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Biomedical subjects

M Blondel

Publications and source records attributed to M Blondel.

At least 19 recordsLinked to original sources

Hopf bifurcation cascade in small-alpha laser diodes subject to optical feedback.

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.

Journal Article↗

Optical feedback induces polarization mode hopping in vertical-cavity surface-emitting lasers.

Vertical-cavity surface-emitting lasers subjected to weak polarization-insensitive optical feedback are studied experimentally and theoretically. We find that the feedback induces random anticorrelated hopping between the two orthogonal linearly polarized modes. This polarization mode hopping is accompanied by rapid anticorrelated oscillations in the linearly polarized intensities at the external-cavity frequency. The study of a simple stochastic delay differential equation suggests that these oscillations generated by the delay are typical of any hopping phenomenon between states.

Journal Article↗

Nonlinear polarization dynamics in directly modulated vertical-cavity surface-emitting lasers.

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.

Journal Article↗

Nuclear-specific degradation of Far1 is controlled by the localization of the F-box protein Cdc4.

Far1 is a bifunctional protein that is required to arrest the cell cycle and establish cell polarity during yeast mating. Here we show that SCF(Cdc4) ubiquitylates Far1 in the nucleus, which in turn targets the multi-ubiquitylated protein to 26S proteasomes most likely located at the nuclear envelope. In response to mating pheromones, a fraction of Far1 was stabilized after its export into the cytoplasm by Ste21/Msn5. Preventing nuclear export destabilized Far1, while conversely cytoplasmic Far1 was stabilized, although the protein was efficiently phosphorylated in a Cdc28-Cln-dependent manner. The core SCF subunits Cdc53, Hrt1 and Skp1 were distributed in the nucleus and the cytoplasm, whereas the F-box protein Cdc4 was exclusively nuclear. A cytoplasmic form of Cdc4 was unable to complement the growth defect of cdc4-1 cells, but it was sufficient to degrade Far1 in the cytoplasm. Our results illustrate the importance of subcellular localization of F-box proteins, and provide an example of how an extracellular signal regulates protein stability at the level of substrate localization.

Amino Acid Sequence↗

The F-box protein Skp2 is a ubiquitylation target of a Cul1-based core ubiquitin ligase complex: evidence for a role of Cul1 in the suppression of Skp2 expression in quiescent fibroblasts.

The ubiquitin protein ligase SCF(Skp2) is composed of Skp1, Cul1, Roc1/Rbx1 and the F-box protein Skp2, the substrate-recognition subunit. Levels of Skp2 decrease as cells exit the cell cycle and increase as cells re-enter the cycle. Ectopic expression of Skp2 in quiescent fibroblasts causes mitogen-independent S-phase entry. Hence, mechanisms must exist for limiting Skp2 protein expression during the G(0)/G(1) phases. Here we show that Skp2 is degraded by the proteasome in G(0)/G(1) and is stabilized when cells re-enter the cell cycle. Rapid degradation of Skp2 in quiescent cells depends on Skp2 sequences that contribute to Cul1 binding and interference with endogenous Cul1 function in serum-deprived cells induces Skp2 expression. Furthermore, recombinant Cul1-Roc1/Rbx1-Skp1 complexes can catalyse Skp2 ubiquitylation in vitro. These results suggest that degradation of Skp2 in G(0)/G(1) is mediated, at least in part, by an autocatalytic mechanism involving a Skp2-bound Cul1-based core ubiquitin ligase and imply a role for this mechanism in the suppression of SCF(Skp2) ubiquitin protein ligase function during the G(0)/G(1) phases of the cell cycle.

Amino Acid Motifs↗

Isolation and characterization of HRT1 using a genetic screen for mutants unable to degrade Gic2p in saccharomyces cerevisiae.

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.

Adaptor Proteins, Signal Transducing↗

Regulation of cytokinesis by the Elm1 protein kinase in Saccharomyces cerevisiae.

A Saccharomyces cerevisiae mutant unable to grow in a cdc28-1N background was isolated and shown to be affected in the ELM1 gene. Elm1 is a protein kinase, thought to be a negative regulator of pseudo-hyphal growth. We show that Cdc11, one of the septins, is delocalised in the mutant, indicating that septin localisation is partly controlled by Elm1. Moreover, we show that cytokinesis is delayed in an elm1delta mutant. Elm1 levels peak at the end of the cell cycle and Elm1 is localised at the bud neck in a septin-dependent fashion from bud emergence until the completion of anaphase, at about the time of cell division. Genetic and biochemical evidence suggest that Elm1 and the three other septin-localised protein kinases, Hsl1, Gin4 and Kcc4, work in parallel pathways to regulate septin behaviour and cytokinesis. In addition, the elm1delta;) morphological defects can be suppressed by deletion of the SWE1 gene, but not the cytokinesis defect nor the septin mislocalisation. Our results indicate that cytokinesis in budding yeast is regulated by Elm1.

Cell Cycle Proteins↗

Nuclear export of Far1p in response to pheromones requires the export receptor Msn5p/Ste21p.

Far1p is a bifunctional protein that is required to arrest the cell cycle and to establish cell polarity during yeast mating. Far1p is localized predominantly in the nucleus but accumulates in the cytoplasm in cells exposed to pheromones. Here we show that Far1p functions in both subcellular compartments: nuclear Far1p is required to arrest the cell cycle, whereas cytoplasmic Far1p is involved in the establishment of cell polarity. The subcellular localization of Far1p is regulated by two mechanisms: (1) Far1p contains a functional bipartite nuclear localization signal (NLS), and (2) Far1p is exported from the nucleus by Msn5p/Ste21p, a member of the exportin family. Cells deleted for Msn5p/Ste21p failed to export Far1p in response to pheromones, whereas overexpression of Msn5p/Ste21p was sufficient to accumulate Far1p in the cytoplasm in the absence of pheromones. Msn5p/Ste21p was localized in the nucleus and interacted with Far1p in a manner dependent on GTP-bound Gsp1p. Two-hybrid analysis identified a small fragment within Far1p that is necessary and sufficient for binding to Msn5p/Ste21p, and is also required to export Far1p in vivo. Finally, similar to Deltamsn5/ste21 strains, cells expressing a mutant Far1p, which can no longer be exported, exhibit a mating defect, but are able to arrest their cell cycle in response to pheromones. Taken together, our results suggest that nuclear export of Far1p by Msn5p/Ste21p coordinates the two separable functions of Far1p during mating.

Amino Acid Sequence↗

G2 cyclins are required for the degradation of G1 cyclins in yeast.

Progression of the eukaryotic cell cycle is controlled by cyclin-dependent kinases (CDKs). Cdc28, the budding yeast homologue of Cdc2 (Cdk1), is required for both the G1/S and G2/M transitions of the cell cycle. The functional specificity of the Cdc28 kinase is determined by its association with G1 or G2 cyclins. Alternation of cell cycle phases is thus mainly due to mechanisms that ensure that one cyclin family succeeds another. Here we show that the G2 cyclins Clb1, Clb2, Clb3 and Clb4 are required for the proteolysis of the G1 cyclins Cln1 and Cln2, providing a mechanism for coupling synthesis of G2 cyclins with the disappearance of G1 cyclins. Our data indicate that this pathway involves the Ubc9 ubiquitin-conjugating enzyme. The Cdc34 ubiquitin-conjugating activity may function redundantly with Ubc9, or it may only be involved in Cln1,2 turnover through its role in promoting the degradation of Sic1, a specific inhibitor of Cdc28-Clb complexes.

Anaphase-Promoting Complex-Cyclosome↗

Juvenile distal cerebral ischemia: angiographic features. A study of 55 cases.

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.

Adolescent↗

[Spinal cord ependymoma: contribution of MRI using gadolinium].

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.

Adult↗

[Rhythmical myoclonus and tremor at rest disclosing mesencephalic metastasis].

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.

Adenocarcinoma↗

[Guillain-Barré syndrome with favorable outcome in a case of recent human immunodeficiency virus infection].

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.

Adult↗

[11 cases of neuropathy induced by almitrine, of which one had optic neuropathy].

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.

Aged↗