Globalization has contributed to several advances in technology including linking people around t... more Globalization has contributed to several advances in technology including linking people around the globe and driving us to modern economies. With fast economic growth and industrialization progress, the negative impact of globalization on biodiversity can be easily ignored. Globalization is an undeniable factor in our planetary devastation from pollution to global warming and climate change. The major intention of our recent analysis was to examine globalization, energy consumption, trade, economic growth, and fuel importation to determine the ecological footprint in Pakistan by taking the annual data variables from 1974–2017. A linear ARDL (autoregressive distributed lag) technique with limited information maximum likelihood and linear Gaussian model estimation were utilized to check the association of the variables. Outcomes show that in the long run, globalization, energy usage, trade, and GDP growth have consistently productive interactions with the ecological footprint, while ...
The current era of computing is witnessing a huge amount of data being generated with every passi... more The current era of computing is witnessing a huge amount of data being generated with every passing moment. This massive data if nourished effectively can open new horizons for the computing world. The modern world is slowly but surely moving towards the automation age where every entity and object is being automated to perform desired tasks without the need of human interventions. This has made the lives of people more convenient and comfortable. Automation has taken over every single field of computing and even beyond. Smart mobility is one such example of automation wherein the users get real time information about the traffic conditions as well as alternate route suggestions in case of traffic jams. Transportation is considered as the backbone of every business. The automated intelligent transportation system (ITS) has completely transformed the way how people, goods and services are transported and is quite important for achieving sustainability. This paper provides an overview of the existing ITS system, concept of smart mobility and existing vulnerabilities in these systems. Their security concerns and scenarios are also analyzed. Furthermore, in this paper the importance and need for securing these intelligent systems is highlighted and future trends in ITS is also suggested. Although ITS and smart mobility technology are already providing convenient transportation and navigational facilities, there is still a huge scope to improve these facilities for the end users. The suggested future trends if integrated in an effective manner can provide exemplary means to provide state-of-the-art navigational facilities and smart mobility in a true sense.
MATTER: International Journal of Science and Technology, Oct 31, 2017
India's future rests on its ability to harness the creative potential of its large young populati... more India's future rests on its ability to harness the creative potential of its large young population. In order to foster innovation and creativity, problem and project-based learning (PBL) play an important role. These help to link education to relevant in real-life experience and this connection is crucial for engaging the young minds and increasing their motivation levels. Undertaking innovative experiments, projects and problem solving exercises in multidisciplinary set up brings joy to learning. The enjoyment factor involved in such engagement enhances young people's motivation and interest levels, thereby opens doors for flow and creativity. Thus, provision of innovation spaces in schools and colleges, museums and science centers or institutions of non-formal learning, where such activities can be undertaken is recognized to play an important role in fostering creativity and inspiring innovation by young students. This will ultimately lead to developed culture of innovation in the country.
In this paper, a voice coil motor (VCM) actuated fast tool servo (FTS) system is developed for di... more In this paper, a voice coil motor (VCM) actuated fast tool servo (FTS) system is developed for diamond turning. To guide motions of the VCM actuator, a crossed double parallelogram flexure mechanism is selected featuring totally symmetric structure with high lateral stiffness. To facilitate the determination of the multi-physical parameters, analytical models of both electromagnetic and mechanical systems are developed. The designed FTS with balanced stroke and natural frequency is then verified through the finite element analysis. Finally, the prototype of the VCM actuated FTS is fabricated and experimentally demonstrated to have a stroke of ±59.02 μm and a first natural frequency of 253 Hz. By constructing a closed-loop control using PID controller with the internal-model based resonant controller, the error for tracking a harmonic trajectory with ±10 μm amplitude and 120 Hz frequency is obtained to be ±0.2 μm, demonstrating the capability of the FTS for high accuracy trajectory t...
Petroleum contamination and its remediation via plant-based solutions have got increasing attenti... more Petroleum contamination and its remediation via plant-based solutions have got increasing attention by environmental scientists and engineers. In the current study, the physiological and growth responses of two diesel-tolerant plant species (tolerance limit: 1500-2000 mg/kg), Italian ryegrass (Lolium multiflorum) and Birdsfoot trefoil (Lotus corniculatus), have been investigated in vegetable oil-and diesel oil-amended soils. A long-term (147-day) greenhouse pot experiment was conducted to differentiate the main focus of the study: physical and chemical effects of oil (vegetable and diesel) in freshly spiked soils via evaluating the plant performance and hydrocarbon degradation. Moreover, plant performance was evaluated in terms of seed germination, plant shoot biomass, physiological parameters, and root biomass. Addition of both diesel oil and vegetable oil in freshly spiked soils showed deleterious effects on seedling emergence, root/shoot biomass, and chlorophyll content of grass and legume plants. Italian ryegrass showed more sensitivity in terms of germination rate to both vegetable and diesel oil as compared to noncontaminated soils while Birdsfoot trefoil reduced the germination rate only in diesel oil-impacted soils. The results of the current study suggest that both physical and chemical effects of oil pose negative effects of plant growth and root development. This observation may explain the phenomenon of reduced plant growth in aged/weathered contaminated soils during rhizoremediation experiments.
Management of primary spontaneous pneumothorax (PSP) depends on the symptoms and size of lung col... more Management of primary spontaneous pneumothorax (PSP) depends on the symptoms and size of lung collapse. The British Thoracic Society recommends needle aspiration (NA) for all PSP requiring intervention, followed by intercostal drain (ICD) if NA fails. We compared the role of NA versus ICD as the first step in PSP with 'complete lung collapse'. This was a retrospective observational study of 877 consecutive pneumothorax episodes at University Hospitals of North Midlands, Stoke on Trent, UK. Chest X-ray (CXR) at presentation was reviewed to identify PSP with complete lung collapse. The primary outcome measure was successful lung re-inflation after initial intervention. Two-hundred and sixty-six PSP patients were identified; 69 had complete lung collapse on CXR of which 35 had NA and 34 had ICD. The ICD group had a significantly better immediate success compared with the NA group (62% versus 11%, odds ratio (OR) = 12.5, p<0.0001; after adjustment for potential confounders, OR increased to 26.4, p=0.0001) although long-term outcomes were comparable. There should be clear consensus on definition and management of complete lung collapse. PSP with complete lung collapse could be managed as a separate subgroup where ICD placement is considered to be the first intervention.
Background: This study explores the electricity access to rural and urban populations and its imp... more Background: This study explores the electricity access to rural and urban populations and its impact on the economic growth in Pakistan. Methods: An autoregressive distributed lag (ARDL) bounds testing approach was applied, and a co-integration test was used to investigate the dynamic causality relationships between the study variables. By using this testing approach, this study filled the literature gap regarding the access of rural and urban population to electricity in Pakistan. Results: The tests shed light on the long-run relationship among the variables, whereas the results revealed that the access of both rural and urban populations to electricity had a positive and significant effect on economic growth. Conclusions: According to these findings, we can conclude that Pakistan should pay further attention to increasing its electricity production from different sources, including not only hydroelectric, solar, wind, oil, gas, and biomass but also fewer and fewer nuclear sources, in order to fulfill the country's demands on its way to a future of sustainable development.
Rapid increase in the quantity of electronic/electrical-waste (e-waste) has become an emerging is... more Rapid increase in the quantity of electronic/electrical-waste (e-waste) has become an emerging issue throughout the world. To avoid higher expenditures on safe disposal and recycling, large quantities of e-waste are being exported from developed to developing countries like Pakistan. Emerging issue of e-waste in Pakistan demands its effective management strategy for the country. However, it cannot be achieved until assessment of e-waste quantification and disposal is carried out. The main objective of this study was to quantify the e-waste inventory and it&amp;amp;#39;s processing from major cities of Pakistan to evaluate its generation (domestic/import) and recycling practices. This study comprises the information of only those e-waste items (desktop computers, laptops/notebooks, computer monitors and liquid-crystal display units) which form the major portion of e-waste imported to Pakistan. Survey based data collected from three major cities/areas have been extrapolated to develop an e-waste generation inventory for the country. The study reveals that approximately 50 kt of e-waste is being imported as scrap in addition to its local generation of about 38 kt per year. During field visits and data collection surveys, it has been observed that the processing of e-waste in the country is being carried out in crude manner without safety gears. Findings of our study strongly recommend dire need for urgent and effective monitoring as well as control of informal e-waste management in Pakistan.
Environmental problems such as the deterioration of groundwater quality, soil degradation and var... more Environmental problems such as the deterioration of groundwater quality, soil degradation and various threats to human, animal and ecosystem health are closely related to the presence of high concentrations of organic xenobiotics in the environment. Employing appropriate technologies to remediate contaminated soils is crucial due to the site-specificity of most remediation methods. The limitations of conventional remediation technologies include poor environmental compatibility, high cost of implementation and poor public acceptability. This raises the call to employ biological methods for remediation. Bioremediation and microbe-assisted bioremediation (phytoremediation) offer many ecological and cost-associated benefits. The overall efficiency and performance of bio- and phytoremediation approaches can be enhanced by genetically modified microbes and plants. Moreover, phytoremediation can also be stimulated by suitable plant-microbe partnerships, i.e. plant-endophytic or plant-rhiz...
International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists, Jan 18, 2018
TP53 gene mutations are known to manifest in distinct p53 immunohistochemical staining patterns; ... more TP53 gene mutations are known to manifest in distinct p53 immunohistochemical staining patterns; overexpression, wild-type, and null. These stratified staining patterns are routinely utilized in subtyping ovarian cancer subtypes. Three ovarian cancer cell lines were used in the construction of an immunohistochemical p53 expression pattern control panel that highlight respective TP53 mutation status. The cell line control panel sections demonstrated consistent clean and easily interpretable p53 immunohistochemical staining. Procured resection, biopsy, and cytologic specimens were submitted along with either standard control tissue or a p53 cell line control panel to pathologists of varying experience for interrater reliability analysis. Individual interrater reliability was near-perfect and was improved with the p53 cell line control panel when compared with the tissue control. The cell line control panel demonstrated decreased misinterpretation of null expression pattern as wild-typ...
Hypoxia-inducible factor-1alpha (HIF-1α) is aberrantly upregulated in tumors and implicated in an... more Hypoxia-inducible factor-1alpha (HIF-1α) is aberrantly upregulated in tumors and implicated in angiogenesis, metastasis, and drug resistance. Therefore, developing treatments that target HIF-1α may be a viable therapeutic approach. In Traditional Chinese Medicine (TCM), Scutellaria baicalensis (SB) is used for the treatment of cancer but the anti-cancer mechanisms are not known. We examined the effects of SB on HIF-1α expression in ovarian cancer (OC) cell lines grown under normoxic and hypoxic conditions. SB treatment attenuated HIF-1α expression in cancer cell lines. Treatment of cells with cycloheximide (CHX) reduced HIF-1α levels similar to cells treated with SB. Furthermore, SB-induced HIF-1α inhibition was abrogated by the proteasomal inhibitor MG132 and a lysosome inhibitor, chloroquine. Activation of PI3K/AKT and MAPK/ERK seen in OC cells was reduced with SB. Pretreatment of cells with LY294002 (phosphoinositide 3-kinase inhibitor) and PD98059 (mitogen-activated protein kina...
The mechanisms whereby progesterone (P 4), acting via the progesterone receptor (PR), inhibits pr... more The mechanisms whereby progesterone (P 4), acting via the progesterone receptor (PR), inhibits proinflammatory/contractile gene expression during pregnancy are incompletely defined. Using immortalized human myometrial (hTERT-HM) cells stably expressing wild-type PR-A or PR-B (PR WT), we found that P 4 significantly inhibited IL-1 induction of the NF-B target genes, COX-2 and IL-8. P 4-PR WT transrepression occurred at the level of transcription initiation and was mediated by decreased recruitment of NF-B p65 and RNA polymerase II to COX-2 and IL-8 promoters. However, in cells stably expressing a PR-A or PR-B DNA-binding domain mutant (PR mDBD), P 4-mediated transrepression was significantly reduced, suggesting a critical role of the PR DBD. ChIP analysis of hTERT-HM cells stably expressing PR WT or PR mDBD revealed that P 4 treatment caused equivalent recruitment of PR WT and PR mDBD to COX-2 and IL-8 promoters, suggesting that PR inhibitory effects were not mediated by its direct DNA binding. Using immunoprecipitation, followed by MS, we identified a transcriptional repressor, GATA zinc finger domaincontaining 2B (GATAD2B), that interacted strongly with PR WT but poorly with PR mDBD. P 4 treatment of PR WT hTERT-HM cells caused enhanced recruitment of endogenous GATAD2B to COX-2 and IL-8 promoters. Further, siRNA knockdown of endogenous GATAD2B significantly reduced P 4-PR WT transrepression of COX-2 and IL-8. Notably, GATAD2B expression was significantly decreased in pregnant mouse and human myometrium during labor. Our findings suggest that GATAD2B serves as an important mediator of P 4-PR suppression of proinflammatory and contractile genes during pregnancy. Decreased GATAD2B expression near term may contribute to the decline in PR function, leading to labor.
Globalization has contributed to several advances in technology including linking people around t... more Globalization has contributed to several advances in technology including linking people around the globe and driving us to modern economies. With fast economic growth and industrialization progress, the negative impact of globalization on biodiversity can be easily ignored. Globalization is an undeniable factor in our planetary devastation from pollution to global warming and climate change. The major intention of our recent analysis was to examine globalization, energy consumption, trade, economic growth, and fuel importation to determine the ecological footprint in Pakistan by taking the annual data variables from 1974–2017. A linear ARDL (autoregressive distributed lag) technique with limited information maximum likelihood and linear Gaussian model estimation were utilized to check the association of the variables. Outcomes show that in the long run, globalization, energy usage, trade, and GDP growth have consistently productive interactions with the ecological footprint, while ...
The current era of computing is witnessing a huge amount of data being generated with every passi... more The current era of computing is witnessing a huge amount of data being generated with every passing moment. This massive data if nourished effectively can open new horizons for the computing world. The modern world is slowly but surely moving towards the automation age where every entity and object is being automated to perform desired tasks without the need of human interventions. This has made the lives of people more convenient and comfortable. Automation has taken over every single field of computing and even beyond. Smart mobility is one such example of automation wherein the users get real time information about the traffic conditions as well as alternate route suggestions in case of traffic jams. Transportation is considered as the backbone of every business. The automated intelligent transportation system (ITS) has completely transformed the way how people, goods and services are transported and is quite important for achieving sustainability. This paper provides an overview of the existing ITS system, concept of smart mobility and existing vulnerabilities in these systems. Their security concerns and scenarios are also analyzed. Furthermore, in this paper the importance and need for securing these intelligent systems is highlighted and future trends in ITS is also suggested. Although ITS and smart mobility technology are already providing convenient transportation and navigational facilities, there is still a huge scope to improve these facilities for the end users. The suggested future trends if integrated in an effective manner can provide exemplary means to provide state-of-the-art navigational facilities and smart mobility in a true sense.
MATTER: International Journal of Science and Technology, Oct 31, 2017
India's future rests on its ability to harness the creative potential of its large young populati... more India's future rests on its ability to harness the creative potential of its large young population. In order to foster innovation and creativity, problem and project-based learning (PBL) play an important role. These help to link education to relevant in real-life experience and this connection is crucial for engaging the young minds and increasing their motivation levels. Undertaking innovative experiments, projects and problem solving exercises in multidisciplinary set up brings joy to learning. The enjoyment factor involved in such engagement enhances young people's motivation and interest levels, thereby opens doors for flow and creativity. Thus, provision of innovation spaces in schools and colleges, museums and science centers or institutions of non-formal learning, where such activities can be undertaken is recognized to play an important role in fostering creativity and inspiring innovation by young students. This will ultimately lead to developed culture of innovation in the country.
In this paper, a voice coil motor (VCM) actuated fast tool servo (FTS) system is developed for di... more In this paper, a voice coil motor (VCM) actuated fast tool servo (FTS) system is developed for diamond turning. To guide motions of the VCM actuator, a crossed double parallelogram flexure mechanism is selected featuring totally symmetric structure with high lateral stiffness. To facilitate the determination of the multi-physical parameters, analytical models of both electromagnetic and mechanical systems are developed. The designed FTS with balanced stroke and natural frequency is then verified through the finite element analysis. Finally, the prototype of the VCM actuated FTS is fabricated and experimentally demonstrated to have a stroke of ±59.02 μm and a first natural frequency of 253 Hz. By constructing a closed-loop control using PID controller with the internal-model based resonant controller, the error for tracking a harmonic trajectory with ±10 μm amplitude and 120 Hz frequency is obtained to be ±0.2 μm, demonstrating the capability of the FTS for high accuracy trajectory t...
Petroleum contamination and its remediation via plant-based solutions have got increasing attenti... more Petroleum contamination and its remediation via plant-based solutions have got increasing attention by environmental scientists and engineers. In the current study, the physiological and growth responses of two diesel-tolerant plant species (tolerance limit: 1500-2000 mg/kg), Italian ryegrass (Lolium multiflorum) and Birdsfoot trefoil (Lotus corniculatus), have been investigated in vegetable oil-and diesel oil-amended soils. A long-term (147-day) greenhouse pot experiment was conducted to differentiate the main focus of the study: physical and chemical effects of oil (vegetable and diesel) in freshly spiked soils via evaluating the plant performance and hydrocarbon degradation. Moreover, plant performance was evaluated in terms of seed germination, plant shoot biomass, physiological parameters, and root biomass. Addition of both diesel oil and vegetable oil in freshly spiked soils showed deleterious effects on seedling emergence, root/shoot biomass, and chlorophyll content of grass and legume plants. Italian ryegrass showed more sensitivity in terms of germination rate to both vegetable and diesel oil as compared to noncontaminated soils while Birdsfoot trefoil reduced the germination rate only in diesel oil-impacted soils. The results of the current study suggest that both physical and chemical effects of oil pose negative effects of plant growth and root development. This observation may explain the phenomenon of reduced plant growth in aged/weathered contaminated soils during rhizoremediation experiments.
Management of primary spontaneous pneumothorax (PSP) depends on the symptoms and size of lung col... more Management of primary spontaneous pneumothorax (PSP) depends on the symptoms and size of lung collapse. The British Thoracic Society recommends needle aspiration (NA) for all PSP requiring intervention, followed by intercostal drain (ICD) if NA fails. We compared the role of NA versus ICD as the first step in PSP with 'complete lung collapse'. This was a retrospective observational study of 877 consecutive pneumothorax episodes at University Hospitals of North Midlands, Stoke on Trent, UK. Chest X-ray (CXR) at presentation was reviewed to identify PSP with complete lung collapse. The primary outcome measure was successful lung re-inflation after initial intervention. Two-hundred and sixty-six PSP patients were identified; 69 had complete lung collapse on CXR of which 35 had NA and 34 had ICD. The ICD group had a significantly better immediate success compared with the NA group (62% versus 11%, odds ratio (OR) = 12.5, p<0.0001; after adjustment for potential confounders, OR increased to 26.4, p=0.0001) although long-term outcomes were comparable. There should be clear consensus on definition and management of complete lung collapse. PSP with complete lung collapse could be managed as a separate subgroup where ICD placement is considered to be the first intervention.
Background: This study explores the electricity access to rural and urban populations and its imp... more Background: This study explores the electricity access to rural and urban populations and its impact on the economic growth in Pakistan. Methods: An autoregressive distributed lag (ARDL) bounds testing approach was applied, and a co-integration test was used to investigate the dynamic causality relationships between the study variables. By using this testing approach, this study filled the literature gap regarding the access of rural and urban population to electricity in Pakistan. Results: The tests shed light on the long-run relationship among the variables, whereas the results revealed that the access of both rural and urban populations to electricity had a positive and significant effect on economic growth. Conclusions: According to these findings, we can conclude that Pakistan should pay further attention to increasing its electricity production from different sources, including not only hydroelectric, solar, wind, oil, gas, and biomass but also fewer and fewer nuclear sources, in order to fulfill the country's demands on its way to a future of sustainable development.
Rapid increase in the quantity of electronic/electrical-waste (e-waste) has become an emerging is... more Rapid increase in the quantity of electronic/electrical-waste (e-waste) has become an emerging issue throughout the world. To avoid higher expenditures on safe disposal and recycling, large quantities of e-waste are being exported from developed to developing countries like Pakistan. Emerging issue of e-waste in Pakistan demands its effective management strategy for the country. However, it cannot be achieved until assessment of e-waste quantification and disposal is carried out. The main objective of this study was to quantify the e-waste inventory and it&amp;amp;#39;s processing from major cities of Pakistan to evaluate its generation (domestic/import) and recycling practices. This study comprises the information of only those e-waste items (desktop computers, laptops/notebooks, computer monitors and liquid-crystal display units) which form the major portion of e-waste imported to Pakistan. Survey based data collected from three major cities/areas have been extrapolated to develop an e-waste generation inventory for the country. The study reveals that approximately 50 kt of e-waste is being imported as scrap in addition to its local generation of about 38 kt per year. During field visits and data collection surveys, it has been observed that the processing of e-waste in the country is being carried out in crude manner without safety gears. Findings of our study strongly recommend dire need for urgent and effective monitoring as well as control of informal e-waste management in Pakistan.
Environmental problems such as the deterioration of groundwater quality, soil degradation and var... more Environmental problems such as the deterioration of groundwater quality, soil degradation and various threats to human, animal and ecosystem health are closely related to the presence of high concentrations of organic xenobiotics in the environment. Employing appropriate technologies to remediate contaminated soils is crucial due to the site-specificity of most remediation methods. The limitations of conventional remediation technologies include poor environmental compatibility, high cost of implementation and poor public acceptability. This raises the call to employ biological methods for remediation. Bioremediation and microbe-assisted bioremediation (phytoremediation) offer many ecological and cost-associated benefits. The overall efficiency and performance of bio- and phytoremediation approaches can be enhanced by genetically modified microbes and plants. Moreover, phytoremediation can also be stimulated by suitable plant-microbe partnerships, i.e. plant-endophytic or plant-rhiz...
International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists, Jan 18, 2018
TP53 gene mutations are known to manifest in distinct p53 immunohistochemical staining patterns; ... more TP53 gene mutations are known to manifest in distinct p53 immunohistochemical staining patterns; overexpression, wild-type, and null. These stratified staining patterns are routinely utilized in subtyping ovarian cancer subtypes. Three ovarian cancer cell lines were used in the construction of an immunohistochemical p53 expression pattern control panel that highlight respective TP53 mutation status. The cell line control panel sections demonstrated consistent clean and easily interpretable p53 immunohistochemical staining. Procured resection, biopsy, and cytologic specimens were submitted along with either standard control tissue or a p53 cell line control panel to pathologists of varying experience for interrater reliability analysis. Individual interrater reliability was near-perfect and was improved with the p53 cell line control panel when compared with the tissue control. The cell line control panel demonstrated decreased misinterpretation of null expression pattern as wild-typ...
Hypoxia-inducible factor-1alpha (HIF-1α) is aberrantly upregulated in tumors and implicated in an... more Hypoxia-inducible factor-1alpha (HIF-1α) is aberrantly upregulated in tumors and implicated in angiogenesis, metastasis, and drug resistance. Therefore, developing treatments that target HIF-1α may be a viable therapeutic approach. In Traditional Chinese Medicine (TCM), Scutellaria baicalensis (SB) is used for the treatment of cancer but the anti-cancer mechanisms are not known. We examined the effects of SB on HIF-1α expression in ovarian cancer (OC) cell lines grown under normoxic and hypoxic conditions. SB treatment attenuated HIF-1α expression in cancer cell lines. Treatment of cells with cycloheximide (CHX) reduced HIF-1α levels similar to cells treated with SB. Furthermore, SB-induced HIF-1α inhibition was abrogated by the proteasomal inhibitor MG132 and a lysosome inhibitor, chloroquine. Activation of PI3K/AKT and MAPK/ERK seen in OC cells was reduced with SB. Pretreatment of cells with LY294002 (phosphoinositide 3-kinase inhibitor) and PD98059 (mitogen-activated protein kina...
The mechanisms whereby progesterone (P 4), acting via the progesterone receptor (PR), inhibits pr... more The mechanisms whereby progesterone (P 4), acting via the progesterone receptor (PR), inhibits proinflammatory/contractile gene expression during pregnancy are incompletely defined. Using immortalized human myometrial (hTERT-HM) cells stably expressing wild-type PR-A or PR-B (PR WT), we found that P 4 significantly inhibited IL-1 induction of the NF-B target genes, COX-2 and IL-8. P 4-PR WT transrepression occurred at the level of transcription initiation and was mediated by decreased recruitment of NF-B p65 and RNA polymerase II to COX-2 and IL-8 promoters. However, in cells stably expressing a PR-A or PR-B DNA-binding domain mutant (PR mDBD), P 4-mediated transrepression was significantly reduced, suggesting a critical role of the PR DBD. ChIP analysis of hTERT-HM cells stably expressing PR WT or PR mDBD revealed that P 4 treatment caused equivalent recruitment of PR WT and PR mDBD to COX-2 and IL-8 promoters, suggesting that PR inhibitory effects were not mediated by its direct DNA binding. Using immunoprecipitation, followed by MS, we identified a transcriptional repressor, GATA zinc finger domaincontaining 2B (GATAD2B), that interacted strongly with PR WT but poorly with PR mDBD. P 4 treatment of PR WT hTERT-HM cells caused enhanced recruitment of endogenous GATAD2B to COX-2 and IL-8 promoters. Further, siRNA knockdown of endogenous GATAD2B significantly reduced P 4-PR WT transrepression of COX-2 and IL-8. Notably, GATAD2B expression was significantly decreased in pregnant mouse and human myometrium during labor. Our findings suggest that GATAD2B serves as an important mediator of P 4-PR suppression of proinflammatory and contractile genes during pregnancy. Decreased GATAD2B expression near term may contribute to the decline in PR function, leading to labor.
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