Biology subjects

Nakamura, T.

Publications and source records attributed to Nakamura, T..

At least 55 records · Page 3Linked to original sources

bioRxiv2024

Evolutionary conserved reciprocal senescence and tumor suppressor signals limit lifetime cancer

Cellular senescence features a durable exit from the cell cycle triggered by stress or carcinogens. The INK4 locus is inactivated in various cancers, yet in senescence, p16Ink4a is activated. Whether senescence is tumor-suppressing or -promoting remains a conundrum. We discovered an evolutionally-conserved Vertebrata INK4-homolog. This ink4ab triggers senescence upon oxidative- and/or carcinogenic-stress. Adult Ink4ab-deficient animals failed to activate senescence and developed spontaneous cancers. Combined Ink4ab and Tp53 deficiency revealed a reciprocal senescence and apoptosis regulation, controlling tumorigenesis, including retinoblastoma. INK4-hematopoietic-deficient mice exhibited p19Arf-dependent enhanced senescence-like phenotypes, uncontrolled cell proliferation, defective stem cell differentiation, and splenomegaly, with single-splenocytes spatially-enriched in senescence-associated secretory profiles. Our studies reveal the evolutionary origin of paradigms co-regulating senescence and tumor suppression and offer strategies to exploit these reciprocal pathways for cancer prevention and therapy.

cancer biology↗

bioRxiv2024

Exploring Organ-Specific Extracellular Vesicles in Metabolic Improvements Following Bariatric Surgery in Adolescents with Obesity

Aims/hypothesisVertical sleeve gastrectomy (VSG) leads to significant metabolic improvements, though the underlying molecular mechanisms are not yet fully understood. Emerging evidence suggests that small extracellular vesicles (sEVs) contribute to metabolic improvements post-VSG; however, it is still unclear which organ-specific sEV correlate with various metabolic parameters and how they exert these effects. The study aimed to establish the role of organ-specific sEVs in the metabolic improvements associated with VSG. MethodsDemographic, anthropometric, and blood samples were collected pre-VSG and 3- and 6-month post-VSG in adolescents with obesity. Blood samples were utilized to measure metabolic parameters and to isolate sEVs. sEV RNAs were analyzed via small RNA sequencing then bioinformatics analyses. ResultsA significant reduction in mRNA cargo from liver-specific genes was observed post- VSG, whereas adipose tissue- or skeletal muscle-specific genes showed no such reduction. Liver-derived RNA correlated with BMI, leptin, and resistin, while adipose-derived RNA correlated with leptin. Analysis of delta values (post-minus pre-surgery) revealed that adipose-derived RNA cargo correlated with markers of liver damage and HOMA-IR, whereas liver-derived RNA cargo correlated with BCAAs. ConclusionsVSG modulates the EV system in the liver and adipose tissue. Liver-derived sEVs appear to regulate adipose metabolism, while adipose-derived sEVs are associated with liver function, suggesting a dynamic crosstalk between these tissues through sEVs that shapes systemic metabolic outcomes. Research in ContextO_ST_ABSWhat is already known about this subject?C_ST_ABS- Vertical sleeve gastrectomy (VSG) is the most performed bariatric surgery, leading to significant metabolic improvements. - Small extracellular vesicles (sEVs) and their RNA cargo play a crucial role in metabolic regulation. - Levels of branched-chain amino acids (BCAAs), which are known metabolic regulators, decrease following bariatric surgery. What is the key question?- How do sEVs, BCAA and other metabolic molecules interact to drive the significant metabolic improvements observed after VSG? What are the new findings?- The levels of liver-specific RNA cargo in sEVs decrease after VSG and are correlated with BMI and leptin levels at 6 months post-surgery, suggesting a potential role for liver-specific RNA cargo in the metabolic benefits associated with VSG. - Changes in BCAA levels from baseline to 6 months post-surgery correlate with changes in liver-specific RNA cargo in sEVs, indicating liver-specific RNA cargo in sEVs may influence metabolic parameters through BCAA modulation. - Changes in the level of adipose-specific RNA cargo in sEVs from baseline to 6 month post-surgery correlate with changes HOMA-IR and ALT levels. How might this impact on clinical practice in the foreseeable future?The study identifies liver- and adipose-derived sEV RNA cargo as potential targets for non-invasive therapies that could replicate the metabolic benefits of VSG. While further investigation is needed, these findings suggest a tentative alternative for adolescents facing obesity who may be ineligible or reluctant to undergo bariatric surgery.

cell biology↗

bioRxiv2024

Induction of cell death in U2OS human cancer cells by Ta3N5

Photocatalysts are widely used in modern society, with their applications extending into the field of medicine. Ultraviolet irradiation is used for photocatalysis to generate reactive oxygen species (ROS). Ta3N5 has attracted attention as a next-generation photocatalyst because it produces ROS upon exposure to visible light. Although ROS generation using visible light irradiation is useful in the field of life sciences, the toxicity of Ta3N5 remains unknown. In the present study, we evaluated the cytotoxicity of Ta3N5 using U2OS cells in terms of the intensity, irradiation time, and wavelength of light and Ta3N5 dose. We also investigated the mode and mechanism of cell death induced by Ta3N5. Cytotoxicity increased with increasing light intensity, irradiation time, and Ta3N5 dose. In contrast, high-intensity blue light irradiation induced cytotoxicity with or without Ta3N5, indicating that irradiation to green and red lights, which can selectively toxify Ta3N5-treated cells, is more useful than irradiation to blue light. Moreover, Ta3N5 induced secondary necrotic death of U2OS cells. These results suggest that Ta3N5 can be used as a photocatalyst in medical and life science fields.

cell biology↗

bioRxiv2024

Engineering rice Nramp5 modifies cadmium and manganese uptake selectivity using yeast assay system

Cd is a seriously hazardous heavy metal for both plants and humans and international regulations regarding Cd intake have become stricter in recent years. Three-quarters of the Cd intake comes from plant-based foods, half of which comes from cereals. Therefore, it is anticipated that the Cd uptake efficiency of cereals, including rice, a staple crop in Asia, will be reduced. Natural resistance-associated macrophage protein (Nramp) is the principal transporter involved in the uptake and translocation of metal ions in various plants. In rice, OsNramp5 is a transporter of Mn, which is an essential micronutrient for plant growth, and is responsible for Cd uptake. Although several attempts have been made to engineer the metal uptake characteristics of OsNramp5, in many cases, both Cd and Mn uptake efficiencies are impaired. Therefore, in this study, we engineered OsNramp5 to reduce Cd uptake while retaining Mn uptake efficiency for low-Cd rice production. OsNramp5 was engineered using amino acid substitution(s) at the 232nd Ala and 235th Met of OsNramp5, which have been suggested to be key residues for metal uptake efficiency and/or selectivity by structural analyses of bacterial Nramps. The metal uptake efficiency was first analyzed using a yeast model assay system. Several mutants showed less than 8.6% Cd and more than 64.1% Mn uptake efficiency compared to the original OsNramp5. The improved metal uptake characteristics were confirmed by direct measurement of the metal content in the yeast using inductively coupled plasma optical emission spectroscopy. Notably, several mutants reduced Cd uptake efficiency to the background level while retaining more than 64.7% Mn uptake efficiency under conditions mimicking heavily polluted soils in the world. In addition, computational structural modeling suggested requirements for the spatial and chemical properties of the metal transport tunnel and metal-binding site, respectively, for Cd/Mn uptake efficiency.

plant biology↗

bioRxiv2024

Epilepsy protein myoclonin1 interacts with inositol 1,4,5-trisphosphate (IP3) receptor and reduces Ca2+ store in endoplasmic reticulum

Mutations of EFHC1 gene have been identified in patients with epilepsies including juvenile myoclonic epilepsy (JME), and mice with Efhc1 deficiency exhibit epileptic phenotypes. Myoclonin1 protein encoded by EFHC1 is not expressed in neurons but in cells with motile cilia including those of choroid plexus and ependymal cells which form an epithelial layer lining brain ventricles. Detailed molecular basis of epilepsies caused by EFHC1 mutations, however, remain unclear. Here we report that myoclonin1 is well co-expressed with inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) at choroid plexus and ependymal cells and these two proteins bind each other. Endoplasmic reticulum (ER) of Efhc1-deficient mouse (Efhc1-/-) cells contains larger levels of calcium ions (Ca2+) than that of wild-type (WT) mice, and IP3-induced Ca2+ release (IICR) from ER is higher in Efhc1-/- cells than that of WT. Furthermore, myoclonin1 revealed to interact with PRKCSH, also known as a protein kinase C substrate 80K-H which interacts with IP3R1. Myoclonin1 further binds to IP3R2 and IP3R3. Thus, our results indicate that myoclonin1 modulates ER-Ca2+ homeostasis through interactions with IP3Rs and PRKCSH, and suggest that myoclonin1 dysfunctions cause impaired intracellular Ca2+ mobilization. Its relevance to the epileptic phenotypes of patients with EFHC1 mutations is now of interest.

physiology↗

bioRxiv2024

Spatial Clustering Analysis with Spectral Imaging-based Single-Step Multiplex Immunofluorescence (SISS-mIF)

Precision medicine, based on spatial biology, is crucial for accurately diagnosing cancer and predicting drug responses. Here, we introduce the Spectral Imaging-based Single-Step Multiplex Immunofluorescence (SISS-mIF) technique, utilizing hyperspectral imaging to capture fluorescence spectra simultaneously. This approach optimizes tissue autofluorescence spectra for each image automatically, allowing the use of fluorescent direct-labeled antibodies for multicolor staining in a single step. Unlike conventional methods, the images are generated as standardized intensity independent of capture conditions, enabling consistent comparisons under different imaging conditions. This technique allows the detection of CD3, CD5, and CD7 in T-cell lymphoma on a single slide. The use of fluorescent direct-labeled antibodies enables triple staining of CD3, CD5, and CD7 without cross-reactivity, maintaining the same intensity as single stains. Furthermore, we developed a joint Non-Negative Matrix Factorization-based Spatial Clustering Analysis (jNMF-SCA) with a modified spectral unmixing system, highlighting its potential as a supportive diagnostic tool for T-cell lymphoma.

pathology↗

bioRxiv2024

PRDX6 dictates ferroptosis sensitivity by directing cellular selenium mobilization

Selenium-dependent glutathione peroxidase 4 (GPX4) is the guardian of ferroptosis and prevents unrestrained (phospho)lipid peroxidation by directly reducing phospholipid hydroperoxides (PLOOH) to their corresponding alcohols. However, it remains unclear whether other phospholipid peroxidases can also contribute to ferroptosis prevention, albeit to a varying degree. Here we show that cells lacking GPX4 still exhibit substantial PLOOH reduction capacity, arguing for the presence of alternative PLOOH peroxidases. By scrutinizing potential candidates, we showed that while overexpression of peroxiredoxin 6 (PRDX6), a thiol-specific antioxidant enzyme with reported PLOOH-reducing activity, failed to prevent ferroptosis, its genetic loss markedly sensitizes cancer cells to ferroptosis. Mechanistically, we uncover that PRDX6 facilitates intracellular selenium handling, which is crucial for selenium incorporation into selenoproteins, including GPX4. Consequently, PRDX6 modulates GPX4 expression, thereby dictating the sensitivity of cells to undergo ferroptosis. Our study highlights PRDX6 as a critical factor in ferroptosis prevention by directing cellular selenium mobilization.

cell biology↗

bioRxiv2024

Antifungal potency of terbinafine as a therapeutic agent against Exophiala dermatitidis in vitro

SynopsisO_ST_ABSBackgroundC_ST_ABSExophiala dermatitidis (E. dermatitidis), which causes skin infections or respiratory diseases, is occasionally fatal in immunocompromised patients. ObjectivesHere, we report the unique antifungal potency of terbinafine (TRB), which targets squalene epoxidase, against E. dermatitidis (SQLEED) using various in vitro approaches. MethodsBased on the human SQLE crystal structure, we created a structure model of SQLEED using SWISS-MODEL and determined the best-fitting model of TRB to the SQLEED. The versatile antifungal activities, including fungicidal activity, biofilm inhibition, biofilm eradication activity, and the combination effect of TRB, posaconazole (PSC), and amphotericin B (AmB) with great antifungal potency against E. dermatitidis were evaluated using crystal violet and cell viability assay. ResultsClinically isolated E. dermatitidis increased most vigorously at 30{degrees}C but decreased at 40{degrees}C. E. dermatitidis hyphae elongated and attached to a cell scaffold, forming a membrane-like biofilm that was distinct from the cell-free biofilm. In the binding model, TRB formed an H-bond with Y102 and was surrounded by key amino acid residues of SQLEED corresponding to TRB-resistant mutations in Trichophyton rubrum, showing an appropriate interaction. Among TRB, PSC, and AmB with potent antifungal activities, TRB and PSC showed more potent antibiofilm activities than AmB. In addition, TRB and PSC exhibited residual potency without incubation against E. dermatitidis, decreasing the growth at lower concentrations than AmB. In contrast, AmB exhibited strong time-dependent killing and eradication activities. The combination of TRB and PSC was more effective than that of TRB and AmB or PSC and AmB in vitro. ConclusionsAlthough the tissue migration of TRB must be considered, these data suggest that TRB and PSC may be useful agents and a potent combination in severely immunocompromised patients with refractory and systemic E. dermatitidis infection.

microbiology↗

bioRxiv2024

Nestmate discrimination expels intrusion of intraspecific cheaters in an ant

Social animals utilise various communication methods to organise their societies. In social insects, nestmate discrimination plays a crucial role in regulating colony membership. Counter to this system, socially parasitic species employ diverse behavioural and chemical strategies to bypass their hosts detection. In this study, we tested whether such parasitic adaptations could be detected in the incipient stage of social parasitism that is observed as intraspecific phenomena in some social insects. The Japanese parthenogenetic ant Pristomyrmex punctatus harbours a genetically distinct cheater lineage which infiltrates and exploits host colonies. We found that intrusion of this intraspecific social parasite was defended by nestmate discrimination of host colonies without any behavioural strategies specialised in social parasitism. Most of the cheaters were eliminated through aggressions by host workers that are typically observed against non-nestmates, resulting in a low intrusion success rate for the cheaters (6.7%). This result contrasts with the expectation from interspecific social parasitism but rather resembles the intraspecific counterpart reported in Cape honeybees (Apis mellifera capensis), illustrating the role of nestmate discrimination against the intrusion of intraspecific social parasites.

animal behavior and cognition↗

bioRxiv2024

A novel genetic mouse model of fatal aortic dissection reveals massive inflammatory cell infiltration in the thoracic aorta

BackgroundAortic dissection (AD) is the separation of medial layers of the aorta and is a major cause of death in patients with connective tissue disorders such as Marfan syndrome. However, molecular triggers instigating AD, its temporospatial progression, and how vascular cells in each vessel layer interact and participate in the pathological process remain incompletely understood. To unravel the underlying molecular mechanism of AD, we generated a spontaneous AD mouse model. MethodsWe incorporated a novel missense variant (p.G234D) in FBN1, the gene for fibrillin-1, identified in a non-syndromic familial AD patient into mice using CRISPR/Cas9 system. We performed histopathological analyses of the aortic lesions by histology, immunofluorescence staining, electron microscopy, synchrotron-based imaging and single-cell (sc)RNA-sequencing. Biochemical analysis was performed to examine the binding capacity of mutant human FBN1G234D protein to latent Tgf{beta} binding proteins (LTBPs), and signaling pathways in the mutant aortic wall were examined by western blot analysis. Results50% of the Fbn1G234D/G234D mutant mice died within 5 weeks of age from multiple intimomedial tears that expanded longitudinally and progressed to aortic rupture accompanied by massive immune cell infiltration. scRNA-sequencing, validated by immunostaining, revealed a significant increase in MHC class II-positive pro-inflammatory macrophages and monocytes at the site of intima tears with upregulation of MMP2/9 and marked disruption of elastic lamina. Subendothelial matrices, such as type IV collagen and laminin, expanded into the medial layer, where fibronectin expression was highly upregulated. Fbn1G234D/G234D endothelial cells exhibited altered mechanosensing with loss of parallel alignment to blood flow and upregulation of VCAM-1 and ICAM-1, all of which likely contributed to the infiltration of immune cells. Biochemically, FBN1G234D lost the ability to bind to latent TGF{beta} binding protein (LTBP)-1, -2, and -4, resulting in the downregulation of TGF{beta} signaling in the aortic wall. ConclusionsWe show that dynamic interactions involving endothelial cells (ECs) and macrophages/monocytes in the intima, where the ECM microenvironment is altered with the reduced TGF{beta} signaling, contributes to the initiation of AD. Our novel AD mouse model provides a unique opportunity to identify target molecules involved in the intimomedial tears that can be utilized for development of therapeutic strategies.

pathology↗

bioRxiv2024

Atlas of Cynomolgus Macaque Hematopoiesis

Self-renewal and differentiation are inherent properties of hematopoietic stem cells (HSCs) that are necessary to support hematopoiesis; however, the underlying mechanisms, especially in human, remain unclear. Here, using the cynomolgus macaque as a surrogate model, we develop a new gating strategy to isolate with high purity transplantable cynomolgus HSCs and generated a single-cell transcriptomic map of cynomolgus HSCs and progenitor cells -- that covering gestational periods previously not analyzed in human. We show that hematopoietic cells from the late-1st to early-3rd trimester fetal liver and late-2nd trimester and thereafter bone marrow have repopulating potential, closely mimicking humans. Unexpectedly however, we found unlike in human, cynomolgus HSCs express CD38 but not CD33, indicating that these cellular counterparts are molecularly distinct. Our transcriptomic analysis reveals the presence of a direct differentiation pathway from HSCs to megakaryocyte lineages, lineage-primed multipotent progenitors and also identified putative HSC surface markers. Taken together, our comprehensive dataset highlights not only the utility of cynomolgus monkeys as model systems to study hematopoiesis but also their potential for translational applications.

cell biology↗

bioRxiv2024

Systematic Discovery of Phage Genes that Inactivate Bacterial Immune Systems

Bacteria have developed numerous defense systems to counter phage infections. However, the extent to which phages possess countermeasures against these defense systems remains unclear. In this study, we combined a phage gene knockout library with a defense system library to analyze the mechanisms by which phages counteract bacterial defense systems. After attempting gene deletions of 105 open reading frames (ORFs) in the DruSM1 phage ({Phi}DruSM1), we successfully generated 73 different ORF knockout phages. By infecting this library with bacteria harboring defense system expression plasmids, we identified inactivators of Druantia type I (Druad1), Brex type I, AVAST type III, Sir2+HerA, DUF4297+HerA, and hhe, as well as an activator of Retron Ec86, in a single phage genome. Synthetic phages incorporating Druad1 effectively eradicated Escherichia coli harboring the robust Druantia type I defense system by altering DNA methylation at m6A sites of the phage. This study highlighted the prevalence of various antidefense mechanisms employed by phages to overcome bacterial defense systems.

microbiology↗

bioRxiv2024

Morphological Study of Left-right Head Asymmetry in Doubledaya bucculenta (Coleoptera: Erotylidae: Languriinae)

Left-right asymmetry in paired organs is well-documented across various species, including the claws of fiddler crabs and snail-eating snakes dentition. However, the mechanisms underlying these asymmetries remain largely elusive. This study investigates Doubledaya bucculenta (Coleoptera: Erotylidae), a lizard beetle species known for pronounced left-sided asymmetry in adult female mandible and gena. Given that insect mouthparts comprise multiple functionally significant appendages, we aimed to clarify the degree of asymmetry extending beyond the mandibles and genae. Phenotypic morphology was assessed through trait measurement and asymmetry index calculations. Our detailed morphometric analyses revealed left-longer asymmetry not only in mandibles and genae but also in maxillae and labium. Notably, the degree of asymmetry in other mouthparts was generally less pronounced compared to outer mandibles, suggesting a potential influence of left mandible development on other mouthparts. Additionally, male mandibles exhibited region-specific asymmetry, potentially indicative of constrained evolutionary adaptations. This study enhances a comprehensive understanding of adult phenotype morphology and offers insights into the developmental basis of asymmetrical mouthparts.

zoology↗

bioRxiv2024

EVOLUTIONARY CO-OPTION OF AN ANCESTRAL CLOACAL REGULATORY LANDSCAPE DURING THE EMERGENCE OF DIGITS AND GENITALS

The transition from fins to limbs has been a rich source of discussion for more than a century. One open and important issue is understanding how the mechanisms that pattern digits arose during vertebrate evolution. In this context, the analysis of Hox gene expression and functions to infer evolutionary scenarios has been a productive approach to explain the changes in organ formation, particularly in limbs. In tetrapods, the transcription of Hoxd genes in developing digits depends on a well-characterized set of enhancers forming a large regulatory landscape1,2. This control system has a syntenic counterpart in zebrafish, even though they lack bona fide digits, suggestive of deep homology3 between distal fin and limb developmental mechanisms. We tested the global function of this landscape to assess ancestry and source of limb and fin variation. In contrast to results in mice, we show here that the deletion of the homologous control region in zebrafish has a limited effect on the transcription of hoxd genes during fin development. However, it fully abrogates hoxd expression within the developing cloaca, an ancestral structure related to the mammalian urogenital sinus. We show that similar to the limb, Hoxd gene function in the urogenital sinus of the mouse also depends on enhancers located in this same genomic domain. Thus, we conclude that the current regulation underlying Hoxd gene expression in distal limbs was co-opted in tetrapods from a preexisting cloacal program. The orthologous chromatin domain in fishes may illustrate a rudimentary or partial step in this evolutionary co-option.

evolutionary biology↗

bioRxiv2023

Integrated Protocol of Protein Structure Modeling for Cryo-EM with Deep Learning and Structure Prediction

Structure modeling from maps is an indispensable step for studying proteins and their complexes with cryogenic electron microscopy (cryo-EM). Although the resolution of determined cryo-EM maps has generally improved, there are still many cases where tracing protein main-chains is difficult, even in maps determined at a near atomic resolution. Here, we have developed a protein structure modeling method, called DeepMainmast, which employs deep learning to capture the local map features of amino acids and atoms to assist main-chain tracing. Moreover, since Alphafold2 demonstrates high accuracy in protein structure prediction, we have integrated complementary strengths of de novo density tracing using deep learning with Alphafold2s structure modeling to achieve even higher accuracy than each method alone. Additionally, the protocol is able to accurately assign chain identity to the structure models of homo-multimers.

bioinformatics↗

bioRxiv2023

Metabolic bypass rescues aberrant S-nitrosylation-induced TCA cycle inhibition and synapse loss in Alzheimer's disease human neurons

In Alzheimers disease (AD), dysfunctional mitochondrial metabolism is associated with synaptic loss, the major pathological correlate of cognitive decline. Mechanistic insight for this relationship, however, is still lacking. Here, comparing isogenic wild-type and AD mutant human induced pluripotent stem cell (hiPSC)-derived cerebrocortical neurons (hiN), we found evidence for compromised mitochondrial energy in AD using the Seahorse platform to analyze glycolysis and oxidative phosphorylation (OXPHOS). Isotope-labeled metabolic flux experiments revealed a major block in activity in the tricarboxylic acid (TCA) cycle at the -ketoglutarate dehydrogenase (KGDH)/succinyl coenzyme-A synthetase step, metabolizing -ketoglutarate to succinate. Associated with this block we found aberrant protein S-nitrosylation of KGDH subunits that are known to inhibit enzyme function. This aberrant S-nitrosylation was documented not only in AD-hiN but also in postmortem human AD brains vs. controls, as assessed by two separate unbiased mass spectrometry platforms using both SNOTRAP identification of S-nitrosothiols and chemoselective-enrichment of S-nitrosoproteins. Treatment with dimethyl succinate, a cell-permeable derivative of a TCA substrate (downstream to the block, resulted in partial rescue of mitochondrial bioenergetic function as well as reversal of synapse loss in AD-hiN. Our findings have therapeutic implications that rescue of mitochondrial energy metabolism can ameliorate synaptic loss in hiPSC-based models of AD.

neuroscience↗

bioRxiv2023

Rhythm Receptive Fields in Striatum of Mice Executing Complex Continuous Movement Sequences

By the use of a novel experimental system, the step-wheel, we investigated the neural underpinnings of complex and continuous movements. We recorded neural activities from the dorsolateral striatum and found neurons sensitive to movement rhythm parameters. These neurons responded to specific combinations of interval, phase, and repetition of movement, effectively forming what we term "rhythm receptive fields." Some neurons even responsive to the combination of movement phases of multiple body parts. In parallel, cortical recordings in sensorimotor areas highlighted a paucity of neurons responsive to multiple parameter combinations, relative to those in the striatum. These findings have implications for comprehending motor coordination deficits seen in brain disorders including Parkinsons disease. Movement encoding by rhythm receptive fields should streamline the brains capacity to encode temporal patterns, help to resolve the degrees of freedom problem. Such rhythm fields hint at the neural mechanisms governing effective motor control and processing of rhythmic information.

neuroscience↗

bioRxiv2023

NuFold: A Novel Tertiary RNA Structure Prediction Method Using Deep Learning with Flexible Nucleobase Center Representation

RNA is not only playing a core role in the central dogma as mRNA between DNA and protein, but also many non-coding RNAs have been discovered to have unique and diverse biological functions. As genome sequences become increasingly available and our knowledge of RNA sequences grows, the study of RNAs structure and function has become more demanding. However, experimental determination of three-dimensional RNA structures is both costly and time-consuming, resulting in a substantial disparity between RNA sequence data and structural insights. In response to this challenge, we propose a novel computational approach that harnesses state-of-the-art deep learning architecture NuFold to accurately predict RNA tertiary structures. This approach aims to offer a cost-effective and efficient means of bridging the gap between RNA sequence information and structural comprehension. NuFold implements a nucleobase center representation, which allows it to reproduce all possible nucleotide conformations accurately.

bioinformatics↗