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PubMed2004

iProLINK: an integrated protein resource for literature mining.

The exponential growth of large-scale molecular sequence data and of the PubMed scientific literature has prompted active research in biological literature mining and information extraction to facilitate genome/proteome annotation and improve the quality of biological databases. Motivated by the promise of text mining methodologies, but at the same time, the lack of adequate curated data for training and benchmarking, the Protein Information Resource (PIR) has developed a resource for protein literature mining--iProLINK (integrated Protein Literature INformation and Knowledge). As PIR focuses its effort on the curation of the UniProt protein sequence database, the goal of iProLINK is to provide curated data sources that can be utilized for text mining research in the areas of bibliography mapping, annotation extraction, protein named entity recognition, and protein ontology development. The data sources for bibliography mapping and annotation extraction include mapped citations (PubMed ID to protein entry and feature line mapping) and annotation-tagged literature corpora. The latter includes several hundred abstracts and full-text articles tagged with experimentally validated post-translational modifications (PTMs) annotated in the PIR protein sequence database. The data sources for entity recognition and ontology development include a protein name dictionary, word token dictionaries, protein name-tagged literature corpora along with tagging guidelines, as well as a protein ontology based on PIRSF protein family names. iProLINK is freely accessible at http://pir.georgetown.edu/iprolink, with hypertext links for all downloadable files.

Computational Biology↗

PubMed2026

Uncovering hub genes and key pathways responsive to drought stress in rice via meta-analysis of transcriptomic data.

Drought stress presents a formidable threat to global rice cultivation, triggering complex molecular responses that impact plant growth and productivity. To decipher the underlying gene expression dynamics, we performed a comprehensive meta-analysis of transcriptomic datasets derived from drought-tolerant rice genotypes. Via microarray data from three independent studies, we identified a set of consistently expressed differentially expressed genes (DEGs) under drought conditions. Integration of functional annotation tools, including GO and KEGG pathway enrichment, revealed key biological processes and signaling cascades involved in stress mitigation, such as ABA signaling, protein folding, and photosynthesis suppression. Protein-protein interaction (PPI) network construction, followed by hub gene identification via maximal clique centrality (MCC), highlighted pivotal regulators including LEA proteins, dehydrins, HSP70, and several transcription factors. Machine learning approaches further prioritize potential biomarkers, with Random Forest models achieving high classification accuracy and pinpointing key predictive genes. Chromosomal localization analysis provided spatial insights into the distribution of these hub genes, whose expression patterns were further compared against qRT-PCR data from previously published studies. This integrative approach identifies candidate genomic markers and mechanistic insights that may support future breeding strategies for drought-tolerant rice, pending experimental validation.

Cytoscape↗

PubMed2026

Integrated experimental and bioinformatics analysis reveals ECM-integrin and redox signaling associated with PMMA/NiO nanocomposites for craniofacial applications.

BACKGROUND: Poly(methyl methacrylate) (PMMA) is widely used in dental and craniofacial applications; however, its clinical performance is limited by poor surface wettability, moderate mechanical strength, and restricted biological activity. Integrating nanomaterial engineering with computational biology offers an opportunity to better understand biomaterial-cell interactions and support the rational design of functional biomaterials. METHODS: Nickel oxide (NiO) nanoparticles were synthesized via chemical precipitation and incorporated into PMMA to fabricate nanocomposites. Physicochemical characterization included contact angle measurements, Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and Vickers hardness testing. Biocompatibility was evaluated using zebrafish embryo developmental assays. To explore biological processes potentially associated with biomaterial-cell interactions, bioinformatics analyses including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and STRING protein-protein interaction (PPI) network analyses were performed. RESULTS: Incorporation of NiO nanoparticles improved the surface and mechanical properties of PMMA, reducing the contact angle from 105.35° to 90.46° and increasing Vickers hardness compared with unmodified PMMA. Structural and morphological analyses confirmed successful synthesis and homogeneous nanoparticle incorporation. Zebrafish embryo studies demonstrated minimal developmental toxicity, supporting the biocompatibility of the nanocomposite. Bioinformatics analyses identified significant enrichment of pathways related to extracellular matrix organization, cell adhesion, focal adhesion, PI3K-Akt signaling, and oxidative stress regulation. Protein-protein interaction analysis revealed highly interconnected networks associated with ECM-integrin signaling and redox homeostasis, highlighting biological processes potentially associated with biomaterial-cell communication. CONCLUSIONS: PMMA/NiO nanocomposites exhibited improved physicochemical performance and favorable biocompatibility characteristics. The integration of experimental characterization with bioinformatics and network-based analyses provides a systems-level perspective on biomaterial-associated cellular processes and identifies ECM-integrin signaling and oxidative stress-related pathways as candidate biological processes for future experimental validation. These findings support the continued development of PMMA/NiO nanocomposites for oral and craniofacial biomedical applications.

Nanocomposites↗

PubMed2005

Mechanisms for allocating auditory attention: an auditory saliency map.

Our nervous system is confronted with a barrage of sensory stimuli, but neural resources are limited and not all stimuli can be processed to the same extent. Mechanisms exist to bias attention toward the particularly salient events, thereby providing a weighted representation of our environment. Our understanding of these mechanisms is still limited, but theoretical models can replicate such a weighting of sensory inputs and provide a basis for understanding the underlying principles. Here, we describe such a model for the auditory system-an auditory saliency map. We experimentally validate the model on natural acoustical scenarios, demonstrating that it reproduces human judgments of auditory saliency and predicts the detectability of salient sounds embedded in noisy backgrounds. In addition, it also predicts the natural orienting behavior of naive macaque monkeys to the same salient stimuli. The structure of the suggested model is identical to that of successfully used visual saliency maps. Hence, we conclude that saliency is determined either by implementing similar mechanisms in different unisensory pathways or by the same mechanism in multisensory areas. In any case, our results demonstrate that different primate sensory systems rely on common principles for extracting relevant sensory events.

Acoustic Stimulation↗

PubMed2004

Stress distributions in adhesively cemented ceramic and resin-composite Class II inlay restorations: a 3D-FEA study.

OBJECTIVES: The purpose of this study was to investigate the effect of differences in the resin-cement elastic modulus on stress-transmission to ceramic or resin-based composite inlay-restored Class II MOD cavities during vertical occlusal loading. METHODS: Three finite-element (FE) models of Class II MOD cavity restorations in an upper premolar were produced. Model A represented a glass-ceramic inlay in combination with an adhesive and a high Young's modulus resin-cement. Model B represented the same glass-ceramic inlay in combination with the same adhesive and a low Young's modulus resin-cement. Model C represented a heat-cured resin-composite inlay in combination with the same adhesive and the same low Young's modulus resin cement. Occlusal vertical loading of 400 N was simulated on the FE models of the restored teeth. Ansys FE software was used to compute the local von Mises stresses for each of the models and to compare the observed maximum intensities and distributions. Experimental validation of the FE models was conducted. RESULTS: Complex biomechanical behavior of the restored teeth became apparent, arising from the effects of the axial and lateral components of the constant occlusal vertical loading. In the ceramic-inlay models, the greatest von Mises stress was observed on the lateral walls, vestibular and lingual, of the cavity. Indirect resin-composite inlays performed better in terms of stress dissipation. Glass-ceramic inlays transferred stresses to the dental walls and, depending on its rigidity, to the resin-cement and the adhesive layers. For high cement layer modulus values, the ceramic restorations were not able to redistribute the stresses properly into the cavity. However, stress-redistribution did occur with the resin-composite inlays. SIGNIFICANCE: Application of low modulus luting and restorative materials do partially absorb deformations under loading and limit the stress intensity, transmitted to the remaining tooth structures.

Bicuspid↗

PubMed2005

Reaction kinetics and mechanics in photo-polymerised networks.

OBJECTIVES: The aim of this paper is to address the relationship, existing in photo-cure composites, between the polymer-network forming reactions, along with their kinetics, and the resultant stress-transmitting micro-mechanical behavior. METHODS: Photon numbers and energies were calculated and compared for a simple model monomer-composite system. Expressions for light irradiance at depth within materials were computed and the consequences of steady-state assumptions in kinetic models of conversion and shrinkage-strain rate were considered. RESULTS: The resultant stress-transmitting properties are a complex function of photon-transport, absorption by photo-initiators, possibly non-steady-state free-radical cross-linking, collapse of free-volume and development of an elastic-network displaying non-homogenous structure, viscoelasticity and aging effects. SIGNIFICANCE: Researchers need to be aware of the complexity of these systems, so as to adequately control experimental variables and to develop more sophisticated models and hypotheses for experimental validation.

Composite Resins↗

PubMed2006

The longevity effect of dietary restriction in Caenorhabditis elegans.

The nematode Caenorhabditis elegans has been subjected to DR by food (Escherichia coli) dilution, growth in axenic medium and using animals having defects in feeding behavior or in specific nutrient transporter proteins. There is evidence that DR causes increased resistance against environmental stressors but no decrease of metabolic rate. The insulin/IGF-1 signaling pathway does not mediate the longevity effect of DR in this species, but TOR signaling may be involved. The metabolic stability-longevity theory offers a plausible explanation of the longevity effect of DR but needs experimental validation.

Aging↗

PubMed2005

Synechocystis ferredoxin/ferredoxin-NADP(+)-reductase/NADP+ complex: Structural model obtained by NMR-restrained docking.

Ferredoxin (Fd) and ferredoxin-NADP(+)-reductase (FNR) are two terminal physiological partners of the photosynthetic electron transport chain. Based on a nuclear magnetic resonance (NMR)-restrained-docking approach, two alternative structural models of the Fd-FNR complex in the presence of NADP+ are proposed. The protein docking simulations were performed with the software BiGGER. NMR titration revealed a 1:1 stoichiometry for the complex and allowed the mapping of the interacting residues at the surface of Fd. The NMR chemical shifts were encoded into distance constraints and used with theoretically calculated electronic coupling between the redox cofactors to propose experimentally validated docked complexes.

Amino Acid Sequence↗

PubMed2006

The cartilage specific microRNA-140 targets histone deacetylase 4 in mouse cells.

MicroRNAs (miRNA) are short RNA molecules regulating the expression of specific mRNAs. We investigated the expression pattern and potential targets of mouse miR-140 and found that miR-140 is specifically expressed in cartilage tissues of mouse embryos during both long and flat bone development. MiR-140 expression was detected in the limbs of E11.5 embryos in the primorida of future bones both in the fore and hindlimb and across autopod, zeugopod and stylopod. All digits of E14.5 fore- and hindlimbs showed accumulation of miR-140, except the first digit of the hindlimb. MiR-140 expression was also detected in the cartilagenous base of E17.5 skulls and in the sternum, the proximal rib heads and the developing vertebral column of E15.5 embryos. A potential target of miR-140, histone deacetylase 4, was validated experimentally and the possible role of miR-140 in long bone development is discussed.

Animals↗

PubMed2005

A mathematical model for evaluation of maternal cell contamination in cultured cells from spontaneous abortions: significance for cytogenetic analysis of prenatal selection factors.

OBJECTIVE: To develop a mathematical model for more precise estimation of the incidence of chromosomal abnormalities and the sex ratio among spontaneous abortions masked by maternal cell contamination. DESIGN: Retrospective analysis. SETTING: Academic medical center. PATIENT(S): One hundred twelve samples of spontaneous abortion with a "46,XX" karyotype and 97 parents with aborted embryos. INTERVENTION(S): The presence of Y chromosome DNA in native tissues of "46,XX" spontaneous abortions was detected by amelogenin locus analysis. Detection of aneuploidies in noncultured tissues of "46,XX" abortions was performed by microsatellite DNA analysis and confirmed by fluorescence in situ hybridization. MAIN OUTCOME MEASURE(S): Accuracy of cytogenetic evaluation of spontaneous abortions. RESULT(S): Y chromosome DNA was revealed in 16% of the embryos with a "46,XX" karyotype. According to the mathematical model proposed, the frequency of chromosomal abnormalities in a sample of 478 abortions increased from 54.6% to 60.3%, and the sex ratio in embryos with normal karyotype changed from 0.66 to 1.02. The experimental validation of the model has shown that the observed and expected incidences of chromosomal abnormalities in "46,XX" abortions were in good agreement. CONCLUSION(S): Maternal cell contamination clearly affects the incidence of registered chromosomal abnormalities and the sex ratio in spontaneous abortions. Correction for maternal cell contamination should be taken into account before invoking biological explanations of sex ratio bias and might be useful to include in diagnostic reporting.

Abortion, Spontaneous↗

PubMed2026

Single-cell transcriptomics reveals heterogeneous stress responses and Mg2+-mediated survival mechanisms in Lactobacillus delbrueckii subsp. bulgaricus during freeze-drying and storage.

Maintaining the viability of lactic acid bacteria during dehydration and subsequent storage remains a significant challenge. Here, we employed single-cell RNA sequencing to reveal the heterogeneous stress responses of Lactobacillus delbrueckii subsp. bulgaricus, identifying seven distinct transcriptional clusters across the liquid culture, freeze-drying, and storage phases. The dominant clusters in the freeze-drying and storage were not completely consistent, showing significant functional differentiation. Genomic stability may be important for survival during freeze-drying and storage, while intracellular energy homeostasis appears important for viability during storage. The magnesium transporter mgtB was highly expressed in clusters tolerant to freeze-drying and storage, suggesting a critical role for Mg2+ homeostasis. Further experimental validation confirmed that Mg2+ treatment significantly bolstered stress resistance, increasing immediate post-freeze-drying survival by over 2-fold (up to 92.90%) and post-storage survival by over 5-fold (up to 5.98%). Proteomic data indicated that Mg2+ supplementation correlated with the maintenance of several biological functions potentially relevant to bacterial survival during freeze-drying and storage, including DNA repair, translation, and central carbon metabolism. These findings provide a map of microbial stress resistance through population heterogeneity and offer a potential strategy that may be adapted for enhancing the stability of other industrial lactic acid bacteria products.

Freeze Drying↗

PubMed2005

Peroxiredoxins: a historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling.

The observation that purified yeast glutamine synthetase is rapidly inactivated in a thiol-containing buffer yet retains activity in crude extracts containing the same thiol led to our discovery of an enzyme that protects against oxidation in a thiol-containing system. This novel antioxidant enzyme was shown to reduce hydroperoxides and, more recently, peroxynitrite with the use of electrons provided by a physiological thiol like thioredoxin. It defined a family of proteins, present in organisms from all kingdoms, that was named peroxiredoxin (Prx). All Prx enzymes contain a conserved Cys residue that undergoes a cycle of peroxide-dependent oxidation and thiol-dependent reduction during catalysis. Mammalian cells express six isoforms of Prx (Prx I to VI), which are classified into three subgroups (2-Cys, atypical 2-Cys, and 1-Cys) based on the number and position of Cys residues that participate in catalysis. The relative abundance of Prx enzymes in mammalian cells appears to protect cellular components by removing the low levels of peroxides produced as a result of normal cellular metabolism. During catalysis, the active site cysteine is occasionally overoxidized to cysteine sulfinic acid. Contrary to the general belief that oxidation to the sulfinic state is an irreversible process in cells, studies on the fate of the overoxidized Prx species revealed a mechanism by which the catalytically active thiol form is recovered. This sulfinic reduction is a slow, ATP-dependent process that is specific to 2-Cys Prx isoforms. This reversible overoxidation may represent an adaptation unique to eukaryotic cells that accommodates the intracellular messenger function of H(2)O(2), but experimental validation of such speculation is yet to come.

Amino Acid Sequence↗

PubMed2025

Utility of genome sequencing and group-enrichment to support splice variant interpretation in Marfan syndrome.

PURPOSE: To quantify the impact of noncanonical FBN1 splice site variants in undiagnosed Marfan syndrome (MFS), a connective tissue disorder associated with skeletal abnormalities and familial thoracic aortic aneurysm disease (FTAAD). METHODS: A systematic analysis of ultrarare FBN1 variants was performed using genome sequencing data from the 100,000 Genomes Project. Variants were annotated with SpliceAI and the significance of enrichment among individuals with FTAAD was assessed using Fisher's exact test. Experimental validation used RNA sequencing, reverse transcriptase polymerase chain reaction, minigene constructs, and replication analysis was with data from UK Biobank. RESULTS: Using aggregate data for 78,195 individuals, we identified 13,864 singleton single-nucleotide variants in FBN1 of which 21 were predicted to affect splicing (SpliceAI > 0.5). Incidence of candidate splice variants in individuals recruited with FTAAD (9/703) was significantly elevated compared with that seen in non-FTAAD participants (12/77,492; odds ratio = 84, P = 9.7 × 10-14). Additional analysis uncovered a further 14 families harboring 11 different FBN1 splice variants. A total of 20 candidate splice variants in 23 families were identified, of which 70% lay beyond the ±8 splice regions. RNA testing confirmed the predicted splice aberration in 16 of 20 and for 9 of 20, pseudoexonization was the likely splicing anomaly. CONCLUSION: Our findings indicate that noncanonical splice variants may account for approximately 3% of families with undiagnosed FTAAD, highlighting the importance of incorporating analysis of introns and confirmatory RNA testing into genetic testing for Marfan syndrome.

Humans↗

PubMed2006

Semi-automated 3-dimensional intracardiac echocardiography: development and initial clinical experience of a new system to guide ablation procedures.

BACKGROUND: Pre-interventional three-dimensional (3D) reconstruction of the heart by CT or MRI provides important information on cardiac anatomy for electrophysiological interventions. However, updates of 3D-imaging modalities with high soft-tissue contrast are not available during ablation procedures. OBJECTIVE: We describe the development and first clinical testing of a close to real-time visualization of cardiac anatomy by intracardiac echocardiography (ICE). METHODS: An electronic phased-array 5-10 MHz ICE-catheter (AcuNav/Siemens/64 elements) was inserted via a straightened femoral vein sheath (12F) and placed in the right atrium in 5 pigs. A custom-made prototype stepper motor allowed automatic rotation around the longitudinal axis from 90 degrees to 360 degrees in 2-5 degrees steps. For every plane 2D images of a complete cardiac cycle were acquired, triggered by respiration and ECG. The ultrasound images were digitized and 3D-reconstruction was performed by a prototype software. After experimental validation the system was tested in 6 patients during electrophysiological studies. RESULTS: From a single location in the right atrium, 3D-acquisition and reconstruction of both atria and ventricles with good image quality were achieved within 3-5 minutes. Doppler-mode facilitated identification of the great vessels including the pulmonary veins and their entry into the heart. 3D-visualization of ablation catheters was also possible in all patients and pigs. CONCLUSION: Semi-automated 3D intracardiac echocardiography from a single site inside the right atrium provides the electrophysiologist with a detailed image of both atria and ventricles with repeated updates of the cardiac anatomy.

Animals↗

PubMed2006

Molecular analysis and solution structure from small-angle X-ray scattering of the human natural killer inhibitory receptor IRp60 (CD300a).

Natural killer (NK) cells are lymphocytes of the innate immune system specialized in recognition and killing of certain virus-infected and tumor cells. To carry out this task, NK cells are equipped with a complex array of germ line encoded receptors. These receptors deliver either positive or negative signals, and a delicate balance between these signals governs the NK cell cytolytic activity against the target cell. IRp60 (CD300a) is a human NK inhibitory receptor with an immunoglobulin-like fold. In the present study the IRp60 protein was expressed in Escherichia coli as inclusion bodies and refolded by dilution. The refolded protein was purified to homogeneity, biochemical characterized and the solution structure was investigated using small-angle X-ray scattering (SAXS). The SAXS data revealed that IRp60 is monomeric in solution with a molecular shape characteristic of the immunoglobulin-like structures. A homology model of IRp60 was built and validated experimentally against the SAXS data.

Antigens, CD↗

PubMed2026

Identifying the regulatory network of the key lipid metabolism transcription factor peroxisome proliferator-activated receptor in oysters.

Rising seawater temperatures driven by global warming have led to summer mass mortality events that pose significant challenges for the oyster industry. Peroxisome proliferator-activated receptor (PPAR) serves as a key transcriptional regulator of lipid metabolism and plays an essential role in thermal adaptation. However, the upstream regulatory mechanisms of PPAR remain poorly understood in marine organisms. In this study, we identified two PPAR subtypes (PPARα and PPARβ/δ) in oysters and compared transcriptomic data in different tissues and under various environmental stressors, with PPARα exhibiting higher expression levels and responsiveness to environmental stresses. We observed significantly higher PPARα gene expression levels and promoter activity in the relatively cold-tolerant Crassostrea gigas compared to C. angulata. The low expression of the inhibitory transcription factor CTNNB1 in C. gigas may contribute to higher gene expression of PPARα. Additionally, the expression genome-wide association study (eGWAS) identified 9 significant SNPs and 124 candidate regulatory genes associated with PPARα expression, including ubiquitination, phosphorylation, signaling pathways, lipid metabolism, and glucose metabolism. We provided the first experimental validation of the PPARα ubiquitination-degradation pathway in marine organisms via Co-IP, which was mediated by the E3 ligase RFWD3. The protein kinase SNF1 and signaling-related proteins PIKA and KCNK2 indirectly modulated PPARα downstream pathway activation to varying degrees. This study presents the first systematic investigation of PPARα expression regulation in marine organisms. It identifies key molecular regulators and provides novel insights into lipid metabolic regulation and molecular targets for genetic improvement of heat tolerance in oysters under global warming.

Animals↗

PubMed2026

Single-cell transcriptional profiling identifies the swimming crab Portunus trituberculatus in response to bacterial infection.

Crustaceans rely entirely on innate immunity, yet the cellular composition, functional specialization, and pathogen-induced remodeling of their immune system remain poorly resolved. Here, we generated a high-resolution single-cell transcriptomic atlas of hemocytes from the swimming crab Portunus trituberculatus following Vibrio parahaemolyticus infection using 10× Genomics scRNA-seq. Seven putatively distinct hemocyte clusters were identified, including granulocytes, semigranular hemocytes, prohemocytes, unresolved hemocytes, hyalinocyte-like hemocytes, biosynthetically active secretory hemocytes, and regulatory hemocytes. Although the overall cellular composition remained relatively stable after infection, hemocytes exhibited pronounced cluster-specific transcriptional reprogramming involving Toll/NF-κB signaling, antimicrobial peptide synthesis and metabolic rewiring. By integrating single-cell and bulk transcriptomes, we identified multiple anti-lipopolysaccharide factors (ALFs) as key secretory effectors and experimentally validated their antibacterial activities. FITC-based bacterial engulfment assays and RNA-seq of sorted phagocytes demonstrated that phagocytic capability was shared across multiple hemocyte clusters. Notably, the immunoglobulin superfamily receptor DSCAM displayed extensive alternative splicing and strong infection-induced activation in unresolved hemocytes. Immune-training experiments showed that prior bacterial exposure was associated with altered DSCAM expression and reduced early cumulative mortality upon secondary challenge, suggesting a memory-like immune phenotype. These findings provide a foundational framework for understanding crustacean immunity and advancing disease-resistant breeding in aquaculture.

Antimicrobial peptides↗

PubMed2004

Modelling effect of physical and chemical parameters on heat inactivation kinetics of hepatitis A virus in a fruit model system.

While thermal destruction of pathogenic bacteria has been thoroughly studied in food industry, heat inactivation of viruses in food has been poorly investigated. Experiments were carried out to characterize the effects of controlled physical and chemical characteristics of a food matrix upon heat resistance parameters (D and z values) of hepatitis A virus (HAV), taken as model because of its reported heat resistance. Sucrose content (28-52 degrees Brix), calcium concentration (90-1700 mg kg(-1)) and pH (3.3-4.3) were selected for possible influence on thermal inactivation of HAV in strawberry mashes and thus included in an experimental design according to a Doehlert matrix. Use of this design not only allowed to detect and quantify the direct influence of sucrose concentration upon the D85 degrees C value to be higher than the one of pH, but also to reveal a sucrose concentration/pH specific interaction, while no effect of calcium concentration was evidenced. Although the model cannot be directly used to predict heat resistance in real fruit systems, because of differences observed between predicted and measured D85 degrees C values, it is useful for predicting the trends and relative changes in D values due to sucrose concentration and pH variations. Results suggested possible effects of other constituents of strawberry products on heat resistance of HAV and confirmed the importance of experimental validation of any model-derived process. Nevertheless, such a modelling approach using response surface methodology provides a rapid answer to heat resistance evaluation of a food-borne virus as a function of specific physical and chemical parameters of specific food products.

Calcium↗