Seasonal changes of sources, volatility, and aging of organic aerosols in eastern Europe reflected in the stable isotopic composition
<p><span lang="EN-GB">The stable carbon isotope <sup... more <p><span lang="EN-GB">The stable carbon isotope <sup>13</sup>C has the potential to give insights into sources and processing of organic aerosol. </span>We use a method to measure d<sup>13</sup>C in OC desorbed from filter samples at three different temperature steps: 200 °C, 350°C and 650°C. The results give a rough indication of aerosol volatility, as more volatile compounds usually desorb at lower temperatures.</p> <p>We demonstrate with an extensive source study that in Lithuania and likely other Eastern European regions, the main anthropogenic primary sources for organic carbon (OC) have distinct isotopic signatures. d<sup>13</sup>C values of vehicular emissions show the most negative values around - 29 ‰, emissions from combustion of the most common wood types are more enriched with values around -26 to -27 ‰, and coal burning is around -25‰. For source samples, d<sup>13</sup>C values at the three desorption temperature steps usually do not differ more than 1 ‰.</p> <p>In the ambient samples, <span lang="EN-US">OC had more negative δ<sup>13</sup>C values in summer than in winter, which can be explained by the contribution of biomass/coal burning sources in winter. At the urban site δ<sup>13</sup>C of OC did not change much with increasing desorption temperature in winter, which is typical for primary sources. In the summer δ<sup>13</sup>C of OC was clearly more negative for lower desorption temperatures at all three sites. This is likely due to the influence of secondary organic aerosol formation in summer, which should have depleted (more negative) isotopic signature and contributes strongly to the more volatile fraction.</span>A higher fraction of more refractory OC in summer compared to winter-time suggests active photochemical processing of the primary organic aerosol as an important process at all three sites.</p> <p>This is consistent with our laboratory studies, where we age source samples in a small reactor under UV light. Photolysis causes mainly mass loss in OC that desorbs at 200 °C. At the same time, <sup>13</sup>C becomes more enriched in OC desorbed at the higher temperature steps, leading to a bigger difference in d<sup>13</sup>C between OC200 and OC350, as observed in the ambient atmosphere.</p> <p>In summary, analyzing stable isotopes of OC at different desorption temperature steps gives a powerful tool for diagnosing aging processes.</p>
In the current decade, the potential side effects caused by synthetic kinase domain inhibitors ha... more In the current decade, the potential side effects caused by synthetic kinase domain inhibitors have paved the way for developing an alternative anti-breast cancer drug from botanical sources. Estrogen receptor-α (ERα) and epidermal growth factor receptor (EGFR) tyrosine kinase receptors play a key role in the activation of genomic and nongenomic related pathways of breast cancer progression. Paris polyphylla Smith (Melanthiaceae) is a rich source of steroidal saponins reported as an anti-breast cancer agent used among the local communities of Asian countries. In the present study, a total of 116 phytocompounds were characterized and identified from P. polyphylla rhizomes using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry tools. They were subjected to virtual screening, molecular docking, and molecular simulation analysis with these two breast cancer receptors. Among them, only three steroidal saponins, namely, diosgenin, pennogenin, and 7-ketodiosgenin acetate binding affinity with target receptors were on the higher side when compared with natural ligands. The highest affinity for the receptors ERα and EGFR tyrosine kinase was shown by 7-ketodiosgenin acetate with docking scores of −10.4 Kcal/mol and −11.2 Kcal/mol, respectively, followed by diosgenin and pennogenin. LigPlot + analysis revealed that the selected three steroidal saponins utilized a combination of hydrogen bonding and hydrophobic interactions to align themselves more efficiently in the ligand-binding pocket of the target receptors. Molecular simulation analysis revealed a stable interaction between the phytocompounds and the target receptors. Lipinski's rule confirmed pennogenin as the best phytocompound that could be used as a potential inhibitor against the two target breast cancer receptors (ERα and EGFR tyrosine kinase).
<i>In-silico</i> based identification of phytochemicals from <i>Houttuynia cordata</i> Thunb. as potential inhibitors for overexpressed HER2 and VEGFR2 cancer genes
Human epidermal growth factor receptor2 (HER2) and Vascular endothelial growth factor receptor2 (... more Human epidermal growth factor receptor2 (HER2) and Vascular endothelial growth factor receptor2 (VEGFR2) – a tyrosine kinase receptors play a key role in breast and stomach cancers. The overexpression of HER2 and VEGFR2 genes increases the number of HER2 and VEGFR2 in the cell which initiates breast and stomach cancer respectively. The phytochemicals from traditional medicinal herb <i>Houttuynia cordata</i> Thunb. are reported to possess anti-inflammatory and anti-cancer potential. However, isolation of phytochemicals from this herb is fraught with uncertainly and time-consuming. Here, a molecular docking approach provides probable binding affinities between the receptors and phytochemicals (ligands) which initiate the first step of anticancer drug discovery and development. In the present study, <i>In-silico</i> docking approaches were used to identify the top-hit phytochemicals from <i>H. cordata</i> as potential inhibitors for overexpressed HER...
Phytochemical, nutritional and antioxidant potential of Panax bipinnatifidus and Panax pseudoginseng: A study of two underutilized and neglected species from the Eastern Himalayan region of India
In this decade, understanding the impact of human activities on climate is one of the key issues ... more In this decade, understanding the impact of human activities on climate is one of the key issues of discussion globally. The continuous rise in the concentration of greenhouse gases, e.g., CO2, CH4, etc. in the atmosphere, predominantly due to human activities, is alarming and requires continuous monitoring to understand the dynamics. Radiocarbon is an important atmospheric tracer and one of the many used in the understanding of the global carbon budget, which includes the greenhouse gases like CO2 and CH4. Measurement of C (or radiocarbon) in atmospheric CO2 generally requires collection of large air samples (few liters) from which CO2 is extracted and then the concentration of radiocarbon is determined. Currently, Accelerator Mass Spectrometry (AMS) is the most precise, reliable and widely used technique for atmospheric radiocarbon detection. However, the regular collection of air samples from troposphere and stratosphere, for example using aircraft, is prohibitively expensive.
In 2016, the new high-resolution, multi-collector isotope ratio mass spectrometer MAT253 ULTRA [1... more In 2016, the new high-resolution, multi-collector isotope ratio mass spectrometer MAT253 ULTRA [1] was installed at Utrecht University. This instrument is designed to reach a mass resolving power of 20,000 to 40,000 (M/∆M). The ion currents are detected with a variable multi-collector unit that allows to register up to 9 ion currents simultaneously with Faraday cups and ion counters. The width of the entrance slit can be varied between 5 and 250μm so that the instrument can be operated under low, medium and high mass resolution, and an optimum balance between resolution and sensitivity can be selected for the respective applications.
My PhD research deals with radiocarbon, the natural radioactive isotope of carbon, known for its ... more My PhD research deals with radiocarbon, the natural radioactive isotope of carbon, known for its application in dating. The first and main part was the exploration of the capabilities of a new, potentially revolutionary technique to measure radiocarbon. This technique, ICOGS (IntraCavity OptoGalvanic Spectroscopy), much cheaper and easier than the accelerators presently in use, was first published as successful for radiocarbon detection by the Murnick group, Rutgers University, USA. Motivated by their results, we collaborated with them in the development and improvement of ICOGS in Groningen. However, after more than two years of experiments, we had to conclude that the results claimed by the Murnick group were not real. We have finally published these -negative- results in the journal Analytical Chemistry ("ICOGS Not Suitable for Ambient Level Radiocarbon Detection"), to discredit the technique and warn other research groups. So far, however, Murnick et al have not given ...
Developing a preconcentration and purification setup for 14C measurements of atmospheric methane
Methane contributes substantially to global warming as the second most important anthropogenic gr... more Methane contributes substantially to global warming as the second most important anthropogenic greenhouse gas. Its sources are diverse and remain poorly quantified and not well understood [1]. The radiocarbon (14C) content of these emissions is of growing interest since it can be used as a tool for a methane source apportionment [2]. Indeed, contemporary methane (e.g. agriculture, biomass burning) contains present-day 14C levels, whereas fossil methane (e.g. fossil fuels, geologic sources) is 14C-free. However, this task is challenging given the very large amounts of methane required and its very low concentration in the atmosphere. Methane is usually separated from other trace gases in a stepwise process: first CO2 is cryogenically removed, then CO is oxidized to CO2 and also cryogenically removed, before methane can finally be oxidized and isolated as CO2. For this simplified process, cross contamination of CO2 from one fraction to the next remains an issue difficult to overcome [...
Identification of tyrosine kinase inhibitors from Panax bipinnatifidus and Panax pseudoginseng for RTK—HER2 and VEGFR2 receptors, by in silico approach
Molecular Diversity, 2021
Breast and stomach cancer is reported as a leading cause for human mortality across the world. Th... more Breast and stomach cancer is reported as a leading cause for human mortality across the world. The overexpression of receptor tyrosine kinase (RTK) proteins, namely the human epidermal growth factor receptor2 (HER2) and the vascular endothelial growth factor receptor2 (VEGFR2), is reported to be responsible for development and metastasis of breast and stomach cancer. Although several synthetic tyrosine kinase inhibitors (TKIs) as drug candidates targeting RTK-HER2 and VEGFR2 are currently available in the market, these are expensive with the reported side effects. This confers an opportunity for development of alternative novel tyrosine kinase inhibitors (TKIs) for RTK-HER2 and VEGFR2 receptors from the botanical sources. In the present study, we characterized 47 bioactive phytocompounds from the methanol extracts of the rhizomes of Asiatic traditional medicinal herbs-Panax bipinnatifidus and Panax pseudoginseng, of Indian Himalayan landraces using HPLC, GC-MS and high-sensitivity LC-MS tools. We performed molecular docking and molecular dynamics simulation analysis using Schrödinger suite 2020-3 to confirm the TKI phytocompounds showing the best binding affinity towards RTK-HER2 and VEGFR2 receptors. The results of molecular docking studies confirmed that the phytocompound (ligand) luteolin 7-O-glucoside (IHP15) showed the highest binding affinity towards receptor HER2 (PDB ID: 3PP0) with docking score and Glide g score (G-Score) of - 13.272, while chlorogenic acid (IHP12) showed the highest binding affinity towards receptor VEGFR2 (PDB ID: 4AGC) with docking score and Glide g score (G-Score) of - 10.673. Molecular dynamics (MD) simulation analysis carried out for 100 ns has confirmed strong binding interaction between the ligand and receptor complex [luteolin 7-O-glucoside (IHP15) and HER2 (PDB ID: 3PP0)] and is found to be stabilized within 40 to 100 ns of MD simulation, whereas ligand-receptor complex [chlorogenic acid (IPH12) and VEGFR2 (PDB ID: 4AGC)] also showed strong binding interaction and is found to be stabilized within 18-30 ns but slightly deviated during 100 ns of MD simulation. In silico ADME-Tox study using SwissADME revealed that the ligands luteolin 7-O-glucoside (IHP15) and chlorogenic acid (IHP12) have passed majority parameters of the common drug discovery rules. The present study has confirmed luteolin 7-O-glucoside (IHP15) and chlorogenic acid (IHP12) as potential tyrosine kinase inhibitors (TKIs) which were found to inhibit RTKs-HER2 and VEGFR2 receptor proteins, and thus paving the way for development of alternative potential TKIs (drug molecules) for treatment of HER2- and VEGFR2-positive breast and stomach cancer.
In-silico based identification of phytochemicals from Houttuynia cordata Thunb. as potential inhibitors for overexpressed HER2 and VEGFR2 cancer genes
Journal of Biomolecular Structure and Dynamics, 2021
Human epidermal growth factor receptor2 (HER2) and Vascular endothelial growth factor receptor2 (... more Human epidermal growth factor receptor2 (HER2) and Vascular endothelial growth factor receptor2 (VEGFR2) - a tyrosine kinase receptors play a key role in breast and stomach cancers. The overexpression of HER2 and VEGFR2 genes increases the number of HER2 and VEGFR2 in the cell which initiates breast and stomach cancer respectively. The phytochemicals from traditional medicinal herb Houttuynia cordata Thunb. are reported to possess anti-inflammatory and anti-cancer potential. However, isolation of phytochemicals from this herb is fraught with uncertainly and time-consuming. Here, a molecular docking approach provides probable binding affinities between the receptors and phytochemicals (ligands) which initiate the first step of anticancer drug discovery and development. In the present study, In-silico docking approaches were used to identify the top-hit phytochemicals from H. cordata as potential inhibitors for overexpressed HER2 (breast) and VEGFR2 (stomach) cancer genes. A total of 100 biologically active phytochemicals from H. cordata were screened and docked against the ligand-binding pocket of HER2 and VEGFR2 kinase domains. Docking results revealed only a few phytochemicals (molecules) which appropriately fit into the ligand-binding pocket with higher binding affinity than the natural ATP ligand. A competitive docking was used to ascertain the top-hit phytochemicals that bind perfectly to the ATP ligand-binding pocket. Among the top-hit phytochemicals docked from H. cordata, the β-sitosterol and Quercetin showed highest binding affinity towards HER2 and VEGFR2 receptors using both hydrogen and hydrophobic interactions. This study confirmed β-sitosterol and Quercetin as potential drug candidates against breast and stomach cancer.Communicated by Ramaswamy H. Sarma.
• 13 C analysis of EC at the sub-μgC level is achieved by the TOA-IRMS system. • OC/EC separation... more • 13 C analysis of EC at the sub-μgC level is achieved by the TOA-IRMS system. • OC/EC separation and possible effects on the isotopic composition were evaluated. • EC can be well isolated for 13 C analysis using the thermal-optical split point. • Incomplete isolation of EC can bias dual isotope source apportionment.
This paper discusses the brief cross cultural ethnobotany of the Abotani tribes of Arunachal Prad... more This paper discusses the brief cross cultural ethnobotany of the Abotani tribes of Arunachal Pradesh which comprises five different indigenous tribal communities, namely Adi, Apatani, Nyishi, Galo and Tagin residing in Arunachal Pradesh, India. A brief ethnobotanical survey was conducted in Abotani Biocultural Landscape (ABL) in 11 districts of Arunachal Pradesh during the year 2018-2019 with fundamental aims to document significant ethnobotanical plants commonly used among all the 05 Abotani tribes in their local biocultural landscape and to document traditional knowledge and skills related to utilization of ethnobotanical plants resources using semi-structured questionnaire format. The survey have revealed impressive number of 45 species of ethnobotanically significant species frequently harvested and used as local food and medicine security as well as cultural materials among the local residents of 05 major tribes of Abotani cultural group residing in Siang,
Present paper discusses ethnobotany of the economically significant food and medicinal plants use... more Present paper discusses ethnobotany of the economically significant food and medicinal plants used among the Monpa and Nyishi community of West Kameng and Kamle District of Arunachal Pradesh in cross-cultural approaches. The 49 species of both cultivated and wild food and medicinal plants recorded from Monpa and Nyishi biocultural landscape are frequently harvested and used by the local communities as antioxidant food, anti-inflammatory agent and for treatment of various diseases including prevention of cancer and liver cirrhosis which has the potential to be used as nutraceuticals and capable of sustaining the rural economy and livelihood of the rural community.
ABSTRACTThe Centre for Isotope Research (CIO) at the University of Groningen has operated a radio... more ABSTRACTThe Centre for Isotope Research (CIO) at the University of Groningen has operated a radiocarbon (14C) dating laboratory for almost 70 years. In 2017, the CIO received a major upgrade, which involved the relocation of the laboratory to new purpose-built premises, and the installation of a MICADAS accelerator mass spectrometer. This period of transition provides an opportunity to update the laboratory’s routine procedures. This article addresses all of the processes and quality checks the CIO has in place for registering, tracking and pretreating samples for radiocarbon dating. Complementary updates relating to radioisotope measurement and uncertainty propagation will be provided in other forthcoming publications. Here, the intention is to relay all the practical information regarding the chemical preparation of samples, and to provide a concise explanation as to why each step is deemed necessary.
Atmospheric flask samples are either collected at atmospheric pressure by simply opening a valve ... more Atmospheric flask samples are either collected at atmospheric pressure by simply opening a valve of a preevacuated flask, or pressurized with the help of a pump to a few bar above ambient providing large air samples for analysis. Under humid conditions, there is a risk that water vapour in the sample leads to condensation on the walls of the flask, notably at higher than ambient sampling pressures. Liquid water in sample flasks is known to affect the CO 2 mixing ratios and also alters the isotopic composition of oxygen (17 O and 18 O) in CO 2 via isotopic equilibration. Hence, for accurate determination of CO 2 mole fractions and its stable isotopic composition, it is vital to dry the air samples to a sufficiently low dew point before they are pressurized in flasks to avoid condensation. Moreover, the drying system itself should not influence the mixing ratio and the isotopic composition of CO 2 , nor of the other constituents under study. For the "Airborne Stable Isotopes of Carbon from the Amazon" (ASICA) project focusing on accurate measurements of CO 2 and its singlysubstituted stable isotopologues over the Amazon, an air drying system was needed capable of removing water vapour from air sampled at a dew point better than −2 °C, high flow rates up to 12 L/min, and without the need for electrical power. Since to date, no commercial air drying device is available that meets these requirements, we designed and built our own consumable-free, power-free, and portable drying system based on multi-tube Nafion™ gas sample driers (Perma Pure, Lakewood, USA). The required dry purge air is provided by feeding the exhaust flow of the flasks sampling system through a dry molecular sieve (type 3A) cartridge. In this study we describe the systematic evaluation of our Nafion-based air sample dryer with emphasis on its performance concerning the measurements of atmospheric CO2 mole fractions and the three singly-substituted isotopologues of CO 2 (16 O 13 C 16 O, 16 O 12 C 17 O and 16 O 12 C 18 O), as well as the trace gas species CH 4 , CO,
, T. (2019). Determination of the triple oxygen and carbon isotopic composition of CO2 from atomi... more , T. (2019). Determination of the triple oxygen and carbon isotopic composition of CO2 from atomic ion fragments formed in the ion source of the 253 Ultra High-Resolution Isotope Ratio Mass Spectrometer. Rapid Communications in Mass Spectrometry, 33(17),
RATIONALE: H 2 is an important gas for atmospheric chemistry, and an indirect greenhouse gas due ... more RATIONALE: H 2 is an important gas for atmospheric chemistry, and an indirect greenhouse gas due to its reaction with OH. The isotopic composition of H 2 (δD values) has been used to investigate its atmospheric budget; here we add a new observable, the clumped isotopic signature ΔDD, to the tools that can be used to study the global cycle of H 2. METHODS. A method for determining ΔDD in H 2 was developed using the high-resolution IRMS MAT-253 Ultra isotope ratio mass spectrometer (Thermo Fisher). The HH, HD and DD abundances are quantified at medium resolution (M/ΔM ≈ 6000), which is sufficient for HD + and DD + to be distinguished from H 3 + and H 2 D + , respectively. The method involves sequential measurement of isotopologues, and DD is measured using an ion counter. For verification, catalytic ΔDD equilibration experiments were performed at temperatures of up to 850°C. RESULTS. The typical precision obtained for ΔDD is 2-6 ‰, close to the theoretical counting statistics limit, and adequate for detecting the expected natural variations. Compatibility and medium term reproducibility are consistent with the precision values. The method was validated using temperature equilibration experiments, which showed a dependence of ΔDD on temperature as expected form theoretical calculations. CONCLUSIONS. We have established a method for determining ΔDD in H 2 at natural isotopic abundances, with a precision that is adequate for observing the expected variations in atmospheric and other natural H 2. This method opens the road to new research on the natural H 2 cycle.
Seasonal changes of sources, volatility, and aging of organic aerosols in eastern Europe reflected in the stable isotopic composition
&lt;p&gt;&lt;span lang="EN-GB"&gt;The stable carbon isotope &lt;sup... more &lt;p&gt;&lt;span lang="EN-GB"&gt;The stable carbon isotope &lt;sup&gt;13&lt;/sup&gt;C has the potential to give insights into sources and processing of organic aerosol.&amp;#160;&lt;/span&gt;We use a method to measure d&lt;sup&gt;13&lt;/sup&gt;C in OC desorbed from filter samples at three different temperature steps: 200 &amp;#176;C, 350&amp;#176;C and 650&amp;#176;C. The results give a rough indication of aerosol volatility, as more volatile compounds usually desorb at lower temperatures.&lt;/p&gt; &lt;p&gt;We demonstrate with an extensive source study that in Lithuania and likely other Eastern European regions, the main anthropogenic primary sources for organic carbon (OC) have distinct isotopic signatures. d&lt;sup&gt;13&lt;/sup&gt;C values of vehicular emissions show the most negative values around - 29 &amp;#8240;, emissions from combustion of the most common wood types are more enriched with values around -26 to -27 &amp;#8240;, and coal burning is around -25&amp;#8240;. For source samples, d&lt;sup&gt;13&lt;/sup&gt;C values at the three desorption temperature steps usually do not differ more than 1 &amp;#8240;.&lt;/p&gt; &lt;p&gt;In the ambient samples,&amp;#160;&lt;span lang="EN-US"&gt;OC had more negative &amp;#948;&lt;sup&gt;13&lt;/sup&gt;C values in summer than in winter, which can be explained by the contribution of biomass/coal burning sources in winter. At the urban site &amp;#948;&lt;sup&gt;13&lt;/sup&gt;C of OC did not change much with increasing desorption temperature in winter, which is typical for primary sources. In the summer &amp;#948;&lt;sup&gt;13&lt;/sup&gt;C of OC was clearly more negative for lower desorption temperatures at all three sites. This is likely due to the influence of secondary organic aerosol formation in summer, which should have depleted (more negative) isotopic signature and contributes strongly to the more volatile fraction.&lt;/span&gt;A higher fraction of more refractory OC in summer compared to winter-time suggests active photochemical processing of the primary organic aerosol as an important process at all three sites.&lt;/p&gt; &lt;p&gt;This is consistent with our laboratory studies, where we age source samples in a small reactor under UV light. Photolysis causes mainly mass loss in OC that desorbs at 200 &amp;#176;C. At the same time, &lt;sup&gt;13&lt;/sup&gt;C becomes more enriched in OC desorbed at the higher temperature steps, leading to a bigger difference in d&lt;sup&gt;13&lt;/sup&gt;C between OC200 and OC350, as observed in the ambient atmosphere.&lt;/p&gt; &lt;p&gt;In summary, analyzing stable isotopes of OC at different desorption temperature steps gives a powerful tool for diagnosing aging processes.&lt;/p&gt;
In the current decade, the potential side effects caused by synthetic kinase domain inhibitors ha... more In the current decade, the potential side effects caused by synthetic kinase domain inhibitors have paved the way for developing an alternative anti-breast cancer drug from botanical sources. Estrogen receptor-α (ERα) and epidermal growth factor receptor (EGFR) tyrosine kinase receptors play a key role in the activation of genomic and nongenomic related pathways of breast cancer progression. Paris polyphylla Smith (Melanthiaceae) is a rich source of steroidal saponins reported as an anti-breast cancer agent used among the local communities of Asian countries. In the present study, a total of 116 phytocompounds were characterized and identified from P. polyphylla rhizomes using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry tools. They were subjected to virtual screening, molecular docking, and molecular simulation analysis with these two breast cancer receptors. Among them, only three steroidal saponins, namely, diosgenin, pennogenin, and 7-ketodiosgenin acetate binding affinity with target receptors were on the higher side when compared with natural ligands. The highest affinity for the receptors ERα and EGFR tyrosine kinase was shown by 7-ketodiosgenin acetate with docking scores of −10.4 Kcal/mol and −11.2 Kcal/mol, respectively, followed by diosgenin and pennogenin. LigPlot + analysis revealed that the selected three steroidal saponins utilized a combination of hydrogen bonding and hydrophobic interactions to align themselves more efficiently in the ligand-binding pocket of the target receptors. Molecular simulation analysis revealed a stable interaction between the phytocompounds and the target receptors. Lipinski's rule confirmed pennogenin as the best phytocompound that could be used as a potential inhibitor against the two target breast cancer receptors (ERα and EGFR tyrosine kinase).
<i>In-silico</i> based identification of phytochemicals from <i>Houttuynia cordata</i> Thunb. as potential inhibitors for overexpressed HER2 and VEGFR2 cancer genes
Human epidermal growth factor receptor2 (HER2) and Vascular endothelial growth factor receptor2 (... more Human epidermal growth factor receptor2 (HER2) and Vascular endothelial growth factor receptor2 (VEGFR2) – a tyrosine kinase receptors play a key role in breast and stomach cancers. The overexpression of HER2 and VEGFR2 genes increases the number of HER2 and VEGFR2 in the cell which initiates breast and stomach cancer respectively. The phytochemicals from traditional medicinal herb <i>Houttuynia cordata</i> Thunb. are reported to possess anti-inflammatory and anti-cancer potential. However, isolation of phytochemicals from this herb is fraught with uncertainly and time-consuming. Here, a molecular docking approach provides probable binding affinities between the receptors and phytochemicals (ligands) which initiate the first step of anticancer drug discovery and development. In the present study, <i>In-silico</i> docking approaches were used to identify the top-hit phytochemicals from <i>H. cordata</i> as potential inhibitors for overexpressed HER...
Phytochemical, nutritional and antioxidant potential of Panax bipinnatifidus and Panax pseudoginseng: A study of two underutilized and neglected species from the Eastern Himalayan region of India
In this decade, understanding the impact of human activities on climate is one of the key issues ... more In this decade, understanding the impact of human activities on climate is one of the key issues of discussion globally. The continuous rise in the concentration of greenhouse gases, e.g., CO2, CH4, etc. in the atmosphere, predominantly due to human activities, is alarming and requires continuous monitoring to understand the dynamics. Radiocarbon is an important atmospheric tracer and one of the many used in the understanding of the global carbon budget, which includes the greenhouse gases like CO2 and CH4. Measurement of C (or radiocarbon) in atmospheric CO2 generally requires collection of large air samples (few liters) from which CO2 is extracted and then the concentration of radiocarbon is determined. Currently, Accelerator Mass Spectrometry (AMS) is the most precise, reliable and widely used technique for atmospheric radiocarbon detection. However, the regular collection of air samples from troposphere and stratosphere, for example using aircraft, is prohibitively expensive.
In 2016, the new high-resolution, multi-collector isotope ratio mass spectrometer MAT253 ULTRA [1... more In 2016, the new high-resolution, multi-collector isotope ratio mass spectrometer MAT253 ULTRA [1] was installed at Utrecht University. This instrument is designed to reach a mass resolving power of 20,000 to 40,000 (M/∆M). The ion currents are detected with a variable multi-collector unit that allows to register up to 9 ion currents simultaneously with Faraday cups and ion counters. The width of the entrance slit can be varied between 5 and 250μm so that the instrument can be operated under low, medium and high mass resolution, and an optimum balance between resolution and sensitivity can be selected for the respective applications.
My PhD research deals with radiocarbon, the natural radioactive isotope of carbon, known for its ... more My PhD research deals with radiocarbon, the natural radioactive isotope of carbon, known for its application in dating. The first and main part was the exploration of the capabilities of a new, potentially revolutionary technique to measure radiocarbon. This technique, ICOGS (IntraCavity OptoGalvanic Spectroscopy), much cheaper and easier than the accelerators presently in use, was first published as successful for radiocarbon detection by the Murnick group, Rutgers University, USA. Motivated by their results, we collaborated with them in the development and improvement of ICOGS in Groningen. However, after more than two years of experiments, we had to conclude that the results claimed by the Murnick group were not real. We have finally published these -negative- results in the journal Analytical Chemistry ("ICOGS Not Suitable for Ambient Level Radiocarbon Detection"), to discredit the technique and warn other research groups. So far, however, Murnick et al have not given ...
Developing a preconcentration and purification setup for 14C measurements of atmospheric methane
Methane contributes substantially to global warming as the second most important anthropogenic gr... more Methane contributes substantially to global warming as the second most important anthropogenic greenhouse gas. Its sources are diverse and remain poorly quantified and not well understood [1]. The radiocarbon (14C) content of these emissions is of growing interest since it can be used as a tool for a methane source apportionment [2]. Indeed, contemporary methane (e.g. agriculture, biomass burning) contains present-day 14C levels, whereas fossil methane (e.g. fossil fuels, geologic sources) is 14C-free. However, this task is challenging given the very large amounts of methane required and its very low concentration in the atmosphere. Methane is usually separated from other trace gases in a stepwise process: first CO2 is cryogenically removed, then CO is oxidized to CO2 and also cryogenically removed, before methane can finally be oxidized and isolated as CO2. For this simplified process, cross contamination of CO2 from one fraction to the next remains an issue difficult to overcome [...
Identification of tyrosine kinase inhibitors from Panax bipinnatifidus and Panax pseudoginseng for RTK—HER2 and VEGFR2 receptors, by in silico approach
Molecular Diversity, 2021
Breast and stomach cancer is reported as a leading cause for human mortality across the world. Th... more Breast and stomach cancer is reported as a leading cause for human mortality across the world. The overexpression of receptor tyrosine kinase (RTK) proteins, namely the human epidermal growth factor receptor2 (HER2) and the vascular endothelial growth factor receptor2 (VEGFR2), is reported to be responsible for development and metastasis of breast and stomach cancer. Although several synthetic tyrosine kinase inhibitors (TKIs) as drug candidates targeting RTK-HER2 and VEGFR2 are currently available in the market, these are expensive with the reported side effects. This confers an opportunity for development of alternative novel tyrosine kinase inhibitors (TKIs) for RTK-HER2 and VEGFR2 receptors from the botanical sources. In the present study, we characterized 47 bioactive phytocompounds from the methanol extracts of the rhizomes of Asiatic traditional medicinal herbs-Panax bipinnatifidus and Panax pseudoginseng, of Indian Himalayan landraces using HPLC, GC-MS and high-sensitivity LC-MS tools. We performed molecular docking and molecular dynamics simulation analysis using Schrödinger suite 2020-3 to confirm the TKI phytocompounds showing the best binding affinity towards RTK-HER2 and VEGFR2 receptors. The results of molecular docking studies confirmed that the phytocompound (ligand) luteolin 7-O-glucoside (IHP15) showed the highest binding affinity towards receptor HER2 (PDB ID: 3PP0) with docking score and Glide g score (G-Score) of - 13.272, while chlorogenic acid (IHP12) showed the highest binding affinity towards receptor VEGFR2 (PDB ID: 4AGC) with docking score and Glide g score (G-Score) of - 10.673. Molecular dynamics (MD) simulation analysis carried out for 100 ns has confirmed strong binding interaction between the ligand and receptor complex [luteolin 7-O-glucoside (IHP15) and HER2 (PDB ID: 3PP0)] and is found to be stabilized within 40 to 100 ns of MD simulation, whereas ligand-receptor complex [chlorogenic acid (IPH12) and VEGFR2 (PDB ID: 4AGC)] also showed strong binding interaction and is found to be stabilized within 18-30 ns but slightly deviated during 100 ns of MD simulation. In silico ADME-Tox study using SwissADME revealed that the ligands luteolin 7-O-glucoside (IHP15) and chlorogenic acid (IHP12) have passed majority parameters of the common drug discovery rules. The present study has confirmed luteolin 7-O-glucoside (IHP15) and chlorogenic acid (IHP12) as potential tyrosine kinase inhibitors (TKIs) which were found to inhibit RTKs-HER2 and VEGFR2 receptor proteins, and thus paving the way for development of alternative potential TKIs (drug molecules) for treatment of HER2- and VEGFR2-positive breast and stomach cancer.
In-silico based identification of phytochemicals from Houttuynia cordata Thunb. as potential inhibitors for overexpressed HER2 and VEGFR2 cancer genes
Journal of Biomolecular Structure and Dynamics, 2021
Human epidermal growth factor receptor2 (HER2) and Vascular endothelial growth factor receptor2 (... more Human epidermal growth factor receptor2 (HER2) and Vascular endothelial growth factor receptor2 (VEGFR2) - a tyrosine kinase receptors play a key role in breast and stomach cancers. The overexpression of HER2 and VEGFR2 genes increases the number of HER2 and VEGFR2 in the cell which initiates breast and stomach cancer respectively. The phytochemicals from traditional medicinal herb Houttuynia cordata Thunb. are reported to possess anti-inflammatory and anti-cancer potential. However, isolation of phytochemicals from this herb is fraught with uncertainly and time-consuming. Here, a molecular docking approach provides probable binding affinities between the receptors and phytochemicals (ligands) which initiate the first step of anticancer drug discovery and development. In the present study, In-silico docking approaches were used to identify the top-hit phytochemicals from H. cordata as potential inhibitors for overexpressed HER2 (breast) and VEGFR2 (stomach) cancer genes. A total of 100 biologically active phytochemicals from H. cordata were screened and docked against the ligand-binding pocket of HER2 and VEGFR2 kinase domains. Docking results revealed only a few phytochemicals (molecules) which appropriately fit into the ligand-binding pocket with higher binding affinity than the natural ATP ligand. A competitive docking was used to ascertain the top-hit phytochemicals that bind perfectly to the ATP ligand-binding pocket. Among the top-hit phytochemicals docked from H. cordata, the β-sitosterol and Quercetin showed highest binding affinity towards HER2 and VEGFR2 receptors using both hydrogen and hydrophobic interactions. This study confirmed β-sitosterol and Quercetin as potential drug candidates against breast and stomach cancer.Communicated by Ramaswamy H. Sarma.
• 13 C analysis of EC at the sub-μgC level is achieved by the TOA-IRMS system. • OC/EC separation... more • 13 C analysis of EC at the sub-μgC level is achieved by the TOA-IRMS system. • OC/EC separation and possible effects on the isotopic composition were evaluated. • EC can be well isolated for 13 C analysis using the thermal-optical split point. • Incomplete isolation of EC can bias dual isotope source apportionment.
This paper discusses the brief cross cultural ethnobotany of the Abotani tribes of Arunachal Prad... more This paper discusses the brief cross cultural ethnobotany of the Abotani tribes of Arunachal Pradesh which comprises five different indigenous tribal communities, namely Adi, Apatani, Nyishi, Galo and Tagin residing in Arunachal Pradesh, India. A brief ethnobotanical survey was conducted in Abotani Biocultural Landscape (ABL) in 11 districts of Arunachal Pradesh during the year 2018-2019 with fundamental aims to document significant ethnobotanical plants commonly used among all the 05 Abotani tribes in their local biocultural landscape and to document traditional knowledge and skills related to utilization of ethnobotanical plants resources using semi-structured questionnaire format. The survey have revealed impressive number of 45 species of ethnobotanically significant species frequently harvested and used as local food and medicine security as well as cultural materials among the local residents of 05 major tribes of Abotani cultural group residing in Siang,
Present paper discusses ethnobotany of the economically significant food and medicinal plants use... more Present paper discusses ethnobotany of the economically significant food and medicinal plants used among the Monpa and Nyishi community of West Kameng and Kamle District of Arunachal Pradesh in cross-cultural approaches. The 49 species of both cultivated and wild food and medicinal plants recorded from Monpa and Nyishi biocultural landscape are frequently harvested and used by the local communities as antioxidant food, anti-inflammatory agent and for treatment of various diseases including prevention of cancer and liver cirrhosis which has the potential to be used as nutraceuticals and capable of sustaining the rural economy and livelihood of the rural community.
ABSTRACTThe Centre for Isotope Research (CIO) at the University of Groningen has operated a radio... more ABSTRACTThe Centre for Isotope Research (CIO) at the University of Groningen has operated a radiocarbon (14C) dating laboratory for almost 70 years. In 2017, the CIO received a major upgrade, which involved the relocation of the laboratory to new purpose-built premises, and the installation of a MICADAS accelerator mass spectrometer. This period of transition provides an opportunity to update the laboratory’s routine procedures. This article addresses all of the processes and quality checks the CIO has in place for registering, tracking and pretreating samples for radiocarbon dating. Complementary updates relating to radioisotope measurement and uncertainty propagation will be provided in other forthcoming publications. Here, the intention is to relay all the practical information regarding the chemical preparation of samples, and to provide a concise explanation as to why each step is deemed necessary.
Atmospheric flask samples are either collected at atmospheric pressure by simply opening a valve ... more Atmospheric flask samples are either collected at atmospheric pressure by simply opening a valve of a preevacuated flask, or pressurized with the help of a pump to a few bar above ambient providing large air samples for analysis. Under humid conditions, there is a risk that water vapour in the sample leads to condensation on the walls of the flask, notably at higher than ambient sampling pressures. Liquid water in sample flasks is known to affect the CO 2 mixing ratios and also alters the isotopic composition of oxygen (17 O and 18 O) in CO 2 via isotopic equilibration. Hence, for accurate determination of CO 2 mole fractions and its stable isotopic composition, it is vital to dry the air samples to a sufficiently low dew point before they are pressurized in flasks to avoid condensation. Moreover, the drying system itself should not influence the mixing ratio and the isotopic composition of CO 2 , nor of the other constituents under study. For the "Airborne Stable Isotopes of Carbon from the Amazon" (ASICA) project focusing on accurate measurements of CO 2 and its singlysubstituted stable isotopologues over the Amazon, an air drying system was needed capable of removing water vapour from air sampled at a dew point better than −2 °C, high flow rates up to 12 L/min, and without the need for electrical power. Since to date, no commercial air drying device is available that meets these requirements, we designed and built our own consumable-free, power-free, and portable drying system based on multi-tube Nafion™ gas sample driers (Perma Pure, Lakewood, USA). The required dry purge air is provided by feeding the exhaust flow of the flasks sampling system through a dry molecular sieve (type 3A) cartridge. In this study we describe the systematic evaluation of our Nafion-based air sample dryer with emphasis on its performance concerning the measurements of atmospheric CO2 mole fractions and the three singly-substituted isotopologues of CO 2 (16 O 13 C 16 O, 16 O 12 C 17 O and 16 O 12 C 18 O), as well as the trace gas species CH 4 , CO,
, T. (2019). Determination of the triple oxygen and carbon isotopic composition of CO2 from atomi... more , T. (2019). Determination of the triple oxygen and carbon isotopic composition of CO2 from atomic ion fragments formed in the ion source of the 253 Ultra High-Resolution Isotope Ratio Mass Spectrometer. Rapid Communications in Mass Spectrometry, 33(17),
RATIONALE: H 2 is an important gas for atmospheric chemistry, and an indirect greenhouse gas due ... more RATIONALE: H 2 is an important gas for atmospheric chemistry, and an indirect greenhouse gas due to its reaction with OH. The isotopic composition of H 2 (δD values) has been used to investigate its atmospheric budget; here we add a new observable, the clumped isotopic signature ΔDD, to the tools that can be used to study the global cycle of H 2. METHODS. A method for determining ΔDD in H 2 was developed using the high-resolution IRMS MAT-253 Ultra isotope ratio mass spectrometer (Thermo Fisher). The HH, HD and DD abundances are quantified at medium resolution (M/ΔM ≈ 6000), which is sufficient for HD + and DD + to be distinguished from H 3 + and H 2 D + , respectively. The method involves sequential measurement of isotopologues, and DD is measured using an ion counter. For verification, catalytic ΔDD equilibration experiments were performed at temperatures of up to 850°C. RESULTS. The typical precision obtained for ΔDD is 2-6 ‰, close to the theoretical counting statistics limit, and adequate for detecting the expected natural variations. Compatibility and medium term reproducibility are consistent with the precision values. The method was validated using temperature equilibration experiments, which showed a dependence of ΔDD on temperature as expected form theoretical calculations. CONCLUSIONS. We have established a method for determining ΔDD in H 2 at natural isotopic abundances, with a precision that is adequate for observing the expected variations in atmospheric and other natural H 2. This method opens the road to new research on the natural H 2 cycle.
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