NF-kB decoy oligodeoxynucleotide preserves disc height in a rabbit anular-puncture model and reduces pain induction in a rat xenograft-radiculopathy model.

While it is known that the degenerated intervertebral disc (IVD) is one of the primary reasons for low-back pain and subsequent need for medical care, there are currently no established effective methods for direct treatment. Nuclear factor-κB (NF-κB) is a transcription factor that regulates various genes' expression, among which are inflammatory cytokines, in many tissues including the IVD. NF-κB decoy is an oligodeoxynucleotide containing the NF-κB binding site that entraps NF-κB subunits, resulting in suppression of NF-κB activity. In the present preclinical study, NF-κB decoy was injected into degenerated IVDs using the rabbit anular-puncture model. In terms of distribution, NF-κB decoy persisted in the IVDs up to at least 4 weeks after injection. The remaining amount of NF-κB decoy indicated that it fit a double-exponential-decay equation. Investigation of puncture-caused degeneration of IVDs showed that NF-κB decoy injection recovered, dose-dependently, the reduced disc height that was associated with reparative cell cloning and morphological changes, as assessed through histology. Gene expression, by quantitative real-time polymerase chain reaction (qRT-PCR), showed that NF-κB decoy attenuated inflammatory gene expression, such as that of interleukin-1 and tumor necrosis factor-α, in rabbit degenerated IVDs. NF-κB decoy also reduced the pain response as seen using the "pain sensor" nude rat xenograft-radiculopathy model. This is the first report demonstrating that NF-κB decoy suppresses the inflammatory response in degenerated IVDs and restores IVD disc height loss. Therefore, the intradiscal injection of NF-κB decoy may have the potential as an effective therapeutic strategy for discogenic pain associated with degenerated IVDs.

Nanofocusing of X-ray free-electron laser using wavefront-corrected multilayer focusing mirrors.

A method of fabricating multilayer focusing mirrors that can focus X-rays down to 10 nm or less was established in this study. The wavefront aberration induced by multilayer Kirkpatrick-Baez mirror optics was measured using a single grating interferometer at a photon energy of 9.1 keV at SPring-8 Angstrom Compact Free Electron Laser (SACLA), and the mirror shape was then directly corrected by employing a differential deposition method. The accuracies of these processes were carefully investigated, considering the accuracy required for diffraction-limited focusing. The wavefront produced by the corrected multilayer focusing mirrors was characterized again in the same manner, revealing that the root mean square of the wavefront aberration was improved from 2.7 (3.3) rad to 0.52 (0.82) rad in the vertical (horizontal) direction. A wave-optical simulator indicated that these wavefront-corrected multilayer focusing mirrors are capable of achieving sub-10-nm X-ray focusing.

Ectopic expression of c-myc fails to overcome downregulation of telomerase activity induced by herbimycin A, but ectopic hTERT expression overcomes it.

Correction to: Leukemia (2000); 14: 1260­1265; doi: 10.1038/sj.leu.2401828. Since the publication of the above article the authors have identified an error in Figure 1. Figure 1 shows the modulation of telomerase activity by herbimycin A in K562 cells: (a) cell cycle and (b) telomerase activity, mRNA expressions of hTERT, hTERC, TEP-1, c-myc, cyclin D1 and b-actin, and c-Myc protein. The authors however wish to inform the readers that Figure 1b incorrectly shows hTERT mRNA, which is the result of herbimycin A treatment of cyclin-D1-transfected K562 cells (Figure 3b, hTERT mRNA). While preparing Figure 1, the authors mistakenly submitted a figure that used the incorrect photo data following confusion regarding file names. The correct figure can be found below: The authors wish to apologise for any inconvenience caused and confirm that the conclusions drawn from this research are not affected by this error.

Perineuronal nets affect parvalbumin expression in GABAergic neurons of the mouse hippocampus.

Recent studies have suggested that the perineuronal net (PNN), a specialised extracellular matrix structure, and parvalbumin (PV), an EF-hand calcium-binding protein, are involved in the regulation of plasticity of neural circuits. Here, we aimed to quantitatively estimate the relationship between the two plasticity regulators, PV and PNNs, in the hippocampus of young adult mice. Dual fluorescence staining for PV and Wisteria floribunda agglutinin (a broad PNN marker) showed that a substantial population of PV-expressing (PV(+) ) GABAergic neurons lacked PNNs. Optical disector analysis demonstrated that there were fewer PNN(+) neurons than PV(+) neurons. The ratio of PNN expression in PV(+) neurons was generally lower in the dendritic layers than in the principal cell layers, whereas the ratio of PV expression in PNN(+) neurons was effectively 100%. The mean PV fluorescence was significantly higher in PNN(+) /PV(+) neurons than in PNN(-) /PV(+) neurons. Cumulative frequencies for single-cell PV fluorescence indicated that intensely stained PV(+) neurons tend to be enwrapped by PNNs, whereas weakly stained PV(+) neurons are likely to lack PNNs. We digested the PNNs by a unilateral injection of chondroitinase ABC (chABC) into the dorsal CA1 region. Although the densities of PV(+) neurons remained unchanged, the PV fluorescence declined 7 days after chABC injection. Quantitative real-time polymerase chain reaction analysis demonstrated a reduction in PV mRNA expression following chABC injection. These findings indicate that the presence or absence of PNNs affects the relative PV expression in GABAergic neurons in the hippocampus.

Observation of orbital resonance Hall effect in (TMTSF)2ClO4.

We report the observation of a Hall effect driven by orbital resonance in the quasi-1-dimensional (q1D) organic conductor (TMTSF)2ClO4. Although a conventional Hall effect is not expected in this class of materials due to their reduced dimensionality, we observed a prominent Hall response at certain orientations of the magnetic field B corresponding to lattice vectors of the constituent molecular chains, known as the magic angles (MAs). We show that this Hall effect can be understood as the response of conducting planes generated by an effective locking of the orbital motion of the charge carriers to the MA driven by an electron-trajectory resonance. This phenomenon supports a class of theories describing the rich behavior of MA phenomena in q1D materials based on altered dimensionality. Furthermore, we observed that the effective carrier density of the conducting planes is exponentially suppressed in large B, which indicates possible density wave formation.

Spatio-temporal differences in perineuronal net expression in the mouse hippocampus, with reference to parvalbumin.

Perineuronal net (PNN) is a specialized aggregate of the extracellular matrix, which is considered to be involved in regulation of structural plasticity of neuronal circuits. Here we examined the spatial and temporal differences in Wisteria floribunda agglutinin-labeled PNN intensity in single cells in the mouse hippocampus, where the neuronal circuits engaged in cognition and emotion are embedded in the dorsal and ventral parts, respectively. In young mice, the intensity of PNN was very low, and there were no significant dorsoventral differences in all hippocampal regions. Developmental increase in PNN intensity was larger in the dorsal part than in the ventral part. As a result, PNN intensity was higher in the dorsal part than in the ventral part in adult mice. Aging dissimilarly affects different regions of the dorsal hippocampus. Namely, PNN intensity in the dorsal part of old mice declined in the CA1 region, remained unchanged in the CA3 region, increased in the dentate gyrus. By contrast, there were no significant aging-related changes in PNN intensity in the ventral hippocampus. We also examined the intensity of parvalbumin (PV), an EF-hand calcium-binding protein, because it has been shown that PNNs are closely related to PV-containing GABAergic inhibitory neurons. Contrary to expectations, developmental and aging-related changes in PV intensity were not comparable to those seen in PNN intensity. The correlation coefficients between PNN and PV intensities in single cells showed gradual decline during development and aging in the CA1 and CA3 regions, while there were little correlations in the dentate gyrus regardless of age. In summary, PNNs are differentially expressed in the dorsal and ventral hippocampal circuits during development and aging, indicating their possible role for cognition and emotion control.

Neural mechanisms mediating association of sympathetic activity and exploration in decision-making.

The somatic marker hypothesis asserts that decision-making can be guided by feedback of bodily states to the brain. In line with this hypothesis, the present study tested whether sympathetic activity shows an association with a tonic dimension of decision-making, exploratory tendency represented by entropy in information theory, and further examined the neural mechanisms of the association. Twenty participants performed a stochastic reversal learning task that required decision-making in an unstable and uncertain situation. Regional cerebral blood flow was evaluated using (15)O-water positron emission tomography (PET), and cardiovascular indices and concentrations of catecholamine in peripheral blood were also measured, during the task. In reversal learning, increased epinephrine during the task positively correlated with larger entropy, indicating a greater tendency for exploration in decision-making. The increase of epinephrine also correlated with brain activity revealed by PET in the somatosensory cortices, anterior insula, dorsal anterior cingulate cortex, and the dorsal pons. This result is consistent with previously reported brain matrixes of representation of bodily states and interoception. In addition, activity of the anterior insula specifically correlated with entropy, suggesting possible mediation of this brain region between peripheral sympathetic arousal and exploration in decision-making. These findings shed a new light about a role of bodily states in decision-making and underlying neural mechanisms.

Hazard Evaluation Support System (HESS) for predicting repeated dose toxicity using toxicological categories.

Repeated dose toxicity (RDT) is one of the most important hazard endpoints in the risk assessment of chemicals. However, due to the complexity of the endpoints associated with whole body assessment, it is difficult to build up a mechanistically transparent structure-activity model. The category approach, based on mechanism information, is considered to be an effective approach for data gap filling for RDT by read-across. Therefore, a library of toxicological categories was developed using experimental RDT data for 500 chemicals and mechanistic knowledge of the effects of these chemicals on different organs. As a result, 33 categories were defined for 14 types of toxicity, such as hepatotoxicity, hemolytic anemia, etc. This category library was then incorporated in the Hazard Evaluation Support System (HESS) integrated computational platform to provide mechanistically reasonable predictions of RDT values for untested chemicals. This article describes the establishment of a category library and the associated HESS functions used to facilitate the mechanistically reasonable grouping of chemicals and their subsequent read-across.

Categorization of nitrobenzenes for repeated dose toxicity based on adverse outcome pathways.

Adoption of the data-gap filling method for complex endpoints such as repeated dose toxicity (RDT) and reproductive/developmental toxicity is one of the most important issues affecting international chemical management at present. A categorization method based on adverse outcome pathways (AOPs) has recently been investigated for such complex endpoints. In this paper, we report results of the categorization of nitrobenzenes for RDT based on the AOPs obtained by analysing the detailed RDT test reports for 24 different nitrobenzenes already evaluated. In most RDT testing of nitrobenzenes without hydroxyl groups or acid groups, findings related to haemolytic anaemia and liver effects were observed at low dosages. It was, therefore, possible to assume common AOPs for haemolytic anaemia and liver effects induced by these nitrobenzenes. As a result, a group of nitrobenzenes was defined as a single category for both haemolytic anaemia and liver effects, respectively, based on these AOPs.

Upregulation of calcium binding protein, S100A6, in activated astrocytes is linked to glutamate toxicity.

S100A6 (calcyclin), an EF-hand calcium binding protein, is considered to exert various functions, e.g., cell proliferation and differentiation, calcium homeostasis, and neuronal degeneration. In this study, we aimed to investigate whether S100A6 might be linked to glutamate toxicity using three animal models and pharmacological interventions. We first examined the age-related changes in S100A6 immunoreactivity in the mouse hippocampus, considering that an important negative aspect of brain aging is linked to increased extracellular glutamate. The surface area of S100A6-positive (+) astrocytes was significantly larger in aged mice than in young mice, while the numbers of S100ß+ astrocytes did not change with age. In the second experiment, we examined the alterations in S100A6 immunoreactivity in the injured hypoglossal nucleus, because glutamate toxicity is considered to contribute to neuronal death after axotomy. There was no apparent S100A6 immunoreactivity in the hypoglossal nucleus of sham control animals. However, intense labeling for S100A6 in activated astrocytes was observed in the axotomized hypoglossal nucleus of mice. Administration of ceftriaxone, an astrocyte glutamate transporter enhancer, to axotomized mice significantly decreased the immunoreactivity for S100A6. In the third experiment, we tested an animal model of epilepsy using kainic acid (KA), a glutamate analog. In the mouse hippocampus after KA injection, S100A6 immunoreactivity was significantly increased in astrocytes, and pyknotic changes were observed in CA3 pyramidal neurons. Treatment of MK-801, an N-methyl-d-aspartate receptor antagonist, counteracted the KA-induced increase in S100A6 immunoreactivity, and reduced the numbers of pyknotic neurons. Our results indicate that upregulation of astrocytic S100A6 in response to extracellular glutamate may be involved in neuronal damage under pathophysiological conditions.

Chronic stress modulates neural and cardiovascular responses during reversal learning.

Animal studies have revealed that chronic stress shifts cognitive strategies from the flexible goal-directed action to the simple and rigid habit action. In addition, stress-induced atrophy in the prefrontal cortex and dorsomedial striatum which are involved in the goal-directed action and hypertrophy of the dorsolateral striatum which is critical for the habit action were parallel with the effects of chronic stress on behaviors. The present study tested whether these previous findings in animal studies are compatible in humans by analyzing effects of chronic stress on neural and cardiovascular responses, which are likely important for performing appropriate actions. Twenty healthy men exposed to low or high chronic job stress performed a stochastic reversal learning task, which required cognitive flexibility and the goal-directed action. Regional cerebral blood flow was evaluated during the task using (15)O-water positron emission tomography, and cardiovascular parameters such as blood pressure and heart rate were also measured. During the reversal learning task, whereas participants with low chronic job stress exhibited activity in the anterior caudate, as well as orbitofrontal cortex, ventrolateral prefrontal cortex, insula, and midbrain, which might be related to the goal-directed action, participants with high chronic job stress exhibited no activity in such brain regions. Furthermore, participants with high chronic job stress exhibited less reactivity in diastolic blood pressure, which might be mediated by anterior cingulate cortical activity. These findings, in line with previous studies, suggested that chronic job stress correlates with less activity in brain regions related to the goal-directed action, and insensitive physiological responses in humans.

Differential involvement of perineuronal astrocytes and microglia in synaptic stripping after hypoglossal axotomy.

Following peripheral axotomy, the presynaptic terminals are removed from lesioned neurons, that is synaptic stripping. To elucidate involvement of astrocytes and microglia in synaptic stripping, we herein examined the motoneuron perineuronal circumference after hypoglossal nerve transection. As reported previously, axotomy-induced slow cell death occurred in C57BL/6 mice but not in Wistar rats. Synaptophysin labeling in the hypoglossal nucleus exhibited a minor reduction in both species after axotomy. Slice patch recording showed that the mean frequency of miniature postsynaptic currents in axotomized motoneurons was significantly lower in rats than in mice. We then estimated the relative coverage of motoneuron perineuronal circumference by line profile analysis. In the synaptic environment, axotomy-induced intrusion of astrocytic processes was significantly more extensive in rats than in mice, whereas microglial intrusion into the synaptic space was significantly more severe in mice than in rats. Interestingly, in the extrasynaptic environment, the prevalence of contact between astrocytic processes and lesioned motoneurons was significantly increased in rats, while no significant axotomy-induced alterations in astrocytic contact were observed in mice. These findings indicate that astrocytic, but not microglial, reaction may primarily mediate some anti-apoptotic effects through synaptic stripping after hypoglossal nerve axotomy. In addition, enlargement of astrocytic processes in the extrasynaptic environment may also be involved in neuronal protection via the increased uptake of excessive glutamate.

Morphological features of the stomach of Malayan pangolin, Manis javanica.

The morphology of the stomach of Malayan pangolin, Manis javanica was studied at macroscopic, light microscopic, and scanning electron microscopic levels. The stomach of M. javanica was C-shaped with short lesser curvature. At the oesophageal junction, the inner smooth muscle was thickened in the greater curvature side. The entire stomach was lined by a thick cornified stratified squamous epithelium, except at the duct orifices of glands and in the pyloric gland region. The wall of the fundus was thin and devoid of glands. The gastric glands consisted of mucous, oxyntic, and pyloric glands. The mucous glands were observed in the lesser curvature (Mg-L), in the greater curvature (Mg-G), and in the pyloric canal (Mg-C) respectively. The oxyntic glands were organized into gland mass, making an oval mound elevated to the gastric lumen, in the middle of the greater curvature. The oxyntic gland mass has a single common duct with opening directed to the pyloric side. This duct was surrounded by mucus gland (Mg-G). The pyloric glands were located caudal to the pylorus. There was no sphincter at the pyloric-duodenal junction. Large mucosal protuberance, the torus pyloricus was observed in the side of the lesser curvature of the pyloric canal. In the lumen of pyloric canal region, numerous spines and small pebbles were observed. The muscle layers in the wall of this region were considerably thickened. The present results on the stomach of M. javanica are thought to be closely related to the toothless and eating habits of this animal species.

Density-of-state oscillation of quasiparticle excitation in the spin density wave phase of (TMTSF)2ClO4.

Systematic measurements of the magnetocaloric effect, heat capacity, and magnetic torque under a high magnetic field up to 35 T are performed in the spin density wave (SDW) phase of a quasi-one-dimensional organic conductor (TMTSF)2ClO4. In the SDW phase above 26 T, where the quantum Hall effect is broken, rapid oscillations (ROs) in these thermodynamic quantities are observed, which provides clear evidence of the density-of-state (DOS) oscillation near the Fermi level. The resistance is semiconducting and the heat capacity divided by temperature is extrapolated to zero at 0 K in the SDW phase, showing that all the energy bands are gapped, and there is no DOS at the Fermi level. The results show that the ROs are ascribed to the DOS oscillation of the quasiparticle excitation.

Antigenic stimulation with cytochrome P450 2J expressed in mouse hepatocellular carcinoma cells regulates host anti-tumour immunity.

Cytochrome P450 2J subfamily (CYP2J) enzymes expressed in mouse hepatocellular carcinoma (HCC) cells were identified as an antigen recognized by specific CD4(+) T cells and the structure of its T cell epitope was determined by proteomics-based exploration. The major histocompatibility complex (MHC) class II binding peptides were isolated from I-A(k)/peptide complex of dendritic cells (DCs) loaded or unloaded with MIH-2 mouse HCC cells. MHC class II-binding peptides found in MIH-2-loaded DCs but not in unloaded DCs were determined by tandem mass spectrometric analysis. The peptide, consisting of amino acid 276-290 (DFIDAFLKEMTKYPE) of mouse CYP2J enzymes, was identified as an antigenic peptide presented in the context of MHC class II. Preventive treatment of mice with CYP2J peptide stimulated interferon (IFN)-gamma production of splenocytes and suppressed the growth of implanted CYP2J-positive MIH-2 cells but not CYP2J-negative murine bladder tumour cells. However, continuous treatment of MIH-2-bearing mice with CYP2J peptide significantly suppressed IFN-gamma production of splenocytes and accelerated the growth of implanted MIH-2 tumours in vivo. Increased frequencies of CD4(+)forkhead box P3 regulatory T cells and CD11b(+)Gr-1(+) myeloid suppressor cells were observed in splenocytes from the continuously immunized mice. These results indicate that antigenecity of CYP2J isoforms expressed in HCC cells activate host anti-tumour immunity at an initial stage of HCC, but suppress host anti-tumour immunity with excessive antigenic stimulation at an advanced stage.

Distribution of lectin-bindings in the testis of the lesser mouse deer, Tragulus javanicus.

The distribution of lectin bindings in the testis of the smallest ruminant, lesser mouse deer (Tragulus javanicus), was studied using 12 biotinylated lectins specific for d-galactose (peanut agglutinin PNA, Ricinus communis agglutinin RCA I), N-acetyl-d-galactosamine (Dolichos biflorus agglutinin DBA, Vicia villosa agglutinin VVA, Soybean agglutinin SBA), N-acetyl-D-glucosamine and sialic acid (wheat germ agglutinin WGA, s-WGA), D-mannose and d-glucose (Lens culinaris agglutinin LCA, Pisum sativum agglutinin PSA, Concanavalin A Con A), L-fucose (Ulex europaeus agglutinin UEA I), and oligosaccharide (Phaseolus vulgaris agglutinin PHA-E) sugar residues. In Golgi-, cap-, and acrosome-phase spermatids, lectin-bindings were found in the acrosome (PNA, RCA I, VVA, SBA, WGA and s-WGA), and in the cytoplasm (PNA, RCA I, VVA, SBA, WGA, LCA, PSA, Con A and PHA-E). s-WGA binding was confined to the spermatid acrosome, but other lectins were also observed in spermatocytes. In spermatogonia, VVA, WGA, Con A, and PHA-E bindings were observed. Sertoli cells were intensely stained with DBA and Con A, and weakly with PHA-E. In interstitial Leydig cells, RCA I, DBA, VVA, Con A, PSA, LCA, WGA and PHA-E were positive. UEA I was negative in all cell types including spermatogenic cells. Unusual distribution of lectin-bindings noted in the testis of lesser mouse deer included the limited distribution of s-WGA only in the spermatid acrosome, the distribution of DBA in Sertoli cells, Leydig cells and lamina propria, and the absence of UEA I in all type cells. The present results were discussed in comparison with those of other animals and their possible functional implications.

Category analysis of the substituted anilines studied in a 28-day repeat-dose toxicity test conducted on rats: correlation between toxicity and chemical structure.

In order to establish methods for estimating the repeat-dose toxicity of chemicals on the basis of their chemical structure, an analysis of a category formed for 14 substituted anilines was conducted. This analysis was based on the results of a 28-day repeat-dose toxicity test conducted on rats in which these 14 chemicals were studied. The intensities of the toxicological effects of the 14 substituted anilines on each target organ at specific dosages were described using the values and histopathological findings of the test. The results clarified the characteristics of the chemical structure that induced specific toxicological effects on specific targets at a particular dosage. Hemolysis was the most frequently observed finding in the test reports in the case of the 14 substituted anilines. Strong linear correlations between the dosage and proportion of decrease in the erythrocyte count were found in the case of chemicals that induced strong hemolytic effects. In particular, for dimethylanilines, strong linear correlations were found between the calculated hemoglobin-binding index and the proportion of decrease in the erythrocyte count at a particular dosage. Thus, the results of our analysis demonstrate that it is possible to correlate the values obtained for substituted anilines from 28-day repeat-dose toxicity tests with their quantitatively determined molecular properties. The intensity of hemolysis and the effects on the liver tended to be low in the case of chemicals with a high water solubility, such as aminophenols and benzene sulfonic acids. However, a similar trend was not observed in the case of the effects of these chemicals on the kidney.

A review of systematic reviews on pain interventions in hospitalized infants.

BACKGROUND: Hospitalized infants undergo multiple, repeated painful procedures. Despite continued efforts to prevent procedural pain and improve pain management, clinical guidelines and standards frequently do not reflect the highest quality evidence from systematic reviews. OBJECTIVE: To critically appraise all systematic reviews on the effectiveness of procedural pain interventions in hospitalized infants. METHODS: A structured review was conducted on published systematic reviews and meta-analyses of pharmacological and nonpharmacological interventions of acute procedural pain in hospitalized infants. Searches were completed in the Cochrane Database of Systematic Reviews, MEDLINE, EMBASE, CINAHL and PsycINFO. Two reviewers independently selected articles for review and rated the methodological quality of the included reviews using a validated seven-point quality assessment measure. Any discrepancies were resolved by a third reviewer. RESULTS: Of 1469 potential systematic reviews on interventions for painful procedures in hospitalized infants, 11 high-quality reviews were included in the analysis. Pharmacological interventions supported by research evidence included premedication for intubation, dorsal penile nerve block and EMLA (AstraZeneca Canada, Inc) for circumcision, and sucrose for single painful procedures. Non-nutritive sucking, swaddling, holding, touching, positioning, facilitative tucking, breast feeding and supplemental breast milk were nonpharmacological interventions supported for procedural pain. CONCLUSION: There is a growing number of high-quality reviews supporting procedural pain management in infants. Ongoing research of single, repeated and combined pharmacological and nonpharmacological interventions is required to provide the highest quality evidence to clinicians for decision-making on optimal pain management.

Antiferromagnetic d-electron exchange via a spin-singlet pi-electron ground state in an organic conductor.

Electron spin resonance reveals the spin behavior of conduction (pi) and localized (d) electrons in beta-(BDA-TTP)2MCl4 (M=Fe, Ga). Both the Ga3+(S=0) and Fe3+(S=5/2) compounds exhibit a metal-insulator transition at 113 K with the simultaneous formation of a spin-singlet ground state in the pi electron system of the donor molecules. The behavior is consistent with charge ordering in beta-(BDA-TTP)2MCl4 at the metal-insulator transition. At 5 K, the Fe3+ compound orders antiferromagnetically, even though the pi electrons, which normally would facilitate magnetic exchange, are localized nonmagnetic singlets.

Cloning and expression analysis of YY1AP-related protein in the rat brain.

YY1AP-related protein (YARP) is a structural homolog of YY1AP, a transcriptional coactivator of the multifunctional transcription factor YY1. We cloned a rat YARP cDNA that encoded a 2256 amino acid protein with 93% homology to the human counterpart. Northern blots revealed significant expression of the YARP gene in the rat brain. In situ hybridization demonstrated its expression in neurons throughout the brain, including pyramidal cells in the cerebral cortex and hippocampus and granule cells in the dentate gyrus. YARP was coexpressed with YY1 in these same neuronal cells. However, there was no evidence of YARP expression in glia. In the developing rat brain, the level of YARP mRNA ( approximately 10 kb) peaked at embryonic day 18 and promptly declined thereafter to reach the steady-state level found in adulthood, by 14 days after birth. These results suggest that YARP functions at a late stage of neurogenesis during perinatal development of the rat brain, as well as in mature neurons.