Biology subjects

Suzuki, T.

Publications and source records attributed to Suzuki, T..

At least 145 records · Page 8Linked to original sources

bioRxiv2023

An engineered ACE2 decoy broadly neutralizes Omicron subvariants and shows therapeutic effect in SARS-CoV-2-infected cynomolgus macaques

The Omicron variant continuously evolves under the humoral immune pressure obtained by vaccination and SARS-CoV-2 infection and the resultant Omicron subvariants exhibit further immune evasion and antibody escape. Engineered ACE2 decoy composed of high-affinity ACE2 and IgG1 Fc domain is an alternative modality to neutralize SARS-CoV-2 and we previously reported its broad spectrum and therapeutic potential in rodent models. Here, we show that engineered ACE2 decoy retains the neutralization activity against Omicron subvariants including the currently emerging XBB and BQ.1 which completely evade antibodies in clinical use. The culture of SARS-CoV-2 under suboptimal concentration of neutralizing drugs generated SARS-CoV-2 mutants escaping wild-type ACE2 decoy and monoclonal antibodies, whereas no escape mutant emerged against engineered ACE2 decoy. As the efficient drug delivery to respiratory tract infection of SARS-CoV-2, inhalation of aerosolized decoy treated mice infected with SARS-CoV-2 at a 20-fold lower dose than the intravenous administration. Finally, engineered ACE2 decoy exhibited the therapeutic efficacy for COVID-19 in cynomolgus macaques. Collectively, these results indicate that engineered ACE2 decoy is the promising therapeutic strategy to overcome immune-evading SARS-CoV-2 variants and that liquid aerosol inhalation can be considered as a non-invasive approach to enhance efficacy in the treatment of COVID-19.

microbiology↗

bioRxiv2022

Identification of inosine monophosphate dehydrogenase as a potential target for anti-monkeypox virus agents

Monkeypox virus (MPXV) is a neglected zoonotic pathogen that caused a worldwide outbreak in May 2022. Given the lack of an established therapy, the development of an anti-MPXV strategy is of vital importance. To identify drug targets for the development of anti-MPXV agents, we screened a chemical library using an MPXV infection cell assay and found that gemcitabine, trifluridine, and mycophenolic acid (MPA) inhibited MPXV propagation. These compounds showed broad-spectrum anti-orthopoxvirus activities and presented lower 90% inhibitory concentrations (0.032-1.40 M) than brincidofovir, an approved anti-smallpox agent. These three compounds have been suggested to target the post-entry step to reduce the intracellular production of virions. Knockdown of inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme of guanosine biosynthesis and a target of MPA, dramatically reduced MPXV DNA production. Moreover, supplementation with guanosine recovered the anti-MPXV effect of MPA, suggesting that IMPDH and its guanosine biosynthetic pathway regulate MPXV replication. By targeting IMPDH, we identified a series of compounds with stronger anti-MPXV activity than MPA. These evidences propose that IMPDH is a potential target for the development of anti-MPXV agents. ImportanceMonkeypox is a zoonotic disease caused by infection with the monkeypox virus, and a worldwide outbreak occurred in May 2022. The smallpox vaccine has recently been approved for clinical use against monkeypox in the United States. Although brincidofovir and tecovirimat are drugs approved for the treatment of smallpox by the U.S. Food and Drug Administration, their efficacy against monkeypox has not been established. Moreover, these drugs may present negative side effects. Therefore, new anti-monkeypox virus agents are needed. This study revealed that gemcitabine, trifluridine, and mycophenolic acid inhibited monkeypox virus propagation, exhibited broad-spectrum anti-orthopoxvirus activities. We also suggested inosine monophosphate dehydrogenase as a potential target for the development of anti-monkeypox virus agents. By targeting this molecule, we identified a series of compounds with stronger anti-monkeypox virus activity than mycophenolic acid.

microbiology↗

bioRxiv2022

Discovery of prevalent natural Wolbachia in Aedes aegypti in Metropolitan Manila, Philippines using locally designed primers: bacterial density is influenced by strain and host sex

Wolbachia are maternally transmitted bacteria that are utilized for arboviral disease prevention. Cytoplasmic incompatibility (CI) and viral blocking, two characteristics that make Wolbachia suitable for vector control, both depend on bacterial infection prevalence and density. Although numerous mosquito species naturally harbor Wolbachia, the prevalence of Wolbachia in Aedes aegypti varies from minimal to absent. The absence of natural Wolbachia in Ae. aegypti is considered advantageous for novel Wolbachia transinfection because interference caused by incompatible Wolbachia strains will not occur. In this study, we screened for Wolbachia density in 429 individual Ae. aegypti collected from Metropolitan Manila, Philippines using locally designed primers to determine whether primer compatibility improves Wolbachia detection in naturally infected Ae. aegypti. We also investigated the effects of host sex and Wolbachia strain on Wolbachia density. We found a high Wolbachia prevalence for 16S rRNA (40%) and wsp (62%) markers. Relative Wolbachia densities ranged from -3.840 to 2.710 for 16S rRNA and from -4.020 to 1.810 for wsp, and these relative densities were higher among male mosquitoes than female mosquitoes. Phylogenetic analysis revealed that most of the Ae. aegypti were clustered into supergroup B, with 63% (142/226) of these sequences representing a unique strain referred to here as "wAegML," which exhibited a significantly lower density in Ae. aegypti than the other two Wolbachia strains detected (wAegB/wAlbB and wAlbA) as well as a higher density in male Ae. aegypti than in females. Overall, locally designed primers improved Wolbachia detection in naturally infected Ae. aegypti. The unique strain wAegML occurs at a low density and is related to the use of wAlbB in mass-release programs; therefore, it is unlikely to interfere with such programs. Further studies on natural Wolbachia infection in Ae. aegypti combining methodological and biological factors are warranted to help resolve current conflicts in the field.

microbiology↗

bioRxiv2022

The canonical E2Fs together with RETINOBLASTOMA-RELATED are required to establish quiescence during plant development

Maintaining stable and transient quiescence in differentiated and stem cells, respectively, requires repression of the cell cycle. The plant RETINOBLASTOMA-RELATED (RBR) has been implicated in stem cell maintenance, presumably by forming repressor complexes with E2F transcription factors. Surprisingly we find that mutations in all three canonical E2Fs do not compromise the cell cycle, but similarly to RBR silencing, result in overproliferation. Contrary to the growth arrest upon RBR silencing, when exit from proliferation to differentiation is inhibited, the e2fabc mutant develops enlarged organs with supernumerary stem and differentiated cells as the quiescence is compromised. While E2F, RBR and the M-phase regulatory MYB3Rs are part of the DREAM repressor complexes, and recruited to overlapping groups of targets, they regulate distinct sets of genes. Only the loss of E2Fs but not the MYB3Rs interferes with quiescence, which might be due to the ability of E2Fs to control both G1-S and some key G2-M targets. We conclude that collectively the three canonical E2Fs in complex with RBR have central roles in establishing cellular quiescence during organ development, leading to enhanced plant growth.

plant biology↗

bioRxiv2022

A land plant specific VPS13 mediates polarized vesicle trafficking in germinating pollen

Pollen has an extraordinary ability to convert from a dry state to an extremely rapidly growing state. During pollination, pollen receives water and Ca2+ from the contacting pistil, which will be a directional cue for pollen tube germination. The subsequent rapid activation of directional vesicular transport must support the pollen tube growth, but the molecular mechanism leading to this process is largely unknown. Here we show that a plant-specific VPS13, AtVPS13a, mediates vesicle trafficking during the polarization process in Arabidopsis pollen. AtVPS13a knockout severely affected pollen germination and lipid droplet discharge, while Ca2+-dynamics after pollination was unchanged. Cellular distribution patterns of AtVPS13a and a secretory vesicle marker were synchronized, with a slight delay to the Ca2+-dynamics in polarizing pollen. The absence of AtVPS13a led to reduced cell wall deposition during pollen germination. These results suggest that AtVPS13a mediates pollen polarization, by regulating proper directional vesicular transport following Ca2+-signaling.

plant biology↗

bioRxiv2022

Metabolic clogging of mannose triggers genomic instability via dNTP loss in human cancer cells

Mannose has anti-cancer activity that inhibits cell proliferation and enhances the efficacy of chemotherapy. How mannose exerts its anti-cancer activity, however, remains poorly understood. Here, using genetically engineered human cancer cells that permit the precise control of mannose metabolic flux, we demonstrate that the large influx of mannose exceeding its metabolic capacity induced metabolic remodeling, leading to the generation of slow-cycling cells with limited deoxyribonucleoside triphosphates (dNTPs). This metabolic remodeling impaired dormant origin firing required to rescue stalled forks by cisplatin, thus exacerbating replication stress. Importantly, pharmacological inhibition of de novo dNTP biosynthesis was sufficient to retard cell cycle progression, sensitize cells to cisplatin, and inhibit dormant origin firing, suggesting dNTP loss-induced genomic instability as a central mechanism for the anti-cancer activity of mannose.

cancer biology↗

bioRxiv2022

CiDRE+ M2c macrophages hijacked by SARS-CoV-2 cause COVID-19 severity

Infection of the lungs with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via the angiotensin I converting enzyme 2 (ACE2) receptor induces a type of systemic inflammation known as a cytokine storm. However, the precise mechanisms involved in severe coronavirus disease 2019 (COVID-19) pneumonia are unknown. Here, we show that interleukin-10 (IL-10) changed normal alveolar macrophages into ACE2-expressing M2c-type macrophages that functioned as spreading vectors for SARS-CoV-2 infection. The depletion of alveolar macrophages and blockade of IL-10 attenuated SARS-CoV-2 pathogenicity. Furthermore, genome-wide association and quantitative trait locus analyses identified novel mRNA transcripts in human patients, COVID-19 infectivity enhancing dual receptor (CiDRE), which has unique synergistic effects within the IL-10-ACE2 system in M2c-type macrophages. Our results demonstrate that alveolar macrophages stimulated by IL-10 are key players in severe COVID-19. Collectively, CiDRE expression levels are potential risk factors that predict COVID-19 severity, and CiDRE inhibitors might be useful as COVID-19 therapies. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=195 HEIGHT=200 SRC="FIGDIR/small/510331v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@1e96c82org.highwire.dtl.DTLVardef@1d2dc32org.highwire.dtl.DTLVardef@7689d1org.highwire.dtl.DTLVardef@520d17_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2022

Impact of reinfection with SARS-CoV-2 Omicron variants in previously infected hamsters

The diversity of SARS-CoV-2 mutations raises the possibility of reinfection of individuals previously infected with earlier variants, and this risk is further increased by the emergence of the B.1.1.529 Omicron variant. In this study, we used an in vivo, hamster infection model to assess the potential for individuals previously infected with SARS-CoV-2 to be reinfected with Omicron variant and we also investigated the pathology associated with such infections. Initially, Syrian hamsters were inoculated with a lineage A, B.1.1.7, B.1.351, B.1.617.2 or a subvariant of Omicron, BA.1 strain and then reinfected with the BA.1 strain 5 weeks later. Subsequently, the impact of reinfection with Omicron subvariants (BA.1 and BA.2) in individuals previously infected with the BA.1 strain was examined. Although viral infection and replication were suppressed in both the upper and lower airways, following reinfection, virus-associated RNA was detected in the airways of most hamsters. Viral replication was more strongly suppressed in the lower respiratory tract than in the upper respiratory tract. Consistent amino acid substitutions were observed in the upper respiratory tract of infected hamsters after primary infection with variant BA.1, whereas diverse mutations appeared in hamsters reinfected with the same variant. Histopathology showed no acute pneumonia or disease enhancement in any of the reinfection groups and, in addition, the expression of inflammatory cytokines and chemokines in the airways of reinfected animals was only mildly elevated. These findings are important for understanding the risk of reinfection with new variants of SARS-CoV-2. IMPORTANCEThe emergence of SARS-CoV-2 variants and the widespread use of COVID-19 vaccines has resulted in individual differences in immune status against SARS-CoV-2. A decay in immunity over time and the emergence of variants that partially evade the immune response can also lead to reinfection. In this study, we demonstrated that, in hamsters, immunity acquired following primary infection with previous SARS-CoV-2 variants was effective in preventing the onset of pneumonia after reinfection with the Omicron variant. However, viral infection and multiplication in the upper respiratory tract were still observed after reinfection. We also showed that more diverse nonsynonymous mutations appeared in the upper respiratory tract of reinfected hamsters that had acquired immunity from primary infection. This hamster model reveals the within-host evolution of SARS-CoV-2 and its pathology after reinfection, and provides important information for countermeasures against diversifying SARS-CoV-2 variants.

microbiology↗

bioRxiv2022

Characterization of SARS-CoV-2 Omicron BA.2.75 clinical isolates

The prevalence of the Omicron subvariant BA.2.75 is rapidly increasing in India and Nepal. In addition, BA.2.75 has been detected in at least 34 other countries and is spreading globally. However, the virological features of BA.2.75 are largely unknown. Here, we evaluated the replicative ability and pathogenicity of BA.2.75 clinical isolates in Syrian hamsters. Although we found no substantial differences in weight change among hamsters infected with BA.2, BA.5, or BA.2.75, the replicative ability of BA.2.75 in the lungs was higher than that of BA.2 and BA.5. Of note, BA.2.75 caused focal viral pneumonia in hamsters, characterized by patchy inflammation interspersed in alveolar regions, which was not observed in BA.5-infected hamsters. Moreover, in competition assays, BA.2.75 replicated better than BA.5 in the lungs of hamsters. These results suggest that BA.2.75 can cause more severe respiratory disease than BA.5 and BA.2 and should be closely monitored.

microbiology↗

bioRxiv2022

The Administration Effect of Lactic Acid Bacteria Reducing Environmental Alkyl and Fatty Acid Hydroperoxides on Piglets in the Absence of Antimicrobial Agents and in the Presence of Iron

A lactic acid bacterium, Lactiplantibacillus plantarum P1-2 (LpP1-2), can reduce environmental fatty acid hydroperoxides. The administration of LpP1-2 to oxygen-sensitive short-lived nematode mutants and iron-overloaded rats reduced the oxidative stress-related index. Since young piglets have a weak defense system against oxidative stress and are vulnerable to environmental stress, antimicrobial agents have been administered in the rearing. Based on these results, we investigated the effect of LpP1-2 administration to prepartum sows and infant piglets until weaning without antimicrobial agents on the growth of young piglets. The group including both sows and piglets that were administrated with lactic acid bacteria containing LpP1-2 (LABLp) until the end of lactation showed the growth-promoting effect of piglet from lactation to early regular rearing, and even in late regular rearing. Blood biochemical markers were in the normal ranges in both LABLp-administrated and non-administrated groups, but various disease-related markers tended to decrease in the administrated group. To investigate the effects of LABLp administration on postpartum piglets, the piglets born from prenatally LABLp-administrated sows were divided into two groups and then administrated with or without LABLp. The piglets in the LABLp-administrated group tended to grow very slightly higher than those in the non-administrated group from lactation to early regular rearing. After that, the growth in both groups was almost the same. These results suggest that LABLp administration to prepartum sows is essential for the growth-promoting effect. The postnatal LABLp-administrated piglets showed a lower serum lipid peroxidation index than the non-administrated piglets, and had higher numbers of lactic acid bacteria and bifidobacteria in feces at the end of LABLp treatment. In fattening performances, the LABLp-administrated group showed a significant improvement in meat quality. We also discuss the growth and physiological effects by LpP1-2 administration with iron on piglets because iron administration is another important issue in piglet farming.

microbiology↗

bioRxiv2022

Structure of a monomeric photosystem I core associated with iron-stress-induced-A proteins from Anabaena sp. PCC 7120

Iron-stress-induced-A proteins (IsiAs) are expressed in cyanobacteria under iron-deficient conditions. The cyanobacterium Anabaena sp. PCC 7120 has four isiA genes; however, their binding property and functional roles in PSI are still missing. We analyzed a cryo-electron microscopy structure of a PSI-IsiA supercomplex isolated from Anabaena grown under an iron-deficient condition. The PSI-IsiA structure contains six IsiA subunits associated with the PsaA side of a PSI core monomer. Three of the six IsiA subunits are identified as IsiA1 and IsiA2. The PSI-IsiA structure lacks a PsaL subunit; instead, a C-terminal domain of IsiA2 is inserted at the position of PsaL, which inhibits the oligomerization of PSI, leading to the formation of a monomer. Furthermore, excitation-energy transfer from IsiAs to PSI appeared with a time constant of 55 ps. These findings provide novel insights into both the molecular assembly of the Anabaena IsiA family and the functional roles of IsiAs.

plant biology↗

bioRxiv2022

Potential anti-monkeypox virus activity of atovaquone, mefloquine, and molnupiravir, and their potential use as treatments

Monkeypox virus (MPXV) is a zoonotic orthopoxvirus that causes smallpox-like symptoms in humans and caused an outbreak in May 2022 that led the WHO to declare global health emergency. In this study, from a screening of approved-drug libraries using an MPXV infection cell system, atovaquone, mefloquine, and molnupiravir exhibited anti-MPXV activity, with 50% inhibitory concentrations of 0.51-5.2 M, which is more potent than cidofovir. Whereas mefloquine was suggested to inhibit viral entry, atovaquone and molnupiravir targeted post-entry process to impair intracellular virion accumulation. Inhibitors of dihydroorotate dehydrogenase, an atovaquones target enzyme, showed conserved anti-MPXV activities. Combining atovaquone with tecovirimat enhanced the anti-MPXV effect of tecovirimat. Quantitative mathematical simulations predicted that atovaquone can promote viral clearance in patients by seven days at clinically relevant drug concentrations. Moreover, atovaquone and molnupiravir exhibited pan-Orthopoxvirus activity against vaccinia and cowpox viruses. These data suggest that atovaquone would be potential candidates for treating monkeypox.

microbiology↗

bioRxiv2022

SARS-CoV-2 ORF8 is a viral cytokine regulating immune responses

Many patients with severe COVID-19 suffer from pneumonia, and thus elucidation of the mechanisms underlying the development of such severe pneumonia is important. The ORF8 protein is a secreted protein of SARS-CoV-2, whose in vivo function is not well understood. Here, we analyzed the function of ORF8 protein by generating ORF8-knockout SARS-CoV-2. We found that the lung inflammation observed in wild-type SARS-CoV-2-infected hamsters was decreased in ORF8-knockout SARS-CoV-2-infected hamsters. Administration of recombinant ORF8 protein to hamsters also induced lymphocyte infiltration into the lungs. Similar pro-inflammatory cytokine production was observed in primary human monocytes treated with recombinant ORF8 protein. Furthermore, we demonstrate that the serum ORF8 protein levels are correlated well with clinical markers of inflammation. These results demonstrated that the ORF8 protein is a viral cytokine of SARS-CoV-2 involved in the in the immune dysregulation observed in COVID-19 patients, and that the ORF8 protein could be a novel therapeutic target in severe COVID-19 patients.

microbiology↗

bioRxiv2022

Three-dimensional visualization of moss rhizoid system by refraction-contrast X-ray micro-computed tomography

Land plants have two types of shoot-supporting systems, root system and rhizoid system, in vascular plants and bryophytes. However, since the evolutionary origin of the systems are different, how much they exploit common systems or distinct systems to architect their structures are largely unknown. To understand the regulatory mechanism how bryophytes architect rhizoid system responding to an environmental factor, such as gravity, and compare it with the root system of vascular plants, we have developed the methodology to visualize and quantitatively analyze the rhizoid system of the moss, Physcomitrium patens in 3D. The rhizoids having the diameter of 21.3 m on the average were visualized by refraction-contrast X-ray micro-CT using coherent X-ray optics available at synchrotron radiation facility SPring-8. Three types of shape (ring-shape, line, black circle) observed in tomographic slices of specimens embedded in paraffin were confirmed to be the rhizoids by optical and electron microscopy. Comprehensive automatic segmentation of the rhizoids which appeared in different three form types in tomograms was tested by a method using Canny edge detector or machine learning. Accuracy of output images was evaluated by comparing with the manually-segmented ground truth images using measures such as F1 score and IoU, revealing that the automatic segmentation using the machine learning was more effective than that using Canny edge detector. Thus, machine learning-based skeletonized 3D model revealed quite dense distribution of rhizoids, which was similar to root system architecture in vascular plants. We successfully visualized the moss rhizoid system in 3D for the first time.

plant biology↗

bioRxiv2022

Photosynthetic-product-dependent Activation of Plasma Membrane H+-ATPase and Nitrate Uptake in Arabidopsis Leaves.

Plasma membrane (PM) H+-ATPase is a pivotal enzyme for plant growth and development that acts as a primary transporter and is activated by phosphorylation of the penultimate residue, threonine, at the C-terminus. Photosynthetically active radiation activates PM H+-ATPase via phosphorylation in mesophyll cells of Arabidopsis thaliana, and phosphorylation of PM H+-ATPase depends on photosynthesis and photosynthesis-related sugar supplementation, such as sucrose, fructose and glucose. However, the molecular mechanism and the physiological role of photosynthesis-dependent PM H+-ATPase activation are still unknown. Analysis using sugar analogues, such as palatinose, turanose, and 2-deoxy glucose, revealed that sucrose metabolites and products of glycolysis such as pyruvate induce phosphorylation of PM H+-ATPase. Transcriptome analysis showed that novel isoform of the Small Auxin Up RNA genes, SAUR30, is upregulated in a light- and sucrose-dependent manner. Time course analyzes of sucrose supplementation showed that phosphorylation level of PM H+-ATPase increased within 10 min, but expression level of SAUR30 increased later than 10 min. The results suggest two temporal regulations may participate in the regulation of PM H+-ATPase. Interestingly, a 15NO3- uptake assay in leaves showed that light increases 15NO3- uptake, and that increment of 15NO3- uptake depends on PM H+-ATPase activity. The results opened the possibility of physiological role of photosynthesis-dependent PM H+-ATPase activation in the uptake of NO3-. We speculate that PM H+-ATPase may connect photosynthesis and nitrogen metabolism in leaves.

plant biology↗

bioRxiv2022

β-catenin obstructs γδ T cell immunosurveillance in colon cancer through loss of BTNL expression

WNT/{beta}-catenin signaling endows cancer cells with proliferative capacity and immune-evasive functions that impair anti-cancer immunosurveillance by conventional, cytoxtoic T cells. However, the impact of dysregulated WNT signalling on unconventional, tissue-resident T cells, specifically in colon cancer is unknown. Here, we show that cancer cells in Apc-mutant mouse models escape immunosurveillance from gut-resident intraepithelial lymphocytes (IELs) expressing {gamma}{delta} T cell receptors ({gamma}{delta}TCRs). Analysis of late-stage tumors from mice and humans revealed that {gamma}{delta}IELs are largely absent from the tumor microenvironment, and that butyrophilin-like (BTNL) molecules, which can critically regulate {gamma}{delta}IEL through direct {gamma}{delta}TCR-interactions, are also downregulated. We could attribute this to {beta}-catenin stabilization, which rapidly decreased expression of the transcription factors, HNF4A and HNF4G, that we found to bind promoter regions of Btnl genes, thereby driving their expression in normal gut epithelial cells. Indeed, inhibition of {beta}-catenin signaling restored Btnl1 gene expression and {gamma}{delta} T cell infiltration into tumors. These observations highlight an immune-evasion mechanism specific to WNT-driven colon cancer cells that disrupts {gamma}{delta}IEL immunosurveillance and furthers cancer progression.

cancer biology↗

bioRxiv2022

SARS-CoV-2-neutralizing humoral IgA response occurs earlier but modest and diminishes faster compared to IgG response.

Secretory immunoglobulin A (IgA) plays a crucial role in the mucosal immunity for preventing the invasion of the exogenous antigens, however, little has been understood about the neutralizing activity of serum IgA. Here, to examine the role of IgA antibodies against COVID-19 illnesses, we determined the neutralizing activity of serum/plasma IgG and IgA purified from previously SARS-CoV-2-infected and COVID-19 mRNA-vaccine-receiving individuals. We found that serum/plasma IgA possesses substantial but rather modest neutralizing activity against SARS-CoV-2 compared to IgG with no significant correlation with the disease severity. Neutralizing IgA and IgG antibodies achieved the greatest activity at approximately 25 and 35 days after symptom onset, respectively. However, neutralizing IgA activity quickly diminished and went down below the detection limit approximately 70 days after onset, while substantial IgG activity was observed till 200 days after onset. The total neutralizing activity in sera/plasmas of those with COVID-19 largely correlated with that in purified-IgG and purified-IgA and levels of anti-SARS-CoV-2-S1-binding IgG and anti-SARS-CoV-2-S1-binding IgA. In individuals who were previously infected with SARS-CoV-2 but had no detectable neutralizing IgA activity, a single dose of BNT162b2 or mRNA-1273 elicited potent serum/plasma neutralizing IgA activity but the second dose did not further strengthen the neutralization antibody response. The present data show that the systemic immune stimulation with natural infection and COVID-19 mRNA-vaccines elicit both SARS-CoV-2-specific neutralizing IgG and IgA response in serum, but the IgA response is modest and diminishes faster compared to IgG response. Author SummaryImmunoglobulin A (IgA) is the most abundant type of antibody in the body mostly located on mucosal surfaces as a dimeric secretory IgA. Such secretory IgA plays an important role in preventing the adherence and invasions of foreign objects by its neutralizing activity, while monomeric serum IgA is thought to relate to the phagocytic immune system activation. Here, we report that individuals with the novel coronavirus disease (COVID-19) developed both systemic neutralizing IgG and IgA active against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the neutralizing IgA response was quick and reached the highest activity 25 days post-symptom-onset, compared to 35 days for IgG response, neutralizing IgA activity was modest and diminished faster than neutralizing IgG response. In individuals, who recovered from COVID-19 but had no detectable neutralizing IgA activity, a single dose of COVID-19 mRNA-vaccine elicited potent neutralizing IgA activity but the second dose did not further strengthen the antibody response. Our study provides novel insights into the role and the kinetics of serum IgA against the viral pathogen both in naturally-infected and COVID-19 mRNA-vaccine-receiving COVID-19-convalescent individuals.

microbiology↗

bioRxiv2022

A very long chain fatty acid responsive transcription factor, MYB93, regulates lateral root development in Arabidopsis

Lateral roots (LRs) are critical to rhizosphere development in plants. Although the molecular mechanisms by which auxin regulates LR development has been studied extensively, many additional regulatory systems are thought to be involved. Based on the expression analysis of LTPG1 and 2, we found that they were specifically expressed at the developing LR primordium (LRP), and the number of LRs were reduced in these mutants. Because LTPG is a protein that transports Very Long Chain Fatty Acids (VLCFAs), we hypothesized that VLCFAs regulated LR development. We revealed that late LRP development was stunted when VLCFA levels were reduced in the synthetic mutant, kcs1-5. In this study, we established a method to analyze the LRP development stages with high temporal resolution using a deep neural network. We identified a VLCFA responsible transcription factor, MYB93, from transcriptome analysis of kcs1-5. Interestingly, MYB93 showed a carbon chain length-specific expression response after treatment of VLCFA. Furthermore, myb93 transcriptome analysis suggested that MYB93 regulated the expression of cell wall organization genes. Our results indicated that VLCFA is a regulator of LRP development through transcription factor-mediated regulation of gene expression.

plant biology↗