all the analogues displayed substrate properties and could incorporate into the deoxyoligonucleotide 3'-end. As it was shown in biochemical experiments and by computer modeling, a linker joining the triphosphate and hydrophobic fragments of the molecule was necessary for these compounds to display substrate properties.

Research paper thumbnail of What residency applicant IMGs need to know when applying to US Family Medicine Residency Programs

Research paper thumbnail of Sensing and control of the advanced LIGO optical configuration

Research paper thumbnail of Novel herpes simplex virus and human immunodeficiency virus inhibitors based on phosphonate nucleoside analogs

Moscow University Chemistry Bulletin, 2008

Two types of novel nucleoside analogs have been synthesized: acyclic (Z)-and (E)-isomers of 9-[3-... more Two types of novel nucleoside analogs have been synthesized: acyclic (Z)-and (E)-isomers of 9-[3-(phosphonometoxy)prop-1-en-1-yl]adenine and a carbocyclic isosteric analog of guanosine monophosphate. The (Z)-and (E)-isomers inhibit the replication of herpes simplex virus (HSV) and human immunodeficiency virus (HIV) and are nontoxic for cells. The (Z)-isomer activities against both viruses are higher than the (E)-isomer activities. Diphosphates of these compounds display substrate activities towards recombinant HSV DNA polymerase and HIV reverse transcriptase (RT). Diphosphate of the carbocyclic guanosine analog has no substrate activity towards HSV DNA polymerase but is active as a RT substrate.

Research paper thumbnail of The Effect of Removing the Lateral Part of the Pars Interarticularis on Stress Distribution at the Neural Arch in Lumbar Foraminal Microdecompression at L3–L4 and L4–L5

Spine, 2007

Study Design. The assessment of L3 and L4 pars interarticularis thickness and finite element anal... more Study Design. The assessment of L3 and L4 pars interarticularis thickness and finite element analysis of stress distribution across L3 and L4 pars interarticularis. Objective. To quantify the morphology of the region of the L3 and L4 pars interarticularis and to assess the stress increase as a function of access size using the finite element lumbar spine model. Summary of Background Data. Inadequate decompression and traction of the nerve structures are several causes of the unsatisfactory outcomes in patients after foraminal stenosis decompression and far lateral disc herniation removal by extraforaminal exposure. Enlarging the access of the foraminal exposure by the removal of the lateral aspect of the pars interarticularis may be able to diminish the inadequate decompression and traction of the nerve structures; however, it may lead to increase stress and fracture of the neural arch. Methods. We used 15 human cadaver L3 and L4 lumbar vertebrae for measuring the thickness of the pars interarticularis. The ventral and dorsal surfaces were subdivided into 4 equal parts, and the thickness of each part was measured using a digital caliper. An experimentally validated 3-dimensional nonlinear finite element model of the intact L3-S1 segment was used to simulate the lateral removal of one fourth and one half of the L3 and L4 pars interarticularis. Results. The mean thicknesses of the pars interarticularis showed a gradual increase toward the lateral edge. Finite element model analyses predicted stresses increased to 35% and 40% after removal of one half of the lateral part of the L3 and L4 pars interarticularis, respectively, and were much closer to the intact spine after removal of one fourth of the lateral part of the pars interarticularis. Conclusion. The removal of one fourth of the lateral aspect of the pars interarticularis has minimal influence on the stresses in the remaining L3 and L4 neural arches. The lateral half of the pars has the largest thickness, and its removal leads to considerable stress increases.

Research paper thumbnail of Allosteric Modulation of PS1/γ-Secretase Conformation Correlates with Amyloid β42/40 Ratio

PLoS ONE, 2009

Background: Presenilin 1(PS1) is the catalytic subunit of c-secretase, the enzyme responsible for... more Background: Presenilin 1(PS1) is the catalytic subunit of c-secretase, the enzyme responsible for the Ab C-terminal cleavage site, which results in the production of Ab peptides of various lengths. Production of longer forms of the Ab peptide occur in patients with autosomal dominant Alzheimer disease (AD) due to mutations in presenilin. Many modulators of csecretase function have been described. We hypothesize that these modulators act by a common mechanism by allosterically modifying the structure of presenilin. Methodology/Principal Findings: To test this hypothesis we generated a genetically encoded GFP-PS1-RFP (G-PS1-R) FRET probe that allows monitoring of the conformation of the PS1 molecule in its native environment in live cells. We show that G-PS1-R can be incorporated into the c-secretase complex, reconstituting its activity in PS1/2 deficient cells. Using Fö rster resonance energy transfer (FRET)-based approaches we show that various pharmacological and genetic manipulations that target either c-secretase components (PS1, Pen2, Aph1) or c-secretase substrate (amyloid precursor protein, APP) and are known to change Ab 42 production are associated with a consistent conformational change in PS1. Conclusions/Significance: These results strongly support the hypothesis that allosteric changes in PS1 conformation underlie changes in the Ab 42/40 ratio. Direct measurement of physiological and pathological changes in the conformation of PS1/c-secretase may provide insight into molecular mechanism of Ab 42 generation, which could be exploited therapeutically.

Research paper thumbnail of Measurement of optical response of a detuned resonant sideband extraction gravitational wave detector

Physical Review D, 2006

We report on the optical response of a suspended-mass detuned resonant sideband extraction (RSE) ... more We report on the optical response of a suspended-mass detuned resonant sideband extraction (RSE) interferometer with power recycling. The purpose of the detuned RSE configuration is to manipulate and optimize the optical response of the interferometer to differential displacements (induced by gravitational waves) as a function of frequency, independently of other parameters of the interferometer. The design of our interferometer results in an optical gain with two peaks: an RSE optical resonance at around 4 kHz and a radiation pressure induced optical spring at around 41 Hz. We have developed a reliable procedure for acquiring lock and establishing the desired optical configuration. In this configuration, we have measured the optical response to differential displacement and found good agreement with predictions at both resonances and all other relevant frequencies. These results build confidence in both the theory and practical implementation of the more complex optical configuration being planned for Advanced LIGO.

Research paper thumbnail of Emsian vertebrate microremains from the Zinzilban section, Uzbekistan

Palaeoworld, 2010

Fossil vertebrate microremains were collected from 22 sampling levels between the Pragian/Emsian ... more Fossil vertebrate microremains were collected from 22 sampling levels between the Pragian/Emsian boundary stratotype point (base of the kitabicus Conodont Zone) and the mid-Emsian (excavatus Conodont Zone) in the Zinzilban section, Kitab State Geological Reserve, Uzbekistan. The material includes scales of acanthodians Radioporacanthodes liujingensis (Wang) and Canadalepis basdenae Burrow, as well as chondrichthyan scales, and scales and dermal bone fragments of acanthothoracid placoderm Xiejiawanaspis pinus Burrow et al., other indeterminate acanthothoracids, and probably a buchanosteid. This restricted fauna shows the closest resemblance with contemporaneous vertebrate assemblages from Sichuan Province in China, Salair in Siberia, Russia, and southeastern Australia.

Research paper thumbnail of Synthesis of Novel Alkyl Triphosphates and Their Substrate Properties Toward Terminal Deoxynucleotidyltransferase

Nucleosides, Nucleotides and Nucleic Acids, 2007

Novel triphosphate derivatives bearing bulky or small groups at alpha-position attached to the tr... more Novel triphosphate derivatives bearing bulky or small groups at alpha-position attached to the triphosphate residue through linkers of different structures and lengths were synthesized and studied as substrates toward terminal deoxynucleotidyltransferase. The substrate efficacy depends on the structure of substituents, linker length, and nature of metal activator. The replacement of hydrophobic groups by small substituents decreased the substrate efficacy by about 20 times in respect to hydrophobic residues. The dependence on metal activator is the following: Co(2+) > Mn(2+) > Mg(2+). The model of interaction of alkyl triphosphates with linkers of different lengths bearing TdT active site is presented.

Research paper thumbnail of Hypocretin/orexin depolarizes and decreases potassium conductance in locus coeruleus neurons

NeuroReport, 2000

Recent studies demonstrated that noradrenergic locus coeruleus (LC) neurons are a particularly st... more Recent studies demonstrated that noradrenergic locus coeruleus (LC) neurons are a particularly strong target of the novel neuropeptide, hypocretin (orexin). The present study sought to elucidate the action of hypocretin-B (HCRT) on LC neurons recorded intracellularly in rat brain slices. Bath (1.0 ìM) or local puff application (50±100 ìM in pipette) of HCRT depolarized LC neurons in rat brain slices and increased their spontaneous discharge rate. Depolarization evoked by HCRT was persistent in the presence of tetrodotoxin (TTX, 1 ìM) and Co 2 (1 mM), indicating that HCRT directly activated LC neurons, and that its effect on the postsynaptic cell was not due to activation of TTX-sensitive sodium channels or Co 2sensitive calcium channels. The apparent input resistance was signi®cantly increased in the majority of LC neurons during the HCRT-evoked depolarization. Moreover, the HCRT-evoked depolarization was decreased in amplitude with hyperpolarization of membrane. The present results indicate that decreased potassium conductance is involved in the effect of HCRT on

Research paper thumbnail of Are bacterial proteins part of the matrix of kidney stones?

Microbial Pathogenesis, 1998

An extracellular protein, produced from Pseudomonas fluorescens strain D with molecular mass of 4... more An extracellular protein, produced from Pseudomonas fluorescens strain D with molecular mass of 41.5 kDa was partially purified. Its first 12 amino acid sequence shows strong similarity to a sequence reported to belong to a protein isolated from a urate-calcium oxalate stone (Binnette & Binnette, Scan Microsc1994; 2: 233-239). A possible involvement of bacterial proteins in stone matrix is discussed.

Research paper thumbnail of Determination of poliovirus-specific IgA in saliva by ELISA tests

Journal of Virological Methods, 2005

This study describes three ELISA methods for detection of immunoglobulin A (IgA) specific to thre... more This study describes three ELISA methods for detection of immunoglobulin A (IgA) specific to three types of Sabin strains of poliovirus in saliva taken from 70 children aged 6-7 years vaccinated with a full course of oral poliovirus vaccine (OPV). Of the three ELISA methods (conventional IgA ELISA and two new methods described in this communication, the alpha-capture ELISA and Inhibition ELISA), alpha-capture ELISA demonstrated the highest sensitivity, with all saliva samples testing positive for Sabin poliovirus strains specific IgA antibodies of 1-3 types. Of 62 available alpha-capture ELISA positive saliva samples, all were also positive by the inhibition ELISA, and a significant correlation was found between the results. Fifty-two available saliva samples were screened by the three ELISA tests with positive results, and a significant correlation was found between the alpha-capture ELISA and the IgA ELISA; the correlation between the IgA ELISA and inhibition ELISA was not significant. The results of this study suggest that determination of Sabin poliovirus-specific IgA in human saliva by the ELISA techniques (especially by the novel alpha-capture ELISA) can be used reliably for evaluation of mucosal immunity in large groups of people immunized with poliovirus vaccines and for epidemiological studies.

Research paper thumbnail of Ongoing electrical activity of superior cervical ganglion cells in mammals of different size

The Journal of Comparative Neurology, 1989

The ongoing synaptic activity of superior cervical ganglion cells in adult mammals was examined i... more The ongoing synaptic activity of superior cervical ganglion cells in adult mammals was examined in situ by intracellular recording in anesthetized mice, hamsters, rats, guinea pigs, and rabbits. The proportion of neurons exhibiting subthreshold and suprathreshold synaptic activity during a standard period of observation was least in a small mammal like the mouse (30%), intermediate among neurons of mammals of intermediate size such as the hamster and rat (48% and 45%, respectively), and greatest in the largest animals in the series, the guinea pig (89%) and rabbit (91%). Ganglion cells in all species fell silent after transection of the cervical trunk. The average frequency of synaptic activity among tonically active cells also increased with animal size, being least in the mouse (1.0/second) and greatest in the rabbit (6.4/second). This variation of ongoing synaptic activity in sympathetic ganglion cells may reflect the demands of progressively larger peripheral targets on relatively fixed populations of autonomic neurons.

Research paper thumbnail of The Early Carboniferous chondrichthyans of the South Urals, Russia

Geological Society, London, Special Publications, 1996

Abstract Vertebrate remains including chondrichthyans were found in the Devonian/Early Carbonifer... more Abstract Vertebrate remains including chondrichthyans were found in the Devonian/Early Carboniferous carbonate beds on the western and eastern slopes of the South Urals. Some of the Late Devonian forms (species of Phoebodus, acanthodians (Devononchus), ...

Research paper thumbnail of Middle/Late Devonian Phoebodontbased ichthyolith zonation

Geobios, 1995

... BIOZONATION, CORR]~LATION STRATIGRAPHIQUE,CRISE BIOLOGIQUE.The provisional ichthyolith zonati... more ... BIOZONATION, CORR]~LATION STRATIGRAPHIQUE,CRISE BIOLOGIQUE.The provisional ichthyolith zonation for the Cen-tral and Eastern Europe presented below is main-ly based on the stratigraphic ranges of the selec-ted species of the Devonian shark genus Phoebo-dus ...

Research paper thumbnail of Discriminative EPR detection of NO and HNO by encapsulated nitronyl nitroxides

Free Radical Research, 2012

Nitric oxide, • NO, is one of the most important molecules in the biochemistry of living organism... more Nitric oxide, • NO, is one of the most important molecules in the biochemistry of living organisms. By contrast, nitroxyl, NO − , one-electron reduced analog of • NO which exists at physiological conditions in its protonated form, HNO, has been relatively overlooked. Recent data shows that HNO might be produced endogenously and display unique biological effects. However, there is a lack of specific and quantitative methods of detection of endogenous HNO production. Here we present a new method for discriminative • NO and HNO detection by nitronyl nitroxides (NNs) using electron paramagnetic resonance (EPR). It was found that NNs react with • NO and HNO with similar rate constants of about 10 4 M −1 s −1 but yield different products: imino nitroxides and the hydroxylamine of imino nitroxides, correspondingly. An EPR approach for discriminative • NO and HNO detection using liposome-encapsulated NNs was developed. The membrane barrier of liposomes protects NNs against reduction in biological systems while is permeable to both analytes, • NO and HNO. The sensitivity of this approach for the detection of the rates of • NO/ HNO generation is about 1 nM/s. The application of encapsulated NNs for real-time discriminative • NO/HNO detection might become a valuable tool in nitric oxide related studies.

Research paper thumbnail of Structural analysis of the products of chymotryptic cleavage of the E1 form of Na,K-ATPase α-subunit: identification of the N-terminal fragments containing the transmembrane H1-H2 domain

FEBS Letters, 1997

Chymotryptic cleavage of the Na,K-ATPase in NaCl medium abolishes ATPase activity and alters othe... more Chymotryptic cleavage of the Na,K-ATPase in NaCl medium abolishes ATPase activity and alters other functional parameters. The structure of this modified enzyme is uncertain since only one product of selective proteolysis, the 83-kDa fragment of the K K-subunit (Ala PTU^C-terminus) has been identified previously. Here, we applied additional tryptic digestion followed by oxidative cross-linking to identify the products originating from the N-terminal part of the K K-subunit. These fragments start at Ala UP or Thr UR and contain the transmembrane H 1-H 2 domain. Formation of cross-linked product between K K-fragments containing H I-H P and H U-H IH demonstrate that the structural integrity of the membrane moiety is preserved. We also determined that secondary cleavage of the 83-kDa fragment leads to the formation of C-terminal 48-kDa K K-fragments with multiple N-termini at Ile SVP , Ser SVQ , Met SVR and Ile SVS .

Research paper thumbnail of Screening of Potential HIV-1 Inhibitors/ Replication Blockers Using Secure Lentiviral in Vitro System

Acta Naturae, 2011

The development and usage of safe cell systems for testing agents which possess anti-HIV activity... more The development and usage of safe cell systems for testing agents which possess anti-HIV activity is a very important factor in the design of new drugs. We have described in detail a system we designed that is based on lentiviral vectors (Prokofjeva et. al., Antiviral Therapy, in print) for swift and completely safe screening of potential HIV-1 replication inhibitors. The system enables one to test the efficiency of the inhibitory activity of compounds whose action is directed towards either wild-type HIV-1 reverse transcriptase or integrase, or mutant enzymes corresponding to the drug-resistant virus form. Testing results of a number of already known drugs, which correlate well with published data as well as data on newly synthesized compounds, were obtained. Application of this system substantially broadens the possibilities of preclinical anti-HIV drugs testing. KEYWORDS HIV; lentiviral vectors; pseudo-HIV-1 particles; nucleoside reverse transcriptase inhibitors; nonnucleoside reverse transcriptase inhibitors; integrase inhibitors. ABBREVIATIONS HIV-human immunodeficiency virus; RT-reverse transcriptase; VSV-vesicular stomatitis virus; eGFP-enhanced green fluorescent protein; AZT-3-azido-3-deoxythymidine; IC 50-half maximal (50%) inhibitory concentration (IC) of a substance.

Research paper thumbnail of Purification of phospholipase-C from Bacillus cereus by affinity chromatography on 2-(4-aminophenylsulphonyl)ethyl-cellulose

Journal of Chromatography B: Biomedical Sciences and Applications, 1990

A new method for the purification of phospholipase-C (phosphatidylcholine chohnephosphohydrolase,... more A new method for the purification of phospholipase-C (phosphatidylcholine chohnephosphohydrolase, EC 3.1.4.3) from Bacillus cereus has been developed, based on its affinity to 2-(4ammophenylsulphonyl)ethyl derivative of beaded cellulose. The enzyme was adsorbed on the affinity sorbent through a site(s) that was clearly distinct from its catalytically active site, because it was still active in the immobilized state. A possible role of enzyme-inhibitor interaction in enzyme binding to the ligand used is discussed.

Research paper thumbnail of Late Devonian - Early Permian chondrichthyans of the Russian Arctic

Acta geologica Polonica

New chondrichthyan material is reported from the Upper Devonian - Lower Permian of the various re... more New chondrichthyan material is reported from the Upper Devonian - Lower Permian of the various regions of the Russian Arctic. Shark remains are recorded from the Novaya Zemlya Archipelago for the first time. Ten species are described, two of which are new, Denaea? decora sp.n. and Adamantina foliacea sp.n. Upper Devonian - Lower Permian shark assemblages are discussed.

Research paper thumbnail of Structure-functional analysis of interactions of terminal deoxynucleotidyl transferase with new non-nucleoside substrates

Russian Journal of Bioorganic Chemistry, 2009

New non-nucleoside esters of phosphoric acid containing various hydrophobic groups, namely (1) N-... more New non-nucleoside esters of phosphoric acid containing various hydrophobic groups, namely (1) N-(2-tripticencarbonyl)-4-aminobutyl; (2) 5-phenylsubstituted N-(2,4-dinitrophenyl)-4-aminobutyl; (3) N-(4-phenylbenzoyl)- and N-(4-(N-benzylamino)benzoyl)-2-aminoethyl groups, as well as (4) diphenylmethyl and fluorenyl groups were synthesized and studied as substrates of terminal deoxynucleotidyl transferase. With the exception of the two latter derivatives, all the analogues displayed substrate properties and could incorporate into the deoxyoligonucleotide 3'-end. As it was shown in biochemical experiments and by computer modeling, a linker joining the triphosphate and hydrophobic fragments of the molecule was necessary for these compounds to display substrate properties.

Research paper thumbnail of What residency applicant IMGs need to know when applying to US Family Medicine Residency Programs

Research paper thumbnail of Sensing and control of the advanced LIGO optical configuration

Research paper thumbnail of Novel herpes simplex virus and human immunodeficiency virus inhibitors based on phosphonate nucleoside analogs

Moscow University Chemistry Bulletin, 2008

Two types of novel nucleoside analogs have been synthesized: acyclic (Z)-and (E)-isomers of 9-[3-... more Two types of novel nucleoside analogs have been synthesized: acyclic (Z)-and (E)-isomers of 9-[3-(phosphonometoxy)prop-1-en-1-yl]adenine and a carbocyclic isosteric analog of guanosine monophosphate. The (Z)-and (E)-isomers inhibit the replication of herpes simplex virus (HSV) and human immunodeficiency virus (HIV) and are nontoxic for cells. The (Z)-isomer activities against both viruses are higher than the (E)-isomer activities. Diphosphates of these compounds display substrate activities towards recombinant HSV DNA polymerase and HIV reverse transcriptase (RT). Diphosphate of the carbocyclic guanosine analog has no substrate activity towards HSV DNA polymerase but is active as a RT substrate.

Research paper thumbnail of The Effect of Removing the Lateral Part of the Pars Interarticularis on Stress Distribution at the Neural Arch in Lumbar Foraminal Microdecompression at L3–L4 and L4–L5

Spine, 2007

Study Design. The assessment of L3 and L4 pars interarticularis thickness and finite element anal... more Study Design. The assessment of L3 and L4 pars interarticularis thickness and finite element analysis of stress distribution across L3 and L4 pars interarticularis. Objective. To quantify the morphology of the region of the L3 and L4 pars interarticularis and to assess the stress increase as a function of access size using the finite element lumbar spine model. Summary of Background Data. Inadequate decompression and traction of the nerve structures are several causes of the unsatisfactory outcomes in patients after foraminal stenosis decompression and far lateral disc herniation removal by extraforaminal exposure. Enlarging the access of the foraminal exposure by the removal of the lateral aspect of the pars interarticularis may be able to diminish the inadequate decompression and traction of the nerve structures; however, it may lead to increase stress and fracture of the neural arch. Methods. We used 15 human cadaver L3 and L4 lumbar vertebrae for measuring the thickness of the pars interarticularis. The ventral and dorsal surfaces were subdivided into 4 equal parts, and the thickness of each part was measured using a digital caliper. An experimentally validated 3-dimensional nonlinear finite element model of the intact L3-S1 segment was used to simulate the lateral removal of one fourth and one half of the L3 and L4 pars interarticularis. Results. The mean thicknesses of the pars interarticularis showed a gradual increase toward the lateral edge. Finite element model analyses predicted stresses increased to 35% and 40% after removal of one half of the lateral part of the L3 and L4 pars interarticularis, respectively, and were much closer to the intact spine after removal of one fourth of the lateral part of the pars interarticularis. Conclusion. The removal of one fourth of the lateral aspect of the pars interarticularis has minimal influence on the stresses in the remaining L3 and L4 neural arches. The lateral half of the pars has the largest thickness, and its removal leads to considerable stress increases.

Research paper thumbnail of Allosteric Modulation of PS1/γ-Secretase Conformation Correlates with Amyloid β42/40 Ratio

PLoS ONE, 2009

Background: Presenilin 1(PS1) is the catalytic subunit of c-secretase, the enzyme responsible for... more Background: Presenilin 1(PS1) is the catalytic subunit of c-secretase, the enzyme responsible for the Ab C-terminal cleavage site, which results in the production of Ab peptides of various lengths. Production of longer forms of the Ab peptide occur in patients with autosomal dominant Alzheimer disease (AD) due to mutations in presenilin. Many modulators of csecretase function have been described. We hypothesize that these modulators act by a common mechanism by allosterically modifying the structure of presenilin. Methodology/Principal Findings: To test this hypothesis we generated a genetically encoded GFP-PS1-RFP (G-PS1-R) FRET probe that allows monitoring of the conformation of the PS1 molecule in its native environment in live cells. We show that G-PS1-R can be incorporated into the c-secretase complex, reconstituting its activity in PS1/2 deficient cells. Using Fö rster resonance energy transfer (FRET)-based approaches we show that various pharmacological and genetic manipulations that target either c-secretase components (PS1, Pen2, Aph1) or c-secretase substrate (amyloid precursor protein, APP) and are known to change Ab 42 production are associated with a consistent conformational change in PS1. Conclusions/Significance: These results strongly support the hypothesis that allosteric changes in PS1 conformation underlie changes in the Ab 42/40 ratio. Direct measurement of physiological and pathological changes in the conformation of PS1/c-secretase may provide insight into molecular mechanism of Ab 42 generation, which could be exploited therapeutically.

Research paper thumbnail of Measurement of optical response of a detuned resonant sideband extraction gravitational wave detector

Physical Review D, 2006

We report on the optical response of a suspended-mass detuned resonant sideband extraction (RSE) ... more We report on the optical response of a suspended-mass detuned resonant sideband extraction (RSE) interferometer with power recycling. The purpose of the detuned RSE configuration is to manipulate and optimize the optical response of the interferometer to differential displacements (induced by gravitational waves) as a function of frequency, independently of other parameters of the interferometer. The design of our interferometer results in an optical gain with two peaks: an RSE optical resonance at around 4 kHz and a radiation pressure induced optical spring at around 41 Hz. We have developed a reliable procedure for acquiring lock and establishing the desired optical configuration. In this configuration, we have measured the optical response to differential displacement and found good agreement with predictions at both resonances and all other relevant frequencies. These results build confidence in both the theory and practical implementation of the more complex optical configuration being planned for Advanced LIGO.

Research paper thumbnail of Emsian vertebrate microremains from the Zinzilban section, Uzbekistan

Palaeoworld, 2010

Fossil vertebrate microremains were collected from 22 sampling levels between the Pragian/Emsian ... more Fossil vertebrate microremains were collected from 22 sampling levels between the Pragian/Emsian boundary stratotype point (base of the kitabicus Conodont Zone) and the mid-Emsian (excavatus Conodont Zone) in the Zinzilban section, Kitab State Geological Reserve, Uzbekistan. The material includes scales of acanthodians Radioporacanthodes liujingensis (Wang) and Canadalepis basdenae Burrow, as well as chondrichthyan scales, and scales and dermal bone fragments of acanthothoracid placoderm Xiejiawanaspis pinus Burrow et al., other indeterminate acanthothoracids, and probably a buchanosteid. This restricted fauna shows the closest resemblance with contemporaneous vertebrate assemblages from Sichuan Province in China, Salair in Siberia, Russia, and southeastern Australia.

Research paper thumbnail of Synthesis of Novel Alkyl Triphosphates and Their Substrate Properties Toward Terminal Deoxynucleotidyltransferase

Nucleosides, Nucleotides and Nucleic Acids, 2007

Novel triphosphate derivatives bearing bulky or small groups at alpha-position attached to the tr... more Novel triphosphate derivatives bearing bulky or small groups at alpha-position attached to the triphosphate residue through linkers of different structures and lengths were synthesized and studied as substrates toward terminal deoxynucleotidyltransferase. The substrate efficacy depends on the structure of substituents, linker length, and nature of metal activator. The replacement of hydrophobic groups by small substituents decreased the substrate efficacy by about 20 times in respect to hydrophobic residues. The dependence on metal activator is the following: Co(2+) > Mn(2+) > Mg(2+). The model of interaction of alkyl triphosphates with linkers of different lengths bearing TdT active site is presented.

Research paper thumbnail of Hypocretin/orexin depolarizes and decreases potassium conductance in locus coeruleus neurons

NeuroReport, 2000

Recent studies demonstrated that noradrenergic locus coeruleus (LC) neurons are a particularly st... more Recent studies demonstrated that noradrenergic locus coeruleus (LC) neurons are a particularly strong target of the novel neuropeptide, hypocretin (orexin). The present study sought to elucidate the action of hypocretin-B (HCRT) on LC neurons recorded intracellularly in rat brain slices. Bath (1.0 ìM) or local puff application (50±100 ìM in pipette) of HCRT depolarized LC neurons in rat brain slices and increased their spontaneous discharge rate. Depolarization evoked by HCRT was persistent in the presence of tetrodotoxin (TTX, 1 ìM) and Co 2 (1 mM), indicating that HCRT directly activated LC neurons, and that its effect on the postsynaptic cell was not due to activation of TTX-sensitive sodium channels or Co 2sensitive calcium channels. The apparent input resistance was signi®cantly increased in the majority of LC neurons during the HCRT-evoked depolarization. Moreover, the HCRT-evoked depolarization was decreased in amplitude with hyperpolarization of membrane. The present results indicate that decreased potassium conductance is involved in the effect of HCRT on

Research paper thumbnail of Are bacterial proteins part of the matrix of kidney stones?

Microbial Pathogenesis, 1998

An extracellular protein, produced from Pseudomonas fluorescens strain D with molecular mass of 4... more An extracellular protein, produced from Pseudomonas fluorescens strain D with molecular mass of 41.5 kDa was partially purified. Its first 12 amino acid sequence shows strong similarity to a sequence reported to belong to a protein isolated from a urate-calcium oxalate stone (Binnette & Binnette, Scan Microsc1994; 2: 233-239). A possible involvement of bacterial proteins in stone matrix is discussed.

Research paper thumbnail of Determination of poliovirus-specific IgA in saliva by ELISA tests

Journal of Virological Methods, 2005

This study describes three ELISA methods for detection of immunoglobulin A (IgA) specific to thre... more This study describes three ELISA methods for detection of immunoglobulin A (IgA) specific to three types of Sabin strains of poliovirus in saliva taken from 70 children aged 6-7 years vaccinated with a full course of oral poliovirus vaccine (OPV). Of the three ELISA methods (conventional IgA ELISA and two new methods described in this communication, the alpha-capture ELISA and Inhibition ELISA), alpha-capture ELISA demonstrated the highest sensitivity, with all saliva samples testing positive for Sabin poliovirus strains specific IgA antibodies of 1-3 types. Of 62 available alpha-capture ELISA positive saliva samples, all were also positive by the inhibition ELISA, and a significant correlation was found between the results. Fifty-two available saliva samples were screened by the three ELISA tests with positive results, and a significant correlation was found between the alpha-capture ELISA and the IgA ELISA; the correlation between the IgA ELISA and inhibition ELISA was not significant. The results of this study suggest that determination of Sabin poliovirus-specific IgA in human saliva by the ELISA techniques (especially by the novel alpha-capture ELISA) can be used reliably for evaluation of mucosal immunity in large groups of people immunized with poliovirus vaccines and for epidemiological studies.

Research paper thumbnail of Ongoing electrical activity of superior cervical ganglion cells in mammals of different size

The Journal of Comparative Neurology, 1989

The ongoing synaptic activity of superior cervical ganglion cells in adult mammals was examined i... more The ongoing synaptic activity of superior cervical ganglion cells in adult mammals was examined in situ by intracellular recording in anesthetized mice, hamsters, rats, guinea pigs, and rabbits. The proportion of neurons exhibiting subthreshold and suprathreshold synaptic activity during a standard period of observation was least in a small mammal like the mouse (30%), intermediate among neurons of mammals of intermediate size such as the hamster and rat (48% and 45%, respectively), and greatest in the largest animals in the series, the guinea pig (89%) and rabbit (91%). Ganglion cells in all species fell silent after transection of the cervical trunk. The average frequency of synaptic activity among tonically active cells also increased with animal size, being least in the mouse (1.0/second) and greatest in the rabbit (6.4/second). This variation of ongoing synaptic activity in sympathetic ganglion cells may reflect the demands of progressively larger peripheral targets on relatively fixed populations of autonomic neurons.

Research paper thumbnail of The Early Carboniferous chondrichthyans of the South Urals, Russia

Geological Society, London, Special Publications, 1996

Abstract Vertebrate remains including chondrichthyans were found in the Devonian/Early Carbonifer... more Abstract Vertebrate remains including chondrichthyans were found in the Devonian/Early Carboniferous carbonate beds on the western and eastern slopes of the South Urals. Some of the Late Devonian forms (species of Phoebodus, acanthodians (Devononchus), ...

Research paper thumbnail of Middle/Late Devonian Phoebodontbased ichthyolith zonation

Geobios, 1995

... BIOZONATION, CORR]~LATION STRATIGRAPHIQUE,CRISE BIOLOGIQUE.The provisional ichthyolith zonati... more ... BIOZONATION, CORR]~LATION STRATIGRAPHIQUE,CRISE BIOLOGIQUE.The provisional ichthyolith zonation for the Cen-tral and Eastern Europe presented below is main-ly based on the stratigraphic ranges of the selec-ted species of the Devonian shark genus Phoebo-dus ...

Research paper thumbnail of Discriminative EPR detection of NO and HNO by encapsulated nitronyl nitroxides

Free Radical Research, 2012

Nitric oxide, • NO, is one of the most important molecules in the biochemistry of living organism... more Nitric oxide, • NO, is one of the most important molecules in the biochemistry of living organisms. By contrast, nitroxyl, NO − , one-electron reduced analog of • NO which exists at physiological conditions in its protonated form, HNO, has been relatively overlooked. Recent data shows that HNO might be produced endogenously and display unique biological effects. However, there is a lack of specific and quantitative methods of detection of endogenous HNO production. Here we present a new method for discriminative • NO and HNO detection by nitronyl nitroxides (NNs) using electron paramagnetic resonance (EPR). It was found that NNs react with • NO and HNO with similar rate constants of about 10 4 M −1 s −1 but yield different products: imino nitroxides and the hydroxylamine of imino nitroxides, correspondingly. An EPR approach for discriminative • NO and HNO detection using liposome-encapsulated NNs was developed. The membrane barrier of liposomes protects NNs against reduction in biological systems while is permeable to both analytes, • NO and HNO. The sensitivity of this approach for the detection of the rates of • NO/ HNO generation is about 1 nM/s. The application of encapsulated NNs for real-time discriminative • NO/HNO detection might become a valuable tool in nitric oxide related studies.

Research paper thumbnail of Structural analysis of the products of chymotryptic cleavage of the E1 form of Na,K-ATPase α-subunit: identification of the N-terminal fragments containing the transmembrane H1-H2 domain

FEBS Letters, 1997

Chymotryptic cleavage of the Na,K-ATPase in NaCl medium abolishes ATPase activity and alters othe... more Chymotryptic cleavage of the Na,K-ATPase in NaCl medium abolishes ATPase activity and alters other functional parameters. The structure of this modified enzyme is uncertain since only one product of selective proteolysis, the 83-kDa fragment of the K K-subunit (Ala PTU^C-terminus) has been identified previously. Here, we applied additional tryptic digestion followed by oxidative cross-linking to identify the products originating from the N-terminal part of the K K-subunit. These fragments start at Ala UP or Thr UR and contain the transmembrane H 1-H 2 domain. Formation of cross-linked product between K K-fragments containing H I-H P and H U-H IH demonstrate that the structural integrity of the membrane moiety is preserved. We also determined that secondary cleavage of the 83-kDa fragment leads to the formation of C-terminal 48-kDa K K-fragments with multiple N-termini at Ile SVP , Ser SVQ , Met SVR and Ile SVS .