A Calf from a Tree-Trunk: From a Rustic Proverb to a Standard Scholastic Argument.

The paper deals with the expression "God is able to make a calf from a tree-trunk"-a very popular phrase in medieval treatises, especially in the context of God's omnipotence. Its attestations are thoroughly documented and considered, contexts discussed, and attributions examined. It is argued that the attribution to Anselm of Canterbury is false and late. It is claimed that the phrase goes back to a popular saying as attested by William of Conches, Peter Comestor, and ps.-Bonaventurian Ars concionandi. Thus, it is a rare example of a rustic proverb used in scholastic debates as a standard scholarly argument.

Oncogenic GNAS drives a gastric pylorus program in intraductal papillary mucinous neoplasms of the pancreas.

OBJECTIVE: Intraductal Papillary Mucinous Neoplasms (IPMNs) are cystic lesions and bona fide precursors for pancreatic ductal adenocarcinoma (PDAC). Recently, we showed that acinar to ductal metaplasia, an injury repair program, is characterized by a transcriptomic program similar to gastric spasmolytic polypeptide expressing metaplasia (SPEM), suggesting common mechanisms of reprogramming between the stomach and pancreas. The aims of this study were to assay IPMN for pyloric markers and to identify molecular drivers of this program. DESIGN: We analyzed RNA-seq studies of IPMN for pyloric markers, which were validated by immunostaining in patient samples. Cell lines expressing Kras G12D +/- GNAS R201C were manipulated to identify distinct and overlapping transcriptomic programs driven by each oncogene. A PyScenic-based regulon analysis was performed to identify molecular drivers in the pancreas. Expression of candidate drivers was evaluated by RNA-seq and immunostaining. RESULTS: Pyloric markers were identified in human IPMN. GNAS R201C drove expression of these markers in cell lines and siRNA targeting of GNAS R201C or Kras G12D demonstrates that GNAS R201C amplifies a mucinous, pyloric phenotype. Regulon analysis identified a role for transcription factors SPDEF, CREB3L1, and CREB3L4, which are expressed in patient samples. siRNA-targeting of Spdef inhibited mucin production. CONCLUSION: De novo expression of a SPEM phenotype has been identified in pancreatitis and a pyloric phenotype in Kras G12D -driven PanIN and Kras G12D ;GNAS R201C -driven IPMN, suggesting common mechanisms of reprogramming between these lesions and the stomach. A transition from a SPEM to pyloric phenotype may reflect disease progression and/or oncogenic mutation. IPMN-specific GNAS R201C amplifies a mucinous phenotype, in part, through SPDEF.

Isolated liver chemo perfusion for hepatic metastases from uveal melanoma: a report of 38 cases.

Aim: To evaluate the outcomes of isolated liver chemo perfusion in patients with hepatic metastases from uveal melanoma. Materials and methods: Cardiovascular surgeons are often involved in the treatment of oncological diseases. Isolated liver chemoperfusion requires the use a heart-lung machine. A little more than 300 operations of isolated liver chemoperfusion have been performed worldwide. From 2020 to 2023, 38 cases of isolated liver chemoperfusion were performed at the Kostroma Clinical Oncological Dispensary. Results: There were 3 deaths, 2 due to liver failure. The remaining patient had hepatic artery thrombosis, who despite emergency thrombectomy and repair of common hepatic artery succumbed to multiorgan failure. Bleeding was diagnosed in 7 patients in the postoperative period. In all cases, relaparotomy was performed to stop bleeding. Subsequently, no special features were noted. The median disease-free survival was 5.4 months. The median overall survival was 20.3 months at the time of submission of this manuscript. Conclusions: Isolated liver chemoperfusion is a safe method of regional chemotherapy and can be considered in patients with isolated hepatic metastases from uveal melanoma. Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-023-01620-6.

Receptor-associated kinases control the lipid provisioning program in plant-fungal symbiosis.

The mutualistic association between plants and arbuscular mycorrhizal (AM) fungi requires intracellular accommodation of the fungal symbiont and maintenance by means of lipid provisioning. Symbiosis signaling through lysin motif (LysM) receptor-like kinases and a leucine-rich repeat receptor-like kinase DOES NOT MAKE INFECTIONS 2 (DMI2) activates transcriptional programs that underlie fungal passage through the epidermis and accommodation in cortical cells. We show that two Medicago truncatula cortical cell-specific, membrane-bound proteins of a CYCLIN-DEPENDENT KINASE-LIKE (CKL) family associate with, and are phosphorylation substrates of, DMI2 and a subset of the LysM receptor kinases. CKL1 and CKL2 are required for AM symbiosis and control expression of transcription factors that regulate part of the lipid provisioning program. Onset of lipid provisioning is coupled with arbuscule branching and with the REDUCED ARBUSCULAR MYCORRHIZA 1 (RAM1) regulon for complete endosymbiont accommodation.

Comparison of external dose estimates using different retrospective dosimetry methods in the settlements located near Semipalatinsk Nuclear Test Site, Republic of Kazakhstan.

For correct assessment of health risks after low-dose irradiation, calculation of radiation exposure estimates is crucial. To verify the calculated absorbed doses, instrumental methods of retrospective dosimetry are used. We compared calculated and instrumental-based estimates of external absorbed doses in the residents of Dolon, Mostik and Cheremushki villages, Kazakhstan, affected by the first nuclear weapon test performed at the Semipalatinsk Nuclear Test Site (SNTS) on August 29, 1949. The 'instrumental' doses were retrospectively estimated using the Luminescence Retrospective Dosimetry (LRD) and Electron Spin Resonance (ESR) methods. Correlation between the calculated individual cumulative external absorbed whole-body doses based on typical input data and ESR-based individual doses in the same people was strong (r = 0.782). It was even stronger between the calculated doses based on individual questionnaires' input data and the ESR-based doses (r = 0.940). Application of the LRD method is useful for validation of the calculated settlement-average cumulated external absorbed dose to air. Reconstruction of external exposure can be supplemented with the data from later measurements of soil contamination with long-lived radionuclides, such as, 137Cs. Our results show the reliability of the calculational method used for the retrospective assessment of individual external doses.

Effects of Radioactive 56MnO2 Particle Inhalation on Mouse Lungs: A Comparison between C57BL and BALB/c.

The effects of residual radiation from atomic bombs have been considered to be minimal because of its low levels of external radioactivity. However, studies involving atomic bomb survivors exposed to only residual radiation in Hiroshima and Nagasaki have indicated possible adverse health effects. Thus, we investigated the biological effects of radioactive dust of manganese dioxide 56 (56MnO2), a major radioisotope formed in soil by neutron beams from a bomb. Previously, we investigated C57BL mice exposed to 56MnO2 and found pulmonary gene expression changes despite low radiation doses. In this study, we examined the effects in a radiation-sensitive strain of mice, BALB/c, and compared them with those in C57BL mice. The animals were exposed to 56MnO2 particles at two radioactivity levels and examined 3 and 65 days after exposure. The mRNA expression of pulmonary pathophysiology markers, including Aqp1, Aqp5, and Smad7, and radiation-sensitive genes, including Bax, Phlda3, and Faim3, was determined in the lungs. The radiation doses absorbed in the lungs ranged from 110 to 380 mGy; no significant difference was observed between the two strains. No exposure-related pathological changes were observed in the lungs of any group. However, the mRNA expression of Aqp1 was significantly elevated in C57BL mice but not in BALB/c mice 65 days after exposure, whereas no changes were observed in external γ-rays (2 Gy) in either strain. In contrast, Faim3, a radiation-dependently downregulated gene, was reduced by 56MnO2 exposure in BALB/c mice but not in C57BL mice. These data demonstrate that inhalation exposure to 56MnO2 affected the expression of pulmonary genes at doses <380 mGy, which is comparable to 2 Gy of external γ-irradiation, whereas the responses differed between the two mouse strains.

Nanoparticles based on MIL-101 metal-organic frameworks as efficient carriers of therapeutic188Re radionuclide for nuclear medicine.

Nuclear medicine presents one of the most promising modalities for efficient non-invasive treatment of a variety of cancers, but the application of radionuclides in cancer therapy and diagnostics is severely limited by their nonspecific tissue accumulation and poor biocompatibility. Here, we explore the use of nanosized metal-organic frameworks (MOFs) as carriers of radionuclides to order to improve their delivery to tumour. To demonstrate the concept, we prepared polymer-coated MIL-101(Cr)-NH2MOFs and conjugated them with clinically utilized radionuclide188Re. The nanoparticles demonstrated high loading efficacy of radionuclide reaching specific activity of 49 MBq mg-1. Pharmacokinetics of loaded MOFs was investigated in mice bearing colon adenocarcinoma. The biological half-life of the radionuclide in blood was (20.9 ± 1.3) h, and nanoparticles enabled it to passively accumulate and retain in the tumour. The radionuclide delivery with MOFs led to a significant decrease of radioactivity uptake by the thyroid gland and stomach as compared with perrhenate salt injection, which is beneficial for reducing the side toxicity of nuclear therapy. The reported data on the functionalization and pharmacokinetics of MIL-101(Cr)-NH2for radionuclide delivery unveils the promising potential of these MOFs for nuclear medicine.

Gene-Activated Materials in Regenerative Dentistry: Narrative Review of Technology and Study Results.

Treatment of a wide variety of defects in the oral and maxillofacial regions requires the use of innovative approaches to achieve best outcomes. One of the promising directions is the use of gene-activated materials (GAMs) that represent a combination of tissue engineering and gene therapy. This approach implies that biocompatible materials will be enriched with gene-carrying vectors and implanted into the defect site resulting in transfection of the recipient's cells and secretion of encoded therapeutic protein in situ. GAMs may be presented in various designs depending on the type of material, encoded protein, vector, and way of connecting the vector and the material. Thus, it is possible to choose the most suitable GAM design for the treatment of a particular pathology. The use of plasmids for delivery of therapeutic genes is of particular interest. In the present review, we aimed to delineate the principle of work and various designs of plasmid-based GAMs and to highlight results of experimental and clinical studies devoted to the treatment of periodontitis, jaw bone defects, teeth avulsion, and other pathologies in the oral and maxillofacial regions.

Mechanism of peroxidasin inactivation in hyperglycemia: Heme damage by reactive oxygen species.

Diabetic complications present a serious health problem. Functional damage to proteins due to post-translational modifications by glycoxidation reactions is a known factor contributing to pathology. Extracellular proteins are especially vulnerable to diabetic damage because robust antioxidant defenses are lacking outside the cell. We investigated glucose-induced inactivation of peroxidasin (PXDN), a heme protein catalyzing sulfilimine crosslinking of collagen IV that reinforce the basement membranes (BM). Experiments using physiological diabetic glucose levels were carried out to exclude several potential mechanisms of PXDN inactivation i.e., direct adduction of glucose, reactive carbonyl damage, steric hindrance, and osmotic stress. Further experiments established that PXDN activity was inhibited via heme degradation by reactive oxygen species. Activity of another extracellular heme protein, myeloperoxidase, was unaffected by glucose because its heme was resistant to glucose-induced oxidative degradation. Our findings point to specific mechanisms which may compromise BM structure and stability in diabetes and suggest potential modes of protection.

Preventive Transoral Endoscopic Thyroidectomy by Vestibular Approach in 6-Year-Old Patient with the High-Risk RET C634R Germline Mutation.

Aggressiveness and age of manifestation of medullary thyroid cancer depend on the risk level of germline RET mutations. For high-risk mutations, preventive thyroidectomy is recommended at young age. In recent years, endoscopic operations for thyroid cancer were introduced in clinical practice. But such experience in pediatrics is very limited. We present a case report of a male patient, 6-year-old with the high-risk germline mutation С634R in RET gene. Close relatives (mother, cousin, and native sister) of the proband, were treated for medullary thyroid cancer. Also, his grandmother on the maternal line and her native brother died at the age of 38 and 37 years because of medullary thyroid cancer progression. Since 3 years old, our patient was under regular exams. At the age of six, calcitonin level was 8 ng/mL, and no evidence of pathology on ultrasound. According to recommendations of American Thyroid Association from 2015 (ATA 2015), preventive thyroidectomy was planned. This operation was performed by transoral vestibular approach. Oral nutrition started on the first day after the operation and the patient was discharged from the hospital. No major complications were observed. Transitory paresthesia and slight edema of the submental compartment were noticed. Consider this, endoscopic operation on the thyroid gland can be performed, as a preventive procedure, for RET gene germline mutation carriers in young age. This method helps avoid scars on the skin of the anterior neck.

Collagen IV of basement membranes: III. Chloride pressure is a primordial innovation that drives and maintains the assembly of scaffolds.

Collagen IV scaffold is a primordial innovation enabling the assembly of a fundamental architectural unit of epithelial tissues-a basement membrane attached to polarized cells. A family of six α-chains (α1 to α6) coassemble into three distinct protomers that form supramolecular scaffolds, noted as collagen IVα121, collagen IVα345, and collagen IVα121-α556. Chloride ions play a pivotal role in scaffold assembly, based on studies of NC1 hexamers from mammalian tissues. First, Cl- activates a molecular switch within trimeric NC1 domains that initiates protomer oligomerization, forming an NC1 hexamer between adjoining protomers. Second, Cl- stabilizes the hexamer structure. Whether this Cl--dependent mechanism is of fundamental importance in animal evolution is unknown. Here, we developed a simple in vitro method of SDS-PAGE to determine the role of solution Cl- in hexamer stability. Hexamers were characterized from 34 animal species across 15 major phyla, including the basal Cnidarian and Ctenophora phyla. We found that solution Cl- stabilized the quaternary hexamer structure across all phyla except Ctenophora, Ecdysozoa, and Rotifera. Further analysis of hexamers from peroxidasin knockout mice, a model for decreasing hexamer crosslinks, showed that solution Cl- also stabilized the hexamer surface conformation. The presence of sufficient chloride concentration in solution or "chloride pressure" dynamically maintains the native form of the hexamer. Collectively, our findings revealed that chloride pressure on the outside of cells is a primordial innovation that drives and maintains the quaternary and conformational structure of NC1 hexamers of collagen IV scaffolds.

Transcriptome-based analysis of human peripheral blood reveals regulators of immune response in different viral infections.

Introduction: There are difficulties in creating direct antiviral drugs for all viruses, including new, suddenly arising infections, such as COVID-19. Therefore, pathogenesis-directed therapy is often necessary to treat severe viral infections and comorbidities associated with them. Despite significant differences in the etiopathogenesis of viral diseases, in general, they are associated with significant dysfunction of the immune system. Study of common mechanisms of immune dysfunction caused by different viral infections can help develop novel therapeutic strategies to combat infections and associated comorbidities. Methods: To identify common mechanisms of immune functions disruption during infection by nine different viruses (cytomegalovirus, Ebstein-Barr virus, human T-cell leukemia virus type 1, Hepatitis B and C viruses, human immunodeficiency virus, Dengue virus, SARS-CoV, and SARS-CoV-2), we analyzed the corresponding transcription profiles from peripheral blood mononuclear cells (PBMC) using the originally developed pipeline that include transcriptome data collection, processing, normalization, analysis and search for master regulators of several viral infections. The ten datasets containing transcription data from patients infected by nine viruses and healthy people were obtained from Gene Expression Omnibus. The analysis of the data was performed by Genome Enhancer pipeline. Results: We revealed common pathways, cellular processes, and master regulators for studied viral infections. We found that all nine viral infections cause immune activation, exhaustion, cell proliferation disruption, and increased susceptibility to apoptosis. Using network analysis, we identified PBMC receptors, representing proteins at the top of signaling pathways that may be responsible for the observed transcriptional changes and maintain the current functional state of cells. Discussion: The identified relationships between some of them and virus-induced alteration of immune functions are new and have not been found earlier, e.g., receptors for autocrine motility factor, insulin, prolactin, angiotensin II, and immunoglobulin epsilon. Modulation of the identified receptors can be investigated as one of therapeutic strategies for the treatment of severe viral infections.

Modeling the Magnetoelectric Composites in a Wide Frequency Range.

This article presents a general theory of the ME effect in composites in the low- and high-frequency ranges. Besides the quasi-static region, the area of electromechanical resonance, including longitudinal, bending, longitudinal shear, and torsional modes, is considered in more detail. To demonstrate the theory, expressions of ME voltage coefficients are obtained for symmetric and asymmetric layered structures. A comparison is made with the experimental results for the GaAs/Metglas and LiNbO3/Metglas structures. The main microwave ME effect, consisting of the FMR line shift in an electric field, for the ferromagnetic metals, their alloys, and YIG ferrite using various piezoelectrics is discussed. In addition to analytical calculations, in the article, finite element modeling is considered. The calculation methods and experimental results are compared for some composites.

Identification of brominated proteins in renal extracellular matrix: Potential interactions with peroxidasin.

Peroxidasin (PXDN) is an extracellular peroxidase, which generates hypobromous acid to form sulfilimine cross-links within collagen IV networks. We have previously demonstrated that mouse and human renal basement membranes (BM) are enriched in bromine due to PXDN-dependent post-translational bromination of protein tyrosine residues. The goal of the present study was identification of specific brominated sites within renal BM. A comprehensive analysis of brominated proteome of mouse glomerular matrix had been performed using liquid chromatography-tandem mass spectrometry. We found that out of over 200 identified proteins, only three were detectably brominated, each containing a single distinct brominated tyrosine site i.e., Tyr-1485 in collagen IV α2 chain, Tyr-292 in TINAGL1 and Tyr-664 in nidogen-2. To explain this highly selective bromination, we proposed that these proteins interact with PXDN within the glomerular matrix. Experiments using purified proteins demonstrated that both TINAGL1 and nidogen-2 can compete with PXDN for binding to collagen IV and that TINAGL1 can directly interact with PXDN. We propose that a protein complex, including PXDN, TINAGL1, nidogen-2 and collagen IV, may exist in renal BM.

Protective Properties of Spheroidal Taxifolin Form in Streptozotocin-Induced Diabetic Rats.

One of the key factors in the pathogenesis of diabetes and its complications is oxidative stress. To inhibit this process, antioxidants may be helpful. Herein, we focused on the protective properties of taxifolin spheroidal form (TS) in the streptozotocin rat model of diabetes mellitus. After 4 weeks of treatment with TS, the fasting blood glucose level of the diabetic animals decreased by 12% compared with the level right after the injection of streptozotocin. While the feed intake in the untreated diabetic rats increased by 5.3% compared with the healthy group, the TS-treated group showed a pronounced 15.3% decrease. Therapeutic administration of TS has a protective effect on the pancreas and the liver against the cytotoxic action of streptozotocin. The plasma antioxidant capacity of all diabetic groups appeared to be approximately 15% lower than in healthy rats with no significant difference between the TS-treated and untreated diabetic animals. Apparently, this can be attributed to taxifolin and plasma proteins binding. These data demonstrate the potential of TS in antidiabetic therapy.

Vortex solitons in moiré optical lattices.

We show that optical moiré lattices enable the existence of vortex solitons of different types in self-focusing Kerr media. We address the properties of such states both in lattices having commensurate and incommensurate geometries (i.e., constructed with Pythagorean and non-Pythagorean twist angles, respectively), in the different regimes that occur below and above the localization-delocalization transition. We find that the threshold power required for the formation of vortex solitons strongly depends on the twist angle and, also, that the families of solitons exhibit intervals where their power is a nearly linear function of the propagation constant and they exhibit a strong stability. Also, in the incommensurate phase above the localization-delocalization transition, we found stable embedded vortex solitons whose propagation constants belong to the linear spectral domain of the system.

Expression of Ceramide-Metabolizing Enzymes in the Heart Adipose Tissue of Cardiovascular Disease Patients.

Here, we examined the expression of ceramide metabolism enzymes in the subcutaneous adipose tissue (SAT), epicardial adipose tissue (EAT) and perivascular adipose tissue (PVAT) of 30 patients with coronary artery disease (CAD) and 30 patients with valvular heart disease (VHD) by means of quantitative polymerase chain reaction and fluorescent Western blotting. The EAT of patients with CAD showed higher expression of the genes responsible for ceramide biosynthesis (SPTLC1, SPTLC2, CERS1, 5, 6, DEGS1, and SMPD1) and utilization (ASAH1, SGMS1). PVAT was characterized by higher mRNA levels of CERS3, CERS4, DEGS1, SMPD1, and ceramide utilization enzyme (SGMS2). In patients with VHD, there was a high CERS4, DEGS1, and SGMS2 expression in the EAT and CERS3 and CERS4 expression in the PVAT. Among patients with CAD, the expression of SPTLC1 in SAT and EAT, SPTLC2 in EAT, CERS2 in all studied AT, CERS4 and CERS5 in EAT, DEGS1 in SAT and EAT, ASAH1 in all studied AT, and SGMS1 in EAT was higher than in those with VHD. Protein levels of ceramide-metabolizing enzymes were consistent with gene expression trends. The obtained results indicate an activation of ceramide synthesis de novo and from sphingomyelin in cardiovascular disease, mainly in EAT, that contributes to the accumulation of ceramides in this location.

Prediction of Adverse Effects of Drug-Drug Interactions on Cardiovascular System Based on the Analysis of Structure-Activity Relationships.

Co-administration of drugs often leads to drug-drug interactions, which could be accompanied by various adverse drug reactions that pose a threat to life and health of the patient. The effect caused by adverse drug reactions on cardiovascular system is one of the most significant manifestations of drug-drug interaction. Clinical assessment of adverse drug reactions resulting from drug-drug interaction between all drug pairs used in therapeutic practice is not possible. The purpose of this work was to build models using structure-activity analysis to predict adverse effects of drugs on cardiovascular system, mediated by pairwise interactions between the drug pairs when they are taken together. Data on the adverse effects resulting from drug-drug interaction were obtained from the DrugBank database. The data on drug pairs that do not cause such effects, which are necessary for building accurate structure-activity models, were obtained from the TwoSides database, which contains the results of analysis of the spontaneous reports. Two types of descriptors were used to describe a pair of drug structures: PoSMNA descriptors and probabilistic estimates of the prediction of biological activities obtained using the PASS program. Structure-activity relationships were established using the Random Forest method. Prediction accuracy was calculated by means of five-fold cross-validation. The highest accuracy values were obtained using PASS probabilistic estimates as descriptors. The area under the ROC curve was 0.94 for bradycardia, 0.96 for tachycardia, 0.90 for arrhythmia, 0.90 for ECG QT prolongation, 0.91 for hypertension, 0.89 for hypotension.

Components of the Phenylpropanoid Pathway in the Implementation of the Protective Effect of Sodium Nitroprusside on Wheat under Salinity.

Nitric oxide (NO) is a multifunctional, gaseous signaling molecule implicated in both physiological and protective responses to biotic and abiotic stresses, including salinity. In this work, we studied the effects of 200 µM exogenous sodium nitroprusside (SNP, a donor of NO) on the components of the phenylpropanoid pathway, such as lignin and salicylic acid (SA), and its relationship with wheat seedling growth under normal and salinity (2% NaCl) conditions. It was established that exogenous SNP contributed to the accumulation of endogenous SA and increased the level of transcription of the pathogenesis-related protein 1 (PR1) gene. It was found that endogenous SA played an important role in the growth-stimulating effect of SNP, as evidenced by the growth parameters. In addition, under the influence of SNP, the activation of phenylalanine ammonia lyase (PAL), tyrosine ammonia lyase (TAL), and peroxidase (POD), an increase in the level of transcription of the TaPAL and TaPRX genes, and the acceleration of lignin accumulation in the cell walls of roots were revealed. Such an increase in the barrier properties of the cell walls during the period of preadaptation played an important role in protection against salinity stress. Salinity led to significant SA accumulation and lignin deposition in the roots, strong activation of TAL, PAL, and POD, and suppression of seedling growth. Pretreatment with SNP under salinity conditions resulted in additional lignification of the root cell walls, decreased stress-induced endogenous SA generation, and lower PAL, TAL, and POD activities in comparison to untreated stressed plants. Thus, the obtained data suggested that during pretreatment with SNP, phenylpropanoid metabolism was activated (i.e., lignin and SA), which contributed to reducing the negative effects of salinity stress, as evidenced by the improved plant growth parameters.

Effects of Internal Exposure of Radioactive 56MnO2 Particles on the Lung in C57BL Mice.

The investigation of the radiation effects of the atomic bombing in Hiroshima and Nagasaki has revealed concerns about the impact of the residual radioactive dust produced in the soil. Manganese-56 is one of the major radioisotopes produced by neutrons from the bomb; hence, we previously examined the biological effects of manganese dioxide-56 (56MnO2) in Wistar rats, in which significant changes were found in the lung. In the present study, ten-week-old male C57BL mice were exposed to three doses of radioactive 56MnO2, stable MnO2 particles, or external γ-rays (2 Gy) to further examine the effects of 56MnO2 in a different species. The estimated absorbed radiation doses from 56MnO2 were 26, 96, and 250 mGy in the lung. The animals were examined at 3, 14, and 70 days post exposure. Histologically, no exposure-related changes were found in the lungs of any group. However, pulmonary mRNA expression of aquaporin 1, which is a useful marker for lung pathophysiology, was significantly elevated at 14 and 70 days, although no such changes were found in the mice exposed to external γ-rays (2 Gy). These data indicated that the inhalation exposure to 56MnO2 particles, with <250 mGy of organ doses, produced significant biological responses in the lung.