Manisha Sharma - Academia.edu (original) (raw)
Papers by Manisha Sharma
Case Reports in Medicine, 2015
Because of increasing antimicrobial resistance, the treatment of the asymptomatic bacteriuria is ... more Because of increasing antimicrobial resistance, the treatment of the asymptomatic bacteriuria is not considered except in specific circumstances like during pregnancy or before invasive urologic procedures. We are reporting a first case of asymptomatic bacteriuria caused byChromobacterium violaceumin a 16-year-old male. With the reporting of theC. violaceumwhich is notorious for its high propensity for hematogenous dissemination causing fatal sepsis (with reported mortality rate up to 65–80%) if prompt proper treatment is not given, as causative agent of asymptomatic bacteriuria, it is recommended to treat the asymptomatic bacteriuria caused by this organism.
2015 International Conference on Electrical, Electronics, Signals, Communication and Optimization (EESCO), 2015
Journal of Biological Chemistry, 2015
Authors are urged to introduce these corrections into any reprints they distribute. Secondary (ab... more Authors are urged to introduce these corrections into any reprints they distribute. Secondary (abstract) services are urged to carry notice of these corrections as prominently as they carried the original abstracts.
During the past few years, the significance of regulated protein degradation has become increasin... more During the past few years, the significance of regulated protein degradation has become increasingly apparent in plants. There has been a remarkable exploration of information on the proteins of the ubiquitin/proteasome system and their role in protein degradation throughout the eukaryotes. The proteasome ubiquitination system selects a number of proteins for post-translational modification and subsequently, subjects them to degradation. E3 ubiquitin ligases play a central role in determining the target specificity in this system. Interestingly, most recently discovered, RING/U-box represents a type of E3 ligases and shows greater prevalence in plants (PUBs, Plant U-box E3 ubiquitin ligases) in comparison to animals. Hence, suggesting their involvement in a range of indispensable processes in plant system. U-box is a highly conserved domain whose physiological function remains unclear, but it has been implicated as a regulator of fundamental cellular processes ranging from cellular ...
The small GTPase superfamily is comprised of four families (ROP, ARF, RAB and RAN) in the plant k... more The small GTPase superfamily is comprised of four families (ROP, ARF, RAB and RAN) in the plant kingdom. The members of this superfamily show diversity in structure and function, despite possessing a conserved G-domain for GTP-binding and hydrolysis. ROP (Rho of Plants) has emerged as plant-specific GTPases to orchestrate unique cellular function such as polarity establishment, stress and plant hormonal signaling. The prominent role in their functional capability is evident from their varied expressional regulation in different developmental and stress conditions. The functional activity of small GTPases is tuned by both positive (guanine exchange factor, GEF) and negative regulators (Guanine Dissociation Inhibitor, GDI and GTPase activating protein, GAP), which favors the ON and OFF state of small GTPases, respectively. The expressional variation of regulators as well as their spatial and temporal expression pattern determine the activity and hence turn-on the switch of small GTPases. In this report, we are exploring the expressional and functional analysis of ROP class of small GTPases in plants under stress and developmental signaling pathways.
International Journal of Reproduction, Contraception, Obstetrics and Gynecology, 2015
Endometriosis is presence of functioning endometrial tissue (glands and stroma) outside the uteri... more Endometriosis is presence of functioning endometrial tissue (glands and stroma) outside the uterine cavity. Endometriosis can sometimes occur in previous surgical scar. Scar endometriosis is rare and difficult to diagnose. It mostly follows obstetrical and gynaecological surgeries. We present here a case report of a patient who developed scar endometriosis following a caesarean section which was dealt adequately in the subsequent caesarean section.
World Journal of Gastroenterology, 2007
AIM: To study the effect of combined omeprazole(Ome) and domperidone(Dom) therapy on asthma sympt... more AIM: To study the effect of combined omeprazole(Ome) and domperidone(Dom) therapy on asthma symptoms and pulmonary function in asthmatics with gastroesophageal refl ux. METHODS: We selected 198 asthmatics with gastroesophageal refl ux diagnosed by 24-h esophageal pH monitoring to receive Ome 20 mg twice daily and Dom 10 mg three times daily or placebo for 16 wk (1:1 double-blind randomization). Spirometry was done at baseline and after 16 wk of treatment. The primary outcome measures were: mean daily daytime and nighttime asthma symptom scores. Mean daily refl ux symptom scores, albuterol use as rescue medication (number of puffs), daytime and nighttime peak expiratory fl ow rate (PEFR), postbronchodilator forced expiratory volume in 1 second (FEV1) and postbronchodilator forced vital capacity (FVC) were secondary outcome measures. RESULTS: Comparison of mean change from baseline between antirefl ux therapy and placebo groups revealed signifi cant reduction in daytime asthma symptom score (17.4% vs 8.9 %), nighttime asthma symptom score (19.6% vs 5.4%), refl ux symptom score (8.7% vs 1.6%) and rescue medication use (23.2% vs 3.1%) after antirefl ux therapy compared to mean change in placebo group (P < 0.001). There was signifi cant improvement in morning PEFR (7.9% vs 0.2%), evening PEFR (9.8% vs 0.5%), FEV1 (11.1% vs 3.78%) and FVC (9.3% vs 1.52%) in the antirefl ux therapy group compared to placebo on comparing the mean change from baseline after 16 wk (P < 0.01). CONCLUSION: Combined therapy with Ome and Dom in adult asthmatics with gastroesophageal refl ux may be benefi cial by reducing asthma symptoms, rescuing medication use, and improving pulmonary function.
TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik, Jan 28, 2015
QTL mapping by two DH mapping populations deciphered allelic variations for five different seed g... more QTL mapping by two DH mapping populations deciphered allelic variations for five different seed glucosinolate traits in B. juncea. Allelic variations for five different seed glucosinolate (GS) traits, namely % propyl, % butyl, % pentyl, aliphatics and total GS content were studied through QTL analysis using two doubled haploid (DH) mapping populations. While the high GS parents in two populations differed in their profiles of seed aliphatic GS, the low GS parents were similar. Phenotypic data of seed GS traits from three environments of the two populations were subjected to QTL analysis. The first population (referred to as DE population) detected a total of 60 QTL from three environments which upon intra-population meta-QTL analysis were merged to 17 S-QTL (Stable QTL) and 15 E-QTL (Environment QTL). The second population (referred to as VH population) detected 58 QTL from the three environments that were merged to 15S-QTL and 16E-QTL. In both the populations, majority of S-QTL wer...
The Journal of Obstetrics and Gynecology of India, 2013
Aim To determine the current prevalence of thyroid dysfunction in normal pregnant women and to st... more Aim To determine the current prevalence of thyroid dysfunction in normal pregnant women and to study the impact of thyroid dysfunction on maternal and fetal outcome. Methods 400 pregnant women between 13 and 26 weeks of gestation were registered for the study. Apart from routine obstetrical investigations, TSH tests were done. Free T4 and anti-TPO antibody tests were done in patients with deranged TSH. Patients were followed up till delivery. Their obstetrical and perinatal outcomes were noted. Results The prevalence of hypothyroidism and hyperthyroidism was 12 and 1.25 %, respectively. Adverse maternal effects in overt hypothyroidism included preeclampsia (16.6 vs. 7.8 %) and placental abruption (16.6 vs. 0.8 %). Subclinical hypothyroidism was associated with preeclampsia (22.3 vs. 7.8 %) as compared to the euthyroid patients. Adverse fetal outcomes in overt hypothyroidism included spontaneous abortion (16.6 vs. 2.39 %), preterm birth (33.3 vs. 5.8 %), low birth weight (50 vs. 12.11 %), intrauterine growth retardation (25 vs. 4.9 %), and fetal death (16.6 vs. 1.7 %) as compared to the euthyroid women. Adverse fetal outcomes in subclinical hypothyroidism included spontaneous abortion (5.5 vs. 2.39 %), preterm delivery (11.2 vs. 5.8 %), low birth weight (25 vs. 12.11 %), and intrauterine growth retardation (8.4 vs. 4.9 %) as compared to the euthyroid women. Conclusions The prevalence of thyroid disorders was high in our study with associated adverse maternal and fetal outcomes. Routine screening of thyroid dysfunction is recommended to prevent adverse fetal and maternal outcome.
Frontiers in Plant Science, 2014
Proceedings of the International Conference & Workshop on Emerging Trends in Technology - ICWET '11, 2011
Machine Translation (MT) refers to the use of a machine for performing translation task which con... more Machine Translation (MT) refers to the use of a machine for performing translation task which converts text or speech from one Natural Language (NL) into another Natural Language. Machine Translation is an important technology for localization, and is particularly relevant in a linguistically diverse country like India. The evaluation of the sentences or a corpus of sentences translated with the
International Journal of Computer Network and Information Security, 2012
Digital images are very easy to manipulate, store, publish and secondary creation this juggle wil... more Digital images are very easy to manipulate, store, publish and secondary creation this juggle will lead to serious consequence in some applications such as military image, medical image. So, integrity of digital image must be authenticated. Tools that help us establish the authenticity and integrity of digital media are thus essential and can prove vital whenever questions are raised about the origin of an image and its content. To project authenticity of images semi fragile watermarking is very concerned by researchers because of its important function in content authentication. Semifragile watermarking aim to monitor contents of images not its representations. In present paper various semi fragile water marking algorithm are studied using some image quality matrices, insertion methods used, verification method. Finally some observations are given based on literature survey of algorithms and techniques of semifragile watermarking techniques
India International Conference on Power Electronics 2010 (IICPE2010), 2011
Abstract Increasing demand of portable devices creating larger scope in the field of Low power de... more Abstract Increasing demand of portable devices creating larger scope in the field of Low power device design. VLSI designing of the efficient circuits is aiming towards the devices consuming less power and produces less delay with capability to operate in wider range ...
The International Journal of Biochemistry & Cell Biology, 2012
-catenin is the central nuclear effector of the Wnt signaling pathway, and regulates other cellu... more -catenin is the central nuclear effector of the Wnt signaling pathway, and regulates other cellular processes including cell adhesion. Wnt stimulation of cells culminates in the nuclear translocation of -catenin and transcriptional activation of target genes that function during both normal and malignant development. Constitutive activation of the Wnt pathway leads to inappropriate nuclear accumulation of -catenin and gene transactivation, an important step in cancer progression. This has generated interest in the mechanisms regulating -catenin nuclear accumulation and retention. Here we discuss recent advances in understanding feedback loops that trap -catenin in the nucleus and provide potential insights into Wnt signaling and the development of anti-cancer drugs.
Seminars in Cancer Biology, 2014
The nuclear localization of specific proteins is critical for cellular processes such as cell div... more The nuclear localization of specific proteins is critical for cellular processes such as cell division, and in recent years perturbation of the nuclear transport cycle of key proteins has been linked to cancer. In particular, specific gene mutations can alter nuclear transport of tumor suppressing and oncogenic proteins, leading to cell transformation or cancer progression. This review will focus on one such factor, -catenin, a key mediator of the canonical wnt signaling pathway. In response to a wnt stimulus or specific gene mutations, -catenin is stabilized and translocates to the nucleus where it binds TCF/LEF-1 transcription factors to transactivate genes that drive tumor formation. Moreover, the nuclear import and accumulation of -catenin correlates with clinical tumor grade. Recent evidence suggests that the primary nuclear transport route of -catenin is independent of the classical Ran/importin import machinery, and that catenin directly contacts the nuclear pore complex to self-regulate its own entry into the nucleus. Here we propose that the -catenin nuclear import pathway may provide an opportunity for identification of specific drug targets and inhibition of -catenin nuclear function, much like the current screening of drugs that block binding of -catenin to LEF-1/TCFs. Here we will discuss the diverse mechanisms regulating nuclear localization of -catenin and their potential as targets for anticancer agent development.
Proceedings of the National Academy of Sciences, 2002
Nitric oxide synthases (NOSs) are flavoheme enzymes that contain a ferredoxin:NADP + -reductase (... more Nitric oxide synthases (NOSs) are flavoheme enzymes that contain a ferredoxin:NADP + -reductase (FNR) module for binding NADPH and FAD and are unusual because their electron transfer reactions are controlled by the Ca 2+ -binding protein calmodulin. A conserved aromatic residue in the FNR module of NOS shields the isoalloxazine ring of FAD and is known to regulate NADPH binding affinity and specificity in related flavoproteins. We mutated Phe-1395 (F1395) in neuronal NOS to Tyr and Ser and tested their effects on nucleotide coenzyme specificity, catalytic activities, and electron transfer in the absence or presence of calmodulin. We found that the aromatic side chain of F1395 controls binding specificity with respect to NADH but does not greatly affect affinity for NADPH. Measures of flavin and heme reduction kinetics, ferricyanide and cytochrome c reduction, and NO synthesis established that the aromatic side chain of F1395 is required to repress electron transfer into and out of t...
Pramana, 2007
A beam of 1 GeV proton coming from Dubna Nuclotron colliding with a lead target surrounded by 6 c... more A beam of 1 GeV proton coming from Dubna Nuclotron colliding with a lead target surrounded by 6 cm paraffin produces spallation neutrons. A Th-foil was kept on lead target (neutron spallation source) in a direct stream of neutrons for activation and other samples of 197 Au, 209 Bi, 59 Co, 115 In and 181 Ta were irradiated by moderated beam of neutrons passing through 6 cm paraffin moderator. The gamma spectra of irradiated samples were analyzed using gamma spectrometry and DEIMOS software to measure the neutron cross-section. For this purpose neutron fluence at the positions of samples is also estimated using PREPRO software. The results of cross-sections for reactions 232 Th(n, γ), 232 Th(n, 2n), 197 Au(n, γ), 197 Au(n, α), 197 Au(n, xn), 59 Co(n, α), 59 Co(n, xn), 181 Ta(n, γ) and 181 Ta(n, xn) are given in this paper. Neutronics validation of the Dubna Cascade Code is also done using cross-section data by other experiments.
Journal of Molecular Catalysis A: Chemical, 2005
The insertion of dimethylvinylidene carbene into azo moiety was investigated in order to synthesi... more The insertion of dimethylvinylidene carbene into azo moiety was investigated in order to synthesize 4,6-dimethyl-5-[2-(2-methylprop-1-enyl)-1H-benzimidazol-1-yl] pyrimidine-2(5H)-thiones [7a-j] under kinetically controlled phase transfer catalysis conditions. In situ generation of dimethylvinylidene carbene was facilitated by the interaction between 3-chloro-3-methyl-1-butyne and alkali at the interface. Interestingly, insertion of this carbene into the N N linkage of 2,4-dimethyl-3-arylazo-6-thiopyrimidine afforded newly synthesized desired benzimidazolo pyrimidines. The reaction follows the pseudo-first order rate law. Rational mechanism of the reaction is proposed according to the experimental evidence. The compounds were synthesized in excellent yields (70-80%) and their structures were established on the basis of their IR and 1 H NMR spectral data.
Case Reports in Medicine, 2015
Because of increasing antimicrobial resistance, the treatment of the asymptomatic bacteriuria is ... more Because of increasing antimicrobial resistance, the treatment of the asymptomatic bacteriuria is not considered except in specific circumstances like during pregnancy or before invasive urologic procedures. We are reporting a first case of asymptomatic bacteriuria caused byChromobacterium violaceumin a 16-year-old male. With the reporting of theC. violaceumwhich is notorious for its high propensity for hematogenous dissemination causing fatal sepsis (with reported mortality rate up to 65–80%) if prompt proper treatment is not given, as causative agent of asymptomatic bacteriuria, it is recommended to treat the asymptomatic bacteriuria caused by this organism.
2015 International Conference on Electrical, Electronics, Signals, Communication and Optimization (EESCO), 2015
Journal of Biological Chemistry, 2015
Authors are urged to introduce these corrections into any reprints they distribute. Secondary (ab... more Authors are urged to introduce these corrections into any reprints they distribute. Secondary (abstract) services are urged to carry notice of these corrections as prominently as they carried the original abstracts.
During the past few years, the significance of regulated protein degradation has become increasin... more During the past few years, the significance of regulated protein degradation has become increasingly apparent in plants. There has been a remarkable exploration of information on the proteins of the ubiquitin/proteasome system and their role in protein degradation throughout the eukaryotes. The proteasome ubiquitination system selects a number of proteins for post-translational modification and subsequently, subjects them to degradation. E3 ubiquitin ligases play a central role in determining the target specificity in this system. Interestingly, most recently discovered, RING/U-box represents a type of E3 ligases and shows greater prevalence in plants (PUBs, Plant U-box E3 ubiquitin ligases) in comparison to animals. Hence, suggesting their involvement in a range of indispensable processes in plant system. U-box is a highly conserved domain whose physiological function remains unclear, but it has been implicated as a regulator of fundamental cellular processes ranging from cellular ...
The small GTPase superfamily is comprised of four families (ROP, ARF, RAB and RAN) in the plant k... more The small GTPase superfamily is comprised of four families (ROP, ARF, RAB and RAN) in the plant kingdom. The members of this superfamily show diversity in structure and function, despite possessing a conserved G-domain for GTP-binding and hydrolysis. ROP (Rho of Plants) has emerged as plant-specific GTPases to orchestrate unique cellular function such as polarity establishment, stress and plant hormonal signaling. The prominent role in their functional capability is evident from their varied expressional regulation in different developmental and stress conditions. The functional activity of small GTPases is tuned by both positive (guanine exchange factor, GEF) and negative regulators (Guanine Dissociation Inhibitor, GDI and GTPase activating protein, GAP), which favors the ON and OFF state of small GTPases, respectively. The expressional variation of regulators as well as their spatial and temporal expression pattern determine the activity and hence turn-on the switch of small GTPases. In this report, we are exploring the expressional and functional analysis of ROP class of small GTPases in plants under stress and developmental signaling pathways.
International Journal of Reproduction, Contraception, Obstetrics and Gynecology, 2015
Endometriosis is presence of functioning endometrial tissue (glands and stroma) outside the uteri... more Endometriosis is presence of functioning endometrial tissue (glands and stroma) outside the uterine cavity. Endometriosis can sometimes occur in previous surgical scar. Scar endometriosis is rare and difficult to diagnose. It mostly follows obstetrical and gynaecological surgeries. We present here a case report of a patient who developed scar endometriosis following a caesarean section which was dealt adequately in the subsequent caesarean section.
World Journal of Gastroenterology, 2007
AIM: To study the effect of combined omeprazole(Ome) and domperidone(Dom) therapy on asthma sympt... more AIM: To study the effect of combined omeprazole(Ome) and domperidone(Dom) therapy on asthma symptoms and pulmonary function in asthmatics with gastroesophageal refl ux. METHODS: We selected 198 asthmatics with gastroesophageal refl ux diagnosed by 24-h esophageal pH monitoring to receive Ome 20 mg twice daily and Dom 10 mg three times daily or placebo for 16 wk (1:1 double-blind randomization). Spirometry was done at baseline and after 16 wk of treatment. The primary outcome measures were: mean daily daytime and nighttime asthma symptom scores. Mean daily refl ux symptom scores, albuterol use as rescue medication (number of puffs), daytime and nighttime peak expiratory fl ow rate (PEFR), postbronchodilator forced expiratory volume in 1 second (FEV1) and postbronchodilator forced vital capacity (FVC) were secondary outcome measures. RESULTS: Comparison of mean change from baseline between antirefl ux therapy and placebo groups revealed signifi cant reduction in daytime asthma symptom score (17.4% vs 8.9 %), nighttime asthma symptom score (19.6% vs 5.4%), refl ux symptom score (8.7% vs 1.6%) and rescue medication use (23.2% vs 3.1%) after antirefl ux therapy compared to mean change in placebo group (P < 0.001). There was signifi cant improvement in morning PEFR (7.9% vs 0.2%), evening PEFR (9.8% vs 0.5%), FEV1 (11.1% vs 3.78%) and FVC (9.3% vs 1.52%) in the antirefl ux therapy group compared to placebo on comparing the mean change from baseline after 16 wk (P < 0.01). CONCLUSION: Combined therapy with Ome and Dom in adult asthmatics with gastroesophageal refl ux may be benefi cial by reducing asthma symptoms, rescuing medication use, and improving pulmonary function.
TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik, Jan 28, 2015
QTL mapping by two DH mapping populations deciphered allelic variations for five different seed g... more QTL mapping by two DH mapping populations deciphered allelic variations for five different seed glucosinolate traits in B. juncea. Allelic variations for five different seed glucosinolate (GS) traits, namely % propyl, % butyl, % pentyl, aliphatics and total GS content were studied through QTL analysis using two doubled haploid (DH) mapping populations. While the high GS parents in two populations differed in their profiles of seed aliphatic GS, the low GS parents were similar. Phenotypic data of seed GS traits from three environments of the two populations were subjected to QTL analysis. The first population (referred to as DE population) detected a total of 60 QTL from three environments which upon intra-population meta-QTL analysis were merged to 17 S-QTL (Stable QTL) and 15 E-QTL (Environment QTL). The second population (referred to as VH population) detected 58 QTL from the three environments that were merged to 15S-QTL and 16E-QTL. In both the populations, majority of S-QTL wer...
The Journal of Obstetrics and Gynecology of India, 2013
Aim To determine the current prevalence of thyroid dysfunction in normal pregnant women and to st... more Aim To determine the current prevalence of thyroid dysfunction in normal pregnant women and to study the impact of thyroid dysfunction on maternal and fetal outcome. Methods 400 pregnant women between 13 and 26 weeks of gestation were registered for the study. Apart from routine obstetrical investigations, TSH tests were done. Free T4 and anti-TPO antibody tests were done in patients with deranged TSH. Patients were followed up till delivery. Their obstetrical and perinatal outcomes were noted. Results The prevalence of hypothyroidism and hyperthyroidism was 12 and 1.25 %, respectively. Adverse maternal effects in overt hypothyroidism included preeclampsia (16.6 vs. 7.8 %) and placental abruption (16.6 vs. 0.8 %). Subclinical hypothyroidism was associated with preeclampsia (22.3 vs. 7.8 %) as compared to the euthyroid patients. Adverse fetal outcomes in overt hypothyroidism included spontaneous abortion (16.6 vs. 2.39 %), preterm birth (33.3 vs. 5.8 %), low birth weight (50 vs. 12.11 %), intrauterine growth retardation (25 vs. 4.9 %), and fetal death (16.6 vs. 1.7 %) as compared to the euthyroid women. Adverse fetal outcomes in subclinical hypothyroidism included spontaneous abortion (5.5 vs. 2.39 %), preterm delivery (11.2 vs. 5.8 %), low birth weight (25 vs. 12.11 %), and intrauterine growth retardation (8.4 vs. 4.9 %) as compared to the euthyroid women. Conclusions The prevalence of thyroid disorders was high in our study with associated adverse maternal and fetal outcomes. Routine screening of thyroid dysfunction is recommended to prevent adverse fetal and maternal outcome.
Frontiers in Plant Science, 2014
Proceedings of the International Conference & Workshop on Emerging Trends in Technology - ICWET '11, 2011
Machine Translation (MT) refers to the use of a machine for performing translation task which con... more Machine Translation (MT) refers to the use of a machine for performing translation task which converts text or speech from one Natural Language (NL) into another Natural Language. Machine Translation is an important technology for localization, and is particularly relevant in a linguistically diverse country like India. The evaluation of the sentences or a corpus of sentences translated with the
International Journal of Computer Network and Information Security, 2012
Digital images are very easy to manipulate, store, publish and secondary creation this juggle wil... more Digital images are very easy to manipulate, store, publish and secondary creation this juggle will lead to serious consequence in some applications such as military image, medical image. So, integrity of digital image must be authenticated. Tools that help us establish the authenticity and integrity of digital media are thus essential and can prove vital whenever questions are raised about the origin of an image and its content. To project authenticity of images semi fragile watermarking is very concerned by researchers because of its important function in content authentication. Semifragile watermarking aim to monitor contents of images not its representations. In present paper various semi fragile water marking algorithm are studied using some image quality matrices, insertion methods used, verification method. Finally some observations are given based on literature survey of algorithms and techniques of semifragile watermarking techniques
India International Conference on Power Electronics 2010 (IICPE2010), 2011
Abstract Increasing demand of portable devices creating larger scope in the field of Low power de... more Abstract Increasing demand of portable devices creating larger scope in the field of Low power device design. VLSI designing of the efficient circuits is aiming towards the devices consuming less power and produces less delay with capability to operate in wider range ...
The International Journal of Biochemistry & Cell Biology, 2012
-catenin is the central nuclear effector of the Wnt signaling pathway, and regulates other cellu... more -catenin is the central nuclear effector of the Wnt signaling pathway, and regulates other cellular processes including cell adhesion. Wnt stimulation of cells culminates in the nuclear translocation of -catenin and transcriptional activation of target genes that function during both normal and malignant development. Constitutive activation of the Wnt pathway leads to inappropriate nuclear accumulation of -catenin and gene transactivation, an important step in cancer progression. This has generated interest in the mechanisms regulating -catenin nuclear accumulation and retention. Here we discuss recent advances in understanding feedback loops that trap -catenin in the nucleus and provide potential insights into Wnt signaling and the development of anti-cancer drugs.
Seminars in Cancer Biology, 2014
The nuclear localization of specific proteins is critical for cellular processes such as cell div... more The nuclear localization of specific proteins is critical for cellular processes such as cell division, and in recent years perturbation of the nuclear transport cycle of key proteins has been linked to cancer. In particular, specific gene mutations can alter nuclear transport of tumor suppressing and oncogenic proteins, leading to cell transformation or cancer progression. This review will focus on one such factor, -catenin, a key mediator of the canonical wnt signaling pathway. In response to a wnt stimulus or specific gene mutations, -catenin is stabilized and translocates to the nucleus where it binds TCF/LEF-1 transcription factors to transactivate genes that drive tumor formation. Moreover, the nuclear import and accumulation of -catenin correlates with clinical tumor grade. Recent evidence suggests that the primary nuclear transport route of -catenin is independent of the classical Ran/importin import machinery, and that catenin directly contacts the nuclear pore complex to self-regulate its own entry into the nucleus. Here we propose that the -catenin nuclear import pathway may provide an opportunity for identification of specific drug targets and inhibition of -catenin nuclear function, much like the current screening of drugs that block binding of -catenin to LEF-1/TCFs. Here we will discuss the diverse mechanisms regulating nuclear localization of -catenin and their potential as targets for anticancer agent development.
Proceedings of the National Academy of Sciences, 2002
Nitric oxide synthases (NOSs) are flavoheme enzymes that contain a ferredoxin:NADP + -reductase (... more Nitric oxide synthases (NOSs) are flavoheme enzymes that contain a ferredoxin:NADP + -reductase (FNR) module for binding NADPH and FAD and are unusual because their electron transfer reactions are controlled by the Ca 2+ -binding protein calmodulin. A conserved aromatic residue in the FNR module of NOS shields the isoalloxazine ring of FAD and is known to regulate NADPH binding affinity and specificity in related flavoproteins. We mutated Phe-1395 (F1395) in neuronal NOS to Tyr and Ser and tested their effects on nucleotide coenzyme specificity, catalytic activities, and electron transfer in the absence or presence of calmodulin. We found that the aromatic side chain of F1395 controls binding specificity with respect to NADH but does not greatly affect affinity for NADPH. Measures of flavin and heme reduction kinetics, ferricyanide and cytochrome c reduction, and NO synthesis established that the aromatic side chain of F1395 is required to repress electron transfer into and out of t...
Pramana, 2007
A beam of 1 GeV proton coming from Dubna Nuclotron colliding with a lead target surrounded by 6 c... more A beam of 1 GeV proton coming from Dubna Nuclotron colliding with a lead target surrounded by 6 cm paraffin produces spallation neutrons. A Th-foil was kept on lead target (neutron spallation source) in a direct stream of neutrons for activation and other samples of 197 Au, 209 Bi, 59 Co, 115 In and 181 Ta were irradiated by moderated beam of neutrons passing through 6 cm paraffin moderator. The gamma spectra of irradiated samples were analyzed using gamma spectrometry and DEIMOS software to measure the neutron cross-section. For this purpose neutron fluence at the positions of samples is also estimated using PREPRO software. The results of cross-sections for reactions 232 Th(n, γ), 232 Th(n, 2n), 197 Au(n, γ), 197 Au(n, α), 197 Au(n, xn), 59 Co(n, α), 59 Co(n, xn), 181 Ta(n, γ) and 181 Ta(n, xn) are given in this paper. Neutronics validation of the Dubna Cascade Code is also done using cross-section data by other experiments.
Journal of Molecular Catalysis A: Chemical, 2005
The insertion of dimethylvinylidene carbene into azo moiety was investigated in order to synthesi... more The insertion of dimethylvinylidene carbene into azo moiety was investigated in order to synthesize 4,6-dimethyl-5-[2-(2-methylprop-1-enyl)-1H-benzimidazol-1-yl] pyrimidine-2(5H)-thiones [7a-j] under kinetically controlled phase transfer catalysis conditions. In situ generation of dimethylvinylidene carbene was facilitated by the interaction between 3-chloro-3-methyl-1-butyne and alkali at the interface. Interestingly, insertion of this carbene into the N N linkage of 2,4-dimethyl-3-arylazo-6-thiopyrimidine afforded newly synthesized desired benzimidazolo pyrimidines. The reaction follows the pseudo-first order rate law. Rational mechanism of the reaction is proposed according to the experimental evidence. The compounds were synthesized in excellent yields (70-80%) and their structures were established on the basis of their IR and 1 H NMR spectral data.