Biology subjects

Sawant, S.

Publications and source records attributed to Sawant, S..

11 recordsLinked to original sources

bioRxiv2026

Sequential vaccination matures VRC01-class HIV-1 neutralizing antibodies in humans

Inducing a broadly neutralizing antibody (bnAb) response is a key goal of HIV-1 vaccine development. Despite significant progress, it is unknown whether vaccine-primed B cells can be reactivated and matured to secrete bona fide bnAbs. In the IAVI C107/C110 single-arm, open-label human trial, VRC01-class memory B cells previously primed by the GT1.1 germline-targeting envelope glycoprotein (Env) trimer were reactivated by a BG505 SOSIP.664 trimer boost. Somatic hypermutation in the activated B cells drove higher antibody affinity for the CD4-binding site on fully glycosylated, heterologous Env trimers. Three VRC01-class monoclonal antibodies derived from independent B cell lineages neutralized 18-31% of 119 viruses in a globally diverse panel. This work advances the HIV-1 germline-targeting vaccination concept from proof-of-priming towards proof-of-breadth and defines a benchmark for bnAb induction.

immunology↗

bioRxiv2026

Cerclage Wire as an Affordable Alternative for Internal Fixation in Murine Critical Sized Defect Models

Critical sized defects (CSDs) are a serious challenge in orthopedics that require the development of more robust and effective treatments to improve quality of life for patients. Current CSD research is limited by the applicable and affordable animal models available. Mice would be the preferred species as they are cheaply housed and have many transgenic variations readily available; however, their small size makes CSD surgeries difficult and expensive. We propose the use of cerclage wires to achieve internal plate fixation. PEEK plates were secured to the right femur of 26 C57BL/6 mice using four cerclage wires to achieve modified double-loop fixation implemented through bicortical holes and defects were created. 10 received 3mm defects and 6 received 4mm defects that were left empty and were taken out to 20 weeks (Group E3, E4). Another 10 received 3mm defects that were filled with a morselized bone graft and were taken out to 8 weeks (Group G3). Blinded longitudinal x-ray grading by orthopedic surgeons was conducted on the empty defects for plate stability and wire fixation. All samples received microCT analysis at their endpoints. There were no significant differences in plate or wire stability between the empty groups and wire scores worsened negligibly over time. MicroCT analysis further supported wire integration as bone growth directly upon the wires was observed in all samples. The efficacy of this model in achieving non-union when left untreated was also confirmed via microCT. Further, only three mice in group G3 achieved union and two of these unions were not optimal. Our study is the first to successfully show that cerclage wire can be used in a murine CSD model to achieve affordability and clinical relevancy.

bioengineering↗

bioRxiv2026

Liquid crystalline mesophase spacing as a quantitative predictor of release kinetics for co-loaded hydrophilic and hydrophobic payloads

Liquid crystalline mesophases exhibit structurally programmable internal architectures that enable co-loading of chemically orthogonal molecules within a single composite material. Realizing the potential of these materials for drug delivery requires a quantitative understanding of how tuning the composition affects internal mesophase architecture and consequently performance metrics such as payload release. Here, Flash NanoPrecipitation with hydrophobic ion pairing is used to prepare nanocarriers containing liquid crystalline mesophases co-encapsulating two compounds from widely different chemical classes: hydrophilic polymyxin B (logP -6) with one of four hydrophobic co-core materials (logP 7-11), achieving >75% encapsulation efficiency and up to 32% and 50% mass loadings for polymyxin and co-core. Synchrotron SAXS is used to quantify characteristic mesophase repeat spacing, which is found to be tunable as a function of composition. A strong correlation between d-spacing and polymyxin release rate is presented. Co-core chemistry and weight fraction jointly govern mesophase architecture, and repeat distance emerges as a structural metric linking these to the hydrophilic payload release kinetics. Mucus diffusivity and antibacterial efficacy are assessed as independent performance metrics, and results corroborate the release behavior. These findings establish a quantitative framework connecting material composition, mesophase architecture, and functional performance that can be applied toward rational co-formulation design. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=86 SRC="FIGDIR/small/734853v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@a0c38eorg.highwire.dtl.DTLVardef@86d33eorg.highwire.dtl.DTLVardef@196c83dorg.highwire.dtl.DTLVardef@3423c3_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOToC Graphic TextC_FLOATNO Flash NanoPrecipitation yields liquid crystalline nanocarriers co-encapsulating with high efficiency payloads with widely distinct physicochemical properties. Synchrotron SAXS establishes characteristic repeat spacing as a quantitative structural metric directly governing hydrophilic release kinetics, providing a rational design framework linking mesophase architecture to functional performance across a range of payload structures. C_FIG

bioengineering↗

bioRxiv2026

Machine Learning Ensemble Reveals Distinct Molecular Pathways of Retinal Damage in Spaceflown Mice

BackgroundSpaceflight-associated neuro-ocular syndrome (SANS) poses significant risks to astronaut visual health during long-duration missions, yet its underlying molecular mechanisms remain incompletely understood. Oxidative stress and apoptosis are candidate molecular drivers, but their transcriptomic signatures in spaceflight-exposed retinal tissue have not been systematically characterized. MethodsWe applied a machine learning ensemble of linear regression models to predict two ocular phenotypes: 4-hydroxynonenal (4-HNE) immunostaining as a marker of lipid peroxidation-mediated oxidative damage; and TUNEL positivity as a marker of apoptotic cell death. In this observational study, we use bulk retinal gene expression data obtained from a controlled experiment with ground control and spaceflown mice to predict these phenotypes. Gene Ontology pathway enrichment was performed on the most predictive gene sets for each phenotype. ResultsThe 4-HNE phenotype was predicted by genes that converge on membrane-associated pathways, photoreceptor protein modification, synaptic dysfunction, and extracellular matrix dysregulation, including B2m, Tf, Cnga1, mt-Nd1, Snap25, and Efemp1. The genes predicting the TUNEL phenotype revealed a distinct signature emphasizing stress-induced apoptosis, rod photoreceptor degeneration, and endoplasmic reticulum dysfunction, with Ddit4, Nrl, Rom1, Reep6, and Gabarapl1 emerging as central regulators. ConclusionsOxidative lipid peroxidation and apoptotic cell death represent complementary and molecularly distinct pathological mechanisms in spaceflight-exposed murine retinal tissue. The gene signatures provide a putative molecular framework for developing noninvasive biomarkers and therapeutic targets to monitor and protect astronaut visual health during long-duration and deep-space missions.

bioinformatics↗

bioRxiv2025

Linguistic Rules of Syntax and Sharing in the Complex Songs of a Tropical Passerine

1. Birdsong offers a powerful model to study the evolution of complex communication systems. While most song syntax and sharing research focuses on temperate species with fixed repertoires, we know far less about tropical songbirds with large, open-ended vocal systems. 2. We examined song structure and cultural transmission in the White-bellied Sholakili Sholicola albiventris, a tropical passerine endemic to the Shola Sky Islands of southern India. We studied song complexity and spectro-temporal variation using over 6,000 songs from 17 color-banded males across five years. We analyzed the song syntax using sequence-based metrics, including Levenshtein Distances and N-gram models. 3. Our results reveal high syntactic variability across short and long timescales, with stable note-type cores and structured expansions of combinatorial sequences. Higher-order N-gram turnover was rapid and strongly individual-specific, while broadly sharing the population-level note pool. Song sharing was significantly higher among neighbors than non-neighbors. 4. Using Generalized Additive Models, we explain how social and ecological factors, including neighbor count, territory area, repertoire size, N-gram usage, and the spectro-temporal structure of N-grams, determine consistency across years and sharing across individuals. This study highlights parallels between human linguistics and syntactic organization in the complex songs of a tropical passerine.

animal behavior and cognition↗

bioRxiv2023

The Arabidopsis Information Resource in 2024

Since 1999, The Arabidopsis Information Resource (www.arabidopsis.org) has been curating data about the Arabidopsis thaliana genome. Its primary focus is integrating experimental gene function information from the peer-reviewed literature and codifying it as controlled vocabulary annotations. Our goal is to produce a gold standard functional annotation set that reflects the current state of knowledge about the Arabidopsis genome. At the same time, the resource serves as a nexus for community-based collaborations aimed at improving data quality, access and reuse. For the past decade, our work has been made possible by subscriptions from our global user base. This update covers our ongoing biocuration work, some of our modernization efforts that contribute to the first major infrastructure overhaul since 2011, the introduction of JBrowse2, and the resources role in community activities such as organizing the structural reannotation of the genome. For gene function assessment, we used Gene Ontology annotations as a metric to evaluate: (1) what is currently known about Arabidopsis gene function, and (2) the set of unknown genes. Currently, 74% of the proteome has been annotated to at least one Gene Ontology term. Of those loci, half have experimental support for at least one of the following aspects: molecular function, biological process, or cellular component. Our work sheds light on the genes for which we have not yet identified any published experimental data and have no functional annotation. Drawing attention to these unknown genes highlights knowledge gaps and potential sources of novel discoveries. Article SummaryThe Arabidopsis Information Resource (TAIR, www.arabidopsis.org) is a comprehensive website about Arabidopsis thaliana, a small plant thats very easy to grow and analyze in the laboratory and is used to understand how many other plants function. We share our progress in data collection and organization, website and tool improvement, and our involvement in community projects.

plant biology↗

bioRxiv2023

Comparative Genomic and Transcriptomic Analysis of Avirulent and Virulent Strains of Fusarium oxysporum f. sp. carthami: Insights into Pathogenesis and Virulence Determinants in Safflower Infections

Vascular wilt disease incited by Fusarium oxysporum f. sp. carthami (Foc) in Safflower poses a significant threat to its production in India. A comprehensive understanding of the molecular underpinning of compatible and incompatible interaction is of extreme economic importance. In the present study, the genome of a virulent (IARI-5175) and a avirulent (F-00845) Foc strain were sequenced and assembled using data generated from Illumina in combination with Nanopore technologies and HiC. Foc genomes were assembled into 88 and 23 scaffolds with an estimated total size of 46 Mb and 42 Mb respectively for IARI-5175 and F-00845 strains. Reference based mapping of Foc genome with F. oxysporum f. sp. lycopersici (Fol) resulted in chromosomal level ordering of genome and simultaneous identification of accessory genome. Additionally, two lineage specific chromosomes were also identified for virulent Foc strain IARI-5175. Genomic comparisons were made on the basis of effectors, CAZymes, secondary metabolites and mycotoxins to understand the global view pathogenicity in Foc. Moreover, the transcriptome of Foc during compatible and incompatible interaction was sequenced and analyzed leading to the identification of differentially regulated genes. Taken together our study laid a solid foundation to explore novel effector genes that play a crucial role in the establishment of disease and can further be used as targets to devise new strategies to curb wilt disease in safflower.

genomics↗

bioRxiv2021

Song Richness Index: A measure to understand the diversity and repetition of notes in a birdsong

Birdsong plays an important role in mate attraction and territorial defense. Many birds, especially Passerines, produce varying sequences of multiple notes resulting in complex songs. Studying the diversity of notes within these songs can give insights into an individuals reproductive fitness. We first looked at the previously described and commonly used diversity measures to understand the possible case-specific limitations. We then developed a new diversity measure-Song Richness Index (SRI). We compared SRI with three measures of diversity using all possible combinations of notes to understand the case-specific advantages and limitations of all approaches. Simulating all possible combinations gave us insights into how each diversity measure works in a real scenario. SRI showed an advantage over conventional measures of diversity like Note Diversity Index (NDI), Shannons Equitability (SH), and Simpsons Diversity (SI), especially in the cases where songs are made up of only one type of repetitive note.

animal behavior and cognition↗

bioRxiv2021

Monocyte-derived transcriptome signature indicates antibody-dependent cellular 1 phagocytosis as the primary mechanism of vaccine-induced protection against HIV-1

A gene signature previously correlated with mosaic adenovirus 26 vaccine protection in simian immunodeficiency virus (SIV) and SHIV challenge models in non-human primates (NHP). In this report we investigated presence of this signature as a correlate of reduced risk in human clinical trials and potential mechanism for protection. The absence of this gene signature in the DNA/rAd5 human vaccine trial which did not show efficacy, strengthens our hypothesis that this signature is only enriched in studies that demonstrated protection. This gene signature was enriched in the partially effective RV144 human trial that administered the ALVAC/protein vaccine, and we find that the signature associates with both decreased risk of HIV-1 acquisition and increased vaccine efficacy. Total RNA-seq in a clinical trial that used the same vaccine regimen as the RV144 HIV vaccine implicated antibody-dependent cellular phagocytosis (ADCP) as a potential mechanism of vaccine protection. CITE-seq profiling of 53 surface markers and transcriptomes of 53,777 single cells from the same trial, showed that genes in this signature were primarily expressed in cells belonging to the myeloid lineage including monocytes, which are major effector cells for ADCP. The consistent association of this transcriptome signature with vaccine efficacy represents a tool both to identify potential mechanisms, as with ADCP here, and to screen novel approaches to accelerate development of new vaccine candidates.

systems biology↗

bioRxiv2021

Spectrogram cross-correlation can be used to measure the complexity of bird vocalizations

O_LIBirdsong is an important signal in mate attraction and territorial defense. Quantifying the complexity of these songs can shed light on individual fitness, sexual selection, and behavior. Several techniques have been used to quantify song complexity and be broadly categorized into diversity indices, measures of stationary probabilities, and measures of sequential variations. However, these methods are unable to account for important acoustic features like the frequency bandwidth and the variety in the shape of syllables which are an integral part of these vocal signals. This study proposes a new complexity measure that considers intra-song note variability and calculates a weighted index for birdsongs using spectral cross-correlation. C_LIO_LIWe compared the previously described methods to understand the advantages and limitations based on the factors that would be affecting the complexity of songs. We developed a new method- Note Variability Index (NVI), which incorporates the spectral features of notes while quantifying complexity. This measure alleviates the need for manual annotations of notes that can be error-prone. We used Spectrogram Cross-Correlation (SPCC) to compare notes within a song and used the output values to quantify song complexity. C_LIO_LITo check for the efficacy of the new method, we generated synthetic songs to caricature extremes in song complexity and compared selected conventional complexity measures along with the NVI. We provide case-specific limitations of these methods. Additionally, to examine the efficacy of this new method in real-world scenarios, we used natural birdsongs from multiple species across the globe with varying song structures to compare conventional methods with NVI. C_LIO_LITo our knowledge, NVI is the only song complexity method that captures the variation of spectral features of notes in songs where the conventional methods fail to distinguish between similar song structures with different note types. As NVI does not need a manual classification of notes, it can be easily implemented for any type of birdsong with existing sound analysis softwares; it is very quick, avoids the possible biases in note classification, and can possibly be automated for large datasets in the future. C_LI

ecology↗

bioRxiv2019

Antinociceptive and Antioxidant Activities of Methanolic Extract of Leaves of Azadirachta Indica (Neem).

Graphical abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=126 SRC=\"FIGDIR/small/694505v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (33K):\norg.highwire.dtl.DTLVardef@a4a41dorg.highwire.dtl.DTLVardef@1127160org.highwire.dtl.DTLVardef@1d175f9org.highwire.dtl.DTLVardef@98596c_HPS_FORMAT_FIGEXP M_FIG C_FIG BackgroundAzadirachta indica (Neem) is a communal plant of Meliaceae family called Neem Or Kadunimb in Maharashtra, India Neem stated anti-inflammatory through regulation of proinflammatory enzyme activities with COX and LOX enzyme. Previous studies show that Azadirachta Indica (neem) and its chief constituents play essential role in anticancer management via the modulation of different molecular pathways including NF-{kappa}B, p53, PI3K/Akt, Bcl-2, pTEN and VEGF. Many parts of the plant are traditionally used in the treatment of various pharmacological action, the analgesic activity of Neem Seed Oil has already reported but Neem Leaves.\n\nMethodsThe antinociceptive activity of Azadirachta Indica Leaves (AZIL) was examined using heat-induced-mechanical (hot-plate and tail-immersion test) and chemical-induced (acetic acid, formalin, glutamic acid, cinnamaldehyde) nociception models in mice at 50,100, and 200 mg/kg doses. ATP-sensitive K+ channel pathway, cyclic guanosine monophosphate (cGMP) pathway and involvement of opioid system was also tested using glibenclamide, methylene blue and naloxone/morphine respectively. The methanolic extract of leaves of A.Indica was assessed by using different in vitro antioxidant models of screening like scavenging of 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical, nitric oxide radical, superoxide anion radical, and hydroxyl radical.\n\nResultsAZIL showed antinociceptive activity and antioxidant activity. In both hot plate and tail immersion tests AZIL significantly increases the latency to the thermal stimuli. In acetic acid-induced writhing test the extract repressed the number of abdominal writhing. Similarly, AZIL produced substantial dose-dependent inhibition of paw licking in both neurogenic and inflammatory pain induced by intraplanar injection of formalin. As well, AZIL also expressively withdrawn cinnamaldehyde-induced pain and the glutamate-induced pain in mice. It was also proved that pretreatment with naloxone significantly reversed the antinociception produced by AZIL in mechanical tests signifying the involvement of opioid system in its effect. Furthermore, administration of methylene blue, enhanced AZIL induced antinociception while glibenclamide, an ATP-sensitive K+ channel antagonist, could not converse antinociceptive activity induced by AZIL.\n\nConclusionBased on the results of the present study it can be said that AZIL keeps significant antinociceptive activity which acts in both central and peripheral mechanisms.\n\nEthnopharmacological relevanceAzadiracta Indica having family Melliases is one of the common medicinal plant in United states and south Asia including India, Pakistan, Bangladesh. Various parts of the plants used in treatment of many inflammatory conditions, skin diseases, tooth protection, antidiabetic in the form of oil and herbal porridge.

pharmacology and toxicology↗