Dose-dependent serological profiling of AdCLD-CoV19-1 vaccine in adults.

AdCLD-CoV19-1, a chimeric adenovirus-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, was previously reported to elicit robust antibody responses in mice and non-human primates after a single dose. In this study, we conducted a systems serology analysis to investigate changes in humoral immune responses induced by varying doses of the AdCLD-CoV19-1 vaccine in a phase I clinical trial. Serum samples from participants receiving either a low or a high dose of the vaccine were analyzed for antibody features against prototype SARS-CoV-2 spike (S) domains (full-length S, S1, S2, and receptor binding domain), as well as Fc receptor binding and effector functions.

Development of a Multiplex Real-Time PCR Assay for the Simultaneous Detection of Two Fungal Pathogens Causing Pneumonia.

Infectious diseases caused by fungal sources are of great interest owing to their increasing prevalence. Invasive fungal infections, including invasive pulmonary aspergillosis caused by , and pneumonia caused by , are significant causes of morbidity and mortality among immunocompromised patients. The accurate and timely detection of these pathogens in this high-risk population is crucial for effective patient management.

Strategy to develop broadly effective multivalent COVID-19 vaccines against emerging variants based on Ad5/35 platform.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron strain has evolved into highly divergent variants with several sub-lineages. These newly emerging variants threaten the efficacy of available COVID-19 vaccines. To mitigate the occurrence of breakthrough infections and re-infections, and more importantly, to reduce the disease burden, it is essential to develop a strategy for producing updated multivalent vaccines that can provide broad neutralization against both currently circulating and emerging variants.

Boosting with variant-matched adenovirus-based vaccines promotes neutralizing antibody responses against SARS-CoV-2 Omicron sublineages in mice.

Global spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron subvariants, such as BA.4, BA.5 and XBB.

The MYST Family Histone Acetyltransferase SasC Governs Diverse Biological Processes in .

The conserved MYST proteins form the largest family of histone acetyltransferases (HATs) that acetylate lysines within the N-terminal tails of histone, enabling active gene transcription. Here, we have investigated the biological and regulatory functions of the MYST family HAT SasC in the opportunistic human pathogenic fungus using a series of genetic, biochemical, pathogenic, and transcriptomic analyses. The deletion (Δ) of results in a drastically reduced colony growth, asexual development, spore germination, response to stresses, and the fungal virulence.

Liver X receptor controls follicular helper T cell differentiation via repression of TCF-1.

Liver X receptor (LXR) is a critical regulator of cholesterol homeostasis that inhibits T cell receptor (TCR)-induced proliferation by altering intracellular sterol metabolism. However, the mechanisms by which LXR regulates helper T cell subset differentiation remain unclear. Here, we demonstrate that LXR is a crucial negative regulator of follicular helper T (Tfh) cells in vivo.

Functional Characterization of the GNAT Family Histone Acetyltransferase Elp3 and GcnE in .

Post-translational modifications of chromatin structure by histone acetyltransferase (HATs) play a pivotal role in the regulation of gene expression and diverse biological processes. However, the function of GNAT family HATs, especially Elp3, in the opportunistic human pathogenic fungus is largely unknown. To investigate the roles of the GNAT family HATs Elp3 and GcnE in the , we have generated and characterized individual null Δ and Δ mutants.

-Fermented Ameliorates Metabolic-Syndrome-Like Pathological Conditions in Long-Term HFHFD-Fed Mice.

In modern society, numerous metabolic disorders are widespread globally. The present study aimed to demonstrate whether -fermented (BSAX) exerts anti-metabolic disturbance effects compared with the ethyl acetate fraction of (EFAX), a previously verified functional fraction. Mice fed with a high-fat, high-fructose diet (HFHFD) for 10 wk presented a typical model of metabolic dysfunction, and BSAX significantly attenuated a string of metabolic-syndrome-related pathological parameters, such as body, fat, organ mass, lipid markers (TGs, TC, free fatty acids), and glucose metabolism (glucose, insulin), without influencing appetite.

Combinatorial Metabolic Engineering Strategies for the Enhanced Production of Free Fatty Acids in .

In this study, we evaluated the effects of several metabolic engineering strategies in a systematic and combinatorial manner to enhance the free fatty acid (FFA) production in . The strategies included (i) overexpression of mutant thioesterase I ('TesA) to efficiently release the FFAs from fatty acyl-ACP; (ii) coexpression of global regulatory protein FadR; (iii) heterologous expression of methylmalonyl-CoA carboxyltransferase and phosphoenolpyruvate carboxylase to synthesize fatty acid precursor molecule malonyl-CoA; and (iv) disruption of genes associated with membrane proteins (GusC, MdlA, and EnvR) to improve the cellular state and export the FFAs outside the cell. The synergistic effects of these genetic modifications in strain SBF50 yielded 7.

The Lysine Demethylases KdmA and KdmB Differently Regulate Asexual Development, Stress Response, and Virulence in .

Histone demethylases govern diverse cellular processes, including growth, development, and secondary metabolism. In the present study, we investigated the functions of two lysine demethylases, KdmA and KdmB, in the opportunistic human pathogenic fungus . Experiments with mutants harboring deletions of genes encoding KdmA (Δ) and KdmB (Δ) showed that KdmA is necessary for normal growth and proper conidiation, whereas KdmB negatively regulates vegetative growth and conidiation.

The Chimeric Adenovirus (Ad5/35) Expressing Engineered Spike Protein Confers Immunity against SARS-CoV-2 in Mice and Non-Human Primates.

Several COVID-19 platforms have been licensed across the world thus far, but vaccine platform research that can lead to effective antigen delivery is still ongoing. Here, we constructed AdCLD-CoV19 that could modulate humoral immunity by harboring SARS-CoV-2 antigens onto a chimeric adenovirus 5/35 platform that was effective in cellular immunity. By replacing the S1/S2 furin cleavage sequence of the SARS-CoV-2 Spike (S) protein mounted on AdCLD-CoV19 with the linker sequence, high antigen expression was confirmed in various cell lines.

Waveguide-type Maxwellian near-eye display using a pin-mirror holographic optical element array.

We propose a novel, to the best of our knowledge, waveguide-type optical see-through Maxwellian near-eye display for augmented reality. A pin-mirror holographic optical element (HOE) array enables the Maxwellian view and eye-box replication. Virtual images with deep depth of field are presented by each pin-mirror HOE, alleviating the discrepancy between vergence and accommodation distance.

Waveguide-type see-through dual focus near-eye display with a polarization grating.

Waveguide-type near-eye displays have useful properties such as compact form factor, lightweight and see-through capability. Conventional systems, however, support only a single image plane fixed at a certain distance, which may induce eye fatigue due to the vergence-accommodation conflict. In this paper, we propose a waveguide-type near-eye display with two image planes using a polarization grating.

Inhibition of topoisomerase I shapes antitumor immunity through the induction of monocyte-derived dendritic cells.

Understanding the rationale of combining immunotherapy and other anticancer treatment modalities is of great interest because of interpatient variability in single-agent immunotherapy. Here, we demonstrated that topoisomerase I inhibitors, a class of chemotherapeutic drugs, can alter the tumor immune landscape, corroborating their antitumor effects combined with immunotherapy. We observed that topotecan-conditioned TC-1 tumors were occupied by a vast number of monocytic cells that highly express CD11c, CD64, and costimulatory molecules responsible for the favorable changes in the tumor microenvironment.

Transcription Factor HSF1 Suppresses the Expression of Surfactant Protein D in Cells Infected with .

Aspergillosis is a life-threatening disease in patients with compromised immune systems. The process of fungal invasion is an important step during host cell infection. We investigated the transcription factor and promoter region of SFTPD, which is activated during the infection process in conidia-treated cells.

Characterization of the Gene Encoding a Putative APSES Transcription Factor in .

The APSES family proteins are transcription factors (TFs) with a basic helix-loop-helix domain, known to regulate growth, development, secondary metabolism, and other biological processes in species. In the genome of the human opportunistic pathogenic fungus , five genes predicted to encode APSES TFs are present. Here, we report the characterization of one of these genes, called (Afu7g05620).

The Putative APSES Transcription Factor RgdA Governs Growth, Development, Toxigenesis, and Virulence in Aspergillus fumigatus.

The APSES transcription factor (TF) in species is known to govern diverse cellular processes, including growth, development, and secondary metabolism. Here, we investigated functions of the gene (Afu3g13920) encoding a putative APSES TF in the opportunistic human-pathogenic fungus The deletion resulted in significantly decreased hyphal growth and asexual sporulation. Consistently, transcript levels of the key asexual developmental regulators , , and were decreased in the Δ mutant compared to those in the wild type (WT).

Heterotrimeric G-protein signalers and RGSs in .

The heterotrimeric G-protein (G-protein) signaling pathway is one of the most important signaling pathways that transmit external signals into the inside of the cell, triggering appropriate biological responses. The external signals are sensed by various G-protein-coupled receptors (GPCRs) and transmitted into G-proteins consisting of the α, β, and γ subunits. Regulators of G-protein signaling (RGSs) are the key controllers of G-protein signaling pathways.

Enhanced Immunogenicity of Engineered HER2 Antigens Potentiates Antitumor Immune Responses.

For cancer vaccines, the selection of optimal tumor-associated antigens (TAAs) that can maximize the immunogenicity of the vaccine without causing unwanted adverse effects is challenging. In this study, we developed two engineered Human epidermal growth factor receptor 2 (HER2) antigens, K965 and K1117, and compared their immunogenicity to a previously reported truncated HER2 antigen, K684, within a B cell and monocyte-based vaccine (BVAC). We found that BVAC-K965 and BVAC-K1117 induced comparable antigen-specific antibody responses and antigen-specific T cell responses to BVAC-K684.

Comparative Characterization of G Protein α Subunits in .

Trimeric G proteins play a central role in the G protein signaling in filamentous fungi and Gα subunits are the major component of trimeric G proteins. In this study, we characterize three Gα subunits in the human pathogen . While the deletion of and led to reduced colony growth, the growth of the Δ strain was increased in minimal media.

GITR Agonism Triggers Antitumor Immune Responses through IL21-Expressing Follicular Helper T Cells.

Although treatment with the glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) agonistic antibody (DTA-1) has shown antitumor activity in various tumor models, the underlying mechanism is not fully understood. Here, we demonstrate that interleukin (IL)-21-producing follicular helper T (Tfh) cells play a crucial role in DTA-1-induced tumor inhibition. The administration of DTA-1 increased IL21 expression by Tfh cells in an antigen-specific manner, and this activation led to enhanced antitumor cytotoxic T lymphocyte (CTL) activity.

Differentiation of c-Kit CD24 natural killer cells into myeloid cells in a GATA-2-dependent manner.

Myeloid progenitor cells have generally been considered the predominant source of myeloid cells under steady-state conditions. Here we show that NK cells contributed to a myeloid cell lineage pool in naïve and tumor-bearing mice. Using fate tracing of NKp46 cells, we found that myeloid cells could be derived from NK cells.

Transcriptomic and Functional Studies of the RGS Protein Rax1 in Aspergillus fumigatus.

In the comparative transcriptomic studies of wild type (WT) and rax1 null mutant strains, we obtained an average of 22,222,727 reads of 101 bp per sample and found that 183 genes showed greater than 2.0-fold differential expression, where 92 and 91 genes were up-and down-regulated in rax1 compared to WT, respectively. In accordance with the significantly reduced levels of gliM and casB transcripts in the absence of rax1, the rax1 mutant exhibited increased sensitivity to exogenous gliotoxin (GT) without affecting levels of GT production.

High-Throughput Screening of Acyl-CoA Thioesterase I Mutants Using a Fluid Array Platform.

Screening target microorganisms from a mutated recombinant library plays a crucial role in advancing synthetic biology and metabolic engineering. However, conventional screening tools have several limitations regarding throughput, cost, and labor. Here, we used the fluid array platform to conduct high-throughput screening (HTS) that identified 'TesA thioesterase mutants producing elevated yields of free fatty acids (FFAs) from a large (10) mutant library.