A dozen mRNAs are edited by multiple insertions and/or deletions of uridine residues in the mitoc... more A dozen mRNAs are edited by multiple insertions and/or deletions of uridine residues in the mitochondrion of Trypanosoma brucei Several protein complexes have been implicated in performing this type of RNA editing, including the mitochondrial RNA-binding complex 1 (MRB1). Two paralogous novel RNA-binding proteins, MRB8170 and MRB4160, are loosely associated with the core MRB1 complex. Their roles in RNA editing and effects on target mRNAs are so far not well understood. In this study, individual-nucleotide-resolution UV-cross-linking and affinity purification (iCLAP) revealed a preferential binding of both proteins to mitochondrial mRNAs, which was positively correlated with their extent of editing. Integrating additional in vivo and in vitro data, we propose that binding of MRB8170 and/or MRB4160 onto pre-mRNA marks it for the initiation of editing and that initial binding of both proteins may facilitate the recruitment of other components of the RNA editing/processing machinery to ensure efficient editing. Surprisingly, MRB8170 also binds never-edited mRNAs, suggesting that at least this paralog has an additional role outside RNA editing to shape the mitochondrial transcriptome. Trypanosoma brucei mitochondrial mRNAs undergo maturation by RNA editing, a unique process involving decrypting open reading frames by the precise deletion and/or insertion of uridine (U) residues at specific positions on an mRNA. This process is catalyzed by multiprotein complexes, such as the RNA editing core complex, which provides the enzymatic activities needed for U insertion/deletion at a single editing site. Less well understood is how RNA editing occurs throughout an mRNA bearing multiple sites. To address this question, we mapped at single-nucleotide resolution the RNA interactions of two unique RNA-binding proteins (RBPs). These RBPs are part of the mitochondrial RNA-binding complex 1, hypothesized to mediate multiple rounds of RNA editing. Both RBPs were shown to mark mRNAs for the process in correlation with the number of editing sites on the transcript. Surprisingly, one also binds mRNAs that bypass RNA editing, indicating that it may have an additional role outside RNA editing.
Whitefly (Bemisia tabaci) complex is a serious insect pest of several crop plants worldwide. It c... more Whitefly (Bemisia tabaci) complex is a serious insect pest of several crop plants worldwide. It comprises several morphologically indistinguishable species, however very little is known about their genetic divergence and biosynthetic pathways. In the present study, we performed transcriptome sequencing of Asia 1 species of B. tabaci complex and analyzed the interaction of host-symbiont genes in amino acid biosynthetic pathways. We obtained about 83 million reads using Illumina sequencing that assembled into 72716 unitigs. A total of 21129 unitigs were annotated at stringent parameters. Annotated unitigs were mapped to 52847 gene ontology (GO) terms and 131 Kyoto encyclopedia of genes and genomes (KEGG) pathways. Expression analysis of the genes involved in amino acid biosynthesis pathways revealed the complementation between whitefly and its symbiont partner Candidatus Portiera aleyrodidarum. Most of the non-essential amino acids and intermediates of essential amino acid pathways we...
Some of the naturally sap sucking insect resistant plant varieties comprise altered amounts of am... more Some of the naturally sap sucking insect resistant plant varieties comprise altered amounts of amino acids asparagine, aspartic acid and glutamic acid in their sap. However, role of these amino acids on insect resistance has not been demonstrated. We evaluated impact of asparagine (N), aspartic acid (D) and glutamic acid (E) on survival of Myzus persicae and Bemisia tabaci by altering concentration in artificial diet. We observed that higher concentration of D or/and E caused ~94-100 % mortality of both insects while higher concentration of N did not show any significant mortality. Deletion of such amino acids from normal diet did not show any effect on survival of M. persicae s and B. tabaci. Asparagine synthetase (AS) and asparginase (ASN) mutant of Arabidopsis thaliana plant, which might have altered level of such amino acids were evaluated for insect resistance. AS-mutants of Arabidopsis thaliana showed significant protection against M. persicae and B.
Background: RNA interference has been emerged as an utmost tool for the control of sap sucking in... more Background: RNA interference has been emerged as an utmost tool for the control of sap sucking insect pests. Systemic response is necessary to control them in field condition. Whitefly is observed to be more prone to siRNA in recent studies, however the siRNA machinery and mechanism is not well established.
Plants naturally emit methanol as volatile organic compound. Methanol is toxic to insect pests; b... more Plants naturally emit methanol as volatile organic compound. Methanol is toxic to insect pests; but the quantity produced by most of the plants is not enough to protect them against invading insect pests. In the present study, we demonstrated that the over-expression of pectin methylesterase, derived from Arabidopsis thaliana and Aspergillus niger, in transgenic tobacco plants enhances methanol production and resistance to polyphagous insect pests. Methanol content in the leaves of transgenic plants was measured using proton nuclear spectroscopy (1H NMR) and spectra showed up to 16 fold higher methanol as compared to control wild type (WT) plants. A maximum of 100 and 85% mortality in chewing insects Helicoverpa armigera and Spodoptera litura larvae was observed, respectively when fed on transgenic plants leaves. The surviving larvae showed less feeding, severe growth retardation and could not develop into pupae. In-planta bioassay on transgenic lines showed up to 99 and 75% reduction in the population multiplication of plant sap sucking pests Myzus persicae (aphid) and Bemisia tabaci (whitefly), respectively. Most of the phenotypic characters of transgenic plants were similar to WT plants. Confocal microscopy showed no deformities in cellular integrity, structure and density of stomata and trichomes of transgenic plants compared to WT. Pollen germination and tube formation was also not affected in transgenic plants. Cell wall enzyme transcript levels were comparable with WT. This study demonstrated for the first time that methanol emission can be utilized for imparting broad range insect resistance in plants.
Peroxidases are the ubiquitous enzyme and reported to be present in all living genera. they catal... more Peroxidases are the ubiquitous enzyme and reported to be present in all living genera. they catalyses reduction of peroxide and generate reactive oxygen species. In the present study we demonstrated that insect infestation induces peroxidase activity in sap and total soluble protein (tSP) of plant leaves. three important crop plants viz. tomato, cowpea and cotton were used for this study. after infestation of chewing insect, peroxidase activity in the sap and tSP of all the studied plants were enhanced in the range of 1.6-3.14 fold. Similar observations were also obtained with feeding of sap sucking insects, in which increment in peroxidase activity of sap and tSP was in the range of 1.8-2.53 fold. enhanced peroxidase activity was reconfirmed by in-gel peroxidase assay. enzyme kinetic study showed turn over efficiency of peroxidase from cotton (~101.3 min-1) was almost similar to tomato (~100.8 min-1) but higher than cowpea (~98.21 min-1). MS/MS analysis of observed band showed significant similarity with the reported peroxidases in database.
Pectin methylesterases (Pme; eC 3.1.1.11) involved in de-esteriication of pectin and have applica... more Pectin methylesterases (Pme; eC 3.1.1.11) involved in de-esteriication of pectin and have applicability in food, textiles, wines, pulp, and paper industries. in the present study, we compared Pme activity of diferent parts of 3 Datura species and found that fruit coat showed maximum Pme activity followed by leaf and seed. Pme from leaves of D. stramonium (DsPme) was puriied and characterized. DsPme showed optimum activity at 60 °C and ph 9 in the presence of 0.3 m naCl. DsPme was stable at 70 °C and retained more than 40% activity after 60 min of incubation. however, enzyme activity completely abolished at 80 after 5 min of incubation. it follows michaelis-menten enzyme kinetics. Km and Vmax with citrus pectin were 0.008 mg/ml and 16.96 µmol/min, respectively. DsPme in combination with polygalactourenase (PGa) increased the clarity of orange, apple, pomegranate and pineapple juices by 2.9, 2.6, 2.3, and 3.6-fold, respectively in comparison to PGa alone. Due to very high de-esteriication activity, easy denaturation and signiicant eicacy in incrementing clariication of fruit juice makes DsPme useful for industrial application.
Diversity studies of enteric Escherichia coli have relied almost entirely on faecal isolations on... more Diversity studies of enteric Escherichia coli have relied almost entirely on faecal isolations on the assumption that they are representative of flora found throughout the gastrointestinal tract. The authors have addressed this belief by analysing isolates obtained from the duodenum, ileum, colon and faeces of pigs. E. coli isolates were obtained from eight pigs and characterized using multi-locus enzyme electrophoresis and PCR-based screening for a range of factors thought to be associated with intestinal and extra-intestinal disease. There are four main genetic groups of commensal E. coli (A, B1, B2, D). Group A strains represented 76 % of the isolates from the duodenum, ileum and colon compared to 58 % of the strains isolated from faeces. A nested molecular analysis of variance based on the allozyme and virulence factor screening results showed that differences among individual pigs accounted for 6 % of the observed genetic diversity, whilst 27 % of the genetic variation could be explained by clonal composition differences among gut regions. Finally, the absence of virulence genes in these commensals indicates that they may be suitable as a probiotic consortium, particularly if they also display increased adherence to enterocytes and antagonistic activity against pathogenic strains of E. coli. 3Present address: NSW Agriculture, PMB 8, Camden, NSW 2570, Sydney, Australia.
Tomatoes are one of the most consumed crops in the whole world because of their versatile importa... more Tomatoes are one of the most consumed crops in the whole world because of their versatile importance in dietary food as well as many industrial applications. They are also a rich source of secondary metabolites, such as phenolics and flavonoids. In the present study, we described a method to produce these compounds from hairy roots of tomato (THRs). Agrobacterium rhizogenes strain A4 was used to induce hairy roots in the tomato explants. The Ri T-DNA was confirmed by polymerase chain reaction amplification of the rolC gene. Biomass accumulation of hairy root lines was 1.7-3.7-fold higher compared to in vitro grown roots. Moreover, THRs efficiently produced several phenolic compounds, such as rutin, quercetin, kaempferol, gallic acid, protocatechuic acid, ferulic acid, colorogenic acid, and caffeic acid. Gallic acid [34.02 μg/g of dry weight (DW)] and rutin (20.26 μg/g of DW) were the major phenolic acid and flavonoid produced by THRs, respectively. The activities of reactive oxygen species enzymes (catalase, ascorbate peroxidase, and superoxide dismutase) were quantified. The activity of catalase in THRs was 0.97 ± 0.03 mM H2O2 min(-1) g(-1), which was 1.22-fold (0.79 ± 0.09 mM H2O2 min(-1) g(-1)) and 1.59-fold (0.61 ± 0.06 mM H2O2 min(-1) g(-1)) higher than field grown and in vitro grown roots, respectively. At 100 μL/g concentration, the phenolic compound extract caused 53.34 and 40.00% mortality against Helicoverpa armigera and Spodoptera litura, respectively, after 6 days. Surviving larvae of H. armigera and S. litura on the phenolic compound extract after 6 days showed 85.43 and 86.90% growth retardation, respectively.
Thioredoxins are vital components of Plasmodium proteome and act as both reducing agents and prot... more Thioredoxins are vital components of Plasmodium proteome and act as both reducing agents and protein disulfide reductases. The malaria parasite P. falciparum thioredoxin-2 (PfTrx-2) is part of the multi-protein complex embedded within the parasite parasitophorous vacuolar membrane (PVM) which purportedly directs protein secretion. We have characterized structural and enzymatic features of PfTrx-2, and we show that PfTrx-2 adopts a canonical thioredoxin fold but with significant structural differences in its N-terminus. Our confocal localization data suggest distinct PVM residency of PfTrx-2. Based on the crystal structure of PfTrx-2, we screened and tested small molecule drug-like libraries for compounds which target unique structural features of PfTrx-2. Disruption of PfTrx-2 interactions using specific inhibitors may result in a dysfunctional parasite translocon that is rendered unable to secrete pathogenic proteins into hosts. This approach therefore offers a new focus for anti-m...
Archives of Physical Medicine and Rehabilitation, 2000
To determine if bone mineral density (BMD) is associated with the probability of stress fractures... more To determine if bone mineral density (BMD) is associated with the probability of stress fractures in premenopausal women. Case-control study. Large Army post, Fort Lewis, WA. Twenty-seven active duty Army women with documented stress fractures within the last 2 years and 158 female controls. All subjects were examined and interviewed. BMD of the femoral neck and posteroanterior lumbar spine (L2-L4) was measured using dual energy X-ray absorptiometry. Univariate comparisons revealed no significant differences in BMD of the femoral neck or lumbar spine between groups. Women with stress fractures had a significantly higher exercise intensity (428 vs 292 minutes per week, p<.05) and were more likely to be entry-level enlisted soldiers (63% vs. 44%, p<.05) than those without stress fractures. Multivariate analyses revealed a strong negative association between femoral neck BMD and the probability of stress fractures (lower BMD, higher risk). Exercise intensity and body mass index had a significant positive effect on BMD of the femoral neck and lumbar spine, yet both were associated with an increased probability of stress fractures. Femoral neck BMD was significantly associated with the probability of stress fractures. Optimal training programs should balance the beneficial indirect effect of increased exercise (through increased BMD) with its detrimental direct effect on stress fractures.
International review of cell and molecular biology, 2015
The importance of mitochondria for a typical aerobic eukaryotic cell is undeniable, as the list o... more The importance of mitochondria for a typical aerobic eukaryotic cell is undeniable, as the list of necessary mitochondrial processes is steadily growing. Here, we summarize the current knowledge of mitochondrial biology of an early-branching parasitic protist, Trypanosoma brucei, a causative agent of serious human and cattle diseases. We present a comprehensive survey of its mitochondrial pathways including kinetoplast DNA replication and maintenance, gene expression, protein and metabolite import, major metabolic pathways, Fe-S cluster synthesis, ion homeostasis, organellar dynamics, and other processes. As we describe in this chapter, the single mitochondrion of T. brucei is everything but simple and as such rivals mitochondria of multicellular organisms.
A dozen mRNAs are edited by multiple insertions and/or deletions of uridine residues in the mitoc... more A dozen mRNAs are edited by multiple insertions and/or deletions of uridine residues in the mitochondrion of Trypanosoma brucei Several protein complexes have been implicated in performing this type of RNA editing, including the mitochondrial RNA-binding complex 1 (MRB1). Two paralogous novel RNA-binding proteins, MRB8170 and MRB4160, are loosely associated with the core MRB1 complex. Their roles in RNA editing and effects on target mRNAs are so far not well understood. In this study, individual-nucleotide-resolution UV-cross-linking and affinity purification (iCLAP) revealed a preferential binding of both proteins to mitochondrial mRNAs, which was positively correlated with their extent of editing. Integrating additional in vivo and in vitro data, we propose that binding of MRB8170 and/or MRB4160 onto pre-mRNA marks it for the initiation of editing and that initial binding of both proteins may facilitate the recruitment of other components of the RNA editing/processing machinery to ensure efficient editing. Surprisingly, MRB8170 also binds never-edited mRNAs, suggesting that at least this paralog has an additional role outside RNA editing to shape the mitochondrial transcriptome. Trypanosoma brucei mitochondrial mRNAs undergo maturation by RNA editing, a unique process involving decrypting open reading frames by the precise deletion and/or insertion of uridine (U) residues at specific positions on an mRNA. This process is catalyzed by multiprotein complexes, such as the RNA editing core complex, which provides the enzymatic activities needed for U insertion/deletion at a single editing site. Less well understood is how RNA editing occurs throughout an mRNA bearing multiple sites. To address this question, we mapped at single-nucleotide resolution the RNA interactions of two unique RNA-binding proteins (RBPs). These RBPs are part of the mitochondrial RNA-binding complex 1, hypothesized to mediate multiple rounds of RNA editing. Both RBPs were shown to mark mRNAs for the process in correlation with the number of editing sites on the transcript. Surprisingly, one also binds mRNAs that bypass RNA editing, indicating that it may have an additional role outside RNA editing.
Whitefly (Bemisia tabaci) complex is a serious insect pest of several crop plants worldwide. It c... more Whitefly (Bemisia tabaci) complex is a serious insect pest of several crop plants worldwide. It comprises several morphologically indistinguishable species, however very little is known about their genetic divergence and biosynthetic pathways. In the present study, we performed transcriptome sequencing of Asia 1 species of B. tabaci complex and analyzed the interaction of host-symbiont genes in amino acid biosynthetic pathways. We obtained about 83 million reads using Illumina sequencing that assembled into 72716 unitigs. A total of 21129 unitigs were annotated at stringent parameters. Annotated unitigs were mapped to 52847 gene ontology (GO) terms and 131 Kyoto encyclopedia of genes and genomes (KEGG) pathways. Expression analysis of the genes involved in amino acid biosynthesis pathways revealed the complementation between whitefly and its symbiont partner Candidatus Portiera aleyrodidarum. Most of the non-essential amino acids and intermediates of essential amino acid pathways we...
Some of the naturally sap sucking insect resistant plant varieties comprise altered amounts of am... more Some of the naturally sap sucking insect resistant plant varieties comprise altered amounts of amino acids asparagine, aspartic acid and glutamic acid in their sap. However, role of these amino acids on insect resistance has not been demonstrated. We evaluated impact of asparagine (N), aspartic acid (D) and glutamic acid (E) on survival of Myzus persicae and Bemisia tabaci by altering concentration in artificial diet. We observed that higher concentration of D or/and E caused ~94-100 % mortality of both insects while higher concentration of N did not show any significant mortality. Deletion of such amino acids from normal diet did not show any effect on survival of M. persicae s and B. tabaci. Asparagine synthetase (AS) and asparginase (ASN) mutant of Arabidopsis thaliana plant, which might have altered level of such amino acids were evaluated for insect resistance. AS-mutants of Arabidopsis thaliana showed significant protection against M. persicae and B.
Background: RNA interference has been emerged as an utmost tool for the control of sap sucking in... more Background: RNA interference has been emerged as an utmost tool for the control of sap sucking insect pests. Systemic response is necessary to control them in field condition. Whitefly is observed to be more prone to siRNA in recent studies, however the siRNA machinery and mechanism is not well established.
Plants naturally emit methanol as volatile organic compound. Methanol is toxic to insect pests; b... more Plants naturally emit methanol as volatile organic compound. Methanol is toxic to insect pests; but the quantity produced by most of the plants is not enough to protect them against invading insect pests. In the present study, we demonstrated that the over-expression of pectin methylesterase, derived from Arabidopsis thaliana and Aspergillus niger, in transgenic tobacco plants enhances methanol production and resistance to polyphagous insect pests. Methanol content in the leaves of transgenic plants was measured using proton nuclear spectroscopy (1H NMR) and spectra showed up to 16 fold higher methanol as compared to control wild type (WT) plants. A maximum of 100 and 85% mortality in chewing insects Helicoverpa armigera and Spodoptera litura larvae was observed, respectively when fed on transgenic plants leaves. The surviving larvae showed less feeding, severe growth retardation and could not develop into pupae. In-planta bioassay on transgenic lines showed up to 99 and 75% reduction in the population multiplication of plant sap sucking pests Myzus persicae (aphid) and Bemisia tabaci (whitefly), respectively. Most of the phenotypic characters of transgenic plants were similar to WT plants. Confocal microscopy showed no deformities in cellular integrity, structure and density of stomata and trichomes of transgenic plants compared to WT. Pollen germination and tube formation was also not affected in transgenic plants. Cell wall enzyme transcript levels were comparable with WT. This study demonstrated for the first time that methanol emission can be utilized for imparting broad range insect resistance in plants.
Peroxidases are the ubiquitous enzyme and reported to be present in all living genera. they catal... more Peroxidases are the ubiquitous enzyme and reported to be present in all living genera. they catalyses reduction of peroxide and generate reactive oxygen species. In the present study we demonstrated that insect infestation induces peroxidase activity in sap and total soluble protein (tSP) of plant leaves. three important crop plants viz. tomato, cowpea and cotton were used for this study. after infestation of chewing insect, peroxidase activity in the sap and tSP of all the studied plants were enhanced in the range of 1.6-3.14 fold. Similar observations were also obtained with feeding of sap sucking insects, in which increment in peroxidase activity of sap and tSP was in the range of 1.8-2.53 fold. enhanced peroxidase activity was reconfirmed by in-gel peroxidase assay. enzyme kinetic study showed turn over efficiency of peroxidase from cotton (~101.3 min-1) was almost similar to tomato (~100.8 min-1) but higher than cowpea (~98.21 min-1). MS/MS analysis of observed band showed significant similarity with the reported peroxidases in database.
Pectin methylesterases (Pme; eC 3.1.1.11) involved in de-esteriication of pectin and have applica... more Pectin methylesterases (Pme; eC 3.1.1.11) involved in de-esteriication of pectin and have applicability in food, textiles, wines, pulp, and paper industries. in the present study, we compared Pme activity of diferent parts of 3 Datura species and found that fruit coat showed maximum Pme activity followed by leaf and seed. Pme from leaves of D. stramonium (DsPme) was puriied and characterized. DsPme showed optimum activity at 60 °C and ph 9 in the presence of 0.3 m naCl. DsPme was stable at 70 °C and retained more than 40% activity after 60 min of incubation. however, enzyme activity completely abolished at 80 after 5 min of incubation. it follows michaelis-menten enzyme kinetics. Km and Vmax with citrus pectin were 0.008 mg/ml and 16.96 µmol/min, respectively. DsPme in combination with polygalactourenase (PGa) increased the clarity of orange, apple, pomegranate and pineapple juices by 2.9, 2.6, 2.3, and 3.6-fold, respectively in comparison to PGa alone. Due to very high de-esteriication activity, easy denaturation and signiicant eicacy in incrementing clariication of fruit juice makes DsPme useful for industrial application.
Diversity studies of enteric Escherichia coli have relied almost entirely on faecal isolations on... more Diversity studies of enteric Escherichia coli have relied almost entirely on faecal isolations on the assumption that they are representative of flora found throughout the gastrointestinal tract. The authors have addressed this belief by analysing isolates obtained from the duodenum, ileum, colon and faeces of pigs. E. coli isolates were obtained from eight pigs and characterized using multi-locus enzyme electrophoresis and PCR-based screening for a range of factors thought to be associated with intestinal and extra-intestinal disease. There are four main genetic groups of commensal E. coli (A, B1, B2, D). Group A strains represented 76 % of the isolates from the duodenum, ileum and colon compared to 58 % of the strains isolated from faeces. A nested molecular analysis of variance based on the allozyme and virulence factor screening results showed that differences among individual pigs accounted for 6 % of the observed genetic diversity, whilst 27 % of the genetic variation could be explained by clonal composition differences among gut regions. Finally, the absence of virulence genes in these commensals indicates that they may be suitable as a probiotic consortium, particularly if they also display increased adherence to enterocytes and antagonistic activity against pathogenic strains of E. coli. 3Present address: NSW Agriculture, PMB 8, Camden, NSW 2570, Sydney, Australia.
Tomatoes are one of the most consumed crops in the whole world because of their versatile importa... more Tomatoes are one of the most consumed crops in the whole world because of their versatile importance in dietary food as well as many industrial applications. They are also a rich source of secondary metabolites, such as phenolics and flavonoids. In the present study, we described a method to produce these compounds from hairy roots of tomato (THRs). Agrobacterium rhizogenes strain A4 was used to induce hairy roots in the tomato explants. The Ri T-DNA was confirmed by polymerase chain reaction amplification of the rolC gene. Biomass accumulation of hairy root lines was 1.7-3.7-fold higher compared to in vitro grown roots. Moreover, THRs efficiently produced several phenolic compounds, such as rutin, quercetin, kaempferol, gallic acid, protocatechuic acid, ferulic acid, colorogenic acid, and caffeic acid. Gallic acid [34.02 μg/g of dry weight (DW)] and rutin (20.26 μg/g of DW) were the major phenolic acid and flavonoid produced by THRs, respectively. The activities of reactive oxygen species enzymes (catalase, ascorbate peroxidase, and superoxide dismutase) were quantified. The activity of catalase in THRs was 0.97 ± 0.03 mM H2O2 min(-1) g(-1), which was 1.22-fold (0.79 ± 0.09 mM H2O2 min(-1) g(-1)) and 1.59-fold (0.61 ± 0.06 mM H2O2 min(-1) g(-1)) higher than field grown and in vitro grown roots, respectively. At 100 μL/g concentration, the phenolic compound extract caused 53.34 and 40.00% mortality against Helicoverpa armigera and Spodoptera litura, respectively, after 6 days. Surviving larvae of H. armigera and S. litura on the phenolic compound extract after 6 days showed 85.43 and 86.90% growth retardation, respectively.
Thioredoxins are vital components of Plasmodium proteome and act as both reducing agents and prot... more Thioredoxins are vital components of Plasmodium proteome and act as both reducing agents and protein disulfide reductases. The malaria parasite P. falciparum thioredoxin-2 (PfTrx-2) is part of the multi-protein complex embedded within the parasite parasitophorous vacuolar membrane (PVM) which purportedly directs protein secretion. We have characterized structural and enzymatic features of PfTrx-2, and we show that PfTrx-2 adopts a canonical thioredoxin fold but with significant structural differences in its N-terminus. Our confocal localization data suggest distinct PVM residency of PfTrx-2. Based on the crystal structure of PfTrx-2, we screened and tested small molecule drug-like libraries for compounds which target unique structural features of PfTrx-2. Disruption of PfTrx-2 interactions using specific inhibitors may result in a dysfunctional parasite translocon that is rendered unable to secrete pathogenic proteins into hosts. This approach therefore offers a new focus for anti-m...
Archives of Physical Medicine and Rehabilitation, 2000
To determine if bone mineral density (BMD) is associated with the probability of stress fractures... more To determine if bone mineral density (BMD) is associated with the probability of stress fractures in premenopausal women. Case-control study. Large Army post, Fort Lewis, WA. Twenty-seven active duty Army women with documented stress fractures within the last 2 years and 158 female controls. All subjects were examined and interviewed. BMD of the femoral neck and posteroanterior lumbar spine (L2-L4) was measured using dual energy X-ray absorptiometry. Univariate comparisons revealed no significant differences in BMD of the femoral neck or lumbar spine between groups. Women with stress fractures had a significantly higher exercise intensity (428 vs 292 minutes per week, p<.05) and were more likely to be entry-level enlisted soldiers (63% vs. 44%, p<.05) than those without stress fractures. Multivariate analyses revealed a strong negative association between femoral neck BMD and the probability of stress fractures (lower BMD, higher risk). Exercise intensity and body mass index had a significant positive effect on BMD of the femoral neck and lumbar spine, yet both were associated with an increased probability of stress fractures. Femoral neck BMD was significantly associated with the probability of stress fractures. Optimal training programs should balance the beneficial indirect effect of increased exercise (through increased BMD) with its detrimental direct effect on stress fractures.
International review of cell and molecular biology, 2015
The importance of mitochondria for a typical aerobic eukaryotic cell is undeniable, as the list o... more The importance of mitochondria for a typical aerobic eukaryotic cell is undeniable, as the list of necessary mitochondrial processes is steadily growing. Here, we summarize the current knowledge of mitochondrial biology of an early-branching parasitic protist, Trypanosoma brucei, a causative agent of serious human and cattle diseases. We present a comprehensive survey of its mitochondrial pathways including kinetoplast DNA replication and maintenance, gene expression, protein and metabolite import, major metabolic pathways, Fe-S cluster synthesis, ion homeostasis, organellar dynamics, and other processes. As we describe in this chapter, the single mitochondrion of T. brucei is everything but simple and as such rivals mitochondria of multicellular organisms.
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