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Indian Journal of Ophthalmology May 2024To investigate the histopathological findings of the anterior lens capsule in pediatric patients who had surgery for cataracts.
PURPOSE
To investigate the histopathological findings of the anterior lens capsule in pediatric patients who had surgery for cataracts.
METHODS
This study is a prospective interventional study. Anterior capsule tissue samples that were obtained by the anterior capsulotomy method during phacoemulsification surgery were fixed and examined under a transmission electron microscope.
RESULTS
Twenty-two eyes of 19 patients who were diagnosed with congenital and juvenile cataracts were included in this study. Five patients had associated systemic diseases, including hydrocephalus, cerebral palsy, prematurity, juvenile myelomonocytic leukemia, and Down's syndrome. Electron microscopic evaluation demonstrated single-layered epithelium under the capsule, degenerated organelles with round-oval and prismatic-oval nuclei, and degenerated mitochondria and heterochromatin-rich nuclei. In the case with cerebral palsy, collagen fibrils of the connective tissue and fibroblast-like cells were observed replacing the epithelium that should be underneath the capsule in both eyes, and there was a disorganized distribution of collagen fibrils and vacuole structures in the cytoplasm of fibroblast-like cells.
CONCLUSION
Similar histopathological findings were found in pediatric cataracts with or without systemic disease except in one cerebral palsy case. The absence of lens epithelium may have been a result of degeneration in this patient, and this can be attributed to the presence of systemic inflammation and gliosis in cerebral palsy. The absence of lens epithelium can play a role in the development of dense subcapsular fibrosis and cataract formation.
PubMed: 38767535
DOI: 10.4103/IJO.IJO_2957_23 -
PeerJ 2024Genetic variation for salt tolerance remains elusive in jamun ().
BACKGROUND
Genetic variation for salt tolerance remains elusive in jamun ().
METHODS
Effects of gradually increased salinity (2.0-12.0 dS/m) were examined in 20 monoembryonic and 28 polyembryonic genotypes of jamun. Six genotypes were additionally assessed for understanding salt-induced changes in gas exchange attributes and antioxidant enzymes.
RESULTS
Salt-induced reductions in leaf, stem, root and plant dry mass (PDM) were relatively greater in mono- than in poly-embryonic types. Reductions in PDM relative to control implied more adverse impacts of salinity on genotypes CSJ-28, CSJ-31, CSJ-43 and CSJ-47 (mono) and CSJ-1, CSJ-24, CSJ-26 and CSJ-27 (poly). Comparably, some mono- (CSJ-5, CSJ-18) and poly-embryonic (CSJ-7, CSJ-8, CSJ-14, CSJ-19) genotypes exhibited least reductions in PDM following salt treatment. Most polyembryonic genotypes showed lower reductions in root than in shoot mass, indicating that they may be more adept at absorbing water and nutrients when exposed to salt. The majority of genotypes did not exhibit leaf tip burn and marginal scorch despite significant increases in Na and Cl, suggesting that tissue tolerance existed for storing excess Na and Cl in vacuoles. Jamun genotypes were likely more efficient in Cl exclusion because leaf, stem and root Cl levels were consistently lower than those of Na under salt treatment. Leaf K was particularly little affected in genotypes with high leaf Na. Lack of discernible differences in leaf, stem and root Ca and Mg contents between control and salt treatments was likely due to their preferential uptake. Correlation analysis suggested that Na probably had a greater inhibitory effect on biomass in both mono- and poly-embryonic types. Discriminant analysis revealed that while stem and root Cl probably accounted for shared responses, root Na, leaf K and leaf Cl explained divergent responses to salt stress of mono- and poly-embryonic types. Genotypes CSJ-18 and CSJ-19 seemed efficient in fending off oxidative damage caused by salt because of their stronger antioxidant defences.
CONCLUSIONS
Polyembryonic genotypes CSJ-7, CSJ-8, CSJ-14 and CSJ-19, which showed least reductions in biomass even after prolonged exposure to salinity stress, may be used as salt-tolerant rootstocks. The biochemical and molecular underpinnings of tissue tolerance to excess Na and Cl as well as preferential uptake of K, Ca, and Mg need to be elucidated.
Topics: Syzygium; Genotype; Salt Stress; Salt Tolerance; Plant Leaves; Plant Roots; Salinity; Antioxidants
PubMed: 38766484
DOI: 10.7717/peerj.17311 -
BioRxiv : the Preprint Server For... May 2024Upon entry into host cells, the facultative intracellular bacterium ( .) uses its type IV secretion system, Dot/Icm, to secrete ~330 bacterial effector proteins into...
Upon entry into host cells, the facultative intracellular bacterium ( .) uses its type IV secretion system, Dot/Icm, to secrete ~330 bacterial effector proteins into the host cell. Some of these effectors hijack endoplasmic reticulum (ER)-derived vesicles to form the -containing vacuole (LCV). Despite extensive investigation over decades, the fundamental question persists: Is the LCV membrane distinct from or contiguous with the host ER network? Here, we employ advanced photobleaching techniques, revealing a temporal acquisition of both smooth and rough ER (sER and rER) markers on the LCV. In the early stages of infection, the sER intimately associates with the LCV. Remarkably, as the infection progresses, the LCV evolves into a distinct niche comprising an rER membrane that is independent of the host ER network. We discover that the effector LidA binds to and recruits two host proteins of the Rab superfamily, Rab10, and Rab4, that play significant roles in acquiring sER and rER membranes, respectively. Additionally, we identify the pivotal role of a host ER-resident protein, BAP31, in orchestrating the transition from sER to rER. While previously recognized for shuttling between sER and rER, we demonstrate BAP31's role as a Rab effector, mediating communication between these ER sub-compartments. Furthermore, using genomic deletion strains, we uncover a novel effector, Lpg1152, essential for recruiting BAP31 to the LCV and facilitating its transition from sER to rER. Depletion of BAP31 or infection with an isogenic strain lacking Lpg1152 results in a growth defect. Collectively, our findings illuminate the intricate interplay between molecular players from both host and pathogen, elucidating how orchestrates the transformation of its residing vacuole membrane from a host-associated sER to a distinct rER membrane that is not contiguous with the host ER network.
PubMed: 38765994
DOI: 10.1101/2024.05.10.593622 -
Cureus Apr 2024The first categorization for renal tumours was made by the WHO in 1981 and included only renal cell carcinoma (RCC). After that, classification was continuously altered... (Review)
Review
The first categorization for renal tumours was made by the WHO in 1981 and included only renal cell carcinoma (RCC). After that, classification was continuously altered over five decades. The WHO 2022 Classification of Urinary and Male Genital Tumours 2022 (5 edition) is molecular-driven and contains major revisions compared to the earlier classification from 2016. This revised edition divided renal tumours into four major broad categories: clear cell renal tumours, papillary renal cell tumours, oncocytic and chromophobe renal tumours, and collecting duct tumours. 'Other renal tumours' and 'molecularly defined renal carcinomas' are two other categories that were also included. Transcription factor binding to IGHM enhancer 3 (TFE3)-rearranged, TFEB-altered, elongin C (ELOC)-mutated (formerly TCEB1)-mutated, fumarate hydratase (FH)-deficient, succinate dehydrogenase (SDH)-deficient, anaplastic lymphoma kinase (ALK)-rearranged, and SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1)-deficient renal cell carcinomas are molecularly defined entities. Eosinophilic vacuolated tumours and low-grade oncocytic tumours are classified as emerging entities. Molecularly characterized renal tumours include those with SMARCB1 deficiencies, TFE3 rearrangements, TFEB alterations, ALK rearrangements, ELOC mutations, etc. Thyroid-like follicular carcinoma, eosinophilic vacuolated tumour, and low-grade oncocytic tumour are a few emerging entities of renal tumours. Improved therapy targets for each kidney tumour can be achieved using immunohistochemistry (IHC) and molecular definition updates. This study aims to highlight new developments in the WHO 2022 categorization of renal tumours with regard to diagnostic, morphological, molecular, IHC, clinical, and prognostic updates.
PubMed: 38765391
DOI: 10.7759/cureus.58470 -
Ecotoxicology and Environmental Safety Jul 2024Polystyrene nanoplastics (PS-NPs) have been reported to accumulate in the testes and constitute a new threat to reproductive health. However, the exact effects of PS-NPs...
Polystyrene nanoplastics (PS-NPs) have been reported to accumulate in the testes and constitute a new threat to reproductive health. However, the exact effects of PS-NPs exposure on testicular cells and the underlying mechanisms remain largely unknown. The C57BL/6 male mice were orally administered with PS-NPs (80 nm) at different dosages (0, 10, and 40 mg/kg/day) for 60 days, and GC-1 cells were treated with PS-NPs in this study. Enlarged seminiferous tubule lumens and a loose and vacuolated layer of spermatogenic cells were observed in PS-NPs-exposed mice. Spermatogenic cells which may be one of the target cells for this reproductive damage, were decreased in the mice from PS-NPs group. PS-NPs caused spermatogenic cells to undergo senescence, manifested as elevated SA-β-galactosidase activity and activated senescence-related signaling p53-p21/Rb-p16 pathways, and induced cell cycle arrest. Mechanistically, Gene Ontology (GO) enrichment suggested the key role of reactive oxygen species (ROS) in PS-NPs-induced spermatogenic cell senescence, and this result was confirmed by measuring ROS levels. Moreover, ROS inhibition partially attenuated the senescence phenotype of spermatogenic cells and DNA damage. Using the male health atlas (MHA) database, Sirt1 was filtrated as the critical molecule in the regulation of testicular senescence. PS-NPs induced overexpression of the main ROS generator Nox2, downregulated Sirt1, increased p53 and acetylated p53 in vivo and in vitro, whereas these disturbances were partially restored by pterostilbene. In addition, pterostilbene intervention significantly alleviated the PS-NPs-induced spermatogenic cell senescence and attenuated ROS burst. Collectively, our study reveals that PS-NPs exposure can trigger spermatogenic cell senescence mediated by p53-p21/Rb-p16 signaling by regulating the Sirt1/ROS axis. Importantly, pterostilbene intervention may be a promising strategy to alleviate this damage.
Topics: Animals; Male; Sirtuin 1; Reactive Oxygen Species; Cellular Senescence; Mice; Mice, Inbred C57BL; Polystyrenes; Testis; Spermatogenesis; Nanoparticles; DNA Damage; Signal Transduction
PubMed: 38763051
DOI: 10.1016/j.ecoenv.2024.116461 -
Cell & Bioscience May 2024Methylmalonic acidemia (MMA) is a rare inborn error of propionate metabolism caused by deficiency of the mitochondrial methylmalonyl-CoA mutase (MUT) enzyme. As matter...
BACKGROUND
Methylmalonic acidemia (MMA) is a rare inborn error of propionate metabolism caused by deficiency of the mitochondrial methylmalonyl-CoA mutase (MUT) enzyme. As matter of fact, MMA patients manifest impairment of the primary metabolic network with profound damages that involve several cell components, many of which have not been discovered yet. We employed cellular models and patients-derived fibroblasts to refine and uncover new pathologic mechanisms connected with MUT deficiency through the combination of multi-proteomics and bioinformatics approaches.
RESULTS
Our data show that MUT deficiency is connected with profound proteome dysregulations, revealing molecular actors involved in lysosome and autophagy functioning. To elucidate the effects of defective MUT on lysosomal and autophagy regulation, we analyzed the morphology and functionality of MMA-lysosomes that showed deep alterations, thus corroborating omics data. Lysosomes of MMA cells present as enlarged vacuoles with low degradative capabilities. Notwithstanding, treatment with an anti-propionigenic drug is capable of totally rescuing lysosomal morphology and functional activity in MUT-deficient cells. These results indicate a strict connection between MUT deficiency and lysosomal-autophagy dysfunction, providing promising therapeutic perspectives for MMA.
CONCLUSIONS
Defective homeostatic mechanisms in the regulation of autophagy and lysosome functions have been demonstrated in MUT-deficient cells. Our data prove that MMA triggers such dysfunctions impacting on autophagosome-lysosome fusion and lysosomal activity.
PubMed: 38760822
DOI: 10.1186/s13578-024-01245-1 -
Food Research International (Ottawa,... May 2024Anthocyanins are polyphenolic compounds that provide pigmentation in plants as reflected by pH-dependent structural transformations between the red flavylium cation,...
Anthocyanins are polyphenolic compounds that provide pigmentation in plants as reflected by pH-dependent structural transformations between the red flavylium cation, purple quinonoidal base, blue quinonoidal anion, colourless hemiketal, and pale yellow chalcone species. Thermodynamically stable conditions of hydrated plant cell vacuoles in vivo correspond to the colourless hemiketal, yet anthocyanin colour expression appears in an important variety of hues within plant organs such as flowers and fruit. Moreover, anthocyanin colour from grape berries is significant in red winemaking processes as it plays a crucial role in determining red wine quality. Here, nonlinear ordinary differential equations were developed to represent the evolution in concentration of various anthocyanin species in both monomeric (chemically reactive) and self-associated (temporally stable) forms for the first time, and simulations were verified experimentally. Results indicated that under hydrating conditions, anthocyanin pigmentation is preserved by self-association interactions, based on pigmented monomeric anthocyanins experiencing colour loss whereas colour-stable self-associated anthocyanins increase in concentration nonlinearly over time. In particular, self-association of the flavylium cation and the quinonoidal base was shown to influence colour expression and stability within Geranium sylvaticum flower petals and Vitis vinifera grape skins. This study ultimately characterises fundamental mechanisms of anthocyanin stabilisation and generates a quantitative framework for anthocyanin-containing systems.
Topics: Anthocyanins; Vitis; Color; Kinetics; Wine; Fruit; Hydrogen-Ion Concentration; Nonlinear Dynamics
PubMed: 38760130
DOI: 10.1016/j.foodres.2024.114195 -
Acta Neuropathologica May 2024Dominantly inherited mutation D395G in the gene encoding valosin-containing protein causes vacuolar tauopathy, a type of behavioural-variant frontotemporal dementia,...
Dominantly inherited mutation D395G in the gene encoding valosin-containing protein causes vacuolar tauopathy, a type of behavioural-variant frontotemporal dementia, with marked vacuolation and abundant filamentous tau inclusions made of all six brain isoforms. Here we report that tau inclusions were concentrated in layers II/III of the frontotemporal cortex in a case of vacuolar tauopathy. By electron cryomicroscopy, tau filaments had the chronic traumatic encephalopathy (CTE) fold. Tau inclusions of vacuolar tauopathy share this cortical location and the tau fold with CTE, subacute sclerosing panencephalitis and amyotrophic lateral sclerosis/parkinsonism-dementia complex, which are believed to be environmentally induced. Vacuolar tauopathy is the first inherited disease with the CTE tau fold.
Topics: Humans; Tauopathies; Chronic Traumatic Encephalopathy; tau Proteins; Valosin Containing Protein; Mutation; Vacuoles; Male; Adenosine Triphosphatases; Cell Cycle Proteins; Middle Aged; Frontotemporal Dementia; Brain; Female
PubMed: 38758288
DOI: 10.1007/s00401-024-02741-x -
The EMBO Journal May 2024While the molecular mechanism of autophagy is well studied, the cargoes delivered by autophagy remain incompletely characterized. To examine the selectivity of autophagy...
While the molecular mechanism of autophagy is well studied, the cargoes delivered by autophagy remain incompletely characterized. To examine the selectivity of autophagy cargo, we conducted proteomics on isolated yeast autophagic bodies, which are intermediate structures in the autophagy process. We identify a protein, Hab1, that is highly preferentially delivered to vacuoles. The N-terminal 42 amino acid region of Hab1 contains an amphipathic helix and an Atg8-family interacting motif, both of which are necessary and sufficient for the preferential delivery of Hab1 by autophagy. We find that fusion of this region with a cytosolic protein results in preferential delivery of this protein to the vacuole. Furthermore, attachment of this region to an organelle allows for autophagic delivery in a manner independent of canonical autophagy receptor or scaffold proteins. We propose a novel mode of selective autophagy in which a receptor, in this case Hab1, binds directly to forming isolation membranes during bulk autophagy.
PubMed: 38755257
DOI: 10.1038/s44318-024-00091-8 -
Nature Communications May 2024The transition between yeast and hyphae is crucial for regulating the commensalism and pathogenicity in Candida albicans. The mechanisms that affect the invasion of...
The transition between yeast and hyphae is crucial for regulating the commensalism and pathogenicity in Candida albicans. The mechanisms that affect the invasion of hyphae in solid media, whose deficiency is more related to the pathogenicity of C. albicans, have not been elucidated. Here, we found that the disruption of VAM6 or VPS41 which are components of the homotypic vacuolar fusion and protein sorting (HOPS) complex, or the Rab GTPase YPT72, all responsible for vacuole fusion, led to defects in hyphal growth in both liquid and solid media, but more pronounced on solid agar. The phenotypes of vac8Δ/Δ and GTR1-vam6Δ/Δ mutants indicated that these deficiencies are mainly caused by the reduced mechanical forces that drive agar and organs penetration, and confirmed that large vacuoles are required for hyphal mechanical penetration. In summary, our study revealed that large vacuoles generated by vacuolar fusion support hyphal penetration and provided a perspective to refocus attention on the role of solid agar in evaluating C. albicans invasion.
Topics: Candida albicans; Hyphae; Vacuoles; Fungal Proteins; Animals; Mice; rab GTP-Binding Proteins; Candidiasis; Vesicular Transport Proteins; Female; Membrane Fusion
PubMed: 38755250
DOI: 10.1038/s41467-024-48525-5