Defect In Synthesis Research Articles

A study on CT detection image generation based on decompound synthesize method

Background Nuclear graphite and carbon components are vital structural elements in the cores of high-temperature gas-cooled reactors(HTGR), serving crucial roles in neutron reflection, moderation, and insulation. The structural integrity and stable operation of these reactors heavily depend on the quality of these components. Helical Computed Tomography (CT) technology provides a method for detecting and intelligently identifying defects within these structures. However, the scarcity of defect datasets limits the performance of deep learning-based detection algorithms due to small sample sizes and class imbalance. Objective Given the limited number of actual CT reconstruction images of components and the sparse distribution of defects, this study aims to address the challenges of small sample sizes and class imbalance in defect detection model training by generating approximate CT reconstruction images to augment the defect detection training dataset. Methods We propose a novel CT detection image generation algorithm called the Decompound Synthesize Method (DSM), which decomposes the image generation process into three steps: model conversion, background generation, and defect synthesis. First, STL files of various industrial components are converted into voxel data, which undergo forward projection and image reconstruction to obtain corresponding CT images. Next, the Contour-CycleGAN model is employed to generate synthetic images that closely resemble actual CT images. Finally, defects are randomly sampled from an existing defect library and added to the images using the Copy-Adjust-Paste (CAP) method. These steps significantly expand the training dataset with images that closely mimic actual CT reconstructions. Results Experimental results validate the effectiveness of the proposed image generation method in defect detection tasks. Datasets generated using DSM exhibit greater similarity to actual CT images, and when combined with original data for training, these datasets enhance defect detection accuracy compared to using only the original images. Conclusion The DSM shows promise in addressing the challenges of small sample sizes and class imbalance. Future research can focus on further optimizing the generation algorithm and refining the model structure to enhance the performance and accuracy of defect detection models.

Transcriptomic and Metabolomic Analysis Reveals Multifaceted Impact of Gcn5 Knockdown in Drosophila Development

Background: General control nonderepressible 5 (Gcn5) is a lysine acetyltransferase (KAT) that is evolutionarily conserved across eukaryotes, with two homologs (Kat2a and Kat2b) identified in humans and one (Gcn5) in Drosophila. Gcn5 contains a P300/CBP-associated factor (PCAF) domain, a Gcn5-N-acetyltransferase (GNAT) domain, and a Bromodomain, allowing it to regulate gene expression through the acetylation of both histone and non-histone proteins. In Drosophila, Gcn5 is crucial for embryonic development, with maternal Gcn5 supporting early development. However, the functional mechanisms of Gcn5 after the depletion of maternal deposits remain unclear. Methods: Our study employed the Gal4/UAS-RNAi system to achieve whole-body or heart-specific Gcn5 knockdown in Drosophila and selected 96-hour-old surviving larvae for transcriptomic and metabolomic analyses. Results: Omics results revealed that Gcn5 knockdown significantly impacts various metabolic pathways, as well as lysosomes, non-homologous end-joining, Toll and Imd signaling pathways, and circadian rhythms, among others. Furthermore, defects in chitin synthesis may be associated with impaired pupation. Additionally, heart-specific Gcn5 knockdown affected cardiac physiology but appeared to have a potential protective effect against age-related cardiac decline. Conclusions: These findings deepen our understanding of Gcn5’s roles in Drosophila development and provide valuable insights for developing Gcn5-targeted therapies, particularly considering its involvement in various human diseases.

Lung function in adult patients with osteogenesis imperfecta: a cohort study

BackgroundOsteogenesis imperfecta (OI) is a rare hereditary bone disease resulting from a defect in collagen synthesis or processing, leading to bone fragility, frequent fractures and skeletal deformities. OI is associated with increased respiratory morbidity and mortality, but the mechanisms of lung involvement are poorly understood, and there are no data on the natural history of lung function. We studied lung function over time in a cohort of adult OI patients at one center.MethodsWe used data from OI patients aged 15 and above followed up at the Lausanne university hospital between 2012 and 2023 with available pre-bronchodilator spirometry. Associations between spirometric measurements at first visit and clinical characteristics were studied through linear regression. Changes of spirometric variables over time were analysed through mixed linear regression. Models were adjusted for age, sex, height and OI type (Sillence classification).ResultsAmong 46 subjects, 24% had impaired spirometry at baseline, with similar distribution between restrictive (8.7%), obstructive (8.7%) and mixed (6.5%) ventilatory patterns. At first visit, higher age was associated with lower FEV1 (β = −0.019 l, p = 0.014) and lower FEV1/FVC (β = −0.175%, p = 0.012). A history of asthma was associated with higher FEV1 (β = 0.636 l, p = 0.028) and FVC (β = 0.834 l, p = 0.010). At first visit, FEV1 (β = −0.750 l, p = 0.006) and FVC (β = −0.859 l, p = 0.004) was lower in individuals with OI Sillence types 3, 4 or 5 compared to type 1. Over a mean follow-up of 3.4 years, smokers had a greater decline of FEV1/FVC compared to non-smokers (β = −6.592%, p = 0.007). Individuals with a mutation in the gene COL1A2 had 740 ml lower FVC compared to those with a mutation in COL1A1 (p = 0.037). After adjustment for sex, age, height and OI type, FEV1 increased by 26 ml (95% CI 8; 45) or 1.28%pred (0.51; 2.05) and FVC increased by 25 ml (95% CI 8; 43) or 0.93%pred (0.31; 1.55) per year of follow-up.ConclusionsAn increase of FEV1 and FVC over time was observed in OI patients after adjustment for other variables, suggesting that the defective collagen synthesis may impact the pulmonary interstitium and lead to increased lung compliance and hyperinflation, in contrast to skeletal deformities, which reduce the thoracic volume. Lung function changes in OI thus result from the interplay of several mechanisms.

Congenital Adrenal Hyperplasia (CAH) - Causes, Diagnosis, Symptoms, Treatment

Introduction and Purpose: Congenital adrenal hyperplasia represents a group of genetic disorders characterized by improper adrenal steroidogenesis, resulting in deficiency or absence of cortisol and/or aldosterone, and varying degrees of disturbances in sexual development. The aim of this study is to raise awareness about the disease, enabling early diagnosis and contributing to reducing neonatal mortality, as the first clinical manifestation of CAH can be the life-threatening salt-wasting syndrome. State of Knowledge: Congenital adrenal hyperplasia (CAH), also known as congenital adrenal hyperplasia, encompasses a group of inherited disorders affecting the adrenal glands located above the kidneys. Adrenal glands produce various hormones, including cortisol, aldosterone, and androgens. CAH involves deficiencies in the enzymes necessary for the production of these hormones, leading to hormonal disturbances. Summary: Congenital adrenal hyperplasia (CAH), also referred to as congenital adrenal hyperplasia (CAH), describes a group of genetic diseases causing defects in adrenal hormone synthesis. CAH results in deficiency or absence of cortisol and/or aldosterone. The most common causes are mutations in the CYP21 gene (21-hydroxylase deficiency), CYP11B2 gene (11β-hydroxylase deficiency), and HSD3B2 gene (3β-hydroxysteroid dehydrogenase deficiency). Enzymatic deficiencies lead to compensatory increases in CRH and ACTH secretion, causing adrenal hyperplasia and excessive androgen synthesis.

Respiratory Outcomes of Interrupted Modulator Therapies in Children With Cystic Fibrosis.

Cystic fibrosis (CF) is a multisystemic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, resulting in defective synthesis or function of the CFTR protein. Historically, CF treatment focused on managing symptoms and complications. Fortunately, modulator drugs are now available to directly target the defective CFTR protein. However, in some countries, such as Turkey, these drugs are not covered by social insurance. Consequently, many CF patients face barriers to accessing modulatory therapies or must interrupt their treatment. This study demonstrates the impact of interrupting modulator therapy on pulmonary function, emphasizing the need for uninterrupted continuous treatment. In this study, 39 CF patients receiving elexacaftor-tezacaftor-ivacaftor (ETI) at our clinic were retrospectively analyzed. Among the patients, 18 experienced one or more interruptions, ranging from 15 to 210 days during ETI treatment. We analyzed pulmonary function test results from 27 interruption periods. At the beginning of the interruption, the mean percent predicted FEV1 (ppFEV1) was 69.59% ± 25.87%, which decreased to 64.96% ± 24.52% by the end of the interruption. There was a significant decrease with a mean change of 4.62 ± 8.49 (p = 0.008). However, no significant correlation was found between the interruption duration and FEV1 change. Our results demonstrate that pulmonary functions are adversely affected by interruption periods, regardless of their duration. Even short interruptions have a significant impact on pulmonary functions. This underscores the need for uninterrupted continuation of modulatory treatment and for improved policies to ensure equitable access to treatment.

Analyses of the gut microbial composition of domestic pig louse Haematopinus suis

Haematopinus suis is an obligatory ectoparasite of the domestic pig, serving as a vector of several swine pathogens and posing great threats to the pig industry. The gut microbiome of lice is thought of an important mediator of their healthy physiology. However, there is a great paucity of lice-associated microbial communities’ structure and function. The current study aimed to profile the gut microbiome and to understand the microbial functions of swine lice by metagenomic sequencing and bioinformatics analyses. In total, 102,358 (77.2 %) nonredundant genes were cataloged, by contrast, only a small proportion of genes were assigned to microbial taxa and functional assemblages. Bacteria of known or potential public health significance such as Anaplasma phagocytophilum, Chlamydia trachomatis, Waddlia chondrophila, Bacillus cereus, and Leptotrichia goodfellowii were observed in all samples. The integrated microbial profile further illustrated the evolutionary relevance of endosymbionts and detailed the functional composition, and findings suggested H. suis may acquire adenosylcobalamin by feeding due to an adenosylcobalamin synthesis defect and a lack of complete synthases of endosymbionts. Sucking lice contained fewer functional genes compared with ticks and fleas probably because of the obligate host specificity of parasitic lice. In addition, the genes from the intestines contained encompassed most of the microbial functional genes in sucking lice. A wide range of unknown taxonomic and functional assemblages were discovered, which improves our understanding related to microbial features and physiological activities of sucking lice. In general, this study increases the characterization of the microbiota of lice and offers clues for preventing and controlling lice infestation in swine production in the future.

Engineered bacterial lipoate protein ligase A (lplA) restores lipoylation in cell models of lipoylation deficiency

Protein lipoylation, a vital lysine posttranslational modification (PTM), plays a crucial role in the function of key mitochondrial TCA cycle enzymatic complexes. In eukaryotes, lipoyl PTM synthesis occurs exclusively through de novo pathways, relying on lipoyl synthesis/transfer enzymes, dependent upon mitochondrial fatty acid and Fe-S cluster biosynthesis. Dysregulation in any of these pathways leads to diminished cellular lipoylation. Efficient restoration of lipoylation in lipoylation deficiency cell states using either chemical or genetic approaches has been challenging due to pathway complexity and multiple upstream regulators. To address this challenge, we explored the possibility that a bacterial lipoate protein ligase (lplA) enzyme, that can salvage free lipoic acid bypassing the dependency on de novo synthesis, could be engineered to be functional in human cells. Overexpression of the engineered lplA in lipoylation null cells restored lipoylation levels, cellular respiration, and growth in low glucose conditions. Engineered lplA restored lipoylation in all tested lipoylation null cell models, mimicking defects in mitochondrial fatty acid synthesis (MECR KO), Fe-S cluster biosynthesis (BOLA3 KO), and specific lipoylation regulating enzymes (FDX1, LIAS and LIPT1 KOs). Furthermore, we describe a patient with a homozygous c.212C>T variant LIPT1 with a previously uncharacterized syndromic congenital sideroblastic anemia. K562 erythroleukemia cells engineered to harbor this missense LIPT1 allele recapitulate the lipoylation deficient phenotype and exhibit impaired proliferation in low glucose that is completely restored by engineered lplA. This synthetic approach offers a potential therapeutic strategy for treating lipoylation disorders.

Prevalence of dental caries, oral health status, malocclusion status, and dental treatment needs in thalassemic children: A cross-sectional study

ABSTRACT Background: Thalassemia is a hemoglobinopathy-associated genetic disease resulting due to defective synthesis of globin chains, causing defects in the skeletal and oral structures. Aim: This cross-sectional study was designed to analyze the prevalence of dental caries, oral health status, malocclusion status, and dental treatment needs in thalassemic children. Materials and Methods: Institutional Ethical committee clearance was obtained before starting the study. The study sample comprised 100 thalassemic and 100 normal children in which oral disease markers like dmft/DMFT index, plaque index, gingival index, and Angle’s classification for malocclusion were used. The statistical tool used was ‘one-way ANOVA’ with the probability set at 0.05. Results and Observations: Statistically significant differences in prevalence of dental caries, periodontal disease, malocclusion, and treatment needs were noted in thalassemic individuals when compared to normal subjects. Conclusion: The present study has given an insight into the various oral and dentomaxillofacial manifestations of thalassemia, thus considering the importance of routine oral examination for the prevention of dental caries and periodontal diseases.

Mitoception, or transfer of normal cell mitochondria to cancer cells, reverses remodeling of store-operated Ca2+ entry in tumor cells

Most cancer cells show the Warburg effect, the rewiring of aerobic metabolism to glycolysis due to defective mitochondrial ATP synthesis. As a consequence, tumor cells display enhanced mitochondrial potential (∆Ψ), the driving force for mitochondrial Ca2+ uptake. Mitochondria control the Ca2+-dependent inactivation of store-operated channels (SOCs), leading to enhanced and sustained store-operated Ca2+ entry (SOCE) involved in cancer hallmarks. We asked here whether the transfer of mitochondria (mitoception) from normal cells to tumor cells may reverse SOCE remodeling in cancer cells. For this end, we labeled mitochondria in normal NCM460 human colonic cells, isolated them and transferred them to tumor HT29 cells. We tested the viability and efficiency of mitoception using flow cytometry and confocal microscopy, as well as calcium imaging to investigate the effects of mitoception on SOCE. Our results show that mitoception of tumor HT29 cells with normal mitochondria restores a low ∆Ψ and SOCE. Conversely, self-mitoception of tumor HT29 cells with tumor cell mitochondria increases further ∆Ψ and SOCE, thus excluding the possibility that effects of mitoception are due to increased mitochondrial mass. Strikingly, mitoception of normal NCM460 cells with tumor cell mitochondria has no effects on either ∆Ψ or SOCE. These results are consistent with the previous proposal that transformed mitochondria may modulate SOC channels involved in SOCE. Further research is warranted to test whether mitoception of cancer cells with normal mitochondria may reverse Ca2+ remodeling associated to cancer.

Absence of the dolichol synthesis gene DHRSX leads to N-glycosylation defects in Lec5 and Lec9 Chinese hamster ovary cells

Glycosylation-deficient Chinese hamster ovary (CHO) cell lines have been instrumental in the discovery of N-glycosylation machinery. Yet, the molecular causes of the glycosylation defects in the Lec5 and Lec9 mutants have been elusive, even though for both cell lines a defect in dolichol formation from polyprenol was previously established. We recently found that dolichol synthesis from polyprenol occurs in three steps consisting of the conversion of polyprenol to polyprenal by DHRSX, the reduction of polyprenal to dolichal by SRD5A3 and the reduction of dolichal to dolichol, again by DHRSX.This led us to investigate defective dolichol synthesis in Lec5 and Lec9 cells. Both cell lines showed increased levels of polyprenol and its derivatives, concomitant with decreased levels of dolichol and derivatives, but no change in polyprenal levels, suggesting DHRSX deficiency. Accordingly, N-glycan synthesis and changes in polyisoprenoid levels were corrected by complementation with human DHRSX but not with SRD5A3. Furthermore, the typical polyprenol dehydrogenase and dolichal reductase activities of DHRSX were absent in membrane preparations derived from Lec5 and Lec9 cells, while the reduction of polyprenal to dolichal, catalyzed by SRD5A3, was unaffected. Long-read whole genome sequencing of Lec5 and Lec9 cells did not reveal mutations in the ORF of SRD5A3, but the genomic region containing DHRSX was absent. Lastly, we established the sequence of Chinese hamster DHRSX and validated that this protein has similar kinetic properties to the human enzyme. Our work therefore identifies the basis of the dolichol synthesis defect in CHO Lec5 and Lec9 cells.

6367 Growth gone Awry: A Rare Case of Acromegaly in a 16-Year-Old Female with Panhypopituitarism Secondary to Craniopharyngioma on Low Doses of Growth Hormone with Low IGF-1 levels

Abstract Disclosure: L.M. Ayala Castro: None. J. Ye Tay: None. A. Diaz: None. This report highlights a rare case of a 16-year-old female with panhypopituitarism due to craniopharyngioma, where GH replacement therapy triggered acromegaly features despite having low IGF-1 levels. Background: Craniopharyngiomas are the most common tumors causing acquired pituitary deficiencies in children. Various mechanisms contribute to acromegaly, and hypersensitivity to hormonal treatment in this benign tumor emerges as a plausible avenue for investigation. Case Presentation: A 16-year-old female diagnosed with craniopharyngioma at age 5 developed secondary panhypopituitarism. Baseline hormonal profiles indicated markedly reduced levels of IGF-1 and insulin growth factor–binding protein 3 (IGF-BP3). Despite the established condition, GH treatment was initiated at age 8 for potential growth and development benefits. Before commencing GH therapy, a bone age assessment revealed normal skeletal development. However, GH replacement therapy led to an unexpectedly robust response, resulting in physical changes consistent with acromegaly. Paradoxically, laboratory evaluations showed low IGF-1 levels. Imaging studies, including pituitary MRI, ruled out new abnormalities or tumors. As the patient approached peak adult height at 16, having been on adult GH therapy since age 13, a decision was made to discontinue GH replacement therapy and address acromegaly symptoms. Frequent follow-up visits were planned to assess growth velocity, monitor hormonal levels, and evaluate potential adverse effects. Discussion: This case demonstrates an unusual sensitivity to exogenous GH, resulting in an exaggerated response contrary to expected IGF-1 elevation. Atypical IGF-1 levels may suggest alterations in liver physiology, GH receptor signaling pathways (e.g., Laron Syndrome), or downstream defects in IGF-1 synthesis. Further research is crucial to elucidate the underlying mechanisms. Conclusion: Only 3 cases of acromegaly as a side effect of GH replacement therapy have been reported in the literature. We report a further case that underscores the complexity of managing hormonal imbalances, especially in unique patient populations with panhypopituitarism secondary to craniopharyngioma. The unexpected response to GH treatment emphasizes the need for individualized approaches and vigilant monitoring.

A Study On Haematological Abnormalities In Decompensated Chronic Liver Disease At Government General Hospital, Vijayawada

Background: chronic liver failure is usually associated with hypersplenism and diminished erythrocyte survival is frequent. Dietary deficiencies, alcoholism, bleeding and defective hepatic synthesis of proteins used in blood formation or coagulation worsen the problem. Plasma volume is increased in patients with cirrhosis,particularly in those with ascites ,this hypervolemia may account for a low peripheral hemoglobin or erythrocyte level. Materials and methods: this is a crosssectional,analytical study of 100 patients conducted in patients with decompensated chronic liver disease admitted in siddhartha medical college hospital during the period january 2023 to december 2023. Results: our study included 100 patients with decompensated chronic liver disease,upon performing haematological profile ,anemia is seen in 88%,thrombocytopenia is seen in 80%,elevated pt,inr in 37% patients which predict the chances of upper gi bleed.derangements in these parameters can ultimately lead to grave complications

MTHFR polymorphisms and vitamin B12 deficiency: correlation between mthfr polymorphisms and clinical and laboratory findings.

Vitamin B12 deficiency is a common condition that causes a variety of disorders ranging from the development of megaloblastic anemia to the building up of neurological damage. Historically one of the leading causes of B12 deficiency appears to be secondary to malabsorption in part caused by the development of atrophic gastritis in pernicious anemia. More recently B12 deficiency could also depend on dietary restrictions. Cobalamin deficiency also appears to be closely related to folate metabolism, causing a reduction in methionine synthase activity. This results in the accumulation of 5-methyltetrahydrofolate (5-MTHF) and defective DNA synthesis. It has been hypothesized that reduced activity of the enzyme methylene-tetrahydrofolate reductase (MTHFR) could reduce the production of 5-MTHF, thereby shifting folate metabolism to thymidylate synthesis and promoting proper DNA synthesis. Our aim was to investigate the role of the C677T and A1298C MTHFR gene polymorphisms, which are associated with reduced enzyme activity, in predisposing to the development of anemia, neurological symptoms, and atrophic gastritis in a population of 105 consecutive Italian patients with cobalamin deficiency. We found statistically significant correlations between the degree of anemia and thrombocytopenia and the C677T MTHFR polymorphism, while hemoglobin levels alone significantly correlated with A1298C polymorphism, contradicting the potential protective role of these polymorphisms. Furthermore, in patients with atrophic gastritis, we found an association between the absence of parietal cell antibodies and the presence of the C677T polymorphism in homozygosity. Our results suggest a role for MTHFR enzyme activity in the severity of hematologic manifestations of vitamin B12 deficiency and as an independent mechanism of predisposition to the development of atrophic gastritis.

Effects of MOF-MoO3-x derivatives synthesis and oxygen defect engineering on photocatalytic CO2 reduction

Photocatalytic conversion of CO2 into valuable fuels is considered a promising approach for the development of sustainable and renewable energy sources. In this study, we utilized Mo-MOF as a precursor to obtain MoO3 by pyrolytic derivatization and treated it to obtain MOF-MoO3-x containing oxygen vacancies as a catalyst for the photocatalytic reduction of CO2 to CO. MOF derivatization altered the morphology of the MoO3, which made the formation of oxygen vacancies easier and facilitated the separation of electron-hole pairs. Meanwhile, the increased specific surface area and the appearance of surface oxygen vacancies enhanced the CO2 adsorption and activation capabilities of MOF-MoO3-x. As a result, MOF-MoO3-x demonstrated a significant enhances in the photoreduction activity of CO2. Its CO yield was 29.1 μmolg−1h−1, which was 3.7 times higher than that of MOF-MoO3 and 2.4 times higher than that of H-MoO3-x. This innovative strategy may provide a new avenue for improving the comprehensive performance of photocatalysts and developing renewable energy sources.

Application of Generative Adversarial Networks in Semi-Annotated Defect Synthesis and Detection Under Limited Resources

Defect detection is a crucial technology that is extensively employed in the manufacturing industry to monitor and ensure the quality of output. Deep learning models have shown remarkable potential for defect detection. However, the success of these models heavily relies on voluminous training data. Collecting substantial amounts of defect data is challenging in practical settings, and the tedious process of pixel-level defect annotation further complicates the task. Among the common defects encountered in manufacturing, scratches are particularly significant. To address these challenges, this study proposes a two-phase generative adversarial network (GAN) approach for synthesizing defect images and generating semi-automatic pixel-wise labels for anomaly detection. The first phase primarily focuses on synthesizing images, while the second phase involves the pixel-wise labeling of the images. The synthesized paired images generated by the GANs serve as input to the semantic network. Notably, the proposed methodology requires only a few real defect samples for training and a small amount of annotated data, making it practical and computationally efficient for implementation in the manufacturing industry. Experimental results indicate the effectiveness of the proposed deep-learning solution in defect detection, specifically in identifying scratches on various textured and patterned surfaces. A notably high detection accuracy is achieved, validating the potential of the approach in real-world manufacturing scenarios.

A Study on the Improvement of YOLOv5 and the Quality Detection Method for Cork Discs

Combining machine vision and deep learning, optical detection technology can achieve intelligent inspection. To address the issues of low efficiency and poor consistency in the quality classification of cork discs used for making badminton heads, research on optimizing the YOLOv5 image-processing algorithm was conducted and applied to cork disc quality detection. Real-time images of cork discs were captured using industrial cameras, and a dataset was independently constructed. A GAN-based defect synthesis algorithm was employed to resolve the lack of defect samples. An attention mechanism was embedded in the YOLOv5 backbone network to enhance feature representation. The number of anchors in the YOLOv5 detection layer was reduced to address similar sample sizes, a center-matching strategy was designed to balance positive samples, and a shortest-distance label assignment algorithm was developed to eliminate ambiguities, improving accuracy and reducing postprocessing complexity. Detection results were integrated into quality classification. Experiments on the NVIDIA RTX3080 GPU demonstrated that the optimized algorithm improved the original YOLOv5 F1 score by 2.4% and mF1 score by 9.0%, achieving a quality classification F1 score of 95.1%, a processing speed of 178.5 FPS, and an mAP of 81.5%. Comparative experiments showed that the improved algorithm achieved the best detection accuracy on the cork disc dataset while maintaining high processing speed.

Nutritional value of a novel EMS-induced cell wall-defective strain of Saccharomyces cerevisiae yeast for Pacific oyster (Magallana gigas) juveniles

The difficulties and high costs of live microalgae production have driven the search for alternative diets in bivalve aquaculture. The baker's yeast (Saccharomyces cerevisiae) represents a promising, cost-effective, high-quality protein for aquaculture. However, its application is restricted by poor digestibility due to its thick, rigid cell wall. Previously, we observed that the deletion of mnn9 gene in S. cerevisiae, leading to defective mannan synthesis and increased β-glucan exposure, enhances growth and immune response in Magallana gigas oysters. Nevertheless, using ∆mnn9 in aquaculture is not feasible due to restrictions on genetically modified organisms (GMO) containing antibiotic-resistance genes. This study aimed to create a non-GMO cell-wall defective yeast mutant (JH40) via ethyl methanesulfonate (EMS) mutagenesis and evaluate its nutritional value for M. gigas juveniles. Phenotypical differences between wild-type S. cerevisiae (WT), ∆mnn9, and JH40 were characterized using fluorescein isothiocyanate (FITC)-labeled lectin analysis, microscopy, cell diameter measurements, growth curves, and osmosensitivity tests. The nutritional value of a microalgae-based diet (Chaetoceros muelleri:Tisochrysis lutea, 50:50 based on dry weight) and its 50% substitution with JH40 or WT was assessed over 21 days in M. gigas juveniles. A complementary test also explored higher substitution levels (63%, 75%, and 100%) of the based diet with JH40 and the addition of extra JH40 (+25 %) in the 63% and 75% replacement diets. Results indicated that JH40 forms clumps, grows slower than the WT, has a larger cell diameter, higher binding affinity to WGA and LEL lectins than the WT, and is highly sensitive to hypo-osmotic stress, which are characteristics of cell-wall defective yeasts. Oysters fed a diet with 50% JH40 substitution showed significantly higher growth compared to those fed the WT-containing diet. JH40 could replace 50% of the algal diet without significantly affecting oyster growth and survival. However, higher inclusion levels of JH40 (62 %, 75 %, and 100 %) did not achieve the oyster growth observed with the algae-based diet, even with additional yeast. These findings are attributed to the limited polyunsaturated fatty acid content in yeast cells. Further research on dosing and administration frequencies is needed to evaluate the immunostimulatory potential of JH40.

HnRNP R promotes O-GlcNAcylation of eIF4G and facilitates axonal protein synthesis

Motoneurons critically depend on precise spatial and temporal control of translation for axon growth and the establishment and maintenance of neuromuscular connections. While defects in local translation have been implicated in the pathogenesis of motoneuron disorders, little is known about the mechanisms regulating axonal protein synthesis. Here, we report that motoneurons derived from Hnrnpr knockout mice show reduced axon growth accompanied by lowered synthesis of cytoskeletal and synaptic components in axons. Mutant mice display denervated neuromuscular junctions and impaired motor behavior. In axons, hnRNP R is a component of translation initiation complexes and, through interaction with O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (Ogt), modulates O-GlcNAcylation of eIF4G. Restoring axonal O-GlcNAc levels rescued local protein synthesis and axon growth defects of hnRNP R knockout motoneurons. Together, these findings demonstrate a function of hnRNP R in controlling the local production of key factors required for axon growth and formation of neuromuscular innervations.

Cant1 Affects Cartilage Proteoglycan Properties: Aggrecan and Decorin Characterization in a Mouse Model of Desbuquois Dysplasia Type 1.

Desbuquois dysplasia type 1 (DBQD1) is a recessive chondrodysplasia caused by mutations in the CANT1 gene, encoding for the Golgi Calcium-Activated Nucleotidase 1 (CANT1). The enzyme hydrolyzes UDP, the by-product of glycosyltransferase reactions, but it might play other roles in different cell types. Using a Cant1 knock-out mouse, we demonstrated that CANT1 is crucial for glycosaminoglycan (GAG) synthesis; however, its impact on the biochemical properties of cartilage proteoglycans remains unknown. Thus, in this work, we characterized decorin and aggrecan from primary chondrocyte cultures and cartilage biopsies of mutant mice at post-natal day 4 by Western blots and further investigated their distribution in the cartilage extracellular matrix (ECM) by immunohistochemistry. We demonstrated that the GAG synthesis defect caused by CANT1 impairment led to the synthesis and secretion of proteoglycans with shorter GAG chains compared with wild-type animals. However, this alteration did not result in the synthesis and secretion of decorin and aggrecan in the unglycanated form. Interestingly, the defect was not cartilage-specific since also skin decorin showed a reduced hydrodynamic size. Finally, immunohistochemical studies in epiphyseal sections of mutant mice demonstrated that the proteoglycan structural defect moderately affected decorin distribution in the ECM.

The Phenomenon of Thrombotic Microangiopathy in Cancer Patients.

Thrombotic microangiopathy (TMA) encompasses a range of disorders characterized by blood clotting in small blood vessels, leading to organ damage. It can manifest as various syndromes, including thrombotic thrombocytopenic purpura (TTP), hemolytic-uremic syndrome (HUS), and others, each with distinct causes and pathophysiology. Thrombo-inflammation plays a significant role in TMA pathogenesis: inflammatory mediators induce endothelial injury and activation of platelet and coagulation cascade, contributing to microvascular thrombosis. Primary TMA, such as TTP, is primarily caused by deficient ADAMTS13 metalloproteinase activity, either due to antibody-mediated inhibition or intrinsic enzyme synthesis defects. In cancer patients, a significant reduction in ADAMTS13 levels and a corresponding increase in VWF levels is observed. Chemotherapy further decreased ADAMTS13 levels and increased VWF levels, leading to an elevated VWF/ADAMTS13 ratio and increased thrombotic risk. Drug-induced TMA (DITMA) can result from immune-mediated or non-immune-mediated mechanisms. Severe cases of COVID-19 may lead to a convergence of syndromes, including disseminated intravascular coagulation (DIC), systemic inflammatory response syndrome (SIRS), and TMA. Treatment of TMA involves identifying the underlying cause, implementing therapies to inhibit complement activation, and providing supportive care to manage complications. Plasmapheresis may be beneficial in conditions like TTP. Prompt diagnosis and treatment are crucial to prevent serious complications and improve outcomes.