Wheat stem rust, caused by the fungal pathogen Puccinia graminis f. sp. tritici (Pgt), has re-emerged as an important disease of wheat. This pathogen continues to spread and evolve new virulent ...races. The international letter-code system of nomenclature has been used to pathotype these new emerging races, and gene SrMcN from 'McNair 701' winter wheat, which is one of the differential lines, was examined in this study. The chromosome and map position of gene SrMcN have not been determined, and thus the objective of this research was to genetically map SrMcN. A doubled haploid population (n = 186) was made from the cross 'LMPG'/'McNair 701' and inoculated with Pgt race QCCJB. The DH population segregated 95 resistant : 91 susceptible lines, which fitted the expected 1 : 1 ratio (χ
2
= 0.09, P = 0.77, NS) for a single gene. SrMcN mapped to chromosome 2DL using the 90K iSelect wheat SNP array, and Kompetitive allele specific (KASP) polymerase chain reaction markers located SrMcN to the same position as Sr54 previously found in 'Norin 40'. Comparison of stem rust seedling reactions using 12 diverse Pgt races indicated that SrMcN and Sr54 had an identical pattern of responses and similar low infection types (from ; to 2
−
) to races LBBLB, LCBNB and QCCJB. Based on the same chromosomal location on 2DL and identical seedling responses as Sr54 to several races of Pgt with diverse virulence, we assert that the resistance gene in 'McNair 701' winter wheat previously designated as SrMcN is most likely Sr54.
Abstract
A two-year field study was conducted during
Rabi
2018–2019 and 2019–20 to find out the influence of different residue and weed management practices on weed dynamics, growth, yield, ...energetics, carbon footprint, economics and soil properties in zero-tilled sown wheat at Research Farm, AICRP-Weed management, SKUAST-Jammu. The experiment with four rice residue management practices and four weed management practices was conducted in a Strip-Plot Design and replicated thrice. The results showed that residue retention treatments recorded lower weed density, biomass and higher wheat growth, yield attributes and yields of wheat as compared to no residue treatment. The magnitude of increase in wheat grain yield was 17.55, 16.98 and 7.41% when treated with 125% recommended dose of nitrogen + residue + waste decomposer (RDN + R + WD), 125% RDN + R, and 100% RDN + R, respectively, compared to no residue treatment. Further, all three herbicidal treatments decreased weed density and biomass than weedy treatments. Consequently, a reduction of 29.30, 28.00, and 25.70% in grain yield were observed in control as compared to sulfosulfuron + carfentrazone, clodinafop-propargyl + metasulfuron, and clodinafop-propargyl + metribuzin, respectively. Moreover, 125% RDN + R + WD obtained significantly higher energy output (137860 MJ ha
−1
) and carbon output (4522 kg CE/ha), but 100% RDN had significantly higher net energy (101802 MJ ha
−1
), energy use efficiency (7.66), energy productivity (0.23 kg MJ
−1
), energy profitability (6.66 kg MJ
−1
), carbon efficiency (7.66), and less carbon footprint (7.66) as compared to other treatments. Despite this, treatments with 125% RDN + R + WD and 125% RDN + R provided 17.58 and 16.96% higher gross returns, and 24.45% and 23.17% net outcomes, respectively, than that of control. However, compared to the control, sulfosulfuron + carfentrazone showed considerably higher energy output (140492 MJ ha
−1
), net energy (104778 MJ ha
−1
), energy usage efficiency (4.70), energy productivity (0.14 kg MJ
−1
), energy profitability (3.70 kg MJ
−1
), carbon output (4624 kg CE ha
−1
), carbon efficiency (4.71), and lower carbon footprint (0.27). Furthermore, sulfosulfuron + carfentrazone, clodinafop-propargyl + metasulfuron, and clodinafop-propargyl + metribuzin recorded 29.29% and 38.42%, 27.99%, and 36.91%, 25.69% and 34.32% higher gross returns and net returns over control treatment, respectively. All three herbicides showed higher gross returns, net returns, and benefit cost ratio over control. The soil nutrient status was not significantly affected either by residue or weed management practices. Therefore, based on present study it can be concluded that rice residue retention with 25% additional nitrogen and weed management by clodinafop-propargyl + metasulfuron herbicide found suitable for zero tillage wheat.
Premature termination codons (PTCs) prevent translation of a full-length protein and trigger nonsense-mediated mRNA decay (NMD). Nonsense suppression (also termed readthrough) therapy restores ...protein function by selectively suppressing translation termination at PTCs. Poor efficacy of current readthrough agents prompted us to search for better compounds. An NMD-sensitive NanoLuc readthrough reporter was used to screen 771,345 compounds. Among the 180 compounds identified with readthrough activity, SRI-37240 and its more potent derivative SRI-41315, induce a prolonged pause at stop codons and suppress PTCs associated with cystic fibrosis in immortalized and primary human bronchial epithelial cells, restoring CFTR expression and function. SRI-41315 suppresses PTCs by reducing the abundance of the termination factor eRF1. SRI-41315 also potentiates aminoglycoside-mediated readthrough, leading to synergistic increases in CFTR activity. Combining readthrough agents that target distinct components of the translation machinery is a promising treatment strategy for diseases caused by PTCs.
In recent years nanoparticles have been widely used in medicines and pharmaceuticals because of their special mechanical, optical, and electrical behaviors, which affect significantly the convective ...nature of the blood liquid. The present work studies the impact of nanoparticles on the thermosolutal sensitivity of non-Newtonian fluid flow and numerical computations are made using blood as a base liquid. Binary and non-Newtonian features of blood are included in the formulation of the problem through solutal variables and the Casson fluid model, respectively. An efficient and simple methodology is applied to the set of equations and an initial state solution is obtained which is further perturbed slightly leading to a realistic expression of the Rayleigh number as a function of the thermophysical characteristics of the system. To capture the complete essence of the problem, a comparative study is also performed by taking blood (non-Newtonian)/water (Newtonian) as base liquids for thermal/thermosolutal cases using metallic/non-metallic nanoparticles and results in some key observations which are not yet established in the literature. Thermosolutal instability is dominated by the solutal effects and makes the system highly sensitive, while the Casson parameter stabilizes liquid and for its higher value, the instability of the layer increases.
Glycosylation is an enzyme-catalyzed post-translational modification that is distinct from glycation and is present on a majority of plasma proteins. N-glycosylation occurs on asparagine residues ...predominantly within canonical N-glycosylation motifs (Asn-X-Ser/Thr) although non-canonical N-glycosylation motifs Asn-X-Cys/Val have also been reported. Albumin is the most abundant protein in plasma whose glycation is well-studied in diabetes mellitus. However, albumin has long been considered a non-glycosylated protein due to absence of canonical motifs. Albumin contains two non-canonical N-glycosylation motifs, of which one was recently reported to be glycosylated.
We enriched abundant serum proteins to investigate their N-linked glycosylation followed by trypsin digestion and glycopeptide enrichment by size-exclusion or mixed-mode anion-exchange chromatography. Glycosylation at canonical as well as non-canonical sites was evaluated by liquid chromatography-tandem mass spectrometry (LC-MS/MS) of enriched glycopeptides. Deglycosylation analysis was performed to confirm N-linked glycosylation at non-canonical sites. Albumin-derived glycopeptides were fragmented by MS3 to confirm attached glycans. Parallel reaction monitoring was carried out on twenty additional samples to validate these findings. Bovine and rabbit albumin-derived glycopeptides were similarly analyzed by LC-MS/MS.
Human albumin is N-glycosylated at two non-canonical sites, Asn
and Asn
. N-glycopeptides were detected at both sites bearing four complex sialylated glycans and validated by MS3-based fragmentation and deglycosylation studies. Targeted mass spectrometry confirmed glycosylation in twenty additional donor samples. Finally, the highly conserved Asn
in bovine and rabbit serum albumin was also found to be glycosylated.
Albumin is a glycoprotein with conserved N-linked glycosylation sites that could have potential clinical applications.
Abstract
Inborn errors of immunity (IEI) are a heterogeneous group of monogenic disorders that include primary immunodeficiency’s and other disorders affecting different aspects of the immune system. ...Next-Generation Sequencing (NGS) is an essential tool to diagnose IEI. We report our 3-year experience in setting up facilities for NGS for diagnosis of IEI in Chandigarh, North India. We used a targeted, customized gene panel of 44 genes known to result in IEI. Variant analysis was done using Ion Reporter software. The in-house NGS has enabled us to offer genetic diagnoses to patients with IEI at minimal costs. Of 121 patients who were included pathogenic variants were identified in 77 patients. These included patients with Chronic Granulomatous Disease, Severe Combined Immune Deficiency, leukocyte adhesion defect, X-linked agammaglobulinemia, Ataxia Telangiectasia, Hyper-IgE syndrome, Wiskott Aldrich syndrome, Mendelian susceptibility to mycobacterial diseases, Hyper-IgM syndrome, autoimmune lymphoproliferative syndrome, and GATA-2 deficiency. This manuscript discusses the challenges encountered while setting up and running targeted NGS for IEI in our unit. Genetic diagnosis has helped our patients with IEI in genetic counselling, prenatal diagnosis, and accessing appropriate therapeutic options.
Holamine and funtumine, steroidal alkaloids with strong and diverse pharmacological activities are commonly found in the Apocynaceae family of
. The selective anti-proliferative and cell cycle arrest ...effects of holamine and funtumine on cancer cells have been previously reported. The present study evaluated the anti-proliferative mechanism of action of these two steroidal alkaloids on cancer cell lines (HT-29, MCF-7 and HeLa) by exploring the mitochondrial depolarization effects, reactive oxygen species (ROS) induction, apoptosis, F-actin perturbation, and inhibition of topoisomerase-I. The apoptosis-inducing effects of the compounds were studied by flow cytometry using the APOPercentage
dye and Caspase-3/7 Glo assay kit. The two compounds showed a significantly greater cytotoxicity in cancer cells compared to non-cancer (normal) fibroblasts. The observed antiproliferative effects of the two alkaloids presumably are facilitated through the stimulation of apoptosis. The apoptotic effect was elicited through the modulation of mitochondrial function, elevated ROS production, and caspase-3/7 activation. Both compounds also induced F-actin disorganization and inhibited topoisomerase-I activity. Although holamine and funtumine appear to have translational potential for the development of novel anticancer agents, further mechanistic and molecular studies are recommended to fully understand their anticancer effects.
Scapolite occurrences are widely observed in the metasedimentary rocks exposed around the Khetri Copper Belt and adjoining Nim ka Thana copper mineralized area in western India. Amoeboidal to ...well-developed and rounded/elliptical-shaped marialitic scapolite (Na-rich end-member) rich zones with variable Cl contents ranging from 1.0 wt % to 2.9 wt % have been identified in proximity to the ore-bearing hydrothermal fluid activity zones. Although scapolite is formed as a product of regional metamorphism in many places, in this study, we propose a strong possibility that scapolite was formed by hydrothermal ore-bearing fluid interaction with metasediments. The evidence of hydrothermal activity and Cl sourcing is attributed to (i) the absence of evaporite beds in the area and no Na-rich plagioclase as inclusions within the scapolite suggesting the formation of marialitic scapolite from sodic plagioclase in the metasediments with the interacting hydrothermal fluid; (ii) an epithermal to mesothermal hydrothermal fluid with moderate salinity responsible for the Cu mineralization that is ascribed to be the source of Cl for the formation of marialitic scapolite; (iii) diffusion of SO2 in the scapolite in close association with the sulfide mineral phase (chalcopyrite) supporting the involvement of ore-bearing fluid in the development of scapolite; (iv) the absence of zoned scapolite, the spatial distribution of scapolite in a particular lithology, the occasional incorporation of sulfur into marialitic scapolite and the texture/geometry in the scapolite suggesting a broad hydrothermal linkage instead of a pure metamorphic origin.
The time required for successful blastocyst formation varies among multiple species. The formation of a blastocyst is governed by numerous molecular cell signaling pathways, such as the Hippo ...signaling pathway. The Hippo signaling pathway is initiated by increased cell-cell contact and via apical polarity proteins (AMOT, PARD6, and NF2) during the period of preimplantation embryogenesis. Cell-cell contact and cell polarity activate (phosphorylates) the core cascade components of the pathway (mammalian sterile twenty like 1 and 2 (MST1/2) and large tumor suppressor 1 and 2 (LATS1/2)), which in turn phosphorylate the downstream effectors of the pathway (YAP1/TAZ). The Hippo pathway remains inactive with YAP1 (Yes Associated protein 1) present inside the nucleus in the trophectoderm (TE) cells (polar blastomeres) of the mouse blastocyst. In the inner cell mass (ICM) cells (apolar blastomeres), the pathway is activated with p-YAP1 present in the cytoplasm. On the contrary, during bovine embryogenesis, p-YAP1 is exclusively present in the nucleus in both TE and ICM cells. Contrary to mouse embryos, transcription co activator with PDZ-binding motif (TAZ) (also known as WWTR1) is also predominantly present in the cytoplasm in all the blastomeres during bovine embryogenesis. This review outlines the major differences in the localization and function of Hippo signaling pathway components of murine and bovine preimplantation embryos, suggesting significant differences in the regulation of this pathway in between the two species. The variance observed in the Hippo signaling pathway between murine and bovine embryos confirms that both of these early embryonic models are quite distinct. Moreover, based on the similarity of the Hippo signaling pathway between bovine and human early embryo development, bovine embryos could be an alternate model for understanding the regulation of the Hippo signaling pathway in human embryos.