The lin-4 RNA acts as a negative regulator of the Michael T. McManus* developmentally important l... more The lin-4 RNA acts as a negative regulator of the Michael T. McManus* developmentally important lin-14 and lin-28 protein-UCSF Diabetes Center coding genes (Lee et al., 1993; Moss et al., 1997; Olsen Department of Microbiology and Immunology and Ambros, 1999; Wightman et al., 1993). The 22-nucle-University of California, San Francisco otide lin-4 RNA contains imperfect homology to specific San Francisco, California 94122 regions of the 3Ј untranslated regions (UTRs) of lin-14 and lin-28 and, likely, other developmentally important genes. Genetic data suggested a potential mechanism Small RNAs of 21-23 nucleotides are powerful regulaof action: deletion of the lin-4 target sequences in the tors of gene expression and play essential roles in UTR causes an unregulated gain-of-function phenotype. biological processes that include development, main-In support of this mechanism, reporter genes containing tenance of genome stability, and viral adaptive defusions of the lin-4 UTR renders it susceptible to develfense mechanisms. Such small RNAs are simple in opmental regulation (Lee et al., 1993; Wightman et al., design yet rich in biology and have captivated the at-1993)
A microsporidium Nosema portugal n. sp. was isolated from gypsy moths, Lymantria dispar L, collec... more A microsporidium Nosema portugal n. sp. was isolated from gypsy moths, Lymantria dispar L, collected near Lisbon, Portugal, in 1985. The life cycle includes two sequential developmental cycles, a primary and a secondary cycle. The primary cycle occurs in midgut epithelial cells, where primary spores are produced within 48 h. The primary spores immediately extrude their polar filaments, presumably to infect other cells. In the target tissues (salivary glands and fat body) the secondary development cycle is followed by the formation of environmental spores. Primary spores were also sometimes present in target tissues. Fresh unfixed and unstained primary spores have a large posterior vacuole and measured 4.8 ؋ 2.7 m. Ultrastructurally, they have 5-8 polar filament coils, a large posterior vacuole, abundant endoplasmic reticulum, and were binucleate. Mature unfixed and unstained environmental spores were highly refractive and the posterior vacuole and nuclei could not be seen through the spore coat. Fresh environmental spores measured 4.5 ؋ 1.9 m. Ultrastructurally, environmental spores were binucleate, with a typical polaroplast, 10-11 isofilar polar filament coils, and a series of 4-6 thin polar filamentlike tubules situated at the posterior end of the row of typical polar filament coils. The ssu rRNA sequences strongly suggest that this species is more closely related to the Vairimorpha subgroup within the Nosema/ Vairimorpha clade than to the Nosema subgroup. 1999
isoforms were recognised by a polyclonal antibody directed differentially during leaf ontogeny in... more isoforms were recognised by a polyclonal antibody directed differentially during leaf ontogeny in white clover (Trifolium against a recombinant polypeptide derived from a white clover ACO gene expressed in mature green leaf tissue, TR-ACO2. repens L.), have been identified and purified to homogeneity.
Macroscopically, Alzheimer’s disease (AD) is characterized by global atrophy that is more pronoun... more Macroscopically, Alzheimer’s disease (AD) is characterized by global atrophy that is more pronounced, at least, initially, in medial temporal lobe structures and accompanied by ventricular enlargement. Rates of hippocampal atrophy (rHVLs) and ventricular volume gain (rVVGs) have been proposed as possible measures to judge the efficacy of treatments designed to be disease modifying. Our interest has focused on whether and
We have previously cloned a cDNA, designated SAT1, corresponding to a gene coding for a serine ac... more We have previously cloned a cDNA, designated SAT1, corresponding to a gene coding for a serine acetyltransferase (SAT) from onion (Allium cepa L.). The SAT1 locus was mapped to chromosome 7 of onion using a single-stranded conformation polymorphism (SSCP) in the 3' UTR of the gene. Northern analysis has demonstrated that expression of the SAT1 gene is induced in leaf tissue in response to low S-supply. Phylogenetic analysis has placed SAT1 in a strongly supported group (100% bootstrap) that comprises sequences that have been characterised biochemically, including Allium tuberosum, Spinacea oleracea, Glycine max, Citrullus vulgaris, and SAT5 (AT5g56760) of Arabidopsis thaliana. This group can be divided further with the SAT1 of A. cepa sequence grouping strongly with the A. tuberosum sequence. Translation of SAT1 from onion generates a protein of 289 amino acids with a calculated molecular mass of 30,573 Da and pI of 6.52. The conserved G277 and H282 residues that have been identified as critical for L-cysteine inhibition are observed at G272 and H277. SAT1 has been cloned into the pGEX plasmid, expressed in E. coli and SAT activity of the recombinant enzyme has been measured as acetyl-CoA hydrolysis detected at 232 nm. A Km of 0.72 mM was determined for l-serine as substrate, a Km of 92 microM was calculated with acetyl-CoA as substrate, and an inhibition curve for L-cysteine generated an IC50 value of 3.1 microM. Antibodies raised against the recombinant SAT1 protein recognised a protein of ca. 33 kDa in whole leaf onion extracts. These properties of the SAT1 enzyme from onion are compared with other SAT enzymes characterised from closely related species.
While significant effort has been dedicated to the characterization of epigenetic changes associa... more While significant effort has been dedicated to the characterization of epigenetic changes associated with prenatal differentiation, relatively little is known about the epigenetic changes that accompany post-natal differentiation where fully functional differentiated cell types with limited lifespans arise. Here we sought to address this gap by generating epigenomic and transcriptional profiles from primary human breast cell types isolated from disease-free human subjects. From these data we define a comprehensive human breast transcriptional network, including a set of myoepithelial- and luminal epithelial-specific intronic retention events. Intersection of epigenetic states with RNA expression from distinct breast epithelium lineages demonstrates that mCpG provides a stable record of exonic and intronic usage, whereas H3K36me3 is dynamic. We find a striking asymmetry in epigenomic reprogramming between luminal and myoepithelial cell types, with the genomes of luminal cells harbour...
Page 1. Risks of Host Range Expansion by Parasites of Insects Population ecology can help us esti... more Page 1. Risks of Host Range Expansion by Parasites of Insects Population ecology can help us estimate the risks that biological control agents pose to nontarget species David W. Onstad and Michael L. McManus The concept ...
The reference human genome sequence set the stage for studies of genetic variation and its associ... more The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic info...
Compared with parasitoids and predators, classical biological control programs targeting arthropo... more Compared with parasitoids and predators, classical biological control programs targeting arthropod pests have used pathogens and nematodes very little. However, some pathogens and nematodes that have been introduced have become established and provided excellent control and have been introduced in increasing numbers of areas over decades, often after distributions of pests have increased. We summarize 131 introductions, the majority of which have occurred since 1950. The most commonly introduced microorganisms have been fungi, viruses and nematodes, although microsporidia, bacteria and oomycetes have also been introduced; among these groups, viruses were the most successful in establishing followed by nematodes, fungi and microsporidia. All major orders of insects and prostigmatid mites have been targeted and in 63.6% of the programs the pests being targeted were invasive species and not native. Pathogens and nematodes yielded excellent success in establishment against sawflies and wood wasps (100% of programs) and 40-48% establishment among other host orders. Classical biological control has been used for long-term control of arthropod pests on islands almost as much as in mainland areas. It has been used most frequently in perennial systems and highest rates of establishment of arthropod pathogens and insect parasitic nematodes were documented from forests (63.0%) and tree crops (66.7%). One explanation for the low number of releases of arthropod pathogens and insect parasitic nematodes has been confusing and difficult regulations but recent changes and institution of the FAO's Code of Conduct is expected to improve scientists' ability to introduce microbial natural enemies for classical biological control.
Isolates of Steinernema feltiae SN from France, Steinernema glaseri NJ from New Jersey, Steinerne... more Isolates of Steinernema feltiae SN from France, Steinernema glaseri NJ from New Jersey, Steinernema riobrave TX from Texas, Steinernema carpocapsae Sal from Indiana, S. carpocapsae All from Georgia, and Heterorhabditis marelata IN from Indiana were screened for efficacy against laboratory colonies of Asian longhorned beetle, Anoplophora, glabripennis collected from Queens, New York and Chicago, Illinois. Two bioassays were used to screen nematode effects on beetle larvae; a filter paper assay using a 24-h exposure of nematode-to-target-insect, and a diet cup bioassay using a 72-h exposure of host larvae to infective juveniles applied to the larval bore hole made in the artificial diet in the cups. First-and third-stage larvae were susceptible to all isolates using a filter paper bioassay. S. feltiae and S. carpocapsae Sal were the most effective, causing 100% mortality. S. feltiae was more infectious than S. carpocapsae Sal against third, sixth, and seventh instars. S. riobrave, S. glaseri, and H. marelata were ineffective against the older instars. In the diet cup bioassay, S. feltiae and S. carpocapsae Sal killed 71-100% of mid-to late instar larvae, but the remaining isolates screened were ineffective. Nematode preconditioning to aqueous A. glabripennis frass extracts inhibited S. carpocapsae Sal infectivity but had no effect on nematode pathogenicity. S. feltiae juveniles were positively attracted to A. glabripennis frass extracts. Our results demonstrate the potential use of S. feltiae and S. carpocapsae isolates as control agents for A. glabripennis. Published by Elsevier Inc.
Extracts from the digestive tract of final instar larvae of Spodoptera litura, reared on artifici... more Extracts from the digestive tract of final instar larvae of Spodoptera litura, reared on artificial diet, contained trypsin-like (BApNA-hydrolysing) activity with a pH optimum of 10.5, an elastase-like (SA2PLpNA-hydrolysing) activity with a pH optimum of 10.5 and leucine aminopeptidase activity with a pH optimum of 8.5. No chymotrypsin amidase-like (BTpNA-hydrolysing) activity could be detected, but chymotrypsin esterase-like (BTEE-hydrolysing) activity was
Microorganisms are enormous but largely untapped natural resources for biological control of pest... more Microorganisms are enormous but largely untapped natural resources for biological control of pests and diseases. There are two primary reasons for their underployment for pest or disease control: (1) the technical difficulties of using microorganisms for biological control, owing to a lack of fundamental information on them and their ecology, and (2) the costs of product development and regulatory approvals required for each strain, formulation, and use. Agriculture and forestry benefit greatly from the resident communities of microorganisms responsible for naturally occurring biological control of pest species, but additional benefits are achieved by introducing/applying them when or where needed. This can be done as (1) an inoculative release, (2) an augmentative application, or (3) an inundative application. Because of their specificity, different microbial biocontrol agents typically are needed to control different pests or the same pest in different environments. Four potential adverse effects are identified as safety issues (hazards) associated with the use of microorganisms for the biological control of plant pests and diseases. These are: (1) displacement of nontarget microorganisms, (2) allergenicity to humans and other animals, (3) toxigenicity to nontarget organisms, and (4) pathogenicity to nontarget organisms. Except for allergenicity, these are the same attributes that contribute to the efficacy of microbial biocontrol agents toward the target pest species. The probability of occurrence of a particular adverse nontarget effect of a microbial biocontrol agent may be a function of geographic origin or a specific trait genetically added or modified, but the safety issues are the still the same, including whether the microorganism intended for pest or disease control is indigenous, nonindigenous (imported and released), or genetically modified by traditional or recombinant DNA (rDNA) technology. Likewise, the probability of occurrence of a particular adverse nontarget effect may vary with method of application, e.g., whether as an aerosol, soil treatment, baits, or seed treatment, and may increase with increased scale of use, but the safety issues are still the same, including whether the microorganism is used for an inoculative release or augmentative or inundative application. Existing practices for managing microorganisms in the environment (e.g., plant pathogens, Rhizobium, plant inoculants) provide experience and options for managing the risks of microorganisms applied for pest and disease control. Moreover, experience to date indicates that any adverse nontarget effects, should they occur, are likely to be short-term or transitory effects that can, if significant, be eliminated by terminating use of the microbial biocontrol agent. In contrast, production agriculture as currently practiced, such as the use of tillage and crop rotations, has significant and long-term effects on nontarget organisms, including the intentional and unintentional displacement of microorganisms. Even the decision to leave plant pests and diseases unmanaged could have significant long-term environmental effects on nontarget organisms. Potential safety issues associated with the use of microbial biocontrol must therefore be properly identified and compared with the impact of other options for managing the pest or leaving the pest unmanaged. This paper provides a scientific framework for this process. r
The host specificity of microsporidian pathogens of Lepidoptera was studied in Bulgaria where nat... more The host specificity of microsporidian pathogens of Lepidoptera was studied in Bulgaria where native populations of Lymantria dispar and their endemic microsporidia occur. L. dispar and sympatric lepidopteran larvae were collected from four sites in central and western Bulgaria. Three species of microsporidia, Vairimorpha sp., Nosema sp., and Endoreticulatus sp. are known to be endemic in three L. dispar populations, with one species in each population. No microsporidia were found in a fourth L. dispar population. In addition to the L. dispar microsporidia, 11 isolates of microsporidia were recovered from the 1494 individual lepidopteran hosts collected in these sites. When fed to L. dispar, 3 isolates produced infections that were atypical of infections in the natural hosts; one additional isolate produced an atypical infection in Spodoptera exigua. A Nosema sp. isolated from a noctuid host produced heavy infections in L. dispar larvae. Sequencing revealed that the noctuid microsporidium and the closely related Vairimorpha sp. and Nosema sp. microsporidia from L. dispar are distinctly different isolates. These investigations strengthen previous laboratory predictions of narrow host ranges for the Nosema and Vairimorpha microsporidia recovered from L. dispar in Europe. In addition, the Endoreticulatus sp., which was predicted from laboratory studies to be a generalist, was not found in Lepidoptera species sympatric with L. dispar. The results from our study indicate that laboratory testing may considerably underestimate the host specificity of many terrestrial microsporidia. Nevertheless, infectivity to nontarget hosts in the laboratory may set the stage for understanding the evolution of closely related microsporidia found in different host species.
The general basis of cancer is the loss of cell identity and inappropriate proliferation of cells... more The general basis of cancer is the loss of cell identity and inappropriate proliferation of cells. Classically, a universal paradigm in oncogenesis is the accumulation of mutations in the open reading frames of protein-encoding oncogenes and tumor suppressors. The identification of new classes of noncoding RNAs (ncRNA) important for development and cell homeostasis will likely change this current paradigm. Recent
Background: Variability in the demand for any service is a significant barrier to efficient distr... more Background: Variability in the demand for any service is a significant barrier to efficient distribution of limited resources. In health care, demand is often highly variable and access may be limited when peaks cannot be accommodated in a downsized care delivery system. Intensive care units may frequently present bottlenecks to patient flow, and saturation of these services limits a hospital's responsiveness to new emergencies.
Proceedings of The National Academy of Sciences, 2006
DICER is a key enzyme that processes microRNA and small interfering RNA precursors into their sho... more DICER is a key enzyme that processes microRNA and small interfering RNA precursors into their short mature forms, enabling them to regulate gene expression. Only a single Dicer gene exists in the mouse genome, and it is broadly expressed in developing tissues. Dicer-null mutants die before gastrulation. Therefore, to study Dicer function in the later event of lung formation, we
The lin-4 RNA acts as a negative regulator of the Michael T. McManus* developmentally important l... more The lin-4 RNA acts as a negative regulator of the Michael T. McManus* developmentally important lin-14 and lin-28 protein-UCSF Diabetes Center coding genes (Lee et al., 1993; Moss et al., 1997; Olsen Department of Microbiology and Immunology and Ambros, 1999; Wightman et al., 1993). The 22-nucle-University of California, San Francisco otide lin-4 RNA contains imperfect homology to specific San Francisco, California 94122 regions of the 3Ј untranslated regions (UTRs) of lin-14 and lin-28 and, likely, other developmentally important genes. Genetic data suggested a potential mechanism Small RNAs of 21-23 nucleotides are powerful regulaof action: deletion of the lin-4 target sequences in the tors of gene expression and play essential roles in UTR causes an unregulated gain-of-function phenotype. biological processes that include development, main-In support of this mechanism, reporter genes containing tenance of genome stability, and viral adaptive defusions of the lin-4 UTR renders it susceptible to develfense mechanisms. Such small RNAs are simple in opmental regulation (Lee et al., 1993; Wightman et al., design yet rich in biology and have captivated the at-1993)
A microsporidium Nosema portugal n. sp. was isolated from gypsy moths, Lymantria dispar L, collec... more A microsporidium Nosema portugal n. sp. was isolated from gypsy moths, Lymantria dispar L, collected near Lisbon, Portugal, in 1985. The life cycle includes two sequential developmental cycles, a primary and a secondary cycle. The primary cycle occurs in midgut epithelial cells, where primary spores are produced within 48 h. The primary spores immediately extrude their polar filaments, presumably to infect other cells. In the target tissues (salivary glands and fat body) the secondary development cycle is followed by the formation of environmental spores. Primary spores were also sometimes present in target tissues. Fresh unfixed and unstained primary spores have a large posterior vacuole and measured 4.8 ؋ 2.7 m. Ultrastructurally, they have 5-8 polar filament coils, a large posterior vacuole, abundant endoplasmic reticulum, and were binucleate. Mature unfixed and unstained environmental spores were highly refractive and the posterior vacuole and nuclei could not be seen through the spore coat. Fresh environmental spores measured 4.5 ؋ 1.9 m. Ultrastructurally, environmental spores were binucleate, with a typical polaroplast, 10-11 isofilar polar filament coils, and a series of 4-6 thin polar filamentlike tubules situated at the posterior end of the row of typical polar filament coils. The ssu rRNA sequences strongly suggest that this species is more closely related to the Vairimorpha subgroup within the Nosema/ Vairimorpha clade than to the Nosema subgroup. 1999
isoforms were recognised by a polyclonal antibody directed differentially during leaf ontogeny in... more isoforms were recognised by a polyclonal antibody directed differentially during leaf ontogeny in white clover (Trifolium against a recombinant polypeptide derived from a white clover ACO gene expressed in mature green leaf tissue, TR-ACO2. repens L.), have been identified and purified to homogeneity.
Macroscopically, Alzheimer’s disease (AD) is characterized by global atrophy that is more pronoun... more Macroscopically, Alzheimer’s disease (AD) is characterized by global atrophy that is more pronounced, at least, initially, in medial temporal lobe structures and accompanied by ventricular enlargement. Rates of hippocampal atrophy (rHVLs) and ventricular volume gain (rVVGs) have been proposed as possible measures to judge the efficacy of treatments designed to be disease modifying. Our interest has focused on whether and
We have previously cloned a cDNA, designated SAT1, corresponding to a gene coding for a serine ac... more We have previously cloned a cDNA, designated SAT1, corresponding to a gene coding for a serine acetyltransferase (SAT) from onion (Allium cepa L.). The SAT1 locus was mapped to chromosome 7 of onion using a single-stranded conformation polymorphism (SSCP) in the 3' UTR of the gene. Northern analysis has demonstrated that expression of the SAT1 gene is induced in leaf tissue in response to low S-supply. Phylogenetic analysis has placed SAT1 in a strongly supported group (100% bootstrap) that comprises sequences that have been characterised biochemically, including Allium tuberosum, Spinacea oleracea, Glycine max, Citrullus vulgaris, and SAT5 (AT5g56760) of Arabidopsis thaliana. This group can be divided further with the SAT1 of A. cepa sequence grouping strongly with the A. tuberosum sequence. Translation of SAT1 from onion generates a protein of 289 amino acids with a calculated molecular mass of 30,573 Da and pI of 6.52. The conserved G277 and H282 residues that have been identified as critical for L-cysteine inhibition are observed at G272 and H277. SAT1 has been cloned into the pGEX plasmid, expressed in E. coli and SAT activity of the recombinant enzyme has been measured as acetyl-CoA hydrolysis detected at 232 nm. A Km of 0.72 mM was determined for l-serine as substrate, a Km of 92 microM was calculated with acetyl-CoA as substrate, and an inhibition curve for L-cysteine generated an IC50 value of 3.1 microM. Antibodies raised against the recombinant SAT1 protein recognised a protein of ca. 33 kDa in whole leaf onion extracts. These properties of the SAT1 enzyme from onion are compared with other SAT enzymes characterised from closely related species.
While significant effort has been dedicated to the characterization of epigenetic changes associa... more While significant effort has been dedicated to the characterization of epigenetic changes associated with prenatal differentiation, relatively little is known about the epigenetic changes that accompany post-natal differentiation where fully functional differentiated cell types with limited lifespans arise. Here we sought to address this gap by generating epigenomic and transcriptional profiles from primary human breast cell types isolated from disease-free human subjects. From these data we define a comprehensive human breast transcriptional network, including a set of myoepithelial- and luminal epithelial-specific intronic retention events. Intersection of epigenetic states with RNA expression from distinct breast epithelium lineages demonstrates that mCpG provides a stable record of exonic and intronic usage, whereas H3K36me3 is dynamic. We find a striking asymmetry in epigenomic reprogramming between luminal and myoepithelial cell types, with the genomes of luminal cells harbour...
Page 1. Risks of Host Range Expansion by Parasites of Insects Population ecology can help us esti... more Page 1. Risks of Host Range Expansion by Parasites of Insects Population ecology can help us estimate the risks that biological control agents pose to nontarget species David W. Onstad and Michael L. McManus The concept ...
The reference human genome sequence set the stage for studies of genetic variation and its associ... more The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic info...
Compared with parasitoids and predators, classical biological control programs targeting arthropo... more Compared with parasitoids and predators, classical biological control programs targeting arthropod pests have used pathogens and nematodes very little. However, some pathogens and nematodes that have been introduced have become established and provided excellent control and have been introduced in increasing numbers of areas over decades, often after distributions of pests have increased. We summarize 131 introductions, the majority of which have occurred since 1950. The most commonly introduced microorganisms have been fungi, viruses and nematodes, although microsporidia, bacteria and oomycetes have also been introduced; among these groups, viruses were the most successful in establishing followed by nematodes, fungi and microsporidia. All major orders of insects and prostigmatid mites have been targeted and in 63.6% of the programs the pests being targeted were invasive species and not native. Pathogens and nematodes yielded excellent success in establishment against sawflies and wood wasps (100% of programs) and 40-48% establishment among other host orders. Classical biological control has been used for long-term control of arthropod pests on islands almost as much as in mainland areas. It has been used most frequently in perennial systems and highest rates of establishment of arthropod pathogens and insect parasitic nematodes were documented from forests (63.0%) and tree crops (66.7%). One explanation for the low number of releases of arthropod pathogens and insect parasitic nematodes has been confusing and difficult regulations but recent changes and institution of the FAO's Code of Conduct is expected to improve scientists' ability to introduce microbial natural enemies for classical biological control.
Isolates of Steinernema feltiae SN from France, Steinernema glaseri NJ from New Jersey, Steinerne... more Isolates of Steinernema feltiae SN from France, Steinernema glaseri NJ from New Jersey, Steinernema riobrave TX from Texas, Steinernema carpocapsae Sal from Indiana, S. carpocapsae All from Georgia, and Heterorhabditis marelata IN from Indiana were screened for efficacy against laboratory colonies of Asian longhorned beetle, Anoplophora, glabripennis collected from Queens, New York and Chicago, Illinois. Two bioassays were used to screen nematode effects on beetle larvae; a filter paper assay using a 24-h exposure of nematode-to-target-insect, and a diet cup bioassay using a 72-h exposure of host larvae to infective juveniles applied to the larval bore hole made in the artificial diet in the cups. First-and third-stage larvae were susceptible to all isolates using a filter paper bioassay. S. feltiae and S. carpocapsae Sal were the most effective, causing 100% mortality. S. feltiae was more infectious than S. carpocapsae Sal against third, sixth, and seventh instars. S. riobrave, S. glaseri, and H. marelata were ineffective against the older instars. In the diet cup bioassay, S. feltiae and S. carpocapsae Sal killed 71-100% of mid-to late instar larvae, but the remaining isolates screened were ineffective. Nematode preconditioning to aqueous A. glabripennis frass extracts inhibited S. carpocapsae Sal infectivity but had no effect on nematode pathogenicity. S. feltiae juveniles were positively attracted to A. glabripennis frass extracts. Our results demonstrate the potential use of S. feltiae and S. carpocapsae isolates as control agents for A. glabripennis. Published by Elsevier Inc.
Extracts from the digestive tract of final instar larvae of Spodoptera litura, reared on artifici... more Extracts from the digestive tract of final instar larvae of Spodoptera litura, reared on artificial diet, contained trypsin-like (BApNA-hydrolysing) activity with a pH optimum of 10.5, an elastase-like (SA2PLpNA-hydrolysing) activity with a pH optimum of 10.5 and leucine aminopeptidase activity with a pH optimum of 8.5. No chymotrypsin amidase-like (BTpNA-hydrolysing) activity could be detected, but chymotrypsin esterase-like (BTEE-hydrolysing) activity was
Microorganisms are enormous but largely untapped natural resources for biological control of pest... more Microorganisms are enormous but largely untapped natural resources for biological control of pests and diseases. There are two primary reasons for their underployment for pest or disease control: (1) the technical difficulties of using microorganisms for biological control, owing to a lack of fundamental information on them and their ecology, and (2) the costs of product development and regulatory approvals required for each strain, formulation, and use. Agriculture and forestry benefit greatly from the resident communities of microorganisms responsible for naturally occurring biological control of pest species, but additional benefits are achieved by introducing/applying them when or where needed. This can be done as (1) an inoculative release, (2) an augmentative application, or (3) an inundative application. Because of their specificity, different microbial biocontrol agents typically are needed to control different pests or the same pest in different environments. Four potential adverse effects are identified as safety issues (hazards) associated with the use of microorganisms for the biological control of plant pests and diseases. These are: (1) displacement of nontarget microorganisms, (2) allergenicity to humans and other animals, (3) toxigenicity to nontarget organisms, and (4) pathogenicity to nontarget organisms. Except for allergenicity, these are the same attributes that contribute to the efficacy of microbial biocontrol agents toward the target pest species. The probability of occurrence of a particular adverse nontarget effect of a microbial biocontrol agent may be a function of geographic origin or a specific trait genetically added or modified, but the safety issues are the still the same, including whether the microorganism intended for pest or disease control is indigenous, nonindigenous (imported and released), or genetically modified by traditional or recombinant DNA (rDNA) technology. Likewise, the probability of occurrence of a particular adverse nontarget effect may vary with method of application, e.g., whether as an aerosol, soil treatment, baits, or seed treatment, and may increase with increased scale of use, but the safety issues are still the same, including whether the microorganism is used for an inoculative release or augmentative or inundative application. Existing practices for managing microorganisms in the environment (e.g., plant pathogens, Rhizobium, plant inoculants) provide experience and options for managing the risks of microorganisms applied for pest and disease control. Moreover, experience to date indicates that any adverse nontarget effects, should they occur, are likely to be short-term or transitory effects that can, if significant, be eliminated by terminating use of the microbial biocontrol agent. In contrast, production agriculture as currently practiced, such as the use of tillage and crop rotations, has significant and long-term effects on nontarget organisms, including the intentional and unintentional displacement of microorganisms. Even the decision to leave plant pests and diseases unmanaged could have significant long-term environmental effects on nontarget organisms. Potential safety issues associated with the use of microbial biocontrol must therefore be properly identified and compared with the impact of other options for managing the pest or leaving the pest unmanaged. This paper provides a scientific framework for this process. r
The host specificity of microsporidian pathogens of Lepidoptera was studied in Bulgaria where nat... more The host specificity of microsporidian pathogens of Lepidoptera was studied in Bulgaria where native populations of Lymantria dispar and their endemic microsporidia occur. L. dispar and sympatric lepidopteran larvae were collected from four sites in central and western Bulgaria. Three species of microsporidia, Vairimorpha sp., Nosema sp., and Endoreticulatus sp. are known to be endemic in three L. dispar populations, with one species in each population. No microsporidia were found in a fourth L. dispar population. In addition to the L. dispar microsporidia, 11 isolates of microsporidia were recovered from the 1494 individual lepidopteran hosts collected in these sites. When fed to L. dispar, 3 isolates produced infections that were atypical of infections in the natural hosts; one additional isolate produced an atypical infection in Spodoptera exigua. A Nosema sp. isolated from a noctuid host produced heavy infections in L. dispar larvae. Sequencing revealed that the noctuid microsporidium and the closely related Vairimorpha sp. and Nosema sp. microsporidia from L. dispar are distinctly different isolates. These investigations strengthen previous laboratory predictions of narrow host ranges for the Nosema and Vairimorpha microsporidia recovered from L. dispar in Europe. In addition, the Endoreticulatus sp., which was predicted from laboratory studies to be a generalist, was not found in Lepidoptera species sympatric with L. dispar. The results from our study indicate that laboratory testing may considerably underestimate the host specificity of many terrestrial microsporidia. Nevertheless, infectivity to nontarget hosts in the laboratory may set the stage for understanding the evolution of closely related microsporidia found in different host species.
The general basis of cancer is the loss of cell identity and inappropriate proliferation of cells... more The general basis of cancer is the loss of cell identity and inappropriate proliferation of cells. Classically, a universal paradigm in oncogenesis is the accumulation of mutations in the open reading frames of protein-encoding oncogenes and tumor suppressors. The identification of new classes of noncoding RNAs (ncRNA) important for development and cell homeostasis will likely change this current paradigm. Recent
Background: Variability in the demand for any service is a significant barrier to efficient distr... more Background: Variability in the demand for any service is a significant barrier to efficient distribution of limited resources. In health care, demand is often highly variable and access may be limited when peaks cannot be accommodated in a downsized care delivery system. Intensive care units may frequently present bottlenecks to patient flow, and saturation of these services limits a hospital's responsiveness to new emergencies.
Proceedings of The National Academy of Sciences, 2006
DICER is a key enzyme that processes microRNA and small interfering RNA precursors into their sho... more DICER is a key enzyme that processes microRNA and small interfering RNA precursors into their short mature forms, enabling them to regulate gene expression. Only a single Dicer gene exists in the mouse genome, and it is broadly expressed in developing tissues. Dicer-null mutants die before gastrulation. Therefore, to study Dicer function in the later event of lung formation, we
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