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Biology subjects

Maharana, S.

Publications and source records attributed to Maharana, S..

7 recordsLinked to original sources

Radiological Patterns in Maxillofacial Ewing Sarcoma: A systematic review with pooled patient-level descriptive analysis

BackgroundEwing sarcoma (ES) is a rare malignant bone tumor with predilection for the mandible and maxilla in the head and neck region. However, existing literature comprises fragmented case reports and small case series that fail to establish consolidated, evidence-based understanding of characteristic radiological patterns in the maxillofacial region, hindering timely diagnosis and potentially leading to misdiagnosis or delayed intervention. MethodologyA systematic review and pooled patient-level descriptive analysis were conducted according to the PRISMA guidelines and pre-registered on PROSPERO. Comprehensive searches of PubMed, OVID, and Cochrane databases (inception to July 2025) identified studies reporting radiological findings of biopsy-confirmed maxillofacial Ewing sarcoma. Quality assessment using Joanna-Briggs Institute criteria ensured inclusion of only high-quality cases (quality score [≥]4/5). Synthesis Without Meta-analysis (SWiM) methodology with pooled prevalence estimation and binomial vote-counting analysis were employed for 68 published cases. ResultsFour radiological features demonstrated consistent predominance across pooled cases: soft tissue mass presence (100%, 95% CI: 94.7-100.0%), enhancing soft tissue (77.6%, 95% CI: 65.8-86.9%), cortical destruction (69.0%, 95% CI: 55.5-80.5%), and notably, absence of periosteal reaction (84.7%, 95% CI: 73.0-92.8%). Location-specific radiological phenotypes were evident: maxillary tumors demonstrated near-universal sinus involvement (100%) with high soft tissue enhancement (92.3%), whereas mandibular tumors showed predominant cortical destruction (80.0%) and teeth involvement (81.2%). ConclusionMRI and CT are essential for characterizing the distinctive radiological profile of maxillofacial Ewing sarcoma, enabling early identification and improving patient outcomes in this rare malignancy. HighlightsO_LIFirst pooled review to summarize imaging features of maxillofacial Ewing sarcoma C_LIO_LIAnalysis of 68 published cases reveals consistent imaging patterns. C_LIO_LIMost tumors show soft tissue mass and bone damage without surface reaction. C_LIO_LIJaw tumors differ from long bone tumors in their imaging appearance. C_LIO_LIUpper and lower jaw tumors show distinct location-specific features. C_LI

cancer biology↗

Stress Granules Buffers Inflammation by Restricting dsRNA-led Mitochondrial Fragmentation

Stress granules (SGs) are dynamic RNA-RBP condensates that form during stress and inflammation, yet how they modulate inflammatory signalling remains unclear. We uncover a rapid, protective SG-mediated mechanism that preserves mitochondrial integrity. During stress and translation inhibition, mitochondrial fragmentation releases double-stranded RNA (dsRNA), which activates PKR and its downstream effector DRP1, generating a self-amplifying loop of mitochondrial fragmentation and inflammation. We find that released dsRNA nucleates nanoSGs within minutes at ER-mitochondria contact sites--the very sites of mitochondrial division. These nanoSGs grow into macroSGs, effectively sequestering PKR-activating dsRNA from the cytosol. By depleting dsRNA, SGs suppress PKR-DRP1-driven positive-feedback inflammation and maintain mitochondrial integrity and function. Our findings reveal SGs as key guardians of mitochondrial homeostasis and position condensate biology at the centre of chronic mitochondrial-driven inflammation relevant to autoimmunity, ageing, and neurodegenerative disease.

cell biology↗

Aging associated RNA loss impairs the dynamics of RNA and protein condensates

Altered biomolecular condensate dynamics are increasingly implicated in age-associated neurodegenerative disorders, yet the molecular principles governing these changes remain incompletely understood. Here, we demonstrate that aged cells across diverse cellular and organismal models harbor pre-formed, viscous, and persistent stress granules (SGs), which we term alt-SGs. These persistent condensates confer protection to senescent cells under fluctuating stress conditions. Comparative analyses reveal that alt-SGs exhibit elevated RNA-binding protein (RBP)-to-RNA ratios, underscoring a shift in condensate stoichiometry. By quantifying SG composition and dynamics in live cells and in vitro, we establish that RNA concentration is a key determinant of condensate material properties, molecular composition, and dissolution capacity. Importantly, aging cells display diminished absolute RNA concentrations due to reduced RNA metabolic activity. Reactivation of RNA metabolism restores RNA/RBP ratios within SGs and alleviates aging-associated phenotypes. Together, our findings highlight RNA metabolism as a central regulator of condensate stoichiometry and function, linking metabolic decline to altered phase behavior and cellular aging. Key findingsO_LIAging and senescence have Alt-SGs with increased protein/RNA Ratio C_LIO_LIAlt-SGs are persistent after stress removal in aging C_LIO_LIAging is associated with reduced total cellular RNA C_LIO_LIReactivating RNA metabolism rescues SG phenotypes C_LIO_LIAlt-SGs are protective for senescent cell C_LI

cell biology↗

Algorithm for automatic detection of insulin granule exocytosis in human beta-cells

Image processing and analysis are two significant areas that are highly important for interpreting enormous amounts of data obtained from microscopy-based experiments. Several image analysis tools exist for the general detection of fundamental cellular processes, but tools to detect highly distinct cellular functions are few. One such process is exocytosis, which involves the release of vesicular content out of the cell. The size of the vesicles and the inherent differences in the imaging parameters demand specific analysis platforms for detecting exocytosis. In this direction, we have developed an image-processing algorithm based on Lagrangian particle tracking. The tool was developed to ensure that there is efficient detection of punctate structures initially developed by mathematical equations, fluorescent beads and cellular images with fluorescently labelled vesicles that can exocytose. The detection of these punctate structures using the tool was compared with other existing tools, such as find maxima in ImageJ and manual detection. The tool not only met the precision of existing solutions but also expedited the process, resulting in a more time-efficient solution. During exocytosis, there is a sudden increase in the intensity of the fluorescently labelled vesicles that look like punctate structures. The algorithm precisely locates the vesicles coordinates and quantifies the variations in their respective intensities. Subsequently, the algorithm processes and retrieves pertinent information from large datasets surpassing that of conventional methods under our evaluation, affirming its efficacy. Furthermore, the tool exhibits adaptability for the image analysis of diverse cellular processes, requiring only minimal modifications to ensure accurate detection of exocytosis.

cell biology↗

Interplay of the folded domain and disordered low-complexity domains along with RNA sequence mediate efficient binding of FUS with RNA

RNA binding ability of Fused in Sarcoma (FUS) protein is crucial to its cellular function. Our molecular simulation study on FUS-RNA complex provides atomic resolution insights into the observations from biochemical studies and also illuminate our understanding of molecular driving forces that mediate the structure, stability, and interaction of RRM and RGG domains of FUS with a stem-loop junction RNA. We observe a clear cooperativity and division of labour among the ordered (RRM) and disordered domains (RGG1 and RGG2 domain) of FUS that leads to an organized and tighter RNA binding. Irrespective of the length of RGG2, the RGG2-RNA interaction is confined to the stem-loop junction and the proximal stem regions. On the other hand, the RGG1-RNA interactions are primarily with the longer RNA stem. We find that the C-terminus of RRM, which make up the "boundary residues" that connect the folded RRM with the long disordered RGG2 stretch of the protein, plays a critical role in RNA binding with the RRM domain. Our study provides high-resolution molecular insights into the FUS-RNA interactions and forms the basis for understanding the molecular origins of full-length FUS interaction with RNA.

biophysics↗

SAMHD1 controls innate immunity by regulating condensation of immunogenic self RNA

Recognition of pathogen-derived foreign nucleic acids is central to innate immune defense. This requires discrimination between structurally highly similar self and nonself nucleic acids to avoid aberrant inflammatory responses as in the autoinflammatory disorder Aicardi-Goutieres syndrome (AGS). How vast amounts of self RNA are shielded from immune recognition to prevent autoinflammation is not fully understood. Here we show that SAM domain and HD domain-containing protein 1 (SAMHD1), one of the AGS-causing genes, functions as a single-stranded RNA (ssRNA) 3exonuclease, the lack of which causes cellular RNA accumulation. Increased ssRNA in cells leads to dissolution of RNA-protein condensates, which sequester immunogenic double-stranded RNA (dsRNA). Release of sequestered dsRNA from condensates triggers activation of antiviral type I interferon via retinoic acid-inducible gene I-like receptors. Our results establish SAMHD1 as a key regulator of cellular RNA homeostasis and demonstrate that buffering of immunogenic self RNA by condensates regulates innate immune responses.

immunology↗

Combined fluorescence, optical diffraction tomography and Brillouin microscopy

Quantitative measurements of physical parameters become increasingly important for understanding biological processes. Brillouin microscopy (BM) has recently emerged as one technique providing the 3D distribution of viscoelastic properties inside biological samples -- so far relying on the implicit assumption that refractive index (RI) and density can be neglected. Here, we present a novel method (FOB microscopy) combining BM with optical diffraction tomography and epi-fluorescence imaging for explicitly measuring the Brillouin shift, RI and absolute density with specificity to fuorescently labeled structures. We show that neglecting the RI and density might lead to erroneous conclusions. Investigating the nucleoplasm of wild-type HeLa cells, we find that it has lower density but higher longitudinal modulus than the cytoplasm. Thus, the longitudinal modulus is not merely sensitive to the water content of the sample -- a postulate vividly discussed in the field. We demonstrate the further utility of FOB on various biological systems including adipocytes and intracellular membraneless compartments. FOB microscopy can provide unexpected scientific discoveries and shed quantitative light on processes such as phase separation and transition inside living cells.

biophysics↗