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1.
J Neurogenet ; 36(4): 98-107, 2022.
Article in English | MEDLINE | ID: mdl-36415932

ABSTRACT

Alterations to the LRRK2 gene have been associated with Parkinson's disease and alcohol consumption in animals and humans. Furthermore, these disorders are strongly related to anxiety disorders (ADs). Thus, we investigated how the LRRK2 gene might influence anxiety in humans and mice. We elaborated a systematic review based on the PRISMA Statement of studies that investigated levels of anxiety in animal or human models with alterations in the LRRK2 gene. The search was conducted in the PubMed, Scopus, and Web of Science databases, and in reference lists with descriptors related to ADs and the LRRK2. From the 62 articles assessed for eligibility, 16 were included: 11 conducted in humans and seven, in mice. Lrrk2 KO mice and the LRRK2 G2019S, LRRK2 R1441G, and LRRK2 R1441C variants were addressed. Five articles reported an increase in anxiety levels concerning the LRRK2 variants. Decreased anxiety levels were observed in two articles, one focusing on the LRRK2 G2019S and the other, on the Lrrk2 KO mice. Eight other articles reported no differences in anxiety levels in individuals with Lrrk2 alterations compared to their healthy controls. This study discusses a possible influence between the LRRK2 gene and anxiety, adding information to the existing knowledge respecting the influence of genetics on anxiety.


Subject(s)
Parkinson Disease , Humans , Mice , Animals , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics , Parkinson Disease/genetics , Anxiety/genetics , Mutation
2.
Opt Lett ; 41(3): 488-91, 2016 Feb 01.
Article in English | MEDLINE | ID: mdl-26907404

ABSTRACT

Coherent anti-Stokes Raman scattering (CARS) spectra of N2 in the hybrid femtosecond/picosecond regime have been recorded with 0.7 cm(-1) resolution. The Q-branch rovibrational structure has been resolved, making it suitable for gas-phase simultaneous rotational and vibrational thermometry applications. Resolving this spectral structure requires synchronization of a narrowband picosecond probe pulse with a broadband femtosecond pair of pump and Stokes pulses. It is achieved using a single femtosecond ytterbium-laser source and a volume Bragg grating in a compact experimental arrangement.


Subject(s)
Nitrogen , Spectrum Analysis, Raman/methods , Thermometry/methods , Vibration , Air , Lasers , Rotation , Temperature , Time Factors
3.
Opt Lett ; 40(12): 2676-9, 2015 Jun 15.
Article in English | MEDLINE | ID: mdl-26076234

ABSTRACT

We demonstrate a nanosecond single-frequency nested cavity optical parametric oscillator (NesCOPO) based on orientation-patterned GaAs (OP-GaAs). Its low threshold energy of 10 µJ enables to pump it with a pulsed single-frequency Tm:YAP microlaser. Stable single-longitudinal-mode emission is obtained owing to Vernier spectral filtering provided by the dual-cavity doubly-resonant NesCOPO scheme. Crystal temperature tuning covers the 10.3-10.9 µm range with a quasi-phase-matching period of 72.6 µm. A first step toward the implementation of this device in a differential absorption lidar is demonstrated by carrying out short-range standoff detection of ammonia vapor around 10.4 µm. Owing to the single-frequency emission, interferences due to absorption by atmospheric water vapor can be discriminated from the analyte signal.

4.
Opt Lett ; 40(2): 280-3, 2015 Jan 15.
Article in English | MEDLINE | ID: mdl-25679864

ABSTRACT

We report on the first experimental investigation of the spectral dynamics of a synchronously pumped optical parametric oscillator (OPO) by use of dispersive Fourier transformation. For standard pumping rates, we observe a reproducible steady-state pulse-to-pulse spectrum. However, at high pumping levels, the OPO delivers pulse trains with nontrivial oscillatory spectral patterns. So as to benefit from a tailored broadband gain spectrum, the investigated OPO contains a chirped quasi-phase matching (QPM) nonlinear crystal. We explore the specific impacts of using such a remarkable parametric amplification medium where nonlinearly coupled frequencies vary with position. Depending on the QPM chirp rate sign, a red- or blue-shift of the emitted wavelength occurs when the OPO is switched on, leading to different spectral steady-states. These singular spectrotemporal dynamics are evidenced and explained for the first time.

5.
Opt Lett ; 39(23): 6719-22, 2014 Dec 01.
Article in English | MEDLINE | ID: mdl-25490661

ABSTRACT

We demonstrate the first emitter, based on a single optical source device, capable of addressing three species of interest (CO2, CH4, and H2O) for differential absorption Lidar remote sensing of atmospheric greenhouse gases from space in the 2 µm region. It is based on an amplified nested cavity optical parametric oscillator. The single frequency source shows a total conversion efficiency of 37% and covers the 2.05-2.3 µm range.

7.
Ann Phys Rehabil Med ; 57(1): 11-23, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24332786

ABSTRACT

OBJECTIVE: By proposing a new terminology (acquired deforming hypertonia or ADH) and a new definition for contractures, the main objective of this study was to establish their prevalence among institutionalized elderly patients. Secondary objectives were to analyze the negative impact of ADH and collect the opinions of clinicians on the possible treatments available. METHODOLOGY: A multicenter cross-sectional study was conducted among residents of 39 geriatric institutions (29 EHPAD and 10 USLD). All subjects presenting at least one ADH were surveyed over a one-week period. RESULTS: Among 3145 observed patients (mean age 88.9±9.7 years) 22% (n=692) presented at least one ADH. In average, each patient presented 4.4±3.2 ADHs. Negative consequences on self-care, nursing and difficulties in getting dressed were most frequently observed. Only 25.4% of clinicians considered the ADH to be potentially reversible. Physical therapy was the therapeutic option most frequently chosen over medication and surgery. CONCLUSION: This study confirms the important prevalence of ADH among elderly institutionalized patients. Consequences on the level of dependence were significant. It seems relevant to elaborate hierarchical therapeutic strategies in order to counter these disorders and the fatalism that ensues.


Subject(s)
Contracture/epidemiology , Homes for the Aged , Muscle Hypertonia/epidemiology , Nursing Homes , Activities of Daily Living , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , France/epidemiology , Humans , Male , Prevalence , Self Care , Terminology as Topic
9.
Genet Mol Res ; 11(1): 404-11, 2012 Feb 17.
Article in English | MEDLINE | ID: mdl-22370943

ABSTRACT

We examined a possible relationship between genes responsible for energy metabolism of the brain and addictive behavior in an animal model. We used non-inbred, Swiss mice exposed to a three-bottle free-choice model [water, 5% (v/v) ethanol, and 10% (v/v) ethanol] over a 16-week period, consisting of four phases: acquisition, withdrawal, reexposure, and quinine-adulteration. The mice were then behaviorally classified into three groups: loss-of-control-drinker (preference for ethanol and high levels of consumption during all phases, N = 6), heavy-drinker (preference for ethanol and high levels of consumption during acquisition and reduction during quinine-adulteration, N = 7), and light-drinker (preference for water during all phases, N = 10). Another group only received tap water (ethanol-naive control mice, N = 9). Further analysis using quantitative real-time PCR showed that in mice behaviorally classified as loss-of-control-drinkers, there was a significant inverse correlation between transcript levels of the Hadh gene and those of other energy metabolism genes in the nucleus of the amygdala, suggesting that this pathway may contribute to ethanol consumption in these mice. We conclude that cerebral energy metabolism is involved with ethanol addiction, meriting further study.


Subject(s)
Alcoholism/genetics , Amygdala/cytology , Brain Chemistry/physiology , Energy Metabolism , Receptors, GABA-B/metabolism , Alcohol Drinking/genetics , Alcoholism/metabolism , Animals , Behavior, Addictive/genetics , Disease Models, Animal , Ethanol/administration & dosage , Male , Mice
11.
Nat Commun ; 2: 425, 2011 Aug 09.
Article in English | MEDLINE | ID: mdl-21829187

ABSTRACT

For many years twin beams originating from parametric down-converted light beams have aroused great interest and attention in the photonics community. One particular aspect of the twin beams is their peculiar intensity correlation functions, which are related to the coincidence rate of photon pairs. Here we take advantage of the huge bandwidth offered by two-photon absorption in a semiconductor to quantitatively determine correlation functions of twin beams generated by spontaneous parametric down-conversion. Compared with classical incoherent sources, photon extrabunching is unambiguously and precisely measured, originating from exact coincidence between down-converted pairs of photons, travelling in unison. These results strongly establish that two-photon counting in semiconductors is a powerful tool for the absolute measurement of light beam photon correlations at ultrashort timescales.

13.
Opt Lett ; 36(5): 678-80, 2011 Mar 01.
Article in English | MEDLINE | ID: mdl-21368946

ABSTRACT

We report on a nested-cavity, doubly resonant optical parametric oscillator (NesCOPO) architecture for widely tunable, mid-IR, single-frequency generation. By use of an achromatic phase-adapted double-pass pumping scheme, this new, low-threshold, semimonolithic architecture only requires two free-standing cavity mirrors and a nonlinear crystal with a mirror coating deposited on its input facet while the other facet is antireflection coated. It is thus as simple and compact as any basic linear optical parametric oscillator cavity, is easily tunable, and displays low sensitivity to mechanical vibrations. Using a high-repetition-rate (4.8 kHz) microlaser as the pump source of the NesCOPO, we demonstrate a compact source that provides pulsed, stable single-frequency output over a wide spectral range (3.8-4.3 µm) with a high peak power (up to 50 W), which are properties well suited for practical gas sensing applications.

14.
Genet Mol Res ; 10(1): 65-74, 2011 Jan 18.
Article in English | MEDLINE | ID: mdl-21264817

ABSTRACT

Adrenoleukodystrophy is a neurodegenerative X-linked recessive disorder. It is characterized by abnormal function of peroxisomes, which leads to an accumulation of very long-chain fatty acids in plasma and tissues, especially in the cortex of adrenal glands and white matter of the central nervous system, causing demyelinating disease and adrenocortical insufficiency (Addison's disease). It is caused by a mutation in the ABCD1 gene (ATP-binding cassette, subfamily D, member 1), which encodes the protein adrenoleukodystrophy that is involved in the transport of fatty acids into the peroxisome for degradation. Variable expression has been recognized in families of patients who have this disease. A Brazilian family from Minas Gerais State, Brazil, was studied. The proband is an adult living in Minas Gerais State, Brazil; he had adrenomyeloneuropathy, adrenocortical insufficiency and a stable cerebral form. DNA was extracted from a blood sample and was sequenced to identify the mutation. The patient's exons were cloned for confirmation. A new mutation was found in exon 5 of the ABCD1 gene (c.1430delA), as well as a single-nucleotide polymorphism in exon 6. The mutation causes a frame shift, resulting in a truncated protein with almost total absence of the ATP binding domain.


Subject(s)
ATP-Binding Cassette Transporters/genetics , Adrenoleukodystrophy/genetics , Exons , Sequence Deletion , ATP Binding Cassette Transporter, Subfamily D, Member 1 , Adult , Base Sequence , Brazil , Female , Genetic Diseases, X-Linked/genetics , Humans , Male , Pedigree , Polymorphism, Single Nucleotide
15.
Ann Phys Rehabil Med ; 52(9): 668-83, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19729357

ABSTRACT

PURPOSE: To study the value and efficacy of botulinum toxin for treatment of cases of non-neurogenic detrusor overactivity (NNDO) that are refractory to anticholinergic drugs. MATERIALS AND METHODS: A systematic review of the literature, based on a keyword search of the Medline database. Selection of articles in French and English (meta-analyses, reviews, case studies and randomized, controlled clinical trials) on intradetrusor botulinum toxin injection in the management of refractory NNDO. RESULTS: Nineteen publications (including three randomized, controlled trials) were selected. Intradetrusor injection of botulinum toxin in patients with refractory NNDO has produced promising results, with a significant improvement in physical symptoms, urodynamic parameters and quality of life. The rare side effects consist primarily of dose-dependent urine retention. CONCLUSION: On the basis of preliminary data, botulinum toxin appears to be a valuable therapeutic option and fills the gap between anticholinergics and surgery in the treatment of NNDO that is refractory to anticholinergic agents. Botulinum toxin has a promising future in urology but requires further scientific evaluation.


Subject(s)
Botulinum Toxins/therapeutic use , Neuromuscular Agents/therapeutic use , Urinary Bladder, Overactive/drug therapy , Humans , Quality of Life , Urodynamics
16.
Genet Mol Res ; 8(2): 487-93, 2009 May 05.
Article in English | MEDLINE | ID: mdl-19551636

ABSTRACT

In view of the serious consequences of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and the absence of information about its incidence in the Brazilian population, we examined the frequency of the A985G mutation in the MCAD gene. A retrospective analysis was made of data on 1722 individuals (844 females) genotyped for the A985G mutation in the MCAD gene, using genomic DNA extracted from peripheral blood leukocytes and genotyping with PCR-RFLP; 0.41% of these individuals were heterozygous for the A985G mutation. The mutant homozygous genotype was not found. The 985G mutant and 985A normal alleles had allelic frequencies of 0.0020 and 0.9980, respectively. Given the A985G allele frequency, genotyping would be recommended in cases of family history of MCAD deficiency and sudden infant death syndrome, and when there is suspicion of medium-chain fatty acid metabolic alterations; genetic counseling should be offered in cases involving 985GG and A985G individuals and consanguineous marriages.


Subject(s)
Acyl-CoA Dehydrogenase/genetics , Gene Frequency/genetics , Mutation/genetics , Adolescent , Adult , Aged , Brazil , Child , Child, Preschool , Female , Genotype , Humans , Infant , Infant, Newborn , Male , Middle Aged , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Young Adult
17.
J Pathol ; 216(4): 451-9, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18798220

ABSTRACT

Immunotherapy by adoptive transfer of autologous tumour-infiltrating lymphocytes (TIL) shows promising clinical results for stage III (lymph nodes metastasis) melanoma patients, but some of them remain unresponsive. Here we analysed retrospectively the impact of resistance of melanoma cells to anti-proliferative cytokines on the clinical outcome of 24 TIL-treated metastatic melanoma patients. Patient relapse-free survival correlated significantly with Oncostatin M (OSM) and/or IL-6 sensitivity of melanoma cells, but not with interferon (IFN) gamma or tumour necrosis factor (TNF) alpha sensitivity. However, OSM/IL-6 sensitivity did not correlate with other known prognostic factors. Moreover, OSM and IL-6 were produced by TIL just before their injection to patients. In immunodeficient mice, OSM reduced human melanoma xenograft tumour growth, this effect being directly through inhibition of tumour cell proliferation rather than induction of apoptosis or necrosis. Thus, OSM/IL-6 resistance of melanoma cells appears to be a new escape mechanism to TIL treatment that could be added to the existing prognostic factors for early stage melanoma patients. This mechanism of action could be also relevant in other immunotherapy protocols, and could lead to better prognosis and anti-cancer treatments.


Subject(s)
Adoptive Transfer/methods , Interleukin-6/therapeutic use , Lymphocytes, Tumor-Infiltrating/transplantation , Melanoma/therapy , Oncostatin M/therapeutic use , Skin Neoplasms/therapy , Animals , Blotting, Western/methods , Cell Line, Tumor , Cell Proliferation/drug effects , Disease-Free Survival , Follow-Up Studies , Humans , Interleukin-6/metabolism , Lymphatic Metastasis , Lymphocytes, Tumor-Infiltrating/metabolism , Melanoma/drug therapy , Melanoma/pathology , Mice , Mice, Nude , Neoplasm Staging , Oncostatin M/metabolism , Receptors, Interleukin-6/metabolism , Receptors, Oncostatin M/metabolism , Retrospective Studies , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Xenograft Model Antitumor Assays
18.
Genet Mol Res ; 7(3): 687-94, 2008 Aug 05.
Article in English | MEDLINE | ID: mdl-18752196

ABSTRACT

Dopa-responsive dystonia (DRD), also known as Segawa syndrome or hereditary progressive dystonia with diurnal fluctuation, is clinically characterized by the occurrence of simultaneous or late Parkinsonism and by an excellent response to treatment with low doses of L-dopa. Diagnosis of DRD is essentially clinical. It is based on clinical history and the response to treatment with low doses of L-dopa. However, due to the low penetrance of the disease, asymptomatic carriers may exist. In these cases, mutational analysis of the GCH1 gene is an alternative to diagnose DRD. In the present study, we investigated a large DRD-carrier family in an attempt to identify the disease-causing mutation. The proband, a young woman diagnosed at the age of 13 years, is the daughter of a healthy non-consanguineous couple with history of several cases, on the maternal side of the family, of tip-toeing, disturbance of gait, Parkinsonism, rigidity and cramps in the lower limbs. Using single strand conformational polymorphism and DNA sequencing techniques to analyze DNA extracted from blood samples, we identified a mutation in the GCH1 gene, IVS5+3insT, which would preclude the formation of the active enzyme due to the formation of truncated peptides.


Subject(s)
Dystonic Disorders/genetics , GTP Cyclohydrolase/genetics , Adolescent , Brazil , DNA Mutational Analysis , Dystonic Disorders/drug therapy , Female , Humans , Introns , Levodopa/therapeutic use , Male , Mutation , Pedigree , Penetrance
19.
Opt Express ; 16(7): 4804-18, 2008 Mar 31.
Article in English | MEDLINE | ID: mdl-18542579

ABSTRACT

We show that optical parametric generation in a nonlinear crystal with a large group velocity mismatch between the pump and nearly-degenerate signal and idler is analogous to laser amplification in the medium with a gain recovery time comparable to the walk-off time. Based on this conclusion we propose to combine an OPO with a nonlinear saturable absorber or Kerr lens to generate directly high peak power sub-picosecond pulses using pump pulses ranging from tens of picoseconds to quasi-CW. Our analytical model predicts better than 80% photon conversion efficiency and pulse lengths that are of the order of a few hundred femtoseconds. Numerical simulations confirm our predictions and show that repetitive passive mode locking is feasible with a quasi-CW pump.


Subject(s)
Amplifiers, Electronic , Computer-Aided Design , Lasers , Models, Theoretical , Oscillometry/instrumentation , Computer Simulation , Equipment Design , Equipment Failure Analysis
20.
Oncogene ; 26(6): 881-92, 2007 Feb 08.
Article in English | MEDLINE | ID: mdl-16909117

ABSTRACT

Oncostatin M (OSM) is an interleukin-6 (IL-6) type cytokine originally described by its capacity to inhibit melanoma proliferation in vitro. Here, the mechanisms involved in resistance to growth inhibition by OSM were analysed for the first time on a large panel of metastatic melanoma cell lines. OSM resistance did not strictly correlate with IL-6, interferon-gamma or tumor necrosis factor-alpha resistance. Rather, it correlated with a specific loss of the OSM receptor-beta (OSMRbeta) subunit, in conjunction with a lower level of histone acetylation in the OSMRbeta promoter region. Treatment of various OSM-resistant melanoma cells with the histone deacetylase inhibitor Trichostatin A increased activity and histone acetylation of the OSMRbeta promoter as well as expression of OSMRbeta mRNA and protein, allowing OSM to activate the signal transducer and activator of transcription 3 (STAT3) and to inhibit proliferation. Other defects associated with OSM resistance were identified at the level of OSMRbeta transcription or protein expression, as well as downstream of or parallel to STAT3 activation. Altogether, our results suggest a role for OSM in the prevention of melanoma progression and that metastatic melanoma cells could escape this growth control by the epigenetic silencing of OSMRbeta.


Subject(s)
Melanoma/metabolism , Melanoma/pathology , Oncostatin M Receptor beta Subunit/metabolism , Acetylation , Base Sequence , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Resistance, Neoplasm , Gene Expression Regulation, Neoplastic , Histones/metabolism , Humans , Melanoma/genetics , Molecular Sequence Data , Neoplasm Metastasis/pathology , Oncostatin M/metabolism , Oncostatin M/pharmacology , Oncostatin M Receptor beta Subunit/genetics , Promoter Regions, Genetic/genetics , RNA, Messenger/genetics , STAT3 Transcription Factor/metabolism , Sensitivity and Specificity , Signal Transduction
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