The scale and accessibility of passive global surveillance have rapidly increased over time. This provides an opportunity to calibrate the performance of models, algorithms, and reflectance ratios between remote sensing devices. Here we test the sensitivity and specificity of Eucalypt chlorophyll-a reflectance ratio (ECARR) and Eucalypt chlorophyll-b reflectance ratio (ECBRR) to remotely identify eucalypt vegetation in Queensland, Australia. We compare reflectance ratio values from Sentinel-2 and Planet imagery across four sites of known vegetation composition. All imagery was transformed to reflectance values and Planet imagery was additionally scaled to harmonize across Planet Scenes. ECARR can identify eucalypt vegetation remotely with high sensitivity, but shows low specificity and is impacted by the density of the vegetation. ECBRR reflectance ratios show similar sensitivity and specificity when identifying eucalypt vegetation but with values an order of magnitude smaller than ECARR. We find that ECARR was better at identifying eucalypt vegetation in the Sentinel-2 imagery than Planet imagery. ECARR can serve as a general chlorophyll indicator but is not a specific index to identify Eucalyptus vegetation with certainty.

Abstract: Targeted ubiquitination and proteasomal degradation regulates various cellular pathways, and the discovery that CPT induced rapid proteasomal degradation of topoI is the primary mechanism of CPT resistance was novel and compelling. CPTs are used extensively to treat various solid tumors like colorectal, gastric, pancreatic, ovarian and small cell lung cancer. The response rate is low and the classical mechanisms of drug resistance are yet to be validated. Remarkably, CPT resistant cells degrade topoI rapidly by UPP and recently we’ve published the molecular determinants of this pathway. To further understand the UPP mediated CPT resistance mechanism we used targeted proteasome prohibition by ixazomib (MLN9708) to stabilize topoI and determine its impact on CPT resistance. CPT resistant and sensitive cancer lines were both treated with ixazomib in combination with CPT. The CPT induced rate of topoI degradation, and its stabilization by ixazomib, was visualized and estimated by immunohistochemistry, immunofluorescence and immunoblotting assays, MTT and subG1 assays provided the drug sensitivity. Our results demonstrate that cells that degrade topoI rapidly are very resistant to CPT, and ixazomib significantly inhibits CPT induced topoI degradation. Notably, inhibition of proteasomal degradation by ixazomib overcomes the drug resistance and sensitizes the cells for CPTs.

In the present era, infertility is one of the major issues which restricts many couples to have their own kids. Infertility is the inability to achieve a clinical pregnancy after regular unprotected sexual intercourse for the period of one year or more. Various factors including defective male or female germ cell development, unhealthy and improper lifestyles, diseases like cancer and associated chemo-or-radiation therapies, congenital disorders etc. may be responsible for infertility. Therefore, it is highly important to understand the basic concepts of germ cell development including primordial germ cell (PGC) formation, specification, migration, entry to genital ridges and their molecular mechanisms, activated pathways, paracrine and autocrine signaling, along with possible alteration which can hamper germ cell development and can cause adversities like cancer progression and infertility. Knowing all these aspects in a proper way can be very much helpful in improving our understanding about gametogenesis and finding possible ways to cure related disorders. Here in this review, various aspects of gametogenesis especially female gametes and relevant factors causing functional impairment have been thoroughly discussed.

Several lines of evidence indicate that high proliferative bias in eutopic endometrium during secretory phase is a hallmark of endometriosis and that high occurrence of implantation failure in patients resulting in infertility is often associated with endometriosis. ErbB family of proteins, which regulate the proliferation capacity in mammalian cells, appear as potential group of proteins to cause higher proliferation and endometrial hostility to implantation process in endometriosis. However, we have no concrete knowledge regarding the involvement of ErbB family in human endometrium during the ‘implantation window’, i.e., days 20-24 of a typical ovulatory cycle in endometriosis associated infertility. In the present study, the cellular profiles of immunopositive ErbBs-1 to -4 in endometrium of endometriosis-free, infertile women (Group 1; n=11), and in eutopic endometrium of infertile women diagnosed with stage IV ovarian endometriosis (Group 2; n=13) during mid-secretory phase were examined and compared using standardized WERF EPHect guidelines. Computer-aided standardized combinative analysis of immunoprecipitation in different compartments revealed an overexpression of ErbB-1 in the epithelial, stromal and vascular compartments along with marginally higher ErbB-3 expressions (P< 0.06) in the vascular compartment and ErbB-4 expression (P< 0.05) in the glandular epithelium and stroma in endometrium during the window of implantation of women with primary infertility associated with stage IV ovarian endometriosis compared with disease-free endometrium from women. A global overexpression of ErbB-1 in the endometrium during implantation window may induce anomalous proliferative, inflammatory and angiogenic activities in it, which antagonizes endometrial preparation for embryo implantation.

Background: Brain oxidative lipid damage and inflammation are common in neurodegenerative diseases such as Alzheimer’s disease (AD). Paraoxonase-1 and 3 (PON1 and PON3) protein expression have been described in tissues with no PON1 and PON3 gene expression. In the present study, we aimed to examine differences in PON1 and PON3 protein expression in the brain of a mouse model of AD. Methods: We used peroxidase-based and fluorescence-based immunohistochemistry in 5 brain regions (olfactory bulb, forebrain, posterior midbrain, hindbrain and cerebellum) of transgenic (Tg2576) mice with the Swedish mutation (KM670/671NL) responsible for a familial form of AD and corresponding wild-type mice. Results: We found intense PON1 and PON3 positive staining in star-shaped cells surrounding Aβ plaques in all Tg2576 mouse brain regions studied. Although we could not co-localize PON1 and PON3 with astrocytes, brain star-shaped cells, we found some co-localization of PON3 with microglia. Conclusions: These results suggest that 1) PON1 and PON3 cross the blood-brain barrier in discoidal HDLs and are transferred to specific brain cell types, and 2) PON1 and PON3 play an important role in preventing oxidative stress and lipid peroxidation in particular cell types, likely astrocytes and microglia, in AD pathology, and potentially in other neurodegenerative diseases

Retinal pigment epithelium (RPE) replacement therapy is evolving as a feasible approach to treat age-related macular degeneration (AMD). In majority of the preclinical studies, RPE cells are transplanted as cell suspension into immunosuppressed animal eyes and transplant effects were monitored only short-term. We investigated long-term effects of human iPSC derived RPE transplants in immunodeficient Royal College of Surgeons (RCS) rat model, in which RPE dysfunction lead to photoreceptor degeneration. iPSC-RPE cultured as polarized monolayer on nanoengineered ultrathin parylene C scaffold was transplanted into the subretinal space of 28-day old immunodeficient RCS rat pups and evaluated after 1, 4 and 11 months. Assessment at early time points showed good iPSC-RPE survival. The transplants remained as a monolayer, expressed RPE specific markers, performed phagocytic function and contributed to vision preservation. At 11-month post-implantation, RPE survival was observed only in 50% of the eyes that were concomitant with vision preservation. Loss of RPE monolayer characteristics at the 11month time point was associated with peri-membrane fibrosis, immune reaction through activation of macrophages (CD 68 expression) and transition of cell fate (expression of mesenchymal markers). The overall study outcome supports the therapeutic potential of RPE grafts despite the loss of some transplant benefits during long-term observations.

The emergence of SARS/MERS drug resistant COVID-19 with high transmission and mortality has recently been declared a deadly pandemic causing economic chaos and significant health problems. Like all coronaviruses, SARS-CoV-2 is a large virus that has many druggable components within its proteome. In this study, we focused on repurposing approved and investigational drugs by identifying potential drugs that are predicted to effectively inhibit critical enzymes within SARS-CoV-2. We shortlisted seven target proteins with enzymatic activities known to be essential at different stages of the virus life cycle. For virtual screening, the energy minimization of a crystal structure or modeled protein was carried out using Protein Preparation Wizard (Schrödinger LLC, 2020-1). Following active site selection based on data mining and COACH predictions, we performed a high-throughput virtual screen of drugs (n=5903) that are already approved by worldwide regulatory bodies including the FDA, using the ZINC database. Screening was performed against viral targets using three sequential docking modes (i.e. HTVS, SP and XP). Our in-silico virtual screening identified ~290 potential drugs based on the criteria of energy, docking parameters, ligand and binding site strain and score. Drugs specific to each target protein were further analyzed for binding free energy perturbation by molecular mechanics (prime MM-GBSA) and pruning the hits to the top 32 candidates. A top lead from each target group was further subjected to molecular dynamics simulation (MDS) using the Desmond module to validate the efficacy of the screening pipeline. All of the simulated hit-target complexes were predicted to strongly interact and with highly stable binding. Thus, we have identified a number of approved and investigational drugs with high likelihood of inhibiting a variety of key SARS-CoV-2 proteins. Follow-up studies will continue to identify inhibitors suitable for combination therapy based on drug-drug synergy to thwart resistance. In addition, the screening hits that we have identified provide excellent probes for understanding the binding properties of the active sites of all seven targets, further enabling us to derive consensus molecules through computer-aided drug design (CADD). While infections are expanding at a rampant pace, it must be recognized that resistance will grow commensurately through either genetic shift and/or genetic drift to all small molecule drugs identified. Vaccines should provide a more permanent solution through prevention, but resistivity is still a possible scenario. Nevertheless, a persistent multi-target drug development program is essential to curb this ongoing pandemic and to keep reemergence in check.

Type 2 diabetes mellitus (T2DM) is a polygenic metabolic disease described by hyperglycemia, which is caused by insulin resistance or reduced insulin secretion. Interaction between various genetic variants and environmental factors triggers T2DM. The main aim of this study was to find the risk associated with genetic variant (rs5210) of KCNJ11gene in the development of T2D in Indian Population. A total number of 300 cases of T2D and 100 control samples were studied to find the polymorphism in KCNJ11 through PCR-RFLP. The genotype and allele frequencies in T2DM cases were significantly different from the control population. We found a significant association of KCNJ11 (rs5210) gene polymorphism with T2DM in North Indian patients indicating the role of this variant in developing risk for T2DM.