Tumor necrosis factor receptor 1 (TNFR1) signaling regulates cell fate in inflammation, immune responses, and tumorigenesis. While TNF-α-mediated TNFR1 pathways are well known, the role of receptor clustering remains unclear. Utilizing homo-FRET using fluorescence anisotropy, we show that intra-cluster receptor density (IRD) governs TNFR1 signaling outcomes. Soluble TNF-α (sTNF-α) increases IRD at cluster cores but decreases it at rims via receptor reorganization. Reducing IRD through membrane tension, zafirlukast, actin depolymerization, or cholesterol depletion suppresses sTNF-α signaling, whereas increasing IRD by lowering membrane tension or exposing cells in a 3D gel-like microenvironment triggers ligand-independent activation. These findings reveal IRD as a key regulator of receptor signaling, with potential relevance across related receptor families and innovative strategies in modulating TNFR1 signaling.

Abstract Hydroxychloroquine (HCQ), a clinically relevant quinoline derivative, impairs both collective and individual cell migration by disrupting actin and vimentin cytoskeletal dynamics during wound healing. In scratch assays with HeLa cells, HCQ treatment significantly reduces wound closure rates and inhibits bursts of coordinated migration, as well as single-cell motility. Quantitative imaging reveals that HCQ diminishes actin filament density at the wound edge and induces reorganization of the vimentin network, resulting in smaller nuclei and compromised structural connectivity. Particle tracking micro-rheology demonstrates that HCQ softens the cytoplasm and decreases cellular mechanical heterogeneity. In vitro spectroscopic studies show that HCQ binds cooperatively to actin with micromolar affinity, perturbing its secondary structure, reducing filament polymerisation rates, and impairs interactions between actin and actin binding proteins (ABPs). HCQ also significantly suppresses lamellipodial protrusive activity, indicating a link between cytoskeletal remodelling and impaired cell migration. Collectively, these findings establish that HCQ disrupts essential mechanisms for directed migration by modulating the cytoskeleton and cell mechanics. This multifaceted impairment may underlie therapeutic potential of HCQ as an anticancer agent by restricting cellular invasive capacity and remodelling required for tumour progression.

The cytoplasm exhibits viscoelastic properties, displaying both solid and liquid-like behaviour, and can actively regulate its mechanical attributes. The cytoskeleton is a major regulator among the numerous factors influencing cytoplasmic mechanics. We explore the interdependence of various cytoskeletal filaments and the impact of their density on cytoplasmic viscoelasticity. The heterogeneous distribution of these filaments gives rise to polarised mechanical properties of the cytoplasm along the dorsoventral axis. Actin filament disassembly softens the ventral cytoplasm while stiffening the mid cytoplasm, due to increased vimentin filament assembly. Disruption of microtubules or depletion of vimentin softens both the ventral and mid cytoplasm. Cytochalasin D (Cyto D) treatment results in a localised increase of vimentin assembly in the mid cytoplasm, which is dependent on the cytolinker plectin. Nocodazole treatment has a negligible effect on F-actin distribution but significantly alters the spatial arrangement of vimentin. We demonstrate that Cyto D treatment upregulates vimentin expression via reactive oxygen species-mediated activation of NF-κΒ. This article investigates how different cytoskeletal filaments influence the rheological characteristics of various cytoplasmic regions.

The excessive cosolute densities in the intracellular fluid create a physicochemical condition called macromolecular crowding (MMC). Intracellular MMC entropically maintains the biochemical thermodynamic equilibria by favoring associative reactions while hindering transport processes. Rapid cell volume shrinkage during extracellular hypertonicity elevates the MMC and disrupts the equilibria, potentially ushering cell death. Consequently, cells actively counter the hypertonic stress through regulatory volume increase (RVI) and restore the MMC homeostasis. Here, we establish fluorescence anisotropy of EGFP as a reliable tool for studying cellular MMC and explore the spatiotemporal dynamics of MMC during cell volume instabilities under multiple conditions. Our studies reveal that the actin cytoskeleton enforces spatially varying MMC levels inside adhered cells. Within cell populations, MMC is uncorrelated with nuclear DNA content but anti-correlated with the cell spread area. Although different cell lines have statistically similar MMC distributions, their responses to extracellular hypertonicity vary. The intensity of the extracellular hypertonicity determines a cell's ability for RVI, which correlates with nuclear factor kappa beta (NFkB) activation. Pharmacological inhibition and knockdown experiments reveal that tumor necrosis factor receptor 1 (TNFR1) initiates the hypertonicity-induced NFkB signaling and RVI. At severe hypertonicities, the elevated MMC amplifies cytoplasmic microviscosity and hinders receptor interacting protein kinase 1 (RIPK1) recruitment at the TNFR1 complex, incapacitating the TNFR1-NFkB signaling and consequently, RVI. Together, our studies unveil the involvement of TNFR1-NFkB signaling in modulating RVI and demonstrate the pivotal role of MMC in determining cellular osmoadaptability.

The present study attempts to obtain an a priori estimate of the absorbed dose received by an individual engaged in the reconnaissance survey in Uranium exploration using a predictive mathematical regression analysis. Other radiation safety parameters such as excess lifetime cancer risk are also calculated. Study reflects that the proper handling of naturally occurring radioactive materials accounts for an absorbed dose significantly less than the prescribed limit.

This study reports the preliminary phytochemical analysis followed by the quantitative determination of ellagic acid in different parts of Cliestanthus collinus using reverse phase liquid chromatography (HPLC) in association with a diode array detector (DAD). The developed RP-HPLC method achieved separation of ellagic acid within 10 min of run time through gradient elution using methanol and water with 1% acetic acid as mobile phase on a C-18 reverse phase column at room temperature and 365 nm of detection wavelength. The method showed excellent linearity across a range of 0.01 µg mL-1 to 10 µg mL-1 with LOD and LOQ values of 0.027 µg mL-1 and 0.091 µg mL-1, respectively, demonstrating lower precision characterized by RSD% of 0.73% and higher accuracy as recovery of 99.5%. Additionally, the insecticidal activity of ellagic acid obtained by isolation from the leaves, bark and fruits of C. collinus was examined against two stored grain pest, Tribolium castaneum and Corcyra cephalonica larvae. The results indicated that ellagic acid showed significant pesticidal activity against T. castaneun with a mortality rate of 98% than against C. cephalonica larvae with a mortality rate of 76% suggesting its use as a natural biopesticide. To our best of knowledge, this is the first report pertaining to phytochemical screening of the whole part of C. collinus and quantitation of ellagic acid in different parts of C. collinus suggesting this plant as a new natural source of ellagic acid along with pesticidal activity of ellagic acid against stored grain pest.

The guest of honour, Shri N. Kutumba Rao, highlighted the importance of new mineral discoveries from Vindhyan Supergroup (VSG) and opined that new mineral exploration blocks will come up soon.The guest of honour Dr D.K. Sinha, mentioned the importance of the western Vindhyan Basin (VB) exposed in Rajasthan and its correlation with the eastern VB of the Son Valley area.Shri N.V. Nitnaware, Chairman VISACOP expressed his hope that the seminar will provide a guiding direction

Bacterial membrane vesicles (MVs) facilitate the long-distance delivery of virulence factors crucial for pathogenicity. The entry and trafficking mechanisms of virulence factors inside host cells are recently emerging; however, whether bacterial MVs can fuse and modulate the physicochemical properties of the host lipid membrane and membrane lipid parameter for fusion remains unknown. In this study, we reconstituted the interaction of bacterial MVs with host cell lipid membranes and quantitatively showed that bacterial MV interaction increases the fluidity, dipole potential, and compressibility of a biologically relevant multicomponent host membrane upon fusion. The presence of cylindrical lipids, such as phosphatidylcholine, and a moderate acyl chain length of C16 help the MV interaction. While significant binding of bacterial MVs to the raft-like lipid membranes with phase-separated regions of the membrane was observed, however, MVs prefer binding to the liquid-disordered regions of the membrane. Furthermore, the elevated levels of cholesterol tend to hinder the interaction of bacterial MVs, as evident from the favorable excess Gibbs free energy of mixing bacterial MVs with host lipid membranes. The findings provide new insights that might have implications for the regulation of host machinery by bacterial pathogens through manipulation of the host membrane properties.

The outcrops of greenstone belt and granite complex along Ramagiri-Penakacherla tract are analyzed for tectonics and associated deformation history related to crustal evolution. Field data connote more than five deformation events. Initial ductile deformation regime (D1-D4) passes through brittle-ductile (D5) to shallow brittle regime (D6). Multiple deformation events (D1-D5) resulted in shear zones with variable trends and sense. Three major generations of folding (F2–F4) imprinted over and obscure F1 folding in ductile regime. Younger granite intruded after F3 hence exhibit only F4 folds. Brittle regime (D6) is manifested by faults with dominant E-W trend affected all earlier deformation features. They show mainly normal and few strike slip motion with episodic reactivation with dominantly N-S stretching (i.e., σ3). Contact relationships between granite and country rocks give insight on depth and associated pressure-temperature condition. From deeper catazone through intermediate mesozone to shallow epizone granite the progressive increase in temperature contrast influence contact relationships with country rocks from concordant through gradational to sharp discordant. Structural attributes of the northern and southern end of the study area exhibit remarkable changes in granite character, which give information on changes in crustal depth. Supportive petro-mineralogical and geochemical evidences also imply for exhumed northerly tilted crust. Bhima and Kaladgi basins are developed due to this crustal block tilting and basin fill sediments were supplied from erosion of uplifted southern parts. During erosion, the exhumation leads to retrograde metamorphism which is better manifested in metabasic rocks. From the surface distance between epizone/mesozone and mesozone/catazone boundaries and average crustal depth difference between these two boundaries, a northerly tilt angle of 1.90 is estimated. The obduction at the southern end of Dharwar Craton and late stage N-S stretching is responsible for such tilting.

T cells are crucial for efficient antigen-specific immune responses and thus their migration within the body, to inflamed tissues from circulating blood or to secondary lymphoid organs, plays a very critical role. T cell extravasation in inflamed tissues depends on chemotactic cues and interaction between endothelial adhesion molecules and cellular integrins. A migrating T cell is expected to sense diverse external and membrane-intrinsic mechano-physical cues, but molecular mechanisms of such mechanosensing in cell migration are not established. We explored if the professional mechanosensor Piezo1 plays any role during integrin-dependent chemotaxis of human T cells. We found that deficiency of Piezo1 in human T cells interfered with integrin-dependent cellular motility on ICAM-1-coated surface. Piezo1 recruitment at the leading edge of moving T cells is dependent on and follows focal adhesion formation at the leading edge and local increase in membrane tension upon chemokine receptor activation. Piezo1 recruitment and activation, followed by calcium influx and calpain activation, in turn, are crucial for the integrin LFA1 (CD11a/CD18) recruitment at the leading edge of the chemotactic human T cells. Thus, we find that Piezo1 activation in response to local mechanical cues constitutes a membrane-intrinsic component of the 'outside-in' signaling in human T cells, migrating in response to chemokines, that mediates integrin recruitment to the leading edge.

The increasing use of pesticides in the agriculture fields strengthen the crop production to meet the needs of increasing population. The residues in water and food materials cause several health hazards. Herein, nitrogen-doped carbon quantum dot (N-CQDs) is designed for determination of methiocarb pesticide in vegetables by fluorescent paper sensor and compared the results with fluorimetry. The fluorescent paper-based detection is performed by recording the change in fluorescence of N-CQDs with introduction of methiocarb using smartphone and ImageJ software. Good linear range was acquired for analysis of methiocarb from 10 to 1000 μgL-1 with a low detection limit (LOD) of 3.5 μgL-1 in fluorimetry; and 700-10,000 μgL-1 with a LOD of 500 μgL-1 in fluorescent paper sensor. A better recovery from 92.0 to 95.4% illustrating the selectivity of both methods for analysis of methiocarb in vegetables. Thus, the advantage of using N-CQDs as a fluorescent sensor for analysis of methiocarb in vegetables is instrument free, portable and user-friendly.

Structural fabrics of schist belt, gneiss, migmatites and younger granitoids are different. Various morphology of migmatites is recognized for the first time in the southern part of EDC along with gneiss. The younger granite plutons are examined from northern through central to southern part of EDC. The paleosome-dominated portions of migmatite were possibly formed from low degree partial melting of older rocks and identified as metatexites. Whereas, the neosome dominated parts were developed by complete melting and marked as diatexites. There is a link between diatexite and granite in the southern part, which is chracterized as catazone segment. The four sub-types of metatexites are observed (viz, patch, dilatant, net and stromatic). The diatexites are dominated by two major structures (viz, schollen or raft and schlieren). Gneisses show lit-per-lit as well as fold and leucocratic material flow features. The litho-structural variation from north to south connotes systematic changes from epizone through mesozone to catazone. The qualitative study of mineral content and textural aspects from rocks at different localities suggest preserved portions of different parts of a pressure–temperature path. However, exact quantification should be possible after thermo-barometry and pseudo section study. The present contribution focuses on documentation of classic representative outcrops and petrographic features of gneissic and migmatitic rocks of EDC. It is observed that the six (6) major ductile deformation stages of Kenoran orogeny implies ductile signature before granite plutonism. Subsequently post granite emplacement deformation phenomenon indicates a transition from ductile to brittle regime and entrance into Hudsonian orogeny.

The Cuddapah Basin (CB) and its basement can be considered as an appropriate uranium metallogenic province. The basement complex of CB in the Eastern Dharwar Craton (EDC), India, has been the target for structurally controlled uranium exploration since the early 1980s. Most of the brittle-ductile deformation induced reactivated narrow linear fracture zones often exhibit significant surface and sub-surface uranium occurrence. There are about 10 fracture zones associated with uranium mineralization. Amongst them, the Kamaguttapalle-Kammapalle fracture zone (KKF) in the south of the CB is quite interesting from an exploration viewpoint with a suitable geologic setting in space and time frame. Geomorphic, structural and petro-mineralogic exploration guides imply the possibility of economic uranium concentration along the NNE-SSW trend where tectonic reactivation took place over pre-existing ductile shear zone. Progressive exhumation and transition from ductile to brittle deformation regime led to the development of dominant strike slip tectonics with an associated riedel fracture system, which are subsidiary coeval shear fractures used in depicting sense of movement. Intense illitization and hematitization are often observed. Quartz reefs and veins along the NNE-SSW trend cut the preexisting mylonites at places. About 9 stages of fracturing is observed out of which 3 stages are related to uranium mineralization. All the 9 deformations are related to strike slip tectonics which in turn is part of Grenville orogeny. Paragenetic sequence and mode of occurrences of uranium phases deciphers about the importance of low to moderate level epi-meso type hydrothermal (100 degrees-250 degrees C) fluids as carrier of U. Reactivated fractures and quartz veination also act as controlling factors of mineralization. Strain analysis points to positive and negative flower structures at different segments of the fracture zone. Based on the litho-structural attributes it is established that maximum compression (sigma 1) acted along the NNW-SSE direction. Fractured quartz veins provide well defined permeability and trapping facility by restricting transverse fluid movement as a mechanical barrier. The presented model gives an idea on role of strike-slip tectonics in uranium mineralization for narrowing down the target zone for sub-surface exploration.

On the western part of the eastern Indian shield, Archaean basement (Bonai granite) is overlain by radioactive conglomerate. The conglomerate contains well-rounded, fractured Mg-poor (<0.18 wt.% MgO), Al-rich (up to 21.14 wt.% Al2O3) Zn-rich chromite (>35.0 wt.% Cr2O3) containing up to 15.5 wt.% ZnO. This is the first reported occurrence of detrital zinc-rich chromite having such unusually high ZnO from India, and to our knowledge, the third reported occurrence in radioactive quartz-pebble conglomerate after Witwatersrand, South Africa and Tarkwa, Ghana. Zinc-rich chromite grains are either clean or contain exsolution blebs/lamella of rutile. The conglomerates show evidence for post-depositional hydrothermal fluid influx and fluid-induced mineral alteration. The strong negative correlation between Zn and Fe2+, Al and Cr, and Al and Fe3+, and strong positive correlation between Zn and Al suggest secondary incorporation of Zn and Al by substitution of Fe2+ and Cr (and Fe3+), respectively, leading to partial transformation of (Fe)(Cr,Al,Fe3+)(2)O-4 towards ZnAl2O4 composition. The chromite grains were possibly derived from komatiite. The timing of Zn enrichment, either at the provenance prior to sedimentation, or at the depositional site post-dating sedimentation, remains unresolved.

In the case of solubility limited absorption, creating supersaturation in the GI fluid is very critical as supersaturation may provide great improvement of oral absorption. The techniques to create the so-called supersaturation in the GI fluid include microemulsions, emulsions, liposomes, complexations, polymeric micelles, and conventional micelles. Ciprofloxacin was chosen because it is practically insoluble in water; hence its salt form is used commercially, which is soluble in water. The objective of the present investigation was to enhance the solubility of ciprofloxacin by formulating solid dispersions techniques in water soluble carriers have attracted considerable interests as a mean of improving the dissolution rate & hence possibly bioavailability range of hydrophobic drugs. The poor solubility of ciprofloxacin leads to poor dissolution & hence variation in bioavailability. The purpose of present investigation was formulation & evaluation of controlled release floating capsule of ciprofloxacin with improved solubility & dissolution rate. In the present study solid dispersions using various carriers like mannitol & lactose in different ratios were prepared by solvent evaporation method. The prepared solid dispersions were characterized for drug content, solubility & dissolution rate. The dissolution rate substantially improved for ciprofloxacin from its solid dispersions compared with the pure drug. Dissolution rate increased with increasing carrier content.

The Rohil uranium deposit, located about 70 km south of the Khetri copper deposit in the North Delhi Fold Belt, Rajasthan, India, is albitite-hosted. This deposit is associated with Na-metasomatism, mainly affecting the metasedimentary wall rocks. Quartzite, quartz biotite schist, quartz amphibole schist, and graphite schist un-derwent variable degrees of albitization, as documented by a wide range of altered wall rocks, including weakly altered metasediments to almost pure albitites. These host rocks consist of metamorphic mineral assemblages such as Ca plagioclase - quartz - biotite - Ca amphibole - graphite - garnet - sillimanite - corundum - ilmenite. The hydrothermal alteration assemblages contain variable amounts of albite, chlorite, biotite, sericite, ortho-clase, sphene, rutile, allanite, actinolite, and calcite. The textural relationships between primary host rock minerals and hydrothermal alteration products suggest four main stages of metasomatism: (1) an early pre-albitization stage, (2) a Na-metasomatic stage, that are followed by (3) a Na-Ca -Mg-and (4) K-metasomatic stage. Albites are of two types: albite-1 is subhedral to euhedral and equidimensional, formed by the alteration of metamorphic plagioclase during the Na-metasomatic stage. Albite-2 is feathery and formed in fractures/cavities by precipitation of alkali-rich fluid during Na-Mg-Ca metasomatic stages. Albitization is pervasive on a regional scale. The hydrothermal metasomatic fluids utilized structures such as shears and breccias in the metasediments as conduits and as the loci of uranium mineralization. Major uranium minerals are uraninite, U-silicate, and brannerite. Uranium-bearing minerals occur as disseminations, in veins and as minute inclusions in biotite and titanite within albitized metasediments. The petrographic studies suggest that the metasomatic alteration of host rocks is characterized by albitization, actinolitization, carbonatization, chloritization, sericitization, biotitization, sulfidation, and silicification. The close association of U, REE-bearing minerals, and albite-2 indicates that the main U-REE mineralization stage was coeval with the Na-Ca-Mg and K-metasomatic stages.

In this paper the first results of anisotropy of magnetic susceptibility (AMS) studies carried out on 10 schist samples taken from different depths of a borehole in the vicinity of Singhbhum Shear Zone (SSZ) are presented. A cube of 8 cm3 volume was extracted from each borehole sample and its AMS was measured; the shallowest sample is from 112 m depth, while the deepest is from 850 m depth. In the depth vs. mean magnetic susceptibility (Km) plot, a sharp decrease in the Km values is noted in samples from 547 m and 588 m depths. Microstructural investigation of the different samples reveals presence of thick quartz veins in samples from the above mentioned depths vis-à-vis other samples. Petrographic studies also reveal presence of the mineral "allanite" in sample from 547 m depth, which contained a thick quartz vein. It is thus suggested that studies involving AMS investigation of borehole samples from the top 1 km depth of the region hold promise in mineral exploration studies.

Non-ionic surfactants, poly oxyethylene sorbitan adipose acid esters (polysorbate), were used in this work to explore the consequence of temperature on CMC throughout a wide temperature range. The phase separation model is used to analyze the enthalpy and entropy of micelle conformation. The Du Nöuys ring was used to determine the results' face pressure. The CMC standards were derived after the strong break down in surfactant attention plots of face pressure vs. logarithms. The CMC at continuous temperature decreases as the chain length of the surfactants rises, which is completely connected to the reduction in hydrophilicity of the motes. Because of the lower possibility of hydrogen bond conformation on high temperatures, the CMC of each surfactant initially declines and then increases as the system temperature rises. As the temperature rises, the commencement of micellization tends to happen at a faster rate. The focus of this research is on the characterization of solubilization of drugs that aren't sufficiently responsive. Face pressure measurements for nonionic surfactant TritonX-100 were also taken in order to assess the solubilization features. In the presence of colourful organic detergent, the medium's opposition and the likely positions of SMX and TMP were also discussed. TritonX-100, a nonionic surfactant, was also tested. In the presence of colourful organic detergents, the medium's opposition and the likely position of SMX and TMP were also discussed.

Results of multi-method geochronological study (U-Pb, Pb-Pb and Sm-Nd), on uranium mineralized rocks along the albitite line in the North Delhi Fold Belt (NDFB, Rajasthan, India) are presented. The Pb-Pb ages obtained, on uranium mineralized core samples, from Rohil uranium deposit, Sikar district, Rajasthan (south western part of NDFB), are 836 ± 5 Ma (Pb Sequential Leaching-PbSL, weighted average of 11 isochron ages), 826 ± 9 Ma (Pb-Pb isochron age on uraninite), 842 ± 18 Ma (U-Pb concordia upper intercept age, on uraninite). Similar ages of uraninites were also obtained from areas close to Rohil uranium deposit i.e. Jahaz (823 ± 10 Ma, U-Pb and 826 ± 14 Ma, Pb-Pb) and Ghateshwar areas (834 ± 14 Ma, U-Pb concordia upper intercept age and 826 ± 25 Ma, Pb-Pb isochron age). The ages of uranium mineralisation (PbSL) further in northeastern part of NDFB i.e. in Gorir area, Jhunjhunu district, Rajasthan, are 827 ± 7 Ma, 818 ± 24 Ma (PbSL) and in Dhancholi area, Mahendragarh Dist., Haryana, are 824 ± 12 Ma (U-Pb) and 824 ± 6.5 Ma (Pb-Pb). The above age data in general indicates age of uranium mineralization as 830 Ma in the NDFB. These ages are consistent with age of uranium mineralization in albitites from Brazil. The Sm-Nd isochron age on uraninite (Rohil) is 824 ± 85 Ma with µNdi 830 Ma= −14 that indicates source of uranium from crustal rocks which is around 1400 Ma older than the age of present dated uraninites. Probably metasediments of the Paleoproterozoic Delhi/ Aravalli Supergroup (c. 2200 Ma) or basement granite gneisses are the main source of uranium in the studied samples.