ABSTRACT
Abstract Birds are among the best bio-indicators, which can guide us to recognize some of the main conservation concerns in ecosystems. Anthropogenic impacts such as deforestation, habitat degradation, modification of landscapes, and decreased quality of habitats are major threats to bird diversity. The present study was designed to detect anthropogenic causative agents that act on waterbird diversity in Tarbella Dam, Indus River, Pakistan. Waterbird censuses were carried out from March 2019 to February 2020 in multiple areas around the dam. A total of 2990 waterbirds representing 63 species were recorded. We detected the highest waterbird richness and diversity at Pehure whereas the highest density was recorded at Kabbal. Human activity impacts seemed to be the main factor determining the waterbird communities as waterbirds were negatively correlated with the greatest anthropogenic impacts. Waterbirds seem to respond rapidly to human disturbance.
Resumo As aves estão entre os melhores bioindicadores, o que pode nos orientar a reconhecer algumas das principais preocupações de conservação dos ecossistemas. Impactos antrópicos como desmatamento, degradação de habitat, modificação de paisagens e diminuição da qualidade dos habitats são as principais ameaças à diversidade de aves. O presente estudo foi desenhado para detectar agentes causadores antropogênicos que atuam na diversidade de aves aquáticas na Represa de Tarbella, rio Indus, Paquistão. Censos de aves aquáticas foram realizados de março de 2019 a fevereiro de 2020 em várias áreas ao redor da barragem. Um total de 2.990 aves aquáticas representando 63 espécies foi registrado. Detectamos a maior riqueza e diversidade de aves aquáticas em Pehure, enquanto a maior densidade foi registrada em Kabbal. Os impactos da atividade humana parecem ser o principal fator determinante das comunidades de aves aquáticas, uma vez que as aves aquáticas foram negativamente correlacionadas com os maiores impactos antrópicos. As aves aquáticas parecem responder rapidamente às perturbações humanas.
ABSTRACT
Abstract This study was aimed to investigate Carbofuran (CF)-induced pathological changes in cattle egret. Two hundred cattle egrets were reared and equally divided into four groups and given different CF concentrations (0.03 mg/L, 0.02 mg/L, 0.01 mg/L and 0 mg/L (control group)). Hematology, serum biochemistry, histopathology, and immunological markers were studied. Our results confirm that CF induces anemic conditions, leukocytosis, elevated liver enzymatic activity, and alterations in renal biomarkers. Moreover, specific microscopic lesions such as multifocal necrosis, pyknotic nuclei, hemorrhages, congestion, and inflammatory cell proliferation were observed in the liver, kidney, spleen, and thymus. These findings suggest that CF can induce harmful effects, so the application of this pesticide in the field must be strictly monitored to mitigate the possibility of exposure to non-target species.
Resumo Este estudo teve como objetivo investigar as alterações patológicas induzidas por carbofurano (CF) em garças-vaqueiras. Duzentas dessas garças foram criadas e divididas igualmente em quatro grupos e receberam diferentes concentrações de CF: 0,03 mg/L; 0,02 mg/L; 0,01 mg/L; e 0 mg/L (grupo controle). Foram realizadas análises de hematologia, bioquímica sérica, histopatologia e marcadores imunológicos. Nossos resultados confirmaram que CF induz condições anêmicas, leucocitose, atividade enzimática hepática elevada e alterações nos biomarcadores renais. Além disso, lesões microscópicas específicas, como necrose multifocal, núcleos picnóticos, hemorragias, congestão e proliferação de células inflamatórias, foram observadas no fígado, rim, baço e timo. Esses achados sugerem que o CF pode causar efeitos nocivos, portanto a aplicação desse agrotóxico no campo deve ser rigorosamente monitorada para mitigar a possibilidade de exposição a espécies não alvo.
ABSTRACT
Abstract Birds are among the best bio-indicators, which can guide us to recognize some of the main conservation concerns in ecosystems. Anthropogenic impacts such as deforestation, habitat degradation, modification of landscapes, and decreased quality of habitats are major threats to bird diversity. The present study was designed to detect anthropogenic causative agents that act on waterbird diversity in Tarbella Dam, Indus River, Pakistan. Waterbird censuses were carried out from March 2019 to February 2020 in multiple areas around the dam. A total of 2990 waterbirds representing 63 species were recorded. We detected the highest waterbird richness and diversity at Pehure whereas the highest density was recorded at Kabbal. Human activity impacts seemed to be the main factor determining the waterbird communities as waterbirds were negatively correlated with the greatest anthropogenic impacts. Waterbirds seem to respond rapidly to human disturbance.
Resumo As aves estão entre os melhores bioindicadores, o que pode nos orientar a reconhecer algumas das principais preocupações de conservação dos ecossistemas. Impactos antrópicos como desmatamento, degradação de habitat, modificação de paisagens e diminuição da qualidade dos habitats são as principais ameaças à diversidade de aves. O presente estudo foi desenhado para detectar agentes causadores antropogênicos que atuam na diversidade de aves aquáticas na Represa de Tarbella, rio Indus, Paquistão. Censos de aves aquáticas foram realizados de março de 2019 a fevereiro de 2020 em várias áreas ao redor da barragem. Um total de 2.990 aves aquáticas representando 63 espécies foi registrado. Detectamos a maior riqueza e diversidade de aves aquáticas em Pehure, enquanto a maior densidade foi registrada em Kabbal. Os impactos da atividade humana parecem ser o principal fator determinante das comunidades de aves aquáticas, uma vez que as aves aquáticas foram negativamente correlacionadas com os maiores impactos antrópicos. As aves aquáticas parecem responder rapidamente às perturbações humanas.
Subject(s)
Humans , Ecosystem , Rivers , Pakistan , Conservation of Natural ResourcesABSTRACT
Abstract This study was aimed to investigate Carbofuran (CF)-induced pathological changes in cattle egret. Two hundred cattle egrets were reared and equally divided into four groups and given different CF concentrations (0.03 mg/L, 0.02 mg/L, 0.01 mg/L and 0 mg/L (control group)). Hematology, serum biochemistry, histopathology, and immunological markers were studied. Our results confirm that CF induces anemic conditions, leukocytosis, elevated liver enzymatic activity, and alterations in renal biomarkers. Moreover, specific microscopic lesions such as multifocal necrosis, pyknotic nuclei, hemorrhages, congestion, and inflammatory cell proliferation were observed in the liver, kidney, spleen, and thymus. These findings suggest that CF can induce harmful effects, so the application of this pesticide in the field must be strictly monitored to mitigate the possibility of exposure to non-target species.
Resumo Este estudo teve como objetivo investigar as alterações patológicas induzidas por carbofurano (CF) em garças-vaqueiras. Duzentas dessas garças foram criadas e divididas igualmente em quatro grupos e receberam diferentes concentrações de CF: 0,03 mg/L; 0,02 mg/L; 0,01 mg/L; e 0 mg/L (grupo controle). Foram realizadas análises de hematologia, bioquímica sérica, histopatologia e marcadores imunológicos. Nossos resultados confirmaram que CF induz condições anêmicas, leucocitose, atividade enzimática hepática elevada e alterações nos biomarcadores renais. Além disso, lesões microscópicas específicas, como necrose multifocal, núcleos picnóticos, hemorragias, congestão e proliferação de células inflamatórias, foram observadas no fígado, rim, baço e timo. Esses achados sugerem que o CF pode causar efeitos nocivos, portanto a aplicação desse agrotóxico no campo deve ser rigorosamente monitorada para mitigar a possibilidade de exposição a espécies não alvo.
Subject(s)
Animals , Carbofuran/toxicity , Birds , CattleABSTRACT
CCS1477 (inobrodib) is a potent, selective EP300/CBP bromodomain inhibitor which induces cell-cycle arrest and differentiation in hematologic malignancy model systems. In myeloid leukemia cells, it promotes rapid eviction of EP300/CBP from an enhancer subset marked by strong MYB occupancy and high H3K27 acetylation, with downregulation of the subordinate oncogenic network and redistribution to sites close to differentiation genes. In myeloma cells, CCS1477 induces eviction of EP300/CBP from FGFR3, the target of the common (4; 14) translocation, with redistribution away from IRF4-occupied sites to TCF3/E2A-occupied sites. In a subset of patients with relapsed or refractory disease, CCS1477 monotherapy induces differentiation responses in AML and objective responses in heavily pre-treated multiple myeloma. In vivo preclinical combination studies reveal synergistic responses to treatment with standard-of-care agents. Thus, CCS1477 exhibits encouraging preclinical and early-phase clinical activity by disrupting recruitment of EP300/CBP to enhancer networks occupied by critical transcription factors.
Subject(s)
Hematologic Neoplasms , Nuclear Proteins , Humans , Cell Line, Tumor , Transcription Factors , Protein Domains , Hematologic Neoplasms/drug therapy , Hematologic Neoplasms/genetics , E1A-Associated p300 ProteinABSTRACT
Birds are very valuable indicators of species richness and endemic patterns in a specified ecosystem, which eventually help the scientist to measure the environmental degradation. The aim of present study was to know human knowledge and attitude toward urban birds in Faisalabad city, Pakistan. The study conducted in four consecutive months: November 2019 to February 2020. Population of birds was noted from eight residential towns of Faisalabad city, data were collected through questionnaire. Faisalabad has a reasonably large population of birds and present data show that, there is a significant difference between favorite bird of residential areas and institutions. The pigeon received the most likeness in bird population among residential area residents, while the myna received the least. The most popular bird in Faisalabad institutions was the sparrow, while the least popular bird was the common myna. Bird adaptation percentage of residential areas and institutional areas of Faisalabad was the highest for parrot and sparrow respectively. People in residential areas and institutions, on the other hand, adapted least to common myna. It is concluded that people of the study area like birds and offered food and high population of birds are present in study area.
Os pássaros são indicadores muito valiosos da riqueza de espécies e padrões endêmicos em um determinado ecossistema, o que acaba ajudando o cientista a medir a degradação ambiental. O objetivo do presente estudo foi conhecer o conhecimento humano e a atitude em relação às aves urbanas na cidade de Faisalabad, Paquistão. O estudo foi conduzido em quatro meses consecutivos: novembro de 2019 a fevereiro de 2020. A população de pássaros foi observada em oito cidades residenciais da cidade de Faisalabad, os dados foram coletados por meio de questionário. Faisalabad tem uma população razoavelmente grande de pássaros, e os dados atuais mostram que há uma diferença significativa entre as aves favoritas de áreas residenciais e instituições. O pombo recebeu mais semelhanças na população de pássaros entre os residentes de áreas residenciais, enquanto o myna recebeu menos. A ave mais popular nas instituições de Faisalabad era o pardal, enquanto a ave menos popular era o myna comum. A porcentagem de adaptação de pássaros em áreas residenciais e institucionais de Faisalabad foi a mais alta para papagaios e pardais, respectivamente. As pessoas em áreas residenciais e instituições, por outro lado, se adaptaram menos ao myna comum. Conclui-se que pessoas da área de estudo como pássaros e alimentos oferecidos e alta população de pássaros estão presentes na área de estudo.
Subject(s)
Animals , Birds/classification , EcosystemABSTRACT
Abstract Birds are very valuable indicators of species richness and endemic patterns in a specified ecosystem, which eventually help the scientist to measure the environmental degradation. The aim of present study was to know human knowledge and attitude toward urban birds in Faisalabad city, Pakistan. The study conducted in four consecutive months: November 2019 to February 2020. Population of birds was noted from eight residential towns of Faisalabad city, data were collected through questionnaire. Faisalabad has a reasonably large population of birds and present data show that, there is a significant difference between favorite bird of residential areas and institutions. The pigeon received the most likeness in bird population among residential area residents, while the myna received the least. The most popular bird in Faisalabad institutions was the sparrow, while the least popular bird was the common myna. Bird adaptation percentage of residential areas and institutional areas of Faisalabad was the highest for parrot and sparrow respectively. People in residential areas and institutions, on the other hand, adapted least to common myna. It is concluded that people of the study area like birds and offered food and high population of birds are present in study area.
Resumo Os pássaros são indicadores muito valiosos da riqueza de espécies e padrões endêmicos em um determinado ecossistema, o que acaba ajudando o cientista a medir a degradação ambiental. O objetivo do presente estudo foi conhecer o conhecimento humano e a atitude em relação às aves urbanas na cidade de Faisalabad, Paquistão. O estudo foi conduzido em quatro meses consecutivos: novembro de 2019 a fevereiro de 2020. A população de pássaros foi observada em oito cidades residenciais da cidade de Faisalabad, os dados foram coletados por meio de questionário. Faisalabad tem uma população razoavelmente grande de pássaros, e os dados atuais mostram que há uma diferença significativa entre as aves favoritas de áreas residenciais e instituições. O pombo recebeu mais semelhanças na população de pássaros entre os residentes de áreas residenciais, enquanto o myna recebeu menos. A ave mais popular nas instituições de Faisalabad era o pardal, enquanto a ave menos popular era o myna comum. A porcentagem de adaptação de pássaros em áreas residenciais e institucionais de Faisalabad foi a mais alta para papagaios e pardais, respectivamente. As pessoas em áreas residenciais e instituições, por outro lado, se adaptaram menos ao myna comum. Conclui-se que pessoas da área de estudo como pássaros e alimentos oferecidos e alta população de pássaros estão presentes na área de estudo.
ABSTRACT
Abstract Birds are very valuable indicators of species richness and endemic patterns in a specified ecosystem, which eventually help the scientist to measure the environmental degradation. The aim of present study was to know human knowledge and attitude toward urban birds in Faisalabad city, Pakistan. The study conducted in four consecutive months: November 2019 to February 2020. Population of birds was noted from eight residential towns of Faisalabad city, data were collected through questionnaire. Faisalabad has a reasonably large population of birds and present data show that, there is a significant difference between favorite bird of residential areas and institutions. The pigeon received the most likeness in bird population among residential area residents, while the myna received the least. The most popular bird in Faisalabad institutions was the sparrow, while the least popular bird was the common myna. Bird adaptation percentage of residential areas and institutional areas of Faisalabad was the highest for parrot and sparrow respectively. People in residential areas and institutions, on the other hand, adapted least to common myna. It is concluded that people of the study area like birds and offered food and high population of birds are present in study area.
Resumo Os pássaros são indicadores muito valiosos da riqueza de espécies e padrões endêmicos em um determinado ecossistema, o que acaba ajudando o cientista a medir a degradação ambiental. O objetivo do presente estudo foi conhecer o conhecimento humano e a atitude em relação às aves urbanas na cidade de Faisalabad, Paquistão. O estudo foi conduzido em quatro meses consecutivos: novembro de 2019 a fevereiro de 2020. A população de pássaros foi observada em oito cidades residenciais da cidade de Faisalabad, os dados foram coletados por meio de questionário. Faisalabad tem uma população razoavelmente grande de pássaros, e os dados atuais mostram que há uma diferença significativa entre as aves favoritas de áreas residenciais e instituições. O pombo recebeu mais semelhanças na população de pássaros entre os residentes de áreas residenciais, enquanto o myna recebeu menos. A ave mais popular nas instituições de Faisalabad era o pardal, enquanto a ave menos popular era o myna comum. A porcentagem de adaptação de pássaros em áreas residenciais e institucionais de Faisalabad foi a mais alta para papagaios e pardais, respectivamente. As pessoas em áreas residenciais e instituições, por outro lado, se adaptaram menos ao myna comum. Conclui-se que pessoas da área de estudo como pássaros e alimentos oferecidos e alta população de pássaros estão presentes na área de estudo.
Subject(s)
Humans , Animals , Birds , Ecosystem , Pakistan , Cities , BiodiversityABSTRACT
Pharmacologic inhibition of LSD1 induces molecular and morphologic differentiation of blast cells in acute myeloid leukemia (AML) patients harboring MLL gene translocations. In addition to its demethylase activity, LSD1 has a critical scaffolding function at genomic sites occupied by the SNAG domain transcription repressor GFI1. Importantly, inhibitors block both enzymatic and scaffolding activities, in the latter case by disrupting the protein:protein interaction of GFI1 with LSD1. To explore the wider consequences of LSD1 inhibition on the LSD1 protein complex we applied mass spectrometry technologies. We discovered that the interaction of the HMG-box protein HMG20B with LSD1 was also disrupted by LSD1 inhibition. Downstream investigations revealed that HMG20B is co-located on chromatin with GFI1 and LSD1 genome-wide; the strongest HMG20B binding co-locates with the strongest GFI1 and LSD1 binding. Functional assays demonstrated that HMG20B depletion induces leukemia cell differentiation and further revealed that HMG20B is required for the transcription repressor activity of GFI1 through stabilizing LSD1 on chromatin at GFI1 binding sites. Interaction of HMG20B with LSD1 is through its coiled-coil domain. Thus, HMG20B is a critical component of the GFI1:LSD1 transcription repressor complex which contributes to leukemia cell differentiation block.
Subject(s)
Histone Demethylases , Leukemia, Myeloid, Acute , Humans , Cell Differentiation/genetics , Chromatin/genetics , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Histone Demethylases/metabolism , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/metabolism , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
Avian pathogenic Escherichia coli (APEC) induces colibacillosis, an acute and systemic disease, resulting in substantial economic losses in the poultry sector. This study aimed to investigate the antibiotic resistance pattern associated with frequent virulence gene distribution in APEC O78:K80 that may cause pathological alterations in chickens. The antibiogram profile showed high resistance to erythromycin, chloramphenicol, tetracycline, ampicillin, and co-trimoxazole, followed by intermediate resistance to ciprofloxacin, levofloxacin, enrofloxacin, norfloxacin, nitrofurantoin, and doxycycline hydrochloride, and sensitive to amikacin, streptomycin, gentamicin, and colistin. Virulence gene distribution identifies eight (irp-2, iutA, ompT, iss, iucD, astA, hlyF, iroN) genes through a conventional polymerase chain reaction. APEC O78:K80 caused significantly high liver enzyme concentrations, serum interleukin-6 and tumor necrosis factor-alpha levels in experimental birds. Also, infected birds have hypoproteinemia, hypoalbuminemia, and hyperglobulinemia. Necropsy examination revealed fibrinous perihepatitis and pericarditis, congested lungs, intestinal ecchymotic hemorrhages and necrotizing granulomatosis of the spleen. Histopathological examination depicted hepatocellular degeneration, myocardial necrosis, interstitial nephritis, intestinal hemorrhages and lymphopenia in the spleen. This study is the first evidence to assess the antibiotic resistance profile linked with virulence genes and clinicopathological potential of APEC O78:K80 in chickens in Pakistan, which could be a useful and rapid approach to prevent and control the disease by developing the control strategies.
Subject(s)
Escherichia coli Infections , Poultry Diseases , Animals , Chickens , Drug Resistance, Microbial , Escherichia coli/genetics , Escherichia coli Infections/veterinary , HemorrhageABSTRACT
This study was aimed to investigate Carbofuran (CF)-induced pathological changes in cattle egret. Two hundred cattle egrets were reared and equally divided into four groups and given different CF concentrations (0.03 mg/L, 0.02 mg/L, 0.01 mg/L and 0 mg/L (control group)). Hematology, serum biochemistry, histopathology, and immunological markers were studied. Our results confirm that CF induces anemic conditions, leukocytosis, elevated liver enzymatic activity, and alterations in renal biomarkers. Moreover, specific microscopic lesions such as multifocal necrosis, pyknotic nuclei, hemorrhages, congestion, and inflammatory cell proliferation were observed in the liver, kidney, spleen, and thymus. These findings suggest that CF can induce harmful effects, so the application of this pesticide in the field must be strictly monitored to mitigate the possibility of exposure to non-target species.
Subject(s)
Carbofuran , Animals , Birds , Carbofuran/toxicity , CattleABSTRACT
Birds are among the best bio-indicators, which can guide us to recognize some of the main conservation concerns in ecosystems. Anthropogenic impacts such as deforestation, habitat degradation, modification of landscapes, and decreased quality of habitats are major threats to bird diversity. The present study was designed to detect anthropogenic causative agents that act on waterbird diversity in Tarbella Dam, Indus River, Pakistan. Waterbird censuses were carried out from March 2019 to February 2020 in multiple areas around the dam. A total of 2990 waterbirds representing 63 species were recorded. We detected the highest waterbird richness and diversity at Pehure whereas the highest density was recorded at Kabbal. Human activity impacts seemed to be the main factor determining the waterbird communities as waterbirds were negatively correlated with the greatest anthropogenic impacts. Waterbirds seem to respond rapidly to human disturbance.
Subject(s)
Ecosystem , Rivers , Conservation of Natural Resources , Humans , PakistanABSTRACT
Birds are very valuable indicators of species richness and endemic patterns in a specified ecosystem, which eventually help the scientist to measure the environmental degradation. The aim of present study was to know human knowledge and attitude toward urban birds in Faisalabad city, Pakistan. The study conducted in four consecutive months: November 2019 to February 2020. Population of birds was noted from eight residential towns of Faisalabad city, data were collected through questionnaire. Faisalabad has a reasonably large population of birds and present data show that, there is a significant difference between favorite bird of residential areas and institutions. The pigeon received the most likeness in bird population among residential area residents, while the myna received the least. The most popular bird in Faisalabad institutions was the sparrow, while the least popular bird was the common myna. Bird adaptation percentage of residential areas and institutional areas of Faisalabad was the highest for parrot and sparrow respectively. People in residential areas and institutions, on the other hand, adapted least to common myna. It is concluded that people of the study area like birds and offered food and high population of birds are present in study area.
Subject(s)
Birds , Ecosystem , Animals , Biodiversity , Cities , Humans , PakistanABSTRACT
BACKGROUND: Disease relapse remains common following treatment of acute myeloid leukemia (AML) and is due to chemoresistance of leukemia cells with disease repopulating potential. To date, attempts to define the characteristics of in vivo resistant blasts have focused on comparisons between leukemic cells at presentation and relapse. However, further treatment responses are often seen following relapse, suggesting that most blasts remain chemosensitive. We sought to characterise in vivo chemoresistant blasts by studying the transcriptional and genetic features of blasts from before and shortly after induction chemotherapy using paired samples from six patients with primary refractory AML. METHODS: Leukemic blasts were isolated by fluorescence-activated cell sorting. Fluorescence in situ hybridization (FISH), targeted genetic sequencing and detailed immunophenotypic analysis were used to confirm that sorted cells were leukemic. Sorted blasts were subjected to RNA sequencing. Lentiviral vectors expressing short hairpin RNAs were used to assess the effect of FOXM1 knockdown on colony forming capacity, proliferative capacity and apoptosis in cell lines, primary AML cells and CD34+ cells from healthy donors. RESULTS: Molecular genetic analysis revealed early clonal selection occurring after induction chemotherapy. Immunophenotypic characterisation found leukemia-associated immunophenotypes in all cases that persisted following treatment. Despite the genetic heterogeneity of the leukemias studied, transcriptional analysis found concerted changes in gene expression in resistant blasts. Remarkably, the gene expression signature suggested that post-chemotherapy blasts were more proliferative than those at presentation. Resistant blasts also appeared less differentiated and expressed leukemia stem cell (LSC) maintenance genes. However, the proportion of immunophenotypically defined LSCs appeared to decrease following treatment, with implications for the targeting of these cells on the basis of cell surface antigen expression. The refractory gene signature was highly enriched with targets of the transcription factor FOXM1. shRNA knockdown experiments demonstrated that the viability of primary AML cells, but not normal CD34+ cells, depended on FOXM1 expression. CONCLUSIONS: We found that chemorefractory blasts from leukemias with varied genetic backgrounds expressed a common transcriptional program. In contrast to the notion that LSC quiescence confers resistance to chemotherapy we find that refractory blasts are both actively proliferating and enriched with LSC maintenance genes. Using primary patient material from a relevant clinical context we also provide further support for the role of FOXM1 in chemotherapy resistance, proliferation and stem cell function in AML.
Subject(s)
Blast Crisis/genetics , Drug Resistance, Neoplasm/genetics , Forkhead Box Protein M1/genetics , Induction Chemotherapy , Leukemia, Myeloid, Acute/genetics , Adolescent , Adult , Aged , Apoptosis/genetics , Blast Crisis/drug therapy , Blast Crisis/metabolism , Blast Crisis/pathology , Cell Differentiation , Cell Proliferation/genetics , Cell Survival , Female , Flow Cytometry , Forkhead Box Protein M1/metabolism , Gene Silencing , Humans , Immunophenotyping , In Situ Hybridization, Fluorescence , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/metabolism , Leukemia, Myeloid, Acute/pathology , Male , Middle Aged , Neoplastic Stem Cells/pathology , RNA, Small Interfering/metabolism , Recurrence , Tumor Stem Cell Assay , Young AdultABSTRACT
The present work focuses the study of effect of solvent on third-order nonlinear optical (NLO) properties of reactive blue 19 dye dissolved in various polar solvents, namely ethanol, DMF and DMSO, respectively. Fourier Transform Infrared Spectroscopy (FT-IR) was used to find the functional groups present in reactive blue 19 dye. Third-order NLO features of reactive blue 19 dye was examined by a low power continuous wave laser of 650 nm wavelength. Reactive blue 19 dye exhibit negative nonlinear index of refraction of the power of 10-7 cm2/W and the nonlinear coefficient of absorption of the order of 10-3 cm/W. Both positive and negative nonlinear absorption coefficient of reactive blue 19 dye in different polar solvents is due to the characteristic behavior of saturable and reverse saturable absorption. Third-order NLO susceptibility of reactive blue 19 dye in polar solvents was determined to be the power of 10-6 esu. The experimental results reveal that the dye sample reactive blue 19 is a potential material for nonlinear optical applications.
ABSTRACT
BACKGROUND: Resistance to chemotherapy is the most common cause of treatment failure in acute myeloid leukemia (AML) and the drug efflux pump ABCB1 is a critical mediator. Recent studies have identified promoter translocations as common drivers of high ABCB1 expression in recurrent, chemotherapy-treated high-grade serous ovarian cancer (HGSC) and breast cancer. These fusions place ABCB1 under the control of a strong promoter while leaving its open reading frame intact. The mechanisms controlling high ABCB1 expression in AML are largely unknown. We therefore established an experimental system and analysis pipeline to determine whether promoter translocations account for high ABCB1 expression in cases of relapsed human AML. METHODS: The human AML cell line THP-1 was used to create a model of chemotherapy resistance in which ABCB1 expression was driven by a promoter fusion. The THP-1 model was used to establish a targeted nanopore long-read sequencing approach that was then applied to cases of ABCB1high HGSC and AML. H3K27Ac ChIP sequencing was used to assess the activity of native promoters in cases of ABCB1high AML. RESULTS: Prolonged in vitro daunorubicin exposure induced activating ABCB1 promoter translocations in human THP-1 AML cells, similar to those recently described in recurrent high-grade serous ovarian and breast cancers. Targeted nanopore sequencing proved an efficient method for identifying ABCB1 structural variants in THP-1 AML cells and HGSC; the promoter translocations identified in HGSC were both previously described and novel. In contrast, activating ABCB1 promoter translocations were not identified in ABCB1high AML; instead H3K27Ac ChIP sequencing demonstrated active native promoters in all cases studied. CONCLUSIONS: Despite frequent high level expression of ABCB1 in relapsed primary AML we found no evidence of ABCB1 translocations and instead confirmed high-level activity of native ABCB1 promoters, consistent with endogenous regulation.
