Small Subunit Research Articles

Infundibulicybe swatica (Basidiomycota, Agaricales), a new species from Pakistan

A new species, Infundibulicybe swatica is described and illustrated from District Swat, Khyber Pakhtunkhwa, Pakistan. The new taxon is characterized by pale yellow to pale yellow brown to brown pileus with a dark brown center; a bicolorous stipe, white at the apex and pale yellow brown hues at the base; hyaline, lacrymoid to sub-lacrymoid, small, inamyloid basidiospores (6.5 × 4.2 µm); and the absence of hymenial cystidia. Molecular phylogenetic analyses based on nuclear ribosomal Internal Transcribed Spacer (ITS) and nuclear ribosomal Large Subunit (LSU) regions confirm the novelty of the taxon.

Diversification of molecular pattern recognition in bacterial NLR-like proteins.

Antiviral STANDs (Avs) are bacterial anti-phage proteins evolutionarily related to immune pattern recognition receptors of the NLR family. Type 2 Avs proteins (Avs2) were suggested to recognize the phage large terminase subunit as a signature of phage infection. Here, we show that Avs2 from Klebsiella pneumoniae (KpAvs2) can recognize several different phage proteins as signature for infection. While KpAvs2 recognizes the large terminase subunit of Seuratvirus phages, we find that to protect against Dhillonvirus phages, KpAvs2 recognizes a different phage protein named KpAvs2-stimulating protein 1 (Ksap1). KpAvs2 directly binds Ksap1 to become activated, and phages mutated in Ksap1 escape KpAvs2 defense despite encoding an intact terminase. We further show that KpAvs2 protects against a third group of phages by recognizing another protein, Ksap2. Our results exemplify the evolutionary diversification of molecular pattern recognition in bacterial Avs2, and show that a single pattern recognition receptor evolved to recognize different phage-encoded proteins.

Multifunctional acyltransferase HBO1: a key regulatory factor for cellular functions.

HBO1, also known as KAT7 or MYST2, is a crucial histone acetyltransferase with diverse cellular functions. It typically forms complexes with protein subunits or cofactors such as MEAF6, ING4, or ING5, and JADE1/2/3 or BRPF1/2/3, where the BRPF or JADE proteins serve as the scaffold targeting histone H3 or H4, respectively. The histone acetylation mediated by HBO1 plays significant roles in DNA replication and gene expression regulation. Additionally, HBO1 catalyzes the modification of proteins through acylation with propionyl, butyryl, crotonyl, benzoyl, and acetoacetyl groups. HBO1 undergoes ubiquitination and degradation by two types of ubiquitin complexes and can also act as an E3 ubiquitin ligase for the estrogen receptor α (ERα). Moreover, HBO1 participates in the expansion of medullary thymic epithelial cells (mTECs) and regulates the expression of peripheral tissue genes (PTGs) mediated by autoimmune regulator (AIRE), thus inducing immune tolerance. Furthermore, HBO1 influences the renewal of hematopoietic stem cells and the development of neural stem cells significantly. Importantly, the overexpression of HBO1 in various cancers suggests its carcinogenic role and potential as a therapeutic target. This review summarizes recent advancements in understanding HBO1's involvement in acylation modification, DNA replication, ubiquitination, immunity, and stem cell renewal.

Identification and biological characteristics of Fusarium tobaccum sp. nov., a novel species causing tobacco root rot in Jilin Province, China.

Fusarium wilt of tobacco (FWT), caused by Fusarium spp., has emerged as a severe threat to tobacco production in China. In all, 132 isolates of Fusarium were isolated from tobacco and pathogenic to tobacco-causing FWT in Jilin Province, China. In this study, we identified 7 of 132 isolates as a novel species Fusarium tobaccum sp. nov. Zhao Xie & Jie Gao, using multi-gene phylogenetic analyses of translation elongation factor (tef1), β-tubulin (tub2), calmodulin (cmdA), and RNA polymerase II second largest subunit (rpb2) genes, along with subtle morphological differences. Isolates of F. tobaccum sp. nov. were clustered in a distinct branch in the maximum parsimony phylogenetic tree generated from the sequences of tef1-rpb2-tub2-cmdA and can be distinguished from closely related species F. cugenangense, F. callistephi, and F. elaeidis. The morphological characteristics of F. tobaccum sp. nov. are distinct from other Fusarium species. F. tobaccum sp. nov. exhibits abundant aerial mycelia and pigment production on potato dextrose agar (PDA), microconidia with 0-1 septa, and macroconidia with 2-5 septa on carnation leaf-piece agar (CLA), and produces abundant chlamydospores on Spezieller Nährstoffarmer agar (SNA) and CLA. The mycelia of F. tobaccum exhibited optimal growth at a pH of 7.1 and a temperature of 23.6°C. Sucrose and NaNO3 significantly promoted the mycelial growth of F. tobaccum. PD medium was optimal for total sporulation. However, the sporulation ratios of the macrospores of F. tobaccum in PD, SN, and CMC were relatively low (0.48%, 2.51%, and 2.16%, respectively). These findings provided valuable insights into the morphological and biological characteristics of F. tobaccum.IMPORTANCEFusarium wilt of tobacco (FWT) is a prevalent issue in tobacco-growing regions globally, leading to significant losses in yield and quality. This study identified F. tobaccum sp. nov., a novel species of Fusarium causing FWT in China. The identification was based on multi-gene phylogenetic analyses and morphological characteristics. The effects of temperature, pH, carbon source, nitrogen source, medium, and light on the mycelial growth of F. tobaccum sp. nov. were determined. These findings might contribute to future research on the pathogenic mechanisms of this novel species and the development of strategies to control FWT.

Biodiversity and Hemolytic Toxicity of the Genus Heterocapsa (Dinophyceae) in the Beibu Gulf, China

The dinoflagellate genus Heterocapsa includes several widely distributed and potentially toxic species associated with Harmful Algal Blooms (HABs), particularly affecting the Western Pacific Ocean. To reveal the biodiversity of Heterocapsa in Beibu Gulf, six strains were morphologically characterized using light and scanning electron microscopy, while large subunit rDNA (LSU rDNA) and internal transcribed spacer (ITS) were sequenced for phylogenetic analysis through maximum likelihood and Bayesian inferences. Two strains (BGERL169, BGERL170) were identified as Heterocapsa philippinensis ribotype I, three (BGERL171-BGERL173) as a new Heterocapsa philippinensis ribotype II, and one strain (BGERL174) as Heterocapsa pseudotriquetra. Cells of H. philippinensis were ovoid to spherical, yellowish-brown, with reticulate chloroplasts, and had a sausage-shaped nucleus positioned longitudinally along the dorsal side of the cell, and the theca was arranged in Po, cp, X, 5′, 3a, 7″, 6c, 5s, 5‴, 2⁗. Additionally, BGERL169 and BGERL171 showed no hemolytic toxicity in rabbit erythrocyte lysis assays. To the best of our knowledge, this research provides the first morphological and phylogenetic analysis of H. philippinensis, including the identification of a new ribotype, as well as the discovery of H. pseudotriquetra in Chinese waters. The findings contribute to the understanding of Heterocapsa species biogeography and toxicity in Chinese waters, offering valuable data for future HAB monitoring in Beibu Gulf.

Mycobacterium tuberculosis Antigen Rv1471 Induces Innate Immune Memory and Adaptive Immunity against Infection.

Protein subunit vaccines form a key pipeline for developing novel tuberculosis (TB) vaccines. Mycobacterium tuberculosis (Mtb) contains approximately 4000 individual proteins. However, only approximately 100 have been evaluated as antigens in the clinical and preclinical stages of vaccine development. Trained immunity-targeting vaccines induce innate immune memory against heterologous infections and enhance antigen-specific adaptive immune responses. However, no trained immunity-targeting subunit TB vaccine has been reported yet. This study tested Rv1471, a thioredoxin secreted by Mtb, as a candidate TB vaccine antigen due to its capacity to stimulate mouse bone marrow-derived macrophages (BMDMs). Rv1471 induced functional and phenotypic maturation of BMDMs in vitro, reflected by the increased production of inflammatory cytokines and surface expression of co-stimulatory molecules. Transcription analysis of Rv1471-trained BMDMs indicated that innate immune memory was activated through pathways of Akt-mTOR-HIF-1α and aerobic glycolysis. Rv1471 also enhanced innate immune memory responses and protection against intracellular infections of different mycobacteria. In a murine model of TB, immunization with Rv1471 formulated with liposomal DDA/MPLA adjuvant produced robust antigen-specific multi-functional CD4+ and CD8+ T-cell immune responses and had substantial protective efficacy against Mtb challenge. Analysis of recall immunity showed that the Rv1471 subunit vaccine triggered robust T-cell immunity post Mtb infection. These findings support the development of an innate immune memory-targeting subunit TB vaccine to increase TB vaccine efficacy.

Explicit description of viral capsid subunit shapes by unfolding dihedrons.

Viral capsid assembly and the design of capsid-based nanocontainers critically depend on understanding the shapes and interfaces of constituent protein subunits. However, a comprehensive framework for characterizing these features is still lacking. Here, we introduce a novel approach based on spherical tiling theory that explicitly describes the 2D shapes and interfaces of subunits in icosahedral capsids. Our method unfolds spherical dihedrons defined by icosahedral symmetry axes, enabling systematic characterization of all possible subunit geometries. Applying this framework to real T = 1 capsid structures reveals distinct interface groups within this single classification, with variations in interaction patterns around 3-fold and 5-fold symmetry axes. We validate our classification through molecular docking simulations, demonstrating its consistency with physical subunit interactions. This analysis suggests different assembly pathways for capsid nucleation. Our general framework is applicable to other triangular numbers, paving the way for broader studies in structural virology and nanomaterial design.

Vanderwaltozyma japonica sp. nov.: a novel yeast isolated from subtropical regions in Japan.

Seven yeast strains, NBRC 11072, NBRC 11076, NBRC 11078T, NBRC 11080, NBRC 116645, NBRC 116646 and NBRC 116647, were isolated from the subtropical regions of Japan. The seven strains share identical nucleotide sequences in the D1/D2 domains of the large subunit (LSU) rRNA gene and internal transcribed spacer (ITS) regions. Six strains (NBRC 11072, NBRC 11076, NBRC 11078T, NBRC 11080, NBRC 116645 and NBRC 116646) share identical mitochondrial cytochrome c oxidase subunit II (COX II) sequences as well, while NBRC 116647 differs from them by one substitution in this region. The yeast strains were closely related to Vanderwaltozyma verrucispora NBRC 1884T in the ITS regions. However, in the D1/D2 domains and COX II, they were closely related to Torulaspora globosa CBS 764T and Naumovozyma castellii NRRL Y-12630T, respectively. They differed from V. verrucispora by 49 nucleotide substitutions with 26 gaps in the ITS region, from T. globosa by 19 nucleotide substitutions with 3 gaps in the D1/D2 domains and from N. castellii by 49 nucleotide substitutions with 6 gaps in the COX II. The phylogenetic analysis of the seven strains based on the sequences of the D1/D2 domains of LSU and ITS regions among related species showed that these strains represent a single novel species within the genus Vanderwaltozyma. The seven strains could be differentiated from other known species of the genus Vanderwaltozyma because of their inability to assimilate glycerol as a carbon source. Therefore, we suggest that these seven strains represent a novel species, designated Vanderwaltozyma japonica sp. nov. The holotype is NBRC 11078T (isotype: TBRC 19102T). The MycoBank number is MB 855476.

Combination application of Pickering emulsion and BLS protein nanoparticles enhances vaccine efficacy.

The deficiency of recombinant protein immune response could be compensated for by using nanoparticle platforms or adding immune enhancers, however existing vaccines or adjuvants struggle to elicit durable cellular immune responses. In this work, a protein nanoscaffold, lumazine synthase isolated from Brucella (BLS) was optimally designed that could facilitate cellular uptake of displayed antigens and the maturation of bone marrow-derived dendritic cells (BMDCs), and enhancing humoral immune responses. To enhance cellular immune response, chitosan hydrochloride-stabilized Pickering emulsion (CHSPE) was evaluated as an adjuvant for the BLS nanoscaffold-based vaccine. CHSPE could enhance the recruitment and activation of DCs at the injection site and the uptake of antigen and activation of DCs in the draining lymph nodes (dLNs), compared with commercial adjuvant ISA 206. In addition, CHSPE induced antigen-specific antibody levels comparable to those of ISA 206 and increased the ratio of central memory T cells (TCM) and effector memory T cells (TEM), and promoted the secretion of Th1-type cytokines. Moreover, CHSPE-formulated vaccine provided a similar level of protection to the live attenuated vaccine and was superior to that of ISA 206. Taken together, the combination of the BLS nanoscaffold and CHSPE provides a feasible strategy for recombinant protein subunit vaccine development.

Possible rapid reduction of anti-RBD antibody titre after SARS-CoV-2 mRNA vaccination in pregnant women: Multicentre prospective study.

Pregnant women are at increased risk for severe illness associated with coronavirus disease 2019 (COVID-19) compared to nonpregnant women. The aim of this multicenter prospective study was to assess the current COVID-19 vaccination status of pregnant women in the southern Osaka district and to compare their antibody titers with those of nonpregnant women. Serum antibody titers of anti-NCP antibodies (antibodies against the SARS-CoV-2 nucleocapsid) and anti-RBD antibodies (the receptor binding domain of the S1 subunit of the spike protein) were evaluated in 753 pregnant women at 34-35 weeks of gestation from October 2021 to March 2022. Anti-RBD antibody titre was also investigated in 1003 health care workers at Kindai University hospital 3 and 6 months after a second dose of the vaccine from March 2021 to April 2021. 519 (68.9%) pregnant women were vaccinated during pregnancy, of whom 497 (95.8%) received two doses. The COVID-19 infection rate calculated from the number of pregnant women with a positive anti-NCP antibody titre or with confirmed diagnosis was 5.1% (12/234) in the unvaccinated and 3.5% (18/519) in the vaccinated. The estimated half-life calculated from anti-RBD antibody titers and the number of days between vaccination and antibody testing was 39.9 days. The antibody titre and half-life in pregnant women were significantly lower and shorter than in nonpregnant women aged 20-39 years (109.4 days). Our study showed that pregnant women may have lower vaccine-acquired COVID-19 immunity than nonpregnant women.

Plasmodium cynomolgi Infections Not Found in Microscopy-Diagnosed Malaria Cases across Sabah, Malaysia.

Zoonotic malaria presents a major public health challenge in Southeast Asia. Plasmodium cynomolgi coinfects the same macaque hosts and mosquito vectors as the most common cause of zoonotic malaria, Plasmodium knowlesi. Plasmodium cynomolgi appears morphologically similar to Plasmodium vivax on microscopy and can amplify P. vivax polymerase chain reaction (PCR) assays, confounding transmission estimates. We screened 2,103 samples for P. cynomolgi across all 26 districts in Sabah, Malaysia, from 2010 to 2021. Samples comprised 1,425 P. knowlesi, 256 P. vivax, 293 P. falciparum, and 31 Plasmodium malariae PCR-confirmed malaria cases and 100 malaria microscopy-positive and species-specific PCR-negative samples. A nested PCR assay targeting P. cynomolgi-specific 18S small subunit ribosomal ribonucleic acid with a detection limit of ∼2 parasites/µL was conducted on whole blood samples. No P. cynomolgi infections were detected. Symptomatic P. cynomolgi co-infections appear rare in Malaysia, although prevalence may be underestimated owing to the absence of routine molecular screening and the sensitivity of available assays.

Abstract 4123630: MRPL44 Plays an Important Role in Cardiac Hypertrophy and Function

Background: Mitochondrial ribosomal large subunit 44 (MRPL44) knockout mice were embryonic lethal, for which mutations are known to cause mitochondrial infantile cardiomyopathy and hypertrophic cardiomyopathy. However, it remains unknown how MRPL44 contributes to cardiac function and hypertrophy. Aims: Our aim is to investigate the effect of MRPL44 haploinsufficiency in mice. Methods: MRPL44 haploinsufficient (MRPL44 +/- ) mice were generated. Mineralocorticoid receptor-associated hypertension mice were induced in MRPL44 +/- and wild-type (WT, MRPL44 +/+ ) mice with subcutaneous infusion of aldosterone(Aldo) and 8% NaCl food for 4 weeks after uninephrectomy. Systolic blood pressure was measured by tail cuffs every week. WB, qPCR, cardiac echo, and histological examinations were performed. RNA sequencing analysis, electron microscopy examinations and mitochondrial activity assay were performed to find differences between MRPL44 +/- and MRPL44 +/+ mice. Results: MRPL44 haploinsufficient mice spontaneously developed left ventricular hypertrophy. Heart rate, blood pressure, and cardiac systolic function were normal in MRPL44 haploinsufficient mice. MRPL44 was decreased about to 70% in MRPL44 haploinsufficient mice and mitochondrial arrangement were impaired in electron microscopic analysis. After Aldo treatment, blood pressure elevation were similar, however, MRPL44 haploinsufficient mice developed left ventricular systolic dysfunction and dilation compared with MRPL44 +/+ mice. WB showed mitochondrial electron transport chain protein complex IV expression was significantly decreased. Furthermore, mitochondrial activity assay showed MRPL44 haploinsufficient mice had a significant reduction in complex IV activity, whereas complex I and II activity were similar to MRPL44 +/+ mice. RNA sequencing analysis showed the significant changes in the expression of ribosomal subunits coded by nucleus in addition to mitochondrial ribosomal subunits. These results indicate MRPL44 plays an important role in the cardiac function of mitochondrial electron transport chain protein complexes via the expression of ribosomal protein subunits coded by both nucleus and mitochondria. Conclusion: MRPL44 haploinsufficient mice spontaneously develop left ventricular hypertrophy and shows systolic dysfunction after aldosterone treatment accompanied with oxidative phosphorylation enzyme dysfunction.

First Report of Root Rot Caused by Fusarium equiseti on Syrian rue (Peganum harmala) in China.

Syrian rue (Peganum harmala L) belongs to the family Zygophyllaceae and is mainly distributed in arid and semi-arid areas of Xinjiang, Gansu, Ningxia, Qinghai, and Inner Mongolia in China. It serves as a pioneer species in soil and water conservation, as well as in reclamation of wastelands, playing a crucial role in soil preservation and stabilization against sand encroachment. In 2023, a disease resembling root rot and wilt affected the quality and yield of Syrian rue in Xilingol (122.67°N, 42.78°E), Inner Mongolia, China. Symptoms ranged from yellowing to wilting, accompanied by darkening of the xylem in the roots. This disease was observed in approximately 50% of Syrian rue plants in desertification-prone grassland. A total number of 45 symptomatic root samples were collected from Syrian rue plants to isolate the pahogen. Small pieces of diseased tissue were surface sterilized with 75% alcohol for five seconds, rinsed twice with sterilized water, dried, and then placed on water agar and incubated for 72 h at 25℃ in darkness. A total of 45 isolates were obtained, showing identical morphology and sequences of the internal transcribed spacer region (ITS), translation elongation factor 1-alpha (EF1-α) and RNA polymerase II second largest subunit (RPB2) genes. Therefore, the isolate LTP-5 was used as the representative for further study. On potato dextrose agar (PDA), fungal colonies of LTP-5 exhibited yellow to light brown colore with white aerial mycelia and irregular growth after 7 days of incubation at 25℃. Conidia and chlamydospre development were observed in carboxymethylcellulose sodium medium. Chlamydospores were abundant, terminal or intergrown between hyphae, rough brown walls of 5.9 to 19.82 μm in diameter (n = 75) were observed in the culture. Macroconidia had 5 to 7 septa, thick in the middle and thin at both ends, measured 28.17 to 62.81 μm in length and 1.50 to 4.19 μm in width (n = 128). Microconidia were absent. The morphological characteristics were consistent with the descriptions of Fusarium equiseti (Nelson et al., 1983). The pathogen was further confirmed to be F. equiseti by sequence analysis of the ITS, EF1-α and RPB2 genes amplified using polymerase chain reaction (PCR) with the primers ITS4/ITS5 (White et al., 1990), EF-1/EF-2 (O'Donnell et al., 1998), and RPB2-5F2 /fRPB2-7cR (Zhen et al., 2017). The sequences showed 100% similarity to the F. equiseti strain in the NCBI GenBank with accession numbers MH054914.1, KJ396323.1, and KT213286.1 for ITS, EF1-α, and RPB2, respectively. The sequences of PCR products were submitted to GenBank with accession numbers PP814863.1 (ITS), PP831628.1 (EF1-α) and PP826937.1 (RPB2). Pathogenicity tests were conducted through a pot assay. Five Syrian rue seedlings were inoculated by immersing plant roots in a suspension of 1×107 spores/mL for 30 min and transplanting to pots containing autoclaved soil. Control plants were immersed in sterile water. The inoculated plants showed yellow and root rot but no symptoms were observed on control plants. The same fungus was successfully re-isolated and identified based on the morphological characterization and sequence analyses from the infected root tissue but not from non-inoculated plants. In addition, F. equiseti has been reported to cause disease on Sugar beet (Khan et al., 2021), Watermelon (Rahman et al., 2021), potato (Cui et al., 2021), and other plants. This is the first report confirming F. equiseti as causal agent of Syrian rue wilt and root rot in China.

Integrated Profiling Identifies Long-Term Molecular Consequences of Prenatal Dexamethasone Treatment in the Rat Brain-Potential Triggers of Depressive Phenotype and Cognitive Impairment.

Prenatal excess of glucocorticoids (GCs) is considered to be one of the highly impacting factors contributing to depression development. Although GCs are crucial for normal fetal development and their administration (mainly dexamethasone, DEX) is a life-saving procedure for those at risk of preterm delivery, exposure to excess levels of GCs during pregnancy can yield detrimental consequences. Therefore, we aimed to systematically investigate the brain molecular alterations triggered by prenatal DEX administration. We used a rat model of depression based on prenatal exposure to DEX and performed integrative multi-level methylomic, transcriptomic, and proteomic analyses of adult rats' brains (i.e., frontal cortex (FCx) and hippocampus (Hp)) to identify the outcomes of DEX action. Each of the investigated levels was significantly affected by DEX in the long-term manner. Particularly, we found 200 CpG islands to be differentially methylated in the FCx and 200 in the Hp of prenatally DEX-treated rats. Global transcriptomic analysis uncovered differential expression of transcripts mostly in FCx (271) and 1 in Hp, while proteomic study identified 146 differentially expressed proteins in FCx and 123 in Hp. Among the identified enriched molecular networks, we found altered pathways involved in synaptic plasticity (i.e., cAMP, calcium, and Wnt signaling pathways or tight junctions and adhesion molecules), which may contribute to cognitive impairment, observed in DEX-treated animals. Moreover, in the FCx, DEX administration in the prenatal period downregulates the expression of ribosome protein genes associated both with large and small ribosomal subunit assembly which can lead to a global decrease in translation and protein synthesis processes and, indirectly, alterations in the neurotransmission process.

The variety of abomasal nematode communities of captive and free-roaming populations of European bison, Bison bonasus (L.): a morphometric and molecular approach.

Most studies concerning parasitic infections in European bison have been performed on free-ranging animals: comparatively little is known about the abomasal nematodes of captive wisents, which are widely used in reintroduction programmes. The aim of the study was to determine the infection level and species composition of abomasal nematodes in captive European bison in enclosures (including zoos) and breeding centres compared to free-ranging individuals. It also includes a morphological analysis of the parasites based on figures and measurement data. Altogether, 11 species of nematodes were detected, with both captive and free-ranging animals demonstrating similar species compositions. Among those, 2 species of blood-sucking nematodes were detected, including Ashworthius sidemi and Haemonchus contortus. Interestingly, A. sidemi was found in almost all free-roaming animals, but only in 1 captive European bison. In addition, H. contortus was predominant in captive animals. The morphological identification was confirmed molecularly for 5 nematode species: A. sidemi, H. contortus, Ostertagia kolchida, O. ostertagi and Spiculopteragia boehmi. The identification was performed using small subunit ribosomal rDNA. The study provides the first available set of specular lengths of the gastric nematodes of European bison, and the first molecular data of O. kolchida and S. boehmi derived from the same host species. Our findings may simplify the morphometrical and molecular identification of Trichostrongylidae species infecting European bison, and can be useful in developing new management strategies for populations of this near-threatened species in Europe.

GNG5 is a novel regulator of Aβ42 production in Alzheimer's disease.

The therapeutic options for Alzheimer's disease (AD) are limited, underscoring the critical need for finding an effective regulator of Aβ42 production. In this study, with 489 human postmortem brains, we revealed that homotrimer G protein subunit gamma 5 (GNG5) expression is upregulated in the hippocampal-entorhinal region of pathological AD compared with normal controls, and is positively correlated with Aβ pathology. In vivo and in vitro experiments confirm that increased GNG5 significantly promotes Aβ pathology and Aβ42 production. Mechanically, GNG5 regulates the cleavage preference of γ-secretase towards Aβ42 by directly interacting with the γ-secretase catalytic subunit presenilin 1 (PS1). Moreover, excessive GNG5 increases the protein levels and the activation of Rab5, leading to the increased number of early endosomes, the major cellular organelle for production of Aβ42. Furthermore, immunoprecipitation and immunofluorescence revealed co-interaction of Aβ42 with GPCR family CXCR2, which is known as the receptor for IL-8, thus facilitating the dissociation of G-proteins βγ from α subunits. Treatment of Aβ42 in neurons combined with structure prediction indicated Aβ42 oligomers as a new ligand of CXCR2, upregulating γ subunit GNG5 protein levels. The co-localizations of GNG5 and PS1, CXCR2 and Aβ42 were verified in eight human brain regions. Besides, GNG5 is significantly reduced in extracellular vesicles (EVs) derived from cerebral cortex or serum of AD patients compared with healthy cognition controls. In brief, GNG5 is a novel regulator of Aβ42 production, suggesting its clinical potential as a diagnosis biomarker and the therapeutic target for AD. The GNG5 content in EVs derived from serum and brain tissue of patients with AD significantly reduced. The GNG5 expression in the hippocampal-entorhinal neurons of donors with pathological AD significantly increased, and can exist in homotrimer subtypes. GNG5 expression positively correlates with Aβ pathology and Aβ42 production. Homotrimer-GNG5 binds to the γ-secretase catalytic subunit PS1 and preferentially generates Aβ42 in early endosome. GNG5 leads to enhanced Rab5 protein and activation levels, increased number of early endosome, promoting Aβ42 production. Further, Aβ42 binds to CXCR2 to upregulate GNG5 levels in a feedback loop.

Mitochondrial Genome Analysis of Babesia ovis (Apicomplexa: Babesiidae) Endemic in Sheep in Türkiye

This study presents the first comprehensive analysis of the mitochondrial genome of Babesia ovis, a significant pathogen in ovine babesiosis in Türkiye. The B. ovis mitochondrial genome is a linear monomeric molecule of 6015 bp with an A + T content of 70.5%, featuring terminal inverted repeats (TIRs) at both ends. It encodes three essential proteins (Cox1, Cox3, and Cob) and six fragments of large subunit rRNA genes. Comparative analysis revealed high sequence identity with Babesia sp. Xinjiang (87.5%) and Babesia sp. Dunhuang (87.5%), suggesting a close evolutionary relationship. The study highlights the conservation of mitochondrial gene content across Babesia and Theileria species, emphasizing their utility in phylogenetic studies. The findings also suggest that TIR variability plays a role in mitochondrial genome size differences, influencing species-specific adaptations. This research provides valuable insights into the evolution and functional adaptations of B. ovis and underscores the potential of mitochondrial genomic data in enhancing diagnostic and therapeutic strategies for babesiosis. Further exploration of mitochondrial genomes in Babesia species is essential for understanding their biology and developing effective control measures.

Combined effect of basic antiherpetic drugs with a new inhibitor of the terminase complex of herpes simplex virus type 1 in Vero cell culture

More than 90% of the world’s population are carriers of herpes simplex virus type 1 (HSV-1). The infection manifests itself in the formation of blisters and ulcers on the face or genitals, and can cause blindness, encephalitis, and generalized infection. All modern first- and second-line antiherpetic drugs selectively inhibit viral DNA-polymerase. The purine-benzoxazine conjugate LAS-131 [(S)-4-[6-(purin-6-yl)aminohexanoyl]-7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine], which we described earlier, uses the large subunit of the HSV-1 terminase complex as a biotarget and selectively inhibits its reproduction in vitro. For the first time, we have obtained fundamentally new results on the combined effect of LAS-131 on human herpesvirus infection with practically significant antiviral compounds – nucleoside analogues (acyclovir [ACV], penciclovir [PCV], ganciclovir [GCV], brivudine [BVDU], iododeoxyuridine [IDU], adenine arabinoside [Ara-A], as well as a nucleoside phosphonate analogue (cidofovir [CDV]) and a pirophosphate analogue (foscarnet [FOS]). Using a inhibition assay of cytopathic effect (CPE) induced by a virus, it was shown that when combined with LAS-131, the concentrations of the compounds in combinations providing inhibition of HSV-1-induced CPE by 50%, decreased by 2 times (additive effect, FOS) or more (synergistic effect, ACV, PCV, GCV, IDU, BVDU, Ara-A, CDV). Reducing the concentrations of agents creates non-permissive conditions for the reproduction of HSV-1 and opens up new real possibilities for controlling human herpesvirus infection.

Morphological, molecular and 3D synchrotron X-ray tomographic characterizations of Helicascus satunensis sp. nov., a novel mangrove fungus.

A new species of Helicascus satunensis sp. nov. was collected on mature dead fruits of the Nypa palm in Satun Province, southern Thailand. Its morphological characteristics are similar to those of the genus Helicascus. Recently, a genus Helicascus with three species from marine habitats worldwide was studied. The morphology of this fungus was investigated and combined with multigene sequence analyzes of small subunit (SSU), large subunit (LSU), internal transcribed spacer (ITS) ribosomal DNA, translation elongation factor 1-alpha (TEF-1α) and RNA polymerase II (RPB2) genes. Morphologically, H. satunensis sp. nov. is characterized by semi-immersed, lenticular ascomata, multilocules, a bitunicate ascus and smooth, obovoid, dark brown ascospores that are one-septate and unequally two-celled. In addition, 3D visualization using synchrotron X-ray tomography was performed to investigate the interaction between fruiting body and substrata. Molecular phylogeny with multigene revealed that H. satunensis sp. nov. belongs to the family Morosphaeriaceae, order Pleosporales, class Dothideomycetes. Furthermore, H. satunensis sp. nov. forms a well-supported clade with Helicascus species described from marine habitats. Based on the unique morphological and molecular evidence, we propose this fungus, H. satunensis sp. nov., as a new species for Helicascus.

Critical and differential roles of eIF4A1 and eIF4A2 in B-cell development and function.

Eukaryotic initiation factor 4 A (eIF4A) plays critical roles during translation initiation of cellular mRNAs by forming the cap-binding eIF4F complex, recruiting the 40S small ribosome subunit, and scanning the 5' untranslated region (5' UTR) for the start codon. eIF4A1 and eIF4A2, two isoforms of eIF4A, are highly conserved and exchange freely within eIF4F complexes. The understanding of their biological and molecular functions remains incomplete if not fragmentary. In this study, we showed that eIF4A1 and eIF4A2 exhibit different expression patterns during B-cell development and activation. Mouse genetic analyses showed that they play critical but differential roles during B-cell development and humoral immune responses. While eIF4A1 controls global protein synthesis, eIF4A2 regulates the biogenesis of 18S ribosomal RNA and the 40S ribosome subunit. This study demonstrates the distinct cellular and molecular functions of eIF4A1 and eIF4A2 and reveals a new role of eIF4A2 in controlling 40S ribosome biogenesis.