Biology subjects

Okamoto, K.

Publications and source records attributed to Okamoto, K..

At least 37 records · Page 2Linked to original sources

bioRxiv2023

The Crucial Role of CTCF in Mitotic Progression during Early Development of Sea Urchin.

CCCTC-binding factor (CTCF), an insulator protein with 11 zinc fingers, is enriched at the boundaries of topologically associated domains (TADs) in eukaryotic genomes. In this study, we isolated and analyzed the cDNAs encoding HpCTCF, the CTCF homolog in the sea urchin Hemicentrotus pulcherrimus, to investigate its expression patterns and functions during early development of sea urchin. HpCTCF contains nine zinc fingers corresponding to fingers 2-10 of the vertebrate CTCF. The expression pattern analysis revealed that HpCTCF mRNA was detected at all developmental stages and in the entire embryo. Upon expressing the HpCTCF-GFP fusion protein in early embryos, we observed its uniform distribution within interphase nuclei. However, during mitosis, it disappeared from the chromosomes and subsequently reassembled on the chromosome during telophase. Moreover, the morpholino-mediated knockdown of HpCTCF resulted in mitotic arrest during the morula-to-blastula stage. Most of the arrested chromosomes were not phospholylated at serine 10 of histone H3, indicating that mitosis was arrested at the telophase by HpCTCF depletion. Furthermore, impaired sister chromatid segregation was observed using time-lapse imaging of HpCTCF-knockdown embryos. Thus, HpCTCF is essential for mitotic progression during the early development of sea urchins, especially during the telophase-to-interphase transition. However, the normal development of pluteus larvae in CRISPR-mediated HpCTCF knockout embryos suggests that disruption of zygotic HpCTCF expression has little effect on embryonic and larval development.

developmental biology↗

bioRxiv2023

HIV viral protein R induces loss of DCT1-type renal tubules

Hyponatremia and salt wasting is a common occurance in patients with HIV/AIDS, however, the understanding of its contributing factors is limited. HIV viral protein R (Vpr) contributes to HIV-associated nephropathy. To investigate the effects of Vpr on the expression level of the Slc12a3 gene, encoding the Na-Cl cotransporter, which is responsible for sodium reabsorption in distal nephron segments, we performed single-nucleus RNA sequencing of kidney cortices from three wild-type (WT) and three Vpr-transgenic (Vpr Tg) mice. The results showed that the percentage of distal convoluted tubule (DCT) cells was significantly lower in Vpr Tg mice compared with WT mice (P < 0.05), and that in Vpr Tg mice, Slc12a3 expression was not different in DCT cell cluster. The Pvalb+ DCT1 subcluster had fewer cells in Vpr Tg mice compared with WT (P < 0.01). Immunohistochemistry demonstrated fewer Slc12a3+ Pvalb+ DCT1 segments in Vpr Tg mice. Differential gene expression analysis comparing Vpr Tg and WT in the DCT cluster showed Ier3, an inhibitor of apoptosis, to be the most downregulated gene. These observations demonstrate that the salt-wasting effect of Vpr in Vpr Tg mice is mediated by loss of Slc12a3+ Pvalb+ DCT1 segments via apoptosis dysregulation.

pathology↗

bioRxiv2023

Structure and its transformation of elliptical nege-like virus Tanay virus

Negeviruses that infect insects are recently identified virus species that are phylogenetically related to several plant viruses. They exhibit a unique virion structure, an elliptical core with a short projection. Negeviruses encode two structural proteins, a glycoprotein that forms a short projection, and an envelope protein that forms an elliptical core. The glycoprotein has been reported only in the negeviruses genes, and not in phylogenetically related plant viruses genes. In this report, we first describe the three-dimensional electron cryo-microscopy (cryo-EM) structure of Tanay virus (TANAV), one of the nege-like viruses. TANAV particle demonstrates a periodical envelope structure consisting of three layers surrounding the centered viral RNA. The elliptical core dynamically changes its shape under acidic and even low detergent conditions to form bullet-like or tubular shapes. The further cryo-EM studies on these transformed TANAV particles reveal their overall structural rearrangement. These findings suggest putative geometries of TANAV and its transformation in the life cycle, and the potential importance of the short projection for enabling cell entry to the insect hosts. Impact statementNegeviridae has recently been declared as a virus family that includes virus species exhibiting a unique particle structure that differs from other known viruses. They are known to be common mosquito viruses isolated around the world, but also phylogenetically related to several plant viruses that impair crop production. Therefore, the negeviruses may also play a role in plant ecosystems that threaten agriculture. However, the mechanism of infection and assembly of the negeviruses as well as their structure were unknown. In this study, intact and dissociated structures of the TANAV were first examined using cryo-EM single particle analysis (SPA) and electron cryo-tomography (cryo-ET). These results reveal new structural geometries of the TANAV particle and its dynamic transformation under acidic and even low-detergent conditions, providing new insights into the infection and assembly mechanism in negeviruses.

biophysics↗

bioRxiv2022

A ubiquitin-proteasome pathway degrades the inner nuclear membrane protein Bqt4 to maintain nuclear membrane homeostasis

Aberrant accumulation of inner nuclear membrane (INM) proteins is associated with deformed nuclear morphology and mammalian diseases. However, the mechanisms underlying the maintenance of INM homeostasis remain poorly understood. In this study, we explored the degradation mechanisms of the INM protein, Bqt4, in the fission yeast Schizosaccharomyces pombe. We have previously shown that Bqt4 interacts with the transmembrane protein Bqt3 at the INM and is degraded in the absence of Bqt3. Here, we revealed that excess Bqt4, unassociated with Bqt3, was targeted for degradation by the ubiquitin-proteasome system localized in the nucleus and Bqt3 antagonized this process. The degradation process involved the Doa10 E3 ligase complex at the INM. Bqt4 is a tail-anchored protein and extraction from the membrane by the Cdc48 complex is required for its degradation. The C-terminal transmembrane domain of Bqt4 is necessary and sufficient for proteasome-dependent protein degradation. Accumulation of Bqt4 at the INM impaired cell viability with nuclear envelope deformation, suggesting that quantity control of Bqt4 plays an important role in nuclear membrane homeostasis. Summary statement Appropriate levels of the inner nuclear membrane protein Bqt4 are maintained by ubiquitin-proteasome-mediated degradation. Aberrant accumulation of Bqt4 disturbs nuclear membrane homeostasis.

cell biology↗

bioRxiv2022

Two closed conformations of CRAF require the 14-3-3 binding motifs and cysteine-rich domain to be intact in live cells

The protein rapidly accelerated fibrosarcoma (RAF) is a kinase downstream of the membrane protein RAS in the cellular signal transduction system. In the structure of RAF, the N- and C-terminus domains are connected with a flexible linker. The open/close dynamics and dimerization of RAF are thought to regulate its activity, although the details of these conformations are unknown, especially in live cells. In this work, we used alternating laser excitation to measure cytosolic CRAF in live HeLa cells and obtained single-molecule Forster resonance energy transfer (smFRET) distributions of the structural states. We compared the results for wild-type (WT)-CRAF before and after epidermal growth factor (EGF) stimulation, with mutations of the 14-3-3 binding sites and cysteine-rich domain, and an N-terminus truncation. The smFRET distributions of full-length CRAFs were analyzed by global fitting with three beta distributions. Our results suggested that a 14-3-3 dimer bound to two sites on a single CRAF molecule and induced the formation of the autoinhibitory closed conformation. There were two closed conformations, which the majority of WT-CRAF adopted. These two conformations showed different responsiveness to EGF stimulation.

biophysics↗

bioRxiv2022

PKR activation-induced mitochondrial dysfunction in HIV-transgenic mice with nephropathy

HIV disease remains prevalent in the USA and chronic kidney disease remains a major cause of morbidity in HIV-1-positive patients. Host double-stranded RNA (dsRNA)-activated protein kinase (PKR) is a sensor for viral dsRNA, including HIV-1. We show that PKR inhibition by compound C16 ameliorates the HIV-associated nephropathy (HIVAN) kidney phenotype in the Tg26 transgenic mouse model, with reversal of mitochondrial dysfunction. Combined analysis of single-nucleus RNA-seq and bulk RNA-seq data revealed that oxidative phosphorylation was one of the most downregulated pathways and identified signal transducer and activator of transcription (STAT3) as a potential mediating factor. We identified in Tg26 mice a novel proximal tubular cell cluster enriched in mitochondrial transcripts. Podocytes showed high levels of HIV-1 gene expression and dysregulation of cytoskeleton-related genes; and these cells dedifferentiated. In injured proximal tubules, cell-cell interaction analysis indicated activation of the profibrogenic PKR-STAT3-platelet derived growth factor (PDGF)-D pathway. These findings suggest that PKR inhibition and mitochondrial rescue are potential novel therapeutic approaches for HIVAN. Translational StatementThis work identified mitochondrial dysfunction in transgenic mice manifesting HIV-associated nephropathy mice kidney, using combination of single-nuclear and bulk RNA-seq analysis. Kidney damage was ameliorated by the PKR inhibitor C16, and mitochondrial rescue was shown by transcriptomic profiling and functional assay. These findings suggest that PKR inhibition and mitochondrial rescue are potential therapeutic approaches for HIV-associated nephropathy.

pathology↗

bioRxiv2022

Capsid structure of a metazoan fungal dsRNA megabirnavirus reveals its uniquely acquired structures

Rosellinia necatrix megabirnavirus 1-W779 (RnMBV1) is a non-enveloped icosahedral double-stranded (ds)RNA virus that infects the ascomycete fungus Rosellinia. necatrix, a causative agent that induces a lethal plant disease white root rot. Herein, we have first resolved the atomic structure of the RnMBV1 capsid at 3.2 [A] resolution using cryo-electron microscopy (cryo-EM) single-particle analysis. Contrary to the other structurally associated viral capsid proteins, the RnMBV1 capsid protein structure exhibits an extra-long C-terminal arm and a surface protrusion domain. In addition, the previously unrecognized crown proteins are identified in a symmetry-expanded cryo-EM model and are present over the 3-fold axes. These exclusive structural features of the RnMBV1 capsid could have been acquired for playing essential roles in transmission, genome packaging, and/or particle assembly of the megabirnaviruses. Our findings, therefore, will reinforce the understanding of how the structural and molecular machineries of the megabirnaviruses influence the virulence of the disease-related ascomycete fungus. Author summaryA fungal plant soil-borne pathogen, Rosellinia necatrix, which can cause devastating disease white root rot in many highly valued fruit trees, is difficult to be controlled with conventional approaches such as fungicide applications. Rosellinia necatrix megabirnavirus 1-W779 (RnMBV1) is a dsRNA virus isolated from the R. necatrix field strain, W779, and this virus can be a viro-control candidate to confer hypovirulence in its host R. necatrix. To make use of RnMBV1 in the white root rot disease control, more molecular and structural investigations will offer us more insights. Here, we have performed cryo-electron microscopy (cryo-EM) single-particle analysis, to obtain the first atomic models of RnMBV1 particles. Based on the atomic structures, we found unique both surface and interior features. In addition, we found a previously unexpected protein on the viral surface. These aforementioned structural features might play important roles in the viral life cycles, and will enable us to apply this fungal virus as a viro-control approach.

molecular biology↗

bioRxiv2022

Single-molecule tracking of Nanog and Oct4 in mouse embryonic stem cells

Nanog and Oct4 are core transcription factors in a gene regulatory network that regulate hundreds of target genes for pluripotency maintenance in mouse embryonic stem cells. To understand their function as a gatekeeper or a pioneer factor at the molecular scale, we quantified the residence time on target loci, fluctuation at the loci, and interaction clustering by visualizing single molecules of Nanog and Oct4 in a living nucleus during the pluripotency loss. Interestingly, Nanog interacted longer with its target loci in the lower Nanog expression state or at the onset of differentiation, indicating the possibility of a new feedback mechanism to maintain Nanog expression. The interaction time of Nanog and Oct4 corresponded to their fluctuation and interaction clustering, which depended on their expression or differentiation state, respectively. The DNA viscoelasticity near the Oct4 target locus remained flexible during the differentiation, reflecting its role as a pioneer factor. Based on these results, we propose a new feedback mechanism for pluripotency maintenance in which Nanog function is prolonged, corresponding to chromatin condensation, and Oct4 reopens the condensation.

biophysics↗

bioRxiv2022

Neuronal SNAP-23 scales hippocampal synaptic plasticity and memory

Soluble NSF Attachment protein REceptor (SNARE)-mediated membrane fusion plays a crucial role not only in presynaptic vesicle exocytosis but also in postsynaptic receptor delivery. The latter is considered particularly important for long-term synaptic plasticity and learning and memory, yet underlying mechanisms including the identity of the key SNARE proteins remain elusive. Here, we investigate the role of neuronal Synaptosomal-Associated Protein-23 (SNAP-23) by analyzing pyramidal-neuron specific SNAP-23 conditional knockout (cKO) mice. SNAP-23 immunostaining in postsynaptic spines was effectively decreased in the SNAP-23 cKO hippocampus. Electrophysiological analysis of SNAP-23 deficient neurons using acute hippocampal slices showed normal basal neurotransmission in CA3-CA1 synapses with unchanged AMPA and NMDA currents. Nevertheless, we found theta-burst stimulation induced long-term potentiation (LTP) was vastly diminished in SNAP-23 cKO. Moreover, unlike syntaxin-4 cKO mice in which both basal neurotransmission and LTP decrease manifested changes in a broad set of behavioral tasks, deficits of SNAP-23 cKO is more limited to spatial memory. Our data reveal that neuronal SNAP-23 is selectively crucial for synaptic plasticity and spatial memory without affecting basal glutamate receptor function.

neuroscience↗

bioRxiv2022

Multifaceted effects of bycatch mitigation measures on target/non-target species for pelagic longline fisheries and consideration for bycatch management

The pelagic longline fishery, in an effort to reduce bycatch of sea turtles, have developed and deployed fisheries bycatch mitigation techniques such as replacing J/tuna hooks and squid bait with circle hooks and whole fish bait. However, little emphasis has been placed on the side effects of bycatch mitigation measures on endangered species other than target bycatch species. Several previous studies of the side effects have been marred by lack of control for the covariates. Here, based on long-term data obtained from research cruises by a pelagic longline vessel, we examined the effects of using circle hooks and whole fish bait to replace squid bait on the fishing mortality of target and non-target fishes, and also bycatch species. A quantitative evaluation analysis of our results, based on a Bayesian approach, showed the use of circle hooks to increase mouth hooking in target and bycatch species, and their size to be proportional to the magnitude of the effect. While deploying circle hooks did not increase fishing mortality per unit effort (MPUE) for shortfin mako sharks, combining to whole fish bait had a significant increase on MPUE. Because the impact of the introduction of bycatch mitigation measures on species other than the focused bycatch species is non-negligible, a quantitative assessment of bycatch mitigation-related fishing mortality is critical before introducing such measures.

ecology↗

bioRxiv2021

Dose-response relationship of pulmonary disorders by inhalation exposure to cross-linked water-soluble acrylic acid polymers in F344 rats

BackgroundIn Japan, six workers handling cross-linked water-soluble acrylic acid polymer (CWAAP) at a chemical plant suffered from lung diseases, including fibrosis, interstitial pneumonia, emphysema, and pneumothorax. We recently demonstrated that inhalation of CWAAP-A, one type of CWAAP, causes pulmonary disorders in rats. It is important to investigate dose-response relationships and recoverability from exposure to CWAAPs for establishing occupational health guidelines, such as setting threshold limit value for CWAAPs in the workplace. MethodsMale and female F344 rats were exposed to 0.3, 1, 3, or 10 mg/m3 CWAAP-A for 6 hours/day, 5 days/week for 13 weeks using a whole-body inhalation exposure system. At 1 hour, 4 weeks, and 13 weeks after the last exposure the rats were euthanized and blood, bronchoalveolar lavage fluid, and all tissues including lungs and mediastinal lymph nodes were collected and subjected to biological and histopathological analyses. In a second experiment, male rats were pre-treated with clodronate liposome or polymorphonuclear leukocyte-neutralizing antibody to deplete macrophages or neutrophils, respectively, and exposed to CWAAP-A for 6 hours/day for 2 days. ResultsCWAAP-A exposure damaged only the alveoli. The lowest observed adverse effect concentration (LOAEC) was 1 mg/m3 and the no observed adverse effect concentration (NOAEC) was 0.3 mg/m3. Rats of both sexes were able to recover from the tissue damage caused by 13 weeks exposure to 1 mg/m3 CWAAP-A. In contrast, tissue damage caused by exposure to 3 and 10 mg/m3 was irreversible due to the development of interstitial lung lesions. There was a gender difference in the recovery from CWAAP-A induced pulmonary disorders, with females recovering less than males. Finally, acute lung effects caused by CWAAP-A were significantly reduced by depletion of alveolar macrophages. ConclusionsPulmonary damage caused by inhalation exposure to CWAAP-A was dose-dependent, specific to the lung and lymph nodes, and acute lung damage was ameliorated by depleting macrophages in the lungs. CWAAP-A had both a LOAEC and a NOAEC, and tissue damage caused by exposure to 1 mg/m3 CWAAP-A was reversible: recovery in female rats was less than for males. These findings indicate that concentration limits for CWAAPs in the workplace can be determined.

pharmacology and toxicology↗

bioRxiv2021

Pathological characteristics of pulmonary toxicity in F344 rats exposed by inhalation to cross-linked water-soluble acrylic acid polymers

BackgroundRecently in Japan, six workers at a chemical plant that manufactures resins developed interstitial lung diseases after being involved in loading and packing cross-linked water-soluble acrylic acid polymers (CWAAPs). Since CWAAPs are not on the list of occupational diseases, the present study examined the lung damage potential of two CWAAPs (CWAAP-A and CWAAP-B) in rats, investigated pathological mechanisms, and established a method to rapidly evaluate the harmfulness of CWAAPs. MethodsUsing a whole-body inhalation exposure system, male F344 rats were exposed once to 40 or 100 mg/m3 of CWAAP-A for 4 hours or to 15 or 40 mg/m3 of CWAAP-A for 4 hours per day once per week for 2 months (a total of 9 exposures). In a separate set of experiments, male F344 rats were administered 1 mg/kg CWAAP-A or CWAAP-B by intratracheal instillation once every two weeks for 2 months (a total of five doses). Lung tissues, mediastinal lymph nodes, and bronchoalveolar lavage fluid were collected and subjected to biological and histopathological analyses. ResultsA single 4-hour exposure to CWAAP caused alveolar injury, and repeated exposures resulted in regenerative changes in the alveolar epithelium with activation of TGF{beta} signaling. During the recovery period after the last exposure, some alveolar lesions were partially healed, but other lesions developed into alveolitis with fibrous thickening of the alveolar septum. Rats administered CWAAP-A by intratracheal instillation developed qualitatively similar pulmonary pathology as rats exposed to CWAAP-A by inhalation. At 2 weeks after intratracheal instillation, rats administered CWAAP-B appeared to have a slightly higher degree of lung lesions compared to rats administered CWAAP-A, however, there was no difference in these lesions of CWAAP-A and CWAAP-B in rats examined 18 weeks after administration of these materials. ConclusionsThe present study provides evidence of rat lung pathogenesis after inhalation exposure to CWAAP-A. This study also demonstrates that the lung pathology of rats exposed to CWAAP-A by systemic inhalation was qualitatively similar to that of rats administered CWAAP-A by intratracheal instillation. The use of intratracheal instillation as an adjunct to systemic inhalation is expected to significantly accelerate the risk assessment for a variety of CWAAPs.

pharmacology and toxicology↗

bioRxiv2021

A full-length infectious cDNA clone of a dsRNA totivirus-like virus

Totivirus-like viruses are icosahedral non-enveloped double-stranded (ds)RNA viruses belonging to a group recently discovered and provisionally assigned in the Totiviridae family. Unlike fungal and protozoan Totiviridae viruses, these totivirus-like viruses infect a diverse spectrum of metazoan hosts and currently have enormous impacts on fisheries and agriculture. We developed the first totivirus-like virus Omono River virus (OmRV) infectious full-length DNA clone and produce the infectious particles using an RNA-transcript-based method. Unlike the parent wild-type particles from nature, the reverse-genetically-generated OmRV particles had an indistinguishable cytopathic effect, infectivity, and morphology. The established system is one of the few systems that have been reported for generating a non-segmented dsRNA virus DNA clone.

microbiology↗

bioRxiv2021

The GET pathway serves to activate Atg32-mediated mitophagy by ER targeting of the Ppg1-Far complex

Mitophagy removes defective or superfluous mitochondria via selective autophagy. In yeast, the pro-mitophagic protein Atg32 localizes to the mitochondrial surface and interacts with the scaffold protein Atg11 to promote degradation of mitochondria. Although Atg32-Atg11 interactions are thought to be stabilized by Atg32 phosphorylation, how this posttranslational modification is regulated remains obscure. Here we show that cells lacking the guided entry of tail-anchored proteins (GET) pathway exhibit reduced Atg32 phosphorylation and Atg32-Atg11 interactions, which can be rescued by additional loss of the ER-resident Ppg1-Far complex, a multi-subunit phosphatase negatively acting in mitophagy. In GET-deficient cells, Ppg1-Far is predominantly localized to mitochondria. An artificial ER anchoring of Ppg1-Far in GET-deficient cells significantly ameliorates defects in Atg32-Atg11 interactions and mitophagy. Moreover, disruption of GET and Msp1, an AAA-ATPase that extracts non-mitochondrial proteins localized to the mitochondrial surface, elicits synthetic defects in mitophagy. Collectively, we propose that the GET pathway mediates ER targeting of Ppg1-Far, thereby preventing dysregulated suppression of mitophagy activation.

cell biology↗

bioRxiv2021

The 4.4 A structure of the giant Melbournevirus virion belonging to the Marseilleviridae family

Members of Marseilleviridae, one family of icosahedral giant viruses classified in 2012 have been identified worldwide in all types of environments. The virion shows a characteristic internal membrane extrusion at the five-fold vertices of the capsid, but its structural details need to be elucidated. We now report the 4.4 [A] cryo-electron microscopy structure of the Melbournevirus capsid. An atomic model of the major capsid protein (MCP) shows a unique cup structure on the trimer that accommodates additional proteins. A polyalanine model of the penton base protein shows internally extended N- and C-terminals, which indirectly connect to the internal membrane extrusion. The Marseilleviruses share the same orientational organisation of the MCPs as PBCV-1 and CroV, but do not appear to possess a protein akin to the "tape measure" of these viruses. Minor capsid proteins named PC-{beta}, zipper, and scaffold are proposed to control the dimensions of the capsid during assembly.

microbiology↗

bioRxiv2021

GLIS1 regulates trabecular meshwork function and intraocular pressure and is associated with glaucoma in humans

Chronically elevated intraocular pressure (IOP) is the major risk factor of primary open- angle glaucoma, a leading cause of blindness. Dysfunction of the trabecular meshwork (TM), which controls the outflow of aqueous humor (AqH) from the anterior chamber, is the major cause of elevated IOP. Here, we demonstrate that mice deficient in the Kruppel- like zinc finger transcriptional factor GLI-similar-1 (GLIS1) develop chronically elevated IOP. Magnetic resonance imaging and histopathological analysis reveal that deficiency in GLIS1 expression induces progressive degeneration of the TM, leading to inefficient AqH drainage from the anterior chamber and elevated IOP. Transcriptome and cistrome analyses identified several glaucoma- and extracellular matrix-associated genes as direct transcriptional targets of GLIS1. We also identified a significant association between GLIS1 variant rs941125 and glaucoma in humans (P=4.73x10-6), further supporting a role for GLIS1 into glaucoma etiology. Our study identifies GLIS1 as a critical regulator of TM function and maintenance, AqH dynamics, and IOP.

molecular biology↗

bioRxiv2021

The Effect of a Fennel Extract on the STAT Signaling and Intestinal Barrier Function

BackgroundFoeniculum vulgare, F. vulgare, commonly known as fennel, is believed to be one of the worlds oldest medicinal herbs and has been exploited by people for centuries as a nutritional aid for digestive disorders. In many southeast Asian countries it is ingested as an after-meal snack, mukhvas, due to its breath-freshening and digestive aid properties. F. vulgare is used in some countries, such as Iran, as a complementary and alternative treatment for inflammatory bowel disease (IBD). MethodsThis study investigated the effects of F. vulgare on the barrier function of the intestinal epithelium Signal Transducer and Activator of Transcription (STAT) pathway, which is active in inflammatory bowel disease. To study the protective effects of F. vulgare extract in vitro, monolayers derived from the T84 colonic cell line were challenged with interferon-gamma (IFN-{gamma}) and monitored with and without F. vulgare extract. To complement our in vitro studies, the dextran sodium sulfate induced murine colitis model was employed to ascertain whether the protective effect of F. vulgare extract can be recapitulated in vivo. ResultsF. vulgare extract was shown to exert a protective effect on TEER in both T84 and murine models and showed increases in tight junction-associated mRNA in T84 cell monolayers. Both models demonstrated significant decreases in phosphorylated STAT1 (pSTAT1), indicating reduced activation of the STAT pathway. Additionally, mice treated with F. vulgare showed significantly lower ulcer indices than control mice. ConclusionsWe conclude barrier function of the gastrointestinal tract is improved by F. vulgare, suggesting the potential utility of this agent as an alternative or adjunctive therapy in IBD.

pharmacology and toxicology↗

bioRxiv2021

Primordial capsid and spooled ssDNA genome structures penetrate ancestral events of eukaryotic viruses

Marine algae viruses are important for controlling microorganism communities in the marine ecosystem and played fundamental roles during the early events of viral evolution. Here, we have focused on one major group of marine algae viruses, the ssDNA viruses from the Bacilladnaviridae family. We present the capsid structure of the bacilladnavirus, Chaetoceros tenuissimus DNA virus type II (CtenDNAV-II), determined at 2.3 [A] resolution. A structure-based phylogenetic analysis supported the previous theory that bacilladnaviruses have acquired their capsid protein via horizontal gene transfer from a ssRNA virus. The capsid protein contains the widespread virus jelly-roll fold, but has additional unique features; a third {beta}-sheet and a long C-terminal tail. Further, low-resolution reconstructions of the CtenDNAV-II genome revealed a partially spooled structure, an arrangement previously only described for dsRNA and dsDNA viruses. Together, these results exemplify the importance of genetic recombination for the emergence and evolution of ssDNA viruses and provide important insights into the underlying mechanisms that dictate genome organisation.

biophysics↗