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Preprint: explore 300 source-linked works published from 2026 to 2026, with original documents and citations.

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Sources: biorxiv. Collection updated 2026-09-15. Counts describe this index, not the complete source archives.

Nuclear Myosin VI stabilises Ku-associated DNA ends during non-homologous end joining

DNA double-strand breaks (DSBs) require rapid signalling and physical stabilisation of broken DNA ends to preserve genome integrity. Here, we identify myosin VI (MVI) as an ATM-regulated component of the DSB response. DNA damage induces rapid nuclear accumulation and nanoscale reorganisation of MVI across multiple cell models, in an ATM-dependent manner. Pharmacological or genetic perturbation of MVI attenuates {gamma}H2AX signalling and disrupts Ku80 organisation, while DNA damage persists. This leads to increased sensitivity to cisplatin and bleomycin. Super-resolution imaging reveals spatial association of MVI with Ku80-containing repair structures, implicating MVI in non-homologous end joining (NHEJ). In a minimal reconstituted system, MVI and actin enhance the proximity of Ku70/80-bound DNA ends. Together, our findings identify MVI as a regulator of DSB repair that links ATM signalling to Ku-associated DNA-end stabilisation and suggest that targeting MVI may sensitise tumour cells to genotoxic therapy.

cancer biology

Heterogeneous and conserved radiation responses reveal FOXM1-dependent regulation of microcephaly genes in glioblastoma

Glioblastoma (GBM) is characterized by marked heterogeneity, glioma stem-like cells (GSCs), and resistance to therapy. Because GSCs share features with neural progenitor cells (NPCs), we investigated whether neurodevelopmental programs contribute to their response to irradiation. Transcriptional profiling of four patient-derived GSC lines revealed cell line-specific responses, with radiosensitivity correlating with the magnitude of p53 activation and basal expression of its negative regulator, MDM2. Despite this heterogeneity, radiation consistently activated p53-dependent pathways and suppressed cell-cycle programs. Among these, genes associated with primary hereditary microcephaly (MCPH) that regulate NPC proliferation were coordinately repressed. Single-cell RNA sequencing localized this response to G2/M-cycling cells. FOXM1 was similarly reduced following irradiation, emerged as a candidate regulator of a subset of MCPH genes, and correlated with their expression in GBM tumors. Pharmacological inhibition of FOXM1 reduced expression of selected MCPH genes and enhanced radiosensitivity in U251 cells. Together, these findings identify coordinated suppression of a FOXM1-associated MCPH program as part of the GBM radiation response, while suggesting that the radiosensitizing effects of pharmacological FOXM1 inhibition extend beyond this transcriptional axis.

cancer biology

Starvation improves epithelial fitness by selectively extruding DNA damaged cells

During homeostasis, crowded cells with the lowest energy levels are eliminated by extrusion via Piezo1 signalling to maintain constant cell numbers. However, crowding-induced extrusion does not necessarily remove damaged or otherwise unfit cells. Here, we show that glucose or glutamine starvation triggers a rapid, regulated wave of extrusion, called starvation-induced cell extrusion (STICE), that selectively eliminates cells bearing DNA damage markers via a p53-dependent, Piezo1-independent pathway, improving monolayer fitness. Unlike non-extruding cells, which recycle contents through autophagy and lysosomal digestion, p53-activated cells instead use LC3 to drive lysosomal exocytosis, promoting extrusion signalling. By eliminating defective and transformed cells, STICE confers resistance to damage and apoptotic stimuli in the remaining monolayer. STICE thus acts as a tissue-level analogue of autophagy: rather than improving individual cells by digesting and recycling damaged components, it improves tissue fitness by eliminating substandard cells.

cell biology

Upcycling banana peduncle fibers into mycelium-based composites for sustainable packaging and thermal insulation

The growing concerns due to plastic pollution in India have intensified the search for sustainable materials. Mycelium-based composites (MBCs) have emerged as bio-based alternatives for packaging and thermal insulation applications. India, the worlds largest producer of bananas, generates significant quantities of banana biomass (~200 tons per hectare per year), much of which remains underutilized. The banana peduncle, the stalk that supports the fruit bunch, is one such underutilized biomass. In this study, banana peduncle fibers were used as the main substrate with Pleurotus ostreatus for the fabrication of MBCs. Banana peduncle fibers were mixed with wood shavings (10-50 wt%) to enhance the dimensional stability and structural integrity of the composites. The properties of developed MBCs such as density, shrinkage, moisture absorption, water absorption, morphology, compressive properties, and thermal conductivity were studied. The 90% banana peduncle fibers-10% wood shavings formulation showed the highest radial mycelial growth rate (7 mm/day). MBCs consisting of 100% banana peduncle fibers had volumetric shrinkage of 36%, while the incorporation of 30-50% wood shavings reduced shrinkage by approximately 17%. Among the formulations, MBCs containing 30% wood shavings had the highest compressive strength (4.82 MPa) and compressive modulus (1.78 MPa), whereas MBCs containing 50% wood shavings had the highest recovery (59.6%). In contrast, MBCs fabricated using 100% banana peduncle fibers had the lowest thermal conductivity (0.04 W/m. K). These results demonstrate that banana peduncle fibers are a promising lignocellulosic substrate for the development of MBCs for sustainable packaging and thermal insulation.

bioengineering

Controlling Molecular Transport through Nanopores by Dynamic Aperture Sizing

Molecular transport through a nanopore determines the information that can be recovered from a translocation signal, yet it remains difficult to control in conventional solid-state nanopores. Rapid translocation reduces the information content and fixed nanopore geometries limit the dimensionality of the signal. Here, we control molecular transport through the development of the pipette-elastomer interfacial nanopore (PEIN), a dynamically reconfigurable solid-state nanopore which addresses these limitations. A PEIN is formed by depressing a glass nanopipette into a soft elastomer, progressively constricting its aperture and enabling continuous control over aperture size, while retaining the simplicity and favourable noise characteristics of glass nanopipette sensing. Using the dynamic aperture size control, DNA velocities could be controlled over more than a twofold range, with dwell times two orders of magnitude greater than observed in glass nanopipettes. DNA-origami rulers further revealed a progressive reduction in polymer velocity during translocation, indicating that hydrodynamic drag alone is insufficient to model forces on the DNA polymer. Finally, by using single- and double-stranded DNA and gold nanoparticles as molecular standards, we demonstrate reversible, size-selective molecular gating with sub-nanometre control. These results establish the PEIN as an accessible platform for controlling molecular transport and probing the relationships among biopolymer conformation, nanoscale confinement and translocation dynamics.

biophysics

Resource supply dynamics control stability and chaos in complex ecosystems

Ecological interactions are often mediated by feedbacks between organisms and their resource environments. Yet, how resource supply dynamics dictate collective dynamical phases of an ecosystem remains unclear. Here, we analyse a generalised consumer--resource model with non-reciprocal interactions to demonstrate that self-renewing versus externally-supplied resources yield fundamentally different dynamical phase diagrams. As interactions become increasingly non-reciprocal, ecosystems relying on self-renewing resources transition from stable dynamics to chaos and ultimately to infeasibility. By contrast, ecosystems with externally-supplied resources remain stable over a broader parameter range and transition to infeasibility without experiencing an intervening chaotic phase. Using the cavity method, we derive a unified stability condition applicable to a broad class of resource supply functions, explaining why externally-supplied resources can expand the stable region. We show that stability hinges crucially on the susceptibility of resources to perturbations, which depends strongly on their supply. Further, we show that external resource supply suppresses chaos in the unstable region by drastically reducing the susceptibility of resources closest to extinction. Our findings demonstrate that resource dynamics fundamentally reshape the accessible dynamical behaviours of an ecosystem, with implications for interpreting microbial community experiments.

ecology

Dynamic coupling of cell fate specification and cell sorting during mouse preimplantation development

During preimplantation development in mice, cells of the inner cell mass undergo a cell fate decision to become either Epiblast (Epi) or Primitive Endoderm (PrE) cells. Cell fate patterns during this stage range from an alternating pattern at the beginning to the separation of Epi and PrE at the end. Several mechanisms guiding this decision and pattern formation have been proposed, including intra- and intercellular signalling, cell division and cell sorting. The current understanding is that signalling generates the cell fates and subsequent sorting introduces the spatial cell fate separation. We used agent-based modelling to investigate whether cell differentiation and cell sorting can act concurrently and how their relative contributions to pattern formation may change over time. Comparing our model to experimental data for mouse blastocysts and ICM organoids, we find two mechanistic regimes that can produce the experimentally observed spatial separation: (i) simultaneous long-range intercellular signalling and cell sorting, and (ii) a gradual transition from short-range signalling to cell sorting, in which the timing is mediated via reducing cell fate plasticity. While the second agrees better with existing experimental evidence for late blastocysts, the first might still be relevant for early and mid blastocysts. Together, our results refine the sequential view of Epi/PrE patterning by showing that fate specification and cell sorting can be dynamically coupled, with their relative contributions changing over the course of blastocyst development.

developmental biology

Germ granules act as repositories for RNA and protein molecules essential for zebrafish germline development

Germ granules are conserved, phase-separated ribonucleoprotein condensates enriched in germline determinants, yet their precise function remains unclear. Using quantitative live imaging, translational reporters, and targeted disruption of germ granule assembly in zebrafish primordial germ cells, we show that germ granules are dispensable for germ cell fate, migration, and gamete production. Instead, granules act as reservoirs, sequestering transcripts and releasing them gradually for cytoplasmic translation. Under heat stress or translational inhibition, granules further accumulate mRNAs and canonical stress granule factors, indicating a role in buffering RNA and regulatory protein availability rather than serving as sites of localized translation, as previously proposed. Consistent with this reservoir model, cytoplasmic expression of the germline determinants Nanos3 and Dead end is sufficient to direct somatic cells toward a germline fate even in the absence of germ granules. Correspondingly, germ cells lacking granules develop normally but show reduced persistence of germline RNA expression and impaired fertility. Together, these findings establish zebrafish germ granules as protective condensates that safeguard germline determinants and enhance developmental robustness by buffering the timing and rate of RNA translation.

cell biology

Beyond Imbalance: An Elasticity Framework for the Distance-averaged Force-Velocity Relationship in Vertical Jump

This study aimed to (1) establish the distance-averaged F-V relationship framework and (2) develop elasticity metrics that quantify how F-V relationship variables govern jump height and inform training prescription. Theoretical derivation and experimental validation across 108 F-V relationship models derived from 1578 jumps (countermovement jump and squat jump at three knee angles; 20 well-trained subjects) yielded a standard error of 2.1% and a nearly perfect correlation (r = 0.96, p < 0.001) between measured and predicted jump height. Four elasticity metrics were formulated: force elasticity (F_{e}), the elasticity of jump height to maximal force (F_{0}); velocity elasticity (v_{e}), the elasticity of jump height to maximal velocity (v_{0}); the force-velocity elasticity norm {(\mathrm{F}-\mathrm{V}}_{\mathrm{EN}}=\sqrt{F_{e}^{2}+v_{e}^{2}}), reflecting the overall sensitivity of jump height to changes in F-V relationship variables; and the force-velocity elasticity ratio {(\mathrm{F}-\mathrm{V}}_{\mathrm{ER}}=F_{e}{\div v}_{e}), indicating which variable dominates the jump height response. Simulations and experiments revealed that F_{e} bore an inverse relationship to F_{0}, and v_{e} was inversely related to v_{0}, reflecting diminishing marginal returns. At a fixed jump height, simulations showed {\mathrm{F}-\mathrm{V}}_{\mathrm{EN}} and {\mathrm{F}-\mathrm{V}}_{\mathrm{ER}} displayed a U-shaped relationship; a balanced profile ({\mathrm{F}-\mathrm{V}}_{\mathrm{ER}}=1) did not always correspond to the lowest {\mathrm{F}-\mathrm{V}}_{\mathrm{EN}}. The distance-averaged F-V elasticity framework offers a physically grounded and quantitative tool for linking F-V relationship variables directly to jump performance, providing a basis for informing individualized training decisions.

biophysics

Developments in the European parasitoid community of Dryocosmus kuriphilus

The invasive gallwasp Dryocosmus kuriphilus was first detected in Italy in 2002, although likely to have initially arrived in the late 90s. Its ability to utilise sweet chestnut species non-native to its original Chinese range has allowed it to spread rapidly, and throughout Europe via European sweet chestnut Castanea sativa. Given the severity of its impact on C. sativa crop production, particularly in Mediterranean countries, previous studies have aimed to assess damage levels caused by D. kuriphilus, the efficacy of and potential non-target effects of the introduced biocontrol agent Torymus sinensis, and the possibility of regulation by native parasitoids. As yet a broad overview and analytical synthesis of these native parasitoid communities are absent. This review focuses on important aspects of the D. kuriphilus invasion. In particular, the invasion history and currently known distribution of D. kuriphilus, and several aspects of its associated parasitoid community. For native species to plausibly suppress D. kuriphilus, we might expect rates of parasitoid attack to increase with establishment time as native populations adapt to exploit the new resource, and this is a key focus of the review. We answer the following questions: 1) What is the distribution of D. kuriphilus in Europe, and has D. kuriphilus fully utilised the available niche space within its 20+ years in Europe? 2) Which species of native parasitoids attack D. kuriphilus in Europe and what are their ecological characteristics? 3) How consistent is the parasitoid community of D. kuriphilus across its range, and are there signs of convergence over time? 4) What effect does establishment time have on the species richness and abundance of parasitoid communities? We report the following: 1) D. kuriphilus has expanded its range throughout Europe and is present in nearly every major region where sweet chestnut is present. Native and non-native naturalised chestnut forests may be less susceptible to invasion than areas of industry due to differing socioeconomic and ecological factors, though areas with large chestnut industries also tend to be in the most heavily forested areas in the non-native range of sweet chestnut. D. kuriphilus has reportedly been eradicated from some countries, and effectively eradicated in a number of countries implementing biocontrol with T. sinensis, although successive invasions from neighbouring regions are still possible, and eradication may be transient. 2) 72 parasitoid species are identified attacking D. kuriphilus in Europe (far more species than any other gallwasp in the Western Palearctic). Its members are predominantly oak gallwasp parasitoids (82% of species), followed by gall-specialists of different host plants, leaf miner parasitoids and a minority of others with differing host life stages and ecologies. Parasitoids attacking D. kuriphilus are dominated by idiobiont ectoparasitoids of the superfamily Chalcidoidea (>96%). 3) The parasitoid community is highly variable, both temporally and spatially, although the vast proportion (>95%) of parasitoids at any one time are composed of locally common generalist oak gall parasitoids. The most common members include Bootanomyia dorsalis, Eupelmus urozonus, Eurytoma brunniventris, Mesopolobus sericeus and Torymus flavipes. 4) The length of establishment time has minimal effect on the species richness, abundance, and composition of the community, suggesting that regulation by natives, if it occurs, may take longer than the 20+ years that D. kuriphilus has persisted. While little evidence of increasing parasitoid attack of D. kuriphilus is apparent, we exercise caution by stating that the heterogeneity in available data are large, and that common biocontrol interventions using T. sinensis interrupt the natural process of community development dramatically. D. kuriphilus has been present in Europe for nearly three decades and few localities have repeated years of data collection. Even fewer studies have communities with establishment times exceeding ten years. Proper biocontrol by natives may not occur within short timeframes, although studies of other gallwasp invaders find similar results over periods exceeding 40 years. Given that many countries have chosen to implement T. sinensis for biocontrol, the focus may be better spent monitoring native gall communities for potential non-target effects.

ecology

Melanophilin, a Myosin Va Adapter Protein, Biases Track Selection of Myosin Va-and Kinesin-1-Transported Liposomes at Actin-Microtubule Intersections In Vitro

Secretory vesicle transport from the Golgi to the cell membrane involves kinesin and myosin Va motors on the vesicle surface cooperatively navigating their shared cargo through numerous actin-microtubule (MT) intersections. How the track on which the cargo exits the intersection is selected so that vesicles are delivered to their destination with spatial and temporal fidelity remains unclear. Here we hypothesized that melanophilin -- the adapter that links myosin Va to pigmented melanosomes and can bind to both actin and MTs -- acts as a phosphorylation-dependent switch to bias track preference at actin-MT intersections. To test this, we modeled melanosome transport in vitro using 350-nm liposomes with ~5 surface-bound molecules each of constitutively active myosin Va, kinesin-1, and full-length melanophilin with varying phosphorylation levels. Liposomes were then challenged with actin-MT intersections. Regardless of the track the liposomes entered the intersection on, liposomes with phosphorylated melanophilin were biased towards exiting the intersection on actin filaments while those with dephosphorylated melanophilin were biased to exit on MTs. Consistent with this, phosphorylated melanophilin showed a 2-fold preference to bind actin over MTs, and slowed liposome transport by myosin Va along actin filaments by ~40% by effectively acting as an anchor. Conversely, dephosphorylated melanophilin preferentially bound (2-fold) MTs over actin and, by acting as a tether, increased the kinesin-1 liposome transport distance on MTs. Therefore, melanophilin, based on its phosphorylation state, can bias track selection of cargo transported by kinesin-1 and myosin Va through the cell's complex cytoskeletal network with its numerous actin-MT intersections.

biophysics

X-ray crystallographic fragment screening reveals novel and conformationally dynamic ligand-binding sites in Mycobacterium tuberculosis FtsZ

Tuberculosis is a leading cause of death globally due to an infectious agent. There is ongoing need for novel mechanisms to inhibit M. tuberculosis (Mtb) growth and infection to improve patient outcomes. FtsZ, a GTPase that assembles into protofilaments at the division site of a replicating cell to produce two individual cells, is an attractive target as an essential protein in bacterial cell division. Here we describe a crystallographic fragment screening campaign of MtbFtsZ. 1,070 crystals were soaked with fragments and 714 datasets were used for downstream PanDDA analysis. 149 datasets exhibited PanDDA-generated event map density to support modeling of fragment binding. 15 novel sites are described. Both the ON and the OFF conformations of FtsZ are found in the asymmetric unit. Asymmetric binding of fragments to each chain in the model is observed. These crystallographic fragment screening results additionally provide opportunities for fragment growing and merging to develop FtsZ binders into drug-like molecules or conformation specific chemical probes.

biophysics

Regulation of a Classical Allosteric Molecular Machine by an Intrinsically Disordered Domain: the C-termini of GroEL

The bacterial chaperonin GroEL is a canonical example of an ATP-dependent molecular machine that must couple ligand binding to productive conformational work. GroEL passes through a series of distinct structural shifts, driven by ATP binding and hydrolysis, which power a facilitated protein folding reaction. How the complex allostery of the GroEL oligomer creates a folding cycle that is both efficient and directional remains incompletely understood. Here, we combine variable-temperature native ion mass spectrometry with single-molecule FRET to examine how the intrinsically disordered, highly conserved GroEL C-terminal tails impact the allosteric behavior of a single GroEL ring. Our observations show that the C-terminal tails restrain the conformational dynamics of the GroEL ring, most likely through direct interactions with the upper apical domains of the GroEL subunits, a constraint that is progressively released as ATP binds. These results support a model in which the C-terminal tails act as an entropic regulator of the GroEL reaction cycle: transient interactions between the tails and GroEL apical domains restrain premature ring opening and tune the energetic threshold for productive engagement by the smaller GroES co-chaperonin. By linking disordered tail dynamics to the classically cooperative reorganization of the GroEL ring, this mechanism enforces an ordered allosteric cascade that minimizes wasteful formation of empty GroEL-GroES cavities. These findings reveal how the conformational properties of an intrinsically disordered element can be exploited to optimize the energetic efficiency and functional timing of a large allosteric machine.

biophysics

Melanin Suppresses Aβ Aggregation and Toxicity

The aggregation of amyloid-{beta} (A{beta}) peptides into insoluble deposits is a characteristic hallmark of Alzheimer's disease (AD) and related neurodegenerative disorders. While AD is the most common cause of dementia, there are currently no disease-modifying treatments which are both affordable and adverse-free. In this study, we report that melanin, a pigment which is commonly found in nature and is abundant in parts of the human brain, suppresses the aggregation of the 42-amino acid A{beta} variant (A{beta}42). Using biophysical and biochemical techniques, we show that melanin delays A{beta}42 aggregation while also reducing the amount of A{beta}42 that converts into aggregates. Using thioflavin T assays paired with chemical kinetics, we characterised the melanin-induced inhibition of A{beta}42 aggregation in vitro. Using MALDI-MS, we elucidate the molecular basis of this effect by showing that melanin prevents A{beta}42 dimerisation. We then demonstrate that melanin also reverts the aggregation process by dissolving pre-formed A{beta}42 fibrils. Finally, we show that melanin reduces A{beta}42 aggregation and rescues A{beta}42 toxicity in an SH-SY5Y neuroblastoma cell model. Our study shows that melanin disrupts the aggregation and cytotoxicity of A{beta}42, and suggests that compounds derived from human metabolites may offer promising avenues to combat amyloid formation.

biophysics

Structural Plasticity and Ligand Promiscuity of CYP3A4 Revealed by Cryo-EM

Cytochrome P450 3A4 (CYP3A4) metabolizes roughly half of all marketed drugs, and its inhibition can cause clinically significant drug-drug interactions. The enzyme accommodates chemically diverse ligands, making binding modes and metabolic outcomes difficult to predict. Previous X-ray crystallography efforts have leveraged a truncated construct without the N-terminal segment that tethers CYP3A4 to the membrane. Here we show that the same construct assembles into a symmetric trimer that can be resolved by cryo-EM and determine structures of both unliganded and ligand-bound CYP3A4. Multiple ligands are resolved with density consistent with several mutually exclusive conformations. Protein remodeling to reshape the binding pocket is concentrated in the F/G loop, which is poorly resolved and unmodeled in many X-ray structures. These features likely underlie the poor predictive performance of co-folding methods on this target. The routine use of cryo-EM to resolve CYP3A4 ligand-bound complexes will provide the ground truth data needed to make predictive models of drug metabolism useful in practice.

biophysics

Beyond Equilibrium Ensembles: Time Rescaling in Coarse-Grained Simulations across Single-Molecule and Condensate Regimes

Residue-level coarse-grained simulations provide a powerful route for modeling biomolecular condensates over length and time scales that are difficult to access with atomistic molecular dynamics. Coarse-grained models have been shown to reproduce many aspects of equilibrium phase behavior. However, it remains unclear to what extent such models can reproduce the relative timescales of molecular dynamics. Here, we examine this question for complex coacervates with markedly different dynamics, formed by the highly acidic intrinsically disordered protein prothymosin with four cationic partners: linker histone H1, protamine, polylysine, and polyarginine. Coexistence simulations using a residue-level coarse-grained model reproduce key equilibrium observables from experiments, including dense-phase concentrations, ionic-strength-dependent phase behavior, and chain dimensions in the dense and dilute phases. Dynamics are accelerated in these simulations, but a composition-specific time-rescaling factor captures the ionic-strength dependence of chain reconfiguration times within a given complex coacervate. In contrast, time rescaling is not transferable between dense and dilute phases or across condensate compositions and can depend on the chosen observable. These results show that agreement with measured equilibrium observables does not imply a universally transferable timescale for conformational dynamics in residue-level coarse-grained simulations. However, we find that the required time rescaling strongly correlates with the interaction energy of the protein chains, suggesting that the missing frictional effects arise from protein-protein interactions rather than solely from protein-solvent interactions, reminiscent of internal friction. Our findings highlight the need to combine thermodynamic validation with kinetic calibration when interpreting chain relaxation, molecular diffusion, and material properties from residue-level coarse-grained simulations of biomolecular condensates.

biophysics

EcoEnamel: Development of a Gelatin-Pectin Film for S. mutans Inhibition and Enamel Preservation in an In Vitro Model

Rinsing-dependent dental hygiene presents a significant public health challenge in water-scarce environments. This study investigated combinations of xylitol (Xyl), chitosan (Chi), glycyrrhizin (Gly), epigallocatechin gallate (EGCG), dicalcium phosphate (DCP), and nano-hydroxyapatite (nHA) on the primary bacteria behind dental caries, S. mutans. These combinations were assessed for markers of dental caries by biofilm reduction, bacterial killing, and acid buffering against S. mutans when applied to an in vitro simulated enamel model using glass bead surfaces for biofilm formation, and gene expression was subsequently examined via RT-qPCR. Separately, mineral retention was also quantified. The EGCG-DCP-Xyl film demonstrated the highest overall efficacy, achieving a significant reduction in biofilm concentration compared to the untreated control and performing similarly in magnitude to the positive toothpaste control. Dead fluorescence staining confirmed that the EGCG-DCP-Xyl film induced the highest rate of non-viable cells, followed by the Chi-Gly film and the Gly-Xyl film. During 10-day pH cycling, the EGCG-DCP-Xyl and DCP-Xyl formulations buffered pH the most, consistently maintaining mean pH levels safely above the demineralization threshold of pH 5.5. The EGCG-DCP-Xyl also optimized mineral stability with the highest retained calcium concentration, significantly outperforming the Chi-Xyl film. At the transcript level, the EGCG-DCP-Xyl film induced substantial downregulation of key virulence genes, yielding decreases in expression for glucosyltransferase B (gtfB), associated with biofilm synthesis, collagen-binding protein (cnm), associated with tissue invasion, and lactate dehydrogenase (ldh), associated with lactic acid production, compared to the untreated control, with effects comparable in magnitude to the positive toothpaste control. This research suggests that targeting bacterial pathways and mineral loss through a portable film may have potential for preventing dental caries, especially in environments where water is limited. However, additional studies are necessary to evaluate real-world effectiveness.

microbiology

Design and Validation of New Primers for Specific and Sensitive Real-time PCR Detection and Quantification of Seven Botulinum Encoding Genes (Serotype A-G) of Clostridium botulinum

Botulinum neurotoxins (BoNTs) comprise a highly diverse group of seven serotypes (from A-G) and over 40 subtypes worldwide. Previous primer- and probe-based nucleic acid amplification tests (NAATs) for detection of BoNT encoding genes are challenged by high levels of nucleotide polymorphism both across and within subtypes. In this study, multiple BoNT gene sequences were aligned to identify highly conserved regions for the design of new primers that enable the detection of all seven serotypes under the same conditions. Specific primer sets were designed and validated using in silico, conventional and real-time PCR with constructed plasmids carrying the target fragments and spiked food matrices. The established procedure achieved highly specific and sensitive detection of BoNT serotypes A-G with sensitivity of 10 copies/reaction and a total turnaround time of approximately 1.5 hours. The procedure also eliminated the carryover PCR product by using uracil-N-glycosylase in combination with dUTP in the assay reaction mix. This study provides an alternative NAAT with higher coverage and compliments the traditional mouse bioassays in enhancing global botulism surveillance capabilities.

molecular biology
Compare source metadata on this page
WorkPublishedSource identifierSource
Nuclear Myosin VI stabilises Ku-associated DNA ends during non-homologous end joining2026-09-0210.64898/2026.09.01.748478v1biorxiv
Heterogeneous and conserved radiation responses reveal FOXM1-dependent regulation of microcephaly genes in glioblastoma2026-09-0210.64898/2026.09.01.748488v1biorxiv
Starvation improves epithelial fitness by selectively extruding DNA damaged cells2026-09-0210.64898/2026.09.01.748489v1biorxiv
Upcycling banana peduncle fibers into mycelium-based composites for sustainable packaging and thermal insulation2026-09-0210.64898/2026.09.01.748491v1biorxiv
Controlling Molecular Transport through Nanopores by Dynamic Aperture Sizing2026-09-0210.64898/2026.09.01.748496v1biorxiv
Resource supply dynamics control stability and chaos in complex ecosystems2026-09-0210.64898/2026.09.01.748502v1biorxiv
Dynamic coupling of cell fate specification and cell sorting during mouse preimplantation development2026-09-0210.64898/2026.09.01.748504v1biorxiv
Germ granules act as repositories for RNA and protein molecules essential for zebrafish germline development2026-09-0210.64898/2026.09.01.748510v1biorxiv
Beyond Imbalance: An Elasticity Framework for the Distance-averaged Force-Velocity Relationship in Vertical Jump2026-09-0210.64898/2026.09.01.748530v1biorxiv
Developments in the European parasitoid community of Dryocosmus kuriphilus2026-09-0210.64898/2026.09.01.748543v1biorxiv
Melanophilin, a Myosin Va Adapter Protein, Biases Track Selection of Myosin Va-and Kinesin-1-Transported Liposomes at Actin-Microtubule Intersections In Vitro2026-09-0210.64898/2026.09.01.748553v1biorxiv
X-ray crystallographic fragment screening reveals novel and conformationally dynamic ligand-binding sites in Mycobacterium tuberculosis FtsZ2026-09-0210.64898/2026.09.01.748605v1biorxiv
Regulation of a Classical Allosteric Molecular Machine by an Intrinsically Disordered Domain: the C-termini of GroEL2026-09-0210.64898/2026.09.01.748644v1biorxiv
Melanin Suppresses Aβ Aggregation and Toxicity2026-09-0210.64898/2026.09.01.748646v1biorxiv
Structural Plasticity and Ligand Promiscuity of CYP3A4 Revealed by Cryo-EM2026-09-0210.64898/2026.09.01.748687v1biorxiv
Beyond Equilibrium Ensembles: Time Rescaling in Coarse-Grained Simulations across Single-Molecule and Condensate Regimes2026-09-0210.64898/2026.09.01.748708v1biorxiv
EcoEnamel: Development of a Gelatin-Pectin Film for S. mutans Inhibition and Enamel Preservation in an In Vitro Model2026-09-0110.64898/2026.08.18.745620v1biorxiv
Design and Validation of New Primers for Specific and Sensitive Real-time PCR Detection and Quantification of Seven Botulinum Encoding Genes (Serotype A-G) of Clostridium botulinum2026-09-0110.64898/2026.08.21.746353v1biorxiv

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