- BioRxiv Biochemistry
- BioRxiv Bioinformatics
- BioRxiv Biophysics
- BioRxiv Cancer Biology
- BioRxiv Pharmacology and Toxicology
- BioRxiv Systems Biology
- BioRxiv Zoology
- by Ranga, U., Saini, C., Roychowdhury, A., Gaikwad, S., Gohil, Y., Panchapakesan, A., Das, P., Thiyagarajan, S., Ramachandra, M., Samajdar, S., Manjithaya, R.HIV-1 latency remains a central obstacle to curing infection, and current latency-modulating agents (LMAs) suffer from poor specificity and inconsistent efficacy. To enable discovery of small molecules (SMs) that directly target the viral master transcriptional regulatory circuit (MTRC), we developed a highly stringent, dual-reporter high-throughput screening (HTS) assay based on a natural HIV-1 subtype C long terminal repeat (LTR) variant, LRhR-HC, which exhibits markedly reduced transcriptional noise and a high activation threshold. We engineered Jurkat cells to stably harbour two […]
- by Xiao, X., Ciudin, A., Simo, R., Aparicio, C., Palomino-Schätzlein, M., Raul Herance, J.In myocardial insulin resistance (mIR), insulin fails to appropriately stimulate myocardial glucose uptake. Identifying biomarkers of early-stage mIR is crucial to halt its progression with appropriate treatment and lifestyle interventions. In this context, we explore, for the first time, specific gut bacteria and fecal and plasma metabolic signatures associated with mIR. Forty-two T2DM patients were divided into two groups, mIR patients and patients with myocardial insulin sensitivity (mIS), depending on their myocardial glucose uptake measured with 18F-FDG PET during the […]
- by Yagoubat, A., Crobu, L., Stanojcic, S., Kuk, N., Sarrazin, A., Blanchard, M.-P., Bastien, P., Leveque, M. F., Berry, L., Sterkers, Y.Trypanosoma brucei is a divergent eukaryote parasite responsible for neglected tropical diseases in human and animals, sleeping sickness or human African trypanosomiasis and nagana respectively. Besides scientific interest, understanding the specific features of its biology has medical and economical relevance. Nuclear pore complexes (NPCs) are large multiprotein channels embedded in the nuclear envelope that regulate nucleo-cytoplasmic transport. Beyond this role, NPCs also participate in essential nuclear processes such as chromosome segregation, transcription, and cytokinesis. Here, we showed that Myosin-like protein-1 […]
- by Santos-Santiago, J. A., Gadda, N., Tamayo, R.Many Clostridioides difficile strains can form two colony morphotypes: rough and smooth. The rough and smooth morphotypes differ in multiple phenotypes, including cell length and chaining, motility, biofilm production, and virulence in the hamster model of C. difficile infection (CDI). Colony morphology undergoes phase variation and is determined by the ON/OFF expression of cmrRST, which encodes a signal transduction system. Here, we test the hypothesis that differences in colony morphology and the associated phenotypes influence pathogenesis and the host response […]
- by Hu, Q., Yang, W., Yu, Y., Yi, R., Zhang, Y., Duan, L., Wang, L., Li, F., Zhang, K., Gong, Q., Li, S.The human RNA m5C methyltransferase NSUN2 catalyzes site-specific cytosine methylation across diverse RNA substrates and thereby regulates a wide range of biological and physiological processes. However, the molecular basis by which NSUN2 achieves broad substrate recognition while maintaining catalytic specificity has remained unclear. Here we determine structures of human NSUN2 in both substrate-free and substrate-bound states using X-ray crystallography and cryo-electron microscopy. Structures of NSUN2 in complex with multiple tRNA substrates reveal a structure-first, sequence-tolerant strategy in which NSUN2 actively […]
- by Chimeh, U. S., Rogers, M. C., Aylor, D. L.Gene-environment interaction (GxE) studies comprise a very small part of the genetics or environmental epidemiology literature, and most existing studies are in populations of European ancestry. We made predictions about GxE in global populations by combining existing GxE studies with genetic data from the 1000 Genomes Project (1kGP), which captured genetic variation in diverse populations worldwide. We modeled susceptibility of 1kGP populations to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) exposures based on variation in the aryl hydrocarbon receptor (AHR) gene. The […]
- by Chuesaard, T., Chaimanee, V., Jobsri, J., Pukklay, P.Propolis, a resinous substance produced by Apis mellifera, is rich in polyphenols and flavonoids and exhibits diverse biological activities, including antioxidant and antimicrobial effects. This study aimed to characterize the chemical composition of Thai propolis and evaluate its free radical scavenging activity. Ethanolic (EEP) and aqueous (WEP) extracts were prepared and analyzed. Gas chromatography-mass spectrometry (GC-MS) identified major constituents of EEP, including phenolic acids, flavonoids, and sugars. Antioxidant activities were assessed using DPPH and hydrogen peroxide scavenging assays. EEP exhibited […]
- by Vargas Urdaneta, C. D., Barros, M. T.Extrusion bioprinting is moving from proof-of-concept demonstrations toward repeatable, manufacturing-style workflows, but the nozzle remains a persistent bottleneck. Inside compact, opaque channels, bioinks experience strong geometric forcing that sets the local shear environment for cells, the pressure demand on the printer, and the uniformity of deposition. Multi-outlet nozzles are attractive because they promise higher throughput by splitting one feed into parallel filaments, yet in practice they often suffer from uneven outlet delivery and junction-driven shear hotspots. As a result, nozzle […]
- by Thorseth, M.-L., Johansen, A. Z., Baker, K. J., Carretta, M., Roemer, A. M. A., Jensen, C., Jurgensen, H. J., Linder, H., Czajkowski, N. K., Kuczek, D. E., Fjaestad, K. Y., Engelholm, L. H., Willumsen, N., Kim, K., Andersen, M. H., Groentved, L., Madsen, D. H.Solid tumors are often characterized by a dense extracellular matrix (ECM) that contributes to increased tissue stiffness. Collagen type I is the main component of the ECM and its abundance in tumors is frequently associated with poor prognosis. In vitro studies suggest that a high collagen density promotes tumor invasion and modulates immune responses. However, recent in vivo findings have questioned the pro-tumorigenic role of collagen type I. In this study, we investigate the role of collagen for pancreatic tumor […]
- by Mugglestone, S., Ganis, G., Hughes, S.High-frequency stimulation (HFS) is a human surrogate model of secondary hyperalgesia and a key experimental tool for understanding the mechanisms and modulation of central nociceptive pathways. An emerging area of research focuses on the role of top-down endogenous analgesic systems during secondary hyperalgesia development. However, the test-retest reliability of the early temporal changes in sensitivity are poorly understood. In the present study, we investigated the between-session reliability of the early temporal dynamics and late-phase expression of HFS-induced changes in mechanical […]
- by Shahbabaie, A., Abdelmotaleb, M., Kocatas, H., Niemann, F., Antonenko, D., Floeel, A., Meinzer, M.Background: Neural network effects of transcranial direct current stimulation (tDCS) are poorly understood. Here, we introduce an empirically informed, multimodal functional magnetic resonance imaging (fMRI) based framework suited for guiding stimulation target selection and hypothesis-based data analysis in focal tDCS-fMRI studies. Methods: We illustrate our approach using data of 37 healthy individuals (19 females; mean +/- SD age = 25.8 +/- 5.9) recruited from a multicenter tDCS-fMRI study (www.memoslap.de/en/home/). Participants completed resting-state (RS- and task-fMRI (object-location memory, OLM, or associative […]
- by Adibpour, P., Karolis, V., Tomazinho, I., Gallo, D., Dacosta, C., St Clair, K., Norman, W., Colford, K., Aitken, F., Kabdebon, C., O'Muircheartaigh, J., Arichi, T.The ability to detect sensory regularities and their violations (i.e. deviance) is fundamental for learning and the orientation of attention across the lifespan. This starts from the prenatal period, where the environment is rich in regular patterns and deviations of auditory stimulation which likely provides the basis for the emergence of early learning capacities. Following birth, EEG recordings of brain activity have demonstrated that neonates detect violations of regularity and show a robust mismatch response to deviant auditory stimuli. However, […]
- by Mormann, F., Niediek, J., Reber, T. P., Bausch, M., Schwimmbeck, F., Gast, H., Coenen, V. A., Bostroem, J., Elger, C. E.How do our brains manage to store our everyday experiences into memory? Neurons in the human temporal lobe that respond to the concept of an individual person or object have been shown to provide the semantic building blocks for episodic memory. Recording from 1433 neurons in neurosurgical patients who learned a story involving specific concepts, we found reactivation of neurons representing these concepts during slow-wave sleep after learning. Concept neurons were conjointly reactivated, particularly during sharp-wave ripples, with time lags […]
- by Murali Mahadevan, H., Rehailia, A. E., Pastor, A. M., Geelhaar, I. M. C., Roman-Albasini, L., Feederle, R., Brill, M. S., Misgeld, T., Harbauer, A. B.Hitch-hiking of transcripts on organelles, including mitochondria, has emerged as a common pathway to transport mRNAs into the axon to enable their local translation. However, the extent of mitochondrial mRNA association in vivo has not been established. Here we report the landscape of mitochondrial mRNA association in two nerve tissues, the retinal ganglion cell derived optic nerve and the motor neuron derived part of the sciatic nerve. This revealed astonishing tissue diversity between mitochondria associated mRNAs that can partly be […]
- by Bhalla, S., Gulsuyu, B., Sanchez, D., Ross, J. M., Arul, S., Gopinadhan, A., Ozturk, M., Mukhtar, T., Augustin, J. J., Wang, J. C., Kim, J., Kim, C. N., Oten, S., Rosen, Y., Barnabei, J. M., Letchuman, V., Weinsheimer, S., Kim, H., Crouch, E. E., Chang, E. F., Haussler, D., Teodorescu, M., Kriegstein, A. R., Nowakowski, T. J., Winkler, E. A.Human cortical development involves the coupling of neurogenesis and cerebrovascular growth. However, interactions between neural and vascular cells are largely missing in most brain organoids, which are crucial models for studying neurodevelopment and disease. Here, we establish vascularized cortical assembloids (vCAs) by fusing mesoderm-derived vascular organoids (VOs) with cortical organoids (COs). vCAs self-assemble lumenized networks of endothelial cells, pericytes, and perivascular fibroblasts that acquire blood-brain barrier (BBB) specialization and arteriovenous specification in vitro. Single-cell RNA-sequencing and immunofluorescence imaging revealed that […]
- by Woods, D. P., Adams, G., Mozumder, R., Dang, W., Chen, A. Y., Constantinidis, C., Gonzales, D. L.Neurophysiological recordings from non-human primates (NHPs) have traditionally relied on rigid microelectrode arrays made from stainless steel or silicon. While these devices enable high-quality recordings, a fundamental mechanical mismatch between rigid materials and soft brain tissue leads to inflammation, gliosis, and signal instability. In particular, brain micromotion causes continuous drifting of neurons relative to fixed electrodes, compromising single-unit tracking during both chronic and acute recordings. Flexible, penetrating electrodes offer a promising solution, but their adoption in NHPs has been hindered […]
- by Waters, R. C., Gore, I. R., Brown, C. J., Skweres-Gilmartin, A. L., Rathaur, A. B., Gould, E.Early-life adversity has a lasting negative impact on social behavior in both humans and rodents. Sex differences exist in functional outcomes of postnatal stress, but underlying mechanisms remain incompletely explored. Using the limited bedding and nesting paradigm, a mouse model of developmental scarcity, we found sex differences in social behavior with adult males showing impaired social recognition and adult females showing intact social recognition with enhanced social novelty preference. Perineuronal nets, specialized extracellular matrix structures, are known to inhibit developmental […]
- by Razmi, N., Dai, X. C., Bakst, L., Nassar, M.People rapidly recalibrate their expectations about the world in the face of surprising observations. This recalibration should depend on the temporal structure of the environment, however how people should and do learn temporal structures remains unknown. To examine this gap, we developed a Bayesian model that infers temporal structure of the environment directly from observations and makes accurate predictions across qualitatively different environments. We tested predictions of our model in an online behavioral study in which participants predicted outcomes generated […]
- by Karjalainen, S., Leukkunen, J., Kullberg, T., Parviainen, T.A central challenge in supporting learning and designing learning environments is to understand individual differences in learning experiences. However, despite growing interest in examining learning experiences in naturalistic contexts, studies employing multimethod and hyperscanning approaches remain scarce. In this study, electroencephalography (EEG) and electrocardiography (ECG) were combined to measure brain activity, heart rate, and heart rate variability simultaneously during authentic learning situations in aviation and forestry. We investigated how students and instructors cardiac and brain activity varied across different phases […]
- by Kana, O. Z., Postupna, N., Agrawal, A., Long, B., Travaglini, K., Gabitto, M., Lai, H.-Y., Mahoney, J. T., Xiao, M., Bajwa, T., Hulsey-Vincent, H., Oyaizu, S. L., Mena, G. E., Hong, J., Gelfand, E. C., Kaplan, E. S., Ariza, J., Smith, K. A., McMillen, D. A., Chakka, A. B., Goldy, J., Melief, E. J., Barta, S., Oyama, A., Ruiz, A., Pom, C. A., Ayala, A., Bixby, M., Huang, A., Martin, N., Cuevas, N. V., Olsen, P., Nagra, J., Chakrabarty, R., Tieu, M., Cardenas, T., Torkelson, A., Bertagnolli, D., Guzman, J., Ferrer, R., Waters, J., Grabowski, T. J., Crane, P. K., Gatto, N. M., Miller, J. A., HodgAmyloid-beta presence in the caudate nucleus (Ca) partially defines Thal stage III in Alzheimer's disease (AD), but little is known about AD's cellular impact on the region. Leveraging a public basal ganglia taxonomy of cellular populations, we generated a cellular-resolution atlas of AD-associated pathological changes in Ca. Unlike cortex, we found that Ca AD pathology is dominated by two key features: phosphorylated tau (pTau)-containing neuropil threads enriched near oligodendrocytes in white matter tracts and amyloid-beta diffuse plaques enriched in gray […]