Journal articles on the topic 'Fly-derived DNA'
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1
Schubert, Grit, Melanie Stockhausen, Constanze Hoffmann, Kevin Merkel, Linda Vigilant, Fabian H. Leendertz, and Sébastien Calvignac-Spencer. "Targeted detection of mammalian species using carrion fly-derived DNA." Molecular Ecology Resources 15, no. 2 (August 4, 2014): 285–94. http://dx.doi.org/10.1111/1755-0998.12306.
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Gogarten, Jan F., Constanze Hoffmann, Mimi Arandjelovic, Andreas Sachse, Kevin Merkel, Paula Dieguez, Anthony Agbor, et al. "Fly‐derived DNA and camera traps are complementary tools for assessing mammalian biodiversity." Environmental DNA 2, no. 1 (October 29, 2019): 63–76. http://dx.doi.org/10.1002/edn3.46.
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Calvignac‐Spencer, Sébastien, Kevin Merkel, Nadine Kutzner, Hjalmar Kühl, Christophe Boesch, Peter M. Kappeler, Sonja Metzger, Grit Schubert, and Fabian H. Leendertz. "Carrion fly‐derived DNA as a tool for comprehensive and cost‐effective assessment of mammalian biodiversity." Molecular Ecology 22, no. 4 (January 8, 2013): 915–24. http://dx.doi.org/10.1111/mec.12183.
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Kamakaka, R. T., P. D. Kaufman, B. Stillman, P. G. Mitsis, and J. T. Kadonaga. "Simian virus 40 origin- and T-antigen-dependent DNA replication with Drosophila factors in vitro." Molecular and Cellular Biology 14, no. 8 (August 1994): 5114–22. http://dx.doi.org/10.1128/mcb.14.8.5114-5122.1994.
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DNA replication of double-stranded simian virus 40 (SV40) origin-containing plasmids, which has been previously thought to be a species-specific process that occurs only with factors derived from primate cells, is catalyzed with an extract derived from embryos of the fruit fly Drosophila melanogaster. This reaction is dependent upon both large T antigen, the SV40-encoded replication initiator protein and DNA helicase, and a functional T-antigen binding site at the origin of DNA replication. The efficiency of replication with extracts derived from Drosophila embryos is approximately 10% of that observed with extracts prepared from human 293 cells. This activity is not a unique property of embryonic extracts, as cytoplasmic extracts from Drosophila tissue culture cells also support T-antigen-mediated replication of SV40 DNA. By using highly purified proteins, DNA synthesis is initiated by Drosophila polymerase alpha-primase in a T-antigen-dependent manner in the presence of Drosophila replication protein A (RP-A; also known as single-stranded DNA-binding protein), but neither human RP-A nor Escherichia coli single-stranded DNA-binding protein could substitute for Drosophila RP-A. In reciprocal experiments, however, Drosophila RP-A was able to substitute for human RP-A in reactions carried out with human polymerase alpha-primase. These results collectively indicate that many of the specific functional interactions among T antigen, polymerase alpha-primase, and RP-A are conserved from primates to Drosophila species. Moreover, the observation that SV40 DNA replication can be performed with Drosophila factors provides a useful assay for the study of bidirectional DNA replication in Drosophila species in the context of a complete replication reaction.
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Kamakaka, R. T., P. D. Kaufman, B. Stillman, P. G. Mitsis, and J. T. Kadonaga. "Simian virus 40 origin- and T-antigen-dependent DNA replication with Drosophila factors in vitro." Molecular and Cellular Biology 14, no. 8 (August 1994): 5114–22. http://dx.doi.org/10.1128/mcb.14.8.5114.
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DNA replication of double-stranded simian virus 40 (SV40) origin-containing plasmids, which has been previously thought to be a species-specific process that occurs only with factors derived from primate cells, is catalyzed with an extract derived from embryos of the fruit fly Drosophila melanogaster. This reaction is dependent upon both large T antigen, the SV40-encoded replication initiator protein and DNA helicase, and a functional T-antigen binding site at the origin of DNA replication. The efficiency of replication with extracts derived from Drosophila embryos is approximately 10% of that observed with extracts prepared from human 293 cells. This activity is not a unique property of embryonic extracts, as cytoplasmic extracts from Drosophila tissue culture cells also support T-antigen-mediated replication of SV40 DNA. By using highly purified proteins, DNA synthesis is initiated by Drosophila polymerase alpha-primase in a T-antigen-dependent manner in the presence of Drosophila replication protein A (RP-A; also known as single-stranded DNA-binding protein), but neither human RP-A nor Escherichia coli single-stranded DNA-binding protein could substitute for Drosophila RP-A. In reciprocal experiments, however, Drosophila RP-A was able to substitute for human RP-A in reactions carried out with human polymerase alpha-primase. These results collectively indicate that many of the specific functional interactions among T antigen, polymerase alpha-primase, and RP-A are conserved from primates to Drosophila species. Moreover, the observation that SV40 DNA replication can be performed with Drosophila factors provides a useful assay for the study of bidirectional DNA replication in Drosophila species in the context of a complete replication reaction.
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Rodgers, Torrey W., Charles C. Y. Xu, Jacalyn Giacalone, Karen M. Kapheim, Kristin Saltonstall, Marta Vargas, Douglas W. Yu, Panu Somervuo, W. Owen McMillan, and Patrick A. Jansen. "Carrion fly-derived DNA metabarcoding is an effective tool for mammal surveys: Evidence from a known tropical mammal community." Molecular Ecology Resources 17, no. 6 (August 19, 2017): e133-e145. http://dx.doi.org/10.1111/1755-0998.12701.
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Abbasi, Ibrahim, Artur Trancoso Lopo de Queiroz, Oscar David Kirstein, Abdelmajeed Nasereddin, Ben Zion Horwitz, Asrat Hailu, Ikram Salah, et al. "Plant-feeding phlebotomine sand flies, vectors of leishmaniasis, preferCannabis sativa." Proceedings of the National Academy of Sciences 115, no. 46 (October 29, 2018): 11790–95. http://dx.doi.org/10.1073/pnas.1810435115.
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Blood-sucking phlebotomine sand flies (Diptera: Psychodidae) transmit leishmaniasis as well as arboviral diseases and bartonellosis. Sand fly females become infected withLeishmaniaparasites and transmit them while imbibing vertebrates’ blood, required as a source of protein for maturation of eggs. In addition, both females and males consume plant-derived sugar meals as a source of energy. Plant meals may comprise sugary solutions such as nectar or honeydew (secreted by plant-sucking homopteran insects), as well as phloem sap that sand flies obtain by piercing leaves and stems with their needle-like mouthparts. Hence, the structure of plant communities can influence the distribution and epidemiology of leishmaniasis. We designed a next-generation sequencing (NGS)–based assay for determining the source of sand fly plant meals, based upon the chloroplast DNA gene ribulose bisphosphate carboxylase large chain (rbcL). Here, we report on the predilection of several sand fly species, vectors of leishmaniasis in different parts of the world, for feeding onCannabis sativa. We infer this preference based on the substantial percentage of sand flies that had fed onC. sativaplants despite the apparent “absence” of these plants from most of the field sites. We discuss the conceivable implications of the affinity of sand flies forC. sativaon their vectorial capacity forLeishmaniaand the putative exploitation of their attraction toC. sativafor the control of sand fly-borne diseases.
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Haymer, David S., Donald O. Mcinnis, and Loretta Arcangeli. "Genetic variation between strains of the Mediterranean fruit fly, Ceratitis capitata, detected by DNA fingerprinting." Genome 35, no. 3 (June 1, 1992): 528–33. http://dx.doi.org/10.1139/g92-077.
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DNA fingerprinting has been used to detect genetic variation in the Mediterranean fruit fly, Ceratitis capitata. Three different probes have been identified that can be used to detect DNA restriction fragment length polymorphisms between strains of this species. The strains used in this study differ only in terms of their geographic origin or genetic background. One of the probes used is the bacteriophage vector M13, and the other two are repetitive sequences derived from the medfly genome based on a weak homology to M13. Within a strain, each probe produces a consistent restriction fragment profile that is not affected by the method or timing of DNA extraction. Between strains, when M13 is used as a probe, an average of 10% of the observable bands are polymorphic. Use of the medfly genomic sequences as a probe increases the proportion of polymorphic bands between strains up to 30%. The fact that genetic differences between even such closely related strains can be reliably detected by this method holds great promise for studies of insect pests including the ability to monitor the movements of pest species, determining the extent of genetic variation in pest populations, and in making identifications from otherwise unidentifiable material.Key words: genetic variation, Ceratitis capitata, DNA fingerprinting.
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Lee, J. H., S. M. Kaeppler, R. A. Graybosch, and R. G. Sears. "A PCR assay for detection of a 2RL.2BS wheat–rye chromosome translocation." Genome 39, no. 3 (June 1, 1996): 605–8. http://dx.doi.org/10.1139/g96-076.
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A 2RL.2BS wheat–rye translocation, present in the wheat germplasm line Hamlet, carries a gene for resistance to Hessian fly biotype L, one of the most virulent biotypes presently encountered in wheat production environments. Unlike several other wheat–rye chromosome translocations common in wheat breeding programs, 2RL lacks genes encoding storage proteins or other easily selected markers. Oligonucleotide primers synthesized from published sequences derived from the R173 family of moderately repetitive rye DNA were used in the DNA polymerase chain reaction (PCR) to identify specific markers for 2RL. The same primers, when used with DNA extracted from additional wheat–rye translocation lines of importance to the wheat breeding community, gave distinctive PCR products for each genotype. The single primer pair, PAWS5 and PAWS6, may, therefore, have wide applicability for the identification of wheat–rye chromosomal translocations presently encountered in wheat breeding populations. Key words : 2RL.2BS wheat–rye chromosome translocation, polymerase chain reaction, detection.
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Duncan, G. A., P. H. Adler, K. P. Pruess, and T. O. Powers. "Molecular differentiation of two sibling species of the black fly Simulium vittatum (Diptera: Simuliidae) based on random amplified polymorphic DNA." Genome 47, no. 2 (April 1, 2004): 373–79. http://dx.doi.org/10.1139/g03-144.
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Larvae of the black fly morphospecies Simulium vittatum from Colorado, Montana, Nebraska, and New Hampshire were cytologically identified as either the IS-7 or the IIIL-1 cytospecies. DNA was PCR amplified from cytotyped larvae using eight 10-mer primers, labeled with 33P, and run on polyacrylamide gels. The entire data set of 96 amplicons produced incomplete separation of the two cytospecies when subjected to neighbor-joining and maximum parsimony analyses. However, when analyzed within geographical regions, separate species status was supported. Bootstrap support for distinctness of the two cytospecies was best in Colorado where they were collected in true sympatry. The IS-7 cytospecies was more polymorphic in the western states, where it differed most from IIIL-1, which was most variable in the eastern states. The frequencies of the 17 most common amplicons in the two cytospecies were inversely correlated. A model of speciation derived from the molecular evidence suggests that IS-7 evolved in the west and spread eastward, whereas IIIL-1 later originated in the east and spread westward.Key words: Simulium vittatum, cytospecies, RAPD analysis, molecular markers, population structure.
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González, Mikel Alexander, Daniel Bravo-Barriga, María Altagracia Rodríguez-Sosa, Juan Rueda, Eva Frontera, and Pedro María Alarcón-Elbal. "Species Diversity, Habitat Distribution, and Blood Meal Analysis of Haematophagous Dipterans Collected by CDC-UV Light Traps in the Dominican Republic." Pathogens 11, no. 7 (June 21, 2022): 714. http://dx.doi.org/10.3390/pathogens11070714.
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Haematophagous insects cause major economic losses by both direct damage and the transmission of pathogens. However, the biting Diptera species in the Caribbean region have been poorly documented. During 2021, CDC downdraft suction traps with UV light were employed to assess both the species occurrence and blood meal sources across three different habitats in the Dominican Republic. Eighteen species of mosquitoes (n = 274), six species of Culicoides (n = 803), two black fly species (n = 2), and one species of muscid fly (n = 25) were identified at species-level by morphology and/or molecular phylogenetic approaches based on the mitochondrial cytochrome c oxidase subunit 1 (COI). Engorged mosquito (n = 5) and Culicoides (n = 28) females showed host preferences derived exclusively from mammals (cows and pigs), except Culex species containing the blood of chickens. Our study provides new records of the Diptera Dominican catalogue (Culex salinarius for the Greater Antilles, Culicoides jamaicensis for Hispaniola, and Culicoides haitiensis and Culicoides borinqueni for the Dominican Republic), the first available COI DNA sequences of different Diptera in the GenBank, some pictures of diagnostic features of closely related specimens, spatial distribution across the habitats studied, and new insights on their feeding preferences in the Caribbean region.
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Kang, David, and Angela E. Douglas. "Functional traits of the gut microbiome correlated with host lipid content in a natural population of Drosophila melanogaster." Biology Letters 16, no. 2 (February 2020): 20190803. http://dx.doi.org/10.1098/rsbl.2019.0803.
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Most research on the nutritional significance of the gut microbiome is conducted on laboratory animals, and its relevance to wild animals is largely unknown. This study investigated the microbiome correlates of lipid content in individual wild fruit flies, Drosophila melanogaster . Lipid content varied 3.6-fold among the flies and was significantly correlated with the abundance of gut-derived bacterial DNA sequences that were assigned to genes contributing to 16 KEGG pathways. These included genes encoding sugar transporters and enzymes in glycolysis/gluconeogenesis, potentially promoting sugar consumption by the gut microbiome and, thereby, a lean fly phenotype. Furthermore, the lipid content of wild flies was significantly lower than laboratory flies, indicating that, as for some mammalian models, certain laboratory protocols might be obesogenic for Drosophila . This study demonstrates the value of research on natural populations to identify candidate microbial genes that influence ecologically important host traits.
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Lawson, Matthew J., Zoe C. Prytherch, Tim P. Jones, Rachel A. Adams, and Kelly A. BéruBé. "Iron-Rich Magnetic Coal Fly Ash Particles Induce Apoptosis in Human Bronchial Cells." Applied Sciences 10, no. 23 (November 25, 2020): 8368. http://dx.doi.org/10.3390/app10238368.
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Svalbard is an arctic archipelago where coal mining generates all electricity via the local coal-fired power station. Coal combustion produces a waste product in the form of particulate matter (PM) coal fly ash (CFA), derived from incombustible minerals present in the feed coal. PM ≤10 µm (diameter) may be “inhaled” into the human respiratory system, and particles ≤2.5 µm may enter the distal alveoli to disrupt normal pulmonary functions and trigger disease pathways. This study discovered that Svalbard CFA contained unusually high levels of iron-rich magnetic minerals that induced adverse effects upon human lungs cells. Iron is a well-characterised driver of reactive oxygen species (ROS) generation, a driving force for cell death and disease. CFA physicochemical characterisation showed non-uniform particle morphologies indicative of coal burnt at inefficient combustion temperatures. The bioreactivity (ROS generation) of PM2.5/10 fractions was measured using plasmid scission assay (PSA, DNA damage) and haemolysis assays (erythrocyte lysis), with PM2.5 CFA showing significant bioreactivity. CFA leached in mild acid caused a significant increase in toxicity, which could occur in CFA waste-stores. The CFA and leachates were exposed to a surrogate model of human bronchial epithelia that confirmed that CFA induced apoptosis in bronchial cells. This study shows that CFA containing magnetic iron-rich minerals mediated adverse reactions in the human lung, and thus CFA should be considered to be an environmental inhalation hazard.
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Feder, Jeffrey L., Joseph B. Roethele, Kenneth Filchak, Julie Niedbalski, and Jeanne Romero-Severson. "Evidence for Inversion Polymorphism Related to Sympatric Host Race Formation in the Apple Maggot Fly, Rhagoletis pomonella." Genetics 163, no. 3 (March 1, 2003): 939–53. http://dx.doi.org/10.1093/genetics/163.3.939.
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Abstract Evidence suggests that the apple maggot, Rhagoletis pomonella (Diptera: Tephritidae) is undergoing sympatric speciation (i.e., divergence without geographic isolation) in the process of shifting and adapting to a new host plant. Prior to the introduction of cultivated apples (Malus pumila) in North America, R. pomonella infested the fruit of native hawthorns (Crataegus spp.). However, sometime in the mid-1800s the fly formed a sympatric race on apple. The recently derived apple-infesting race shows consistent allele frequency differences from the hawthorn host race for six allozyme loci mapping to three different chromosomes. Alleles at all six of these allozymes correlate with the timing of adult eclosion, an event dependent on the duration of the overwintering pupal diapause. This timing difference differentially adapts the univoltine fly races to an ∼3- to 4-week difference in the peak fruiting times of apple and hawthorn trees, partially reproductively isolating the host races. Here, we report finding substantial gametic disequilibrium among allozyme and complementary DNA (cDNA) markers encompassing the three chromosomal regions differentiating apple and hawthorn flies. The regions of disequilibrium extend well beyond the previously characterized six allozyme loci, covering substantial portions of chromosomes 1, 2, and 3 (haploid n = 6 in R. pomonella). Moreover, significant recombination heterogeneity and variation in gene order were observed among single-pair crosses for each of the three genomic regions, implying the existence of inversion polymorphism. We therefore have evidence that genes affecting diapause traits involved in host race formation reside within large complexes of rearranged genes. We explore whether these genomic regions (inversions) constitute coadapted gene complexes and discuss the implications of our findings for sympatric speciation in Rhagoletis.
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Stoffolano, John G. "Synanthropic Flies—A Review Including How They Obtain Nutrients, along with Pathogens, Store Them in the Crop and Mechanisms of Transmission." Insects 13, no. 9 (August 27, 2022): 776. http://dx.doi.org/10.3390/insects13090776.
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An attempt has been made to provide a broad review of synanthropic flies and, not just a survey of their involvement in human pathogen transmission. It also emphasizes that the crop organ of calliphorids, sarcophagids, and muscids was an evolutionary development and has served and assisted non-blood feeding flies in obtaining food, as well as pathogens, prior to the origin of humans. Insects are believed to be present on earth about 400 million years ago (MYA). Thus, prior to the origin of primates, there was adequate time for these flies to become associated with various animals and to serve as important transmitters of pathogens associated with them prior to the advent of early hominids and modern humans. Through the process of fly crop regurgitation, numerous pathogens are still readily being made available to primates and other animals. Several studies using invertebrate-derived DNA = iDNA meta-techniques have been able to identify, not only the source the fly had fed on, but also if it had fed on their feces or the animal's body fluids. Since these flies are known to feed on both vertebrate fluids (i.e., from wounds, saliva, mucus, or tears), as well as those of other animals, and their feces, identification of the reservoir host, amplification hosts, and associated pathogens is essential in identifying emerging infectious diseases. New molecular tools, along with a focus on the crop, and what is in it, should provide a better understanding and development of whether these flies are involved in emerging infectious diseases. If so, epidemiological models in the future might be better at predicting future epidemics or pandemics.
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Odgers, Wendy A., Charles F. Aquadro, Christopher W. Coppin, Marion J. Healy, and John G. Oakeshott. "Nucleotide Polymorphism in theEst6Promoter, Which Is Widespread in Derived Populations ofDrosophila melanogaster, Changes the Level of Esterase 6 Expressed in the Male Ejaculatory Duct." Genetics 162, no. 2 (October 1, 2002): 785–97. http://dx.doi.org/10.1093/genetics/162.2.785.
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AbstractPrevious analysis of an Australian population of D. melanogaster revealed two predominant Est6 promoter haplotypes, P1 and P7. These haplotypes, which differ at 14 sites over a 325-bp region, are associated with a 15-20% difference in male EST6 activity. Here we show that the P1/P7 sequence difference causes the male activity variation by recreating the activity difference among >60 independently transformed lines containing representative P1 or P7 promoter alleles fused to an identical Est6 coding region. Furthermore we find that the whole fly difference reflects about a twofold difference in EST6 activity in the anterior sperm ejaculatory duct. EST6 activity variation in this tissue is known to affect reproductive fitness. Using a combination of RFLP analysis and DNA sequencing, we show that P1 and P7 are predominant in six populations from America, Asia, and Australia, albeit less frequent in a population from the presumptively ancestral east African range of the species. The sequence data show significant departures from neutral expectations for the derived American and Australian populations but not the presumptively ancestral Zimbabwean population. Thus the P1/P7 difference could be a major source of adaptively significant EST6 activity variation through much of the now cosmopolitan range of D. melanogaster.
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Ang, S. L., A. Wierda, D. Wong, K. A. Stevens, S. Cascio, J. Rossant, and K. S. Zaret. "The formation and maintenance of the definitive endoderm lineage in the mouse: involvement of HNF3/forkhead proteins." Development 119, no. 4 (December 1, 1993): 1301–15. http://dx.doi.org/10.1242/dev.119.4.1301.
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Little is known about genes that govern the development of the definitive endoderm in mammals; this germ layer gives rise to the intestinal epithelium and various other cell types, such as hepatocytes, derived from the gut. The discovery that the rat hepatocyte transcription factor HNF3 is similar to the Drosophila forkhead gene, which plays a critical role in gut development in the fly, led us to isolate genes containing the HNF3/forkhead (HFH) domain that are expressed in mouse endoderm development. We recovered mouse HNF3 beta from an embryo cDNA library and found that the gene is first expressed in the anterior portion of the primitive streak at the onset of gastrulation, in a region where definitive endoderm first arises. Its expression persists in axial structures derived from the mouse equivalent of Hensen's node, namely definitive endoderm and notochord, and in the ventral region of the developing neural tube. Expression of the highly related gene, HNF3 alpha, appears to initiate later than HNF3 beta and is first seen in midline endoderm cells. Expression subsequently appears in notochord, ventral neural tube, and gut endoderm in patterns similar to HNF3 beta. Microscale DNA binding assays show that HNF3 proteins are detectable in the midgut at 9.5 days p.c. At later stages HNF3 mRNAs and protein are expressed strongly in endoderm-derived tissues such as the liver. HNF3 is also the only known hepatocyte-enriched transcription factor present in a highly de-differentiated liver cell line that retains the capacity to redifferentiate to the hepatic phenotype. Taken together, these studies suggest that HNF3 alpha and HNF3 beta are involved in both the initiation and maintenance of the endodermal lineage. We also discovered a novel HFH-containing gene, HFH-E5.1, that is expressed transiently in posterior ectoderm and mesoderm at the primitive streak stage, and later predominantly in the neural tube. HFH-E5.1 is highly similar in structure and expression profile to the Drosophila HFH gene FD4, suggesting that HFH family members have different, evolutionarily conserved roles in development.
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Wang, Liangjun, Neal Jahren, Marcus L. Vargas, Erica F. Andersen, Judith Benes, Junyu Zhang, Ellen L. Miller, Richard S. Jones, and Jeffrey A. Simon. "Alternative ESC and ESC-Like Subunits of a Polycomb Group Histone Methyltransferase Complex Are Differentially Deployed during Drosophila Development." Molecular and Cellular Biology 26, no. 7 (April 1, 2006): 2637–47. http://dx.doi.org/10.1128/mcb.26.7.2637-2647.2006.
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ABSTRACT The Extra sex combs (ESC) protein is a Polycomb group (PcG) repressor that is a key noncatalytic subunit in the ESC-Enhancer of zeste [E(Z)] histone methyltransferase complex. Survival of esc homozygotes to adulthood based solely on maternal product and peak ESC expression during embryonic stages indicate that ESC is most critical during early development. In contrast, two other PcG repressors in the same complex, E(Z) and Suppressor of zeste-12 [SU(Z)12], are required throughout development for viability and Hox gene repression. Here we describe a novel fly PcG repressor, called ESC-Like (ESCL), whose biochemical, molecular, and genetic properties can explain the long-standing paradox of ESC dispensability during postembryonic times. Developmental Western blots show that ESCL, which is 60% identical to ESC, is expressed with peak abundance during postembryonic stages. Recombinant complexes containing ESCL in place of ESC can methylate histone H3 with activity levels, and lysine specificity for K27, similar to that of the ESC-containing complex. Coimmunoprecipitations show that ESCL associates with E(Z) in postembryonic cells and chromatin immunoprecipitations show that ESCL tracks closely with E(Z) on Ubx regulatory DNA in wing discs. Furthermore, reduced escl + dosage enhances esc loss-of-function phenotypes and double RNA interference knockdown of ESC/ESCL in wing disc-derived cells causes Ubx derepression. These results suggest that ESCL and ESC have similar functions in E(Z) methyltransferase complexes but are differentially deployed as development proceeds.
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Schroeder, Analyne M., Massoud Allahyari, Georg Vogler, Maria A. Missinato, Tanja Nielsen, Michael S. Yu, Jeanne L. Theis, et al. "Model system identification of novel congenital heart disease gene candidates: focus on RPL13." Human Molecular Genetics 28, no. 23 (October 18, 2019): 3954–69. http://dx.doi.org/10.1093/hmg/ddz213.
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Abstract Genetics is a significant factor contributing to congenital heart disease (CHD), but our understanding of the genetic players and networks involved in CHD pathogenesis is limited. Here, we searched for de novo copy number variations (CNVs) in a cohort of 167 CHD patients to identify DNA segments containing potential pathogenic genes. Our search focused on new candidate disease genes within 19 deleted de novo CNVs, which did not cover known CHD genes. For this study, we developed an integrated high-throughput phenotypical platform to probe for defects in cardiogenesis and cardiac output in human induced pluripotent stem cell (iPSC)-derived multipotent cardiac progenitor (MCPs) cells and, in parallel, in the Drosophila in vivo heart model. Notably, knockdown (KD) in MCPs of RPL13, a ribosomal gene and SON, an RNA splicing cofactor, reduced proliferation and differentiation of cardiomyocytes, while increasing fibroblasts. In the fly, heart-specific RpL13 KD, predominantly at embryonic stages, resulted in a striking ‘no heart’ phenotype. KD of Son and Pdss2, among others, caused structural and functional defects, including reduced or abolished contractility, respectively. In summary, using a combination of human genetics and cardiac model systems, we identified new genes as candidates for causing human CHD, with particular emphasis on ribosomal genes, such as RPL13. This powerful, novel approach of combining cardiac phenotyping in human MCPs and in the in vivo Drosophila heart at high throughput will allow for testing large numbers of CHD candidates, based on patient genomic data, and for building upon existing genetic networks involved in heart development and disease.
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Mandell, Michael A., Wandy L. Beatty, and Stephen M. Beverley. "Quantitative single-cell analysis of Leishmania major amastigote differentiation demonstrates variably extended expression of the lipophosphoglycan (LPG) virulence factor in different host cell types." PLOS Neglected Tropical Diseases 16, no. 10 (October 27, 2022): e0010893. http://dx.doi.org/10.1371/journal.pntd.0010893.
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Immediately following their deposition into the mammalian host by an infected sand fly vector, Leishmania parasites encounter and are engulfed by a variety of cell types. From there, parasites may transit to other cell types, primarily macrophages or dendritic cells, where they replicate and induce pathology. During this time, Leishmania cells undergo a dramatic transformation from the motile non-replicating metacyclic stage to the non-motile replicative amastigote stage, a differentiative process that can be termed amastigogenesis. To follow this at the single cell level, we identified a suite of experimental ‘landmarks’ delineating different stages of amastigogenesis qualitatively or quantitatively, including new uses of amastigote-specific markers that showed interesting cellular localizations at the anterior or posterior ends. We compared amastigogenesis in synchronous infections of peritoneal and bone-marrow derived macrophages (PEM, BMM) or dendritic cells (BMDC). Overall, the marker suite expression showed an orderly transition post-infection with similar kinetics between host cell types, with the emergence of several amastigote traits within 12 hours, followed by parasite replication after 24 hours, with parasites in BMM or BMDC initiating DNA replication more slowly. Lipophosphoglycan (LPG) is a Leishmania virulence factor that facilitates metacyclic establishment in host cells but declines in amastigotes. Whereas LPG expression was lost by parasites within PEM by 48 hours, >40% of the parasites infecting BMM or BMDC retained metacyclic-level LPG expression at 72 hr. Thus L. major may prolong LPG expression in different intracellular environments, thereby extending its efficacy in promoting infectivity in situ and during cell-to-cell transfer of parasites expressing this key virulence factor.
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Li, Hongde, Geetanjali Chawla, Alexander J. Hurlburt, Maria C. Sterrett, Olga Zaslaver, James Cox, Jonathan A. Karty, Adam P. Rosebrock, Amy A. Caudy, and Jason M. Tennessen. "Drosophila larvae synthesize the putative oncometabolite L-2-hydroxyglutarate during normal developmental growth." Proceedings of the National Academy of Sciences 114, no. 6 (January 23, 2017): 1353–58. http://dx.doi.org/10.1073/pnas.1614102114.
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L-2-hydroxyglutarate (L-2HG) has emerged as a putative oncometabolite that is capable of inhibiting enzymes involved in metabolism, chromatin modification, and cell differentiation. However, despite the ability of L-2HG to interfere with a broad range of cellular processes, this molecule is often characterized as a metabolic waste product. Here, we demonstrate that Drosophila larvae use the metabolic conditions established by aerobic glycolysis to both synthesize and accumulate high concentrations of L-2HG during normal developmental growth. A majority of the larval L-2HG pool is derived from glucose and dependent on the Drosophila estrogen-related receptor (dERR), which promotes L-2HG synthesis by up-regulating expression of the Drosophila homolog of lactate dehydrogenase (dLdh). We also show that dLDH is both necessary and sufficient for directly synthesizing L-2HG and the Drosophila homolog of L-2-hydroxyglutarate dehydrogenase (dL2HGDH), which encodes the enzyme that breaks down L-2HG, is required for stage-specific degradation of the L-2HG pool. In addition, dLDH also indirectly promotes L-2HG accumulation via synthesis of lactate, which activates a metabolic feed-forward mechanism that inhibits dL2HGDH activity and stabilizes L-2HG levels. Finally, we use a genetic approach to demonstrate that dLDH and L-2HG influence position effect variegation and DNA methylation, suggesting that this compound serves to coordinate glycolytic flux with epigenetic modifications. Overall, our studies demonstrate that growing animal tissues synthesize L-2HG in a controlled manner, reveal a mechanism that coordinates glucose catabolism with L-2HG synthesis, and establish the fly as a unique model system for studying the endogenous functions of L-2HG during cell growth and proliferation.
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Lustofin, Krzysztof, Piotr Świątek, Piotr Stolarczyk, Vitor F. O. Miranda, and Bartosz J. Płachno. "Do food trichomes occur in Pinguicula (Lentibulariaceae) flowers?" Annals of Botany 126, no. 6 (June 27, 2020): 1039–48. http://dx.doi.org/10.1093/aob/mcaa123.
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Abstract Background and Aims Floral food bodies (including edible trichomes) are a form of floral reward for pollinators. This type of nutritive reward has been recorded in several angiosperm families: Annonaceae, Araceae, Calycanthaceae, Eupomatiaceae, Himantandraceae, Nymphaeaceae, Orchidaceae, Pandanaceae and Winteraceae. Although these bodies are very diverse in their structure, their cells contain food material: starch grains, protein bodies or lipid droplets. In Pinguicula flowers, there are numerous multicellular clavate trichomes. Previous authors have proposed that these trichomes in the Pinguicula flower play the role of ‘futterhaare’ (‘feeding hairs’) and are eaten by pollinators. The main aim of this study was to investigate whether the floral non-glandular trichomes of Pinguicula contain food reserves and thus are a reward for pollinators. The trichomes from the Pinguicula groups, which differ in their taxonomy (species from the subgenera: Temnoceras, Pinguicula and Isoloba) as well as the types of their pollinators (butterflies/flies and bees/hummingbirds), were examined. Thus, it was determined whether there are any connections between the occurrence of food trichomes and phylogeny position or pollination biology. Additionally, we determined the phylogenetic history of edible trichomes and pollinator evolution in the Pinguicula species. Methods The species that were sampled were: Pinguicula moctezumae, P. esseriana, P. moranensis, P. emarginata, P. rectifolia, P. mesophytica, P. hemiepiphytica, P. agnata, P. albida, P. ibarrae, P. martinezii, P. filifolia, P. gigantea, P. lusitanica, P. alpina and P. vulgaris. Light microscopy, histochemistry, and scanning and transmission electron microscopy were used to address our aims with a phylogenetic perspective based on matK/trnK DNA sequences. Key Results No accumulation of protein bodies or lipid droplets was recorded in the floral non-glandular trichomes of any of the analysed species. Starch grains occurred in the cells of the trichomes of the bee-/fly-pollinated species: P. agnata, P. albida, P. ibarrae, P. martinezii, P. filifolia and P. gigantea, but not in P. alpina or P. vulgaris. Moreover, starch grains were not recorded in the cells of the trichomes of the Pinguicula species that have long spurs, which are pollinated by Lepidoptera (P. moctezumae, P. esseriana, P. moranensis, P. emarginata and P. rectifolia) or birds (P. mesophytica and P. hemiepihytica), or in species with a small and whitish corolla that self-pollinate (P. lusitanica). The results on the occurrence of edible trichomes and pollinator syndromes were mapped onto a phylogenetic reconstruction of the genus. Conclusion Floral non-glandular trichomes play the role of edible trichomes in some Pinguicula species (P. agnata, P. albida, P. ibarrae, P. martinezii, P. filifolia and P. gigantea), which are mainly classified as bee-pollinated species that had originated from Central and South America. It seems that in the Pinguicula that are pollinated by other pollinator groups (Lepidoptera and hummingbirds), the non-glandular trichomes in the flowers play a role other than that of a floral reward for their pollinators. Edible trichomes are symplesiomorphic for the Pinguicula species, and thus do not support a monophyletic group such as a synapomorphy. Nevertheless, edible trichomes are derived and are possibly a specialization for fly and bee pollinators by acting as a food reward for these visitors.
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Rohman, Rosyid Kholilur, Setiyo Daru Cahyono, and A. R. Hanung Triyono. "The Influence of Fly Ash Addition on the Compressive Strength of Concrete Containing Recycle Concrete Aggregates." Advanced Materials Research 626 (December 2012): 391–95. http://dx.doi.org/10.4028/www.scientific.net/amr.626.391.
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The rapid economy growth in Indonesia encourages the developments in all fields. One of them is the development of infrastructure on housings, transportations, and irrigation. Constructions of concrete building are used on the road, bridges, buildings, housing, and water buildings. A concrete is a material structure of building that made from mix of sand, gravel, cement and water as adhesive. All the materials of the concrete were derived from the nature. To avoid the excessive exploration of nature resource the method of recycling of used concrete to become new one were needed. The used concrete was used for coarse aggregate. To improve the quality of concrete from the used one, additional material was required, that is, fly ash. The test material were formed of cube of 15x15x15 cm in size. From the result of research, the analysis can be done in order to find the relationship between quantity of fly ash to be added and the quality of concrete can be formulated as y =-34.921x2 + 11.45x + 25.465, in which y is compressive strength and x is the percentage of fly ash. Thus, for maximum addition of fly ash of 16.4 %, it obtains the maximum compressive strength of concrete of 26.4 MPa and the age of concrete is 28 days. The method of recycling of used concrete and the use of fly ash to become the material of new concrete are safe environmentally, which can overcome the nature filthy especially from the waste of used concrete and coal. Therefore, this is in line with the principal of nature preservation, those are Reduce, Reuse dan Recycle.
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Syahrizal, Syahrizal, Ediwarman, Safratilofa, and Muhamat Ridwan. "Analysis of the use of media resulting from bioconversion of organic waste in the production of maggots BSF (black soldier fly)." Jurnal Akuakultur Indonesia 21, no. 1 (January 13, 2022): 1–10. http://dx.doi.org/10.19027/jai.21.1.1-10.
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Maggots is an organism derived from the eggs of the black fly, Hermentia illucens (black soldier fly, BSF), which undergoes metamorphosis in the second phase after the egg phase and before the pupa phase which then turns into an adult fly. The purpose of this study was to analyze the utilization of organic waste substrate on the production of BSF maggots cultivation. This research was conducted outdoor at the Freshwater Aquaculture Fisheries Center (BPBAT) Sungai Gelam Jambi with a completely randomized design (CRD) with 4 treatments and 3 replications; Treatment A: PKM (palm kernel meal) 100%, B (PKM 50% + cabbage vegetable waste 50%), C (PKM 50% + coconut pulp 50%) and D (PKM 50% + coconut pulp 25% + vegetable waste cabbage 25%). The average yield parameter of high maggots biomass in treatment A was 673.67 g/4 kg substrate and the lowest biomass in treatment D was 239.67 g/4 kg substrate. For the average weight and length of the best maggots in treatment A (0.20 g/individual) and (1.83 cm), the lowest was in B (0.12 g/Ind. and 1.58 cm). The highest was in treatment B (5,182.31 individual/4 kg substrate) and the lowest was in D (1,479.44 ind./4 kg substrate. The highest bioconversion value of maggots to organic matter OSE (organic substrate efficiency) was highest in treatment A (16, 84%) and the lowest was in D (5.99%). Technically, treatment A was slightly better than B, while economically the best organic substrate medium for maggots cultivation was in treatment B with a production cost of Rp. 7.257 and the ECR (economic conversion ratio) value of 5.81 was lower than the other 3 treatments.
Keywords: Maggots, black soldier fly, Hermentia illucens, organic waste.
ABSTRAK
Maggots merupakan organisme yang berasal dari telur seranga lalat hitam, Hermentia illucens (black soldier fly, BSF). Tujuan penelitian ini yaitu menganalisis pemanfaatan subtrat limbah organik terhadap produksi budidaya maggots BSF. Penelitian ini dilaksanakan di Balai Perikanan Budidaya Air Tawar (BPBAT) Sungai Gelam, Jambi dengan rancangan acak lengkap (RAL) 4 perlakuan 3 ulangan yaitu perlakuan A : PKM (palm kernel meal) 100%, B (PKM 50% + limbah sayur kol 50%), C (PKM 50% + ampas kelapa 50%), dan D (PKM 50% + ampas kelapa 25%+ limbah sayur kol 25%).Rata-rata biomassa tertinggi didapatkan pada perlakuanA (673,67g/4 kg subtrat) dan biomassa terendah dihasilkan pada perlakuan D (239.67g/4 kg subtrat). Untuk bobot rata-rata dan panjang maggots terbaik dihasilkan pada perlakuan A (0,20 g/individu dan 1,83 cm/individu), terendah pada B (0,12 g/individu dan (1,58 cm). Jumlah populasi maggots yang terbanyak dihasilkan pada perlakuan B (5.182,31 ind./4 kg subtrat) dan terendah pada D (1.479,44 individu/4 kg subtrat). Nilai biokonversi maggots terhadap bahan organik OSEterbaik (organic substrate efficiency) tertinggi pada perlakuan A (16,84%) dan terendah pada D (5,99%). Secara teknis perlakuan A sedikit lebih baik dari B sedangkan secara ekonomi media subtrat organik terbaik untuk budidaya maggots terdapat pada perlakuan B dengan biaya produksi sebesar Rp. 7.257 dan nilai ECR (economic convertion ratio) sebesar 5.81 lebih rendah dari ke 3 perlakuan lainnya.
Kata kunci: Maggots, black soldier fly, Hermentia illucens, limbah organik.
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Selan, Yulfia, Filphin A. Amalo, Inggrid Trinidad Maha, Antin Y. N. Widi, Cynthia D. Gaina, and Beatrix Barut. "KARAKTERISTIK MORFOLOGI DAN DISTRIBUSI KARBOHIDRAT NETRAL PADA UTERUS KELELAWAR BUAH (Pteropus vampyrus) ASAL PULAU TIMOR." JURNAL KAJIAN VETERINER 7, no. 1 (June 11, 2019): 80–84. http://dx.doi.org/10.35508/jkv.v7i1.948.
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Timorese fruit bat(Pteropusvampyrus)is the only fly mammalian with its unique behavior which hanging upside down inspite of its pregnancy. This research is aimed to reveal the morphology of the Timorese fruit bats and the distribution of neutral carbohydrate within this organ. Three uterus samples derived from three different Timorese fruit bats were used in the research.Both macroscopical and microscopical examinations using H&E and PAS methods were applied. Macroscopically, Timorese fruit bats showedsoft reddish white duplex uterus. Meanwhile microscopically, endometrium consisted of epithelial layer and lamina propria and was the place where simple tubular glands located. The epithelial layer comprised of simple cylindric secretory cells and ciliated cells. Neutral carbohydrate distribution was seen within this epithelial layer. Myometrium was a thick circular smooth muscle layer which consisted of smooth muscle separated by collagen and elastic fibre. Perimetrium was a visceral layer and consisted of mesothelial cells.
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Fonseca, Paula, Flavia Ferreira, Felipe da Silva, Liliane Santana Oliveira, João Trindade Marques, Aristóteles Goes-Neto, Eric Aguiar, and Arthur Gruber. "Characterization of a Novel Mitovirus of the Sand Fly Lutzomyia longipalpis Using Genomic and Virus–Host Interaction Signatures." Viruses 13, no. 1 (December 23, 2020): 9. http://dx.doi.org/10.3390/v13010009.
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Hematophagous insects act as the major reservoirs of infectious agents due to their intimate contact with a large variety of vertebrate hosts. Lutzomyia longipalpis is the main vector of Leishmania chagasi in the New World, but its role as a host of viruses is poorly understood. In this work, Lu. longipalpis RNA libraries were subjected to progressive assembly using viral profile HMMs as seeds. A sequence phylogenetically related to fungal viruses of the genus Mitovirus was identified and this novel virus was named Lul-MV-1. The 2697-base genome presents a single gene coding for an RNA-directed RNA polymerase with an organellar genetic code. To determine the possible host of Lul-MV-1, we analyzed the molecular characteristics of the viral genome. Dinucleotide composition and codon usage showed profiles similar to mitochondrial DNA of invertebrate hosts. Also, the virus-derived small RNA profile was consistent with the activation of the siRNA pathway, with size distribution and 5′ base enrichment analogous to those observed in viruses of sand flies, reinforcing Lu. longipalpis as a putative host. Finally, RT-PCR of different insect pools and sequences of public Lu. longipalpis RNA libraries confirmed the high prevalence of Lul-MV-1. This is the first report of a mitovirus infecting an insect host.
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Nugraha, Noviyanti, Muhammad Pramuda Sirodz, and Benardino Hadiwijaya. "Perancangan Alat Pembuangan Abu Pada Gasifier Sistem Kontinu Berbahan Bakar Tongkol Jagung." Jurnal Rekayasa Energi dan Mekanika 1, no. 2 (October 12, 2021): 102. http://dx.doi.org/10.26760/jrem.v1i2.102.
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Abstrak Indonesia membutuhkan energi alternatif yang berpeluang besar untuk dikembangkan pemanfaatannya, salah satunya adalah energi biomassa yang berasal dari jagung. Pada penelitian sebelumnya sudah dirancang dan dibuat sistem gasifikasi kontinu, tetapi masih terdapat kekurangan pada pemisahan abu setelah pembakaran. Tujuan dari penelitian ini adalah untuk merancang sistem pemisah abu pada sistem gasifikasi kontinu sehingga didapatkan spesifikasi dari sistem pemisah abu tersebut. Sistem pemisah abu yang dirancang adalah screw conveyor untuk memisahkan bottom ash dan siklon untuk memisahkan fly ash. Hasil perancangan diperoleh spesifikasi yang dibutuhkan yaitu diameter screw sebesar 6 inci, motor listrik yang digunakan memiliki daya 1 HP, putaran screw sebesar 0,31 rpm dan poros screw conveyor sebesar 2 inci. Dengan standar yang sudah diberikan, dengan mengasumsikan diameter body siklon sebesar 0,1 m maka diperoleh seluruh dimensi siklon. Dengan diameter sebesar 0,1 m secara perhitungan didapat efisiensi siklon sebesar 78% dan secara simulasi menggunakan software ANSYS didapat efisiensi sebesar 80%. Kata kunci: tongkol jagung, gasifikasi, screw conveyor, siklon, ANSYS Abstract Indonesia needs alternative energy that has a great opportunity to be developed its utilization, one of which is biomass energy derived from corn. In previous studies, a continuous gasification system has been designed and built, but there are still deficiencies in the separation of ash after combustion. The purpose of this research is to design an ash separator system in a continuous gasification system so that the specifications of the ash separator system can be obtained. The ash separator system designed is a screw conveyor for separating bottom ash and cyclones for separating fly ash. The design results obtained the required specifications, the screw diameter is 6 inches, the electric motor used has a power of 1 HP, the screw rotation is 0.31 rpm and the screw conveyor shaft is 2 inches. With the standards that have been given, assuming the diameter of the cyclone body is 0.1 m, all the dimensions of the cyclone are obtained. With a diameter of 0.1 m, the calculation is that the cyclone efficiency is 78% and by simulation using the ANSYS software, the efficiency is 80%. Key words: corn cobs, gasification, screw conveyor, cyclone, ANSYS
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Piya, Sujan, Seemana Bhattacharya, Hong Mu, Philip L. Lorenzi, Teresa McQueen, Eric Richard Davis, Vivian Ruvolo, et al. "BRD4 Proteolysis Targeting Chimera (PROTAC) ARV-825, Causes Sustained Degradation of BRD4 and Modulation of Chemokine Receptors, Cell Adhesion and Metabolic Targets in Leukemia Resulting in Profound Anti-Leukemic Effects." Blood 128, no. 22 (December 2, 2016): 748. http://dx.doi.org/10.1182/blood.v128.22.748.748.
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Abstract Background: Mutational or non-mutational epigenetic events that aberrantly modify the chromatin regulatory machinery to enhance oncogene expression are a hallmark of myeloid malignancies. BRD4, a member of the bromodomain and extra terminal domain (BET) family, is a transcriptional coactivator that co-occupies super enhancer complexes associated with transcription of oncogenes (MYC, SOX2, NF-kB etc.) - and apoptosis regulators (Bcl-2, Bcl-XL, etc.) and has been validated as a target in AML therapy1. ARV-825 is a hetero-bifunctional PROteolysis TArgeting Chimera (PROTAC) that recruits BRD4 to the E3 ubiquitin ligase cereblon and leads to efficient and sustained degradation of BRD4 resulting in down-regulation of MYC2. Objectives: We examined the anti-leukemic effect of ARV-825 against AML cell lines, primary AML blasts and a mouse model of disseminated leukemia. Since tumor-stroma interactions driven by oncogene activation play a major role in resistance to AML therapy, we tested whether ARV-825 could overcome stroma-mediated drug resistance. As MYC harmonizes nutrient acquisition by cancer cells through regulation of the metabolites antiporter systems (SLC7A11, SLC5A5) 3, we profiled changes in a few important amino acids and organic acids in AML cell in response to ARV-825. Results : The IC50s for all tested cell lines and primary AML cells at 72 hours were in the low nanomolar range (2-50 nM) and 10-100 times lower than JQ1, a small molecule BRD4 inhibitor. ARV-825 induces sustained BRD4 degradation accompanied by down-regulation of targets such as MYC, anti-apoptotic BCL-2 family molecules and an increase in apoptosis and DNA damage4. In an in vitro tumor-stroma co-culture model including hypoxic conditions, bone marrow derived mesenchymal stromal cells (MSCs) protected OCI-AML3 cells from cytarabine ( 55.4% apoptosis with vs. 35.0% without MSCs in normoxia and 50.6% vs. 32.8%, respectively, in hypoxia), but no such protection was observed against ARV-825 (58.7% apoptosis vs. 55.2% in normoxia and 57.4% vs. 58.3%, respectively, in hypoxia). Mass cytometry based proteomic analysis (CyTOF) (Fig. 1), immunoblotting and flow cytometry showed that among apoptotic, cell adhesion and signaling proteins, MYC, CD44 and surface CXCR4 were the most down-regulated proteins in AML cells. The functional relevance of surface CXCR4 down regulation was confirmed in migration assays against the CXCR4 ligand SDF-1. Phosphorylation of CXCR4 by PIM1 kinase is necessary for surface expression of CXCR4, ARV-825 treatment reduced PIM1 levels and phosphorylation of CXCR4 in AML cells while overexpression of PIM1 or Myc reversed the phenomena. Quantitative PCR and immunoblotting analysis confirmed the transcriptional down regulation of total CD44 and CD44 variants 8-10 (2-fold change treated vs. untreated). As a functional correlate of CD44 variants, mass spectrometry based intracellular metabolomics and flow cytometry confirmed reduction in cysteine uptake and increased reactive oxygen species (ROS) generation (Fig. 2). Additional metabolic readouts using the Sea horse system revealed inhibition of mitochondrial respiration as indicated by decreased in oxygen consumption rate and production of ATP upon treatment of ARV-825. Furthermore, array based gene expression profiling showed down-regulation of additional amino acid transporters and the Wnt/β-catenin pathway. Finally, in a mouse model of human leukemia, the leukemia burdens were significantly lower in the ARV-825 treated mice as confirmed by luciferase imaging, flow cytometry, spleen size and survived longer compared to control mice (p=0.0005) (Fig.3). Conclusion : ARV-825 has substantial, broad anti-AML activity and importantly modulates the tumor microenvironment and metabolism to overcome stroma-mediated drug resistance. Together, our data suggest that ARV-825 is an effective in targeting BET family of proteins for the treatment of AML Reference: 1. Nature 2011; 478(7370): 524-528. doi: 10.1038/nature10334 2. Chem Biol 2015; 22(6): 755-763. doi: 10.1016/j.chembiol.2015.05.009 3. Cancer Res 2015; 75(9): 1782-1788. doi: 10.1158/0008-5472.CAN-14-3745 4. 604(675): ASH 2015,San franscisco,USA. Disclosures Lorenzi: Erytech Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: NIH-held patent related to L-asparaginase. Qian:Arvinas, LLC: Employment. Kantarjian:Bristol-Myers Squibb: Research Funding; ARIAD: Research Funding; Amgen: Research Funding; Pfizer Inc: Research Funding; Delta-Fly Pharma: Research Funding; Novartis: Research Funding.
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Awalyah, Siti N., Rooije R. H. Rumende, and Hanry J. Lengkong. "KELIMPAHAN DAN KEKAYAAN SPESIES KELELAWAR DI GUNUNG TANGKOKO SULAWESI UTARA." PHARMACON 8, no. 3 (August 28, 2019): 671. http://dx.doi.org/10.35799/pha.8.2019.29391.
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ABSTRACT Bats are included into Chiroptera that originally derived from Greek. “Cheir” means hand and “Pteros” means wing or on the different side we can say it “wing hand”. Bats are mammals that can fly. They are nocturnal because they are active to find their food, flying at midnight, sleeping by hanging upside down during the day. They habitually do that kind of sleep because bat wings only have slight membrane which are susceptible to sunlight. Bats have two Ordo, they are Megachiroptera dan Microchirotera. The purpose of this research is to analyze abundance and richness of Bat Species in Tangkoko Mountain North Sulawesi. The method applying in this research is purposive sampling method by using Mist net. The locations of this research are coastal forest, lowland forest, sub montane forest, and moss forest. The obtained bats belong to one family, five genus, seven species with the total number of individuals is 260 bats. The species of the netted bats are Thoopterus nigrescens, Rosettus celebensis, R. amplexicaudatus, Macroglossus minimus, Nyctimene cephalotes, Cynopterus brachyotis, and Cynopterus luzoniensis. The catch rate of species of bats on Tangkoko Mountain has the result of abundance, which is calssified as low, that is 0.23 ind/net/hour/day. The richness of bat species at the second location is 1.08 that is classified as low. Keywords : Bats, Abundance, Richness, Tangkoko Mountain, North Sulawesi ABSTRAK Kelelawar termasuk ordo Chiroptera yang berasal dari bahasa yunani “Cheir” yang berarti tangan dan “Pteros” yang berarti sayap, atau bisa di sebut sebagai “sayap tangan”. kelelawar merupakan anggota hewan meyusui yang bisa terbang. Kelelawar bersifat nokturnal karena aktif mencari makan, terbang pada malam hari dan tidur dengan bergelantung terbalik pada siang hari. Karena hal tersebut di karenakan sayap kelelawar hanya berupa selaput tipis yang rentan terkena cahaya matahari. Kelelawar memiliki dua sub ordo yaitu sub ordo Megachiroptera dan Microchirotera. Tujuan penelitian ini adalah menganalisis kelimpahan dan kekayaan kelelawar di Gunung Tangkoko Sulawesi Utara. Metode yang digunakan dalam penelitian ini adalah metode purposive sampling dengan menggunakan jaring kabut (Mist net). Titik lokasi penelitian yaitu hutan pantai, hutan dataran rendah, hutan sub montana, dan hutan lumut. Kelelawar yang didapat termasuk ke dalam satu family, lima genus, tujuh spesies dengan jumlah seluruh individu 260 kelelawar. Spesies kelelawar yang terjaring yaitu Thoopterus nigrescens, Rosettus celebensis, R. amplexicaudatus, Macroglossus minimus, Nyctimene cephalotes, Cynopterus brachyotis, dan Cynopterus luzoniensis. Laju tangkapan spesies kelelawar di Gunung Tangkoko, memiliki hasil kelimpahan yang tergolong rendah yaitu sebesar 0.23 ind/net/jam/hari. Kekayaan spesies kelelawar pada kedua lokasi ialah 1,08 yang tergolong rendah.Kata kunci : Kelelawar, Kelimpahan, Kekayaan, Gunung Tangkoko, Sulawesi Utara.
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Kanagal-Shamanna, Rashmi, Guillermo Montalban Bravo, Panagiotis Katsonis, Koji Sasaki, Caleb Class, Christopher B. Benton, Elias Jabbour, et al. "Evolutionary Action Score Identifies a Subset of TP53 Mutated Myelodysplastic Syndrome with Favorable Prognosis." Blood 136, Supplement 1 (November 5, 2020): 4–5. http://dx.doi.org/10.1182/blood-2020-141411.
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Introduction TP53 mutations (TP53MT) are seen in ~10% of myelodysplastic syndromes (MDS). TP53MT are distributed across the entire coding region, with less than a third occurring in focal hotspots. In vitro and in silico studies suggest that different types of TP53MT lead to distinct functional consequences that include oncogenic gain-of-function and protein loss-of-function with dominant-negative effect. The functional effects of these mutations likely influence disease biology and outcome, either independently or by influencing known variables such as VAF and karyotype. While studies have shown that TP53MT MDS with complex/monosomal karyotype (CK/MK) and multiallelic TP53 alterations have a worse prognosis, however, the impact of different types of TP53MT on phenotype, prognosis and outcome of MDS is not known. To assess this, we quantified the deleterious effects of missense TP53MT using the computationally-derived evolutionary action score (EAp53, range, 0-100, higher score indicates worse impact), followed by 3D protein mapping to identify prognostic subsets. Methods We selected 270 consecutive newly-diagnosed MDS and oligoblastic AML with at least 1 missense TP53MT by NGS. EA53 scores were determined using evolutionary trace approach. TP53 immunohistochemistry (IHC) was performed on selected cases. The optimal EAp53 cutoff was determined using recursive partitioning and regression trees (RPART) based on Classification & Regression Trees. TP53 protein structural analysis was conducted using the PyMOL molecular visualization system and the crystal structure of the TP53 core domain in complex with DNA (PDB ID of 4HJE). Results The median age was 68 (18-90)]. Majority (81%) had a CK. The median EAp53 score was 79 (4-98) [Fig 1A, 1B]. Using RPART, we identified an EAp53 score >52 predicted for worse OS (median, 10 vs. 48 months; HR: 2.6 [1.22-5.56]; p=0.01) [Fig 1C]. We divided our cohort into low-EAp53 (≤52; n=17, 6%) and high-EAp53 (n=253, 94%). Low-EA MDS had fewer cytogenetic abnormalities [median, 3 vs. 7; p=0.019], lower frequency of CK/MK (p=0.02), lower number of additional TP53MT (6% vs. 32%, p=0.027), lower frequency of multiallelic TP53 alterations (29% vs. 63%, p=0.009), and higher number of additional gene mutations (63% vs. 33%; p=0.05) involving NRAS and RUNX1 genes (p=0.02). There was no difference in median TP53 VAF or R-IPSS scores (Table 1). By TP53 immunohistochemistry, TP53 protein expression was significantly different between wild-type (median H-score, 6), low EAp53 (48) and high EAp53 (158) [wild-type vs. low EA, p=0.04; low vs. high EA, p=0.0014]. Low EAp53 showed clearance of TP53 mutation in 67% (vs. 45%) in those that achieved partial/ complete response. Due to observed differences in outcome despite similar EAp53 score, we correlated survival with the mutant location within 3D protein structure. Majority of mutations mapped to the evolutionarily important sites of the TP53 core domain, residues near the DNA binding site or within the protein structural core and solvent inaccessible (Fig 1D). We divided our cohort into two groups based on a survival cut-off of 10 months. TP53MT associated with OS <10 months formed two clusters: a large cluster interfacing with the DNA binding site and a small cluster formed by residues V157, Y220, L257 and E258 (Fig 1E). By univariate analysis, the following associated with worse OS: higher TP53 VAF (as a continuous variable), higher number of TP53MT, high-risk EAp53 (>52) group, higher IPSS-R score, presence of CK/MK, higher serum LDH and creatinine levels, lower platelet, hemoglobin, and serum albumin. TP53 allele state and del(17p) did not associate with OS. By multivariable analysis (CK excluded due to due to a strong association with EAp53), high-EAp53 was associated with worse OS independent of R-IPSS score [HR 5.1; CI 1.5-17.2; p=0.009]. Neither TP53 VAF nor the number of TP53MT was independently prognostic. Conclusions A subset of TP53MT MDS patients with low-EAp53 (≤52) showed improved outcomes independent of TP53 VAF or IPSS-R scores in HMA treated MDS, and associated with specific clinico-pathologic features. High-EAp53 associated with worse OS independent of R-IPSS score. Mutational mapping using 3D protein model showed clustering of poor-outcome mutations, suggesting that structural location further influences the outcome. Combination of EAp53 and 3D mapping can be help identify prognostic subsets. Figure 1 Disclosures Sasaki: Novartis: Consultancy, Research Funding; Pfizer Japan: Consultancy; Daiichi Sankyo: Consultancy; Otsuka: Honoraria. Jabbour:AbbVie: Other: Advisory role, Research Funding; Adaptive Biotechnologies: Other: Advisory role, Research Funding; Amgen: Other: Advisory role, Research Funding; Takeda: Other: Advisory role, Research Funding; Pfizer: Other: Advisory role, Research Funding; Genentech: Other: Advisory role, Research Funding; BMS: Other: Advisory role, Research Funding. Kadia:Celgene: Research Funding; Cyclacel: Research Funding; BMS: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Novartis: Honoraria; Ascentage: Research Funding; JAZZ: Honoraria, Research Funding; Incyte: Research Funding; Amgen: Research Funding; Genentech: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Pulmotec: Research Funding; Astellas: Research Funding; Cellenkos: Research Funding; Astra Zeneca: Research Funding. Andreeff:Centre for Drug Research & Development; Cancer UK; NCI-CTEP; German Research Council; Leukemia Lymphoma Foundation (LLS); NCI-RDCRN (Rare Disease Clin Network); CLL Founcdation; BioLineRx; SentiBio; Aptose Biosciences, Inc: Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo; Breast Cancer Research Foundation; CPRIT; NIH/NCI; Amgen; AstraZeneca: Research Funding; Daiichi-Sankyo; Jazz Pharmaceuticals; Celgene; Amgen; AstraZeneca; 6 Dimensions Capital: Consultancy; Amgen: Research Funding. Short:Takeda Oncology: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy; Astellas: Research Funding; Amgen: Honoraria. Daver:Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Research Funding; Servier: Research Funding; Genentech: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novimmune: Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Trovagene: Research Funding; Fate Therapeutics: Research Funding; ImmunoGen: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Trillium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Syndax: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Borthakur:BioLine Rx: Consultancy; BioTherix: Consultancy; Nkarta Therapeutics: Consultancy; Treadwell Therapeutics: Consultancy; PTC Therapeutics: Consultancy; Argenx: Consultancy; FTC Therapeutics: Consultancy; Curio Science LLC: Consultancy; Oncoceutics: Research Funding; Xbiotech USA: Research Funding; Polaris: Research Funding; AstraZeneca: Research Funding; BMS: Research Funding; BioLine Rx: Research Funding; Cyclacel: Research Funding; GSK: Research Funding; Jannsen: Research Funding; Abbvie: Research Funding; Novartis: Research Funding; Incyte: Research Funding; PTC Therapeutics: Research Funding. Ravandi:Amgen: Consultancy, Honoraria, Research Funding; Astellas: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Xencor: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding; Orsenix: Consultancy, Honoraria, Research Funding; Macrogenics: Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria. Kantarjian:Immunogen: Research Funding; Jazz: Research Funding; Novartis: Honoraria, Research Funding; Aptitute Health: Honoraria; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive biotechnologies: Honoraria; Oxford Biomedical: Honoraria; Delta Fly: Honoraria; BioAscend: Honoraria; Daiichi-Sankyo: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Sanofi: Research Funding; Janssen: Honoraria; Abbvie: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Ascentage: Research Funding; BMS: Research Funding. Garcia-Manero:Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; H3 Biomedicine: Research Funding; AbbVie: Honoraria, Research Funding; Acceleron Pharmaceuticals: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy; Helsinn Therapeutics: Consultancy, Honoraria, Research Funding; Astex Pharmaceuticals: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Amphivena Therapeutics: Research Funding; Merck: Research Funding; Novartis: Research Funding; Onconova: Research Funding.
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Pemmaraju, Naveen, Giovanni Martinelli, Elisabetta Todisco, Andrew A. Lane, Evelyn Acuña-Cruz, Eric Deconinck, Eunice S. Wang, et al. "Clinical Profile of IMGN632, a Novel CD123-Targeting Antibody-Drug Conjugate (ADC), in Patients with Relapsed/Refractory (R/R) Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)." Blood 136, Supplement 1 (November 5, 2020): 11–13. http://dx.doi.org/10.1182/blood-2020-139903.
Full textAbstract:
BACKGROUND: BPDCN is a rare, aggressive hematologic malignancy characterized by poor overall survival and limited therapeutic options. Overexpression of CD123 (IL-3Rα) is present in all BPDCN cases, therefore establishing this marker as a rational target for therapeutic intervention. Despite the recent approval of tagraxofusp-erzs (Pemmaraju NEJM 2019), outcomes remain poor in the setting of R/R BPDCN. IMGN632 is a CD123-targeting ADC, comprised of a high affinity anti-CD123 antibody coupled to a DNA-alkylating payload of the novel IGN class. Preclinically, BPDCN patient-derived xenografts demonstrated high sensitivity to IMGN632 (Zhang 2018, Kovtun 2018), establishing a rationale for the clinical evaluation of IMGN632 in this patient population. AIMS: Safety and efficacy of single agent IMGN632 in patients with R/R BPDCN. METHODS: Adult patients with R/R BPDCN with no more than three prior lines of therapy were eligible. IMGN632 was administered IV at 0.045 mg/kg on day 1 of a 21-day cycle. RESULTS: 23 patients with R/R BPDCN; median age of 73 years [19-82]; 74% male. Fifty-two percent of patients had at least 2 prior therapies, 52% had received prior intensive therapies (eg HyperCVAD, FLAG, CHOP), 22% had prior allogeneic stem cell transplant, and importantly 43% had prior exposure to tagraxofusp-erzs (n=10). At enrollment, 70% had skin involvement, 61% had bone marrow involvement, and 48% had lymph node involvement. The most common treatment emergent adverse events (TEAEs) include: nausea (35% all grade; 0% grade 3+), peripheral edema (26% all grade; 0% grade 3+), and infusion related reactions (22% all grade; 4% grade 3+). There were no Grade 3+ treatment-related AEs observed in >1 patient. No capillary leak syndrome (CLS) was reported; grade 3+ LFT elevations, neutropenia, and thrombocytopenia were all noted in 1 patient each, and there were no deaths within 30-days after last IMGN632 dose. Seven of 23 patients had an objective response (2 CR, 2 CRc, 1 CRi and 2 PR) for an ORR of 30% (95% CI 13-53%) and a composite complete remission rate of 22%. The duration of response (DOR including time from PR) for the four CR/CRc patients were 9.2, 6.8+, 3.1 and 3+ months without transplantation (Figure 1A). Examples of responses are shown in Figure 1B-D. Of note, among the 10 patients with prior exposure to tagraxofusp (none had achieved a CR with tagraxofusp), 30% (n=3) achieved an objective response to IMGN632 (1 CR, 1 CRi, 1 PR). Two remarkable responders had received 3 prior regimens including tagraxofusp followed by intense and other therapies (CLAG-M/CLAG; or CHOP/allogeneic transplant/decitabine with venetoclax) and presented with diffuse disease involvement with skin, nodal, and bone marrow infiltration. After 1 and 2 doses respectively, both patients cleared all three disease compartments (CR/CRi) with one remaining in CR for 9.2 months. Additionally, among 12 patients who had bone marrow involvement and response assessment, 75% (9 of 12) had a reduction in bone marrow blasts, and 50% (6 of 12) achieved a bone marrow complete remission (<5% blasts, grey bars), including 3 patients with prior tagraxofusp. (Figure 1E). CONCLUSION: The current available therapy for patients with R/R BPDCN has limited efficacy and significant safety and tolerability concerns that underscore the high unmet need for this patient population. In heavily pretreated R/R BPDCN patients, including patients who had progressed following tagraxofusp, intense chemotherapies and transplant, IMGN632 demonstrated a 30% (n=7) ORR, with 4 CR/CRc responses with notable DORs. In addition, IMGN632 demonstrated a favorable safety profile that included limited grade 3+ TEAEs/SAEs, no cases of CLS, and no deaths. In addition, IMGN632 is given once every 3 weeks, without the need for hospitalization. This clinical trial represents the largest-to-date prospective group of uniformly treated patients with R/R BPDCN and demonstrates promising activity and favorable tolerability in a cohort of heavily pretreated patients, including nearly half with prior anti-CD123 targeted therapy. FIGURE: A) Swimmers plot for all responders (CR, CRc, CRi, and PR); ^ = HSCT, arrows indicate patients in ongoing remission. Examples of resolution of B) PET and C) skin lesions from one patient, and D) PET lesions from another patient. E) Waterfall graph demonstrating best bone marrow response, gray bars = blasts <5%, arrows indicate prior exposure to tagraxofusp. Disclosures Pemmaraju: Pacylex Pharmaceuticals: Consultancy; Affymetrix: Other: Grant Support, Research Funding; Cellectis: Research Funding; Roche Diagnostics: Honoraria; Samus Therapeutics: Research Funding; Novartis: Honoraria, Research Funding; Daiichi Sankyo: Research Funding; DAVA Oncology: Honoraria; AbbVie: Honoraria, Research Funding; Celgene: Honoraria; Incyte Corporation: Honoraria; SagerStrong Foundation: Other: Grant Support; Stemline Therapeutics: Honoraria, Research Funding; Plexxikon: Research Funding; Blueprint Medicines: Honoraria; LFB Biotechnologies: Honoraria; MustangBio: Honoraria. Todisco:Jannsen, Abbvie, Jazz: Membership on an entity's Board of Directors or advisory committees. Lane:Stemline Therapeutics: Research Funding; Abbvie: Research Funding; Qiagen: Consultancy. Deconinck:ImmunoGen: Consultancy, Research Funding; Stemline: Consultancy. Wang:Abbvie: Consultancy; Jazz Pharmaceuticals: Consultancy; Bristol Meyers Squibb (Celgene): Consultancy; Astellas: Consultancy; Macrogenics: Consultancy; Stemline: Speakers Bureau; Genentech: Consultancy; Pfizer: Speakers Bureau; PTC Therapeutics: Consultancy. Sweet:Stemline: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Astellas: Honoraria; Agios: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding. Rizzieri:Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Stemline: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite: Honoraria, Speakers Bureau; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; abbvie: Membership on an entity's Board of Directors or advisory committees; AROG: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Celltrion: Membership on an entity's Board of Directors or advisory committees; Mustang: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees; Acrobiotech: Membership on an entity's Board of Directors or advisory committees. Mazzarella:Tethis: Membership on an entity's Board of Directors or advisory committees. DeAngelo:Agios: Consultancy; Abbvie: Research Funding; Glycomimetics: Research Funding; Incyte Corporation: Consultancy; Jazz: Consultancy; Novartis: Consultancy, Research Funding; Pfizer: Consultancy; Shire: Consultancy; Takeda: Consultancy; Blueprint Medicines Corporation: Consultancy, Research Funding; Autolos: Consultancy; Amgen: Consultancy; Forty-Seven: Consultancy. Montesinos:Astellas, Novartis, Janssen: Speakers Bureau; Celgene, Pfizer, Abbvie: Consultancy; Pfizer, Abbvie, Daiichi Sankyo: Research Funding. Tarella:TG-therapeutics: Research Funding; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; ImmunoGen: Research Funding. Konopleva:Stemline Therapeutics: Consultancy, Research Funding; Amgen: Consultancy; Ablynx: Research Funding; Rafael Pharmaceutical: Research Funding; Eli Lilly: Research Funding; Genentech: Consultancy, Research Funding; Cellectis: Research Funding; Calithera: Research Funding; Forty-Seven: Consultancy, Research Funding; Kisoji: Consultancy; Ascentage: Research Funding; Reata Pharmaceutical Inc.;: Patents & Royalties: patents and royalties with patent US 7,795,305 B2 on CDDO-compounds and combination therapies, licensed to Reata Pharmaceutical; F. Hoffmann La-Roche: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; AstraZeneca: Research Funding; Sanofi: Research Funding; Agios: Research Funding. Kantarjian:BMS: Research Funding; Janssen: Honoraria; Oxford Biomedical: Honoraria; BioAscend: Honoraria; Delta Fly: Honoraria; Immunogen: Research Funding; Sanofi: Research Funding; Abbvie: Honoraria, Research Funding; Adaptive biotechnologies: Honoraria; Aptitute Health: Honoraria; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz: Research Funding; Novartis: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Ascentage: Research Funding. Sloss:ImmunoGen, Inc.: Current Employment. Malcolm:ImmunoGen, Inc.: Current Employment. Zweidler-McKay:ImmunoGen, Inc.: Current Employment. Daver:Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Trillium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Syndax: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Research Funding; Servier: Research Funding; Genentech: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novimmune: Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Trovagene: Research Funding; Fate Therapeutics: Research Funding; ImmunoGen: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Results from a Phase 1/2 clinical trial using a non-approved experimental therapy
32
Tawich, Simon K., Joel L. Bargul, Daniel Masiga, and Merid N. Getahun. "Supplementing Blood Diet With Plant Nectar Enhances Egg Fertility in Stomoxys calcitrans." Frontiers in Physiology 12 (March 30, 2021). http://dx.doi.org/10.3389/fphys.2021.646367.
Full textAbstract:
Stomoxys calcitrans (stable fly) is a cosmopolitan biting fly of both medical and veterinary importance. Unlike blood-feeding-related behavior of stable fly, its plant feeding, the fitness value, and the S. calcitrans–plant interaction are less understood. Here we show based on two chloroplast DNA genes, ribulose bisphosphate carboxylase large chain (rbcL) and the intergenic spacer gene trnH-psbA, that field-collected male and female stable flies fed on various plant species. We investigated the fitness cost of plant feeding using Parthenium hysterophorus, one of the plant species identified to have been fed on by the field-collected flies. Supplementation of blood feeding with a flowering P. hysterophorus plant as nectar source enhanced egg hatchability significantly as compared to blood alone, showing the fitness value of nectar supplementation. However, nectar supplementation did not affect the number of eggs laid or longevity of S. calcitrans as compared to flies that fed on blood alone. S. calcitrans maintained on sugar alone failed to lay eggs. The various plants stable flies fed on demonstrated chemodiversity with their own signature scent. The behavioral response of S. calcitrans to these signature compounds varied from strong attraction (γ-terpinene) to neutral (linalool oxide and myrcene) to repellency (butanoic acid). Our study demonstrated that stable flies feed on nectar, and plant nectar supplementation of blood feeding enhanced larval emergence. Thus, our result has implication in stable fly reproduction, survival, disease transmission, boosting laboratory colony, and the possibility of using plant-derived odors for mass trapping of stable fly, for instance, using γ-terpinene.
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Crane, Yan M., Charles F. Crane, Sue E. Cambron, Lucy J. Springmeyer, and Brandon J. Schemerhorn. "Molecular characterization of eliminated chromosomes in Hessian fly (Mayetiola destructor (Say))." Chromosome Research 31, no. 1 (January 24, 2023). http://dx.doi.org/10.1007/s10577-023-09718-8.
Full textAbstract:
AbstractLike other cecidomyiid Diptera, Hessian fly has stable S chromosomes and dispensable E chromosomes that are retained only in the germ line. Amplified fragment length polymorphisms (AFLP), suppressive subtractive hybridization (SSH), fluorescent in-situ hybridization (FISH), and sequencing were used to investigate similarities and differences between S and E chromosomes. More than 99.9% of AFLP bands were identical between separated ovary and somatic tissue, but one band was unique to ovary and resembled Worf, a non-LTR retrotransposon. Arrayed clones, derived by SSH of somatic from ovarian DNA, showed no clones that were unique to ovary. FISH with BAC clones revealed a diagnostic banding pattern of BAC positions on both autosomes and both sex chromosomes, and each E chromosome shared a pattern with one of the S chromosomes. Sequencing analysis showed that E chromosomes are nearly identical to S chromosomes, since no sequence could be confirmed to belong only to E chromosomes. There were a few questionably E-specific sequences that are candidates for further investigation. Thus, the E chromosomes appear to be derived from S chromosomes by the acquisition or conversion of sequences that produce the negatively heteropycnotic region around the centromere.
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Pacakova, Lenka, Karel Harant, Petr Volf, and Tereza Lestinova. "Three types of Leishmania mexicana amastigotes: Proteome comparison by quantitative proteomic analysis." Frontiers in Cellular and Infection Microbiology 12 (November 9, 2022). http://dx.doi.org/10.3389/fcimb.2022.1022448.
Full textAbstract:
Leishmania is the unicellular parasite transmitted by phlebotomine sand fly bite. It exists in two different forms; extracellular promastigotes, occurring in the gut of sand flies, and intracellular, round-shaped amastigotes residing mainly in vertebrate macrophages. As amastigotes originating from infected animals are often present in insufficient quality and quantity, two alternative types of amastigotes were introduced for laboratory experiments: axenic amastigotes and amastigotes from macrophages infected in vitro. Nevertheless, there is very little information about the degree of similarity/difference among these three types of amastigotes on proteomic level, whose comparison is crucial for assessing the suitability of using alternative types of amastigotes in experiments. In this study, L. mexicana amastigotes obtained from lesion of infected BALB/c mice were proteomically compared with alternatively cultivated amastigotes (axenic and macrophage-derived ones). Amastigotes of all three types were isolated, individually treated and analysed by LC-MS/MS proteomic analysis with quantification using TMT10-plex isobaric labeling. Significant differences were observed in the abundance of metabolic enzymes, virulence factors and proteins involved in translation and condensation of DNA. The most pronounced differences were observed between axenic amastigotes and lesion-derived amastigotes, macrophage-derived amastigotes were mostly intermediate between axenic and lesion-derived ones.
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Kovács, Tibor, Janka Szinyákovics, Viktor Billes, Gábor Murányi, Virginia B. Varga, Annamária Bjelik, Ádám Légrádi, et al. "A conserved MTMR lipid phosphatase increasingly suppresses autophagy in brain neurons during aging." Scientific Reports 12, no. 1 (December 17, 2022). http://dx.doi.org/10.1038/s41598-022-24843-w.
Full textAbstract:
AbstractAgeing is driven by the progressive, lifelong accumulation of cellular damage. Autophagy (cellular self-eating) functions as a major cell clearance mechanism to degrade such damages, and its capacity declines with age. Despite its physiological and medical significance, it remains largely unknown why autophagy becomes incapable of effectively eliminating harmful cellular materials in many cells at advanced ages. Here we show that age-associated defects in autophagic degradation occur at both the early and late stages of the process. Furthermore, in the fruit fly Drosophila melanogaster, the myotubularin-related (MTMR) lipid phosphatase egg-derived tyrosine phosphatase (EDTP) known as an autophagy repressor gradually accumulates in brain neurons during the adult lifespan. The age-related increase in EDTP activity is associated with a growing DNA N6-adenine methylation at EDTP locus. MTMR14, the human counterpart of EDTP, also tends to accumulate with age in brain neurons. Thus, EDTP, and presumably MTMR14, promotes brain ageing by increasingly suppressing autophagy throughout adulthood. We propose that EDTP and MTMR14 phosphatases operate as endogenous pro-ageing factors setting the rate at which neurons age largely independently of environmental factors, and that autophagy is influenced by DNA N6-methyladenine levels in insects.
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Ebhodaghe, Faith I., Armanda D. S. Bastos, Michael N. Okal, and Daniel K. Masiga. "Entomological assessment of tsetse-borne trypanosome risk in the Shimba Hills human-wildlife-livestock interface, Kenya." Frontiers in Veterinary Science 9 (August 16, 2022). http://dx.doi.org/10.3389/fvets.2022.931078.
Full textAbstract:
Shimba Hills is a wildlife area in Kenya and a major focus of tsetse-borne trypanosomes in East Africa. In Shimba Hills, tsetse-borne trypanosomes constrain animal health and smallholder livelihoods. However, epidemiological data to guide hotspot-targeted control of infections are limited. This study assessed the dynamics of tsetse-borne trypanosome risk in Shimba Hills with the objective to describe infection hotspots for targeted control. Tsetse flies (n = 696) collected in field surveys between November 2018 and September 2019 in Shimba Hills were characterized for chronological age and phenotypic sizes and screened for trypanosome and cattle DNA. Entomological inoculation rates for trypanosome risk assessment were derived from the product of fly abundance and molecular rates of vector infection and confirmed cattle bloodmeals in tsetse flies. In addition, cattle health indicators including anemia scores were assessed in contemporaneous parasitological surveys that screened livestock blood samples (n = 1,417) for trypanosome using the buffy-coat technique. Compared with Glossina brevipalpis and G. austeni, G. pallidipes was the most abundant tsetse fly species in Shimba Hills and had a wider spatial distribution and greater likelihood for infectious bites on cattle. The risk of cattle infection was similar along the Shimba Hills human-wildlife-livestock interface and high within one thousand meters of the wildlife reserve boundary. Trypanosomes in tsetse flies were highly diverse and included parasites of wild-suids probably acquired from warthogs in Shimba Hills. Age and phenotypic sizes were similar between tsetse fly populations and did not affect the probability of infection or cattle bloodmeals in the vectors. Anemia was more likely in trypanosome-positive cattle whilst parasitological infection rates in cattle samples maintained a weak relationship with entomological inoculation rates probably because of the limited time scale of sample collection. Trypanosome risk in Shimba Hills is high in locations close to the wildlife reserve and driven by G. pallidipes infectious bites on cattle. Therefore, trypanosome vector control programmes in the area should be designed to reduce G. pallidipes abundance and tailored to target sites close to the wildlife reserve.
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Markova, Dragomira N., Fatema B. Ruma, Claudio Casola, Ayda Mirsalehi, and Esther Betrán. "Recurrent co-domestication of PIF/Harbinger transposable element proteins in insects." Mobile DNA 13, no. 1 (November 30, 2022). http://dx.doi.org/10.1186/s13100-022-00282-2.
Full textAbstract:
Abstract Background Transposable elements (TEs) are selfish DNA sequences capable of moving and amplifying at the expense of host cells. Despite this, an increasing number of studies have revealed that TE proteins are important contributors to the emergence of novel host proteins through molecular domestication. We previously described seven transposase-derived domesticated genes from the PIF/Harbinger DNA family of TEs in Drosophila and a co-domestication. All PIF TEs known in plants and animals distinguish themselves from other DNA transposons by the presence of two genes. We hypothesize that there should often be co-domestications of the two genes from the same TE because the transposase (gene 1) has been described to be translocated to the nucleus by the MADF protein (gene 2). To provide support for this model of new gene origination, we investigated available insect species genomes for additional evidence of PIF TE domestication events and explored the co-domestication of the MADF protein from the same TE insertion. Results After the extensive insect species genomes exploration of hits to PIF transposases and analyses of their context and evolution, we present evidence of at least six independent PIF transposable elements proteins domestication events in insects: two co-domestications of both transposase and MADF proteins in Anopheles (Diptera), one transposase-only domestication event and one co-domestication in butterflies and moths (Lepidoptera), and two transposases-only domestication events in cockroaches (Blattodea). The predicted nuclear localization signals for many of those proteins and dicistronic transcription in some instances support the functional associations of co-domesticated transposase and MADF proteins. Conclusions Our results add to a co-domestication that we previously described in fruit fly genomes and support that new gene origination through domestication of a PIF transposase is frequently accompanied by the co-domestication of a cognate MADF protein in insects, potentially for regulatory functions. We propose a detailed model that predicts that PIF TE protein co-domestication should often occur from the same PIF TE insertion.
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Liu, Qinwen, Pinar Onal, Rhea R. Datta, Julia M. Rogers, Urs Schmidt-Ott, Martha L. Bulyk, Stephen Small, and Joseph W. Thornton. "Ancient mechanisms for the evolution of the bicoid homeodomain's function in fly development." eLife 7 (October 9, 2018). http://dx.doi.org/10.7554/elife.34594.
Full textAbstract:
The ancient mechanisms that caused developmental gene regulatory networks to diversify among distantly related taxa are not well understood. Here we use ancestral protein reconstruction, biochemical experiments, and developmental assays of transgenic animals carrying reconstructed ancestral genes to investigate how the transcription factor Bicoid (Bcd) evolved its central role in anterior-posterior patterning in flies. We show that most of Bcd’s derived functions are attributable to evolutionary changes within its homeodomain (HD) during a phylogenetic interval >140 million years ago. A single substitution from this period (Q50K) accounts almost entirely for the evolution of Bcd’s derived DNA specificity in vitro. In transgenic embryos expressing the reconstructed ancestral HD, however, Q50K confers activation of only a few of Bcd’s transcriptional targets and yields a very partial rescue of anterior development. Adding a second historical substitution (M54R) confers regulation of additional Bcd targets and further rescues anterior development. These results indicate that two epistatically interacting mutations played a major role in the evolution of Bcd’s controlling regulatory role in early development. They also show how ancestral sequence reconstruction can be combined with in vivo characterization of transgenic animals to illuminate the historical mechanisms of developmental evolution.
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Silitonga, Ernesto. "IDENTIFIKASI KARAKTERISTIK ABU TERBANG JENIS ALUMINO-SILIKAT." Educational Building 3, no. 2 (December 4, 2017). http://dx.doi.org/10.24114/eb.v3i2.8260.
Full textAbstract:
Circulating Fluidized Bed (CFB) merupakan teknik dimana pekerjaan mengutamakan material yang dihasilkan memiliki emisi polutan yang lebih rendah dibanding metode klasik. Tujuan utama dari penelitian ini adalah mengidentifikasi dua jenis abu terbang Alumino-Silikat yang berbeda yang berasal dari pembakaran Circulating Fluidized Bed (CFB). Dalam upaya mengidentifikasi karakteristik kedua abu terbang ini, langkah pertama yaitu melalui karakteristik origin dari abu terbang tersebut, contohnya berdasarkan distribusi diameter partikel, karakteristik mineralogi. Langkah berikutnya dalam mengidentifikasi karakteristik abu terbang direalisasikan dengan bantuan Percobaan Chapelle yang bertujuan untuk menentukan persentase CaOfree yang tersedia untuk reaksi pozzolanic dari abu terbang. Percobaan memperlihatkan bahwa abu terbang AT/AS-1 memiliki aktivitas yang lebih intens dibanding AT/AS-2. Berdasarkan hasil percobaan dapat disimpulkan dapat kita katakan bahwa rumusan ideal untuk Sodeline adalah campuran yang mengandung 75% Sodeline, 15% kapur dan 10% semen. Memang, campuran ini lebih kuat dan lebih tahan terhadap serangan sulfat Kata Kunci : abu terbang, distribusi diameter partikel, karakter mineralogy. Percobaan Chapelle ABSTRACT Circulating Fluidized Bed (CFB) is a technique where the job of prioritizing the resulting material has lower pollutant emissions than the classical method. The main purpose of this study was to identify two different types of fly ash Alumino-Silicate derived from CFB. In order to identify the characteristics of these two fly ashes, the first step is through the origin characteristics of the fly ash, for example based on the particle diameter distribution, mineralogical characteristics. The next step in identifying the characteristics of fly ash is realized with the help of the Chapelle Test. This test is aimed to determine the percentage of CaOfree which will be available for the pozzolanic reaction of fly ash. Experiments show that AT / AS-1 ash fly has more intense activity than AT / AS-2. Based on the results of the experiment it can be concluded that we can say that the ideal formula for Sodeline is a mixture containing 75% Sodeline, 15% lime and 10% cement. Indeed, this mixture is stronger and more resistant to sulfate attacks. Keywords: fly ash, particle diameter distribution, mineralogy character. Chapelle's experiment
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Firdausy, Muhammad Abrar, Andy Mizwar, Muhammad Firmansyah, and Muhammad Fazriansyah. "PEMANFAATAN LARVA BLACKxSOLDIER FLY (HERMETIA ILLUCENS) SEBAGAI PEREDUKSI SAMPAH ORGANIK DENGAN VARIASI JENIS SAMPAH DAN FREKUENSI FEEDING." Jukung (Jurnal Teknik Lingkungan) 7, no. 2 (November 5, 2021). http://dx.doi.org/10.20527/jukung.v7i2.11948.
Full textAbstract:
Sampah sudah menjadi persoalan serius bagi masyarakat. Produksi sampah di dunia semakin meningkat, sedangkan laju pengurangan sampah lebih kecil dari pada laju produksinya, hal ini menyebabkan sampah semakin menumpuk. Berbagai upaya pemanfaatan sampah organik dengan teknologi baru telah dilakukan, salah satunya dengan memanfaatkan larva Black Soldier Fly (Hermetia illucens). Tujuan dari penelitian ini untuk menganalisis besar persentase kemampuan larva BSF dalam mereduksi sampah organik sayuran/buah-buahan dan lauk. Penelitian ini dilakukan dengan metode percobaan skala laboratorium. Sampah organik yang digunakan sebagai sampel adalah sampah yang berasal dari sampah makanan khususnya sampah sayuran/buah-buahan dan lauk dengan frekuensi feeding sekali dalam 3 hari. Analisis data yang digunakan pada penelitian ini yaitu Rancangan Acak Lengkap (RAL) dengan 2 kali replikasi (pengulangan) dan metode analisis yang digunakan adalah Analysis of Variance (ANOVA). Berdasarkan penelitian ini, persentase terbesar reduksi sampah oleh larva BSF sebesar 74% dan berdasarkan persentase yang diperoleh ditentukan bahwa variasi jenis sampah sayuran/buah-buahan dengan frekuensi feeding sekali dalam 3 hari lebih efektif untuk menghasilkan persentase reduksi sampah yang optimal. Kata kunci: frekuensi feeding, jenis sampah, larva BSF, reduksi sampah organik. Waste has become a serious problem for the community. Waste production in the world is increasing, while the rate of waste reduction is smaller than the rate of production, this causes waste to accumulate more. Various efforts to use organic waste with new technology have been carried out, one of which is by utilizing the larvae ofxBlack Soldier Fly (Hermetia illucens). The purpose of this study was to analyze the large percentage of BSF larvae' ability in reducing organic waste of vegetables/fruits and side dishes. This research was conducted by laboratory-scale experimental method. Organic waste used as a sample is garbage derived from food waste, especially vegetable / fruit waste and side dishes with feeding frequency once every 3 days. Data analysis used in this study is Complete RandomIzedxDesign (RAL) with 2 times replication (repetition) and the analysis method used is Analysis of Variance (ANOVA). Based on this study, the largest percentage of waste reduction by BSF larvae is 74% and based on the percentage obtained it is determined that variations in the type of vegetable/fruit waste with feeding frequency once in 3 days are more effective to produce an optimal percentage of waste reduction. Keyword: BSF larvae, feeding frequency, reduction of organic waste, types of waste.