Biology subjects

Rahman, S.

Publications and source records attributed to Rahman, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Comparative Mitogenomics and Molecular Phylogeny of Agriculturally Significant Tephritid Fruit Fly Pests in Bangladesh

Tephritid fruit flies of the tribe Dacini rank among the most economically destructive agricultural pests globally, with several Bactrocera Macquart and Zeugodacus Hendel species causing severe losses to fruit and vegetable production across South and Southeast Asia. Bangladesh harbors five dacine species of primary agricultural significance: Bactrocera dorsalis (Hendel), B. carambolae Drew & Hancock, B. zonata (Saunders), B. correcta (Bezzi), and Zeugodacus cucurbitae (Coquillett). Here we present a comparative mitogenomic and molecular phylogenetic framework based on 21 unique mitogenome records retrieved from NCBI GenBank, representing 19 dacine ingroup taxa and two outgroups. Direct parsing of the GenBank sequences confirmed the canonical complement of 13 protein-coding genes (PCGs) and two rRNA genes in all 21 records. Among the 14 Bactrocera ingroup taxa, genome size ranged from 15,273 to 15,977 bp. Whole-genome AT content ranged from 66.6% in Bactrocera tsuneonis to 82.2% in Drosophila melanogaster; the five Bangladesh-relevant dacine pest species showed tightly clustered AT content of 72.9-73.6%. A concatenated alignment of 13,600 nucleotide sites (13 PCGs + 12S + 16S rRNA) was analyzed by maximum-likelihood inference under the GTR+FO model (IQ-TREE v1.6.11; 1,000 ultrafast bootstrap replicates). The ML tree recovers the B. dorsalis complex (UFBoot = 79-100) and places B. correcta and B. zonata as a maximally supported sister pair (UFBoot = 100). This study provides a sequence-verified mitogenomic reference framework for molecular identification and pest surveillance in Bangladesh, and should be interpreted as a curated comparative baseline rather than a population-genomic analysis, as no newly collected Bangladeshi specimens were sequenced.

bioinformatics↗

bioRxiv2026

Sequence-Derived Representations versus Pfam-Domain Content for Biosynthetic Gene Cluster Retrieval

Retrieving BGCs related to those of a known producer can be regarded as a representation-learning objective. We hypothesize that ESM-2 sequence-derived representations of BGCs can improve retrieval beyond the Pfam-domain content metric. Our toolkit is the following: group-disjoint train, validation, and test assignments, validation-frozen model selection, [fi]ve seeds, and family-level paired inference. Of 6,953 atlas BGCs from 182 deduplicated Streptomyces griseus genome accessions, 5,325 silver-labeled BGCs are split into 98 training, 21 validation, and 21 test reference groups. Of the test reference groups, 16 are eligible for retrieval diagnostics. Pfam Jaccard scored Recall@50 of 0.8788, while Pfam-augmented BGC-SetNet scored 0.8472. The combination of ESM and Pfam-augmented BGC-SetNet scored 0.8769. A weighted Pfam Jaccard obtained a slightly higher score of 0.8789, which has a negligible difference compared to unweighted Pfam accard. Our results do not support the claim that sequence-derived representations can recover alternative biosynthetic pathways on this benchmark. Instead, explicit Pfam remains the major signal for this objective. Our results de[fi]ne the curation and pathway-level validation processes that are necessary for a more robust biological test.

bioinformatics↗

bioRxiv2026

A Chromatin Biology Assessment of AlphaFold3

Biomolecular structure prediction tools such as AlphaFold have achieved remarkable success in predicting structures of single proteins and multiprotein complexes. AlphaFold3 now incorporates the capability to model complexes containing nucleic acids and chemically modified side chains. Investigators can now predict structures of proteins bound to chromatin, where interactions with nucleosomal DNA and histone post-translational modifications converge to control genome function. To evaluate its robustness in modeling chromatin complexes, we benchmarked AlphaFold3 on 115 structures containing nucleosomes whose coordinates were released by the Protein Data Bank after the training set cutoff date. We find that AlphaFold3 excels at predicting histone-driven interactions and accurately models complexes that deposit and recognize post-translational modifications. By contrast, AlphaFold3 struggles to predict structures of chromatin factors that primarily engage nucleosomal DNA, notably transcription factors and chromatin remodelers. Finally, we show that AlphaFold3 can faithfully recapitulate known post-translational modification recognition patterns, matching experimentally determined specificity profiles. This assessment of the capabilities and limitations of AF3 in chromatin structural biology provides a roadmap for its effective application to studies of chromatin regulation and PTM readout, while identifying key areas for future algorithmic refinement. SignificanceStructure prediction with AlphaFold has become an invaluable tool in experimental biology, and the accuracy of many of its predictions has been verified in structural and biochemical studies. With the recent incorporation into AlphaFold3 of nucleic acids and post-translational modifications, this prediction tool can now be applied to chromatin structural biology. Our benchmarking of AlphaFold3 reveals its strengths and weaknesses in predicting structures of proteins bound to nucleosomes, thereby providing a framework for using these models in mechanistic studies of chromatin regulation. We introduce metrics for evaluating structures of nucleosome complexes that highlight AlphaFold3s strengths in predicting protein-nucleosome interactions and post-translational modification specificity.

biophysics↗

bioRxiv2026

Short-Term Combined Tat-Beclin1 and Endurance Training Improves Age-Related Decline in Physical Function in Male Mice

Autophagy is a hallmark of aging, but autophagy-related proteins have not been exclusively targeted to attenuate the progressive decline in physical function associated with aging. Here, we combined Tat-Beclin1, an autophagy agonist, and endurance training to determine whether Tat-Beclin1 enhances exercise adaptation in old male mice. Tat-Beclin1 was administered intraperitoneally (TB group, 15 mg/kg, 2x/week) as a standalone therapy, or in combination with endurance training (TB+Exe group, 70% of maximal running speed 3x/week) for 1 month in 23-month-old male C57BL/6J mice. Control groups were age-matched cage controls and exercise-only groups. Animals were assessed for grip strength, endurance capacity on a treadmill, and balance and coordination on a rotarod. Gastrocnemius/plantaris (G/P) and tibialis anterior muscles were harvested for western blotting, myofiber typing, and proteomic profiling (G/P only). TB+Exe led to significant increases in grip strength, endurance capacity, and balance and coordination performance beyond those observed in the TB and Exe groups alone. Autophagy markers, including Beclin1, the LC3B-II/I ratio, and p62, did not differ among groups. A proteomic analysis of the G/P muscle revealed that TB upregulated biological processes involved in muscle contraction and adaptation, whereas TB+Exe increased mitochondrial bioenergetic processes and, surprisingly, upregulated acute inflammatory responses, including proteins such as haptoglobin and orosomucoid-1. We conclude that combining Tat-Beclin1 and endurance training may represent a new approach to attenuate aging-related decline in physical function. New & NoteworthyWe show evidence that combining Tat-Beclin1 and endurance training (TB+Exe) resulted in greater improvements in physical function in 24-month-old male mice than either standalone therapy. We also show that TB+Exe upregulates traditional exercise-like biological processes and unexpectedly upregulates acute-inflammatory proteins (e.g., orosomucoid-1), which are thought to improve physical function in preclinical studies. Our study suggests that TB may be a new drug enhancing physical function, especially when combined with endurance training in old male mice.

physiology↗

bioRxiv2026

Optical Spectral Fingerprinting Enables Sensitive Detection of Anthracycline Chemotherapeutics in Synthetic Clinical Biofluids

Anthracycline chemotherapeutics are commonly used as frontline treatments for a wide array of cancers. However, their administration to patients results in substantial side effects, primarily cardiotoxicity, as well as myelosuppression and gastrointestinal toxicity. Current clinical management of such side effects is solely based on a lifetime dosage limit, which inhibits their anti-tumor efficacy. Many individualized factors, including age, family history of cardiovascular disease, treatment regimen, and other co-morbidities influence drug pharmacology. Despite this heterogeneity, there is no method for determining actual organ or tumor exposure to the treatment in an individual. Here, we developed an optical nanosensor array for four anthracyclines--doxorubicin, daunorubicin, epirubicin, and idarubicin. We used single-walled carbon nanotubes as the signal transducer due to their tunable near-infrared fluorescence. We screened twelve distinct ssDNA sequences paired with seven SWCNT (n,m) species at increasing concentrations of each of the four anthracyclines. The spectral responses were then used to develop machine learning-based classification models to identify different anthracycline types and concentrations. The optimized extreme gradient boosting model was able to classify high levels of each anthracycline with 100% accuracy. Concentration-based classification by PCA was performed for each anthracycline, distinguishing low ([≤] 5 {micro}M) and high (> 5 {micro}M) concentrations. Finally, we validated the sensor performance using synthetic urine and sweat. Our findings demonstrate the potential of carbon nanotube-based sensor array to measure the pharmacokinetics of anthracyclines in patients with the goal of enhancing anti-tumor efficacy and monitoring off-target toxicities.

bioengineering↗

bioRxiv2026

Metabolic trade-offs in sugar beet under drought and beet leaf miner infestation: implications for herbivore success

Increasing frequency of drought under climate change threatens crop production and intensifies pest pressures, yet the interactive effects of drought and herbivory on plant metabolism and ecological outcomes remain incompletely understood. We subjected sugar beet (Beta vulgaris) plants to moderate and high drought, alone or with infestation by the beet leaf miner (Pegomya cunicularia), and analyzed plant physiology, central metabolites, and volatile organic compound (VOC) emissions. Drought alone reduced growth and photosynthetic efficiency, while combined stress led to accentuated metabolic reprogramming, including increased amino acids and organic acids, and a concurrent suppression and alteration of VOC emissions, especially in plants affected by high drought and leaf mining. The resulting changes in VOC blends reduced plant attractiveness to ovipositing females, leading to fewer eggs laid on severely stressed plants. Contrastingly, moderate drought generated a nutrient-rich environment: larvae feeding on these plants exhibited the highest growth rates, larger pupae and adults, and increased feeding damage. High drought strongly limited both plant water content and larval development. These findings reveal a stress-dependent tradeoff between enhanced leaf nutritional quality and reduced host detectability, underscoring the importance of integrating multi-stress plant biology for future pest management and crop resilience. HighlightCombined drought and herbivory in sugar beet plant triggered stress-intensity-dependent trade-offs between leaf nutritional quality and volatile emissions, affecting beet leaf miner performance and oviposition--highlighting how multi-stress interactions shape plant-insect dynamics. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/708914v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@1d92105org.highwire.dtl.DTLVardef@70693org.highwire.dtl.DTLVardef@140dc82org.highwire.dtl.DTLVardef@14cf411_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract C_FIG

plant biology↗

bioRxiv2026

Assessing the impact of mono- and bi-allelic deletions in NRXN1 on synaptic function

Neurexin 1 (NRXN1) is an adhesion protein involved in synapse development and function. Mutations in NRXN1 are strongly linked with neurodevelopmental and psychiatric conditions. Mono-allelic NRXN1 mutations are associated with autistic traits, with increased likelihood of co-occurring intellectual disability. However, mono-allelic mutations have variable penetrance and occur in individuals without neurodevelopmental phenotypes. Conversely, bi-allelic mutations, though rarer, are associated with more stable penetrance and severe neurodevelopmental phenotypes. Human induced pluripotent stem cells (iPSC) have been used to study how mutations in NRXN1 impacts its function, with most studies focusing on monoallelic mutations. In this study, we systematically compared monoallelic and biallelic mutations in NRXN1, characterising their effects on molecular, synaptic, and functional phenotypes. Using CRISPR-Cas9, we introduced indels in NRXN1 exon 19, in an iPSC line containing inducible NGN2. These edits caused either mono-allelic or compound bi-allelic frameshift mutations. iPSCs containing either mutation robustly generated glutamatergic neurons, but these neurons displayed reduced expression of major NRXN1 isoforms. Transcriptomic profiling revealed modest gene expression changes in mono-allelic mutant neurons, whereas bi-allelic mutants exhibited extensive dysregulation of gene networks associated with neuronal maturation and synaptic function. Furthermore, synaptic phenotypes were mild in mono-allelic mutants but pronounced in bi-allelic mutant neurons. Both mono-allelic and bi-allelic mutant neurons displayed alterations in neuronal network activity and reduced peak depolarisation responses to KCl stimulation. Together, these data demonstrate that NRXN1 exhibits gene-dosage sensitivity, with bi-allelic disruption of exon 19 unmasking molecular, synaptic, and functional phenotypes that are only modest in mono-allelic mutant neurons.

neuroscience↗

bioRxiv2026

The fossil record of siliceous sponge spicules can be taken at face value

Modern sponges (Porifera) diverged by the Cryogenian, but their silicious skeletons do not appear in the fossil record until one hundred million years later, a time-span termed the "spicule gap" and thought to be a taphonomic artifact even though sponges convergently evolved siliceous spicules. Due to sponges position in animal phylogeny and important role in regulating ocean chemistry, the timing of their biomineralization has major implications for the changing tempo and mode of Earth systems as animals radiate. In a comprehensive dataset of Ediacaran and Cambrian sponges, we find that spicules are readily preserved in Cambrian environments more extreme than those of the Ediacaran. Given the convergent evolution of siliceous spicules, we find that the fossil record accurately represents when spicules first evolved in the different sponge lineages.

paleontology↗

bioRxiv2026

High-throughput SWCNT NIR-II screening enables cell and in vivo applications

Diagnostic sensor development and clinical translation lag, in part, due to a lack of rapid, high-throughput screening methodology. Optimization of high-throughput sensor development and deployment will likely help in expediting tools toward the clinic. To address this issue, we optimized high-throughput screening parameters using a near-infrared (NIR-II) plate reader attached to an external probe for in vivo testing. We assessed spectroscopy parameters to improve speed and precision in screening a single-walled carbon nanotube (SWCNT)-based optical sensor. To do so, we assessed the appropriate well plate specifications, including laser power, excitation wavelength, exposure time, and focal height parameters for SWCNT-based optical sensor development. We also used the plate reader to screen fluorescent SWCNT which were endocytosed by a macrophage cell line. We then performed NIR probe spectroscopy to assess SWCNT embedded within a methylcellulose hydrogel. Finally, we used the NIR probe to measure SWCNT center wavelength and intensity from live immunocompetent mice. We anticipate that this framework may be broadly applicable to the development of near infrared nanosensors with the potential for more rapid clinical diagnostic translation.

bioengineering↗

bioRxiv2026

Screening Molecular Recognition Element-Based SWCNT Optical Sensors for the Inflammatory Cytokine TNF-α

TNF- (Tumor Necrosis Factor) is a proinflammatory cytokine that amplifies inflammatory response and promotes leukocyte recruitment. TNF- is primarily produced by activated macrophages, among others, in response to infection, inflammation, or tissue damage. Given its central role in normal and abnormal immune responses, it is the target of several therapeutics, such as adalimumab and etanercept. TNF- is also a prognostic and diagnostic biomarker associated with Rheumatoid Arthritis, Alzheimers disease, Multiple Sclerosis, several kidney diseases, several cancers, Type 2 diabetes, sepsis, and others. Spatial quantification of TNF- in disease models can also be a powerful tool to understand the contributions of inflammatory processes to disease progression. Single-walled carbon nanotubes (SWCNT) are cylindrical carbon lattices that emit distinct near-infrared bandgap photoluminescence. In this work, we evaluated three aptamer-based sensor constructs, plus an additional two iterations of one aptamer sequence, and two antibody-based sensor constructs for TNF- that use SWCNT near-infrared photoluminescence signal transduction. Several, but not all, of these aptamer and antibody-based sensors sensitively and selectively detected TNF- in serum in a physiologically relevant range, and we found that their sensing was improved by both passivation and incorporating an exogenous quencher onto the aptamer sequence. Specifically, we found that modification of one aptamer sequence with a Black Hole Quencher induced selective detection in serum when passivated with poly-L-Lysine. This study highlights the importance, and challenges, of translating previously-validated molecular recognition elements to new detection conditions, in this case on the surface of SWCNT and in challenging serum conditions. It also validated a lead sensor construct that builds upon constructs that failed in serum. We anticipate that the sensors evaluated here will have utility in both the diagnosis and study of inflammation-driven chronic disease, while the sensor assessment framework will help drive the broader field of molecularly specific diagnostics.

bioengineering↗

bioRxiv2025

Temporal transcriptomics and molecular dynamics identify a serine-type endopeptidase as a key regulator of dengue virus infection in Aedes aegypti

The dengue virus (DENV), a major global pathogen causing over 400 million annual infections, relies on the mosquito Aedes aegypti as its primary vector. Intriguingly, A. aegypti sustains persistent DENV infection without exhibiting apparent pathology, indicating a highly adapted and regulated host-virus relationship. However, the temporal gene expression dynamics that govern this finely balanced interaction remain poorly understood. We performed a comprehensive transcriptomic analysis using 12 paired-end RNA-seq datasets from gene expression omnibus (GEO; GSE222893), comparing naive and DENV-infected A. aegypti samples at Days 1, 2, and 7 post-infection. A robust bioinformatics pipeline (STAR [->] FeatureCounts [->] DESeq2 [->] g:Profiler) was employed to identify differentially expressed genes (DEGs), explore functional annotations, and resolve temporal patterns via principal component analysis. Finally, a molecular dynamics simulation (MDS) was performed to check the molecular stability of the highly expressed gene. Our temporal analysis identified LOC5570687, a gene encoding a serine-type endopeptidase, as the most significantly differentially expressed transcript across all infection time points. Functional annotation confirmed its role in proteolysis, implicating it in the cleavage of flaviviral polyproteins, a critical step in viral replication. Principal component analysis revealed distinct transcriptional divergence at Day 1, immune modulation at Day 2, and convergence by Day 7--marking virion maturation. Downregulation of LOC5570687 in DENV-exposed mosquitoes was temporally associated with enhanced viral replication, indicating its potential role as a molecular switch between antiviral defense and viral exploitation. A 100 ns MDS was proof of the structural stability, compactness, and dynamic properties of the highly expressed protein. This study uncovers the temporally dynamic transcriptional landscape of A. aegypti during DENV infection and the serine-type endopeptidase LOC5570687 as a critical regulator of viral pathogenesis. These findings provide a molecular framework for understanding vector competence and propose the LOC5570687 as a promising target for vector-based intervention strategies to disrupt DENV transmission.

microbiology↗

bioRxiv2025

Vagal nerve stimulation alters task-evoked pupillary responses in older adults but not younger adults in a single-blind sham-controlled crossover trial

IntroductionThe locus coeruleus (LC) undergoes age-related changes and is involved in Alzheimers disease pathogenesis. Vagal nerve stimulation (VNS) may modulate LC activity and could be used therapeutically, but age-related differences in VNS responses remain unexplored. MethodsWe used a single-blind, sham-controlled, crossover design in 41 participants (21 younger, 20 older adults). Participants completed a visual oddball task with pupillometry during transcutaneous auricular VNS (verum: cymba concha; sham: earlobe) with [~]30-minute washout between conditions. ResultsOlder adults showed smaller baseline pupil diameter but larger normalized task-evoked responses than younger adults a priori. VNS produced age-specific effects: older adults demonstrated increased tonic pupil size throughout stimulation and reduced oddball-evoked responses, with stronger effects with more current. Younger adults showed no consistent VNS effects. DiscussionVNS affects LC-related physiological measures differently across age groups, with older adults showing more robust responses. These age-specific effects may reflect different baseline LC activity states.

neuroscience↗

bioRxiv2025

Oviposition behavior, nymphal development, and below-ground olfactory preference of Pentastiridius leporinus on twelve Beta vulgaris genotypes

The planthopper Pentastiridius leporinus (Hemiptera: Cixiidae) is the primary vector of two phloem-restricted prokaryotes, which can cause the disease syndrome de basses richesses (SBR) in sugar beet (Beta vulgaris L.). Heavy infestations of this insect have contributed to significant yield losses in Central Europe, but little is known about how different B. vulgaris genotypes influence vector behavior and performance. Understanding such interactions is critical for both pest management and the development of sugar beet cultivars that are less favorable to the vector. We investigated oviposition decisions, nymphal development, and belowground chemotaxis of P. leporinus using twelve B. vulgaris genotypes: eight sugar beet genotypes with contrasting SBR tolerance, two Swiss chard, and two beetroot varieties. In no-choice assays, females oviposited at similar rates on all tested genotypes, indicating broad host suitability. However, in three-choice tests, significant differences emerged, with several genotypes receiving more egg batches than the reference variety Vasco. Despite adult host preferences, nymphal survival, growth, and instar development did not differ among genotypes. In contrast, belowground olfactometer assays revealed that nymphs exhibited clear chemotactic responses: several genotypes attracted significantly more individuals than others. This represents the first documentation of chemotactic host location in P. leporinus nymphs. Our findings reveal a mismatch between adult oviposition preference and nymphal performance, a pattern not uncommon in other generalist herbivores. Both adult and nymphal behaviors were nevertheless influenced by genotype-specific traits, likely linked to plant chemistry. Identifying these cues could inform breeding strategies aimed at reducing vector attraction, thereby complementing pathogen-targeted approaches and supporting integrated management of SBR in sugar beet.

ecology↗

bioRxiv2025

Relative value learning in Drosophila melanogaster larvae

The ability to learn from past experiences to inform future decision-making is crucial for humans and animals alike. One question with important implications for adaptive decision-making is whether we learn about the absolute values of cues we encounter (how good or bad?), or about their relative values (how much better or worse than the alternative?). Humans have been shown to use relative value learning, even when it leads to suboptimal decisions. In this study, we ask whether insects employ absolute or relative value learning. Using the larvae of the fruit fly Drosophila melanogaster, we designed associative odour-taste learning experiments to distinguish both kinds of learning and find that larvae learn about the relative rather than the absolute values of both rewards and punishments, irrespective of the number and sequence of training trials. This suggests that relative value learning is a facility shared across the animal kingdom from maggots to humans, and can be accomplished even by small insect brains. Given the potential of D. melanogaster as a model organism for in-depth neurobiological analyses, our study opens up an opportunity to reveal the detailed mechanisms underlying relative value learning.

neuroscience↗

bioRxiv2025

Mixed fertilization strategies but not mono fertilization enhances the net primary productivity and quality of chili (Capsicum frutescens)

While the effects of different fertilization strategies on chili (Capsicum frutescens) cultivation have been extensively studied, the comparative assessment of mixed versus mono fertilization approaches remains still under the shadow. To address this gap, we have conducted an experiment using a completely randomized design (CRD) with five fertilization treatments along with four replications of each treatment (e.g., Leucaena leucocephala leaf litter and recommended dose of fertilizers (RFD)) to observed the effect of these treatments on plant productivity traits, NPP (net primary productivity), quality and overall yield of chili. Our results revealed that the mixed fertilization treatment (T: 100 g kg-1 L. leucocephala + [1/2] RFD) produced the highest yield (15.50 t ha-{superscript 1}), a 63.9% increase over the control. We also found that plant height (73.75 cm), number of leaves (1000.25 plant-1), number of fruits (93.00 plant-1) were higher at 60 DAT (days after transplanting) however, number of flowering (44.50 plant-1) at 45 DAT. Similarly, Above- and belowground NPP (26.47 g plant-1), vitamin C (124.65 mg 100 g-{superscript 1} ), capsaicin content (1.22 %) and SPAD chlorophyll index (48.61) were higher in T4 treatment compared to T0 treatment. Furthermore, regression results showed that ANPP and yield significantly increased with increase the number of leaves (ANPP: R{superscript 2} = 0.51, p = 0.02; Yield: R{superscript 2} = 0.34, p = 0.002) and number of flowering (ANPP: R{superscript 2} = 0.41, p = 0.014; Yield: R{superscript 2} = 0.42, p = 0.037) as well. Our results suggest that mixed fertilization enhances both productivity and quality traits in chili. Therefore, promotion of integrated (organic and inorganic together) nutrient management practices is recommended to improve yield and quality of chili.

ecology↗

bioRxiv2025

Next Generation AAV-F Capsid gene therapy rescues disease pathology in a model of Pyruvate Dehydrogenase Complex Deficiency

Pyruvate dehydrogenase complex deficiency (PDHD) is a severe mitochondrial disorder most frequently caused by pathogenic variants in PDHA1, leading to neurodevelopmental delay and early mortality, necessitating brain-targeted interventions. Using a brain-specific Pdha1 knockout mouse model, we compared intracerebroventricular delivery of AAV9 capsid and a recently described synthetic neurotropic AAV-F capsid, both expressing human PDHA1 coding sequence driven by a constitutive CAG promoter. Newborn mice received, titre matched AAV9 or AAV-F or AAV9 at ten-fold higher dose. Low-dose AAV-F and high-dose AAV9 significantly improved survival, and restored PDH enzyme activity, metabolite profiles, and brain histopathology to near wild-type levels. However, treated mice showed reduced locomotion by P100 and impaired motor function. Importantly, AAV-F achieved broad CNS transduction with minimal liver expression, outperforming AAV9 at lower dose. There results support the therapeutic potential of AAV-based gene therapy for PDHD and highlighting AAV-F as a promising capsid for efficient, CNS specific delivery.

neuroscience↗

bioRxiv2025

Longitudinal TCR repertoires in ulcerative colitis patients show features distinguishing disease states

ABSTRACT AND KEY WORDSO_ST_ABSBackgroundC_ST_ABSUlcerative colitis (UC) affects an estimated 10 million people worldwide. The exact etiology of the disease is unknown, but T cell dysregulation and aberrant activation is associated with UC--prompting research into T cell receptor (TCR) repertoires in UC patients. However, few studies have compared UC patients TCR repertoires in flare (inflamed) and remission (uninflamed) states. Moreover, this is the first dataset to our knowledge examining multiple repertoires from UC patients over time, enabling longitudinal analyses. MethodsTCR repertoires were obtained for 21 patients across multiple timepoints, yielding a total of 58 samples. Repertoires clonality, diversity, overlap, and gene usage frequencies were compared across all patients. CDR3 sequences were split into K-mers (sequences of length K), and enriched K-mers in flare and remission states were identified using GLIPH2. ResultsAlthough repertoires vary across patients, there were significant differences in the usage of 20 V{beta} genes across flare and remission states. Moreover, calculating the overlap in repertoires with enriched K-mers showed higher overlap scores than when using full TCR sequences. 622 unique enriched K-mers were identified in flare states and 495 in remission states, with only 57 overlapping between the two states. ConclusionsOverall, these results highlight the importance of analyzing V{beta} gene usage and K-mer enrichment in TCR repertoires, particularly given the lack of public clones across patient cohorts. Future studies characterizing the specific antigenic targets associated with these features will pave the way for biomarker discovery in UC. KEY MESSAGESO_LIWhat is already known? UC is a chronic condition characterized by fluctuating periods of flares and remissions, as well as aberrant immune activity. C_LIO_LIWhat is new here? TCR repertoires were obtained from UC patients colonoscopies, with multiple timepoints per patient--enabling the analysis of repertoire characteristics within and across patients over time. C_LIO_LIHow can this study help patient care? Understanding the exact immune mechanisms in UC can pave the way for biomarker discovery and advance the state of care for patients, given that current treatments are non-specific and have adverse side effects. C_LI SummaryThis article presents an analysis of T cell receptor repertoires from ulcerative colitis patient samples collected during colonoscopies, identifying genes and motifs associated with patients flare (inflamed) and remission (uninflamed) states.

immunology↗

bioRxiv2025

Hylocereus polyrhizus peel extract restricts DMBA- Croton oil induced skin carcinogenesis: An integrated in vivo and in silico approach

Hylocereus polyrhizus, locally known as red dragon fruit, is valued for its nutritional benefits including high levels of antioxidants and is gaining popularity as both a food and a medicinal plant. The present study addressed the in vivo and in silico chemopreventive potential of Hylocereus polyrhizus peel extract (HPPE) in DMBA-croton oil induced skin carcinogenic model mice. The mRNA expression level of pro-inflammatory cytokines and inflammatory mediators in tumor mass were estimated by real time-RT-qPCR. In addition, molecular docking and molecular dynamic simulation analyses were conducted on the reported compounds. In the in vivo chemopreventive activity assessment, the peel extract at 500 mg/kg was found effective in reducing total tumor number, yield, burden, incidence, and weight. Total proteins and endogenous antioxidants (GSH, SOD, CAT) levels in liver and skin tissues from mice were significantly (P<0.05) elevated. In addition, the HPPE at 500 mg/kg dose significantly reduced (P<0.05) the gene expression of pro-inflammatory cytokines such as TNF-, IL-1{beta}, IL-6, IL-18, and inflammatory mediators like TGF-{beta}1, COX-2, and NF{kappa}B. In the molecular docking studies, reported compounds including Quercimeritrin, Rutin, and Kaempferol 3-O-{beta}-D-glucopyranoside were identified as the top-performing compounds, with a docking score of - 7.4, -7.1 and -7.0 kcal/mol against TGF-{beta}1 protein. This indicates stronger binding interactions compared to vincristine (-5.3 kcal/mol). In drug-likeness assessment, all compounds demonstrated the most favourable ADMET and pharmacokinetic profile. Furthermore, MDS data showed greater dynamic stability for Kaempferol 3-O-{beta}-D-glucopyranoside and Rutin, while vincristine exhibited higher fluctuations. The results suggest that HPPE may serve as a potential inhibitor of skin carcinogenesis through upregulating endogenous antioxidants as well as suppressing different proinflammatory and inflammatory cytokines. Quercimeritrin, Rutin, and Kaempferol 3-O-{beta}-D-glucopyranoside might be the probable leads responsible for this chemopreventive activity. Highlights{checkmark} Hylocereus polyrhizus peel extract (HPPE) demonstrated notable chemopreventive potential against skin cancer. {checkmark}HPPE significantly increased endogenous antioxidants (GSH, SOD, CAT) in liver and skin tissues, suggesting enhanced cellular defense mechanisms. {checkmark}Gene expression of pro-inflammatory cytokines (TNF-, IL-1{beta}, IL-6, IL-18) and inflammatory mediators (TGF-{beta}1, COX-2, NF{kappa}B) were notably suppressed by HPPE. {checkmark}Quercimeritrin (CID: 5282160) demonstrated strong binding to TGF-{beta}1 with a docking score of -7.4 kcal/mol, outperforming vincristine (-5.3 kcal/mol). {checkmark}Kaempferol 3-O-beta-D-glucopyranoside (CID: 5282102) and rutin (CID: 5280805) showed the best ADMET, pharmacokinetic profiles, and molecular stability, supporting their potential as lead compounds.

cancer biology↗