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At least 19 recordsLinked to original sources
PubMed2026

Mutual Information-based Prognostic Biomarker Discovery in Cancer Genomics: Conceptual Framework and Representative Applications of MI-POG.

Mutual information (MI)-based approaches have increasingly been applied to cancer genomics; however, their use for genome-wide prognostic biomarker discovery remains relatively underexplored. The present article summarizes the conceptual workflow of Mutual Information-based Prognostic Omics Gene (MI-POG) based on previously published applications in breast cancer, lower-grade glioma, and other cancer datasets. The framework consists of clinical endpoint discretization, genome-wide MI-based screening, candidate ranking, and downstream validation using conventional survival-analysis approaches. Previous MI-POG applications identified solute carrier family 20 member 1 (SLC20A1) as a prognostic biomarker in hormone receptor-positive breast cancer. Elevated SLC20A1 expression was associated with unfavorable survival outcomes and was independently validated in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort. Methodological analyses demonstrated how survival endpoints can be integrated into an information-theoretic framework through fixed-time outcome discretization, enabling model-independent assessment of molecular-clinical dependencies. Applications across multiple cancer datasets suggested the potential applicability of the framework across biologically distinct tumor types, although further validation will be required to establish its robustness and generalizability. In conclusion, MI-POG can be formalized as an information-theoretic framework for genome-wide identification of prognostic biomarkers by quantifying molecular-clinical dependencies using mutual information. Representative applications from previously published studies suggest that MI-POG may complement conventional survival-analysis approaches and provide a useful strategy for biomarker discovery, although additional benchmarking and prospective validation will be required.

Humans↗
PubMed2026

Concurrent ecological and evolutionary processes contribute to mutualism breakdown between legumes and rhizobia.

Though they jointly shape community responses to environmental perturbations, ecology and evolution are often examined separately, even in microorganisms where both occur over short timescales. Here we examine ecological and evolutionary responses to 33 years of nitrogen fertilization using the legume-rhizobium mutualism. Pairing a manipulative inoculation study with full-length 16S rRNA gene amplicon sequencing and structural equation modeling allows us to synthesize across biological scales: whole bacterial community, genus Rhizobium, Rhizobium ASVs, and symbiosis plasmids. Clover's preferred partner decreases in N-addition soils, limiting host growth, while a diverse and largely uncharacterized Rhizobium community increases. This ecological change is compounded by a concurrent evolutionary degradation of symbiont partner quality via changing frequencies of symbiotic plasmids. Ecological (rarer symbionts) and evolutionary (inferior symbionts) processes each accounted for roughly half of this loss of host benefit, revealing that ecology and evolution jointly shape mutualism breakdown over the short timescales typical of microbial systems.

ecology↗
PubMed2026

Resolving the "Yucca queretaroensis problem": Phylogenomic analysis of Yucca reveals the identity of an enigmatic species and the origin of an obligate pollination mutualism.

PREMISE: The genus Yucca is a group of ~50 species of woody monocots endemic to the North American arid regions. Their obligate pollination mutualism with yucca moths is considered a "textbook example" of coevolution and is hypothesized to have promoted rapid diversification. However, testing this hypothesis has been difficult due to uncertainty about the placement of a rogue taxon, Yucca queretaroensis, a rare endemic of the Sierra Gorda region of central Mexico. Past work placed this species in different positions within the Agavoideae, producing starkly different age estimates for Yucca (25 to 4 million years). METHODS: We generated new sequence capture data for 353 nuclear genes and for all coding regions of the plastid genome from wild-collected plants and samples included in previous studies to provide a new phylogeny and new age estimate for Yucca. RESULTS: The data presented here suggest that Y. queretaroensis is closely related to other species of Yucca. A relaxed molecular clock analysis of the plastid genome produced an estimated age for the genus of approximately 6.8 million years. CONCLUSIONS: The results resolve a mystery that has bedeviled evolutionary biologists for decades and provide a surprisingly young estimate for the age of Yucca, suggesting rapid diversification. The past difficulties in identifying the correct placement of Y. queretaroensis appear to be the product of laboratory errors, mistakes in field identification, and frequent hybridization with co-distributed taxa. The "Yucca queretaroensis problem" reaffirms the essential role for traditional botanical tools in phylogenomics.

ASTRAL↗
PubMed1978

The formation of contacts between HeLa cells. Directed mutual outgrowth of cell surface protrusions.

The contacting behavior of HeLa cells in subconfluent monolayer cultures has been studied by phase contrast and scanning electron microscopy. We present further evidence that cells separated from each other by a cell-free space up to 20 micron width can simultaneously form directed and mutual protrusions against each other. A statistical analysis demonstrated that in more than half of the possible contact events a reciprocal outgrowth of cell surface protrusions had occurred. This suggests that contact formation is not just a random process, but may be influenced by so far unrecognized factors.

Cells, Cultured↗
PubMed1975

Correlation proton magnetic resonance studies at 250 MHz of bovine pancreatic ribonuclease. III. Mutual electrostatic interaction between histidine residues 12 and 119.

The two adjacent active site histidine residues of bovine pancreatic ribonuclease A (histidine-12 and -119) yield proton magnetic resonance titration curves having Hill coefficients significantly less than unity (0.7 and 0.8, respectively). Three models postulating interactions with other titrating groups in the molecule have been used to approximate these anomalous experimental titration curves. Very good agreement with the data was obtained with models postulating mutual electrostatic interaction between histidine-12 and -119. The additional low pH perturbation of the chemical shift of the C(2)-H peak (but not the C(4)-H peak) of histidine-12 is attributed to a local conformational change with a pHmid of about 3.5.

Amino Acid Sequence↗
PubMed2025

Spatial mutual nearest neighbors for spatial transcriptomics data.

MOTIVATION: Mutual nearest neighbors (MNN) is a widely used computational tool to perform batch correction for single-cell RNA-sequencing data. However, in applications such as spatial transcriptomics, it fails to take into account the 2D spatial information. RESULTS: Here, we present spatialMNN, an algorithm that integrates multiple spatial transcriptomic samples and identifies spatial domains. Our approach begins by building a k-nearest neighbors (kNN) graph based on the spatial coordinates, prunes noisy edges, and identifies niches to act as anchor points for each sample. Next, we construct a MNN graph across the samples to identify similar niches. Finally, the spatialMNN graph can be partitioned using existing algorithms, such as the Louvain algorithm to predict spatial domains across the tissue samples. We demonstrate the performance of spatialMNN using large datasets, including one with N = 31 10x Genomics Visium samples. We also evaluate the computing performance of spatialMNN to other popular spatial clustering methods. AVAILABILITY AND IMPLEMENTATION: Our software package is available on GitHub (https://github.com/Pixel-Dream/spatialMNN). The code is available on Zenodo (https://doi.org/10.5281/zenodo.15073963).

Algorithms↗
PubMed1978

Initiation factor IF-3 and the binary complex between initiation factor IF-2 and formylmethionyl-tRNA are mutually exclusive on the 30-S ribosomal subunit.

The formation of 30-S initiation complexes depends strongly on initiation factor IF-3; at molar ratios of IF-3 to 30-S ribosomes up to one a stimulation is observed, whereas at ratios higher than one, initiation complex formation declines strongly. The target of the observed inhibition of fMet-tRNA binding at high concentrations of IF-3 is the 30-S initiation complex itself. On the one hand addition of IF-3 to preformed 30-S initiation complexes leads to a release of bound fMet-tRNA which is linear with the amount of factor added, whereas no effect on isolated 70-S initiation complexes is seen. The release of fMet-tRNA from preformed 30-S initiation complexes is accompanied by a release of IF-2 in a one-to-one molar ratio which is in agreement with our previous findings showing that binding of fMet-tRNA takes place via a binary complex: IF-2 . fMet-tRNA (Eur. J. Biochem. 66, 181--192 and 77, 69--75). On the other hand increasing amounts of both IF-2 and fMet-tRNA relieve the IF-3-induced inhibition of 30-S initiation complex formation. From these findings it is concluded that IF-3 and the IF-2 . fMet-tRNA complex are mutually exclusive on the 30-S ribosome. This implies that under our experimental conditions MS2 RNA binding precedes fMet-tRNA binding if one accepts that the presence of IF-3 on the 30-S subunit is obligatory for messenger binding.

Escherichia coli↗
PubMedDate not supplied

[Mutual stimulation of oncornavirus and herpetic infections in experiments in vivo and in vitro].

The evidence of mutual stimulation of herpes simplex virus (HSV) and oncornaviruses (OV) reproduction was obtained. HSV titers in mice pre-infected with Rauscher leukosis virus (RLV) were 2.25-3.0 lg LD50 higher than in mice of the same batch but without RLV infection. The continuous HEp-2 culture chronically infected with oncornaviruses was found to be more sensitive to the cytopathic effect of HSV strains, types 1 and 2, and in the culture fluid HSV accumulated to a greater titer than in primarily trypsinized culture of chick embryo fibroblasts. Electron microscope examinations of the continuous J-96 cell culture chronically infected with OV and HSV simultaneously revealed an 8.3-fold increase in the number of oncornavirus particles as compared to the control culture, infected with OV alone.

Animals↗
PubMed2025

CaXML: Chemistry-informed machine learning explains mutual changes between protein conformations and calcium ions in calcium-binding proteins using structural and topological features.

Proteins' flexibility is a feature in communicating changes in cell signaling instigated by binding with secondary messengers, such as calcium ions, associated with the coordination of muscle contraction, neurotransmitter release, and gene expression. When binding with the disordered parts of a protein, calcium ions must balance their charge states with the shape of calcium-binding proteins and their versatile pool of partners depending on the circumstances they transmit. Accurately determining the ionic charges of those ions is essential for understanding their role in such processes. However, it is unclear whether the limited experimental data available can be effectively used to train models to accurately predict the charges of calcium-binding protein variants. Here, we developed a chemistry-informed, machine-learning algorithm that implements a game theoretic approach to explain the output of a machine-learning model without the prerequisite of an excessively large database for high-performance prediction of atomic charges. We used the ab initio electronic structure data representing calcium ions and the structures of the disordered segments of calcium-binding peptides with surrounding water molecules to train several explainable models. Network theory was used to extract the topological features of atomic interactions in the structurally complex data dictated by the coordination chemistry of a calcium ion, a potent indicator of its charge state in protein. Our design created a computational tool of CaXML, which provided a framework of explainable machine learning model to annotate ionic charges of calcium ions in calcium-binding proteins in response to the chemical changes in an environment. Our framework will provide new insights into protein design for engineering functionality based on the limited size of scientific data in a genome space.

Machine Learning↗
PubMed1979

Mutual antagonism of behavioral effects of TRH and thiobarbiturate on an operant task in rhesus monkeys.

Similar excitatory or depressant response rate dependent effects on monkeys responding on a variable interval reinforcement schedule were observed following intravenous administration of either thyrotropin releasing hormone (TRH) or thiobarbiturate. However, these agents were mutally antagonistic when given together even though the response rate altering effects of each agent were in the same direction. These findings establish an additional behavioral effect of exogenously administered TRH in primates and suggest that barbiturates might alter behavior in part through an interaction with brain TRH receptive mechanisms.

Animals↗
PubMed1979

Mutual homology of mouse immunoglobulin gamma-chain gene sequences.

We have assessed the relative homology of mouse immunoglobulin heavy-chain gene sequence using complementary DNAs (cDNAs) synthesized against gamma-chain mRNAs (gamma 1, gamma 2a, gamma 2b, and gamma 3) purified from mouse myelomas. cDNAs complementary to the gamma-chain mRNAs did not cross-hybridize with the mu- and alpha-chain mRNAs, whereas they cross-hybridized to significant extents (22--66%) with the gamma-chain mRNAs of other subclasses. The heterologous hybrids formed, however, melt at 5--13 degrees C lower temperatures as compared to the homologous hybrids, indicating that significant portions of the heterologous hybrids are mismatched. The rates of the cross-hybridization reactions are 2- to 17-fold slower than those of the homologous hybridization reactions. Therefore, the gamma-chain gene sequences of four subclasses share a part of homology with each other, but they are different enough to be measured separately. Cross-hybridization analysis indicate that the gamma 2a and gamma 2b genes are the most closely related, while the gamma 1 and gamma 3 genes are the least related among the gamma subclass genes.

Animals↗
PubMed1977

Mutual entrainment of bilaterally distributed circadian pacemaker.

The interactions between the bilaterally distributed components of the circadin system that controls the locomotor activity rhythm of the cockroach Leucophaea maderae were investigated in a series of surgical lesion experiments. Complete excision of one optic lobe (either right or left) or its surgical isolation from the central nervous system had no effect on the animals' ability to free-run in constant darkness nor was there any indication, as judged by postoperative pi values of any difference between left and right lobe pacemakers. However, these surgical procedures consistently resulted in a significant increase in tau over preoperative value while optic nerve section had no effect on tau. The propostion is developed that the left and right pacemakers in the two optic lobes are mutally coupled and that the compound pacemaker's period is shorter than either of its constituent pacemakers. It was also found that the integrity of either compound eye is sufficient to assure entrainment of both left and right pacemakers.

Animals↗
PubMed1975

Mutual modification of glucose-stimulated serum insulin responses in female rhesus monkeys by ethinyl estradiol and nortestosterone derivatives.

Changes in iv glucose tolerance (IVGTT) and serum insulin responses to glucose infusion have been measured in intact female rhesus monkeys treated per os with norethindrone or medroxyprogesterone acetate (500 mug/day) both alone and in combination with mestranol or ethinyl estradiol (10 mug/day) orally for 3 weeks. When administered as the sole contraceptive steroid, neither norethindrone, medroxyprogesterone acetate, mestranol, or ethinyl estradiol produced consistent changes in fasting serum insulin or glucose concentration, mean intravenous serum glucose disappearance rates (K) or mean integrated serum insulin response to glucose (sigmal40). By contrast, concurrent administration of norethindrone with mestranol or ethinyl estradiol resulted in a significant increase in the fasting serum insulin concentration and the mean sigmal40. An increase in the mean K was also observed after norethindrone + mestranol. These results show that synthetic estrogens have the ability to potentiate the metabolic effects of norethindrone. However, the improvement in glucose tolerance produced in rhesus monkeys by concurrent mestranol + norethindrone treatment was marginal because of wide variation in glucose assimilation rates uncer control conditions. Thus, the IVGTT in the rhesus monkey appears to have limited use as a model for studying glucose homeostasis in man.

Administration, Oral↗
PubMed1978

Mutual expectations in the process of joining a dental health group.

Productivity can be seriously affected when new persons join an existing group and little or no attention is given to the process by which that person becomes a member of the group practice. Parallels can be drawn between organizational management and the functioning of the dental team. Observations were made of three clinicians who attempted to join an existing dental delivery group. There are some predictable phases through which the joiner passes to acceptance or lack of acceptance in an existing group. Recommendations for groups to consider before either hiring or training members of a dental health group are given.

Cooperative Behavior↗
PubMed1978

Does smoking kill workers or working kill smokers? OR The mutual relationship between smoking, occupation, and respiratory disease.

Evidence accumulated since 1964 appears to show that occupation, not cigarette smoking, may be the primary cause of lung disease, especially of cancer and chronic obstructive disease. Comparisons of groups of individuals who smoke more with those who smoke less actually serve to contrast groups with a high proportion of blue-collar workers exposed to toxic fumes and a low proportion of professionals, managers, and proprietors with groups having lower proportions of blue-collar workers and higher proportions of professionals, managers, and proprietors. Thus, many diseases associated with smoking actually may be of occupational origin. Indeed, more than a dozen recent investigations of lung cancer epidemics among industrial workers have failed to find smoking to be a major cause (in some, not even a contributing cause). This evidence is strengthened further by shifts in the incidence of lung cancer that follow in time shifts in industrial employment patterns. Yet a worker's past smoking habits seem to play a key role in decreasing compensation awards for injuries that actually may be due to occupational exposure rather than personal habits. Thus, the relationship between smoking, occupation, and disease needs serious clarification. Smoking appears to have been used to divert attention away from the effects of occupational and environmental exposures to toxic substances.

Adult↗