Biology subjects

Mukherjee, A.

Publications and source records attributed to Mukherjee, A..

At least 19 recordsLinked to original sources

bioRxiv2026

Activation of basal forebrain cholinergic neurons promotes the attribution of incentive salience to reward cues in male rats

Background: Reward-associated environmental stimuli (cues) can gain incentive salience in some individuals, thereby becoming attractive, reinforcing, and instigators of motivational states. In rodents, the tendency to attribute incentive salience can be measured using a Pavlovian Conditioned Approach (PavCA) procedure, in which approach to a food cue (sign-tracking), relative to approach to the food delivery location (goal-tracking) is the operational definition of the incentive salience attributed to the cue. Growing evidence suggests that acetylcholine promotes this process, thus the current study tested the effect of activating cholinergic neurons in the basal forebrain on sign- and goal-tracking during PavCA. Methods: We injected a Cre-dependent virus with excitatory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) into the horizontal limb of the diagonal band of Broca of transgenic rats expressing cre-recombinase in acetylcholine containing neurons. We then injected clozapine-n-oxide (CNO) before each of eight sessions of PavCA. On the ninth session, no CNO was given to test if any effects were immediately reversible. Results: We found that activation of basal forebrain cholinergic neurons increased sign-tracking over time without an overall effect on goal-tracking, relative to a control group injected with a control virus. Changes in responding from the final CNO session to the saline test did not differ between virus groups. Conclusions: This effect demonstrates that acetylcholine promotes the attribution of incentive salience to a reward-related cue. Future studies should investigate the effect of inhibiting this area on sign-tracking as well as how activation of this area influences reactivity to cues associated with other rewards such as drugs of abuse.

neuroscience↗

bioRxiv2026

Can We Really See the World in Three Dimensions? An Exploratory Study with Finger Alignment Task and Ponzo Illusion

Stereopsis is the perception of depth when two 2-dimensional (2D) images of an object from slightly different angles align with corresponding retinal positions in both eyes. However, when we consider the blind spot (BS), a new set of challenges arises. In binocular vision, one eye's higher visual areas compensate for the other's non-receptive region. However, our brain only receives information from one image patch in the BS region, and another visual patch does not contribute to constructing a comprehensive 3-dimensional (3D) representation of the scene. This suggests that the brain adeptly manages this dimensional transition. We aimed to determine the extent to which we perceive 3D across our entire field of view (FoV). We employed the Ponzo illusion, a stimulus relying on visual depth cues (pictorial depth cues), and an eye-tracking technique to assess participants' accurate fixation and eye movement patterns. The participants attempted to align their index fingers before a chart paper to create a Horopter-like setup, supporting the hypothesis about our capacity for stereoscopic perception. The results of our exploratory pilot study with two specific tasks revealed that our ability to perceive depth diminishes beyond approximately 8$^{\circ}$ of retinal eccentricity (in the horizontal meridian) in both halves of the visual field centered around the fovea. This limitation is not apparent in our day-to-day experience.

neuroscience↗

bioRxiv2026

Stepwise Proteinase K Digestion Improves Genomic DNA Yield and Purity from Goat Semen: A Comparative Pilot Study of Five Extraction Protocols

Background: Genomic DNA of high quality is a prerequisite for molecular genetic analyses. However, DNA extraction from goat semen is frequently challenged by highly compacted sperm chromatin and the presence of enzymatic inhibitors within the seminal plasma. Objectives: This pilot study aimed to identify a reliable and cost-effective method for isolating high-quality genomic DNA from caprine semen. Methods: Five extraction protocols were evaluated: an unmodified blood protocol (Protocol B), two modifications of a sperm protocol (Modified Protocols 1 and 2), and a stool protocol (Protocol BS) using a commercial spin-column kit (Kit A), alongside a second commercial silica membrane kit (Kit B). Three technical replicates per protocol were processed from a single frozen semen straw of a Black Bengal buck (with one replicate evaluated for Protocol B). Extracted DNA was evaluated based on concentration, purity (absorbance ratios A260/A280 and A260/A230), cost per sample, and PCR amplification success of the mitochondrial hypervariable region 1 (HVR1). Results: Modified Protocol 2 utilizing 100 uL of semen and two sequential 1.5-hour proteinase K incubations at 55 degrees C yielded the highest normalized DNA concentration (mean +/- SD: 55.9 +/- 30.4 ng/uL semen), optimal purity ratios (A260/A280 = 1.78; A260/A230 = 2.06), and the lowest cost per nanogram of DNA (INR 0.073 +/- 0.037). All extracts from this protocol were successfully amplified via PCR. While the Kruskal-Wallis test for normalized yield did not reach statistical significance (p = 0.075), rendering yield differences exploratory, Modified Protocol 2 demonstrated the strongest overall performance. Conclusions: Modified Protocol 2 offers a promising, cost-efficient workflow for caprine sperm DNA isolation. Given that this pilot study sampled a single animal, these findings must be validated using biological replicates from multiple bucks prior to widespread implementation.

molecular biology↗

bioRxiv2026

Cytoplasmic recapping commences the translation of a micropeptide, MARS from MALAT1 after the removal of an inhibitory RNA G-quadruplex

Long non-coding RNAs (lncRNAs), conventionally defined as RNA transcripts longer than 200 nucleotides that lack protein-coding potential, have emerged as key regulators of diverse biological processes, including metabolism, development, cellular differentiation, and stress responses. They modulate cellular functions through multiple mechanisms, including chromatin remodeling, transcriptional regulation, and the control of RNA stability and translation. Most lncRNAs are transcribed by RNA polymerase II and undergo canonical RNA processing, including splicing, polyadenylation, and 5' N7-methylguanosine (mG) capping. However, whether cytoplasmic recapping of lncRNAs can promote the production of functional micropeptides remains poorly understood. In this study, we investigated the functional consequences of cytoplasmic recapping of MALAT1, a highly abundant and broadly expressed lncRNA. We demonstrate that cytoplasmic processing and recapping of a MALAT1 decay intermediate support the production of a previously uncharacterized micropeptide, designated MARS (MALAT1 Responsive to Stress). We further identify RNA G-quadruplex (rG4) structures in the 5' region of MALAT1 that inhibit MARS translation, revealing an additional layer of structural regulation. MARS expression increases in response to arsenite-induced oxidative stress and is associated with nuclear factor erythroid 2-related factor 2 (Nrf2)-containing complexes. Furthermore, MARS is implicated in the regulation of antioxidant response element-associated genes, including SOD and CAT, suggesting a potential role in cellular antioxidant defense. Collectively, our findings identify a previously unrecognized functional output of cytoplasmic RNA recapping and expand the potential coding repertoire of lncRNAs. This study highlights a mechanism through which cytoplasmic RNA processing may contribute to micropeptide production and suggests a role for MALAT1-derived MARS in oxidative stress-responsive gene regulation.

molecular biology↗

bioRxiv2026

Feasibility of adopting water displacement and 3D scanning methods to quantify lung volume reduction in ex vivo models

Lung volume reduction is a treatment for chronic obstructive pulmonary disease (COPD) patients with severe emphysema. Currently, in vivo animal models are used as a first step to quantify the efficiency of novel lung volume reduction treatments. By quantifying lung volume reduction in ex vivo samples, animal testing may be reduced. This study proposes two new methods for quantifying lung volume reduction in ex vivo tissue: water displacement and three-dimensional (3D) scanning. Porcine lung lobes were inflated and treated with cyanoacrylate glue to simulate lung volume reduction. Volume changes were measured using a custom water displacement setup and in a ventilated setting using a handheld Artec Space Spider 3D surface scanner. Both techniques detected post-treatment volume reductions. Water displacement offers a simple, cost-effective approach for isolated lung lobes, while 3D scanning enables volumetric analysis of intact lungs under ventilated conditions. These methods provide a reliable intermediate step between in vitro and in vivo testing, reducing animal use and improving preclinical assessment of novel lung volume altering interventions.

bioengineering↗

bioRxiv2026

Rescue of ribosomal protein bL27 in Streptococcus pneumoniae TIGR4 by an alternate protease

Streptococcus pneumoniae is a major human respiratory pathogen. The bacterial 70S ribosome is a target of many clinically important antibiotics. The N-terminus of ribosomal protein bL27 extends into the peptidyl transferase center and contributes to the translation process. In Firmicutes, full length bL27 contains an 8-12 amino acid N-terminal extension that is absent from Gram-negative bacteria. This extension is cleaved by the protease Prp, which is absent from organisms lacking the extension. Prp-mediated cleavage of bL27 is essential in Staphylococcus aureus, and Prp has been proposed as a potential antibiotic target. Here, we show that in S. pneumoniae strain TIGR4, a {Delta}prp mutant remained viable, and produced ribosomes containing cleaved bL27, whereas deletion of prp was not tolerated in strain D39. These results suggested the presence of an alternate bL27-processing protease in TIGR4 that was absent from D39. Using a combination of genomics, proteomics and biochemical analyses, we identified this enzyme as the product of previously uncharacterized gene SP_1145, encoding a protease that we named Ribosome rescue protease (Rrp). SP_1145 is carried on a mobile genetic element that is present in strain TIGR4, but absent from D39. Our findings shed light on an alternative mechanism for bL27 maturation, and indicate that some strains of S. pneumoniae harbor horizontally acquired redundant pathways for this essential ribosome processing step.

microbiology↗

bioRxiv2026

Scalable Extraction of Information on Protein-Protein Interactions using Topological Data Analysis

Protein-protein interactions (PPIs) govern a wide range of cellular functions. The ability to predict PPI interfaces from protein molecular surfaces is important for understanding protein function and enabling therapeutic discovery. While recent advances in structure-based learning, particularly molecular-surface geometric deep learning frameworks, have demonstrated that protein surfaces encode rich geometric and physicochemical information, such approaches often remain computationally intensive and data-hungry. Alternatively, topological data analysis (TDA) has emerged as a mathematically rigorous framework for extracting robust, multiscale shape information from complex data. In this work, we introduce a scalable TDA framework for extracting information on PPIs directly from localized protein surface patches. Our approach leverages multiscale topological descriptors, evaluated from patch-wise point cloud representations of protein mesh surfaces, combined with supervised machine learning models for interface prediction. On a full dataset of 3,362 proteins, the proposed approach substantially reduced computational cost relative to an established geometric deep learning method, MaSIF-site, decreasing preprocessing time from approximately 27 s/protein to 5-8 s/protein and total training time from approximately 6 h to 1-1.3 h. Importantly, this computational reduction is achieved while maintaining mean test area under the receiver operating characteristic curve (AUC) values of 0.76 and 0.77 for patch radii of 9 [A] and 12 [A], respectively, thus approaching the MaSIF-site test AUC of 0.84. Our results suggest that topology offers a scalable and computationally efficient approach for high-throughput extraction of information from complex biomolecular interfaces.

bioinformatics↗

bioRxiv2026

Experimental evolution and functional genetics identify KIC1 as a determinant of reduced artemisinin susceptibility in Bangladeshi Plasmodium falciparum

Bangladesh has greatly reduced malaria transmission, but persistent Plasmodium falciparum transmission in the Chittagong Hill Tracts (CHT), bordering Myanmar, remains a concern for elimination. Emerging artemisinin resistance could threaten remaining control efforts, making it important to identify determinants of reduced artemisinin susceptibility in CHT parasites. We combined long-term in vitro dihydroartemisinin (DHA) selection, whole-genome sequencing, functional genetics, and analysis of contemporaneous clinical isolates to define artemisinin-response variation in CHT P. falciparum. Starting with a 2018 patient-isolated, artemisinin-sensitive CHT clone, three independent cultures were exposed over 18 months to 27 cycles of stepwise DHA pressure up to 1600 nM. This generated CHT-R lines with elevated RSA survival relative to parental/sibling controls (4.0-6.5% versus <1%; 7-11-fold increase) and faster post-DHA recovery than CHT-S-sib (5.2 {+/-} 0.3 versus 10.1 {+/-} 0.57 days). Whole-genome sequencing identified convergent disruption of PF3D7_0606000, encoding KIC1 (Kelch13 Interacting Candidate1), a protein linked to the Kelch13-associated endocytic compartment; no pfkelch13 mutations emerged. Independent DHA-selected lines acquired distinct stop-gain or frameshift mutations predicted to truncate KIC1, and targeted pfkic1 disruption in parental CHT-S increased RSA survival and accelerated recovery, functionally validating KIC1 as a contributor to reduced artemisinin susceptibility. To link the in vitro selection findings to naturally circulating parasites, we tested whether pfkic1 variation was associated with artemisinin response in an independent set of CHT isolates. We integrated newly generated RSA measurements and whole-genome variation from lab adapted field isolates all carrying wild-type pfkelch13, with patient clearance values from our CHT artemether-lumefantrine efficacy study. Among 22 isolates, RSA survival ranged from 0.00 to 6.44%, with 12 exceeding the 1% in vitro ART-R threshold and was associated with PC50, the time required to clear 50% of the initial parasite density, but not parasite clearance half-life (PCt1/2). In this field-isolate dataset, targeted pfkic1 gene-score analysis and elastic-net modeling provided supportive evidence that natural variation at the pfkic1 locus is associated with PC50 and RSA survival; an exploratory genome-wide gene-score scan nominated additional candidate loci for future study. Together, these findings identify KIC1 as a functionally validated determinant of reduced artemisinin susceptibility in a Bangladeshi parasite background and suggest that artemisinin-response variation in CHT parasites may involve perturbation of the Kelch13-associated endocytic pathway beyond canonical pfkelch13 mutations.

microbiology↗

bioRxiv2026

Seizure-related gene 6 (SEZ6) encodes a Cancer stem cell-specific proangiogenic molecule: A novel glioma therapeutic target

Cancer stem-like cells (CSCs) not only initiate tumors but also orchestrate angiogenesis through multiple mechanisms, thereby sustaining vascularization and promoting tumor growth. In glioblastoma (GBM; WHO grade IV glioma), the most aggressive adult brain tumor, glioma stem-like cells (GSCs; glioma CSCs) are the main drivers of tumor progression, drug resistance, and recurrence. An interrogated multi-omic secretome analysis identified Wnt-{beta}-catenin signaling-regulated, membrane-localized Seizure Related 6 Homolog (SEZ6) as a patient-derived GSC-specific proangiogenic molecule. Silencing of SEZ6 inhibited the ability of the GSC secretome to induce angiogenic network formation by brain- and lung-derived endothelial cells, but not GSC growth as neurospheres in vitro. SEZ6 silencing also suppressed patient-derived GSC-initiated glioma tumors, resulting in reduced tumor vasculature in an orthotopic mouse model. We also found that SEZ6 induces TGF{beta}-dependent IL-8 expression in endothelial cells to promote angiogenesis. Coimmunoprecipitation and molecular dynamics simulation experiments determined that the Sushi 3 domain of SEZ6 mediates the interaction with TGF{beta} RII to activate the TGF{beta} pathway. Pharmacological inhibition of BACE1 with an in-house-developed small molecule, or blockade of the SEZ6-TGF{beta} RII interaction using a rationally designed peptide, markedly attenuated SEZ6-driven TGF{beta} signaling, and suppressed angiogenesis. Thus, our findings identify SEZ6 as a novel CSC-specific therapeutic target for GBM.

cancer biology↗

bioRxiv2026

A chemically reactive and Raman-active non-canonical amino acid reveals photocycle complexity in a blue-light receptor

Photosensory protein function spans multiple time and length scales, demanding integrative approaches. We introduce 4-diacetylenyl-phenylalanine (DAF), a dual-purpose non-canonical amino acid (ncAA) that enables both chemical control and spectroscopic readout of photoreceptor dynamics. Genetically encoded in E. coli, DAF combines a reactive diyne for bioorthogonal ligations (thiols, azides, tetrazines) with a strong, solvatochromic Raman signal in the cell-silent region. Applied to the light-oxygen-voltage (LOV) transcription factor EL222, DAF enables multifaceted interrogation of its photocycle. We engineer a covalently cross-linked variant that suppresses light-driven conformational changes and DNA binding, and generate a donor-acceptor construct for Forster resonance energy transfer (FRET) tracking of photoinduced structural dynamics. Time-resolved stimulated Raman spectroscopy following flavin mononucleotide (FMN) excitation reveals additional processes -from vibrational energy transfer to local unfolding-spanning femtoseconds to milliseconds. DAF thus constitutes a versatile tool to resolve protein dynamics with high spatiotemporal resolution.

biochemistry↗

bioRxiv2026

Fluoroquinolone resistance-conferring gyrA variants alter the fitness cost and potentiate the resistance of the zoliflodacin resistance mutation gyrB D429N in Neisseria gonorrhoeae

Neisseria gonorrhoeae is a major public health concern due to its high global prevalence and rapid evolution of antibiotic resistance. A first-in-class topoisomerase inhibitor, zoliflodacin (a spiropyrimidinetrione) recently received FDA approval for treatment of gonorrhea, but its potential for cross-resistance with another topoisomerase inhibitor, the fluoroquinolone antibiotic ciprofloxacin, remains poorly understood. Here, we investigated how genetic diversity in the fluoroquinolone target gyrA influences the resistance and fitness effects of the zoliflodacin resistance mutation gyrBD429N. We constructed an isogenic panel of N. gonorrhoeae to determine how the resistance and fitness effects of the gyrBD429N mutation are modulated by the most common ciprofloxacin resistance-associated variants in gyrA. In the presence of gyrBD429N, the zoliflodacin minimum inhibitory concentration (MIC) was 2-4-fold higher in strains that also contained ciprofloxacin resistance-associated gyrA alleles, and the gyrBD429N mutation reciprocally increased ciprofloxacin MICs of these strains 3-6-fold. Fitness cost of the gyrBD429N mutation varied from modest to severe across gyrA backgrounds, with the largest cost in ciprofloxacin resistant gyrA91F/95G and gyrA91F/95N backgrounds and comparatively minimal cost in the ciprofloxacin resistant gyrA91F/95A background. These results demonstrate the capacity for epistatic interactions among resistance-associated gyrA and gyrB mutations, underscoring the need for genomic surveillance to monitor high-risk combinations of resistance determinants as new therapies are deployed.

microbiology↗

bioRxiv2026

Urbanisation Reshapes Freshwater Microbiomes: A Systematic Review of Ecological Patterns and Functional Shifts

Rapid urbanisation has profoundly shaped microbial diversity across different ecosystems. Freshwater microbiomes are particularly affected by urbanisation activities, such as eutrophication, pollution, runoff, and sewage. This is of significant concern as marginalised communities often depend on waterbodies for their livelihood. Freshwater bodies play a crucial role in maintaining both human and ecological health at population level. Currently, we lack a systematic understanding of the global impacts of urbanisation on freshwater microbiomes in relation to human health, ecosystem functioning, and sustainability. We identified 90 eligible papers from the last 25 years after screening based on the inclusion exclusion criteria. We extracted data that examined changes in the functional traits such as antimicrobial resistance (AMR), nutrient cycling of the microbiome in urban waterbodies and several other factors. Data were extracted by a thematic analysis followed by a narrative synthesis on specific functional traits. This systematic review presents a comprehensive analysis on the changes and challenges brought about by urbanisation on freshwater bodies. Our results indicate that urbanisation leads to reduced bacterial diversity of urban waterbodies, with a striking increase in reporting of Proteobacteria, Cyanobacteria and Coliform bacteria. These insights will help inform public health strategies and sustainable urban planning. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/715732v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@1198ae7org.highwire.dtl.DTLVardef@1ee7db3org.highwire.dtl.DTLVardef@7e959corg.highwire.dtl.DTLVardef@90653b_HPS_FORMAT_FIGEXP M_FIG C_FIG Waterbodies in urban areas function as convergence platforms for anthropogenic and environmental microbiomes. Runoffs, wastewater and effluents contain antimicrobial resistance genes and other pathogens that survive in water due to inadequate treatment. Disposal, use, and overflow of wastewater cause restructuration of microbial communities, proliferation of opportunistic microorganisms, and spread of antimicrobial resistance in aquatic ecosystems.

genomics↗

bioRxiv2026

Influence of transglutaminase mediated crosslinking on the structure-function-digestion properties of Lupinus angustifolius protein evaluated using a multiscale approach

This study presents a multidisciplinary approach to evaluate the structure formation and digestion of lupin protein crosslinked with transglutaminase (TG). TG was applied at 0-10 U/g protein, and structural development was assessed by oscillatory rheology (G, G"), while SDS-PAGE and o-phthaldialdehyde (OPA) assays were used to evaluate protein participation and the reduction of free {varepsilon}-amino groups, respectively. Proteomics was further employed to characterise molecular features associated with crosslinking behaviour. Lupin protein showed a clear dose-dependent increase in gel strength during incubation, with G values reaching 214 {+/-} 43.9 Pa at 10 U/g TG, compared to 7.2 {+/-} 0.6 Pa in the untreated control. Across all conditions, G remained higher than G" throughout frequency sweeps, and low tan {delta} values confirmed the formation of elastic networks driven by covalent crosslinks. SDS-PAGE and OPA results consistently demonstrated efficient crosslink formation, which increased with both incubation time and TG dosage, with SDS-PAGE indicating involvement of specific protein fractions. Proteomic analysis revealed disordered structural domains in the protein are preferred regions to form crosslinks. Furthermore, TG treatment was found to slow the digestibility of the crosslinked lupin protein. Overall, this work demonstrates how integrating proteomic insights with functional measurements can guide the selection and optimisation of plant proteins for enzymatic structuring. The approach offers a rational pathway to enhance the functionality of alternative protein sources such as lupin, supporting the development of sustainable food systems, including applications in meat and dairy analogues.

bioengineering↗

bioRxiv2026

Functional validation of the Plasmodium falciparum K13 C580Y mutation in recently collected Ethiopian isolates

Recent genomic investigation in Ethiopia identified the first detection of the Plasmodium falciparum kelch13 (K13) C580Y substitution in the Horn of Africa. To assess its functional impact, we introduced C580Y into two recently collected Ethiopian clinical isolates using CRISPR-Cas9 genome editing. Ring-stage survival assays showed significantly elevated in vitro dihydroartemisinin (DHA) survival in edited parasites relative to isogenic controls, demonstrating that C580Y confers artemisinin tolerance in contemporary Ethiopian parasite genetic backgrounds.

microbiology↗

bioRxiv2026

Formation and role of the portal of Staphylococcus aureus bacteriophage 80α

Bacteriophages play an important role in the pathogenicity of Staphylococcus aureus, an important human pathogen. Phages are involved in generalized and specialized transduction as well as a more specific process by which they mobilize elements known as phage-inducible chromosomal islands, of which S. aureus pathogenicity islands (SaPIs) are an important group. SaPIs are mobilized at high frequency through interactions with specific "helper" bacteriophages, such as 80, leading to packaging of the SaPI genomes into virions made from structural proteins supplied by the helper. Among these structural proteins is the portal protein, which forms a ring-like portal at a fivefold vertex of the capsid, through which the DNA is packaged during virion assembly and ejected upon infection of the host. We previously showed that portal protein expressed in E. coli forms tridecameric rings, while portals found in virions are always dodecamers. To understand the role of the portal in capsid assembly, DNA packaging and ejection, we have here examined this phenomenon further. We show that portals assembled at lower temperature form unclosed rings that may represent portal assembly intermediates. By analyzing portal protein deletion mutants, we demonstrate the involvement of the different functional domains in phage assembly and protein incorporation.

microbiology↗

bioRxiv2025

Potential probiotic application of a novel commensal E. coli with antagonistic activity against different enteric pathogens

Diarrheal diseases remain a leading cause of global morbidity and mortality, and treatment options are increasingly compromised by the global rise in multidrug-resistant (MDR) pathogens. Furthermore, the absence of effective vaccines against many causative agents renders large populations vulnerable. This critical gap necessitates the development of novel alternatives that can function both prophylactically to prevent infection and therapeutically to treat established diseases. Here, we investigated the commensal Escherichia coli strain HK220822 (HK5), which was isolated from a healthy human, as a potential live biotherapeutic. Comprehensive genomic and phenotypic characterization established a robust safety profile, confirming the absence of key virulence genes while demonstrating essential probiotic traits, including high tolerance to gastrointestinal stressors, such as acid and bile. The functional efficacy of Escherichia coli HK5 has been validated in murine models of infection. Prophylactic administration before pathogen exposure significantly inhibited intestinal colonization by Salmonella Typhimurium, Shigella flexneri 2a, and Vibrio cholerae (El Tor O1 strain). Moreover, HK5 demonstrated therapeutic potential by significantly reducing pathogen shedding when administered to previously infected animals. These findings establish commensal E. coli (HK5) as a potent candidate with dual preventative and therapeutic efficacy, offering a promising non-antibiotic strategy to combat diarrheal diseases.

microbiology↗

bioRxiv2025

Interplay of Spoonbill, Larp7 and survival motor neuron, in Drosophila model of Spinocerebellar Ataxia 8 non-coding RNA associated neurodegeneration

A deeper understanding of neurodegenerative disorders at the level of genetic or environmental risk factors as well as contributing genes, pathways, and networks suggests the presence of shared molecular mechanisms. Previously, we have reported that the KH domain of the Spoonbill protein alone can suppress non-coding Spinocerebellar Ataxia 8 (SCA8) associated neurodegeneration. In the current study, we have identified dLarp7 as a novel interacting partner of Spoonbill in Drosophila. Mammalian Larp7 is associated with a neurodevelopmental disorder, Alazami Syndrome (AS). In this study, we report that dLarp7 protein is recruited into the pathogenic SCA8 RNA foci, which leads to depletion of its downstream target, 7SKsnRNA. Soaking away of Larp7 into toxic RNA foci results in its depletion from the physiological pool resulting in destabilization and depletion of 7SKsnRNP. Hence, increasing the dose of dLarp7 suppressed SCA8 associated neurodegeneration, by restoring the physiological levels of dLarp7 and 7SKsnRNP. In addition, it was observed that dLarp7 interacts with the somatic motor neuron (SMN) protein which is associated with spinal muscular atrophy (SMA). This observation led us to explore the interaction of Drosophila SMN1 orthologue with pathogenic SCA8 associated neurodegeneration. Intriguingly, SMN protein modulated molecular neuropathogenesis associated with SCA8. The presence of orthologues of Drosophila RNA binding proteins, dLarp7 and SMN, with mammalian counterparts underlines the translational importance of our findings. Our study also hints at the shared molecular mechanisms that underlies multiple neurodegenerative diseases. A novel association of Drosophila homologs of AS-linked Larp7 and SMA-causing SMN1 with SCA8 associated neurodegeneration suggests an overlap of molecular threads underlying the pathogenesis of neurodegenerative disorders.

neuroscience↗

bioRxiv2025

Zoliflodacin and gepotidacin cross-resistance in Neisseria gonorrhoeae

Resistance to zoliflodacin, a first-in-class antibiotic for gonorrhea treatment, can occur through gyrBD429N, but this mutations impact on fitness and resistance to other topoisomerase targeting drugs, including gepotidacin, have been unclear. Here, we show that gyrBD429N confers cross-resistance to gepotidacin in some clinical isolates and that its fitness effect varies with strain back-ground. These findings inform strategies for introducing the new topoisomerase inhibitors into clinical use and for surveillance of resistance.

microbiology↗