RESUMO
Bcs1p is a chaperone that is required for the incorporation of the Rieske subunit within complex III of the mitochondrial respiratory chain. Mutations in the human gene BCS1L (BCS1-like) are the most frequent nuclear mutations resulting in complex III-related pathologies. In yeast, the mimicking of some pathogenic mutations causes a respiratory deficiency. We have screened chemical libraries and found that two antibiotics, pentamidine and clarithromycin, can compensate two bcs1 point mutations in yeast, one of which is the equivalent of a mutation found in a human patient. As both antibiotics target the large mtrRNA of the mitoribosome, we focused our analysis on mitochondrial translation. We found that the absence of non-essential translation factors Rrf1 or Mif3, which act at the recycling/initiation steps, also compensates for the respiratory deficiency of yeast bcs1 mutations. At compensating concentrations, both antibiotics, as well as the absence of Rrf1, cause an imbalanced synthesis of respiratory subunits which impairs the assembly of the respiratory complexes and especially that of complex IV. Finally, we show that pentamidine also decreases the assembly of complex I in nematode mitochondria. It is well known that complexes III and IV exist within the mitochondrial inner membrane as supramolecular complexes III2/IV in yeast or I/III2/IV in higher eukaryotes. Therefore, we propose that the changes in mitochondrial translation caused by the drugs or by the absence of translation factors, can compensate for bcs1 mutations by modifying the equilibrium between illegitimate, and thus inactive, and active supercomplexes.
Assuntos
ATPases Associadas a Diversas Atividades Celulares/genética , Complexo III da Cadeia de Transporte de Elétrons/genética , Proteínas de Membrana/genética , Mitocôndrias/genética , Proteínas Mitocondriais/genética , Chaperonas Moleculares/genética , Biossíntese de Proteínas , Proteínas de Saccharomyces cerevisiae/genética , ATPases Associadas a Diversas Atividades Celulares/química , Claritromicina/farmacologia , Complexo III da Cadeia de Transporte de Elétrons/química , Complexo III da Cadeia de Transporte de Elétrons/efeitos dos fármacos , Humanos , Proteínas de Membrana/química , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Proteínas Mitocondriais/química , Chaperonas Moleculares/química , Proteínas Mutantes/química , Proteínas Mutantes/genética , Pentamidina/farmacologia , Respiração/genética , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/químicaRESUMO
A 1-year-old male Cane Corso was presented for progressive hindlimb neurologic deficits, with a history of suspected recurrent meningitis. Physical examination and advanced diagnostic imaging findings were suggestive of a thoracic dermoid sinus extending into the dura mater, and spina bifida. After initial medical treatment, the lesion was surgically excised, and the presence of an intramedullary cyst in continuation with the dermoid sinus was confirmed, requiring partial durectomy and myelotomy for removal. Histopathological examination of the excised tissue confirmed the diagnosis of a dermoid sinus associated with an intramedullary dermoid cyst. After surgery, the dog temporarily declined neurologically but then showed progressive neurological improvement. This report describes presentation and successful surgical treatment of a type IVa dermoid sinus associated with an intramedullary dermoid cyst and spina bifida in a dog.
Assuntos
Cisto Dermoide , Doenças do Cão , Espinha Bífida Oculta , Disrafismo Espinal , Animais , Bengala , Cisto Dermoide/cirurgia , Cisto Dermoide/veterinária , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/cirurgia , Cães , Masculino , Espinha Bífida Oculta/cirurgia , Espinha Bífida Oculta/veterinária , Disrafismo Espinal/cirurgia , Disrafismo Espinal/veterináriaRESUMO
Mechanical properties of cancellous bone is of increasing interest due to its involvement in aging pathologies and oncology. Characterization of fragile bone tissue is challenging and available methodologies include quasi-static compressive tests of small size specimens, ultrasound and indentation techniques. We hypothesized that modal analysis of flexure beams could be a complementary methodology to obtain Young modulus. The sampling methodology was adapted such that the uniqueness of the linear dynamic response was available to determine the elastic modulus from natural frequencies and mode shapes. In a first step, the methodology was validated using a synthetic bone model as control. Then, water-jet cutting allowed collecting fourteen small beam-like specimens in canine distal femurs. X-ray microtomography confirmed the microarchitecture preservation, the homogeneity and the isotropy at the specimen scale to derive effective properties. The first natural frequency in clamped-free boundary conditions was used to obtain mean values of Young modulus, which ranged from 210 MPa to 280 MPa depending on the specimen collection site. Experimental tests were rapid and reproducible and our preliminary results were in good agreement with literature data. In conclusion, beam modal analysis could be considered for exploring mechanical properties of fragile and scarce biological tissues.
Assuntos
Osso Esponjoso , Fêmur , Animais , Fenômenos Biomecânicos , Osso Esponjoso/diagnóstico por imagem , Cães , Módulo de Elasticidade , Fêmur/diagnóstico por imagem , Análise de Elementos Finitos , Estresse MecânicoRESUMO
The ORF YOL018c (TLG2) of Saccharomyces cerevisiae encodes a protein that belongs to the syntaxin protein family. The proteins of this family, t-SNAREs, are present on target organelles and are thought to participate in the specific interaction between vesicles and acceptor membranes in intracellular membrane trafficking. TLG2 is not an essential gene, and its deletion does not cause defects in the secretory pathway. However, its deletion in cells lacking the vacuolar ATPase subunit Vma2p leads to loss of viability, suggesting that Tlg2p is involved in endocytosis. In tlg2Delta cells, internalization was normal for two endocytic markers, the pheromone alpha-factor and the plasma membrane uracil permease. In contrast, degradation of alpha-factor and uracil permease was delayed in tlg2Delta cells. Internalization of positively charged Nanogold shows that the endocytic pathway is perturbed in the mutant, which accumulates Nanogold in primary endocytic vesicles and shows a greatly reduced complement of early endosomes. These results strongly suggest that Tlg2p is a t-SNARE involved in early endosome biogenesis.
Assuntos
Endocitose/fisiologia , Fatores de Troca do Nucleotídeo Guanina , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Proteínas de Transporte de Nucleotídeos , Organelas/fisiologia , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/fisiologia , ATPases Vacuolares Próton-Translocadoras , Sequência de Aminoácidos , Cromossomos Fúngicos , Clonagem Molecular , Proteínas Fúngicas/biossíntese , Proteínas Fúngicas/genética , Deleção de Genes , Cinética , Fator de Acasalamento , Proteínas de Membrana/genética , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Dados de Sequência Molecular , Fases de Leitura Aberta , Organelas/ultraestrutura , Peptídeos/genética , Peptídeos/metabolismo , ATPases Translocadoras de Prótons/genética , ATPases Translocadoras de Prótons/metabolismo , Proteínas Qa-SNARE , Proteínas Recombinantes de Fusão/biossíntese , Saccharomyces cerevisiae/genética , Alinhamento de Sequência , Homologia de Sequência de AminoácidosRESUMO
Traumatic injuries to the knee are frequent (road or sports related accidents, falls in elderly people). The Ottawa knee rules are applied and dictate the need for additional evaluation. Some fractures are adequately assessed on plain radiographs alone whereas other fractures (tibial plateau fracture) require additional evaluation with CT. Some fractures may be occult: the significance of lipohemarthrosis (indirect sign of intra-articular fracture on the lateral radiograph with horizontal beam) must be known. Benign appearing avulsion fractures suggest the presence of underlying capsuloligamentous injuries requiring further evaluation with MRI. The imaging work-up of sprains is usually negative. MRI may show areas of bone contusion that further the understanding of the mechanism of injury, predict and confirm the presence of capsuloligamentous injuries. Angiography is performed to detect popliteal artery injuries after knee dislocation which is associated with a risk of ischemia.
Assuntos
Fraturas do Fêmur/cirurgia , Processamento de Imagem Assistida por Computador , Luxações Articulares/diagnóstico , Traumatismos do Joelho/diagnóstico , Imageamento por Ressonância Magnética , Fraturas da Tíbia/diagnóstico , Tomografia Computadorizada por Raios X , Adolescente , Angiografia , Corpos Estranhos/diagnóstico , Fraturas Ósseas/diagnóstico , Humanos , Masculino , Patela/lesões , Artéria Poplítea/lesõesRESUMO
Skp1p-cullin-F-box (SCF) protein complexes are ubiquitin ligases required for degradation of many regulatory proteins involved in cell cycle progression, morphogenesis, and signal transduction. Using a genetic screen, we have isolated a novel allele of the HRT1/RBX1 gene in budding yeast (hrt1-C81Y). hrt1-C81Y mutant cells exhibited an aberrant morphology but were viable at all temperatures. The cells displayed multiple genetic interactions with mutations in known SCF components and were defective for the degradation of several SCF targets including Gic2p, Far1p, Sic1p, and Cln2p. In addition, they also failed to degrade the F-box proteins Grr1p, Cdc4p, and Met30p. Wild-type Hrt1p but not Hrt1p-C81Y was able to bind multiple F-box proteins in an F-box-dependent manner. Hrt1p-C81Y harbors a single mutation in its ring-finger domain, which is conserved in subunits of distinct E3 ligases. Finally, Hrt1p was localized in both nucleus and cytoplasm and despite a short half-life was expressed constitutively throughout the cell cycle. Taken together, these results suggest that Hrt1p is a core subunit of multiple SCF complexes.
Assuntos
Proteínas de Transporte/metabolismo , Proteínas de Ciclo Celular/isolamento & purificação , Proteínas de Ciclo Celular/metabolismo , Proteínas F-Box , Mutação/genética , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Complexos Ubiquitina-Proteína Ligase , Ubiquitina-Proteína Ligases , Proteínas Adaptadoras de Transdução de Sinal , Alelos , Proteínas de Transporte/genética , Ciclo Celular/fisiologia , Proteínas de Ciclo Celular/genética , Núcleo Celular/metabolismo , Proteínas Inibidoras de Quinase Dependente de Ciclina , Ciclinas/metabolismo , Citoplasma/metabolismo , Proteínas Fúngicas/metabolismo , Mutagênese Sítio-Dirigida , Peptídeo Sintases/metabolismo , Processamento de Proteína Pós-Traducional/genética , Proteínas Recombinantes/metabolismo , Proteínas Repressoras/metabolismo , Proteínas Ligases SKP Culina F-Box , Saccharomyces cerevisiae/crescimento & desenvolvimento , Temperatura , Técnicas do Sistema de Duplo-Híbrido , Ubiquitinas/metabolismoRESUMO
We analyze theoretically the dynamics of a semiconductor laser subject to optical feedback, on the basis of the well-known Lang-Kobayashi equations. Previous investigations on this laser system suggest that a small linewidth enhancement factor (alpha factor) stabilizes the laser dynamics. By contrast, we unveil here optical feedback induced instabilities which are present for a small value of alpha but which disappear when alpha increases above alpha approximately 1. By combining numerical simulations and modern continuation methods for delay-differential equations, we unveil cascades of subcritical and supercritical Hopf bifurcations on the first external-cavity mode (ECM). We unveil for the first time, to our knowledge, the occurrence of subcritical Hopf bifurcation points for intermediate values of the EC length, i.e. close to the boundary between the short and the long EC regimes. They lead to severe laser instabilities such as large intensity and possibly chaotic pulsations. Moreover, these Hopf bifurcation cascades for small values of alpha are shown to be responsible for different bifurcation scenarios leading to restabilization of the first ECM and to ECM bistability.
RESUMO
We investigate numerically the low-frequency fluctuation regime in a laser diode subject to optical feedback. We demonstrate that a saddle-node ghost can induce this regime.
RESUMO
A current-modulated vertical-cavity surface-emitting laser is shown to exhibit interesting nonlinear dynamics in its two orthogonal linearly polarized (LP), fundamental transverse modes. The intensities of the two LP modes may exhibit in-phase time-periodic dynamics or chaotic regimes with combination of in-phase and antiphase dynamics at two different time scales. Chaotic dynamics are found in a large range of laser and modulation parameters.
RESUMO
We study numerically two distant unidirectionally coupled single-mode semiconductor lasers subject to coherent optical feedback. We show that two fundamentally different types of chaotic synchronization can occur depending on the strengths of the coupling and of the feedback of the receiver laser.
RESUMO
A paravertebral ganglioneuroma was discovered in a 25 year-old woman presenting a transverse spinal syndrome at the same level. Exeresis necessitated sacrifice of the ninth left intercostal artery, but paraplegia regressed completely under corticotherapy. Additional exploration and subsequent clinical evolution revealed multiple sclerosis, of which the pavaplegia had been a manifestation. The authors discuss ganglioneuroma in the adult, a rare tumour, and the possibility of a link with multiple sclerosis. The association seems fortuitous despite the fact that the tumour and the transverse myelitis occurred at the same level.
Assuntos
Ganglioneuroma/complicações , Esclerose Múltipla/complicações , Paraplegia/etiologia , Neoplasias do Sistema Nervoso Periférico/complicações , Sistema Nervoso Simpático , Corticosteroides/uso terapêutico , Adulto , Feminino , Ganglioneuroma/patologia , Humanos , Esclerose Múltipla/tratamento farmacológico , Neoplasias do Sistema Nervoso Periférico/patologiaRESUMO
Total lateral paralysis in a case of "One and half" Fisher's syndrome accompanied by paralytic pontine exotropia is described. Oculographic investigation indicates involvement of the nucleus of the VIth cranial nerve. Paralytic pontine exotropia, may therefore be encountered where the VIth nucleus is involved.
Assuntos
Ataxia/fisiopatologia , Oftalmoplegia/fisiopatologia , Reflexo Anormal/fisiopatologia , Nervo Troclear/fisiopatologia , Convergência Ocular , Exotropia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Oftalmoplegia/complicações , SíndromeRESUMO
A case of Refsum's disease in a 62-year-old man, with an ophthalmologic symptomatology dominated by a tight bilateral miosis, is reported. The miosis mechanism in this disease is discussed. The clinical evolution has been stabilized by a diet poor in phytanic acid.
Assuntos
Miose/etiologia , Doença de Refsum/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Miose/fisiopatologia , Doença de Refsum/complicações , Doença de Refsum/fisiopatologiaRESUMO
Panmedullary ependymoma is an unusual disease last reported by Fuentes in 1986. The present case is the first to have been studied by magnetic resonance, using gadolinium. The findings indicated a panmedullary lesion rather than a tumour. Histopathological investigation confirmed the hypothesis.
Assuntos
Ependimoma/diagnóstico , Neoplasias da Medula Espinal/diagnóstico , Adulto , Ependimoma/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias da Medula Espinal/cirurgiaRESUMO
We report a case in which rhythmical myoclonus and tremor at rest revealed a thalamo-subthalamic metastasis from a bronchial carcinoma. Tremor of the upper limbs and face (4 Hz) disappeared with sustained posture and action. A cogwheel phenomenon, hypotonia and disorders of automatic and voluntary movements were also present. Surface electromyographic recordings showed a rhythmical, synchronous activity of the biceps brachialis and triceps muscles at rest. Pathology disclosed lesions of the red nucleus and neighbouring area and severe compression of the substantia nigra which were likely to be the cause of the signs and symptoms.
Assuntos
Adenocarcinoma/secundário , Neoplasias Encefálicas/secundário , Mesencéfalo , Mioclonia/etiologia , Tremor/etiologia , Adenocarcinoma/complicações , Adenocarcinoma/fisiopatologia , Neoplasias das Glândulas Suprarrenais , Encéfalo/patologia , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/fisiopatologia , Eletromiografia , Humanos , Neoplasias Pulmonares , Masculino , Pessoa de Meia-Idade , Mioclonia/fisiopatologia , Descanso , Tremor/fisiopatologiaRESUMO
An acute polyradiculoneuropathy occurred in a 30 years homosexual male. E.L.I.S.A. test and Western Blot showed recent infection by H.I.V. Besides, endogenous reinfestation by cytomegalovirus was found: high concentrations of specific IgG antibodies and presence of the virus in the blood. T4 helper cells were severely reduced, without any other sign of cellular immunity failure. None of the two viruses was found in the nervous biopsy. This Guillain-Barre syndrome with a subsequent cellular reaction in the CSF, is probably to be related to an immunoallergic mechanism. Brief increase of antibodies specific for HBsAg and Borrelia Burgdorferri and the beneficial effect of plasmapheresis, supported this view. Two months later, the patient showed superficial lymph nodes hyperplasia, without any other symptom of pre-Acquired Immuno-Depression Syndrome.
Assuntos
Soropositividade para HIV , Polirradiculoneuropatia/etiologia , Adulto , Anticorpos Antivirais/análise , Infecções por Citomegalovirus/etiologia , Soropositividade para HIV/diagnóstico , Humanos , Masculino , Infecções Oportunistas/etiologia , Plasmaferese , Polirradiculoneuropatia/imunologia , Polirradiculoneuropatia/terapia , Prognóstico , Recidiva , Testes SorológicosRESUMO
The only etiologic factor retained in 11 patients with sensory or sensory-motor neuropathy was almitrine therapy. In one patient there was in addition an optic neuropathy. The reduction in visual acuity in this patient coincided with the onset of the sensory-motor neuropathy of lower limbs after treatment with 100 mg/day of almitrine over a 2-year period. No other metabolic, inflammatory, toxic, vascular or immunologic cause was found. There was a moderate chronic respiratory insufficiency. Visual recuperation started one month after the arrest of almitrine treatment and was satisfactory 7 months later. The other 10 patients had neuropathy of limbs without visual disorders. Neuromuscular biopsy in one case showed lesions to be of the axonal type.
Assuntos
Estimulantes do Sistema Nervoso Central/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Piperazinas/efeitos adversos , Idoso , Almitrina , Axônios/ultraestrutura , Eletrofisiologia , Potenciais Evocados Visuais/efeitos dos fármacos , Feminino , Humanos , Perna (Membro)/inervação , Masculino , Pessoa de Meia-Idade , Neurite Óptica/induzido quimicamente , Doenças do Sistema Nervoso Periférico/patologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Visão Ocular/efeitos dos fármacosRESUMO
In a case of panmedullary ependymoma, a rare tumour, MRI was performed before and after gadolinium injection. The latter clearly demonstrated the borders of the tumour. Throughout the procedure, neurophysiological exploration was carried out with recording of motor and somatosensory evoked potentials.
Assuntos
Ependimoma/diagnóstico , Gadolínio , Imageamento por Ressonância Magnética , Neoplasias da Medula Espinal/diagnóstico , Adulto , Ependimoma/fisiopatologia , Potenciais Evocados , Humanos , Masculino , Neoplasias da Medula Espinal/fisiopatologiaRESUMO
This study of juvenile distal cerebral ischaemia is based on 55 patients aged from 18 to 30 years. The authors describe the circumstances of discovery, as well as the clinical features and the course of the disease which may be severe and lead to non-resolutive neurological accidents and sometimes dementia. Paraclinical evaluation includes capillaroscopy, finger and toe pads biopsy (which clearly shows a pathological process with fibrocellular promontories narrowing the lumen of arterioles), and above all angiography which displays two typical signs: arterial narrowness and bands of peripheral ischaemia. In advanced forms of the disease angiography reveals classical signs of ischaemic lesions, but charateritically these are very distal. Associated abnormalities of the carotid siphon can also be found. Finally, positive CT scans show an isolated widening of the sulci which is fairly suggestive of the disease.
Assuntos
Isquemia Encefálica/diagnóstico por imagem , Angiografia Cerebral , Adolescente , Adulto , Angiografia Digital , Artérias/patologia , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/patologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pele/irrigação sanguínea , Tomografia Computadorizada por Raios XRESUMO
The authors describe a case of brachial plexus'lesion at axillary level in a patient under anticoagulation therapy. They underline the use of CT scan and digitalized angiography to establish the diagnosis and choice the treatment.