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Deg phenotype of Escherichia coli lon mutants.

Deg. one of the Escherichia coli systems for degrading abnormal polypeptides (e.g., nonsense fragments), is also involved in the degradation of some classes of missense proteins. Both missense proteins of beta-galactosidase and temperature-sensitive phage products appear to be degraded by the Deg system. Mutations in the Deg system are indistinguishable from mutations classically called lon or capR; all map near proC, all are mucoid, defective in protein degradation, sensitive to radiomimetic agents, and defective in P1 lysogenization. All are able to propagate temperature-sensitive phage better than lon+ parental strains. Mutations that suppress the radiation sensitivity of these strains (sul) also suppress the P1 lysogenization defect, but do not affect mucoidy or the degradation defect.

Bacterial Proteins

Development of the filiform hairs on the cerci of Gryllus bimaculatus deg. (saltatoria, gryllidae).

The filiform hairs, mechanoreceptors of Gryllus, pass through six developmental stages during the last larval stage. The cytoplasm of their sense cells suggests intensive synthesis of protein for cellular metabolism and intercytoplasmic exchange of material via glial evaginations. Ultrahistochemical tests demonstrated acid phosphatase in the lysosomes as well as in components of the Golgi apparatus. There was no significant change in the appearance of the sense cell cytoplasm, indicating a maintained functional state also during molting. The new cuticular apparatus is formed after apolysis by the three enveloping cells. Formation of the replacement hairs is initiated by a cytoplasmic outgrowth of the trichogen cell. During morphogenesis of the new hair, the microtubules serve as a cytoskeleton and probably control the flow of vesicles, which contain phenol oxidase, also demonstrated in the Golgi apparatus, and are incorporated into the new cuticle. Bundles of microfibrils are involved in the surface sculpturing of the replacement hair. The trichogen cell also forms a number of structural elements, e.g. the "cup" and "strut" marked geometric peculiarities of which indicate that they are important in the spatial orientation of the dendrite and thus also in transduction. Reduction of the apical cell membrane of the tormogen cell after apolysis permits unrestricted growth of the new hair into the exuvial space. The tormogen cell participates in the formation of the joint membrane, parts of the socket and the articulation of the hair.

Acid Phosphatase

Distinct spatial transcriptomic patterns of substantia Nigra in Parkinson disease and Parkinsonian subtype of multiple system atrophy.

To investigate transcriptomic signatures of Parkinson's disease (PD) and the Parkinsonian subtype of Multiple System Atrophy (MSA-P) in substantia nigra pars compacta (SNpc), we conducted transcriptome analysis using in-situ hybridization on paraffin-embedded SNpc tissues from post-mortem brains. The study included 2 MSA-P patients, 2 PD patients, and 2 healthy controls (HC), with 12 regions of interest (ROIs) selected from the dorsal to ventral and medial to lateral aspects of the SNpc. A total of 72 ROIs from 6 participants were analyzed, and differentially expressed genes (DEGs) were identified by comparing MSA-P, PD and HC groups. The MSA-P group showed 88 upregulated DEGs and 326 downregulated DEGs (adjusted &#x1d45d;<0.05) compared to HC. The downregulated DEGs were significantly enriched in pathways related to ribosomal translation, immune processes, mitochondrial function, and autophagy. Notably, the dorsomedial quadrant was uniquely linked to antigen presentation, while other quadrants showed downregulation of protein synthesis. The PD group exhibited 165 upregulated DEGs and 350 downregulated DEGs (adjusted &#x1d45d;<0.05) compared to HC, with downregulated DEGs associated with ribosomal translation, mitochondrial function, and the ubiquitin-proteasome system. In both MSA-P and PD, the upregulated DEGs were not associated with any pathways or biological process in gene enrichment analysis. In network propagation analysis, amyloid precursor protein was the most significant network hub among DEGs in both MSA-P and PD. Comparing the transcriptomic signatures of SNpc between MSA-P and PD, we found immune/inflammation, mitochondrial function and neural signaling related genes were significantly downregulated in MSA-P compared to PD. Overall, the transcriptomic signature of the SNpc in MSA-P and PD revealed overlapping but distinct features, including alterations in protein synthesis, immune processes, mitochondrial function, and protein degradation systems. Future studies with larger cohorts and functional validation are needed to further elucidate these findings.

Humans

Common Molecular Mechanisms and Candidate Drug Targets in Type 2 Diabetes Mellitus and Atherosclerotic Cardiovascular Disease.

This study examined the mechanisms underlying the comorbidity between type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD), while identifying potential therapeutic targets. Common differentially expressed genes (C-DEGs) between T2DM and ASCVD were extracted from the GSE78721 and GSE12288 datasets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, protein-protein interaction (PPI) network construction, hub gene identification, and Drug-Gene Interaction Database (DGIdb) analysis were conducted. The association between hub C-DEGs and immune-infiltrating cells was analyzed using the CIBERSORT method. Expression levels of hub C-DEGs were quantified through qRT-PCR and Western blot analyses. A total of 32 C-DEGs were identified, comprising 20 upregulated and 12 downregulated genes. C-DEGs were predominantly enriched in key pathways, including viral myocarditis, arrhythmogenic right ventricular cardiomyopathy, hypertrophic cardiomyopathy, and dilated cardiomyopathy. PPI analysis revealed 29 nodes and 39 edges, leading to the identification of eight hub C-DEGs (HSP90B1, PLAU, SLPI, TOP3A, NCF4, PRF1, TUBA1C, and CS) across both datasets. Furthermore, hub C-DEGs (TOP3A, SLPI, NCF4, PRF1, and PLAU) demonstrated significant correlations with immune-infiltrating cell levels. Drugs specifically targeting these hub C-DEGs present promising candidates for the treatment of T2DM and ASCVD. Additionally, the expression of hub C-DEGs at both mRNA and protein levels was validated in patients with T2DM and ASCVD. An integrated bioinformatics analysis facilitated the screening of candidate therapeutic targets, mechanisms, and drugs for T2DM and ASCVD, offering new insights into molecular therapies for these conditions.

Diabetes Mellitus, Type 2

Morphological, Physiological and Transcriptomic Changes in Response to Water Deficit Stress in Brassica napus L.

Yield losses due to water-deficit (WD) conditions, especially during the reproductive stages of plant development, pose a significant threat to global canola (Brassica napus L.) production. Therefore, it is critical to investigate traits contributing to improved productivity under increased WD conditions. Here we present phenotypic, physiological and transcriptomic changes in response to WD across contrasting canola accessions exhibiting variation in drought resistance-related traits. WD significantly reduced shoot biomass, plant height, harvest index, leaf water content, photosynthetic CO2 assimilation rate, intrinsic water-use efficiency and carbon isotope discrimination. WD caused 49 to 100% of the seed yield reduction: the minimum seed yield reduction (49.66%) was observed in a doubled-haploid (DH) line, 06-5101.137, while the maximum yield reduction (94.1 to 100%) occurred in the late-flowering DH lines (06.5101.088 and 06-5101.306). Seed yield showed a positive correlation (r = 0.29 to 0.95) with shoot biomass and harvest index, leaf water content, photosynthetic CO2 assimilation rate, intrinsic water use efficiency and carbon isotope discrimination. However, it showed negative correlations with days to flower, leaf specific weight, root length, root biomass (r = -0.04 to -0.79) across water treatments. The specific leaf transcriptome analysis of the two parental lines of DH population that exhibit variation for effective water use under well-watered and water-deficient conditions revealed different categories of differentially expressed genes (DEGs): WD-responsive DEGs in BC1329 parental line (1116) and BC9102 (1205) with 754 and 853 DEGs unique to BC1329 and BC9102, respectively, WD-responsive DEGs (906), genotype-dependent DEGs (8465) and genotype &#xd7; treatment interaction DEGs (353). DEG annotations revealed that the WD-treatment-affected genes were involved in stress responses and growth and development. We further located 235 DEGs within the QTL regions underlying agronomic and physiological performance. Our study provides a conceptual framework for the morphological, physiological and molecular determinants involved in water-use efficiency. Seedlings' traits with high heritability values, such as shoot biomass, leaf weight, leaf water content and &#x394;13C, serve as proxies for trait-based selection for improved seed yield under both water-limited and non-water-limited conditions.

Brassica napus

Cellular transcriptomic signatures underpinning the heterogeneity of depression in Alzheimer's disease.

INTRODUCTION: Late-onset Alzheimer's disease (LOAD) and major depressive disorder (MDD) share genetic etiologies. Here, we investigated brain transcriptomic landscapes to gain insights into shared and divergent molecular and biological etiologies across LOAD and MDD. METHODS: Brain single-nucleus RNA sequencing (snRNA-seq) datasets from cognitively normal older and young individuals and LOAD patients stratified by comorbid MDD were analyzed to identify differential expressed genes (DEGs). Using cell type-specific DEGs we performed biological pathway and intercellular-communication networks analyses. We investigated shared DEGs across MDD and LOAD cohorts and sex-specific DEGs. Results were validated by comparison with four transcriptomic and proteomic studies of MDD and depression. RESULTS: MDD-associated dysregulated genes and pathways were shared between LOAD and cognitive-normal individuals, including JUNB and DUSP1 in glutamatergic neurons, and PRAM1 and SNX9 in microglia. DEGs shared between the MDD and LOAD cohorts included HSPA1A and NDUFB7 in glutamatergic neurons. Sex interaction analysis identified numerous new DEGs in the MDD cohorts, whereas there were &#x2248;5 to 10 times more DEGs in female than in male individuals. LOAD and MDD common microglial pathways included neuronal injury, stress, peroxisome proliferator-activated receptor (PPAR) signaling and interferon alpha/beta signaling. DISCUSSION: LOAD and MDD exhibited common molecular profiles, dysregulated pathways, and cellular communication changes. MDD develops earlier in life, thus, our findings provide a window into early molecular and biological processes preceding LOAD-onset.

Humans

Comparative transcriptomic analysis of the gills and hepatopancreas of freshwater-cultured Litopenaeus vannamei under chronic nitrite stress.

To investigate the differences in molecular responses between the gills and hepatopancreas of freshwater-cultured Litopenaeus vannamei under chronic nitrite stress, a 30-day chronic stress experiment was conducted with a control group and a stress group. Transcriptomic analysis of the gills and hepatopancreas was performed using Illumina sequencing; differentially expressed genes (DEGs) were identified, and GO, KEGG, GSEA, PPI, and RT-qPCR validation were carried out. The results showed that 196 DEGs (161 up-regulated and 35 down-regulated) were identified in the gills, and 287 DEGs (199 up-regulated and 88 down-regulated) in the hepatopancreas, with only 18 DEGs shared between the two tissues. DEGs in the gills were enriched in oxidoreductase activity, glycerophospholipid metabolism, and tyrosine metabolism; DEGs in the hepatopancreas were enriched in lipid transporter activity, phagosome, ECM-receptor interaction, and riboflavin metabolism. GSEA revealed significant suppression of the mTOR pathway in the gills and the Polycomb complex pathway in the hepatopancreas. PPI network analysis identified hub genes P5CS and eEF2 in the gills, and PER, TUBB1, SHMT, and TUBB4B in the hepatopancreas. RT-qPCR validation was consistent with the RNA-seq results (R2&#xa0;=&#xa0;0.764). This study indicates that, under chronic nitrite stress, the gill response is centered on redox regulation and inhibition of growth metabolism, whereas the hepatopancreas response primarily involves lipid transport, cytoskeletal remodeling, and phagosome activation. The two tissues synergistically adapt through fundamental biosynthetic and motor protein pathways. This research provides molecular evidence for deciphering the nitrite tolerance mechanisms in freshwater-cultured shrimp.

Animals

Comprehensive analysis of mRNA-microRNA-lncRNA expression profiles in post-traumatic elbow heterotopic ossification using RNA sequencing and experimental validation.

BACKGROUND: This study aimed to profile the molecular signatures of post-traumatic elbow heterotopic ossification (HO) to identify key regulators and potential therapeutic targets. METHODS: Total RNA from post-traumatic elbow HO tissues (n=4) and normal bone tissues (n=6) was subjected to high-throughput sequencing to identify differentially expressed mRNAs (DEGs), microRNAs (DEMs), and lncRNAs (DELs). Bioinformatics analyses included Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein-protein interaction network construction, and transcription factor (TF)-microRNA-mRNA network analysis. The expression trends of four most upregulated and four most downregulated DEGs were validated by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: We identified 2,138 DEGs, 40 DEMs, and 905 DELs. DEGs were significantly enriched in biological process "bone mineralization," cellular component "plasma membrane," molecular function "integrin binding," and pathways including PI3K-Akt, NF-&#x3ba;B, JAK-STAT, and TNF signaling pathways. Hub genes with high connectivity included MMP9, IL6, MMP3, CTSK, and BGLAP. Integrated network analysis highlighted the transcription factor JUN and key microRNAs (hsa-miR-124-3p, hsa-miR-548c-3p, and hsa-miR-135b). The qRT-PCR results confirmed the expression trends of selected DEGs. CONCLUSIONS: This study, for the first time, profiled the differentially expressed mRNAs, microRNAs, and lncRNAs in post-traumatic elbow HO using high-throughput RNA sequencing. These findings provide valuable insights into the molecular mechanisms of HO following elbow trauma. The identified hub genes (MMP9, IL6, MMP3, CTSK, and BGLAP), key TF (JUN), and key microRNAs (hsa-miR-124-3p, hsa-miR-548c-3p, and hsa-miR-135b) may serve as potential therapeutic targets for preventing and treating post-traumatic elbow HO.

Humans

Identification of novel cytoskeleton protein involved in spermatogenic cells and sertoli cells of non-obstructive azoospermia based on microarray and bioinformatics analysis.

BACKGROUND: During mammalian spermatogenesis, the cytoskeleton system plays a significant role in morphological changes. Male infertility such as non-obstructive azoospermia (NOA) might be explained by studies of the cytoskeletal system during spermatogenesis. METHODS: The cytoskeleton, scaffold, and actin-binding genes were analyzed by microarray and bioinformatics (771 spermatogenic cellsgenes and 774 Sertoli cell genes). To validate these findings, we cross-referenced our results with data from a single-cell genomics database. RESULTS: In the microarray analyses of three human cases with different NOA spermatogenic cells, the expression of TBL3, MAGEA8, KRTAP3-2, KRT35, VCAN, MYO19, FBLN2, SH3RF1, ACTR3B, STRC, THBS4, and CTNND2 were upregulated, while expression of NTN1, ITGA1, GJB1, CAPZA1, SEPTIN8, and GOLGA6L6 were downregulated. There was an increase in KIRREL3, TTLL9, GJA1, ASB1, and RGPD5 expression in the Sertoli cells of three human cases with NOA, whereas expression of DES, EPB41L2, KCTD13, KLHL8, TRIOBP, ECM2, DVL3, ARMC10, KIF23, SNX4, KLHL12, PACSIN2, ANLN, WDR90, STMN1, CYTSA, and LTBP3 were downregulated. A combined analysis of Gene Ontology (GO) and STRING, were used to predict proteins' molecular interactions and then to recognize master pathways. Functional enrichment analysis showed that the biological process (BP) mitotic cytokinesis, cytoskeleton-dependent cytokinesis, and positive regulation of cell-substrate adhesion were significantly associated with differentially expressed genes (DEGs) in spermatogenic cells. Moleculare function (MF) of DEGs that were up/down regulated, it was found that tubulin bindings, gap junction channels, and tripeptide transmembrane transport were more significant in our analysis. An analysis of GO enrichment findings of Sertoli cells showed BP and MF to be common DEGs. Cell-cell junction assembly, cell-matrix adhesion, and regulation of SNARE complex assembly were significantly correlated with common DEGs for BP. In the study of MF, U3 snoRNA binding, and cadherin binding were significantly associated with common DEGs. CONCLUSION: Our analysis, leveraging single-cell data, substantiated our findings, demonstrating significant alterations in gene expression patterns.

Male

Analysis of differentially expressed genes in schizophrenia based on bioinformatics and corresponding mRNA expression levels.

OBJECTIVE: This study aimed to use bioinformatics analysis to identify differentially expressed genes (DEGs) involved in the pathogenesis of schizophrenia and validate their mRNA expression levels through real-time quantitative PCR (qPCR). MATERIAL/METHODS: Datasets from the publicly available Gene Expression Omnibus (GEO) database were analyzed using R software to identify DEGs. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, were conducted. A protein-protein interaction (PPI) network was constructed using Cytoscape software to identify key genes with notable expression changes. The expression levels of these key genes were subsequently validated in schizophrenia patients using qPCR to assess potential susceptibility genes. RESULTS: In total, 813 DEGs were identified, with six key genes highlighted through GO analysis and PPI network screening. Among these, HDAC1, UBA52, and FYN demonstrated statistically significant differences in mRNA expression between schizophrenia patients and healthy controls (P&#xa0;<&#xa0;0.05). CONCLUSIONS: This study identified several DEGs potentially linked to the pathogenesis of schizophrenia, suggesting that HDAC1, UBA52, and FYN could serve as candidate susceptibility genes and diagnostic biomarkers. These findings provide new insights and directions for future schizophrenia research.

Humans

Response variability and orientation discrimination of single cells in striate cortex of cat.

The response of single cells in the striate cortex of cat to a moving light bar of variable orientation was measured by a method providing data on the mean response as well as the standard deviation (SD) at the different stimulus orientations. At the optimal stimulus orientation the SD was about 1/3 of the mean response. Marked differences in this respect were found between simple and complex cells, i.e., the SD for the simple cells was about 1/2 of the mean response and about 1/4 for the complex cells. The variation coefficient (Vc = SD/mean) was minimal at the optimal orientation and increased relatively in the same manner for simple and complex cells as the stimulus orientation was varied away from optimal orientation. The Vc varied with the mean response at optimal orientation in a nonlinear manner. A function is proposed which fits this relationship and which is equally applicable for both simple and complex cells. The mean orientation discrimination (MOD) was defined as that change in orientation angle away from the optimal which produced a response statistically different--on the 1% level--from the response to the optimal orientation. There were differences in MOD between the two sides of the orientation tuning curve: the mean of the smaller of the two values was 13.5 deg and of the larger 19.7 deg. No significant difference in MOD was found between simple and complex cells despite the fact that the halfwidth of the tuning curves for the two cell types was 19.5 deg and 31.6 deg, respectively. The preciseness in localization of the most sensitive part within the receptive field of single cells was calculated from the variability in time of occurrence of the smallest interspike interval. The degree of preciseness was found to be of the order of 1/4 of the receptive field diameter in both simple and complex cells. When nonoptimal stimulus orientations were presented, the preciseness significantly decreased in complex cells whereas it remained unchanged in simple cells. It is suggested that the same type of intracortical wiring produces orientation selectivity in simple and complex cells, and that the differences in tuning width are mainly due to a larger extension of inhibitory fields in the simple cells. Considering the cortical visual cells as elementary units in a network built for orientation detection and discrimination, the tuning width seems of minor importance for that function.

Animals

Dynamic and non-additive gene regulation shapes maize responses to simultaneous salt and cold stress.

Salt and cold stresses often occur together in nature and severely impact crop productivity, yet their transcriptional regulation remains poorly understood. Here, we conducted a time-series transcriptomic analysis of maize under salt, cold, and their combination at 0, 6, 12, and 24&#xa0;h. Differential expression analysis revealed dynamic, condition-specific gene responses grouped into eight distinct temporal patterns. Promoter motif analysis of genes within each pattern identified 5-39 significantly enriched motifs, with over 40% lacking known counterparts, suggesting the involvement of previously uncharacterized cis-regulatory elements in stress-responsive transcriptional regulation. By comparing combined stress responses to the sum of single-stress effects, we found that about 74% of DEGs showed non-additive patterns, suggesting that combined stress triggers a distinct transcriptional program. Evolutionary analysis showed that additive DEGs tend to be more recently evolved, subject to weaker purifying selection, and enriched in transposed duplications, contrasting with the stronger constraint observed in non-additive DEGs. WGCNA identified 24 co-expression modules, among which 65 hub DEGs were detected in modules significantly correlated with specific stress conditions. Furthermore, we reconstructed 228, 20, and 200 sequential transcription factor cascades spanning 6&#xa0;h, 12&#xa0;h, and 24&#xa0;h under cold, salt, and combined stress, respectively, with no cascade shared across all three conditions. Together, these results reveal that maize responses to combined salt and cold stress are largely non-additive and temporally dynamic, with distinct evolutionary patterns underlying different response types, offering insights and candidate regulators for enhancing crop stress resilience.

Zea mays

Transcriptomic characterization of the intestine in Stichopus monotuberculatus under gradient temperature stress and HSP gene family-mediated molecular adaptation.

The increasing frequency of extreme temperature events under climate change poses a growing threat to the stability of tropical sea cucumber aquaculture. To characterize the molecular responses of the tropical sea cucumber Stichopus monotuberculatus to acute temperature stress, juveniles were exposed for 96&#xa0;h to 15&#xa0;&#xb0;C, 20&#xa0;&#xb0;C, 25&#xa0;&#xb0;C, 30&#xa0;&#xb0;C, and 35&#xa0;&#xb0;C, followed by transcriptomic profiling of the intestine. By transcriptomic analysis, 2258, 634, 1618, and 2980 differentially expressed genes (DEGs) were identified at 15, 20, 30, and 35&#xa0;&#xb0;C compared to control, respectively. More DEGs were generally detected at temperatures further from 25&#xa0;&#xb0;C, with the 35&#xa0;&#xb0;C group showing the largest transcriptional response. Although cold and heat stress both affected metabolism and protein homeostasis, their enrichment profiles differed. At 15&#xa0;&#xb0;C, DEGs were mainly enriched in the spliceosome and p53 signaling pathways, highlighting RNA processing and p53 signaling as prominent features of the cold-stress response. At 35&#xa0;&#xb0;C, DEGs were mainly enriched in the PI3K-Akt signaling pathway, ubiquitin-mediated proteolysis, and mitophagy, indicating enhanced regulation of cell survival, protein turnover, and mitochondrial quality control. HSP genes also responded differently to cold and heat stress. Most HSP70 and HSP90 family members were downregulated at low temperatures, whereas HSP70 genes and small heat shock proteins were markedly upregulated at high temperatures. Overall, the intestinal transcriptome showed distinct responses to cold and heat stress. These results identify pathways and HSP genes potentially involved in the temperature response of S. monotuberculatus and provide useful information for evaluating temperature tolerance and defining suitable temperatures for its aquaculture.

Heat shock protein

Key hub genes and pathways associated with HCV-related hepatocellular carcinoma as potential diagnostic biomarkers.

BACKGROUND: Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) remains a major global health challenge, with high morbidity and mortality despite recent therapeutic advances. Early detection and identification of reliable molecular biomarkers are essential to improve patient outcomes. Therefore, the present study aimed to investigate key hub genes and pathways associated with HCV-related HCC as potential diagnostic biomarkers. METHODS: The datasets GSE69715 and GSE62232 were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were recognized according to an adjusted p-value and a log fold change (logFC). The GEO2R tool facilitated the identification of common DEGs across the two datasets. Pathways were explored using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases. Furthermore, protein-protein interactions (PPIs) were assessed through Cytoscape. The target genes were confirmed through a GEPIA analysis. RESULTS: A total of 421 common DEGs were identified, and 80 hub genes were subsequently determined through GEO and PPI network analyses, respectively. The GO and KEGG pathways analysis presented DEGs were enhanced in metabolic pathways, cellular components, extracellular exosome, detoxification of copper ion and monooxygenase activity. The GEPIA analysis indicated a notable variation in the expression levels of four specific genes -CDKN2A, CDK1, CCNB1, and TOP2A-when comparing normal samples to tumor samples. CONCLUSION: The present study discovered novel genes by expression variation in HCV-related hepatocellular carcinoma development. These findings suggest that CDKN2A, CDK1, CCNB1, and TOP2A are promising candidates for diagnostic biomarkers and present a valuable opportunity for the early identification of HCV-HCC, which could lead to improved treatment outcomes.

Bioinformatics

Comprehensive analysis of metabolomics and transcriptomics of radiation-induced rectal injury.

Radiation-induced rectal injury (RRI) significantly affects the quality of life in patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiotherapy (NCRT). Non-targeted liquid chromatography-mass spectrometry metabolomics analysis and transcriptomic analysis were conducted to explore RRI characteristics. Hematoxylin-eosin and Masson staining confirmed radiation-induced injury in rectal tissue within the radiotherapy target region. Orthogonal partial least squares discriminant analysis identified 823 differentially expressed metabolites (DEMs). Transcriptomic analysis revealed 400 differentially expressed genes (DEGs). Enrichment analysis revealed that DEMs and DEGs were primarily involved in metabolic, immune, and signal transduction pathways. Integrated analysis demonstrated significant enrichment of DEMs and DEGs in the arachidonic acid metabolism pathway. Pearson's correlation and canonical correlation analyses were used to assess the association between DEMs and DEGs within this pathway. In conclusion, this study identified key biological regulatory pathways involved in RRI through a multi-omics approach, offering potential targets for its diagnosis and treatment.

Humans

Circular dichroic studies of the DNA and RNA of nucleoli.

Circular dichroism (CD) in the 240-300-nm region was used to study the conformation of DNA and RNA complexed with proteins in isolated nucleoli form HeLa cells. Deoxyribonuclease or ribonuclease digestion was employed to obtain (1) the individual CD spectra of nucleolar DNA or RNA in complex form with proteins, or in free form; and (2) the experimental CD baseline correction to exclude contributions from nonnucleic acid sources such as light scattering artifacts and proteins. The CD spectrum of nucleolar DNA in DNA-protein complexes was highly reduced in ellipticity in comparison with protein-free DNA. It showed a positive peak at 283 nm with a molar ellipticity [theta]283 = 1200 deg cm2 dmol-1 and a crossover at 262 nm. Addition of sodium dodecylsulfate shifted the peak to 276 nm with [theta]276 8000 deg cm2 dmol-1 and a crossover at 254 nm. The CD spectrum of nucleolar RNA in RNA-protein complexes was also reduced in comparison with protein-free RNA, showing a peak at 269 nm ([theta]269 = 6900 deg cm2 dmol-1), and a crossover at 250 nm. Addition of sodium dodecyl sulfate shifted the peak to 265 nm with [theta]265 = 18 000 deg cm2 dmol-1 and a crossover at 246 nm. The low ellipticity of both nucleolar DNA and RNA when complexed with proteins was increased by treatment with sodium chloride, urea, or heparin. This suggests that some ionic, hydrophobic, and hydrogen bondings are involved in the nucleic acid-protein interaction in nucleolar chromatin similar to that observed in nuclear chromatin.

Amanitins