Biology subjects

Sunder, S.

Publications and source records attributed to Sunder, S..

4 recordsLinked to original sources

bioRxiv2026

Reh1 is Required for Nonfunctional 25S RNA Decay

25S nonfunctional RNA decay (NRD) eliminates 60S ribosomal subunits carrying inactivating mutations in the RNA. However, how cells identify defective subunits has not been described. We recently showed that the zinc-finger protein Reh1 is the last assembly factor to be released from a nascent 60S subunit. We now show that in yeast Reh1 is required for the degradation of 25S NRD substrates. 25S rRNAs carrying mutations in the catalytic center, A2820G or U2954A (A2451 and U2585, respectively in E coli numbering), are unstable in wildtype cells but are fully stabilized when REH1 is deleted. However, not all 25S rRNA mutations are recognized by Reh1. Ribosomes with a truncated L1 stalk engage in translation but cannot support viability. These ribosomes display a half-life indistinguishable from wild-type rRNA, suggesting that yeast does not have a robust surveillance system for such mutant ribosomes. Deletion of REH1 also has no impact on the levels of defective 18S rRNA. These results indicate that Reh1 and 25S NRD are specific for mutations in or near the catalytic center of the ribosome.

molecular biology↗

bioRxiv2026

Development of a UVGI System and Evaluation of Germicidal Potential Against Biofilm-Forming Bacteria and Fungi Under Controlled Laboratory Conditions

A compact, in-house developed ultraviolet germicidal irradiation (UVGI) system adaptable to static, mobile, or robotic platforms was developed for the effective sterilization of bacteria and fungi using a wireless mode of operation. Under controlled laboratory conditions, its efficacy was evaluated against three representative biofilm-forming pathogens: Bacillus subtilis (Gram-positive, spore-forming, motile bacterium), Escherichia coli K12 (Gram-negative, non-spore-forming, non-motile bacterium), and Candida albicans M-207 (multi-drug-resistant, clinical yeast isolate). Microbial viability following UVGI exposure was assessed using colony-forming unit (CFU) and MTT assays, and morphological alterations were characterized by scanning electron microscopy (SEM). Cultures were exposed to UV-C radiation at distances of 1-5 m for 15-90 min. CFU assay demonstrated 100% kill of all tested organisms at 1 m and 15 min, corresponding to doses of 600.3, 576 & 697.5 mJ/cm{superscript 2}. Although MTT assays indicated residual metabolic activity under the same conditions, CFU results confirmed that surviving cells were unable to proliferate, highlighting the robustness of UV treatment for long-term inactivation. SEM confirmed distinct morphological alterations such as complete destruction of extracellular matrix & reduction in number of cells indicating cell death with increase in UV dose as compared to controls. A dose & time-dependent inactivation of biofilm-forming bacteria & fungi was observed on exposure to UVGI. Therefore, this pilot study validates the effectiveness of the newly developed UVGI surface sterilizer against biofilm-forming bacterial and fungal pathogens. Overall, the system demonstrates proof-of-concept efficacy under laboratory conditions and holds strong potential for future development and validation in hospitals and other contaminated public spaces. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=91 SRC="FIGDIR/small/715580v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@150cefcorg.highwire.dtl.DTLVardef@450831org.highwire.dtl.DTLVardef@1cfd6borg.highwire.dtl.DTLVardef@1419ba8_HPS_FORMAT_FIGEXP M_FIG C_FIG IMPORTANCEMicroorganisms that form biofilms on surfaces are difficult to eliminate and contribute to the spread of infections in healthcare and indoor environments. There is a need for practical, easy-to-use disinfection technologies that can effectively reduce such contamination. In this study, we developed a compact, in-house, wireless UV-C disinfection system designed for flexible operation across different surface types. The system was evaluated under controlled laboratory conditions using representative biofilm-forming bacterial and fungal pathogens. Our findings show that the system can effectively reduce microbial contamination, demonstrating proof-of-concept efficacy. This work highlights the potential of accessible, non-chemical UV-based technologies and supports their further validation for applications in real-world disinfection settings.

microbiology↗

bioRxiv2024

Neural mechanisms of attention, not expectation, govern spatial selection by probabilistic cueing

Spatial probabilistic "Posner" cueing is widely employed in studies of endogenous spatial attention. Such cueing guides attention by providing prior knowledge about the likely spatial location of task-relevant events. Yet, it has been compellingly argued that such spatial priors also elicit expectation effects, rendering Posner cueing unsuitable for measuring attentional effects in isolation. We address this debate by combining signal detection theory models of behavior with concurrent electrophysiological recordings, and directly compare Posner cueing effects with those of attention and expectation cueing. Participants performed two tasks: a dual cueing task, with orthogonal relevance (attention) and probability (expectation) cues, as well as a Posner cueing task. Relevance and probability cueing independently modulated distinct behavioral parameters - perceptual sensitivity and decisional criterion, respectively - whereas Posner cueing modulated both sensitivity and criterion. However, only sensitivity modulations by Posner cueing were correlated with those of relevance cueing. Criterion modulations by Posner cueing were uncorrelated with those of probability cueing. Both Posner and relevance cueing, but not probability cueing, modulated various neural markers of spatial attention, including steady-state visually evoked potential (SSVEP) amplitude and alpha-band (8-12 Hz) oscillation power. Representational similarity analysis and cue-label prediction with deep convolutional neural networks revealed dissociable underpinnings of relevance and probability cueing, and identified Posner cueings neural representations with those of relevance cueing. Our results address a long-standing debate in the attention literature and clearly demonstrate that spatial selection by probabilistic cueing is governed by neural mechanisms of attention, not expectation. Significance StatementHow does our brain select relevant information for accomplishing task goals? "Posner cueing" is a popular choice for studying brain mechanisms of goal-driven attention in the lab. Posner cues guide attention by providing advance information about the likely location of task-relevant events. Yet, Posner cueing has been criticized because it engages brain mechanisms not only of attention but of event expectation, as well. We address this critique by employing state-of-the-art neural decoding approaches, including deep convolutional neural networks, and show that behavioral and neural underpinnings of Posner cueing closely match those of attention, not expectation. The results address a long-standing debate in the attention literature and validate Posner cueing as a reliable method for measuring attentions effects in the brain.

neuroscience↗

bioRxiv2024

Fluoride export is required for competitive fitness of pathogenic microorganisms in dental biofilm models

Microorganisms resist fluoride toxicity using fluoride export proteins from one of several different molecular families. Cariogenic species Streptococcus mutans and Candida albicans extrude intracellular fluoride using a CLCF F-/H+ antiporter and FEX fluoride channel, respectively, whereas commensal eubacteria, such as Streptococcus gordonii, export fluoride using a Fluc fluoride channel. In this work, we examine how genetic knockout of fluoride export impacts pathogen fitness in single-species and three-species dental biofilm models. For biofilms generated using S. mutans with genetic knockout of the CLCF transporter, exposure to low fluoride concentrations decreased S. mutans counts, synergistically reduced the populations of C. albicans, increased the relative proportion of commensal S. gordonii, and reduced properties associated with biofilm pathogenicity, including acid production and hydroxyapatite dissolution. Biofilms prepared with C. albicans with genetic knockout of the FEX channel also exhibited reduced fitness in the presence of fluoride, but to a lesser degree. Imaging studies indicate that S. mutans is highly sensitive to fluoride, with the knockout strain undergoing complete lysis when exposed to low fluoride for a moderate amount of time, and biochemical purification the S. mutans CLCF transporter and functional reconstitution establishes that the functional protein is a dimer encoded by a single gene. Together, these findings suggest that fluoride export by oral pathogens can be targeted by specific inhibitors to restore biofilm symbiosis in dental biofilms, and that S. mutans is especially susceptible to fluoride toxicity. ImportanceDental caries is a globally prevalent condition that occurs when pathogenic species, including Streptococcus mutans and Candida albicans, outcompete beneficial species, such as Streptococcus gordonii, in the dental biofilm. Fluoride is routinely used in oral hygiene to prevent dental caries. Fluoride also has antimicrobial properties, although most microbes possess fluoride exporters to resist its toxicity. This work shows that sensitization of cariogenic species Streptococcus mutans and Candida albicans to fluoride by genetic knockout of fluoride exporters alters the microbial composition and pathogenic properties of dental biofilms. These results suggest that the development of drugs that inhibit fluoride exporters could potentiate the anticaries effect of fluoride in over-the-counter products like toothpastes and mouth rinses. This is a novel strategy to treat dental caries.

microbiology↗