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PubMed2026

Research on identification of key genes and immune-metabolic mechanisms in atrial fibrillation through integrated multi-cohort transcriptomic analysis and machine learning.

This study aimed to integrate multiple datasets for the identification of atrial fibrillation (AF)-related differentially expressed genes (DEGs), analyze their underlying mechanisms through functional enrichment and machine learning, construct diagnostic models, and explore immune-metabolic interactions to provide novel biomarkers and theoretical foundations. Gene expression datasets were integrated and normalized, with batch effects removed using principal component analysis. Differential expression analysis, functional enrichment analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways), and machine learning-based feature gene selection and model construction were performed. Shapley additive explanations analysis was utilized to interpret the constructed models, while gene set enrichment analysis, gene set variation analysis, and immune cell infiltration analysis were conducted to investigate the associations between feature genes and immune infiltration. After integrating and normalizing gene expression data and eliminating batch effects via principal component analysis, 6 DEGs were identified, including 4 upregulated and 2 down-regulated ones. Functional enrichment analysis showed these DEGs were significantly enriched in neuro-related biological processes and pathways, indicating their key roles in AF pathogenesis. Five key feature genes were selected using LASSO, random forest, and support vector machine-recursive feature elimination algorithms. They had significant expression differences between the AF and control groups (P&#x2005;<&#x2005;.001) and were located on distinct chromosomes. The constructed random forest and support vector machine models performed excellently (area under the curve&#x2005;&#x2265;&#x2005;0.85). Shapley additive explanations analysis revealed TNNI1 contributed most to model prediction, with its expression significantly positively correlated with immune cell infiltration. Gene set enrichment analysis and gene set variation analysis analyses further showed feature genes participated in AF pathogenesis by regulating immune modulation, metabolic pathways, and autophagy. Immune cell infiltration analysis found altered proportions of T-cell subsets and M0 macrophages in the AF group, along with complex links between feature gene expression and immune cell function. This study systematically elucidated the unique gene expression patterns and key regulatory pathways associated with AF, clarifying the crucial roles of feature genes in immune regulation, metabolic imbalance, and cellular dysfunction. These findings provide a theoretical basis and potential therapeutic targets for understanding AF pathogenesis and developing targeted treatment strategies.

Atrial Fibrillation↗
PubMed1996

A correlation between thermal stability and structural features of staphylokinase and selected mutants: a Fourier-transform infrared study.

Variants of recombinant staphylokinase (Sak) were investigated by Fourier-transform infrared spectroscopy: Sak (wild type), Sak-M26A, Sak-M26L, and Sak-G34S/R36G/R43H (Sak-B). Estimation of the secondary structure and hydrogen-deuterium exchange experiments revealed the existence of fast-exchanging and strongly solvent-exposed fractions of the helical structures in the two samples Sak and Sak-M26L. These two samples are also thermally less stable with unfolding transition temperatures of 43.7 degrees C (Sak) and 43.5 degrees C (Sak-M26L), respectively. On contrast, Sak-M26A and Sak-G34S/R36G/R43H have a slower hydrogen-deuterium exchange, have a smaller solvent-exposed portion of the helical part, and are more resistant against thermal unfolding; the transition temperatures are 51.7 degrees C and 59.3 degrees C, respectively. The secondary structure analysis was performed by two different approaches, by curve-fitting after band narrowing and by pattern recognition (factor analysis) based upon reference spectra of proteins with known crystal structure. Within the limits of the used methods, we are unable to detect significant differences in the secondary structure of the four variants of Sak. According to the results of the factor analysis, the portions of secondary structure elements were obtained to 16-20% alpha-helix, 28-30% beta-sheet, 23-27% turns, 28-30% irregular (random) and other structure. The sharp differences in the specific plasminogen-activating capacity (Sak, Sak-G34S/R36G/R43H and Sak-M26L are fully active, but Sak-M26A does not form a stable complex with plasminogen) are not reflected in the structural features revealed by the infrared spectra of this study.

Deuterium↗
PubMed1985

Common features of polyomavirus mutants selected on PCC4 embryonal carcinoma cells.

The genomic rearrangements of six polyomavirus mutants selected on PCC4 embryonal carcinoma cells have been compared and their common characteristics pointed out. All mutants show a duplication which includes at least the adenovirus type 5 (Ad5) E1A-like enhancer core sequence plus a deletion of variable size and location. The presence of the second enhancer core sequence, the SV40-like enhancer, is not required for expression of the PyEC PCC4 phenotype. Two of these mutants are also able to express polyomavirus T antigen on F9 and LT1 cells. Multiadaptation seems to require the duplication of the Ad5 E1A-like core sequence, the maintenance of the SV40-like core sequence and a local change in DNA stability.

Animals↗
PubMed2000

Solution structure of a DNA three-way junction containing two unpaired thymidine bases. Identification of sequence features that decide conformer selection.

The solution structure of a DNA three-way junction (3H) containing two unpaired thymidine bases at the branch site (3HT2), was determined by NMR. Arms A and B of the 3HT2 form a quasi-continuous stacked helix, which is underwound at the junction and has an increased helical rise. The unstacked arm C forms an acute angle of approximately 55 degrees with the unique arm A. The stacking of the unpaired thymidine bases on arm C resembles the folding of hairpin loops. From this data, combined with the reported stacking behavior of 23 other 3HS2 s, two rules are derived that together correctly reproduce their stacking preference. These rules predict, from the sequence of any 3HS2, its stacking preference. The structure also suggests a plausible mechanism for structure-specific recognition of branched nucleic acids by proteins.

Base Pairing↗
PubMed1988

Studies on prolactin-secreting cells in aging rats of different strains. II. Selected morphological and immunocytochemical features of pituitary tumors correlated with serum prolactin levels.

Sixty pituitary tumors from 151 aging rats of the BN/BiRij strain, the WAG/Rij strain and their F1 hybrid were studied light microscopically. The lowest tumor incidence (18%) was found in the BN/BiRij strain, the highest incidence (71%) in the WAG/Rij strain. In the F1 hybrid the incidence (45%) was intermediate between those of the parental strains. With a hematoxylin-phloxin-saffron (HPS) staining two tumor types, i.e. hemorrhagic and solid could be distinguished. Immunocytochemical staining with anti-r-PRL antiserum revealed a positive reaction in the hemorrhagic and a negative reaction in the solid type, whereas staining with anti-sh-GH and anti-ACTH generally were negative. In animals with hemorrhagic as well as with solid tumors elevated serum PRL levels were found, although some differences were noticed. Serum levels in females of the WAG/Rij strain with hemorrhagic adenomas were significantly higher than the levels in females with solid adenomas. In the same strain, age-related differences in PRL levels were found. Significantly higher serum PRL levels were found at the age of 26-32 months than in older animals. The same tendencies were noticed in both other strains.

Adenoma↗
PubMed2006

Selective synthesis of epolactaene featuring efficient construction of methyl (Z)-2-iodo-2-butenoate and (2R,3S,4S)-2-trimethylsilyl-2,3-epoxy-4-methyl- gamma-butyrolactone.

[reaction: see text] (+)-Epolactaene was synthesized in 14 steps in the longest linear sequence. The synthesis is highlighted by a highly efficient preparation of the lactone intermediate 4, which only requires three steps from the commercially available (S)-3-butyn-2-ol. It also features a fully stereocontrolled synthesis of the intermediate 9, which was constructed through the use of Zr-catalyzed methylalumination of alkynes and a series of Pd-catalyzed organozinc cross-coupling reactions, such as homopropargylation, direct ethynylation, and alkenylation of the methyl ester of (Z)-alpha-iodocrotonic acid (3).

Butyrates↗
PubMed1977

Individual differences in the selection and use of features for classifying visual stimuli.

Two experiments were performed to investigate the classification of pot-like outlines by human judges. In experiment 1, seventy-two pot-like shapes, drawn by using all possible combinations of values of four pot ratios, were classified by twenty subjects and by a computer program. The shapes varied only in quantitative features and possessed no all-or-none characteristics. In experiment 2,256 shapes traced from drawings of existing pots were classified by fifteen judges. The pots varied in both quantitative and all-or-none features. The results showed that there were differences between judges in the weightings they assigned to different features, and the judges themselves could be classified according to the weightings they gave the features. There were even differences in the way different judges used all-or-none features for classifying. Possible mechanisms are suggested for the basis of these differences.

Adult↗
PubMed2002

Selective attention to stimulus features modulates interocular suppression.

Psychological and neurophysiological studies have shown that attention modulates various sorts of perceptual processing. Here, we report that attention affects the perceptual dominance of binocular rivalry. Experiments using a dichoptic masking paradigm revealed that when an observer was attending to one of the two orientations of the elements of a monocular texture, a texture briefly presented to the opposite eye suppressed the perception of the elements with the attended orientation, while the elements with the orientation which was ignored sustained their dominance. Moreover, subsequent experiments indicated that the suppression depended on the orientation of the texture elements constituting the mask, but was independent of their locations. These results suggest that attention to specific features modulates interocular suppression in a mode which is different from that found in a previous study [Ooi and He, 1999 Perception 28 551 -574].

Attention↗
PubMed2004

Behavioral and physiological features of chickens diversely selected for resistance to Avian Disease. 1. Selected inbred lines differ in behavioral and physical responses to social stress.

To test the hypothesis that genetic variations in response to social stress modulate susceptibility to disease in poultry, aggressive behaviors induced by social stress were measured in chickens of different inbred lines selected for disease resistance (line 63) or susceptibility (lines 72 and 15I5), as well as 2 recombinant congenic strains (B and X). At 15 wk of age, roosters from each genetic line or strain were randomly assigned to pairs for intraline male-male aggression tests (n = 8 per line). Based on the results of the intraline aggression tests, the roosters were divided into 2 groups, winners and losers. At 16 wk of age, the roosters were randomly paired as winners vs. winners and losers vs. losers for interline aggression tests, i.e., line 63 vs. 72 and 15I5; line 73 vs. line 15I5; and strain X vs. strain B. Similarly, at 17 wk of age, line 63 vs. strains X and B, and line 72 vs. strains X and B were tested. The tests were conducted in a novel cage that was similar to their home cages, to provide a neutral space for both roosters being tested. Each pair was videotaped for 15 min. Male-male interaction-induced aggressive behaviors were markedly different among the genetic lines. Compared with roosters of lines 15I5 and 72, line 63 roosters generally showed fewer aggressive behaviors, including aggressive pecks and fights, as well as durations (P < 0.05). Roosters of the recombinant congenic strains X and B, each possessing a unique random 87.5% genome of line 63, exhibited low aggressive behaviors, which were similar or equal to the level of line 63 in both intraline and interline aggression tests (P = 0.05). These results may indicate that some of the gene(s) commonly carried between strains X and B as well as line 63 likely played an important role in governing their lower levels of aggression. The present chicken lines may be used as animal models for investigation of the cellular mechanisms of genetic-environmental interactions on disease resistance and stress responses.

Aggression↗
PubMed1993

Selection of myocardial electrogram features for use by implantable devices.

Implantable devices that terminate ventricular tachycardia must be capable of correctly classifying heart rhythms to a high degree of reliability. We evaluated the relative discriminating power of several myocardial electrogram (ME) features in six human subjects by reducing the order of their corresponding feature spaces using three different optimization methods: 1) minimizing univariate Bayes error rates (univariate parametric), 2) maximizing the Kullback divergence (multivariate parametric), and 3) pruning classification trees (nonparametric). We found that although the composition of the optimal subspaces varied considerably from one subject to another, one frequency domain feature was common to most of the optimal subspaces.

Bayes Theorem↗
PubMed2004

Clinical features and management of selected hypertensive emergencies.

A hypertensive emergency, defined as an elevated blood pressure with evidence of acute target organ damage, can manifest in many forms, including neurological, cardiac, renal, and obstetric. After diagnosis, effective parenteral antihypertensive therapy (typically, nitroprusside starting at 0.5 microg/kg/min, but some physicians prefer fenoldopam or nicardipine) should be given in the hospital. In general, blood pressure should be reduced about 10% during the first hour and another 15% gradually over 2-3 more hours. The exception is aortic dissection, for which treatment includes a b blocker, and the target is systolic blood pressure <120 mm Hg after 20 minutes. Oral antihypertensive therapy can usually be instituted after 6-12 hours of parenteral therapy. Consideration should be given to secondary causes of hypertension after transfer from the intensive care unit. Because of advances in antihypertensive therapy and management, "malignant hypertension" should be malignant no longer.

Adrenergic beta-Antagonists↗
PubMed2000

[Biomorphological features of "minimal" carcinomas selected from a series of 2077 breast cancer cases].

Two hundred eighty nine pT1a/pT1b (less than < or = 1 cm in diameter) mammary carcinomas were selected from a series of 2077 consecutive cases of breast carcinoma. When compared with carcinomas of a larger size, they were significantly associated with a lower histological grade (SBR), a lower growth fraction (Ki-67 antigen in less than 20% of neoplastic cells) and a lower number of positive cases (more than 10% of neoplastic cells) as far as p53, c-erbB-2 oncoproteins and EGF-R, as detected by immunohistochemical methods, are concerned. Moreover, a significantly higher number of estrogen and progesterone receptors positive cases (more than 10% of positive cells), and a higher frequency of "other" histotypes with a favourable prognosis, was detected. No difference between pT1a and pT1b cases was noted so that "1 cm size" only stratifies a class with a better prognosis. It is possible that small cases, although invasive, did not undergone sufficient mytotic cycles to produce the sequence of genetic changes that characterize the "no return" phase of breast cancer. A 17% of pT1a and pT1b cases displayed lymph node metastases (mean 26 lymph node/case examined): the number is so high that cautions about simple lumpectomies and about sentinel lymphadenectomy, even in cases of small cancers, are necessary, until a larger number of studies will become available.

Biomarkers, Tumor↗