An extremely young massive clump forming by gravitational collapse in a primordial galaxy.

When cosmic star formation history reaches a peak (at about redshift z ≈ 2), galaxies vigorously fed by cosmic reservoirs are dominated by gas and contain massive star-forming clumps, which are thought to form by violent gravitational instabilities in highly turbulent gas-rich disks. However, a clump formation event has not yet been observed, and it is debated whether clumps can survive energetic feedback from young stars, and afterwards migrate inwards to form galaxy bulges. Here we report the spatially resolved spectroscopy of a bright off-nuclear emission line region in a galaxy at z = 1.987. Although this region dominates star formation in the galaxy disk, its stellar continuum remains undetected in deep imaging, revealing an extremely young (less than ten million years old) massive clump, forming through the gravitational collapse of more than one billion solar masses of gas. Gas consumption in this young clump is more than tenfold faster than in the host galaxy, displaying high star-formation efficiency during this phase, in agreement with our hydrodynamic simulations. The frequency of older clumps with similar masses, coupled with our initial estimate of their formation rate (about 2.5 per billion years), supports long lifetimes (about 500 million years), favouring models in which clumps survive feedback and grow the bulges of present-day galaxies.

NUDT15 R139C causes thiopurine-induced early severe hair loss and leukopenia in Japanese patients with IBD.

The efficacy of thiopurines, including azathioprine (AZA) and 6-mercaptopurine (6MP), has been demonstrated for the treatment of inflammatory bowel disease (IBD). The most common and serious adverse event of treatment with thiopurines altered by doctors is leukopenia. Hair loss is also a serious event that could be a critical reason for patients to decline thiopurine treatment. Thiopurine-induced severe hair loss causes cosmetic problems, and it takes a long time to recover. In a recent study, NUDT15 R139C was strongly associated with thiopurine-induced leukopenia in Korean and Caucasian populations. In this study, we performed an association study to investigate and replicate the association of R139C with adverse events of thiopurines in Japanese patients. A total of 142 Japanese patients with IBD, with histories of thiopurine treatment, were examined. NUDT15 R139C was genotyped using a custom TaqMan genotyping assay. Adverse events including leukopenia were reviewed from medical records. The 6MP dose was adjusted to AZA equivalents by multiplying with 2 as a thiopurine dose. Five patients developed severe hair loss and all of them were risk homozygous (T/T) for R139C. No early severe hair loss was observed in patients with the C/T or C/C genotype (P=3.82 × 10(-16), odds ratio=212). The association of R139C with early (<8 weeks) leukopenia (white blood cells<3000 mm(-3)), which was previously reported in Korean patients, was replicated in our Japanese IBD cohort (P=1.92 × 10(-16), odds ratio=28.4). However, we could not confirm the association with late leukopenia in the Japanese subjects. Patients with the C/T genotype discontinued treatment or required thiopurine dose reduction significantly earlier than patients with the C/C genotype (P=1.45 × 10(-4)); however, on manipulating the doses, there was no significant difference in the thiopurine continuation rates between the groups. In the maintenance period, the frequencies of 6MP usage were higher, and the doses of thiopurines were significantly lower in patients with the C/T genotype than in those with the C/C genotype (0.574±0.316 mg kg(-1) per day vs 1.03±0.425 mg kg(-1) per day, P=6.21 × 10(-4)). NUDT R139C was significantly associated with early severe hair loss in Japanese patients with IBD. We also verified the previously reported association of R139C with early leukopenia in a different East Asian population. It is recommended that treatment with thiopurines should be avoided for patients with the T/T genotype. Low-dose 6MP (0.2-0.3 mg kg(-1) per day) could be used rather than AZA for the patients with C/T genotype to continue thiopurine treatments. However, late leukopenia and other several adverse events could not be completely predicted by R139C genotypes.

Control of algal production in a high rate algal pond: investigation through batch and continuous experiments.

For decades, arid and semi-arid regions in Africa have faced issues related to water availability for drinking, irrigation and livestock purposes. To tackle these issues, a laboratory scale greywater treatment system based on high rate algal pond (HRAP) technology was investigated in order to guide the operation of the pilot plant implemented in the 2iE campus in Ouagadougou (Burkina Faso). Because of the high suspended solids concentration generally found in effluents of this system, the aim of this study is to improve the performance of HRAPs in term of algal productivity and removal. To determine the selection mechanism of self-flocculated algae, three sets of sequencing batch reactors (SBRs) and three sets of continuous flow reactors (CFRs) were operated. Despite operation with the same solids retention time and the similarity of the algal growth rate found in these reactors, the algal productivity was higher in the SBRs owing to the short hydraulic retention time of 10 days in these reactors. By using a volume of CFR with twice the volume of our experimental CFRs, the algal concentration can be controlled during operation under similar physical conditions in both reactors.

Risk factors for early re-bleeding and associated hospitalization in patients with colonic diverticular bleeding.

AIM: The annual incidence of colonic diverticular bleeding is increasing, but treatments are not yet well established. Here we aimed to identify the risk factors for early re-bleeding and to determine the associated duration of hospitalization. METHOD: Records of 90 emergent patients with colonic diverticular bleeding between 1999 and May 2012 were retrospectively reviewed. They were divided into an early re-bleeding within 1 month group (n = 24) and a no re-bleeding group (n = 66) and we investigated the risk factors for early re-bleeding. In the former group, we calculated the time from the first haemostasis to early re-bleeding and the associated duration of hospitalization. RESULTS: Univariate analysis showed that there were significantly more patients with signs of shock (P = 0.00055) and active bleeding on the first colonoscopy after admission (P = 0.020) in the early re-bleeding group. Multivariate conditional logistic regression analysis using stepwise variable selection showed that signs of shock on admission (odds ratio, 5.23; 95% confidence interval, 1.84-14.90; P = 0.0019) remained statistically significant. All patients who re-bled without signs of shock (n = 7) and 16 of 17 with signs of shock re-bled within 126 h (5.25 days) of initial hospitalization. CONCLUSION: Shock was an independent risk factor for early re-bleeding. The associated duration of hospitalization was 6 days.

The expression of CD36 in vessels with blood-brain barrier impairment in a stroke-prone hypertensive model.

AIMS: The class B scavenger receptor CD36, the receptor for oxidized low-density lipoprotein, mediates free radical production and brain injury in cerebral ischaemia. Free radical production is known to be involved in the remodelling of the cerebral vasculature of stroke-prone spontaneously hypertensive rats (SHRSP). Accordingly, we examined whether the expression of CD36 is increased in the vasculature with blood-brain barrier (BBB) impairment and collagen deposition of SHRSP. METHODS: The gene and protein expression of CD36 was examined in the vessels of the hippocampus of SHRSP with BBB impairment and those of Wistar Kyoto rats without the impairment, by real-time RT-PCR, Western blotting and immunohistochemical techniques. RESULTS: The gene and protein expression of CD36 was increased in the hippocampus of SHRSP compared with that of Wistar Kyoto rats. Confocal microscopic examination revealed CD36 immunoreactivity in perivascular microglial cells immunopositive for ED1. Immunoelectron microscopic examination revealed that the immunosignals for CD36 were located mainly in the cytoplasm of perivascular cells in vessels showing increased vascular permeability and a few in the cytoplasmic membranes of endothelial cells. CONCLUSIONS: These findings indicate that the expression of CD36 was increased in vessels with BBB impairment in the hippocampus of SHRSP and was mainly seen in the cytoplasm of perivascular microglial cells, suggesting a role of CD36 in cerebrovascular injury.

Osteomyelitis due to trimethoprim/sulfamethoxazole-resistant Edwardsiella tarda infection in a patient with X-linked chronic granulomatous disease.

Edwardsiella tarda, a catalase-positive bacillus widely distributed throughout nature, is generally susceptible to trimethoprim/sulfamethoxazole. We describe osteomyelitis due to trimethoprim/sulfamethoxazole-resistant E. tarda in a patient with chronic granulomatous disease (CGD). Once E. tarda acquires antibiotic resistance, infected CGD patients may develop severe infections with unforeseeable consequences.

The expression of P-glycoprotein is increased in vessels with blood-brain barrier impairment in a stroke-prone hypertensive model.

AIMS: We previously reported that the blood-brain barrier (BBB) function was impaired in vessels in the hippocampus in 3-month-old stroke-prone spontaneously hypertensive rats (SHRSP). In this study, we examined gene and protein expressions of P-glycoprotein, a representative efflux transporter of cerebral vessels, in the BBB-damaged hippocampal vessels of SHRSP and in the vessels of Wistar Kyoto (WKY) rats as controls, to clarify roles of the efflux transporter in the BBB-damaged vessels. METHODS: The expression of P-glycoprotein in hippocampal and cortical samples was examined by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting and immunoelectron microscopic techniques. RESULTS: Real-time RT-PCR and Western blotting analyses revealed that the gene and protein expressions of P-glycoprotein were increased in the hippocampal samples of 3-month-old SHRSP compared with hippocampal samples of 3-month-old WKY rats or with cortical samples of SHRSP. The gene expression of P-glycoprotein was also increased in the hippocampal samples of 4-week-old SHRSP. Immunoelectron microscopic examination revealed that immunosignals of P-glycoprotein were seen in the luminal and ab-luminal cytoplasmic membranes of endothelial cells and the basal lamina, that the labelling density of P-glycoprotein in the vessel wall was higher in the hippocampus of 3-month-old SHRSP than in other groups and that the immunosignals of P-glycoprotein were occasionally co-located with those of albumin. CONCLUSIONS: These findings indicate that the expression of P-glycoprotein is increased in BBB-damaged hippocampal vessels in hypertensive SHRSP compared with those in WKY rats.

Effects of platelet release products on neutrophilic activity in human whole blood.

OBJECTIVES: To investigate the effects of Platelet release products (PRPr) and their phagocytosis activators including ATP, ADP, and macromolecular activators of phagocytosis (MAPPs) on phagocytosis and oxidative burst activity by neutrophils in human whole blood. METHODS: A whole blood-based flow cytometric assay was used to assess neutrophilic activity. Escherichia coli were used as the target organisms. RESULTS: Phagocytosis and oxidative burst by neutrophils were markedly increased after treatment with PRPr or MAPPs + ATP + ADP. The phagocytosis activation was more prominent in the first minute, and displayed a maximum enhancement of 4-fold. The maximum augmentation of oxidative burst was 5-fold which occurred at 5 mins. A striking finding was that the effect of MAPPs was evident from 5 mins onwards and increased with further incubation in both the phagocytosis and oxidative burst assays. CONCLUSION: These data suggest that the neutrophilic activity enhanced by PRPr depends more on ATP and ADP during the early phase and on MAPPs during the later phase of the phagocytic process. The present study reveals an important role for PRPr and their phagocytosis activators in the enhancement of neutrophilic activity in human whole blood.

Micro-CT analysis of alveolar bone healing using a rat experimental model of critical-size defects.

OBJECTIVE: This study was designed to establish a rat model of a critical size alveolar bone defect. MATERIALS AND METHODS: Standardized buccal or mesiobuccal alveolar bone defects were made around the right first mandibular molar of 12-week-old rats, and the left was used as a control. Alveolar bone healing was examined quantitatively by three-dimensional micro-computed tomographic imaging. Bone matrix production of osteoblasts and osteocytes during repair of alveolar bone defects was examined with in situ hybridization for type I collagen. RESULTS: Buccal defects were repaired significantly and the volume decreased by 88.3% in week 24, whereas mesiobuccal defects were repaired little. Osteoblasts and osteocytes expressed type I collagen in both defects in week 3 but showed little expression by week 6 and thereafter, leaving the mesiobuccal defects largely unrepaired. CONCLUSION: The mesiobuccal defect is a critical-size defect that is not ultimately repaired with bone. It may be an appropriate experimental model for investigating the effectiveness of bone regenerative agents in human alveolar bone loss.

Overexpression of retinoic acid receptor alpha suppresses myeloid cell differentiation at the promyelocyte stage.

Retinoic acid receptor (RAR) alpha is required to heterodimerize with retinoid X receptor (RXRs) in order to regulate myeloid differentiation. If so, it is expected that overexpression of normal RAR alpha may perturb the RAR alpha/RXR heterodimer formation and also the differentiation of myeloid cells. We have described here the morphology and the RA response of human RAR alpha cDNA transduced murine bone marrow cells using a retroviral vector. Most of RAR alpha transduced cells displayed promyelocyte like morphology and their proportion of c-kit expressing population was increased remarkably compared with the control (Neor gene transduced cells). Furthermore, this morphology was observed even after these cells were brought into the semisolid culture containing IL-3 alone. Interestingly, immature RAR alpha transduced cells differentiated into mature granulocytes under the condition of the high concentration of RA(10(-6) M). We did not observe any effect of RAR alpha on monocytes. These results indicate that overexpression of normal RAR alpha is sufficient for inducing maturation arrest of myeloid cell lineage that is similar to the phenotype found in the acute promyelocytic leukemia bearing PML-RAR alpha translocation.

Responses induced by arginine-vasopressin injection in the plasma concentrations of adrenocorticotropic hormone, cortisol, growth hormone and metabolites around weaning time in goats.

In order to assess the biological significance of weaning and water deprivation on the control of plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol, growth hormone (GH) and metabolites in response to stimulation with arginine-vasopressin (AVP) and corticotropin-releasing hormone (CRH), we carried out three experiments in which male goats before and after weaning were intravenously injected with AVP or CRH alone, or in combination with each other. In experiment 1, 17-week-old (post-weaning) goats were intravenously injected with AVP or CRH alone at the doses of 0.1, 0.3 and 1.0 nmol/kg body weight (BW). The AVP injection significantly and dose dependently increased plasma levels of ACTH, cortisol, GH and metabolites, whereas the injection with CRH did not cause significant increases in the levels of these parameters. In experiment 2, 4-week-old (pre-weaning) and 13-week-old (post-weaning) goats were injected with either AVP or CRH alone, followed by a combined injection of both secretagogues at a dose of 0.3 nmol/kg BW. Although the basal levels of the hormones and metabolites, with the exception of glucose, were greater in the 4-week-old goats, the hormone responses induced by stimulation with AVP were weaker than those induced in 13-week-old goats. Additionally, there were no responses in any hormone patterns to CRH stimulation in 4-week-old goats. In experiment 3, 13-week-old goats were injected with CRH alone followed by injection with AVP for two consecutive days of water deprivation. The animals were subjected to withdrawal of up to 20% of the total blood volume and water deprivation for up to 28 h. However, no significant differences in plasma ACTH, cortisol or GH levels were observed between days 1 and 2. Based on these results, we concluded that: (1) AVP is a more potent stimulant than CRH in terms of its ability to induce increases in plasma levels of ACTH, cortisol and GH; (2) the role of AVP as a secretagogue of hypothalamus-pituitary-adrenal hormones is strengthened, whereas the ineffective role of CRH remains unaltered, by weaning; (3) acute stress such as massive withdrawal of blood volume and subjection to water deprivation may not be sufficient burdens to alter stress-related hormone levels in young goats.

Dominant expansion of human T cells in non-obese diabetic/severe combined immunodeficiency mice implanted with human bone fragments.

OBJECTIVE: To establish an in vivo animal model in which human T cells develop and function normally, a step toward developing new vaccines or chemical compounds that modulate immune functions and toward understanding T-cell immunity in humans. MATERIALS AND METHODS: Human bone fragments were implanted into non-obese diabetes/severe combined immunodeficiency (NOD/SCID) mice. The presence of human blood cells in the peripheral blood of these mice was monitored periodically by immunostaining and fluorescence-activated cell sorting. RESULTS: After implantation of bone fragments, dominant expansion of human T lymphocytes, rather than myeloid and B cells, was observed over a 3-month period. In some cases, the proportion of human T cells rose to 40% of the peripheral blood mononuclear cells. These T cells showed CD4/CD8 ratios similar to those observed in human peripheral blood lymphocytes and had a broad repertoire of rearranged T-cell receptor genes. Graft-versus-host reaction was not noted in any organ analyzed. To assess the suitability of NOD/SCID mice implanted with human bone fragments (hu-bone-NOD/SCID mice) as an in vivo model for HIV infection, the mice were infected with a T-lymphotropic strain of HIV-1 (NL4-3) at 7 weeks posttransplant. Serum p24 gag was detected at 2 weeks after inoculation, after which total CD4-positive cell numbers declined, as seen clinically in patients infected with HIV. CONCLUSION: Although the precise mechanism is yet to be determined by which predominant expansion of human T cells occurs in hu-bone-NOD/SCID mice, such mice appear likely to serve as a useful and versatile model for studies involving human T-cell immunity.

Galaxy evolution. Evidence for mature bulges and an inside-out quenching phase 3 billion years after the Big Bang.

Most present-day galaxies with stellar masses ≥10(11) solar masses show no ongoing star formation and are dense spheroids. Ten billion years ago, similarly massive galaxies were typically forming stars at rates of hundreds solar masses per year. It is debated how star formation ceased, on which time scales, and how this "quenching" relates to the emergence of dense spheroids. We measured stellar mass and star-formation rate surface density distributions in star-forming galaxies at redshift 2.2 with ~1-kiloparsec resolution. We find that, in the most massive galaxies, star formation is quenched from the inside out, on time scales less than 1 billion years in the inner regions, up to a few billion years in the outer disks. These galaxies sustain high star-formation activity at large radii, while hosting fully grown and already quenched bulges in their cores.

Simplified retroviral vector gcsap with murine stem cell virus long terminal repeat allows high and continued expression of enhanced green fluorescent protein by human hematopoietic progenitors engrafted in nonobese diabetic/severe combined immunodeficient mice.

Despite efforts toward improvements in retrovirus-mediated gene transfer, stable high-level expression of a therapeutic gene in human hematopoietic stem cells remains a great challenge. We have evaluated the efficiency of different viral long terminal repeats (LTRs) in long-term expression of a transgene in vivo, using severe combined immunodeficiency (SCID)-repopulating cell assays. Vectors used were variants of the simplified retroviral vector GCsap with the different LTRs of Moloney murine leukemia virus (MLV), myeloproliferative sarcoma virus (MPSV), and murine stem cell virus (MSCV). The enhanced green fluorescent protein (EGFP) gene was used as a marker to assess levels of transduction efficiency. CD34+ cells isolated from human cord blood were transduced by exposure to virus-containing supernatants on fibronectin fragments and in the presence of stem cell factor, interleukin 6, Flt-3 ligand, and thrombopoietin, and then transplanted into nonobese diabetic/SCID mice. Engraftment of human cells highly expressing EGFP, with differentiation along multiple cell lineages, was demonstrated for up to 18 weeks posttransplant, although the three different vectors showed different transduction frequencies (MLV, <0.1-33.2%; MPSV, <0.1-22.8%; MSCV, 0.3-51.7%). Of importance is that high-level transduction frequencies in human progenitor cells were also confirmed by colony-forming cell assays using bone marrow from transplanted mice, in which EGFP-expressing, highly proliferative potential colonies were observed by fluorescence microscopy. In these mice the vector carrying the MSCV LTR generated more EGFP-expressing human cells than did either of the other two constructs, indicating that GCsap carrying the MSCV LTR may be an efficient tool for stem cell gene therapy.

A simple and reliable method for screening retroviral producer clones without selectable markers.

Simplified retroviral vectors that lack dominant selectable markers are being used with increasing frequency. These simplified vectors may offer a number of advantages over selectable marker-containing constructs, including potentially higher titers and less immunogenicity. However, the use of these vectors has been limited by the cumbersome experimental approaches in establishing and characterizing useful producer cell clones. To address this issue, a simple and reliable assay was developed to identify retroviral producer cell lines with or without dominant selectable markers. Producer cells were first generated by standard transfection/transduction and clones isolated by limiting dilution. Supernatant from each clone was then screened by RNA dot blot to identify the best producer clone candidates. The semiquantitative nature of the RNA dot blot assay was validated using a retroviral vector containing neomycin phosphotransferase (neo). Titers obtained by conventional G418-resistant colony forming units/ml (G418(R) cfu/ml) assays strongly correlated with the values by RNA dot blot procedure. RNA dot blot results also correlated well with titers estimated by Southern analysis of HeLa cells transduced with supernatant from each clone. The RNA dot blot technique is a rapid (2 days) and reliable method to screen retroviral producer cells, thereby facilitating the generation and characterization of simplified retroviral producer cell clones.

Characterization of diverse viral vector preparations, using a simple and rapid whole-virion dot-blot method.

A number of different viruses have been adapted as gene transfer vectors, including retroviruses, adenoviruses, adenoassociated viruses (AAVs), herpes simplex virus, SV40 viruses, and alphaviruses (both Semliki Forest and Sindbis viruses). One of the major rate-limiting and time-consuming steps in the characterization of these vectors is the process of determining the viral vector titers. In addition, there is no "universal" method that can be used to rapidly estimate the titer and the utility of viral vector preparations. We demonstrate here that supernatant from diverse classes of viral vectors, with either RNA or DNA genomes, can be rapidly evaluated by a simple virus dot-blot hybridization without prior extraction of nucleic acids. This system can provide a reliable screen for physical titer of viral vector supernatants in 1 day.

Ultrastructural and permeability features of microvessels in the hippocampus, cerebellum and pons of senescence-accelerated mice (SAM).

We previously reported that the accumulation of blood-borne radiolabelled serum albumin in brain parenchyma increased with aging, especially in senescence-accelerated mice (SAMP8), which showed age-related deficits in learning and memory. In this study, in order to examine morphological events related to the age-related increase of the brain accumulation of serum albumin, the transvascular passage of blood-borne horseradish peroxidase (HRP) and ultrastructural features of microvessels were examined in the hippocampus, cerebellum and pons of SAMP8 and SAMR1 (control) mice. Ultrastructural examination of the hippocampus showed that the staining for HRP was occasionally spreading throughout the parajunctional cytoplasm of the endothelial cell of aged SAMP8 mice, but not in young SAMP8 mice nor in SAMR1 mice. The number of vessels showing the staining reaction for HRP in the parajunctional cytoplasm of the endothelial cells in aged SAMP8 mice increased significantly compared with that in the others. Electron microscopic morphometry showed that there were no significant differences among the number of HRP-positive vesicles per unit area of the endothelial cell cytoplasm in young and old mice of both strains. The staining reaction for HRP was not seen in the basal lamina of microvessels and the perivascular neuropil in all mice examined. Perivascular lipofuscin-like granules and collagen deposits, swelling of astroglial perivascular endfeet and perivascular cells containing foamy, lipid-like droplets were frequently found in several brain regions of aged SAMP8 mice. The perivascular cells with a few lipid-like droplets and more electron-homogeneous lysosomes were occasionally seen in SAMR1 and young SAMP8, while the other findings were scarcely observed in SAMR1 and young SAMP8 mice. These findings suggest that the blood-brain barrier to HRP was preserved in microvessels in three brain regions of SAM mice but the blood microvessels showed some age-related ultrastructural alterations in SAMP8 brains. Uncontrolled passage of HRP through the parajunctional cytoplasm of the endothelial cells may partly contribute to the age-related increase of accumulation of serum albumin in SAMP8 brains.

Induction of therapeutic antitumor antiangiogenesis by intratumoral injection of genetically engineered endostatin-producing Semliki Forest virus.

Antiangiogenic therapy using Semliki Forest virus (SFV) carrying Endostatin gene for malignant brain tumor was investigated to improve the therapeutic efficacy. The efficiency of SFV-mediated gene delivery was first evaluated for B 16 cells and compared with the efficiency in cells of endothelial origin (HMVECs). HMVECs are more susceptible to SFV infection than B 16 cells. For the in vivo treatment model, phosphate-buffered saline, SFV-LacZ, retrovirus vector GCsap-Endostatin, and SFV-Endostatin were injected to mice bearing B 16 brain tumors. A very significant inhibition of tumor growth was observed in the group that had been treated with SFV-Endostatin. A marked reduction of intratumoral vascularization was seen in the tumor sections from the SFV-Endostatin group compared with tumor sections from the SFV-LacZ or GCsap-Endostatin groups. Moreover, at day 7 after intravenous administration of SFV-Endostatin, the serum level of endostatin was augmented more than 3-fold compared to that after intravenous administration of GCsap-Endostatin. The results indicated that treatment with SFV-Endostatin inhibited the angiogenesis with established tumors. Gene therapy with Endostatin delivered via SFV may be a candidate for the development of new therapy for brain tumors.

Neurogenesis in olfactory bulb identified by retroviral labeling in normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated adult mice.

Neurogenesis occurs during development and in the normal adult brain. Recent studies identified areas exhibiting postlesional selective neurogenesis and neuronal repair. In the olfactory bulb (OB), one of the most studied regions of the brain for neurogenesis, seizures and strong odor exposure are known to enhance neurogenesis. Here, we report enhanced neurogenesis in OB after dopaminergic neuronal loss induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a selective toxin for dopaminergic neurons. The neurogenesis has been previously confirmed mainly by the uptake of 5-bromodeoxyuridine (BrdU), a marker of proliferating cells, but methodological problems related to BrdU labeling might result in inaccurate findings with respect to specificity, toxicity and incorporation into normal/lesioned brain. For a better identification of neurogenesis, we used a retroviral vector. First, we investigated the population dynamics of newly formed neurons in different regions of OB including the glomerular layer, the most superficial layer of OB. Quantification of neurogenesis in OB revealed by our retroviral vector was substantially similar to that by BrdU-based method. One week after MPTP application and dopaminergic neuronal loss in OB, neurogenesis of dopaminergic neurons in OB increased by three-fold, but no such process was noted in non-dopaminergic neurons. Our results indicate selective dopaminergic neurogenesis in OB in response to neuronal damage/loss.