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Results for “CCD”

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PubMed2026

A system-level metastable model of cancer evolution: integrating replication stress, cell cycle deregulation and chromosomal instability.

INTRODUCTION: Cancer cell proliferation occurs within the context of persistent genomic instability. In this review, we propose the RS-CCD-CIN axis as a systems-level framework in which replication stress (RS), cell cycle deregulation (CCD) and chromosomal instability (CIN) form an interdependent triad that shapes tumour evolution. This axis represents a constrained metastable state in which genomic instability is tolerated and buffered. The objective of this review is to synthesize the current understanding of how the RS-CCD-CIN axis contributes to tumour heterogeneity, adaptability and therapy response. DISCUSSION: Evidence indicates that RS, CCD and CIN operate as a dynamic, interconnected network rather than as independent processes. Replication stress induces DNA damage and mutagenesis, while partial checkpoint disruption permits cells with unresolved lesions to proliferate. Chromosomal instability generates both structural and numerical alterations, contributing to intratumoural heterogeneity. Together, these processes facilitate adaptation to environmental and therapeutic pressures. Extrachromosomal DNA, micronuclei formation and cytosolic DNA signalling, including the cGAS-STING pathway, connect genomic instability to adaptive responses and immune modulation. Single-cell and spatial profiling reveal temporal and spatial variability in RS, CCD and CIN states, highlighting the limitations of static biomarkers. Therapeutically, targeting individual components often yields limited durability, whereas approaches that simultaneously perturb multiple aspects of the RS-CCD-CIN axis may improve clinical outcomes. CONCLUSIONS: This review highlights the RS-CCD-CIN axis as a fragile and metastable architecture that supports cancer evolution, while also being susceptible to collapse. A deeper understanding of this interconnected framework may inform the development of therapeutic strategies and enhance the management of resistance.

Humans↗

PubMed1979

Cleidocranial dysplasia. A family study.

The incidental observation of Wormian bones in the skull and defective ossification of the public symphysis in a mildly scoliotic 12-year-old girl prompted a clinical and radiological study of members of her family. The diagnosis of cleidocranial dysplasia (CCD) was established by observing similar skeletal abnormalities in eight out of ten of them but the classical clavicular defect in only one, the last to be examined. Abnormal modelling of the medial end of both clavicles was observed in all those affected. A modelling defect of the public bones is suggested as an additional, hitherto undescribed, radiological sign. The progression with age of certain radiological features of CCD is discussed. It is suggested that this family represents an atypical variant of CCD. Such variance may be more prevalent in patients with mild scoliosis than presently suspected. A complete skeletal survey with espeical attention to the skull, pelvis and medial aspect of the clavicle and family studies may be essential for the definitive diagnosis of CCD in certain patients.

Adolescent↗

PubMed2026

Evolutionary adaptation of CCD4 enzymes in Buddleja alternifolia for crocetin biosynthesis.

INTRODUCTION: Carotenoid cleavage dioxygenase 4 (CCD4) enzymes play central roles in carotenoid turnover and apocarotenoid biosynthesis in plants. Despite their importance, the evolutionary mechanisms underlying diversification of CCD4 catalytic functions remain poorly understood. This study investigated the CCD gene family in Buddleja alternifolia, with particular emphasis on the expansion and functional evolution of the CCD4 subfamily. METHODS: A genome-wide identification and comparative analysis of CCD genes were performed in B. alternifolia. Genomic organization, phylogenetic relationships, and syntenic patterns were analyzed to investigate gene family expansion. Functional characterization of 11 BaCCD4 paralogs was conducted through biochemical assays, while structural analyses were used to identify sequence features associated with differences in substrate cleavage specificity. Gene expression profiling was performed to assess patterns of tissue-specific regulation. RESULTS: Twenty-three CCD genes were identified, including 12 CCD4 paralogs, representing one of the largest CCD4 expansions reported within Lamiales. Syntenic and genomic analyses revealed that recent tandem duplication events, particularly within a CCD4-rich region on chromosome 10, were the primary drivers of this expansion. The presence of pseudogenes in the same region supported an ongoing birth-and-death evolutionary process. Functional analyses demonstrated extensive biochemical diversification among BaCCD4 enzymes despite their high sequence similarity. Several paralogs catalyzed asymmetric carotenoid cleavage leading to citraurin production, whereas two paralogs, KAG8367281 and KAG8375220, exhibited symmetric zeaxanthin cleavage activity, producing crocetin dialdehyde, the direct precursor of crocins. Notably, these crocetin-producing enzymes belonged to closely related paralogous pairs whose counterparts displayed distinct cleavage specificities, indicating rapid neofunctionalization after duplication. Structural analyses suggested that subtle sequence variations, including indels affecting loop regions adjacent to the substrate access channel, may underlie changes in regioselectivity. Expression profiling further revealed tissue-specific expression patterns consistent with functional divergence among paralogs. DISCUSSION: These findings indicate that crocetin-forming activity in B. alternifolia likely evolved through progressive modifications of ancestral CCD4 functions rather than through a single evolutionary event. The remarkable expansion and diversification of the CCD4 subfamily provide evidence for the role of gene duplication and neofunctionalization in shaping carotenoid cleavage specificity. Collectively, this work establishes B. alternifolia as a valuable model for investigating the molecular evolution of CCD4 enzymes and the emergence of specialized apocarotenoid metabolism in plants.

CCD4 evolution↗

PubMed1979

Reintroduction of gluten in adults and children with treated coeliac disease.

Twenty-eight patients, thought to have coeliac disease and on gluten free diets, were put on a normal diet to confirm their diagnoses. Nineteen had been diagnosed in adult life (ACD) and nine in childhood (CCD). Patients were assessed on jejunal, morphological, and symptomatic parameters. Eighteen patients with ACD relapsed within seven weeks. Nine patients with CCD relapsed at variable times but five took longer than seven weeks, the longest period beint 10 months. Seven patients had no symptoms despite morphological deterioration during challenge and one patient, with ACD, did not relapse and was HLA B8 negative. This patient with ACD had subtotal villous atrophy on two jejunal biopsies and later showed morphological improvement on a gluten free diet. There was no correlation between the relapse time and time spent on a gluten free diet.

Adolescent↗

PubMed1979

Subfractionation of human peripheral blood lymphocytes on the basis of their surface properties by partitioning in two-polymer aqueous phase systems.

Partitioning of cells in dextran-poly(ethylene glycol) aqueous-aqueous two-phase systems is a sensitive method for separating cells and for obtaining information on their surface properties. Highly purified lymphocytes were obtained by velocity sedimentation of human peripheral blood mononuclear cells and fractionated by countercurrent distribution (CCD, a multiple-step extraction procedure) in a charged two-polymer aqueous phase system. The lymphocytes remained viable after separation (order of 90%) and the E-rosetting cells responded (after adding back monocytes) to mitogens (PHA, Con A, PWM). Not only was the total lymphocyte population found to be highly heterogeneous (as evidenced by a broad and skewed distribution curve), but we were able to show that cells that rosetted with E, or had complement or Fc receptors were composed of additional subpopulations as well. The bulk of complement-receptor-bearing cells had the lowest partition coefficient (K), E-rosetting cells an intermediate K, and Fc-receptor-containing cells the highest K. The largest lymphocytes were among the subpopulation having the highest K and neither responded to T cell mitogens nor rosetted with E. Our results thus demonstrate that human peripheral blood lymphocytes can be subfractionated by CCD. The fractions are differentially enriched with lymphocyte subpopulations having characteristic surface markers and functional abilities.

Animals↗

PubMed1977

Possible genetic predisposition for alcohol addiction.

In a group of male addictive alcoholics, some palmar and fingerprint characteristics were determined, as well as the ABO, MN, Ss, Kell, Duffy, Lewis, and P blood groups, Rh and Hp phenotypes, HLA and Au antigens, immunoglobulins, blood sugar, cholesterol, SGOT, SGPT, and karyotypes. In comparison with the normal population the alcoholics show increased occurrence of whorls and arches on the fingers, decrease in the total ridge count, sharpening of the atd angle, and separation of the lower from the upper transverse line. Genetic markers in the blood of alcoholics show different frequencies of A, Lewis a-b+, Lewis a-b-, Duffy a-, Duffy a+, SS, and M blood groups, CcD-ee, Hpl-1, Hp2-1 phenotypes, and HLA-5, HLA-7, w10, w16, and w5 antigens. These findings may be expected to lead soon to detection of the predisposition to the development of alcohol addiction caused by some genetic malformations.

ABO Blood-Group System↗

PubMed1977

On the ability of Salmonella typhimurium cells to form deoxycytidine nucleotides.

It is known that cdd- S. typhimurium mutants selected for resistance to 5-fluorodeoxycytidine (FdCyd) possess no deoxycytidine kinase activity. The present study postulates that this method of screening selects double mutants defective in cytidine deaminase and in deoxycytidine kinase. To prove this hypothesis, the cdd mutant of S. typhimurium was constructed by P1-mediated transfer of ccd- gene into a new genetic background, and the activity of deoxycytidine kinase was assayed. Transductants exhibited no deoxycytidine kinase activity, showing that the absence of this enzyme is not limited to a specific cdd- mutant, but includes all strains of S. typhimurium. The toxicity of FdCyd for the bacterial strains possessing deoxycytidine kinase, as well as the role of nucleoside phosphorylase in nucleotide formation by S. typhimurium, is discussed.

Cytidine Deaminase↗

PubMed2026

Natural deep eutectic solvent in situ formation-based extraction method coupled to high-performance anion-exchange chromatography with pulsed amperometric detection for multiclass carbohydrates in hot pot bases.

A novel method was developed for the simultaneous extraction of fourteen multiclass carbohydrates from high-fat foods via the in situ formation of deep eutectic adducts from analytes and acetate ions. Different natural deep eutectic solvents (NADESs) composed of fructose and organic acids were tested as extraction solvents. A model NADES formulated with sodium acetate and fructose was characterized using Fourier transform infrared (FTIR) spectroscopy and hydrogen nuclear magnetic resonance (1H-NMR) spectroscopy. The critical extraction parameters were systematically optimized using multi-response surface methodology (MRSM) with a central composite design (CCD). The extract was analyzed using high-performance anion-exchange chromatography coupled with pulsed amperometric detection (HPAEC-PAD) using a sodium hydroxide-sodium acetate eluent, which did not require organic solvents. This approach exhibited good linearity over the concentration range of 0.02-10 mg L-1, with correlation coefficients (r) ranging from 0.9994 to 0.9999. The limits of detection and quantification were in the ranges of 0.06-0.42 mg kg-1 and 0.19-1.3 mg kg-1, respectively, which were significantly lower than those of liquid chromatography (LC). The protocol was successfully applied to the determination of fourteen carbohydrates in forty-five hotpot seasoning samples. The recoveries ranged from 86.3% to 104.1%, with relative standard deviations (RSDs) of 0.9-7.1%. By integrating multiple techniques, this strategy simplifies operations, shortens extraction time, and achieves baseline separation of three carbohydrate classes that exhibit poor resolution using a conventional LC method. This study describes an efficient procedure for the simultaneous determination of multiple trace-level carbohydrates in complex samples using HPAEC-PAD.

Journal Article↗

PubMed2026

Genome-wide identification of the carotenoid cleavage dioxygenase gene family in wheat and analysis of the TaDREB-7A-TaNCED9a regulatory module conferring drought tolerance.

Carotenoid cleavage dioxygenases (CCDs) play critical roles in plant growth, development, and abiotic stress responses, yet their genome-wide identification and drought response mechanisms remain unexplored in wheat. In this study, 34 TaCCD genes were identified in wheat, distributed across 15 chromosomes and phylogenetically classified into five subfamilies. Gene structure analysis indicated that members within each subfamily shared conserved motifs and similar intron-exon arrangements. Cis-regulatory element analysis suggested the potential roles of these genes in stress adaptation, developmental processes, and hormone signaling. Moreover, prediction of tertiary structures and protein-protein interactions revealed unique structural features and potential interacting partners of the TaCCD proteins. In addition, TaNCED9a, a member of the TaCCD family, showed the highest transcript level in wheat roots among all detected TaCCD genes and was significantly induced by drought stress. Subcellular localization assay indicated that TaNCED9a was located in chloroplasts. Downregulation of TaNCED9a expression led to reduced drought resistance in wheat, accompanied by an accumulation of reactive oxygen species and a decrease in endogenous abscisic acid levels. Using yeast one-hybrid, dual-luciferase, and tobacco transient co-expression assays, the upstream regulatory factor TaDREB-7A was identified, which can regulate the expression of TaNCED9a. Additionally, a KASP molecular marker was developed to identify the superior haplotype TaNCED9a-HapI, which exhibited a significantly higher germination rate compared to TaNCED9a-HapII under drought conditions, and was predominant in wheat. These results offer valuable insights into the TaCCD gene family's response mechanisms to drought stress in wheat, simultaneously identifying promising genetic resources for enhancing drought tolerance through molecular breeding.

CCD↗