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1.
Occup Med (Lond) ; 67(1): 75-77, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27694375

RESUMO

Compression neuropathy of the common peroneal nerve (CPN) at the fibula head is a common condition, but it has not attracted attention in working environments. Here, we report a 38-year-old sewer pipe worker who presented with bilateral CPN palsy following 6h working with a squatting posture in a narrow sewer pipe. During the work, he could not stretch his legs sufficiently because of the confined space. His symptoms deteriorated with repetition of the same work for 1 week. Motor nerve conduction study showed conduction block at the fibula head of bilateral CPNs, compatible with compression neuropathy at this lesion. Three months after cessation of work requiring the causative posture, his symptoms and neurophysiological abnormalities had resolved completely. Almost all seven of his co-workers presented transiently with similar and milder symptoms, although one showed CPN palsy for 6 months. Prolonged squatting posture in a confined space causes acute compression neuropathy at the fibula head in the CPN. More attention should be paid to 'confined space worker's compression neuropathy'.


Assuntos
Artrogripose/complicações , Neuropatia Hereditária Motora e Sensorial/complicações , Nervo Fibular/fisiopatologia , Postura/fisiologia , Adulto , Artrogripose/diagnóstico , Neuropatia Hereditária Motora e Sensorial/diagnóstico , Humanos , Masculino , Neuropatias Fibulares/complicações , Neuropatias Fibulares/diagnóstico , Neuropatia Tibial/complicações , Neuropatia Tibial/diagnóstico
2.
Soft Matter ; 12(21): 4794-804, 2016 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-27109907

RESUMO

Submicrometer-sized polystyrene (PS) particles carrying stimuli-responsive poly[2-(diethylamino)ethyl methacrylate] (PDEA) hairs with degrees of polymerization of 30, 60 and 90 were synthesized by dispersion polymerization and used as a particulate foam stabilizer. The effects of the composition of these PDEA-PS particles and foam formation conditions on foamability, foam stability and foam microstructures were extensively investigated. The hairy particles were found to work as an effective stabilizer of aqueous foams in basic media, in which the PDEA hairs are not protonated and thus the particle surfaces exhibit suitable wettability at the air-water interface. In contrast, little to no foam or unstable foams were formed in acidic aqueous media, in which the hairs are protonated and are therefore water soluble. Particles carrying longer hairs resulted in greater foamability and more highly stabilized foams that were capable of persisting for more than one month. Foams were found to form in a narrower pH range when using PS particles with longer hairs, due to both entropic and image charge effects. Data obtained from the touch mixer mixing method showed that both foamability and foam stability increased with increases in the concentration of polymer particles up to 10 wt%, because higher concentrations allowed greater air-water interfacial areas to be stabilized. Conversely, only minimal foam was obtained at and above 15 wt% because of the high viscosity of the resulting aqueous particle dispersion. Trials using the homogenizer mixing method showed that foam with a cream-like texture could be formed even at 40 wt% particle concentration as a result of the improved mixing efficiency. Defoamation could be induced by exposing the foams to HCl vapor. Exposure to acidic vapor led to in situ protonation of the 2-(diethylamino)ethyl methacrylate residues, rendering the PDEA hairs hydrophilic and water soluble, and desorption of the PDEA-PS particles from the air-water interface.

3.
J Clin Pharm Ther ; 41(5): 579-82, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27477206

RESUMO

WHAT IS KNOWN AND OBJECTIVE: We measured the levels of irinotecan and its active metabolite, SN-38, in human milk after the administration of irinotecan to assess the potential risks when women treated with irinotecan nurse their infants. CASE SUMMARY: Human milk was collected for 6 days starting on the day after irinotecan was administered. The levels of irinotecan and SN-38 in human milk were measured using liquid chromatography-mass spectrometry. Irinotecan was detected on Days 2 and 3 but not after Day 4. A strong signal indicating the presence of SN-38 was detected on Day 2 and the signal was readily detected until Day 7, indicating that SN-38 remained in human milk. WHAT IS NEW AND CONCLUSION: Intravenously administered CPT-11 continues to pass into human milk over a prolonged period in the form of its active metabolite, SN-38. The relationship between administration of CPT-11 and SN-38 exposure and toxicity is still not well defined, so patients should avoid nursing their infants while they are being treated with CPT-11.


Assuntos
Camptotecina/análogos & derivados , Leite Humano/metabolismo , Adulto , Camptotecina/administração & dosagem , Camptotecina/metabolismo , Feminino , Humanos , Irinotecano
4.
Opt Express ; 22(10): 12189-99, 2014 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-24921339

RESUMO

Optical properties of single gold nanodiscs were studied by scanning near-field optical microscopy. Near-field transmission spectra of a single nanodisc exhibited multiple plasmon resonances in the visible to near-infrared region. Near-field transmission images observed at these resonance wavelengths show wavy spatial features depending on the wavelength of observation. To clarify physical pictures of the images, theoretical simulations based on spatial correlation between electromagnetic fundamental modes inside and outside of the disc were performed. Simulated images reproduced the observed spatial structures excited in the disc. Mode-analysis of the simulated images indicates that the spatial features observed in the transmission images originate mainly from a few fundamental plasmon modes of the disc.

5.
Phys Rev Lett ; 113(10): 101801, 2014 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-25238348

RESUMO

The trilepton nucleon decay modes p→e+νν and p→µ+νν violate |Δ(B-L)| by two units. Using data from a 273.4 kt yr exposure of Super-Kamiokande a search for these decays yields a fit consistent with no signal. Accordingly, lower limits on the partial lifetimes of τp→e+νν>1.7×10(32) years and τp→µ+νν>2.2×10(32) years at a 90% confidence level are obtained. These limits can constrain Grand Unified Theories which allow for such processes.

6.
Phys Rev Lett ; 113(12): 121802, 2014 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-25279622

RESUMO

We present the results of searches for nucleon decay via n→ν[over ¯]π0 and p→ν[over ¯]π+ using data from a combined 172.8 kt·yr exposure of Super-Kamiokande-I,-II, and-III. We set lower limits on the partial lifetime for each of these modes: τn→ν[over ¯]π0>1.1×10(33) years and τp→ν[over ¯]π+>3.9×10(32) years at a 90% confidence level.

7.
Phys Rev Lett ; 112(9): 091805, 2014 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-24655245

RESUMO

We report an indication that the elastic scattering rate of solar B8 neutrinos with electrons in the Super-Kamiokande detector is larger when the neutrinos pass through Earth during nighttime. We determine the day-night asymmetry, defined as the difference of the average day rate and average night rate divided by the average of those two rates, to be [-3.2 ± 1.1(stat) ± 0.5(syst)]%, which deviates from zero by 2.7 σ. Since the elastic scattering process is mostly sensitive to electron-flavored solar neutrinos, a nonzero day-night asymmetry implies that the flavor oscillations of solar neutrinos are affected by the presence of matter within the neutrinos' flight path. Super-Kamiokande's day-night asymmetry is consistent with neutrino oscillations for 4 × 10(-5) eV(2) ≤ Δm 2(21) ≤ 7 × 10(-5) eV(2) and large mixing values of θ12, at the 68% C.L.

8.
Phys Rev Lett ; 112(13): 131803, 2014 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-24745406

RESUMO

A search for the dinucleon decay pp → K+ K+ has been performed using 91.6 kton·yr data from Super-Kamiokande-I. This decay provides a sensitive probe of the R-parity-violating parameter λ112''. A boosted decision tree analysis found no signal candidates in the data. The expected background was 0.28±0.19 atmospheric neutrino induced events and the estimated signal detection efficiency was 12.6%±3.2%. A lower limit of 1.7×10(32) years has been placed on the partial lifetime of the decay O16 → C14K+ K+ at 90% C.L. A corresponding upper limit of 7.8×10(-9) has been placed on the parameter λ112''.

9.
Br J Cancer ; 108(8): 1659-67, 2013 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-23538390

RESUMO

BACKGROUND: The purpose of this study was to identify prostate cancer (PC) oncogenic microRNAs (miRs) based on miR microarray and to investigate whether these oncogenic miRs may be useful as PC biomarkers. METHODS: Initially, we carried out miR microarray and real-time PCR using RWPE-1, PC-3, DU-145 and LNCaP cells. To investigate the function of miR-183, we used a miR-183 knockdown inhibitor in cell growth and wound-healing assays. We used several algorithms and confirmed that they are directly regulated by miR-183. RESULTS: We identified three potential oncogenic miRs (miR-146a, miR-183 and miR-767-5P). The expression of miR-183 in PC cells (PC-3, DU-145 and LNCaP) was upregulated compared with RWPE-1 cells. MiR-183 expression was also significantly higher in PC tissues compared with that in matched normal prostate tissues. Additionally, miR-183 expression was correlated with higher prostate-specific antigen, higher pT and shorter overall survival. MiR-183 knockdown decreased cell growth and motility in PC cells and significantly decreased prostate tumour growth in in vivo nude mice experiments. We identified Dkk-3 and SMAD4 as potential target genes of miR-183. CONCLUSION: Our data suggest that oncogenic miR-183 may be useful as a new PC biomarker and that inhibition of miR-183 expression may be therapeutically beneficial as a PC treatment.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/genética , MicroRNAs/genética , Neoplasias da Próstata/genética , Proteína Smad4/genética , Proteínas Adaptadoras de Transdução de Sinal , Processos de Crescimento Celular/genética , Linhagem Celular Tumoral , Quimiocinas , Técnicas de Silenciamento de Genes , Humanos , Hibridização In Situ , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/biossíntese , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteína Smad4/biossíntese , Transfecção , Proteínas Wnt/metabolismo , Via de Sinalização Wnt , beta Catenina/metabolismo
10.
Br J Cancer ; 108(10): 2070-8, 2013 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-23591200

RESUMO

BACKGROUND: Wnt-signalling has an important role in renal cancer and it is modulated by genistein in other cancers. Recently, microRNAs (miRNAs) have emerged as new regulators of gene expression. Thus, we focused on miRNAs to examine the regulatory mechanism of genistein on the Wnt-signalling pathway in renal cell carcinoma (RCC). METHODS: Initially, we investigated the effect of genistein on Wnt-signalling (TOPflash reporter assay (TCF reporter assays)) in renal cancer cells, and using microarray identified candidate miRNAs whose expression was decreased by genistein. We performed functional analyses and investigated the relationship between miRNA expression and renal cancer patient outcomes. We also did 3'UTR luciferase assays to look at direct miRNA regulation of Wnt-signalling-related genes. RESULTS: Genistein promoted apoptosis while inhibiting RCC cell proliferation and invasion. Genistein also decreased TCF reporter activity in RCC cells. We found that miR-1260b was highly expressed and significantly downregulated by genistein in RCC cells. The expression of miR-1260b was significantly higher in renal cancer tissues compared with normal, and significantly related to overall shorter survival. In addition, miR-1260b promoted renal cancer cell proliferation and invasion in RCC cells. The 3'UTR luciferase activity of target genes (sFRP1, Dkk2, Smad4) was significantly decreased and their protein expression significantly upregulated in miR-1260b inhibitor-transfected renal cancer cells. CONCLUSION: Our data suggest that genistein inhibited Wnt-signalling by regulating miR-1260b expression in renal cancer cells.


Assuntos
Carcinoma de Células Renais/genética , Genisteína/farmacologia , Neoplasias Renais/genética , MicroRNAs/genética , Via de Sinalização Wnt/efeitos dos fármacos , Adulto , Idoso , Anticarcinógenos/farmacologia , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Proliferação de Células , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Avaliação Pré-Clínica de Medicamentos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Oncogenes/efeitos dos fármacos , Oncogenes/genética , Células Tumorais Cultivadas
11.
Phys Rev Lett ; 110(18): 181802, 2013 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-23683190

RESUMO

Super-Kamiokande atmospheric neutrino data were fit with an unbinned maximum likelihood method to search for the appearance of tau leptons resulting from the interactions of oscillation-generated tau neutrinos in the detector. Relative to the expectation of unity, the tau normalization is found to be 1.42 ± 0.35(stat)(-0.12)(+0.14)(syst) excluding the no-tau-appearance hypothesis, for which the normalization would be zero, at the 3.8σ level. We estimate that 180.1 ± 44.3(stat)(-15.2)(+17.8) (syst) tau leptons were produced in the 22.5 kton fiducial volume of the detector by tau neutrinos during the 2806 day running period. In future analyses, this large sample of selected tau events will allow the study of charged current tau neutrino interaction physics with oscillation produced tau neutrinos.

12.
APL Bioeng ; 7(1): 016108, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36747972

RESUMO

Conductive rubber composites are mixtures of stretchable rubber and conductive materials. They can achieve conductivity and high elasticity and are used in soft robots and wearable devices. In general, these composites exhibit high electrical resistance owing to their bonds between the fillers breaking during elongation. However, there are several types of composite materials that decrease resistance by increasing contact between the conductive materials during elongation through optimization of the shape and size of the filler. These composite materials can rapidly decrease the resistance and are expected to be applicable to switch in electric circuits and sensors. However, to use such composite materials in circuits, the electrical resistance at the time of resistance reduction must be sufficiently low to not affect the electric circuit. To achieve this, a considerable amount of filler must be mixed; however, this reduces the elasticity of the composite. Simultaneously achieving elasticity of the composite and a sufficient decrease in the resistance is challenging. This study developed a conductive rubber composite gel by mixing silicone rubber, ionic liquid, and metal filler. Consequently, the composite achieved an elongation rate of over six times and a decrease in the resistance of less than 1/105. In addition, this composite material was used as a switch circuit wherein an electric circuit is turned on and off according to elongation through a connection to a DC power source.

13.
mBio ; 14(5): e0212323, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37800917

RESUMO

IMPORTANCE: Cryptococcosis studies often utilize the common C57BL/6J mouse model. Unfortunately, infection in these mice fails to replicate the basic course of human disease, particularly hampering immunological studies. This work demonstrates that SJL/J mice can recapitulate human infection better than other mouse strains. The immunological response to Cryptococcus infection in SJL/J mice was markedly different from C57BL/6J and much more productive in combating this infection. Characterization of infected mice demonstrated strain-specific genetic linkage and differential regulation of multiple important immune-relevant genes in response to Cryptococcus infection. While our results validate many of the previously identified immunological features of cryptococcosis, we also demonstrate limitations from previous mouse models as they may be less translatable to human disease. We concluded that SJL/J mice more faithfully recapitulate human cryptococcosis serving as an exciting new animal model for immunological and genetic studies.


Assuntos
Criptococose , Cryptococcus neoformans , Humanos , Camundongos , Animais , Cryptococcus neoformans/genética , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
14.
Clin Immunol ; 142(2): 160-6, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22079330

RESUMO

Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder caused by mutations in the WAS gene. Glomerulonephritis is a frequent complication, however, histopathological data from affected patients is scarce because the thrombocytopenia that affects most patients is a contraindication to renal biopsies. We found that WASp-deficient mice develop proliferative glomerulonephritis reminiscent of human IgA nephropathy (IgAN). We examined whether increased aberrant IgA production is associated with the development of glomerulonephritis in WASp-deficient mice. Serum IgA and IgA production by splenic B cells was increased in WASp-deficient mice compared to wild-type (WT) mice. A lectin-binding study revealed a reduced ratio of sialylated and galactosylated IgA in the sera from old WASp-deficient mice. Circulating IgA-containing immune complexes showed significantly higher titers in WASp-deficient mice compared to WT mice. These results indicate that the increased IgA production and aberrant glycosylation of IgA may be critically involved in the pathogenesis of glomerulonephritis in WAS.


Assuntos
Glomerulonefrite por IGA/imunologia , Imunoglobulina A/metabolismo , Proteína da Síndrome de Wiskott-Aldrich/deficiência , Síndrome de Wiskott-Aldrich/imunologia , Animais , Linfócitos B/imunologia , Modelos Animais de Doenças , Glomerulonefrite por IGA/metabolismo , Glomerulonefrite por IGA/patologia , Glicosilação , Humanos , Imunoglobulina A/sangue , Camundongos , Camundongos Knockout , Baço/imunologia , Trombocitopenia/metabolismo
15.
Scand J Immunol ; 75(1): 120-6, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21923741

RESUMO

Neutropenia associated with Kawasaki Syndrome (KS) has been rarely reported, and the detailed mechanisms responsible for this state are not yet elucidated. The aim of this study was to clarify the mechanisms of neutropenia in KS. We examined antibodies to known neutrophil antigens (HNA1a, HNA1b, HNA null, HNA2, HNA3, HNA4 and non-HLA antigen 9a) in a KS patient with neutropenia. We also performed the granulocyte immunofluorescence test (GIFT) using patient or control neutrophils incubated with the patient's serum at serial time points over the patient's clinical course. No specific antibody to known neutrophil antigens was detected. Flow cytometric analysis showed that autoantibodies bound to immature CD13-positive myeloid cells, which resulted in myeloid lineage maturation arrest in the bone marrow. GIFT showed that neutrophil-specific autoantibodies were produced by the patient, and the amount of autoantibody inversely correlated with the patient's neutrophil counts. The presence of an autoantibody to a novel antigen on immature myeloid cells or neutrophils is the likely the cause of severe neutropenia in this patient with KS.


Assuntos
Autoanticorpos/imunologia , Síndrome de Linfonodos Mucocutâneos/imunologia , Neutropenia/imunologia , Autoanticorpos/sangue , Medula Óssea/imunologia , Pré-Escolar , Citometria de Fluxo , Humanos , Hidrocortisona/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Neutropenia/sangue , Neutropenia/tratamento farmacológico
16.
Phys Rev Lett ; 108(25): 257401, 2012 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-23004656

RESUMO

We have investigated the ultrafast spin dynamics in EuO thin films by time-resolved Faraday rotation spectroscopy. The photoinduced magnetization is found to be increased in a transient manner, accompanied with subsequent demagnetization. The dynamical magnetization enhancement showed a maximum slightly below the Curie temperature with prolonged tails toward both lower and higher temperatures and dominates the demagnetization counterpart at 55 K. The magnetization enhancement component decays in ~1 ns. The realization of the transient collective ordering is attributable to the enhancement of the f-d exchange interaction.

17.
Proc Natl Acad Sci U S A ; 106(43): 18379-84, 2009 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-19820167

RESUMO

We used noninvasive MRI and voxel-based morphometry (VBM) to detect changes in brain structure in three adult Japanese macaques trained to use a rake to retrieve food rewards. Monkeys, who were naive to any previous tool use, were scanned repeatedly in a 4-T scanner over 6 weeks, comprising 2 weeks of habituation followed by 2 weeks of intensive daily training and a 2-week posttraining period. VBM analysis revealed significant increases in gray matter with rake performance across the three monkeys. The effects were most significant (P < 0.05 corrected for multiple comparisons across the whole brain) in the right superior temporal sulcus, right second somatosensory area, and right intraparietal sulcus, with less significant effects (P < 0.001 uncorrected) in these same regions of the left hemisphere. Bilateral increases were also observed in the white matter of the cerebellar hemisphere in lobule 5. In two of the monkeys who exhibited rapid learning of the rake task, gray matter volume in peak voxels increased by up to 17% during the intensive training period; the earliest changes were seen after 1 week of intensive training, and they generally peaked when performance on the task plateaued. In the third monkey, who was slower to learn the task, peak voxels showed no systematic changes. Thus, VBM can detect significant brain changes in individual trained monkeys exposed to tool-use training for the first time. This approach could open up a means of investigating the underlying neurobiology of motor learning and other higher brain functions in individual animals.


Assuntos
Encéfalo/anatomia & histologia , Encéfalo/fisiologia , Aprendizagem/fisiologia , Macaca/anatomia & histologia , Macaca/fisiologia , Comportamento de Utilização de Ferramentas/fisiologia , Animais , Imageamento por Ressonância Magnética , Masculino
18.
Br J Cancer ; 104(2): 308-15, 2011 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-21119662

RESUMO

BACKGROUND: The purpose of this study was to identify new tumour suppressor microRNAs (miRs) in clear cell renal cell carcinoma (ccRCC), carry out functional analysis of their suppressive role and identify their specific target genes. METHODS: To explore suppressor miRs in RCC, miR microarray and real-time PCR were performed using HK-2 and A-498 cells. Cell viability, invasion and wound healing assays were carried out for functional analysis after miR transfection. To determine target genes of miR, we used messenger RNA (mRNA) microarray and target scan algorithms to identify target oncogenes. A 3'UTR luciferase assay was also performed. Protein expression of target genes in ccRCC tissues was confirmed by immunohistochemistry and was compared with miR-584 expression in ccRCC tissues. RESULTS: Expression of miR-584 in RCC (A-498 and 769-P) cells was downregulated compared with HK-2 cells. Transfection of miR-584 dramatically decreased cell motility. The ROCK-1 mRNA was inhibited by miR-584 and predicted to be target gene. The miR-584 decreased 3'UTR luciferase activity of ROCK-1 and ROCK-1 protein expression. Low expression of miR-584 in ccRCC tissues was correlated with high expression of ROCK-1 protein. The knockdown of ROCK-1 by siRNA inhibited cell motility. CONCLUSION: miR-584 is a new tumour suppressor miR in ccRCC and inhibits cell motility through downregulation of ROCK-1.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , MicroRNAs/fisiologia , Invasividade Neoplásica/genética , Quinases Associadas a rho/genética , Regiões 3' não Traduzidas , Sequência de Bases , Carcinoma de Células Renais/genética , Linhagem Celular Tumoral , Primers do DNA , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Renais/genética
19.
Phys Rev Lett ; 107(24): 241801, 2011 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-22242990

RESUMO

We present a search for differences in the oscillations of antineutrinos and neutrinos in the Super-Kamiokande-I, -II, and -III atmospheric neutrino sample. Under a two-flavor disappearance model with separate mixing parameters between neutrinos and antineutrinos, we find no evidence for a difference in oscillation parameters. Best-fit antineutrino mixing is found to be at (Δm2,sin2 2θ)=(2.0×10(-3) eV2, 1.0) and is consistent with the overall Super-K measurement.

20.
Nat Med ; 5(7): 832-5, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10395331

RESUMO

The Bax protein is widely known as a pro-apoptotic Bcl-2 family member that when overexpressed can trigger apoptosis in multiple cell types and is important for the developmental cell death of neurons. However, Bax was found here to be a potent inhibitor of neuronal cell death in mice infected with Sindbis virus. Newborn mice, which are highly susceptible to a fatal infection with neurotropic Sindbis virus, were significantly protected from neuronal apoptosis and fatal disease when infected with a recombinant Sindbis virus encoding Bax. Deletion of the N terminus of Bax, which mimics cleaved Bax, converted Bax into a pro-apoptotic factor in vivo. As mice mature during the first week after birth, they acquire resistance to a fatal Sindbis virus infection. However, Bax-deficient mice remained very sensitive to fatal disease compared with their control littermates, indicating that endogenous Bax functions as a survival factor and contributes to age-dependent resistance to Sindbis virus-induced mortality. The protective effects of Bax were reproduced in cultured hippocampal neurons but not in cultured dorsal root ganglia neurons. These findings indicate that cell-specific factors determine the anti-apoptotic versus pro-apoptotic function of Bax.


Assuntos
Infecções por Alphavirus/patologia , Apoptose/fisiologia , Encéfalo/patologia , Encéfalo/virologia , Neurônios/patologia , Neurônios/virologia , Proteínas Proto-Oncogênicas c-bcl-2 , Proteínas Proto-Oncogênicas/fisiologia , Sindbis virus/patogenicidade , Infecções por Alphavirus/genética , Infecções por Alphavirus/fisiopatologia , Animais , Linhagem Celular , Células Cultivadas , Cricetinae , Gânglios Espinais/citologia , Gânglios Espinais/fisiologia , Gânglios Espinais/virologia , Vetores Genéticos , Hipocampo/citologia , Hipocampo/fisiologia , Hipocampo/virologia , Humanos , Camundongos , Camundongos Knockout , Neurônios/fisiologia , Proteínas Proto-Oncogênicas/deficiência , Proteínas Proto-Oncogênicas/genética , Ratos , Ratos Sprague-Dawley , Sindbis virus/isolamento & purificação , Transfecção , Proteína X Associada a bcl-2
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