Search

Increasing incidences of fungal infections and prevailing antifungal resistance in healthcare settings has given rise to an antifungal crisis on a global scale. The members of the genus Candida , owing to their ability to acquire sessile growth, are primarily associated with superficial to invasive fungal infections, including the implant-associated infections. The present study introduces a novel approach to combat the sessile/biofilm growth of Candida by fabricating nanofibers using a nanoencapsulation approach. This technique involves the synthesis of tyrosol (TYS) functionalized chitosan gold nanocomposite, which is then encapsulated into PVA/AG polymeric matrix using electrospinning. The FESEM, FTIR analysis of prepared TYS-AuNP@PVA/AG NF suggested the successful encapsulation of TYS into the nanofibers. Further, the sustained and long-term stability of TYS in the medium was confirmed by drug release and storage stability studies. The prepared nanomats can absorb the fluid, as evidenced by the swelling index of the nanofibers. The growth and biofilm inhibition, as well as the disintegration studies against Candida , showed 60–70 % biofilm disintegration when 10 mg of TYS-AuNP@PVA/AG NF was used, hence confirming its biological effectiveness. Subsequently, the nanofibers considerably reduced the hydrophobicity index and ergosterol content of the treated cells. Considering the challenges associated with the inhibition/disruption of fungal biofilm, the fabricated nanofibers prove their effectiveness against Candida biofilm. Therefore, nanocomposite-loaded nanofibers have emerged as potential materials that can control fungal colonization and could also promote healing. [Display omitted] • TYS-AuNP successfully encapsulated into PVA/AG nanofiber. • Encapsulation improved the sustained release of TYS. • TYS-AuNP@PVA/AG NF effectively disrupted fungal biofilms. [ABSTRACT FROM AUTHOR]

The development of economy and society makes the heavy metal(loid)s pollution more serious and contamination of rice grains by heavy metal(loid)s is a worldwide problem. In order to appraise the health risks associated with heavy metal(loid)s (As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb and Zn) in rice grains, we performed a meta-analysis based on the datasets collected from the literature (n = 248) between 2010 and 2023. The global mean values obtained for heavy metal(loid)s are as: Fe (214.1 µg g−1) > Zn (38 µg g−1) > Mn (29.3 µg g−1) > As (1.9 µg g−1) > Cu (6.8 µg g−1) > Cr (3.7 µg g−1) > Pb (6.6 µg g−1) > Ni (7.6 µg g−1) > Co (1.0 µg g−1) > Cd (0.20 µg g−1) and Hg (0.01 µg g−1). The relatively higher content of Pb, As, Cu, Hg and Zn was reported in China; Cr, Fe, Mn, Zn and Cu in Bangladesh; and Fe, Zn and Mn in Nigeria and India. The hazard quotient values of As were found greater than one for all the studied countries in both adults and children. These results suggest that contamination of rice grains with heavy metal(loid)s might lead different countries to establish strict legal guidelines and policies for preventing the heavy metal(loid)s contamination crop cultivation near contaminated areas. ● Analysis of heavy metal(loid)s in rice grains was conducted from 2010 to 2023. ● Global average concentrations of Pb, Co, Ni, As and Hg surpassed their acceptable limits. ● High hazard index values were found in China, India, Bangladesh, Nigeria and Vietnam ● China, Nigeria, India and Thailand showed higher carcinogenic risks due to metals. [ABSTRACT FROM AUTHOR]

The emergence of algal biorefineries has garnered considerable attention to researchers owing to their potential to ensure carbon neutrality via mitigation of atmospheric greenhouse gases. Algae-derived biofuels, characterized by their carbon-neutral nature, stand poised to play a pivotal role in advancing sustainable development initiatives aimed at enhancing environmental and societal well-being. In this context, algae-based wastewater treatment systems are greatly appreciated for their efficacy in nutrient removal and simultaneous bioenergy generation. These systems leverage the growth of algae species on wastewater nutrients—including carbon, nitrogen, and phosphorus—alongside carbon dioxide, thus facilitating a multifaceted approach to pollution remediation. This review seeks to delve into the realization of carbon neutrality through algae-mediated wastewater treatment approaches. Through a comprehensive analysis, this review scrutinizes the trajectory of algae-based wastewater treatment via bibliometric analysis. It subsequently examines the case studies and empirical insights pertaining to algae cultivation, treatment performance analysis, cost and life cycle analyses, and the implementation of optimization methodologies rooted in artificial intelligence and machine learning algorithms for algae-based wastewater treatment systems. By synthesizing these diverse perspectives, this study aims to offer valuable insights for the development of future engineering applications predicated on an in-depth understanding of carbon neutrality within the framework of circular economy paradigms. • Utilization of algae in wastewater treatment helps in acheiving carbon neutrality. • Research trend of algal wastewater treatment is analyzed via bibliometric analysis. • Chlorella vulgaris is the most investigated species in wastewater treatment system. • Binary culture approach has shown significant benefits over conventional systems. • AI and ML integration in algal system has potential benefits in carbon neutrality. [ABSTRACT FROM AUTHOR]

Ascorbate is an important cellular antioxidant that gets readily oxidized to dehydroascorbate (DHA). Recycling of DHA is therefore paramount in the maintenance of cellular homeostasis and preventing oxidative stress. Dehydroascorbate reductases (DHARs), in conjunction with glutathione (GSH), carry out this vital process in eukaryotes, among which plant DHARs have garnered considerable attention. A detailed kinetic analysis of plant DHARs relative to their human counterparts is, however, lacking. Chloride intracellular channels (Hs CLICs) are close homologs of plant DHARs, recently demonstrated to share their enzymatic activity. This study reports the highest turnover rate for a plant DHAR from stress adapted Pennisetum glaucum (Pg DHAR). In comparison, Hs CLICs 1, 3, and 4 reduced DHA at a significantly lower rate. We further show that the catalytic cysteine from both homologs was susceptible to varying degrees of oxidation, validated by crystal structures and mass-spectrometry. Our findings may have broader implications on crop improvement using pearl millet DHAR vis-à-vis discovery of cancer therapeutics targeting Vitamin-C recycling capability of human CLICs. • Stress adapted pearl millet DHA reductase (DHAR) possess higher turnover rate. • Detailed kinetic analysis presented for a plant DHAR and human CLIC1, 3 and 4. • Crystal structures reveal different oxidation states of catalytic cysteine. • Possible implications in crop improvement and anti-cancer drug-discovery. [ABSTRACT FROM AUTHOR]

In the present work, a pigment paste was prepared by adding strontium titanate (SrTiO 3) nanoparticles (NPs) particles to a water and adhesive binder paste. Screen printing was utilized to embed the cotton fabric with the prepared pigment paste. Sonocatalytic induced antibacterial and dye mineralization abilities were evaluated for the printed fabric. The produced samples were examined for efficacy against the pathogens E. coli and S. aureus. The prepared SrTiO 3 embedded cotton fabric inhibited (after 2 h) E. coli and S. aureus by 99.3% and 96.09%, respectively. The coated fabric was able to reduce pathogens by more than 92% even after 15 washing cycles. The Rhodamine B (RhB) dye was mineralized by 53% in 210 min by STO printed fabric as opposed to about 8% by pristine cotton. The results revealed that the intrinsic properties of cotton including tensile, abrasion, and air permeability remained unaffected by the printing of STO-NPs onto fabric. • SrTiO3 nanoparticles were embedded on cotton fabric by employing screen printing. • Coated fabric sonocatalytic dye degradation and antibacterial performance were evaluated. • After a 2 h bacterial contact period, the modified fabric reduced E. coli and S. aureus by 99.3% and 96.09%, respectively. • The coated fabric degraded RhB dye by 53% in 210 min as opposed to about 8% by pristine cotton. [ABSTRACT FROM AUTHOR]

Ganoderma lucidum is an important medicinal fungus that possesses exceedingly high lignocellulose degrading ability. Evidently, Cu2+ has decisive roles on the mycelial growth and enzyme production. To reveal the effect of Cu2+ on G. lucidum transcriptome, predominantly associated with lignocellulolytic progression, we conducted comparative NGS based de novo transcriptome assembly using Illumina Hi SeqTM sequencing platform. We obtained 26,083,372 and 35,713,076 high-quality reads from induced and uninduced cultures. For wood degrading activity, 194 transcript coding for oxidoreductases and 402 transcripts for CAZymes were predicted. Further, secretome studies revealed high score GO terms related to oxidoreductases, glycosyl hydrolases, and chitinases from Cu-induced mycelia. The increased Cu2+ concentrations showed higher secretion of lignocellulases such as laccases, cellulases, and xylanases along with increased production of phenolics and antioxidants. Several differences in the transcriptomic and proteomic signatures for lignocellulolytic enzymes provide vital clues about Cu2+ mediated gene regulation and metabolic pathways in basidiomycetous fungi. • Copper supplementation increases laccase production Ganoderma • Transcriptome reveals copper mediated gene regulation in Ganoderma • Upregulation of genes for lignin degradation, secondary metabolites and autophaghy • LCMS/MS analysis also suggests increase in glycosyl hydrolase and oxidoreductase [ABSTRACT FROM AUTHOR]

• Genetic analysis of VIR gene of ORFVs revealed high percentage of identity. • VIR gene showed low identity among parapoxviruses (PPVs). • VIR gene based phylogeny showed species-specific clustering among PPVs. • Host species-specific sub-clusters among ORFVs was observed. • Conserved N-terminal DNA-binding and C-terminal dsRNA binding domains were predicted. Orf is a contagious disease posing a serious threat to animal and human health. E3L is one of the evolutionarily acquired immunomodulatory proteins present in orf virus (ORFV) and is responsible for conferring resistance to interferons among poxviruses. Genetic analysis of ORFV isolates of different geographical regions including Indian subcontinent targeting viral interferon resistance (VIR) gene (a homolog of vaccinia virus E3L gene) revealed a high percentage of identity among themselves and other ORFV isolates at both nt and aa levels as compared to low identity among parapoxviruses (PPVs). Phylogenetic analysis showed species-specific clustering among PPVs along with sub-clusters based on host species of origin among ORFVs infecting sheep and goats. Conserved amino acids in N-terminal Z-DNA binding domain and C-terminal ds RNA binding domain of VIR proteins of PPVs corresponding to ORFV VIR positions namely N37, Y41, P57, and W59 (necessary for Z-DNA binding) and E116, F127, F141, and K160 (necessary for dsRNA binding) were found. Further, the predicted protein characteristics and homology model of VIR protein of ORFV showed high structural conservation among poxviruses. This study on E3L genetic analysis of ORFV isolates may provide a better understanding of the molecular epidemiology of circulating strains in India and neighboring countries. Also, E3L deleted or mutated ORFV may be an as vaccine candidate and/or compounds blocking E3L may prove as an effective method for treating broad spectrum poxviral infections, suggesting a wider application in control of poxvirus infections. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Series of hydroxylated 2-phenylbenzofuran were synthesized. • Compounds displayed activity against butyrylcholinesterase enzyme. • Importance of number and position of hydroxyl substitution in enzyme activity. • Physicochemical properties of derivatives were characterized. • Docking studies assisted in explaining the structure-activity. Abstract We have designed, synthesized and evaluated a series of hydroxylated 2-phenylbenzofuran derivatives as potential cholinesterase inhibitors. Starting from a series of 2-phenylbenzofurans previously published, in this paper we present a complete synthesis and the influence on the activity of one or two hydroxyl groups located in meta or in meta and para positions respectively of the 2-phenyl ring and highlight the importance of position of hydroxyl groups. Moreover, simultaneous introduction of halogen at position 7 of the benzofuran scaffold resulted in an improved inhibitory activity against the enzyme. To further provide molecular insight and to identify the most probable ligand-binding site of the protein, docking studies were performed for the top-ranked compounds. Docking results revealed conserved ligand-binding residues and supported the role of catalytic site residues in enzyme inhibition. [ABSTRACT FROM AUTHOR]

Abstract Rational designing of metal-free carbon nitride based photocatalysts can lead to an excellent optical response and a higher photocatalytic activity driven by visible and solar light. This combines green photocatalytic technology with greener materials prepared by facile approaches for environmental remediation. Herein we report utilization of star photocatalyst g-C 3 N 4 (CN) to form highly efficient hetero-assemblies along with acidified g-C 3 N 4 (ACN), polyaniline (PANI), reduced graphene oxide (RGO) and biochar. By use of these organic semiconductors we synthesize g-C 3 N 4 /ACN/RGO@Biochar (GARB), g-C 3 N 4 /PANI/RGO@Biochar (GPRB) and ACN/PANI/RGO@Biochar (APRB) nano-assemblies with different optical response and band edge positions for a better charge flow and reduced recombination of carriers. These synthesized catalysts were used for visible light powered degradation of 2,4-Dichlorophenoxy acetic acid (2,4-D) and ibuprofen (IBN). APRB performs the best and degrades 99.7% and 98.4% of 2,4-D and IBN (20 mg L−1) under Xe lamp exposure in 50 min and retention of high activity in natural sunlight. Optical analysis, photoelectrochemical response and radical quenching studies show both hydroxyl and superoxide radical anions as major reactive species and a Z-scheme photocatalytic mechanism. RGO acts as an electron mediator and protects higher positioned bands of PANI and ACN in APRB for a remarkable photocatalytic activity for a metal free material. The degradation pathway was analyzed by LC-MS analysis and 42% and 40% total organic carbon was removed in 2 h for 2,4-D and IBN degradation respectively. The toxicity of degraded products was analyzed by analyzing viability of human peripheral blood cells with retaining of 99.1% cells. Graphical abstract Image 1 Highlights • Metal free organic semiconductors based nano-assemblies as photocatalysts. • Utilizing g-C 3 N 4 , acidified C 3 N 4 , PANI for designing efficient photocatalyst. • Z-scheme mechanism-high spectral response and charge separation. • Excellent photo-degradation of Ibuprofen and 2,4-D under artificial and solar light. • Complete mineralization and no toxicity on human PBL cells. [ABSTRACT FROM AUTHOR]

Smokeless tobacco (SLT) products are consumed by millions of people in over 130 countries around the world. Consumption of SLT has been estimated to cause a number of diseases accounting to more than 0.65 million deaths per year. There is sufficient epidemiological evidence on the association of SLT products with nicotine addiction, cancers of oral cavity and digestive systems but there is a lack of understanding of the role of toxic chemicals in these diseases. We provide the first comprehensive in-silico analysis of chemical compounds present in different SLT products used worldwide. Many of these compounds are found to have good absorption, solubility and permeability along with mutagenic and toxic properties. They are also found to target more than 350 human proteins involved in a plethora of human biological processes and pathways. Along with all the previously known diseases, the present study has identified the association of compounds of SLT products with a number of unknown diseases like neurodegenerative, immune and cardiac diseases (Left ventricular non compaction, dilated cardiomyopathy etc). These findings indicate far-reaching impact of SLT products on human health than already known which needs further validations using epidemiological, in-vitro and in-vivo methodologies. Thus, this study will provide one stop information for the policy makers in development of regulatory policies on toxic contents of SLT products. [ABSTRACT FROM AUTHOR]

Current study details about the impact of solid state fermentation and subsequent extrusion on the physicochemical, sensory and bioactive properties of the rice-black gram dough. Influence of the solid-state fermentation was evaluated, at three levels of yeast concentration (1–3%), sugar (4–8%) and fermentation time (2–6 h). Fermentation resulted in decreased pH and residual sugar, from 6.38 to 5.41 and 1.07 to 0.69%, respectively, whereas the titratable acidity was increased from 0.86 to 1.79%, after 6 h of fermentation. Moreover, solid state fermentation for 6 h leads to increased total phenolic content, antioxidant activity and protein content from 29.80 to 44.12 mg GAE/100 g, 3.38–5.10 mg GAE/100 g and 10.36–13.65%, respectively. FTIR analysis showed decreased crystallinity up on fermentation. Subsequently, dough fermented for 6 h with 3% yeast and 4% sugar (optimized condition) was considered for the extrusion processing, which leads to increased phenolic content and antioxidant activity up to 77.3 mg GAE/100 g, and 11.39 mg GAE/100 g, respectively. Expansion ratio, bulk density, water solubility and water absorption index were determined for product characterization. Furthermore, extrudate prepared from the fermented flour had slightly higher acceptability (mean score: 4.12) than the unfermented counter part (mean score: 3.75) out of 5. [ABSTRACT FROM AUTHOR]

X-linked Charcot-Marie-Tooth type 1 X (CMTX1) disease is a subtype of Charcot-Marie-Tooth (CMT), which is mainly caused by mutations in the GJB1 gene. It is also known as connexin 32 (Cx32) that leads to Schwann cell abnormalities and peripheral neuropathy. CMTX1 is considered as the second most common form of CMT disease. The aim of this study is to computationally predict the potential impact of different single amino acid substitutions at position 75 of Cx32, from arginine (R) to proline (P), glutamine (Q) and tryptophan (W). This position is known to be highly conserved among the family of connexin. To understand the structural and functional changes due to these single amino acid substitutions, we employed a homology-modeling technique to build the three-dimensional structure models for the native and mutant proteins. The protein structures were further embedded into a POPC lipid bilayer, inserted into a water box, and subjected to molecular dynamics simulation for 50 ns. Our results show that the mutants R75P, R75Q and R75W display variable structural conformation and dynamic behavior compared to the native protein. Our data proves useful in predicting the potential pathogenicity of the mutant proteins and is expected to serve as a platform for drug discovery for patients with CMT. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the effect of 460 nm light-emitting diode (LED) on the inactivation of foodborne bacteria. Additionally, the change in the endogenous metabolic profile of LED illuminated cells was analyzed to understand the bacterial response to the LED illumination. Six different species of bacteria ( Bacillus cereus , Listeria monocytogenes, Staphylococcus aureus , Escherichia coli O157:H7, Pseudomonas aeruginosa and Salmonella Typhimurium) were illuminated with 460 nm LED to a maximum dose of 4080 J/cm 2 at 4, 10 and 25 °C. Inactivation curves were modeled using Hom model. Metabolic profiling of the non-illuminated and illuminated cells was performed using a Liquid chromatography–mass spectrometry system. Results indicate that the 460 nm LED significantly (p < 0.05) reduced the populations of all six bacterial species. For example, the population of S. aureus reached below detection limit within 7 h. B. cereus was most resistant to photo-inactivation and exhibited about 3-log reduction in 9 h. Metabolic profiling of the illuminated cells indicated that several metabolites e.g. 11-deoxycortisol, actinonin, coformycin, tyramine, chitobiose etc. were regulated during LED illumination. These results elucidate the effectiveness of 460 nm LED against foodborne bacteria and hence, its suitability as a novel antimicrobial control method to ensure food safety. [ABSTRACT FROM AUTHOR]

[Display omitted] • Multidisciplinary biophysical analyses of FapA, FapB, and FapC. • FapA forms complex with preamyloid FapC, but not with FapB. • FapA inhibits amyloid formation of FapC at the nucleation step. • FapA is an intrinsically disordered chaperone of Pseudomonas functional amyloid. Bacterial functional amyloids contribute to biofilm development by bacteria and provide protection from the immune system and prevent antibiotic treatment. Strategies to target amyloid formation and interrupt biofilm formation have attracted recent interest due to their antimicrobial potential. Functional amyloid in Pseudomonas (Fap) includes FapC as the major component of the fibril while FapB is a minor component suggested to function as a nucleator of FapC. The system also includes the small periplasmic protein FapA, which has been shown to regulate fibril composition and morphology. The interplay between these three components is central in Fap fibril biogenesis. Here we present a comprehensive biophysical and spectroscopy analysis of FapA, FapB and FapC and provide insight into their molecular interactions. We show that all three proteins are primarily disordered with some regions with structural propensities for α-helix and β-sheet. FapA inhibits FapC fibrillation by targeting the nucleation step, whereas for FapB the elongation step is modulated. Furthermore, FapA alters the morphology of FapC (more than FapB) fibrils. Complex formation is observed between FapA and FapC, but not between FapA and FapB, and likely involves the N-terminus of FapA. We conclude that FapA is an intrinsically disordered chaperone for FapC that guards against fibrillation within the periplasm. This new understanding of a natural protective mechanism of Pseudomonas against amyloid formations can serve as inspiration for strategies blocking biofilm formation in infections. [ABSTRACT FROM AUTHOR]

Constructions of dams/reservoirs all over the world are reported to emit significant amount of greenhouse gases (GHGs) and are considered as environmental polluters. Organic carbon is contributed by the forest in the catchment, part of soil organic carbon is transported through the runoffs to the reservoir and undergoes aerobic and anaerobic degradation with time to release GHGs to the atmosphere. Literature reveals that no work is available on the estimation of ‘C’ stock of trees of forest catchment for assessing/predicting the GHGs emissions from the reservoirs to atmosphere. To assess the GHGs emission potential of the reservoir, an attempt is made in the study to estimate the ‘C’ stock in the forest catchment of Kotli Bhel 1A hydroelectric reservoir located in Tehri Garhwal district of Uttarakhand, India. For this purpose, the selected area was categorized into the site-I, II and III along the Bhagirathi River based on type of forest available in the catchment. The total carbon density (TCD) of tree species of different forest types was calculated using diameter at breast height (dbh) and trees height. The results found that the TCD of forest catchment was found 76.96 Mg C ha −1 as the highest at the site-II and 29.93 Mg C ha −1 as lowest at site-I with mean of 51.50 Mg C ha −1 . The estimated forest ‘C’ stock shall be used to know the amount of carbon present before and after construction of the dam and to predict net GHGs emissions. The results may be helpful to study the potential of a given reservoir to release GHG and its subsequent impacts on global warming/climate challenges. [ABSTRACT FROM AUTHOR]

Arsenic (As) is a toxic element with the potential to cause health effects in humans. Besides rice is a source of both amino acids (AAs) and mineral nutrients, it is undesired source of As for billions of people consuming rice as the staple food. Selenium (Se) is an essential metalloid, which can regulate As toxicity by strengthening antioxidant potential. The present study was designed to investigate As III stress mitigating effect of Se VI in rice. The level of As, thiolic ligands and AAs was analyzed in rice seedlings after exposure to As III /Se VI alone and As III +Se VI treatments. Selenate supplementation (As III 25 μM+Se VI 25 μM) decreased total As accumulation in both root and shoot (179 & 144%) as compared to As III alone treatment. The As III +Se VI treatment also induced the levels of non-protein thiols (NPTs), glutathione (GSH) and phytochelatins (PCs) as compared to As III alone treatment and also modulated the activity of enzymes of thiol metabolism. The content of amino acids (AAs) was significantly altered with Se VI supplementation. Importantly, essential amino acids (EAAs) were enhanced in As III +Se VI treatment as compared to As III alone treatment. In contrast, stress related non-essential amino acids (NEAAs) like GABA, Glu, Gly, Pro and Cys showed enhanced levels in As III alone treatment. In conclusion, rice supplemented with Se VI tolerated As toxicity with reduced As accumulation and increased the nutrition quality by increasing EAAs. [ABSTRACT FROM AUTHOR]

Hemoglobins with diverse characteristics have been identified in all kingdoms of life. Their ubiquitous presence indicates that these proteins play important roles in physiology, though function for all hemoglobins are not yet established with certainty. Their physiological role may depend on their ability to bind ligands, which in turn is dictated by their heme chemistry. However, we have an incomplete understanding of the mechanism of ligand binding for these newly discovered hemoglobins and the measurement of their kinetic parameters depend on their coordination at the heme iron. To gain insights into their functional role, it is important to categorize the new hemoglobins into either penta- or hexa-coordinated varieties. We demonstrate that simple pH titration and absorbance measurements can determine the coordination state of heme iron atom in ferric hemoglobins, thus providing unambiguous information about the classification of new globins. This method is rapid, sensitive and requires low concentration of protein. Penta- and hexa-coordinate hemoglobins displayed distinct pH titration profiles as observed in a variety of hemoglobins. The pentacoordinate distal histidine mutant proteins of hexacoordinate hemoglobins and ligand-bound hexacoordinate forms of pentacoordinate hemoglobins reverse the pH titration profiles, thus validating the sensitivity of this spectroscopic technique. [ABSTRACT FROM AUTHOR]

Human Protein tyrosine kinase 6 (PTK6) (EC:2.7.10.2), also known as the breast tumor kinase (BRK), is an intracellular non-receptor Src-related tyrosine kinase expressed in a majority of human breast tumors and breast cancer cell lines, but its expression is low or completely absent in normal mammary glands. In the recent past, several studies have suggested that PTK6 is a potential therapeutic target in cancer. To understand its structural and functional properties, the PTK6 kinase domain (PTK6-KD) gene was cloned, overexpressed in a baculo-insect cell system, purified and crystallized at room temperature. X-ray diffraction data to 2.33 Å resolution was collected on a single PTK6-KD crystal, which belonged to the triclinic space group P1. The Matthews coefficient calculation suggested the presence of four protein molecules per asymmetric unit, with a solvent content of ∼50%.The structure has been solved by molecular replacement and crystal structure data submitted to the protein data bank under the accession number 5D7V. This is the first report of apo PTK6-KD structure crystallized in DFG-in and αC-helix-out conformation. [ABSTRACT FROM AUTHOR]

Dehydroascorbate reductase (DHAR), a member of the glutathione-S-transferase (GST) family, reduces dehydroascorbate (DHA) to ascorbate (AsA; Vitamin-C) in a glutathione (GSH)-dependent manner and in doing so, replenishes the critical AsA pool of the cell. To understand the enzyme mechanism in detail, we determined the crystal structure of a plant DHAR from Pennisetum glaucum (PgDHAR) using Iodide-Single Anomalous Dispersion (SAD) and Molecular replacement methods, in two different space groups. Here, we show Pg DHAR in complex with two non-native ligands, viz. an acetate bound at the G-site, which resembles the γ-carboxyl moiety of GSH, and a glycerol at the H-site, which shares the backbone of AsA. We also show that, in the absence of bound native substrates, these non-native ligands help define the critical ‘hook points’ in the DHAR enzyme active site. Further, our data suggest that these non-native ligands can act as the logical bootstrapping points for iterative design of inhibitors/analogs for DHARs. [ABSTRACT FROM AUTHOR]

[Display omitted] • Summative view of tail-approach based selective as well as potent hCA IX and XII inhibitors reported in the last decade. • Listing of the most promising molecules in terms of selectivity and potency from the available 181 research papers. • One stop solution to tailor the tail-approach based rational design of novel libraries of carbonic anhydrase inhibitors. Human carbonic anhydrase (hCA) isoforms hCA IX and hCA XII are well established anticancer drug targets and their selective inhibition is highly desired for the proper treatment of cancer. Lack of isoform-selectivity in current clinically used CA inhibitors (CAIs) is a major concern as it leads to undesired side effects, associated with off-target inhibition. Thus, there is need to explore alternative approaches for the design of isoform-selective inhibitors and the leading promising approach for the design of isoform-selective CAIs is "the tail-approach". Virtually, most drug design studies in the last decade were done by considering the tail-approach reported in 1999. The past decade of 2010–2020 witnessed progressive maturation of this approach as a large number of CAIs have been designed and synthesised based on it, many of which turned out to be effective as well as selective hCA IX and hCA XII inhibitors. This review covers the past decade (2010–2020) research, considering selective as well as potent inhibitors of tumor associated isoforms, hCA IX and hCA XII, which include newer generation inhibitors containing sulfonamides or their bioisosteres, non-classical inhibitors (including carboxylic acid/ester, coumarin and sulfocoumarin classes) and various other novel classes of inhibitors belonging to newly identified chemotypes/scaffolds. [ABSTRACT FROM AUTHOR]

The present study was undertaken to characterize the distinct immune response in indigenous Ghurrah and exotic Landrace pigs by challenging monocyte-derived macrophages (MDMs) with CSF virus under in-vitro conditions and assessing the variations in the transcriptome profile at 48 h post-infection (hpi). RNA-sequencing was carried out in infected and non-infected MDMs of Ghurrah (n = 3) and Landrace (n = 3) piglets prior- as well as post-stimulation. MDMs of Ghurrah showed greater immune regulation in response to CSF infection with 518 significantly differentially expressed genes (DEG) in infected versus non-infected MDMs, as compared to only 31 DEGs in Landrace MDMs. In Landrace, the principal regulators of inflammation (IL1α , IL1β and TNF) were upregulated in infected cells while in Ghurrah, these were downregulated. Overall, macrophages from indigenous Ghurrah showed more immunological dysregulation in response to virulent CSF virus infection as compared to the exotic Landrace pigs. • The present study aimed to characterize the distinct immune response in indigenous Ghurrah and exotic Landrace pigs against CSF vaccination. • Monocyte-derived macrophages (MDMs) were stimulated with CSF virus under in-vitro conditions. • The variations in the transcriptome profile via RNA-Seq approach were assessed in stimulated cells at 48 h post-infection. • MDMs of Ghurrah showed greater immune regulation in response to CSF infection with 518 significantly differentially expressed genes in infected versus non-infected MDMs, as compared to only 31 DEGs in Landrace MDMs. • In Landrace, the principal regulators of inflammation (IL1α, IL1β and TNF) were upregulated in infected cells while in Ghurrah, these were downregulated. • Macrophages from indigenous Ghurrah showed more immunological dysregulation in response to virulent CSF virus infection as compared to the exotic Landrace pigs. [ABSTRACT FROM AUTHOR]

Background Cerebral ischemia-reperfusion (I-R) injury is one of the primary causes of ischemic stroke. Ischemic postconditioning (iPoCo) is evolving as an important adaptive technique to contain I-R injury. Some recent studies have shown neuroprotective effects of iPoCo. However, the neuroprotective mechanism of iPoCo is not clear. So, the present study has been undertaken to investigate the possible role of Sirtinol, a selective class III histone deacetylase (HDAC) inhibitor in the neuroprotective mechanism of iPoCo in mice. Material and methods Bilateral carotid artery occlusion (BCAO) for 12 min followed by reperfusion for 24 h was used to produce I-R-induced cerebral injury in Swiss albino mice. iPoCo involving three episodes of 10-s carotid artery occlusion and reperfusion instituted immediately after BCAO just before prolonged reperfusion of 24 h. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was evaluated using a Morris water maze test. Rotarod test, inclined beam-walking test, and neurologic severity score (NSS) were used to assess motor incoordination. Acetylcholine esterase levels, brain thiobarbituric acid reactive species (TBARS), and glutathione level were also estimated. Results BCAO for 12 min followed by reperfusion for 24 h produced a significant rise in cerebral infarct size and NSS along with impairment of memory and motor coordination and biochemical alteration (↑acetylcholine esterase, ↓glutathione, and ↑TBARS). iPoCo, involving three episodes of 10-s carotid artery occlusion with intermittent reperfusion of 10 s applied just after ischemic insult of 12 min produced a significant decrease in cerebral infarct size and NSS along with the reversal of I-R-induced impairment of memory and motor coordination. iPoCo-induced neuroprotective effects were significantly abolished by pretreatment with selective SIRT 1 (class III HDAC) blocker Sirtinol (10 mg/kg intraperitoneal). Conclusions It may be concluded that the neuroprotective effect of iPoCo probably involves activation of SIRT 1 (class III HDAC) enzyme. [ABSTRACT FROM AUTHOR]

Background Previous studies have suggested a significant role of pannexin 1 (Panx1)/P2X7 receptor complex in cardioprotective mechanism of ischemic preconditioning and postconditioning (IPC). The present study has been undertaken to investigate whether Panx1/P2X7 purinoceptors are also involved in the neuroprotective mechanism of IPC in mice. Materials and methods Bilateral carotid artery occlusion (BCAO) for 12 min followed by reperfusion for 24 h was used to produce ischemia-reperfusion-induced cerebral injury in Swiss albino mice. For IPC immediately after BCAO of 12 min, three cycles of 10-s ischemia and reperfusion each were given and then prolonged reperfusion of 24 h was used. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was evaluated using a Morris water maze test. Rotarod test, inclined beam walking test, and neurologic severity score (NSS) were used to assess motor dysfunction. Acetylcholine esterase levels, brain thiobarbituric acid reactive species, and glutathione level were also estimated. Results BCAO followed by reperfusion produced a significant increase in cerebral infarct size, NSS along with impairment of memory and motor dysfunction. It also increased brain acetylcholine esterase, thiobarbituric acid reactive species levels, and decreased the glutathione level. IPC produced a significant decrease in the cerebral infarct size and NSS along with reversal of ischemia-reperfusion-induced impairment of memory, motor dysfunction, and altered biochemical levels in the brain. IPC-induced neuroprotective effects were significantly abolished by pretreatment of mefloquine (15.0 mg/kg orally; 30.0 mg/kg orally), blocker of Panx1/P2X7 purinoceptor. Conclusions Therefore, activation of Panx1/P2X7 purinoceptors appears to play a significant role in the neuroprotective mechanism of IPC. [ABSTRACT FROM AUTHOR]

Nitric oxide is a versatile and powerful signaling molecule in plants. However, most of our understanding stems from studies on terrestrial plants and very little is known about marine autotrophs. This review summarizes current knowledge about the source of nitric oxide synthesis in marine photosynthetic organisms and its role in various physiological processes under normal and stress conditions. The interactions of nitric oxide with other stress signals and cross talk among secondary messengers are also highlighted. [ABSTRACT FROM AUTHOR]

Pipeline hydrotransport of agricultural residue in a carrier liquid could be an economically viable alternative to replace truck delivery of biomass materials, as well as encouraging the increase in scale of bio-refineries. The feasibility of this concept, together with friction loss behaviour and corresponding mechanisms of biomass slurry flows through pipelines, was previously studied by the authors. A 50 mm diameter, 25 m long pipeline facility was used to measure the longitudinal pressure gradient of wheat straw and corn stover slurries over a range of particle dimensions, slurry solid mass fractions, and slurry velocities. Econometric software and a nonlinear least square regression model were used to analyse the measured pressure gradients and an empirical correlation was proposed to predict slurry pressure gradients as a function of slurry specifications and operating conditions. The correlation was then modified using scale-up methods to account for the effects of pipe diameter. The pressure gradient was found to be proportional to the pipe diameter to the power of −1.2. The final correlation was able to predict the longitudinal pressure gradient of the flow of agricultural residues (i.e., non-wood fibres) as biomass slurries in pipes and, with a small uncertainty (<10%), could be applied to design commercial pipelines to hydraulically transport various agricultural residue biomass slurries. This knowledge of the slurry flow pressure gradient is essential to specify slurry pumps, determine the number of booster stations, and estimate the capital and operational costs of a slurry pipeline. [ABSTRACT FROM AUTHOR]

[Display omitted] • Tail-approach based design, synthesis and characterization of a library of twenty-two arylthiazolylhydrazono-1,2,3-triazoles incorporating sulfanilamide and metanilamide moieties are disclosed. • All newly synthesized compounds were screened in vitro for their inhibition efficacy against hCA I, II, IV and IX isoforms. • Some compounds showed either comparable or better inhibition potential than clinically used reference drug AAZ against the targeted isoforms. • In broader sense, sulfanilamide analogues (4a - 4 k) were found to be better inhibitors of cytosolic hCA I and II isoforms than metanilamide analogues (5a - 5 k), whereas exactly opposite trend was observed in case of inhibition of membrane bound hCA IV and tumor associated transmembrane hCA IX. A library of twenty-two arylthiazolylhydrazono-1,2,3-triazoles incorporating sulfanilamide and metanilamide moieties have been synthesized by utilizing tail-approach and characterized by their IR, 1H NMR, 13C NMR, HRMS and single crystal studies. Further, these newly synthesized compounds were screened in-vitro for their inhibition efficacy against physiologically relevant hCA I, II, IV and IX isoforms. Inhibition data revealed that, in broader sense, sulfanilamide analogues (4a - 4 k) were comparatively better inhibitors of cytosolic hCA I and II isoforms than metanilamide analogues (5a - 5 k), whereas exactly opposite trend was observed in case of inhibition of membrane bound hCA IV and transmembrane hCA IX. For hCA I, more than half of the synthesized compounds were found to be moderate inhibitors and three compounds 4b , 5b and 5e (K i of 40.6, 224.7 and 74.4 nM, respectively) appeared as better inhibitors than reference drug AAZ (K i = 250 nM). hCA II was potently inhibited by 4e - 4 g and 5e with K i of 18.1, 14.1, 14.9 and 17.8 nM, respectively. Interestingly, 4e - 4 g selectively inhibited hCA II with selectivity of > 15-fold over hCA I, IV and IX isoforms. All the compounds presented moderate to weak inhibition profiles against glaucoma associated hCA IV with K i of 88 nM-8.87 μM and except 4f , 5 k , significant inhibition profiles against tumor associated hCA IX isoform with K i spanning in range of 0.113 μM-0.318 μM. Moreover, 5e was the only compound among the whole series which effectively inhibited all the tested isoforms. [ABSTRACT FROM AUTHOR]

[Display omitted] • Band-selective 13Cα-15N het-TOCSY mixing can be an effective module in RF pulse schemes for resonance assignments in IDPs. • One-shot correlation spectra via simultaneous 15N x and 13Cα x magnetisation transfer from residue i to i+/-1 may be obtained. • The method may be modified to collect RN[NCA HEHAHA]NH and R'CA[CAN HEHAHA](CACO)NH data (with R = 'HN' or 'HNCO' and R' = 'Hα' or sidechain 'HscCsc'). Intrinsically disordered proteins (IDPs) or protein regions represent functionally important biomolecules without unique structure. Their inherent flexibility prevents high-resolution structure determination by X-ray or cryo-EM methods. In contrast, NMR spectroscopy provides an extensive and still growing set of experimental approaches to obtain detailed information on structure and dynamics of IDPs. Here, it is experimentally demonstrated that 15N-13Cα band-selective heteronuclear cross-polarisation that has been successfully employed recently to achieve the efficient transfer of 15N x magnetisation from amino acid residue 'i' to 'i + 1' and 'i − 1' residues in uniformly (15N,13C)-labelled intrinsically disordered proteins can also be applied to transfer, without significant relaxation losses, 13Cα x magnetisation from an amino acid residue to its neighbouring residues. The possibility to obtain in one-shot correlation spectra arising from the simultaneous transfer of 15N x and 13Cα x magnetisations from an amino acid residue to neighbouring residues is also demonstrated. [ABSTRACT FROM AUTHOR]

Abstract: Cytokines are known to play pivotal roles in cancer initiation, progression and pathogenesis. Accumulating evidences suggest differences in basal and stress-induced cytokine profiles of cancers with diverse origin. However, a comprehensive investigation characterising the cytokine profile of various tumor types after acute and fractionated doses of gamma-irradiation, and its effect on survival of bystander cells is not well known in literature. In the present study, we have evaluated the cytokine secretion profile of human tumor cell lines (HT1080, U373MG, HT29, A549 and MCF-7) either before (basal) or after acute (2, 6Gy) and fractionated doses (3×2Gy) of gamma-irradiation in culture medium obtained from these cells by multiplex bead array/ELISA. Moreover, clonogenic assays were performed to evaluate the effect of conditioned medium (CM) on the survival and growth of respective cells. Based on the screening of 28 analytes, our results showed that the basal profiles of these cell lines varied considerably in terms of the number and magnitude of secreted factors, which was minimum in MCF-7. Interestingly, TNF-α, IL-1β, PDGF-AA, TGF-β1, fractalkine, IL-8, VEGF and GCSF were found in CM of all the cell lines. However, secretion of certain cytokines was cell line-specific. Moreover, CM caused increase in clonogenic survival of respective tumor cells (in the order HT1080>U373MG>HT29>A549>MCF-7), which was correlated with the levels of IL-1β, IL-6, IL-8, GMCSF and VEGF in their CM. After irradiation, the levels of most of the cytokines increased markedly in a dose dependent manner. The fold change in cytokine levels was lower in irradiated conditioned medium (ICM) of tumor cells collected after fractionated than respective acute dose, except in MCF-7. Interestingly, amongst these cell lines, the radiation-induced fold increase in cytokine levels was maximum in ICM of A549 cells. Moreover, bystander A549 cells treated with respective ICM showed dose dependent decrease in clonogenic survival. In conclusion, present study revealed the similarities and subtle differences in basal and radiation-induced cytokine profile of different tumor cell lines, and its influence on growth and survival of respective bystander cells. These findings may add a new dimension to our current understanding about role of cytokines in cancer biology. [Copyright &y& Elsevier]

Abstract: MicroRNAs (miRNAs) are small non-coding RNAs that play a role in post-transcriptional regulation of gene expression in most eukaryotes. They help in fine-tuning gene expression by targeting messenger RNAs (mRNA). The interactions of miRNAs and mRNAs are sequence specific and computational tools have been developed to predict miRNA target sites on mRNAs, but miRNA research has been mainly focused on target sites within 3′ untranslated regions (UTRs) of genes. There is a need for an easily accessible repository of genome wide full length mRNA — miRNA target predictions with versatile search capabilities and visualization tools. We have created a web accessible database of miRNA target predictions for human, mouse, cow, chicken, Zebra fish, fruit fly and Caenorhabditis elegans using two different target prediction algorithms, The database has target predictions for miRNA''s on 5′ UTRs, coding region and 3′ UTRs of all mRNAs. This database can be freely accessed at http://mamsap.it.deakin.edu.au/mirna_targets/. [Copyright &y& Elsevier]

Abstract: An accelerated boundary integral method for Stokes flow of a suspension of deformable particles is presented for an arbitrary domain and implemented for the important case of a planar slit geometry. The computational complexity of the algorithm scales as or ), where N is proportional to the product of number of particles and the number of elements employed to discretize the particle. This technique is enabled by the use of an alternative boundary integral formulation in which the velocity field is expressed in terms of a single layer integral alone, even in problems with non-matched viscosities. The density of the single layer integral is obtained from a Fredholm integral equation of the second kind involving the double layer integral. Acceleration in this implementation is provided by the use of General Geometry Ewald-like method (GGEM) for computing the velocity and stress fields driven by a set of point forces in the geometry of interest. For the particular case of the slit geometry, a Fourier-Chebyshev spectral discretization of GGEM is developed. Efficient implementations employing the GGEM methodology are presented for the resulting single and the double layer integrals. The implementation is validated with test problems on the velocity of rigid particles and drops between parallel walls in pressure driven flow, the Taylor deformation parameter of capsules in simple shear flow and the particle trajectories in pair collisions of capsules in simple shear flow. The computational complexity of the algorithm is verified with results from several large scale multiparticle simulations. [Copyright &y& Elsevier]

Abstract: Diospyrin diethylether (D7), a bisnaphthoquinonoid derivative, exhibited an oxidative stress-dependent apoptosis in several human cancer cells and tumor models. The present study was aimed at evaluation of the increase in cytosolic calcium [Ca2+]c leading to the apoptotic cell death triggered by D7 in MCF7 human breast carcinoma cells. A phosphotidylcholine-specific phospholipase C (PC-PLC) inhibitor, viz. U73122, and an antioxidant, viz. N-acetylcysteine, could significantly prevent the D7-induced rise in [Ca2+]c and PC-PLC activity. Using an endoplasmic reticulum (ER)-Ca2+ mobilizer (thapsigargin) and an ER-IP3R antagonist (heparin), results revealed ER as a major source of [Ca2+]c which led to the activation of calpain and caspase12, and cleavage of fodrin. These effects including apoptosis were significantly inhibited by the pretreatment of Bapta-AM (a cell permeable Ca2+-specific chelator), or calpeptin (a calpain inhibitor). Furthermore, D7-induced [Ca2+]c was found to alter mitochondrial membrane potential and induce cytochrome c release, which was inhibited by either Bapta-AM or ruthenium red (an inhibitor of mitochondrial Ca2+ uniporter). Thus, these results provided a deeper insight into the D7-induced redox signaling which eventually integrated the calcium-dependent calpain/caspase12 activation and mitochondrial alterations to accentuate the induction of apoptotic cell death. [Copyright &y& Elsevier]

Abstract: The ability of pathogenic bacteria to sense and respond to periods of host stress is critical to their lifestyle. Adrenaline and norepinephrine are catecholamines that mediate acute host stress in vertebrates and invertebrates. Catecholamines are also used as environmental cues to enhance growth, motility and virulence of bacterial pathogens via specific binding receptors. Incidence of multidrug resistant and highly virulent bacterial pathogens is on the rise, and majority of the genes for antimicrobial resistance (AMR) and virulence are carried on horizontally transferable genetic elements. Conjugation machinery offers an efficient method for acquisition of AMR and virulence genes, which may be responsible for propelling the evolution of pathogenic bacteria. Here we show that norepinephrine (NE) at physiological concentrations enhances horizontal gene transfer (HGT) efficiencies of a conjugative plasmid from a clinical strain of Salmonella Typhimurium to an Escherichia coli recipient in vitro. Expressions of plasmid encoded transfer (tra) genes necessary for conjugation were also significantly upregulated in the presence of NE. Phentolamine, an α-adrenergic receptor antagonist, negated the effects of NE on conjugation more strongly than propranolol, a β-adrenergic receptor antagonist. This study for the first time provides evidence that innate mediators of acute host stress may influence evolution and adaptation of bacterial pathogens. [Copyright &y& Elsevier]

Abstract: In the present study, the in vivo effects of λ-cyhalothrin and cypermethrin on the activity of acetylcholinesterase (AChE, EC 3.1.1.7) were evaluated for 96h in brain, muscle and gills of Channa punctatus. Both compounds exhibited tissue specific as well as dose dependent decrease in the activity of AChE. The treated fish showed a significant decrease in the activity of AChE in brain and a lesser inhibition in muscle and gills in response to the increasing concentrations of λ-cyhalothrin as well as cypermethrin. Our results indicated that the brain was the main target organ for both insecticides, followed by muscle and gills, as determined by AChE inhibition study. However, these organs showed variations in the degree of AChE inhibition for separate treatments of both insecticides. The λ-cyhalothrin was a more potent AChE inhibitor as compared to cypermethrin. These findings indicated that apart from the established mechanism of delayed closure of sodium ion channels, these pyrethroids inhibit the activity of AChE in C. punctatus which could further aggravate their neurotoxic effects. [Copyright &y& Elsevier]

The NSP6 protein of SARS-CoV-2 is a transmembrane protein, with some regions lying outside the membrane. Besides a brief role of NSP6 in autophagosome formation, this is not studied significantly. Also, there is no structural information available to date. Based on the prediction by TMHMM server for transmembrane prediction, it is found that the N-terminal residues (1-11), middle region residues (91–112), and C-terminal residues (231–290) lies outside the membrane. Molecular Dynamics (MD) simulations showed that NSP6 consists of helical structures. In contrast, the membrane outside lying region (91–112) showed partial helicity, which was further used as a model and obtained disordered type conformation during 1.5 μs. Additionally, a 200ns simulation study of residues 231–290 have shown significant conformational changes. As compared to helical and beta-sheet conformations in its structure model, the 200ns simulation resulted in the loss of beta-sheet structures while helical regions remained intact. Further, we have experimentally characterized the residue 91–112 by using reductionist approaches. CD spectroscopy suggests that the NSP6 (91–112) is disordered-like region in isolation, which gains helical conformation in different biological mimic environmental conditions. These studies can be helpful to study NSP6 (91–112) interactions with host proteins, where different protein conformations might play a significant role. The present study adds up more information about the NSP6 protein aspect, which could be exploited for its host protein interaction and pathogenesis. The schematic representation of NSP6 membrane topology and conformational dynamics of residue 91–112. The N-terminal and C-terminal are shown in cytoplasmic side based on the experimental evidence on coronaviruses reported by Oostra et al., 2008. The membrane anchoring domain are shown based on the TMHMM server prediction. [Display omitted] • MD simulations study of SARS-CoV-2 NSP6 model is conducted to reveal its dynamics due to unavailability of its 3D structure. • Transmembrane regions are predicted using TMHMM web-server which predicted seven transmembrane regions. • Two non-transmembrane regions (residues 91–112 and 231–290) are investigated through extensive MD simulations. • NSP6 (91–112) region is investigated for its structural conformations using CD spectroscopy and fluorescence spectroscopy. [ABSTRACT FROM AUTHOR]

The pulp and paper industry consumes a huge amount of water and releases more polluted and colored wastewater every year. Many conventional techniques are used in the treatment of paper industry wastewater. However, for color removal from paper mill effluent, there is no proven method so far, on an industrial scale. Due to high energy input and high cost, there is an urgent need to find out a new technique that must be sustainable, economical, and environment friendly. Various methods have been investigated on bench scale and pilot scale also but no proven method for color removal on an industrial scale. The paper provides an overview of the color removal techniques from different sources of pulp and paper mill wastewater discharged by various industries. The review described various components involved in various processes for color removal from paper mill waste water. The present works focus on processes like chemical, chemical/physical, biological, physicochemical, and electrochemical applied in color removal from paper mill wastewater. The present review gives key information on the effectiveness, use, betterment, and limitations of numerous methods of treatment targeted at color removal from paper mill wastewater using various techniques still under evolution. • A critical study made on color removal from paper mill effluent using various methods. • Examined color removal efficiencies using conventional and advanced techniques. • Study on Cost analysis in color removal from paper mill effluent. • Future research suggestions described for better implementation of the processes. [ABSTRACT FROM AUTHOR]

In the present study, a combination of microwave and thermosonication treatment was introduced in the soymilk extraction process, and the process was optimized to minimize the enzymatic activity of Soybean Trypsin Inhibitor (STI) and Lipoxygenase (LOX) enzymes. Protein content, fat content, TSS (Total Soluble Solids), and viscosity of soymilk increased upon thermosonication process and was most affected by microwave time followed by ultrasonification time. The inactivation rate constant for STI and LOX was 0.2034 min−1 and 0.3232 min−1, respectively, indicating LOX was more susceptible to inactivation under microwave treatment as compared to STI. The activation energy of STI and LOX decreased from 48.44 to 10.24 kJ/mol and 53.47 to 3.07 kJ/mol after 5 min of microwave pasteurization. FTIR analysis confirmed the conformational deformation of proteins and enhanced molecular interactions in the optimized soymilk. The optimized condition was obtained as 3 min of microwave pasteurization followed by 30 min of ultrasonication at 60 °C in an ultrasonic bath of 28 ± 2 kHz frequency. The optimized treatment produced the soymilk with enhanced nutritional quality and low enzymatic activities. [Display omitted] • Effect of microwave and ultrasound on soymilk quality attributes was analyzed. • Thermosonication increased TSS, fat, and viscosity of extracted soymilk. • LOX enzyme was more sensitive to microwave and ultrasound than STI enzyme. • The activation energy of LOX and STI enzymes decreased after microwave treatment. • Soymilk extraction process was optimized for minimum STI and LOX activities. [ABSTRACT FROM AUTHOR]

Abstract: T-cell-restricted intracellular antigen-1 (TIA-1) regulates alternative pre-mRNA splicing in the nucleus, and mRNA translation in the cytoplasm, by recognizing uridine-rich sequences of RNAs. As a step towards understanding RNA recognition by this regulatory factor, the X-ray structure of the central RNA recognition motif (RRM2) of human TIA-1 is presented at 1.95Å resolution. Comparison with structurally homologous RRM-RNA complexes identifies residues at the RNA interfaces that are conserved in TIA-1–RRM2. The versatile capability of RNP motifs to interact with either proteins or RNA is reinforced by symmetry-related protein–protein interactions mediated by the RNP motifs of TIA-1–RRM2. Importantly, the TIA-1–RRM2 structure reveals the locations of mutations responsible for inhibiting nuclear import. In contrast with previous assumptions, the mutated residues are buried within the hydrophobic interior of the domain, where they would be likely to destabilize the RRM fold rather than directly inhibit RNA binding. [Copyright &y& Elsevier]

Falcipain-2 is one of the principal hemoglobinases of Plasmodium falciparum, a human malaria parasite. It has a typical papain family cysteine protease structural organization, a large pro-domain, a mature domain with conserved active site amino acids. Pro-domain of falcipain-2 also contains two important conserved motifs, “GNFD” and “ERFNIN.” The “GNFD” motif has been shown to be responsible for correct folding and stability in case of many papain family proteases. In the present study, we carried out site-directed mutagenesis to assess the roles of active site residues and pro-domain residues for the activity of falcipain-2. Our results showed that substitutions of putative active site residues; Q36, C42, H174, and N204 resulted in complete loss of falcipain-2 activity, while W206 and D155 mutants retained partial/complete activity in comparison to the wild type falcipain-2. Homology modeling data also corroborate the results of mutagenesis; Q36, C42, H174, N204, and W206 residues form the active site loop of the enzyme and D155 lie outside the active pocket. Substitutions in the pro-region did not affect the activity of falcipain-2. This implies that falcipain-2 shares active site residues with other members of papain family, however pro-region of falcipain-2 does not play any role in the activity of enzyme. [Copyright &y& Elsevier]

The scale-up of biorefineries to compete with fossil fuel production is limited by the high overland transportation cost of lignocellulosic biomass. Pipeline hydro-transport of agricultural or forest residue biomass to biorefineries could be a cost-effective and sustainable solution to this problem. The upward flow of chopped maize stover (also known as corn stover) aqueous slurries through a vertical pipe section of a 29 m long, 50 mm diameter in a closed pipeline loop was studied. The frictional pressure drops of maize stover slurries were measured at several particle sizes (from <3.2–19.2 mm), slurry solid concentrations (5–40% [mass]), and slurry velocities (0.5–4.3 m s−1). The results were analysed and compared with wheat straw. For specific concentrations and flow rates, particle size, shape, and flexibility are the factors that most reduced drag, which was highest (by 32%) for the largest particle size of maize stover. For velocities ≥2.5 m s−1, maize stover suspensions (other than the 3.2 mm particle size) were more effective in reducing drag than wheat straw, whereas at lower velocities (≤2.0 m s−1), wheat straw had more influence (other than the 19.2 mm). The results for critical concentrations for maximum drag reduction, onset velocity, threshold concentration for minimum onset velocity, and their variations with respect to particle size, particle type, and slurry concentrations provide new insights that require further investigation in larger diameter pipes. The results here will be beneficial for the design and operation of long-distance pipeline hydro-transport of biomass. • Hydro-transport of ground maize stover was examined in a vertical pipe section. • Frictional behaviour of two feedstocks was compared at various flow conditions. • Particle size, shape, and fibre flexibility were dominant in drag reduction (DR). • Onset velocity of DR lowest for largest particle size of maize stover. • Critical concentration for the maximum DR of maize stover lower than wheat straw. [ABSTRACT FROM AUTHOR]

Anthropogenic influences significantly modify the hydrochemical properties and material flow in riverine ecosystems across Asia, potentially accounting for 40–50% of global emissions. Despite the pervasive impact on Asian rivers, there is a paucity of studies investigating their correlation with carbon dioxide (CO 2) emissions. In this study, we computed the partial pressure of CO 2 (pCO 2) using the carbonate equilibria-based model (pCO 2 SYS) and examined its correlation with hydrochemical parameters from historical records at 91 stations spanning 2013–2021 in the Ganga River. The investigation unveiled substantial spatial heterogeneity in the pCO 2 across the Ganga River. The pCO 2 concentration varied from 1321.76 μatm, 1130.98 μatm, and 1174.33 μatm in the upper, middle, and lower stretch, respectively, with a mean of 1185.29 μatm. Interestingly, the upper stretch exhibited elevated mean pCO 2 and FCO 2 levels (fugacity of CO 2 : 3.63 gm2d−1) compared to the middle and lower stretch, underscoring the intricate interplay between hydrochemistry and CO 2 dynamics. In the context of pCO 2 fluctuations, nitrate concentrations in the upper segment and levels of biological oxygen demand (BOD) and dissolved oxygen (DO) in the middle and lower segments are emerging as crucial explanatory factors. Furthermore, regression tree (RT) and importance analyses pinpointed biochemical oxygen demand (BOD) as the paramount factor influencing pCO 2 variations across the Ganga River (n = 91). A robust negative correlation between BOD and FCO 2 was also observed. The distinct longitudinal patterns of both parameters may induce a negative correlation between BOD and pCO 2. Therefore, comprehensive studies are necessitated to decipher the underlying mechanisms governing this relationship. The present insights are instrumental in comprehending the potential of CO 2 emissions in the Ganga River and facilitating riverine restoration and management. Our findings underscore the significance of incorporating South Asian rivers in the evaluation of the global carbon budget. [Display omitted] • PCO 2 concentration higher in upstream region than downstream region of Ganges. • Nitrate predict pCO 2 well in upstream region. • BOD and DO are best predictors of pCO 2 in downstream regions. • BOD emerged as a crucial influencing factor for pCO 2 across the Ganga River. [ABSTRACT FROM AUTHOR]

This work reports synthesis of a dual-function facile heterojunction and investigation of role of the charge transfer dynamism between individual semiconductor components for superior photocatalytic and electrochemical sensing application. The bio-benevolent and sturdy ZnO/Fe 2 O 3 heterojunctions were utilized for visible light facilitated photo-degradation of sulfamethoxazole (SMX) antibiotic and electrochemical sensing of dopamine drug (DA). The fabricated heterojunction were characterized for structural, optical, and magnetic properties. Structural studies revealed the formation of nano heterojunction containing both phases. Magnetic studies confirmed the highly pure magnetic nature of photocatalysts. ZnO/30 wt%Fe 2 O 3 heterojunction (S2) shows 95.2% SMX degradation under visible light and high retention of performance under solar light. The scavenging experiments infer that OH radicals are the active species responsible for degradation. A Z-scheme photocatalytic mechanism was predicted for higher performance with protection of high potential VB of ZnO and CB of Fe 2 O 3 for high generation of reactive oxygen species. LC-MS was employed to predict a plausible degradation route. The sample modified glassy carbon electrodes (GCE) were used for electrochemical sensing of dopamine via cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The S2 junction exhibited 0.18 μM limit of detection with concentration range of 1 μM–50 μM. The stability test was successfully carried out at room temperature for 15 days. In addition, the S2 modified electrodes were spiked in real urine samples and good results were obtained. DPV reveals that S2 modified electrode is best sensor for dopamine sensing among all synthesized heterojunctions. The detection mechanism was also discussed in detail. The in-built metal redox i.e Zn2+/Zn+ and Fe3+/Fe2+ facilitate the Z-scheme transfer, improve the charge transfer capacity and reduce the recombination. This study is beneficial because it reports utilization of popular and well-tested semiconductor metal oxides to form heterojunctions with dual capabilities of environmental detoxification and cost-effective electrochemical detection of biomolecules. [Display omitted] • Dual functional facile ZnO/Fe 2 O 3 Z-scheme heterojunction with in-built metal redox. • Visible light assisted high performance photocatalytic removal of sulfamethoxazole. • OH as active species high potential band protection-Z-scheme • Sensitive and selective dopamine sensing with 0.18 μM limit of detection. [ABSTRACT FROM AUTHOR]

• A series of nitro- and methoxy-2-phenylbenzofuran was synthesized. • Compounds displayed activity against monoamine oxidase enzymes. • Relevance of number/position of methoxyl substitution in enzyme activity. • Importance of nitro substitution in MAO-A enzyme activity. • Physicochemical properties are suitable for good bioavailability. • Docking studies assisted in explaining the structure-activity relationship. A new series of 2-phenylbenzofuran derivatives were designed and synthesized to determine relevant structural features for the MAO inhibitory activity and selectivity. Methoxy substituents were introduced in the 2-phenyl ring, whereas the benzofuran moiety was not substituted or substituted at the positions 5 or 7 with a nitro group. Substitution patterns on both the phenyl ring and the benzofuran moiety determine the affinity for MAO-A or MAO-B. The 2-(3-methoxyphenyl)-5-nitrobenzofuran 9 was the most potent MAO-B inhibitor (IC 50 = 0.024 µM) identified in this series, whereas 7-nitro-2-phenylbenzofuran 7 was the most potent MAO-A inhibitor (IC 50 = 0.168 µM), both acting as reversible inhibitors. The number and position of the methoxyl groups on the 2-phenyl ring, have an important influence on the inhibitory activity. Molecular docking studies confirmed the experimental results and highlighted the importance of key residues in enzyme inhibition. [ABSTRACT FROM AUTHOR]

A major thrust of our laboratory has been to identify how physiological stress is transduced into transcriptional responses that feed back to overcome the inciting stress or its consequences, thereby fostering survival and repair. To this end, we have adopted the use of an in vitro model of ferroptosis, a caspase-independent, but iron-dependent form of cell death (Dixon et al., 2012 ; Ratan, 2020). In this review, we highlight three distinct epigenetic targets that have evolved from our studies and which have been validated in vivo studies. In the first section, we discuss our studies of broad, pan-selective histone deacetylase (HDAC) inhibitors in ferroptosis and how these studies led to the validation of HDAC inhibitors as candidate therapeutics in a host of disease models. In the second section, we discuss our studies that revealed a role for transglutaminase as an epigenetic modulator of proferroptotic pathways and how these studies set the stage for recent elucidation of monoamines as post-translation modifiers of histone function. In the final section, we discuss our studies of iron-, 2-oxoglutarate-, and oxygen-dependent dioxygenases and the role of one family of these enzymes, the HIF prolyl hydroxylases, in mediating transcriptional events necessary for ferroptosis in vitro and for dysfunction in a host of neurological conditions. Overall, our studies highlight the importance of epigenetic proteins in mediating prodeath and prosurvival responses to ferroptosis. Pharmacological agents that target these epigenetic proteins are showing robust beneficial effects in diverse rodent models of stroke, Parkinson's disease, Huntington's disease, and Alzheimer's disease. [ABSTRACT FROM AUTHOR]

The drug resistance of Plasmodium vivax in clinical cases remains largely unknown till date because of the difficulty in diagnosing the resistant P. vivax strains. The present study was undertaken to determine the prevalence of mutant alleles in drug resistance genes viz P. vivax multi-drug resistance (pvmdr-1), chloroquine resistance transporter (pvcrt-o) , dihydrofolate reductase (pvdhfr) and dihydropteroate synthase (pvdhps) along with in vitro chloroquine (CQ) sensitivity in P. vivax clinical isolates. During August–October 2017 a total of 86 samples of the febrile patients were screened and 31 samples were found to be positive for P. vivax in Safdarjung hospital, New Delhi. Sequence genotyping of the drug resistance genes was carried out in these P. vivax samples and in vitro CQ susceptibility for 23 isolates was determined by the schizont maturation assay (SMA). The CQ inhibitory concentrations (IC 50) for the clinical isolates was found to be in the range of 25.6–176.7 nM. All the 31 clinical isolates analyzed for pvmdr-1 gene, showed mutant alleles and in only two isolates novel mutations at 861 and 898 codons were observed. Sequence analysis of pvcrt-o , pvdhfr and pvdhps genes revealed wild type genotypes in all the 31 studied isolates. The presence of mutations in pvmdr-1 gene and the increase in the CQ IC 50 value indicates the possibility of shift in drug tolerance where CQ with primaquine (PQ) is still the first line of treatment for P. vivax malaria in the country. The regular molecular surveillance in P. vivax would provide useful information for the policy makers of the malaria control programme. Graphical work flow of the study. Image 1 • Plasmodium vivax clinical isolates analyzed for pvcrt-o , dhfr and dhps genes revealed wild type genotypes. • Mutations in pvmdr-1 gene were seen with two novel mutations in only two isolates. • Increase in IC 50 values of CQ drug indicates the emerging/possible shift towards CQ resistance in P. vivax. • The molecular surveillance needed regularly in P. vivax. [ABSTRACT FROM AUTHOR]

Wheat is one of the most widely consumed cereals, and it witnesses huge variation in its physicochemical properties due to pre- and post-harvest operations, hence, it undergoes many physicochemical treatments to achieve optimum baking characteristics. In the current study, ultraviolet (UV) radiation is proposed as a green technology to modify the wheat flour characteristics. Irradiation of Wheat flour with UV-C radiation (254 nm) of different radiation power and exposure time resulted a significant change in the physicochemical properties (water-binding capacity, amylose content, reducing sugar, sulfhydryl (SH), disulfide (SS) groups level). Further, decrease in gluten content, increase in total volatile basic nitrogen (TVBN) content, and photo-induced thiol-disulfide bridge exchange was observed upon irradiation. FTIR analysis of flour, gluten and gliadin protein confirmed the modification in protein conformations upon irradiation. The β-sheet had the highest contribution in protein conformation for wheat flour, while for gluten protein powder, random coils showed the maximum contribution. The first two principal components could explain 92.55% of total variance during principal component analysis, and the gluten content was correlated positively with SS content but negatively with SH and TVBN content. This study will help researchers and industrialist to understand the interactions of UV radiation with biological material. Image 1 • Modification in wheat flour under the influence of UV radiation. • Radiation power and exposure time significantly affected functional properties. • FTIR analysis confirmed the conformational changes in flour and gluten. • Gluten content positively correlated with SS group but negatively with SH group. • Loss of gluten forming ability was observed upon UV irradiation. [ABSTRACT FROM AUTHOR]

This paper reports the fabrication, characterization and simulation of hybrid perovskite solar cells (PSCs) in ambient condition. The proposed PSC structures use a CH 3 NH 3 PbI 3 hybrid perovskite based active layer sandwiched between a ZnO nanorods (NRs) electron transport layer (ETL) and a spiro-OMeTAD (undoped and doped) hole transport layer (HTL). The ZnO NRs are grown using low-cost solvothermal process at relatively low temperature. The performance of fabricated PSCs are analyzed for both the undoped and doped (with TBP and LiTFSI) spiro-OMeTAD based HTLs. All the solar parameters namely, short circuit current density (J SC), open circuit voltage (V OC), fill factor (FF), power conversion efficiency (PCE) and external quantum efficiency (EQE) are calculated from experimentally measured current density versus voltage (J-V) and wavelength transient characteristics in ambient condition. The maximum PCE of 10.18% is obtained for the doped HTL whereas 9.51% for undoped HTL. The improved performance due to HTL doping is attributed to the enhanced charge transportation of the HTL. The experimental results obtained from the fabricated PSCs are also compared with the SetFos™ TCAD simulation data using drift-diffusion model. The simulated results are observed to be well matched to the experimental data. • PSCs with 10.18% PCE fabricated under ambient-air atmosphere. • PSCs for undoped and doped HTL validated using SetFos™ TCAD simulation. • ZnO NRs grown by solvothermal process upon ZnO QDs sheet layer coated on FTO. [ABSTRACT FROM AUTHOR]

Proteins of the p53 family are best known for their role in the regulation of cell cycle. The p53 protein, as a model system, has been extensively explored in numerous cancer-related studies. The C-terminal domain (CTD) of p53 is an intrinsically disordered region that gains multiple different conformations at interaction with different binding partners. However, the impact of the surrounding environment on the structural preference of p53-CTD is not known. We investigated the impact of the surrounding environment on the conformational behavior and folding of p53-CTD. Although the entire CTD is predicted as a highly disordered region by several commonly used disorder predictors, based on the secondary structure prediction, we find that a part of the CTD sequence (residues 380–388) is "confused", being predicted to shuffle between the irregular, α-helical and β-strand structures. First time, we are observing the effect of folding-induced organic solvents, trifluoroethanol and methanol, on the conformation of CTD. Water-miscible organic solvents exert hydrophobic interactions, which are major driving force to trigger structural changes in CTD. By lowering the solution dielectric constant, organic solvents can also strengthen electrostatic interactions. We have also performed Replica Exchange Molecular Dynamic (REMD) simulations for enhanced conformation sampling of the peptide. These simulation studies have also provided detailed insight into the peculiarities of this peptide, explaining its folding behavior in the presence of methanol. We consider that these hydrophobic interactions may have important roles for function-related structural changes of this disordered region. • Organic solvents induce structural changes in p53 CTD. • MD simulation showed role of MoRFs region in structural conformations. • Liposome, ions have no effect of p53CTD structural conformation. • Temperature induce compaction in this IDP system. [ABSTRACT FROM AUTHOR]

People derive more satisfaction from experiential purchases (e.g., travel, entertainment, outdoor activities, meals out) than material purchases (e.g., clothing, jewelry, furniture, gadgets), both in prospect and retrospect. Because different types of well-being can have different determinants, we examined whether experiences have the same advantage over possessions in the here-and-now of consumption as they do in anticipation or remembrance. Participants in two large-scale experience-sampling studies were contacted in the midst of consuming an experiential or material purchase and asked about their momentary happiness. Experiential consumption was consistently associated with significantly greater happiness than either non-consumption or the consumption of material goods. In-the-moment happiness, furthermore, was greater for all subcategories of experiential purchases than for any category of material goods. Experiences thus appear to be a more promising route to enhancing well-being than possessions, irrespective of when happiness is measured. • Relative to possessions, experiences elicit greater in-the-moment happiness. • Our research fills a notable gap in the literature on the "experiential advantage." • Happiness was higher for all experiential categories than all material categories. [ABSTRACT FROM AUTHOR]

• Improved mapping of transient heme binding to intrinsically disordered proteins. • HCBCACON allows to employ prolines as additional probes in interaction mapping. • Residue-specific mapping of heme-protein interactions at physiological conditions. • Unraveling the heme interaction of a segment of human cystathionine-β-synthase. The N-terminal segment of human cystathionine-β-synthase (CBS(1–40)) constitutes an intrinsically disordered protein stretch that transiently interacts with heme. We illustrate that the HCBCACON experimental protocol provides an efficient alternative approach for probing transient interactions of intrinsically disordered proteins with heme in situations where the applicability of the conventional [1H, 15N]-HSQC experiment may be limited. This experiment starting with the excitation of protein side chain protons delivers information about the proline residues and thereby makes it possible to use these residues in interaction mapping experiments. Employing this approach in conjunction with site-specific mutation we show that transient heme binding is mediated by the Cys15-Pro16 motif of CBS(1–40). [ABSTRACT FROM AUTHOR]