Miracle-dz/UniFAR-FTUs huggingface dataset:
Modification de l'expression de gènes impliqués dans le métabolisme cérébral du cholestérol par l'exposition à l'alcool et à la cocaïne

L’addiction aux drogues est une maladie comportementale recidivante caracterisee par une recherche et une prise compulsive de drogues, une perte de controle sur la prise malgre les consequences negatives et l’emergence d'un etat emotionnel negatif lors de l’absence de la drogue. L’addiction implique des neuroadaptations cerebrales persistantes. Des etudes recentes montrent que le cholesterol joue un role crucial dans le fonctionnement cerebral en participant a divers processus cellulaires et, en particulier, au controle de la neurotransmission. L’objectif de ce travail de these consistait a etudier l’implication potentielle du metabolisme du cholesterol dans l’addiction et en particulier si ce metabolisme etait affecte par les drogues d’abus. Dans ce travail, nous avons etudie l’expression de genes codant des proteines impliquees dans le metabolisme du cholesterol cerebral apres une consommation volontaire chronique d’alcool par des rats et apres des injections aigues ou chroniques de cocaine. Nous avons analyse l’expression de ces genes dans des structures cerebrales impliquees dans l’addiction, notamment le cortex prefrontal, le noyau accumbens, l’amygdale et l’hippocampe. Nous avons trouve que l’exposition a l’alcool et a la cocaine modifient l’expression des proteines impliquees dans la synthese, le transport et la degradation du cholesterol de facon specifique de la drogue, du traitement (aigu/chronique) et de la region cerebrale etudiee. Dans une deuxieme partie de la these, nous avons utilise une approche virale permettant de surexprimer la CYP46A1, l’enzyme de degradation du cholesterol cerebral dans le cortex prefrontal afin d’evaluer l’impact de cette surexpression sur la recherche de cocaine dans un modele de rechute. La surexpression de la CYP46A1dans cette structure n’a eu aucun impact sur la recherche de cocaine. Des etudes futures seront necessaires pour determiner si l’alteration de l’expression de cette enzyme dans d’autres structures, comme par exemple le noyau accumbens, pourrait avoir des effets benefiques sur la rechute. L’ensemble de ces travaux montrent que l’exposition aux drogues d’abus modulerait le metabolisme cerebral du cholesterol dans certaines structures cerebrales. Ce projet de these ouvre de nouvelles perspectives quant au role du metabolisme du cholesterol cerebral dans l’addiction, et il pourrait en resulter de nouvelles therapeutiques dans le traitement de cette maladie psychiatrique couteuse.
A Novel Stator and Rotor Dual PM Vernier Motor With Space Vector Pulse Width Modulation

In this paper, an electric machine with dual permanent magnet (PM) structures in both stator and rotor is proposed. Multi-pole PMs are buried both in stator and rotor slots of the proposed machine and the magnetic field is modulated through the stator and rotor teeth. This machine with dual magnetic flux modulation can be categorized as one special case of flux-modulating machines. A time-stepping finite-element method combined with space vector pulse width modulation-based vector control method is used to analyze the steady-state and transient performance of the machine and its control system.
Low-cost computationally hyperspectral simulator for highly dynamic marine environments

Hyperspectral optical observations and the development of new processing strategies are key for a better understanding of complex marine ecosystems and space-time distribution of ecological parameters. In this paper, the methodologies to implement a simulator of hyperspectral-resolved optical data corresponding to highly dynamic marine environments are presented. The simulator is based on a coupled radiative transfer and Lagrangian hydrodynamic model, which is organized in four basic blocks: a hydrodynamic model, a particle tracking model, a transformation function and a radiative transfer model. The transformation function is needed to adapt the output of the tracking model (given in number of particles per unit volume) to mass concentration, suitable for the radiative transfer model. The transformation function has been derived considering an allometric relationship between both magnitudes, since it is found in nature. The simulator is finally tested by considering the Alfacs Bay (NW Mediterranean Sea), as a case study site.
Interleukin-12 as an adjuvant for cancer immunotherapy.

Interleukin-12 (IL-12) is a cytokine whose main effect is to drive Th-cell differentiation throughout a T helper type 1 cell type of response, thus inducing interferon gamma (IFNgamma) and favoring a switch from Ig to IgG2a. These properties make IL-12 a candidate adjuvant for vaccination against cancer and infection disease. Enthusiasm was generated in many animal studies where IL-12 was given either systemically or locally. The experience of some toxicity in humans has hampered its further development into clinical applications, which, however, are still possible if restricted to local administration. Gene transfer seems to be the preferred approach to obtain this local release of cytokine. Here we review the applications of IL-12 as adjuvant.
Simultaneous measurement of right and left ventricular volume by the conductance catheter technique in the newborn lamb.

BACKGROUND Measurement of absolute ventricular volume with the conductance catheter technique has been documented extensively for the left ventricle (LV). More recently, the same technique has been applied in studies of right ventricular (RV) performance. In the present study we performed simultaneous measurements of LV and RV volumes. Conversion of measured conductances to absolute volumes requires the assessment of slope factor alpha (α) and parallel conductance correction volume (Vc) for both the RV and LV. We investigated the magnitude and variability of these calibration factors during a typical study period of four hours. METHODS In five anaesthetised, ventilated newborn lambs, conductance catheters were introduced into the LV and RV and a thermodilution catheter was positioned in the pulmonary artery. Alphas and Vc's were determined by thermodilution and hypertonic saline dilution, respectively, at one hourly intervals. At the same time points, biventricular haemodynamic parameters were obtained. Results were analysed by multiple linear regression analysis. RESULTS During the course of the experiments all haemodynamic parameters were stable. There were no significant changes in Vc or α for either ventricle. RV-Vc was systematically higher than LV-Vc: both as absolute values and as percentage of the uncalibrated conductance signal (79% for RV, and 49% for LV, respectively). This probably reflects the geometrical differences of the two ventricles. Right ventricular ejection fraction (RV-EF) was higher than left ventricular ejection fraction (LV-EF), and neither changed significantly during four hours. CONCLUSION These results show that calibration factors α and Vc for the RV, as well as EF, show values that are consistent with the observed haemodynamic stability and in line with the LV factors. These results indicate that the conductance catheter method can be used satisfactorily for biventricular function assessment.
The effect of interventions to prevent and treat malnutrition in patients admitted for rehabilitation: a systematic review with meta-analysis.

BACKGROUND Malnutrition occurs frequently among patients in rehabilitation, leading to poorer outcomes. Evidence of the effects of interventions to prevent or treat malnutrition is required to guide clinical practice in this setting. This systematic review aimed to determine the effect of oral nutrition interventions implemented in rehabilitation on nutritional and functional outcomes. METHODS Five databases were searched to identify relevant publications; intervention trials of oral nutrition interventions (such as oral nutrition supplements, foodservice interventions, clinical care processes, enhanced eating environments) conducted with patients admitted for rehabilitation, reporting dietary intake, anthropometric, biochemical or functional outcomes. The reviewers determined study eligibility and assessed the included studies for risk of bias. Outcome data were combined narratively and by meta-analyses. RESULTS From 1765 publications, 10 studies trialling oral nutrition supplements, foodservice interventions and clinical care processes (of neutral or positive quality) were identified. Compared to meals alone, oral nutritional supplements significantly improved energy and protein intake, with some evidence for improvements in anthropometry and length of stay. There was little evidence that speciality supplements were beneficial compared to standard versions. Meta-analyses demonstrated significantly greater energy [weighted mean difference (WMD) = 324 kcal, 212-436 kcal 95% confidence interval (CI)] and protein (WMD = 9.1 g, 0.2-17.9 g 95% CI) intake with energy dense meals. Opposing results were reported in studies investigating enhanced clinical care processes. CONCLUSIONS The provision of oral nutrition supplements and energy dense meals improved energy and protein intake and therefore may comprise effective strategies for addressing malnutrition in rehabilitation. The effect of these strategies on other nutritional and functional outcomes should be explored further.
Current status and future strategy for development of medicinal plants sector in Uttaranchal, India

As elsewhere, in the Indian Himalayan Region, ethnic communities in the state of Uttaranchal rely, to a large extent, on native plant species for sustenance of their traditional health-care system, both logistically as well as economically. However, the present scenario shows a decline in these traditional, plant-based health-care practices. These age-old practices are conservation-oriented and have tremendous potential to uplift the state economy. The excessive extraction of medicinal plant resources for use in the pharmaceutical industry has resulted in ruthless destruction of natural populations of medicinal plants. This work attempts to assess the current status of knowledge of medicinal plant resources of the state. It also focuses on the importance of documenting traditional knowledge and practices related to conservation and sustainable utilization of medicinal plants in Uttaranchal. A collaborative work plan involving scientists, government institutions and non-governmental organizations is suggested for preserving the traditional knowledge system and practices, conservation of medicinal plants and upliftment of the rural economy of this mountain state.
Absence of Activation-induced Cytidine Deaminase, a Regulator of Class Switch Recombination and Hypermutation in B Cells, Suppresses Aorta Allograft Vasculopathy in Mice

Background Antibody-mediated rejection is caused in part by increasing circulation/production of donor-specific antibody (DSA). Activation-induced cytidine deaminase (AID) is a key regulator of class switch recombination and somatic hypermutation of immunoglobulin in B cells, yet its role in antibody-mediated transplant rejection remains unclear. We show here that AID deficiency in mice enables suppression of allograft vasculopathy (AV) after aorta transplantation, a DSA-mediated process. Methods Splenocytes from C57BL/6 J (B6) AID−/− mice were used for determining in vitro proliferation responses, alloreactivity, cell surface marker expression, and antibody production. BALB/c mouse aortas were transplanted into B6 AID−/− mice with or without FK506 treatment. Blood and aorta grafts were harvested on day 30 after transplantation and were subjected to DSA, histological, and immunohistological analyses. Results The AID−/− splenocytes were comparable to wild type splenocytes in proliferation responses, alloreactivity, and expression of cell surface markers in vitro. However, they completely failed to produce immunoglobulin G, although they were not impaired in immunoglobulin M production relative to controls. Furthermore, BALB/c aorta grafts from B6 AID−/− recipient mice on day 30 after transplantation showed reduced signs of AV compared to the grafts from B6 wild type recipient mice which had severe vascular intimal hyperplasia, interstitial fibrosis, and inflammation. Treatment with FK506 produced a synergistic effect in the grafts from AID−/− recipients with further reduction of intimal hyperplasia and fibrosis scores. Conclusions The AID deficiency inhibits DSA-mediated AV after aorta transplantation in mice. We propose that AID could be a novel molecular target for controlling antibody-mediated rejection in organ transplantation.
Twisted Gastrulation Modulates Bone Morphogenetic Protein-induced Collagen II and X Expression in Chondrocytes in Vitro and in Vivo*

Twisted gastrulation (TSG) is an extracellular modulator of bone morphogenetic protein (BMP) activity and regulates dorsoventral axis formation in early Drosophila and Xenopus development. Studies on tsg-deficient mice also indicated a role of this protein in skeletal growth, but the mechanism of TSG activity in this process has not yet been investigated. Here we show for the first time by in situ hybridization and immunohistochemistry that TSG is strongly expressed in bovine and mouse growth plate cartilage as well as in fetal ribs, vertebral cartilage, and cartilage anlagen of the skull. Furthermore we provide evidence that TSG is directly involved in BMP-regulated chondrocyte differentiation and maturation. In vitro, TSG impaired the dose-dependent BMP-2 stimulation of collagen II and X expression in cultures of MC615 chondrocytes and primary mouse chondrocytes. In the presence of chordin, a BMP antagonist, the inhibitory effect of TSG was further enhanced. TSG also inhibited BMP-2-stimulated phosphorylation of Smad factors in chondrocytes, confirming the role of TSG as a modulator of BMP signaling. For analysis of TSG functions in cartilage development in vivo, the gene was overexpressed in transgenic mice under the control of the cartilage-specific Col2a1 promoter. As a result, Col10a1 expression was significantly reduced in the growth plates of transgenic embryos and newborns in comparison with wild type littermates as shown by in situ hybridization and by real time PCR analysis. The data suggest that TSG is an important modulator of BMP-regulated cartilage development and chondrocyte differentiation.
Observations on the effects of vibration stress and sound on pregnancy, parturition and respiration in the rabbit

Rabbits, 5-29 days pregnant, were placed for 2 h either in or near a machine designed to simulate transport, which exposed them to vibration stress and sound. There was no apparent effect on the maintenance of pregnancy, gestation length, litter size, perinatal mortality or condition of the young at birth compared with control rabbits. However, respiration rate, normally 65/min, was increased to 120/min by moving the animals from their cages and to 160/min in the machine; noise alone produced an intermediate response. Respiration returned to normal values after 20 min to 4 h, depending upon the initial level of response.
Lysosomal acid lipase A and the hypercholesterolaemic phenotype

Purpose of review Mutations in lysosomal acid lipase A (LIPA) result in two phenotypes depending on the extent of lysosomal acid lipase (LAL) deficiency: the severe, early-onset Wolman disease or the less severe cholesteryl ester storage disease (CESD). In CESD, the severity of the symptoms, hepatomegaly and hypercholesterolaemia, can be highly variable, presenting in childhood or adulthood. Therefore, it is likely that many patients are undiagnosed or misdiagnosed. Nevertheless, LAL deficiency has been recognized for more than 25 years, but adequate therapeutic strategies are limited. Recent findings CESD has an estimated prevalence of one in 90 000 to 170 000 individuals in the general population, confirming the likelihood that this disease is currently underdiagnosed. A number of studies have shown that in LIPA deficient patients the hypercholesterolaemic phenotype can be attenuated using statin therapy, and favourable effects on reduction of lipid accumulation in lysosomes have been reported. Targeting lysosomal exocytosis with LAL replacement therapy was shown to be successful in animal models and recently a phase I/II study demonstrated its safety and its potential metabolic efficacy on transaminase levels. Summary The hypercholesterolaemic phenotype in CESD can be difficult to distinguish from other known hypercholesterolaemic disorders. In the majority of CESD cases with hypercholesterolaemia favourable responses on statin treatment are observed, but the effect on reduction of lipid accumulation in lysosomes needs to be further evaluated. Combining statins with LAL replacement therapy may provide a promising approach for optimal treatment of LIPA deficiencies in the future.
Identification and Characterization of a Stereospecific Human Enzyme That Catalyzes 9-cis-Retinol Oxidation

All-trans- and 9-cis-retinoic acid are active retinoids for regulating expression of retinoid responsive genes, serving as ligands for two classes of ligand-dependent transcription factors, the retinoic acid receptors and retinoid X receptors. Little is known, however, regarding 9-cis-retinoic acid formation. We have obtained a 1.4-kilobase cDNA clone from a normalized human breast tissue library, which when expressed in CHO cells encodes a protein that avidly catalyzes oxidation of 9-cis-retinol to 9-cis-retinaldehyde. This protein also catalyzes oxidation of 13-cis-retinol at a rate approximately 10% of that of the 9-cis isomer but does not catalyze all-trans-retinol oxidation. NAD+ was the preferred electron acceptor for oxidation of 9-cis-retinol, although NADP+ supported low rates of 9-cis-retinol oxidation. The rate of 9-cis-retinol oxidation was optimal at pHs between 7.5 and 8. Sequence analysis indicates that the cDNA encodes a protein of 319 amino acids that resembles members of the short chain alcohol dehydrogenase protein family. mRNA for the protein is most abundant in human mammary tissue followed by kidney and testis, with lower levels of expression in liver, adrenals, lung, pancreas, and skeletal muscle. We propose that this cDNA encodes a previously unknown stereospecific enzyme, 9-cis-retinol dehydrogenase, which probably plays a role in 9-cis-retinoic acid formation.
Transfer of Diabetes in the NOD-scid Mouse by CD4 T-Cell Clones: Differential Requirement for CD8 T-Cells

Transfer of an interleukin 2/interferon-γ-secreting islet-specific CD4+ T-cell clone, BDC-6.9, in the immunodeficient NOD-scid mouse induces destruction of pancreatic β-cells without help from host B-cells, CD4+ T-cells, or CD8+ T-cells. However, a second islet-specific T-cell clone, BDC-2.5, showing the same cytokine profile and T-cell receptor Vβ expression as BDC-6.9 was not capable of inducing diabetes or insulitis in NOD-scid mice. Even though BDC-2.5 by itself readily induces diabetes in young unmanipulated NOD mice, cotransfer of CD8-enriched T-cells was required to induce disease in NOD-scid mice. Immunohistochemical staining of pancreatic lesions in young NOD mice receiving either BDC-2.5 or BDC-6.9 showed the presence of CD4+, CD8+, Vβ4+, and MAC-1+ cells within the infiltrate, similar to infiltrates in lesions of spontaneously diabetic female NOD mice. In contrast, NOD-scid mice that received BDC-6.9 showed only the presence of CD4+Vβ4+ T-cells and a large population of MAC-1+ cells in islet lesions. NOD-scid recipients of cotransferred BDC-2.5/CD8+ splenic T-cells showed a small population of CD4+ T-cells and a larger population of CD8+ T-cells within the infiltrated islets, whereas no infiltrate was detectable in recipients of CD8+ splenocytes or BDC-2.5 alone. Our results suggest that at least two types of islet-specific CD4+ T-cell clones play a role in diabetes pathogenesis.
General Modulation Strategy for Seven-Phase Inverters With Independent Control of Multiple Voltage Space Vectors

This paper focuses on the analysis of a seven-phase voltage-source inverter for high-performance motor drives. The problem of the modulation strategy of the inverter is solved by combining the multiple space vector representation with traditional carrier-based pulsewidth modulation. This approach leads to the definition of a general modulation strategy that can be usefully utilized in multimotor drives, as well as in multiphase motor drives for improving the torque density. The inverter output voltage capability is investigated, showing that the proposed modulation strategy is able to fully exploit the dc input voltage either in sinusoidal or nonsinusoidal operating conditions. The results obtained in the analytical investigation are confirmed by experimental tests.
Design and optimization of high-efficiency resonant wireless power transfer system

Magnetic resonant coupling is widely considered a promising candidate for the midrange transfer of power because of its long range and compact dimensions. This paper reports the process of designing a high-efficiency resonant wireless power transfer (RWPT) system. It discusses the optimal parameters for maintaining high power transfer efficiency with respect to distance and load variations. The design method is based on circuit theory, analytical derivation, and the use of Matlab to find the relationships of the parameters and to simulate the overall system. The analytical derivation is used for determining the average values of voltage and power in the circuit. The proposed system consists of a class E amplifier with a 6.78 MHz resonant frequency, coupling coils, and a class E rectifier. With a mutual inductance coefficient of k = 0.2, the expected efficiency is 93% for a power of 5 W.
GRP78 and Raf‐1 cooperatively confer resistance to endoplasmic reticulum stress‐induced apoptosis

The chaperone glucose‐regulated protein, 78/immunoglobulin binding protein (GRP78/Bip), protects cells from cytotoxicity induced by DNA damage or endoplasmic reticulum (ER) stress. In this study, we showed that GRP78 is a major inducible protein in human non‐small cell lung cancer H460 cells treated with ER stress inducers, including A23187 and thapsigargin. AEBSF, an inhibitor of serine protease, diminished GRP78 induction, enhanced mitochondrial permeability, and augmented apoptosis in H460 cells during ER stress. Simultaneously, AEBSF promoted Raf‐1 degradation and suppressed phosphorylation of Raf‐1 at Ser338 and/or Tyr340 during ER stress. Coimmunoprecipitation assays and subcellular fractionations showed that GRP78 associated and colocalized with Raf‐1 on the outer membrane of mitochondria, respectively. While treatment of cells with ER stress inducers inactivated BAD by phosphorylation at Ser75, a Raf‐1 phosphorylation site; AEBSF attenuated phosphorylation of BAD, leading to cytochrome c release from mitochondria. Additionally, overexpression of GRP78 and/or Raf‐1 protected cells from ER stress‐induced apoptosis. Taken together, our results indicate that GRP78 may stabilize Raf‐1 to maintain mitochondrial permeability and thus protect cells from ER stress‐induced apoptosis. J. Cell. Physiol. 215: 627–635, 2008. © 2007 Wiley‐Liss, Inc.
Using canalography to visualize the in vivo aqueous humor outflow conventional pathway in humans.

Amicrocatheter filled with 1.25 μg of indocyanine green (ICG) diluted in 1 mL of viscoelastic solution was placed into the Schlemm canal (SC) to enlarge the drainage canal; the dye was then injected into the SC. Near-infrared fluorescence real images of aqueous humor outflow structures in in vivo human eyes were obtained. A, Introduction of the flexible microcatheter into the lumen of the SC. B, Infrared picture at the beginning of ICG injection. C, After injection of ICG plus viscoelastic, visualization of the SC, collector channels, and 3 aqueous veins (arrowheads). The fourth aqueous vein is masked by themicrocatheter. D, Higher-magnification image showing in detail the aqueous vein morphology. Themethod is simple and safe andmakes possible the real visualization of the aqueous humor outflow system during canaloplasty. Proteomic Landscape of the Choroid-RPE Complex Original Investigation Research