Impact of COVID lockdowns on spatio-temporal variability in land surface temperature and vegetation index.

In urban areas, industrial and human activities are the prime cause that exacerbates the heating effects, also called the urban heat island (UHI) effect. The land surface temperature (LST), normalized difference vegetation index (NDVI), and the proportion of vegetation (Pv) are indicators of measurement of the heating/urbanization effects. In the present work, we investigated the impact of the COVID-19 lockdown, i.e., restricted human activities. We used Landsat-8 OLI/TIRS (level 1) data to investigate spatial and temporal heterogeneity changes in these urbanization indicators during full and partial lockdown periods in 2020 and 2021, with 2019 as the base year. We have selected three cities in India's eastern coal mining belt, Bokaro, Dhanbad, and Ranchi, for the study. Results showed a significant decrease in LST values over all sites, with a maximum reduction over mining sites, i.e., Bokaro and Dhanbad. The LST value decreased by about 13-19% during the lockdown period. Vegetation indices (i.e., NDVI and Pv) showed a substantial increase of about 15% overall sites. With decreased LST values and increased NDVI values, these quantities' correlations became more negative during the lockdown period. More positive changes are noticed over mining sites than non/less mining sites. This indirectly indicates the reduction in the heat-absorbing particles in the environment and surface of these sites, a possible cause for the reduction in LST values substantially. Reduction in coal particles at the land and vegetation surface likely contributed to decreased LST and enhanced vegetation indices. To check the statistical significance of changes in the UHI indicators in the lockdown period, statistical tests (ANOVA and Tukey's test) are performed. Results indicate that most of the case changes have been significant. The study's finding suggests the lockdown's positive impact on the heating/UHI effects. It emphasizes the need for planned lockdowns as city mitigation strategies to overcome pollution and environmental issues.

Comprehensive study of aerosols properties over various terrain types.

Aerosols are a crucial part of the climate system. Numerous factors, including aerosols, govern Earth's radiation balance. Different aerosols have distinct radiational effects on the earth system, and thus the slight change in their composition may lead to a drastic change in their radiative effects. Aerosols' chemical and physical properties also depend on generation processes, generation source, and geographical location. Significant spatio-temporal inconsistency is noticed in the distribution of aerosols. It makes it much difficult task to assess their radiative properties. We attempted to explore aerosol's optical properties and wavelength dependence over different locations. We have used AERONET (Aerosol Robotic Network) data over various stations (Kanpur, Jaipur, Gandhi College, Pune) with varying terrain properties in the Indian continent. We have studied the variation of different optical parameters: aerosol optical depth (AOD), single scattering albedo (SSA), and Angstrom exponent (α), and their wavelength dependence. This study indicated that Jaipur is the cleanest site, with dust aerosols as a primary aerosol. Though over Pune also aerosol concentration was relatively low but the anthropogenic aerosols contributed primarily over this site. Over the Indo-Gangetic Plain (IGP) sites, dust aerosols dominated the pre-monsoon season, while anthropogenic aerosols dominated the post-monsoon and winter seasons. The scatter plot of AOD with α gives the details of different aerosols (desert dust, continental aerosols, mixed aerosol, biomass burning aerosols, and sulfate aerosols) in the different seasons and places. This study provides an overview of aerosol properties, dominant aerosols in the aerosol system, and their seasonal and spectral variation.

Kinome Profiling of Primary Endometrial Tumors Using Multiplexed Inhibitor Beads and Mass Spectrometry Identifies SRPK1 as Candidate Therapeutic Target.

Endometrial carcinoma (EC) is the most common gynecologic malignancy in the United States, with limited effective targeted therapies. Endometrial tumors exhibit frequent alterations in protein kinases, yet only a small fraction of the kinome has been therapeutically explored. To identify kinase therapeutic avenues for EC, we profiled the kinome of endometrial tumors and normal endometrial tissues using Multiplexed Inhibitor Beads and Mass Spectrometry (MIB-MS). Our proteomics analysis identified a network of kinases overexpressed in tumors, including Serine/Arginine-Rich Splicing Factor Kinase 1 (SRPK1). Immunohistochemical (IHC) analysis of endometrial tumors confirmed MIB-MS findings and showed SRPK1 protein levels were highly expressed in endometrioid and uterine serous cancer (USC) histological subtypes. Moreover, querying large-scale genomics studies of EC tumors revealed high expression of SRPK1 correlated with poor survival. Loss-of-function studies targeting SRPK1 in an established USC cell line demonstrated SRPK1 was integral for RNA splicing, as well as cell cycle progression and survival under nutrient deficient conditions. Profiling of USC cells identified a compensatory response to SRPK1 inhibition that involved EGFR and the up-regulation of IGF1R and downstream AKT signaling. Co-targeting SRPK1 and EGFR or IGF1R synergistically enhanced growth inhibition in serous and endometrioid cell lines, representing a promising combination therapy for EC.

Functional proteomics interrogation of the kinome identifies MRCKA as a therapeutic target in high-grade serous ovarian carcinoma.

High-grade serous ovarian carcinoma (HGSOC) is the most lethal gynecological cancer with few effective, targeted therapies. HGSOC tumors exhibit genomic instability with frequent alterations in the protein kinome; however, only a small fraction of the kinome has been therapeutically targeted in HGSOC. Using multiplexed inhibitor beads and mass spectrometry, we mapped the kinome landscape of HGSOC tumors from patients and patient-derived xenograft models. The data revealed a prevalent signature consisting of established HGSOC driver kinases, as well as several kinases previously unexplored in HGSOC. Loss-of-function analysis of these kinases in HGSOC cells indicated MRCKA (also known as CDC42BPA) as a putative therapeutic target. Characterization of the effects of MRCKA knockdown in established HGSOC cell lines demonstrated that MRCKA was integral to signaling that regulated the cell cycle checkpoint, focal adhesion, and actin remodeling, as well as cell migration, proliferation, and survival. Moreover, inhibition of MRCKA using the small-molecule BDP9066 decreased cell proliferation and spheroid formation and induced apoptosis in HGSOC cells, suggesting that MRCKA may be a promising therapeutic target for the treatment of HGSOC.

Novel derivatives of plant monomeric phenolics: act as inhibitors of bacterial cell-to-cell communication.

The aim of the present study was to synthesize novel active Anti-Quorum sensing derivatives from secondary metabolites viz. Gallic acid, Protocatechuic acid and Vanillic acid present in the plant Bergenia ciliata. Efficacy of all synthesized derivatives have been evaluated on the formation of bacterial biofilm and inhibition of cell-to-cell communication. Anti-Quorum Sensing activity and biofilm formation of all synthesized compounds was measured on biomonitor strain Chrobacterium violaceum, ATCC 12472 using standard paper disk-diffusion assay and quantification of violacein pigment. Among all derivatives, five derivatives 3,4,5-Trihydroxy-benzoic acid methyl ester (9a), 3,4-Dihydroxy-benzoic acid methyl ester (10a), 3,4,5-Tris-(2,4-dichloro-benzyloxy)-benzoic acid methyl ester (12), 3,4,5-Tris-(2,5-dichloro-benzyloxy)-benzoic acid methyl ester (13) and 4-(2,4-Dichloro-benzyloxy)-3-methoxy-benzoic acid methyl ester (15) has shown Anti-Quorum Sensing activity by inhibiting violacein pigment production and biofilm formation without interfering with its growth. The inhibitory effects in violacein pigment production were: positive control (C-30) 72%, (9a), (10a) 47.2%, (12) 27.3%, (13) 40.1% and (15) 22.7% at the concentration of 1 mg/mL and biofilm percent inhibition were found (C-30) 64% (9a) 46.2%, (10a) 40.3%, (12) 18.4%, (13) 35.2%, and (15) 17.3% when compared with the untreated control. Results reveal that synthesized derivatives seem to be good compounds for inhibition and formation of biofilm and AHL-mediated Quorum-sensing mechanism. The present article highlights the importance of derivatives derived from secondary metabolites as potent drug for biofilm formation and inhibition of cell-to-cell communication.

Simultaneous Quantification of Syringic Acid and Kaempferol in Extracts of Bergenia Species Using Validated High-Performance Thin-Layer Chromatographic-Densitometric Method.

A rapid, sensitive, selective and robust quantitative densitometric high-performance thin-layer chromatographic method was developed and validated for separation and quantification of syringic acid (SYA) and kaempferol (KML) in the hydrolyzed extracts of Bergenia ciliata and Bergenia stracheyi. The separation was performed on silica gel 60F254 high-performance thin-layer chromatography plates using toluene : ethyl acetate : formic acid (5 : 4: 1, v/v/v) as the mobile phase. The quantification of SYA and KML was carried out using a densitometric reflection/absorption mode at 290 nm. A dense spot of SYA and KML appeared on the developed plate at a retention factor value of 0.61 ± 0.02 and 0.70 ± 0.01. A precise and accurate quantification was performed using linear regression analysis by plotting the peak area vs concentration 100-600 ng/band (correlation coefficient: r = 0.997, regression coefficient: R(2) = 0.996) for SYA and 100-600 ng/band (correlation coefficient: r = 0.995, regression coefficient: R(2) = 0.991) for KML. The developed method was validated in terms of accuracy, recovery and inter- and intraday study as per International Conference on Harmonisation guidelines. The limit of detection and limit of quantification of SYA and KML were determined, respectively, as 91.63, 142.26 and 277.67, 431.09 ng. The statistical data analysis showed that the method is reproducible and selective for the estimation of SYA and KML in extracts of B. ciliata and B. stracheyi.

Inhibition of cancer cell proliferation by PPARγ is mediated by a metabolic switch that increases reactive oxygen species levels.

The nuclear receptor peroxisome-proliferation-activated receptor gamma (PPARγ), a transcriptional master regulator of glucose and lipid metabolism, inhibits the growth of several common cancers, including lung cancer. In this study, we show that the mechanism by which activation of PPARγ inhibits proliferation of lung cancer cells is based on metabolic changes. We found that treatment with the PPARγ agonist pioglitazone triggers a metabolic switch that inhibits pyruvate oxidation and reduces glutathione levels. These PPARγ-induced metabolic changes result in a marked increase of reactive oxygen species (ROS) levels that lead to rapid hypophosphorylation of retinoblastoma protein (RB) and cell-cycle arrest. The antiproliferative effect of PPARγ activation can be prevented by suppressing pyruvate dehydrogenase kinase 4 (PDK4) or ß-oxidation of fatty acids in vitro and in vivo. Our proposed mechanism also suggests that metabolic changes can rapidly and directly inhibit cell-cycle progression of cancer cells by altering ROS levels.

Ablation of the oncogenic transcription factor ERG by deubiquitinase inhibition in prostate cancer.

The transcription factor E-twenty-six related gene (ERG), which is overexpressed through gene fusion with the androgen-responsive gene transmembrane protease, serine 2 (TMPRSS2) in ∼40% of prostate tumors, is a key driver of prostate carcinogenesis. Ablation of ERG would disrupt a key oncogenic transcriptional circuit and could be a promising therapeutic strategy for prostate cancer treatment. Here, we show that ubiquitin-specific peptidase 9, X-linked (USP9X), a deubiquitinase enzyme, binds ERG in VCaP prostate cancer cells expressing TMPRSS2-ERG and deubiquitinates ERG in vitro. USP9X knockdown resulted in increased levels of ubiquitinated ERG and was coupled with depletion of ERG. Treatment with the USP9X inhibitor WP1130 resulted in ERG degradation both in vivo and in vitro, impaired the expression of genes enriched in ERG and prostate cancer relevant gene signatures in microarray analyses, and inhibited growth of ERG-positive tumors in three mouse xenograft models. Thus, we identified USP9X as a potential therapeutic target in prostate cancer cells and established WP1130 as a lead compound for the development of ERG-depleting drugs.

EphB2 receptor forward signaling controls cortical growth cone collapse via Nck and Pak.

EphB receptors and their ephrinB ligands transduce bidirectional signals that mediate contact-dependent axon guidance primarily by promoting growth cone repulsion. However, how EphB receptor-mediated forward signaling induces axonal repulsion remains poorly understood. Here, we identify Nck and Pak proteins as essential forward signaling components of EphB2-dependent growth cone collapse in cortical neurons. We show that kinase-active EphB2 binds to Pak and promotes growth cone repulsion via Pak kinase activity, Pak-Nck binding, RhoA signaling and endocytosis. However, Pak's function in this context appears to be independent of Rac/Cdc42-GTP, consistent with the absence of Rac-GTP production after ephrinB treatment of cortical neurons. Taken together, our findings suggest that ephrinB-activated EphB2 receptors recruit a novel Nck/Pak signaling complex to mediate repulsive cortical growth cone guidance, which may be relevant for EphB forward signaling-dependent axon guidance in vivo.

Plexins are GTPase-activating proteins for Rap and are activated by induced dimerization.

Plexins are cell surface receptors that bind to semaphorins and transduce signals that regulate neuronal development, immune responses, and other processes. Signaling through plexins has been proposed to rely on specific guanosine triphosphatase (GTPase)-activating protein (GAP) activity for R-Ras and M-Ras. Activation of this GAP activity of plexins appears to require simultaneous binding of semaphorin to the plexin extracellular domain and of the Rho GTPases Rac1 or Rnd1 to the cytoplasmic region. However, GAP activity of plexins has eluded detection in several recent studies. We show that the purified cytoplasmic region of plexin uses a noncanonical catalytic mechanism to act as a GAP for Rap, but not for R-Ras or M-Ras. The RapGAP activity of plexins was autoinhibited and was activated by induced dimerization. Biochemical and crystallographic analyses demonstrated that binding of Rho GTPases did not directly contribute to activation of plexin RapGAP activity. Semaphorin stimulated the RapGAP activity of full-length plexin in cells, which was required for plexin-mediated neuronal growth cone collapse. Together, these findings define a pathway for plexin signaling and provide insights into the mechanism for semaphorin-induced activation of plexins.

Biosynthesis of andrographolide in Andrographis paniculata.

Andrographolide, a diterpene lactone, is isolated from Andrographis paniculata which is well known for its medicinal properties. The biosynthetic route to andrographolide was studied using [1-(13)C]acetate, [2-(13)C]acetate and [1,6-(13)C(2)]glucose. The peak enrichment of eight carbon atoms in the (13)C NMR spectra of andrographolide suggested that deoxyxylulose pathway (DXP) is the major biosynthetic pathway to this diterpene. The contribution of the mevalonic acid pathway (MVA) is indicated by the observed (13)C-labeling pattern, and because the labeling patterns indicate a simultaneous contribution of both methyl erythritol phosphate (MEP) and MVA pathways it can be deduced that cross-talk occurs between plastids and cytoplasm.

Functional restoration using basic fibroblast growth factor (bFGF) infusion in Kainic acid induced cognitive dysfunction in rat: neurobehavioural and neurochemical studies.

Neurogenesis occurs in dentate gyrus of adult hippocampus under the influence of various mitogenic factors. Growth factors besides instigating the proliferation of neuronal progenitor cells (NPCs) in dentate gyrus, also supports their differentiation to cholinergic neurons. In the present study, an attempt has been made to investigate the neurotrophic effect of bFGF in Kainic acid (KA) induced cognitive dysfunction in rats. Stereotaxic lesioning using (KA) was performed in hippocampal CA3 region of rat's brain. Four-weeks post lesioning rats were assessed for impairment in learning and memory using Y maze followed by bFGF infusion in dentate gyrus region. The recovery was evaluated after bFGF infusion using neurochemical, neurobehavioural and immunohistochemical approaches and compared with lesioned group. Significant impairment in learning and memory (P < 0.01) observed in lesioned animals, four weeks post lesioning exhibited significant restoration (P < 0.001) following bFGF infusion twice at one and four week post lesion. The bFGF infused animals exhibited recovery in hippocampus cholinergic (76%)/ dopaminergic (46%) receptor binding and enhanced Choline acetyltransferase (ChAT) immunoreactivity in CA3 region. The results suggest restorative potential of bFGF in cognitive dysfunctions, possibly due to mitogenic effect on dentate gyrus neurogenic area leading to generation and migration of newer cholinergic neurons.