"Rust stain": a rare mark in firearm suicide-a case report and review of the literature.

Rust stains are marks left by firearms in case of prolonged contact with the cutaneous surfaces. These peculiar signs along with other well-documented findings can guide the medical examiner in the determination of the manner of death, especially in case of firearm suicide. This paper presents the case of a 33-year-old male soldier who committed suicide by using a short-barreled weapon, whose trigger remained in contact with the first finger of his right hand, leading to the formation of a rust stain that perfectly reproduced its design. The forensic examination of the scene, the external cadaveric inspection, and the autopsy are described. For the evaluation of the histological findings typical of rust spots, the authors decided to replicate the phenomenon in an experimental setting using porcine skin. In order to provide an exhaustive overview on the formation and the features of rust stains, a review of the forensic literature concerning this rare mark was performed.

Dysplasia features of myelodysplastic syndrome in ethnically Chinese people.

OBJECTIVE: It was our aim to study the diagnostic significances of various dysplasia characteristics in myelodysplastic syndrome (MDS). METHODS: We analyzed 160 cases of primary MDS and a control group including 28 cases of paroxysmal nocturnal hemoglobinuria (PNH), 104 cases of idiopathic thrombocytopenic purpura (ITP), 53 cases of non-severe aplastic anemia (NSAA), 40 cases of megaloblastic anemia and 50 cases of infectious and autoimmune diseases. Peripheral blood smears and bone marrow morphology were reviewed. RESULTS: There was no significant difference in the occurrence rates of a variety of dysplasias in three lineages among MDS, megaloblastic anemia and PNH; however, changes in qualities and quantities in three lineages between NSAA and MDS were significantly different. ITP and MDS showed statistical differences in multiple changes in myeloid and erythroid cells. Significant differences also existed in multiple changes in erythroid series and megakaryocytes between infectious and autoimmune diseases and MDS. Morphological abnormalities highly related with MDS included multinucleated erythroblasts, ringed sideroblasts, poikilocytosis and gigantocytes, pseudo-Pelger neutrophils, ring-shaped nucleus, and micromegakaryocytes. CONCLUSIONS: It is difficult to discriminate megaloblastic anemia and PNH from MDS by means of cell morphology. Different dysplasias of MDS have specific diagnostic values.

Construction of a SERS platform for sensitive detection of aflatoxin B1 based on CRISPR strategy.

Aflatoxin B1, a pathogen in the aflatoxin family, has attracted much attention due to the harmfulness in production and life. However, the common methods like high performance liquid chromatography used for detection of AFB1 have deficiency in complicated pretreatment processes, and the purification effect is not ideal. Herein, a SERS platform based on CRISPR strategy was designed for sensitive detection of AFB1. By synthesizing core-shell nanoparticles embedded with Raman silent region dye molecules, Prussian blue (PB), the detection of the sensor reduced background interference and the SERS signal was calibrated. At the same time, the high-efficiency reverse cleavage activity of cas12a was used to convert non-nucleic acid targets into nucleic acid, so as to achieve the effect of sensitive detection of AFB1 with a detection limit of 3.55  pg/mL. This study provides a new thought for SERS detection of non-nucleic acid targets in the future.

Brain iron accumulation in unexplained fetal and infant death victims with smoker mothers--the possible involvement of maternal methemoglobinemia.

BACKGROUND: Iron is involved in important vital functions as an essential component of the oxygen-transporting heme mechanism. In this study we aimed to evaluate whether oxidative metabolites from maternal cigarette smoke could affect iron homeostasis in the brain of victims of sudden unexplained fetal and infant death, maybe through the induction of maternal hemoglobin damage, such as in case of methemoglobinemia. METHODS: Histochemical investigations by Prussian blue reaction were made on brain nonheme ferric iron deposits, gaining detailed data on their localization in the brainstem and cerebellum of victims of sudden death and controls. The Gless and Marsland's modification of Bielschowsky's was used to identify neuronal cell bodies and neurofilaments. RESULTS: Our approach highlighted accumulations of blue granulations, indicative of iron positive reactions, in the brainstem and cerebellum of 33% of victims of sudden death and in none of the control group. The modified Bielschowsky's method confirmed that the cells with iron accumulations were neuronal cells. CONCLUSIONS: We propose that the free iron deposition in the brain of sudden fetal and infant death victims could be a catabolic product of maternal methemoglobinemia, a biomarker of oxidative stress likely due to nicotine absorption.

Prussian blue nanozyme-mediated nanoscavenger ameliorates acute pancreatitis via inhibiting TLRs/NF-κB signaling pathway.

Rationale: Acute pancreatitis (AP) is a serious acute condition affecting the abdomen and shows high morbidity and mortality rates. Its global incidence has increased in recent years. Inflammation and oxidative stress are potential therapeutic targets for AP. This study was conducted to investigate the intrinsic anti-oxidative and anti-inflammatory effects of Prussian blue nanozyme (PBzyme) on AP, along with its underlying mechanism. Methods: Prussian blue nanozymes were prepared by polyvinylpyrrolidone modification method. The effect of PBzyme on inhibiting inflammation and scavenging reactive oxygen species was verified at the cellular level. The efficacy and mechanism of PBzyme for prophylactically treating AP were evaluated using the following methods: serum testing in vivo, histological scoring following hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling fluorescence staining, polymerase chain reaction array, Kyoto Encyclopedia of Genes and Genomes analysis and Western blotting analysis. Results: The synthetic PBzyme showed potent anti-oxidative and anti-inflammatory effects in reducing oxidative stress and alleviating inflammation both in vitro and in vivo in the prophylactic treatment of AP. The prophylactic therapeutic efficacy of PBzyme on AP may involve inhibition of the toll-like receptor/nuclear factor-κB signaling pathway and reactive oxygen species scavenging. Conclusion: The single-component, gram-level mass production, stable intrinsic biological activity, biosafety, and good therapeutic efficacy suggest the potential of PBzyme in the preventive treatment of AP. This study provides a foundation for the clinical application of PBzyme.

Discrepancies between the fate of myoblast xenograft in mouse leg muscle and NMR label persistency after loading with Gd-DTPA or SPIOs.

1H-NMR (nuclear magnetic resonance) imaging is regularly proposed to non-invasively monitor cell therapy protocols. Prior to transplantation, cells must be loaded with an NMR contrast agent (CA). Most studies performed so far make use of superparamagnetic iron oxide particles (SPIOs), mainly for favorable detection sensitivity. However, in the case of labeled cell death, SPIO recapture by inflammatory cells might introduce severe bias. We investigated whether NMR signal changes induced by preloading with SPIOs or the low molecular weight gadolinium (Gd)-DTPA accurately monitored the outcome of transplanted cells in a murine model of acute immunologic rejection. CA-loaded human myoblasts were grafted in the tibialis anterior of C57BL/6 mice. NMR imaging was repeated regularly until 3 months post-transplantation. Label outcome was evaluated by the size of the labeled area and its relative contrast to surrounding tissue. In parallel, immunohistochemistry assessed the presence of human cells. Data analysis revealed that CA-induced signal changes did not strictly reflect the graft status. Gd-DTPA label disappeared rapidly yet with a 2-week delay compared with immunohistochemical evaluation. More problematically, SPIO label was still visible after 3 months, grossly overestimating cell survival (<1 week). SPIOs should be used with extreme caution to evaluate the presence of grafted cells in vivo and could hardly be recommended for the long-term monitoring of cell transplantation protocols.

A simple and sensitive assay for ascorbate using potassium ferricyanide as spectroscopic probe reagent.

We have developed a rapid, inexpensive, and reliable assay to determine ascorbate using potassium ferricyanide as spectroscopic probe reagent. In this assay, Fe(III) was deoxidized to Fe(II) by ascorbate at pH 4.0 and then Fe(II) reacted with potassium ferricyanide to form a blue product, soluble Prussian blue (KFe(III)[Fe(II)(CN)6]). The absorbance of this product was monitored over time using a spectrophotometer at an absorption maximum of 735 nm and the amount of ascorbate can be calculated based on absorbance. A good linear relationship of the concentration of ascorbate versus absorbance was observed, and the linear regression equation was A=-0.01911+0.16208C (microg/ml). Moreover, the apparent molar absorption coefficient of indirect determination of ascorbate was 2.85 x 10(4) L/mol x cm. To demonstrate the usefulness of this assay, it was used to determine ascorbate in different samples, and we particularly investigated the uptake of ascorbate and ascorbate phosphate in osteoblasts. We found similar plateau levels of intracellular ascorbate at 24h for ascorbate and ascorbate phosphate. The assay was robust for a variety of samples, including orange juice, fruits, and swine plasma. The assay was quick and very economical and provides results with uncertainties on the order of only 5%.

In vivo removal of radioactive cesium compound using Prussian blue-deposited iron oxide nanoparticles.

Aim: To mitigate the side effects of medical treatment by Prussian blue (PB), a well-known adsorbent for radioactive cesium (Cs), PB-deposited magnetic nanoparticles (MNPs), were prepared and analyzed on the adsorbent capacity for Cs removal. Materials & methods: The PB-deposited MNPs were prepared by photo-deposition method and investigated for their Cs adsorption properties in vitro and in vivo. The distribution of the adsorbents was also evaluated in C57BL/6 mice. Results: PB-deposited MNPs provided an improved adsorbent capacity for Cs removal and reduced toxicity to blood cells compared with those of bulk PB. Conclusion: PB-deposited MNPs could be considered as an alternative of PB-based medicine to reduce the possible hazards caused by high dose of PB intake.

In vivo monitoring of magnetically labeled mesenchymal stem cells administered intravascularly in rat acute renal failure.

QUESTIONS UNDER STUDY: Many studies have demonstrated that mesenchymal stem cells (MSCs) contribute to the recovery of acute renal failure (ARF). The purpose of the present study was to evaluate tracking of MSCs intravascularly administered in a rat model of ARF for cellular therapy using a 1.5 T MRI system. METHODS: Fe2O3-PLL nanoparticle-labelled and unlabelled MSCs were injected into the abdominal aortas by transcatheterisation of 20 ARF rats, whose renal failure was induced by intramusclar injection of glycerol, while phosphate-buffered saline (PBS) was injected in 20 control rats. Magnetic resonance (MR) images of the kidneys were obtained, before injection of MSCs, after 1 hour, after 1, 2, and 4 days respectively. The MR imaging findings were correlated with the distribution of transplanted MSCs. The kidney injury was histologically evaluated, and the expression of proliferating cell nuclear antigen (PCNA) protein was examined. The Renal function was estimated by quantitative analysis. RESULTS: In the rat model of ARF the labelled MSCs showed a bilateral loss of signal intensity in the outer zone of the renal cortex on T2*-weighted MR images, which was visible up to 4 days after transplantation. Labelled MSCs were detected in glomerular capillaries by histological examination, the corresponding areas where signal intensity decreased in MR images. Compared to the control group, those ARF rats with MSCs injection had less renal injury, more enhanced tubular cell proliferation and better renal function. CONCLUSIONS: MR imaging visualises those intravascularly administered MSCs in vivo, which promoted recovery of ARF.

[Preparation of Prussian Blue@Yeast Catalyst and Its Heterogeneous Fenton Performance].

A novel heterogeneous Fenton catalyst, Prussian blue@yeast (PB@yeast), was prepared via facile self-assembly synthesis. The as-synthesized composite was characterized by field emission scanning electron microscopy (FE-SEM), energy-dispersive spectroscopy (EDS), powder X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). All of the results indicated that PB nanoparticles were uniformly dispersed on the surface of yeasts with stable core-shell morphology. Degradation of the model anionic fluorescent whitening agent CXT indicated that the PB@yeast catalyst presented a synergistic effect of adsorption and heterogeneous Fenton performance. Owing to the high adsorption capacity of yeast, the CXT molecules were easy to move to the active site of the catalyst, promoting the electron transfer between Fe(Ⅲ) and Fe(Ⅱ) and then enhancing the catalytic activity of the Fenton reaction effectively. Furthermore, the yeast support could improve the dispersity and stability of PB nanoparticles, which maintained excellent catalytic activity and stability after being recycled four times.

Parenteral iron therapy is associated with a characteristic pattern of iron staining on bone marrow aspirate smears.

We developed anecdotal evidence that parenteral iron therapy is associated with a characteristic pattern of iron staining in bone marrow aspirate smears. In this pattern, uniform blue granules are observed within reticuloendothelial cells/stromal cells with Prussian blue staining, many times in curvilinear arrays. To test this hypothesis, marrow cases submitted for morphologic evaluation to our laboratory during an approximate 2-month period in 2006 were assessed for this pattern, and, when it was observed, clinical information was sought to determine if the patient had received parenteral iron. Fourteen cases were identified that displayed the pattern of interest. In 10 of these cases, the pattern was widespread (numerous granules present within virtually all marrow spicules), whereas in 4 cases, the pattern was seen only focally. In all cases in which the pattern was widespread, patients were found to have received parenteral iron at some point before the aspiration procedure. Our findings indicate that parenteral iron therapy is associated with a characteristic pattern of iron staining in bone marrow aspirate smears.

Gastric siderosis: patterns and significance.

Recently, we encountered 2 cases of diffuse iron deposition in gastric antral and fundic glandular epithelium, which in 1 patient eventually led to the diagnosis of hemochromatosis. Gastric mucosal siderosis (GS) has previously been described in hemochromatosis patients, alcoholics, and in association with iron medications. However, the prevalence of various patterns of iron deposition in the gastric mucosa and their clinical significance have not been studied in detail. The 2 index cases mentioned above and 500 additional consecutive gastric biopsies examined over a period of 8 months at our institution were stained for iron by the Prussian blue method. In addition, all patients with genetic hemochromatosis diagnosed by liver biopsy in our department between 1998 and 2003 who also had gastric biopsies were identified from the surgical pathology files and included in the study (n = 3). The location of iron deposition [stromal cells (endothelium, fibroblasts, macrophages), glandular epithelium, or extracellular] was recorded and subjectively graded as 1+ to 3+ according to the severity of deposition within the mucosa. Relevant histologic changes (inflammation, presence of H. pylori, ulceration) and clinical features were reviewed. Three patterns of GS were identified: A) "nonspecific GS" with predominant iron deposition in the stromal cells including macrophages, and focally in epithelium; B) "iron-pill gastritis" with often mild gastritis and reactive gastropathy type changes, and mostly extracellular deposition with focal stromal cells and epithelial deposition; and C) predominant deposition in antral and fundic glandular epithelium. Of the 500 cases studied, a total of 18 (3.6%) cases were found to have GS. Of these 18 cases, 11 (2.2%) showed pattern A, 4 (0.8%) showed pattern B, and 3 (0.6%) showed pattern C. The GS in patterns A and B was always focal or patchy (1+ to 2+), whereas in pattern C it was generally diffuse and strong (2+ to 3+). A history of oral iron medication was present in 2 (n = 11, 0.4%) patients with pattern A, in all patients with pattern B (n = 4, 100%), and in none of patients with pattern C (n=3, 0%). Varying degrees of mucosal inflammation were noted in patients with pattern A cases, and 2 had evidence of active Helicobacter pylori infection. Of the 3 cases with known hemochromatosis, only one gastric biopsy showed pattern C GS (1+). In conclusion, gastric mucosal siderosis is relatively uncommon (3%) but is important to look for as it may lead to a diagnosis of hemochromatosis in some cases. Three patterns are recognized: A) a "nonspecific" stromal cell predominant pattern, which may be associated with gastric inflammation, possibly prior mucosal hemorrhages or iron medications; B) extracellular coarse clumps of crystalline iron deposition associated with oral iron medications, mild gastritis, and reactive gastropathy type changes ("Iron-pill gastritis"); and C) gastric glandular siderosis, which may be associated with systemic iron overload/hemochromatosis.

Erythrocyte plasma membrane redox system in human aging.

Eukaryotic cells display a plasma membrane redox system (PMRS) that transfers electrons from intracellular substrates to extracellular electron acceptors. The physiologic importance of PMRS is still not fully understood. The authors have carried out studies to determine the activity of PMRS in human erythrocytes as a function of age and correlate the activity with total plasma antioxidant capacity in an effort to understand the role of PMRS in human aging. The study was carried out on 80 normal healthy subjects of both genders between the ages of 18 and 85 years. The activity of erythrocyte PMRS was estimated by following the reduction of ferricyanide. The total antioxidant capacity of the plasma was estimated in terms of Ferric Reducing Ability of Plasma (FRAP) values. A significant (p < 0.0001) positive correlation (r = 0.7797) is observed between PMRS activity of erythrocytes and human age. There is an age-dependent decrease in total plasma antioxidant capacity measured in terms of FRAP values. A highly significant correlation is observed between PMRS activity and plasma FRAP values. The authors hypothesize that the increased PMRS in erythrocytes during aging may be a protective mechanism of the system for efficient extracellular DHA reduction and ascorbate recycling under condition of increased oxidative stress.

Phenotypic study of human gingival fibroblasts labeled with superparamagnetic anionic nanoparticles.

BACKGROUND: A specific labeler of the human gingival fibroblast (HGF) does not exist. Anionic maghemite nanoparticles allow labeling of a wide cell variety and their recognition in cellular, organotypical, and animal models. METHODS: We studied internalization effects of nanoparticles on an HGF phenotype in vitro, evaluating transcription and secretion of connective tissue remodeling molecules, i.e., matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and cytokines controlling their activation/inhibition, i.e., transforming growth factor-beta (TGF-beta1), tumor necrosis factor-alpha (TNF-alpha), and interleukins 1beta and 4 (IL-1beta and IL-4). After proliferation kinetics, cellular uptake was studied by Perls coloration and magnetophoresis on labeled culture. Dot blotting, Western blotting, and zymography were used to detect MMP-1, -2, and -3 and TIMP-1 and -2 secretions in culture supernatants, and reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect the mRNA expression of these molecules. Enzyme-linked immunosorbent assay (ELISA) tests were used to determine TGF-beta1, TNF-alpha, IL-1beta, and IL-4 levels. RESULTS: Our data indicated high (15.3+/-5.8 pg/cell) but heterogeneous distribution of nanoparticles in HGF. Twenty-four hours after labeling, MMP-1, -2, and -3 and TIMP-2 secretion increased (P<0.001) with RT-PCR confirmation at 12 hours, whereas TIMP-1 did not. IL-1beta increased at day 1 (D1) (P<0.001) and IL-4 at D3 (P<0.01), but not TGF-beta1 or TNF-alpha. CONCLUSIONS: After labeling with these maghemite nanoparticles, HGF increased secretion of IL-1beta at D1, probably inducing the increase of MMP-1, -2, and -3 and TIMP-2. The increase of IL-4 secretion began with the decreased synthesis of MMPs and TIMPs at D3. Despite this transitory inflammatory reaction at 3 days following internalization, maghemite nanoparticles did not affect HGF phenotype, thereby authorizing their use as labelers.

DNA as a support for glucose oxidase immobilization at Prussian blue-modified glassy carbon electrode in biosensor preparation.

An amperometric glucose biosensor has been developed using DNA as a matrix of Glucose oxidase (GOx) at Prussian-blue (PB)-modified glassy carbon (GC) electrode. GC electrode was chemically modified by the PB. GOx was immobilized together with DNA at the working area of the PB-modified electrode by placing a drop of the mixture of DNA and GOx. The response of the biosensor for glucose was evaluated amperometrically. Upon immobilization of glucose oxidase with DNA, the biosensor showed rapid response toward the glucose. On the other hand, no significant response was obtained in the absence of DNA. Experimental conditions influencing the biosensor performance were optimized and assessed. This biosensor offered an excellent electrochemical response for glucose concentration in micro mol level with high sensitivity and selectivity and short response time. The levels of the relative standard deviation (RSDs), (<4%) for the entire analyses reflected a highly reproducible sensor performance. Through the use of optimized conditions, a linear relationship between current and glucose concentration was obtained up to 4 x 10(-4) M. In addition, this biosensor showed high reproducibility and stability.

Death by electrocution: Histological technique for copper detection on the electric mark.

The current observation of deaths by electrocution, both for domestic and work-related accidents as well as those in other contexts, has deepened the scope of investigation into electric marks, especially from the histological point of view. This is one of the few investigation tools that may lead to the diagnosis of death by electrocution in this distinct area, bearing in mind the diagnostic difficulties that this type of fatality presents. Our attention has been placed on the phenomenon of metallization. In particular, we focused on using the Timm's method [1] to locate the copper deposits. The phenomenon of metallization, usually could be caused by the copper deposit, this happens due to the copper debris released onto the skin by the live conductor. To date, this technique has only been used in the pathological field. Nevertheless, we tried to assess its application in seven selected cases, after partially modifying the technique, comparing it with the most common staining detection techniques and analysing the specificity, sensitivity as well as the potential for its application in the routine.

Magnetic resonance imaging of atherosclerotic plaque with ultrasmall superparamagnetic particles of iron oxide in hyperlipidemic rabbits.

BACKGROUND: Based on the observation that ultrasmall superparamagnetic particles of iron oxides (USPIOs) are phagocytosed by cells of the mononuclear phagocytic system, the purpose of this study was to evaluate their use as a marker of atherosclerosis-associated inflammatory changes in the vessel wall before luminal narrowing is present. METHODS AND RESULTS: Experiments were conducted on 6 heritable hyperlipidemic and 3 New Zealand White rabbits. 3D MR angiography (MRA) of the thoracic aorta was performed on all rabbits by use of a conventional paramagnetic contrast agent that failed to reveal any abnormalities. One week later, all rabbits except 1 of the hyperlipidemic animals were injected with a USPIO contrast agent (Sinerem, Guerbet) at a dose of 1 mmol Fe/kg. 3D MRA data sets collected over the subsequent 5 days showed increasing signal in the aortic lumen. Whereas the aortic wall of the control rabbits remained smooth and bright, marked susceptibility effects became evident on day 4 within the aortic walls of hyperlipidemic rabbits. Ex vivo imaging of aortic specimens confirmed the in vivo results. Histopathology documented marked Fe uptake in macrophages embedded in atherosclerotic plaque of the hyperlipidemic rabbits. Electron microscopy showed multiple cytoplasmic Fe particles in macrophages. No such changes were seen in control rabbits or in the hyperlipidemic rabbit that had not received Sinerem. CONCLUSIONS: USPIOs are phagocytosed by macrophages in atherosclerotic plaques of the aortic wall of hyperlipidemic rabbits in a quantity sufficient to cause susceptibility effects detectable by MRI.

Transfection of neuroprogenitor cells with iron nanoparticles for magnetic resonance imaging tracking: cell viability, differentiation, and intracellular localization.

PURPOSE: Magnetic resonance imaging (MRI) can track labeled cells in the brain. The use of hemagglutinating virus of Japan envelopes (HVJ-Es) to effectively introduce the contrast agent to neural progenitor cells (NPCs) is limited to date despite their high NPC affinity. PROCEDURES: HVJ-Es and Lipofectamine 2000 were compared as transfection vehicles of superparamagnetic iron oxide (SPIO). Labeled NPCs were examined for iron content, MRI signal change, and fundamental cell characteristics. Prussian Blue staining was used after differentiation to determine SPIO localization. RESULTS: HVJ-Es transfected up to 12.5 +/- 8.8 times more SPIO into NPCs. HVJ-Es do not affect cell viability or differentiation capability. Superparamagnetic iron oxide was disseminated in both the soma and neurites. CONCLUSIONS: These findings indicate that HVJ-Es are an effective vehicle for SPIO transfection of NPCs. The intracellular localization after differentiation raises the question as to the capability of MRI to distinguish cell migration from axonal or dendritic growth in vivo.

Sequential histochemical staining for resident and recruited macrophages.

A new histochemical technique is described that permits differentiation of resident from recruited macrophages by staining of paraffin sections of tissues from rats and mice. Resident macrophages are identified by their ability to phagocytose and retain intravenously injected colloidal Prussian blue. New macrophages that emigrate into tissue are identified by phagocytosis of a second colloid, iron dextran. Paraffin sections of formalin-fixed tissues are sequentially stained for the presence of the two colloids with different chromogens, the endogenous pseudo-peroxidase activity of colloidal Prussian blue used to catalyze the polymerization of diaminobenzidine and after conversion of iron dextran to Prussian blue, the second colloid used to catalyze the polymerization of tetramethylbenzidine. The staining results in resident macrophages staining brown while newly recruited macrophages stain blue. The studies have shown that colloidal Prussian blue is stable in vivo and neither loses its catalytic activity nor undergoes extensive redistribution. They also show that the technique can be used to measure Kupffer cell recruitment stimulated by complete Freund's adjuvant in rats and tumor-associated macrophage recruitment in subcutaneous and spontaneous liver metastases in mice.

Ultrastructural analysis of a putative magnetoreceptor in the beak of homing pigeons.

With the use of different light and electron microscopic methods, we investigated the subcellular organization of afferent trigeminal terminals in the upper beak of the homing pigeon, Columba livia, which are about 5 microm in diameter and contain superparamagnetic magnetite (SPM) crystals. The SPM nanocrystals are assembled in clusters (diameter, approximately 1-2 microm). About 10 to 15 of these clusters occur inside one nerve terminal, arranged along the cell membrane. Each SPM cluster is embedded in a solid fibrous cup, open towards the cell surface, to which the cluster adheres by delicate fiber strands. In addition to the SPM clusters, a second inorganic iron compound has been identified: noncrystalline platelets of iron phosphate (about 500 nm wide and long and maximally 100 nm thick) that occur along a fibrous core of the terminal. The anatomic features suggested that these nerve endings could detect small intensity changes of the geomagnetic field. Such stimuli can induce deformations of the SPM clusters, which could be transduced into primary receptor potentials by mechanosensitive membrane receptor channels. The subepidermal fat cells surrounding the nerve endings prevent the inside from external mechanical stimuli. These structural findings corresponded to conclusions inferred from rock magnetic measurements, theoretical calculations, model experiments, and behavioral data, which also matched previous electrophysiologic recordings from migratory birds.