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PLoS Genetics Jun 2024Sperm heads contain not only the nucleus but also the acrosome which is a distinctive cap-like structure located anterior to the nucleus and is derived from the Golgi...
Sperm heads contain not only the nucleus but also the acrosome which is a distinctive cap-like structure located anterior to the nucleus and is derived from the Golgi apparatus. The Golgi Associated RAB2 Interactors (GARINs; also known as FAM71) protein family shows predominant expression in the testis and all possess a RAB2-binding domain which confers binding affinity to RAB2, a small GTPase that is responsible for membrane transport and vesicle trafficking. Our previous study showed that GARIN1A and GARIN1B are important for acrosome biogenesis and that GARIN1B is indispensable for male fertility in mice. Here, we generated KO mice of other Garins, namely Garin2, Garin3, Garin4, Garin5a, and Garin5b (Garin2-5b). Using computer-assisted morphological analysis, we found that the loss of each Garin2-5b resulted in aberrant sperm head morphogenesis. While the fertilities of Garin2-/- and Garin4-/- males are normal, Garin5a-/- and Garin5b-/- males are subfertile, and Garin3-/- males are infertile. Further analysis revealed that Garin3-/- males exhibited abnormal acrosomal morphology, but not as severely as Garin1b-/- males; instead, the amounts of membrane proteins, particularly ADAM family proteins, decreased in Garin3 KO spermatozoa. Moreover, only Garin4 KO mice exhibit vacuoles in the sperm head. These results indicate that GARINs assure correct head morphogenesis and some members of the GARIN family function distinctively in male fertility.
PubMed: 38935810
DOI: 10.1371/journal.pgen.1011337 -
International Journal of Molecular... Jun 2024Inclusion body myositis (IBM) is a slowly progressive disorder belonging to the idiopathic inflammatory myopathies, and it represents the most common adult-onset...
Inclusion body myositis (IBM) is a slowly progressive disorder belonging to the idiopathic inflammatory myopathies, and it represents the most common adult-onset acquired myopathy. The main clinical features include proximal or distal muscular asymmetric weakness, with major involvement of long finger flexors and knee extensors. The main histological findings are the presence of fiber infiltrations, rimmed vacuoles, and amyloid inclusions. The etiopathogenesis is a challenge because both environmental and genetic factors are implicated in muscle degeneration and a distinction has been made previously between sporadic and hereditary forms. Here, we describe an Italian patient affected with a hereditary form of IBM with onset in his mid-forties. Next-generation sequencing analysis disclosed a heterozygous mutation c.76C>T (p.Pro26Ser) in the PDZ motif of the gene, a mutation already described in a family with a late-onset myopathy and highly heterogenous degree of skeletal muscle weakness. In the proband's muscle biopsy, the expression of ZASP, myotilin, and desmin were increased. In our family, in addition to the earlier age of onset, the clinical picture is even more peculiar given the evidence, in one of the affected family members, of complete ophthalmoplegia in the vertical gaze. These findings help extend our knowledge of the clinical and genetic background associated with inclusion body myopathic disorders.
Topics: Humans; Myositis, Inclusion Body; Male; Pedigree; LIM Domain Proteins; Adaptor Proteins, Signal Transducing; Middle Aged; Muscle, Skeletal; Mutation; Adult
PubMed: 38928252
DOI: 10.3390/ijms25126547 -
International Journal of Molecular... Jun 2024This study aimed to investigate obesity-related glomerulopathy (ORG) at cellular, structural, and transcriptomic levels. Thirty Wistar rats were randomized into two...
This study aimed to investigate obesity-related glomerulopathy (ORG) at cellular, structural, and transcriptomic levels. Thirty Wistar rats were randomized into two groups: 15 rats were fed with a standard diet (SD-rats), and 15 rats were fed with a high-fat diet (HFD-rats). After 10 weeks, the weight, kidney function, histological features, and transcriptomic changes were assessed. HFD-rats gained significantly more weight (55.8% vs. 29.2%; < 0.001) and albuminuria (10,384.04 ng/mL vs. 5845.45 ng/mL; < 0.001) compared to SD-rats. HFD-rats exhibited early stages of ORG, with predominant mesangial matrix increase and podocyte hypertrophy (PH). These lesions correlated with differentially expressed (DE) genes and miRNAs. Functional analysis showed that miR-205, which was DE in both the kidneys and urine of HFD-rats, negatively regulated the PTEN gene, promoting lipid endocytosis in podocytes. The downregulation of PTEN was proved through a higher PTEN/nephrin ratio in the SD-rats and the presence of lipid vacuoles in HFD-podocytes. This study has found a specific targetome of miRNAs and gene expression in early stages of ORG. Also, it emphasizes the potential value of miR-205 as a urinary biomarker for detecting podocyte injury in ORG, offering a tool for early diagnosis, and opening new avenues for future therapeutic research of obesity-related glomerulopathy.
Topics: Animals; MicroRNAs; Obesity; Rats; Diet, High-Fat; Male; Podocytes; Rats, Wistar; RNA, Messenger; Kidney Diseases; Gene Expression Profiling; Gene Expression Regulation; Transcriptome; PTEN Phosphohydrolase
PubMed: 38928144
DOI: 10.3390/ijms25126437 -
Genes Jun 2024The citrus cultivar 'Local Juhong', which has historically been used as a traditional Chinese medicinal material, originated in Yuanjiang County, Hunan Province.Its...
The citrus cultivar 'Local Juhong', which has historically been used as a traditional Chinese medicinal material, originated in Yuanjiang County, Hunan Province.Its parental type and genetic background are indistinct as of yet. Morphological observation shows that 'Local Juhong' has a slight oblateness in fruit shape, a relatively smooth pericarp, a fine and slightly raised oil vacuole, and an inward concave at the blossom end. The tree form and fruit and leaf morphology of 'Local Juhong' are similar to those of 'Huangpi' sour orange. To reveal the genetic background of 'Local Juhong', 21 citrus accessions were evaluated using nuclear and chloroplast SSR markers and whole-genome SNP information. 'Local Juhong' was grouped with mandarins and sub-grouped with 'Miyagawa Wase' and 'Yanxi Wanlu' in a nuclear SSR analysis, which indicated that its pollen parent might be mandarins. It was closely clustered with orange and pummelo in the chloroplast SSR analysis. The genomic sequence similarity rate of 'Local Juhong' with mandarin and pummelo heterozygosity was 70.88%; the main part was the heterozygosity, except for the unknown (19.66%), mandarin (8.73%), and pummelo (3.9%) parts. Thus, 'Local Juhong' may be an F hybrid with pummelo as the female parent and mandarin as the male parent, sharing sisterhood with 'Huangpi' sour orange.
Topics: Citrus; Microsatellite Repeats; Polymorphism, Single Nucleotide; Plants, Medicinal; Genomics; Genome, Plant; Genetic Markers; Phylogeny; Chloroplasts
PubMed: 38927655
DOI: 10.3390/genes15060719 -
Brazilian Journal of Biology = Revista... 2024Hepatozoon spp. are the most common haemoparasites reported from reptiles around the world, however, only six species have been described infecting crocodilians. In...
Hepatozoon spp. are the most common haemoparasites reported from reptiles around the world, however, only six species have been described infecting crocodilians. In Brazil, Hepatozoon caimani Carini, 1909 is currently the only recognized species from the caiman hosts. This study provides new data on the diversity of species of Hepatozoon infecting Caiman crocodilus (Linnaeus) using molecular data and phylogenetic analysis, with additional support of morphological data of developmental stages from host blood and tissue. Forty-four individuals were collected and screened for haemogregarines, and blood and tissue samples were analysed by light microscopy with 31 (70.45%) infected. Hepatozoon spp. blood developmental stages included immature and mature gamonts with or without cytoplasmic vacuoles and free gamonts. Additionally, merogonic developmental stages were found in the liver and spleen of infected hosts. Based on the morphological and molecular data, this study identified two possible different species of Hepatozoon, being one of them the H. caimani with intragenotypic divergence.
Topics: Animals; Phylogeny; Brazil; Alligators and Crocodiles; Eucoccidiida; Coccidiosis; Coccidia
PubMed: 38922198
DOI: 10.1590/1519-6984.282989 -
Reumatologia Clinica Jun 2024VEXAS syndrome is a rare entity secondary to UBA1 gene mutations, located on the X chromosome. This mutation generates, as a consequence, a characteristic vacuolation on...
VEXAS syndrome is a rare entity secondary to UBA1 gene mutations, located on the X chromosome. This mutation generates, as a consequence, a characteristic vacuolation on haematopoietic stem-cells. It is characterized by multiple autoinflammatory and haematologic manifestations, which respond and end up being dependent on corticosteroid treatment. In this publication we present a 2-case series diagnosed at our hospital and make a brief literature review of the published evidence so far.
PubMed: 38918162
DOI: 10.1016/j.reumae.2024.05.006 -
Reumatismo Jun 2024Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a recently characterized disease associated with somatic mutations in the UBA1 gene, which...
Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a recently characterized disease associated with somatic mutations in the UBA1 gene, which cause dysregulation of ubiquitin-mediated processes. This case describes a 71-year-old male patient with VEXAS syndrome who presented with refractory lung inflammation with a pattern similar to computed tomography hypersensitivity pneumonitis, a novel finding in VEXAS syndrome. The presented clinical case highlights the protean involvement of the lung in VEXAS syndrome and emphasizes the importance of considering interstitial lung disease in the differential diagnosis.
Topics: Humans; Male; Aged; Alveolitis, Extrinsic Allergic; Ubiquitin-Activating Enzymes; Syndrome; Vacuoles; Diagnosis, Differential; Tomography, X-Ray Computed; Genetic Diseases, X-Linked; Hereditary Autoinflammatory Diseases; Mutation; Lung Diseases, Interstitial; Lung
PubMed: 38916169
DOI: 10.4081/reumatismo.2024.1611 -
Scientific Reports Jun 2024Floating seedling cultivation technique is a novel seedling method in cotton and it provides an ideal model to study cotton growing under waterlogging stress....
Floating seedling cultivation technique is a novel seedling method in cotton and it provides an ideal model to study cotton growing under waterlogging stress. Morphological character and proteomic profile of the primary root from the seedling cultured by the new technology were evaluated in this study. Compared to seedlings cultured by the traditional method, the diameter of the taproot from floating technology is small at all five seedling stages from one-leaf stage to five-leaf stage. There are similar changes between the thickness of cortex and diameter of stele, which increased from the one- to the two-leaf stage but decreased from the two- to the five-leaf stage. At the one-leaf stage, the number and volume of mitochondria in the primary root-tip cells were less than those in the control. At the two-leaf stage, there was significantly less electron-dense material in the primary root-tip cells than those in the control group. From the one- to the two-leaf stage, the vacuole volume was significantly smaller than that in the control. Total 28 differentially expressed proteins were revealed from aquatic and control group roots of cotton seedlings at the three-leaf stage by two-dimensional electrophoresis, which included 24 up-regulated and four down-regulated proteins. The relative expression of the phosphoglycerate kinase (PGK) gene in aquatic roots increased from the one- to the four-leaf stage but declined rapidly from the four- to the five-leaf stage. The relative expression of the 14-3-3b gene tended to decrease from the one- to the five-leaf stage. The PGK and 14-3-3b genes were specifically expressed in the aquatic roots at the three-leaf stage. In brief, these changes induced waterlogging resistance in the aquatic roots of cotton seedlings in the floating nursery, thereby causing the roots to adapt to the aquatic environment, promoting the growth and development of cotton seedlings.
Topics: Gossypium; Proteomics; Plant Roots; Seedlings; Plant Proteins; Gene Expression Regulation, Plant; Stress, Physiological; Proteome
PubMed: 38914604
DOI: 10.1038/s41598-024-64322-y -
Journal of Pathology and Translational... Jun 2024The identification of idiopathic inflammatory myopathies (IIMs) requires a comprehensive analysis involving clinical manifestations and histological findings. This study...
BACKGROUND
The identification of idiopathic inflammatory myopathies (IIMs) requires a comprehensive analysis involving clinical manifestations and histological findings. This study aims to provide insights into the histopathological and immunohistochemical aspects of IIMs.
METHODS
This retrospective case series involved 56 patients diagnosed with IIMs at the Department of Pathology, University of Medicine and Pharmacy at Ho Chi Minh City, from 2019 to 2023. The histology and immunohistochemical expression of HLA-ABC, HLA-DR, C5b-9, Mx1/2/3, and p62 were detected.
RESULTS
We examined six categories of inflammatory myopathy, including immunemediated necrotizing myopathy (58.9%), dermatomyositis (DM; 23.2%), overlap myositis (8.9%), antisynthetase syndrome (5.4%), inclusion body myositis (IBM; 1.8%), and polymyositis (1.8%). The average age of the patients was 49.7 ± 16.1 years, with a female-to-male ratio of 3:1. Inflammatory cell infiltration in the endomysium was present in 62.5% of cases, perifascicular atrophy was found in 17.8%, and fiber necrosis was observed in 42 cases (75.0%). Rimmed vacuoles were present in 100% of cases in the IBM group. Immunohistochemistry showed the following positivity rates: HLA-ABC (89.2%), HLA-DR (19.6%), C5b-9 (57.1%), and Mx1/2/3 (10.7%). Mx1/2/3 expression was high in DM cases. p62 vacuole deposits were noted in the IBM case. The combination of membrane attack complex and major histocompatibility complex I helped detect IIMs in 96% of cases.
CONCLUSIONS
The diagnosis of IIMs and their subtypes should be based on clinical features and histopathological characteristics. Immunohistochemistry plays a crucial role in the diagnosis and differentiation of these subgroups.
PubMed: 38910358
DOI: 10.4132/jptm.2024.05.02 -
Lipids in Health and Disease Jun 2024Lipid droplet (LD)-laden microglia is a key pathological hallmark of multiple sclerosis. The recent discovery of this novel microglial subtype,...
BACKGROUND
Lipid droplet (LD)-laden microglia is a key pathological hallmark of multiple sclerosis. The recent discovery of this novel microglial subtype, lipid-droplet-accumulating microglia (LDAM), is notable for increased inflammatory factor secretion and diminished phagocytic capability. Lipophagy, the autophagy-mediated selective degradation of LDs, plays a critical role in this context. This study investigated the involvement of microRNAs (miRNAs) in lipophagy during demyelinating diseases, assessed their capacity to modulate LDAM subtypes, and elucidated the potential underlying mechanisms involved.
METHODS
C57BL/6 mice were used for in vivo experiments. Two weeks post demyelination induction at cervical level 4 (C4), histological assessments and confocal imaging were performed to examine LD accumulation in microglia within the lesion site. Autophagic changes were observed using transmission electron microscopy. miRNA and mRNA multi-omics analyses identified differentially expressed miRNAs and mRNAs under demyelinating conditions and the related autophagy target genes. The role of miR-223 in lipophagy under these conditions was specifically explored. In vitro studies, including miR-223 upregulation in BV2 cells via lentiviral infection, validated the bioinformatics findings. Immunofluorescence staining was used to measure LD accumulation, autophagy levels, target gene expression, and inflammatory mediator levels to elucidate the mechanisms of action of miR-223 in LDAM.
RESULTS
Oil Red O staining and confocal imaging revealed substantial LD accumulation in the demyelinated spinal cord. Transmission electron microscopy revealed increased numbers of autophagic vacuoles at the injury site. Multi-omics analysis revealed miR-223 as a crucial regulatory gene in lipophagy during demyelination. It was identified that cathepsin B (CTSB) targets miR-223 in autophagy to integrate miRNA, mRNA, and autophagy gene databases. In vitro, miR-223 upregulation suppressed CTSB expression in BV2 cells, augmented autophagy, alleviated LD accumulation, and decreased the expression of the inflammatory mediator IL-1β.
CONCLUSION
These findings indicate that miR-223 plays a pivotal role in lipophagy under demyelinating conditions. By inhibiting CTSB, miR-223 promotes selective LD degradation, thereby reducing the lipid burden and inflammatory phenotype in LDAM. This study broadens the understanding of the molecular mechanisms of lipophagy and proposes lipophagy induction as a potential therapeutic approach to mitigate inflammatory responses in demyelinating diseases.
Topics: Animals; MicroRNAs; Microglia; Mice; Autophagy; Lipid Droplets; Mice, Inbred C57BL; Demyelinating Diseases; Cathepsin B; Lysophosphatidylcholines; Disease Models, Animal; Male; Gene Expression Regulation; Cell Line
PubMed: 38909243
DOI: 10.1186/s12944-024-02185-y