The role of surface vertical mixing in phytoplankton distribution in a stratified reservoir

We investigated convection caused by surface cooling and mixing attributable to wind shear stress and their roles as agents for the transport of phytoplankton cells in the water column by carrying out two daily surveys during the stratified period of the Sau reservoir. Green algae, diatoms, and cryptophyceae were the dominant phytoplankton communities during the surveys carried out in the middle (July) and end (September) of the stratified period. We show that a system with a linear stratification and that is subject to weak surface forcing, with weak winds , < 4 m S (-1) and low energy dissipation rate values of the order of 1028 m2 s23 or lower, enables the formation of thin phytoplankton layers. These layers quickly disappear when water parcels mix because there is a medium external forcing (convection) induced by the night surface cooling, which is characterized by energy dissipation rates on the order of , 5x10(-8)m2s(-3). During both surveys the wind generated internal waves during the entire diurnal cycle. During the day, and because of the weak winds, phytoplankton layers rise in the water column up to a depth determined by both solar heating and internal waves. In contrast, during the night phytoplankton mixes down to a depth determined by both convection and internal waves. These internal waves, together with the wind-driven current generated at the surface, seem to be the agents responsible for the horizontal transport of phytoplankton across the reservoir.

Redirecció de l'especificitat de les cél·lules T contra epítops del VIH restringit per la HLA-A2 mitjaçant transferència genética

Existeixen creixents evidències què la resposta dels limfòcits T CD8+ alpha beta citotòxics (CTLs) és un element fonamental en la infecció produïda pel VIH. Les CTLs VIH especifiques es consideren molt importants en la reducció de la càrrega viral i en la contenció de la infecció. Encara que la combinació dels antiretrovirals (HAART) ha suposat una millora considerable en la lluita contra el VIH induint una important reducció de la càrrega viral i augmentant el nombre de cèl•lules T CD4+, diverses complicacions han fet ressaltar la necessitat de noves alternatives terapèutiques. Les complicacions inclouen: manca de recuperació d’una resposta immune sòlida contra el VIH, toxicitat a llarg termini de la teràpia i el descobriment que les cèl•lules T CD4+ constitueixen un reservori pel virus. Les noves alternatives controlaran la replicació viral i reconstituiran la immunitat. L’eficàcia de la immunoteràpia cel•lular amb transferència adoptiva de CTLs virals específics s’ha provat en diferents infeccions virals humanes, incloent el VIH. Proposem una modificació de la immunoteràpia adoptiva redirigint l’especificitat de les cèl•lules T contra el VIH mitjançant la transfecció dels gens del TCR. En aquest assaig preclínic, ens aprofitarem de la tecnologia dels animals transgènics per les molècules de HLA, amb la finalitat de generar TCRs d’alta afinitat dirigits contra epitops del VIH restringits per la molècula HLA. Aquests TCRs seran induïts in vivo i seleccionats in vitro. Les cadenes alpha i beta dels TCRs VIH específics procedents de les CTLs seran clonades mitjançant tècniques de biologia molecular. Aquests TCRs VIH específics seran transferits a cèl•lules T CD8+ humanes i la seva especificitat i capacitat citolítica contra cèl•lules diana que presentin antígens de VIH-1 s’estudiaran mitjançant la combinació de diverses tècniques noves (FCC, transfecció mitjançant Nucleoefector). Finalment, una construcció retroviral adient per la seva transducció en cèl•lules T humanes s’establirà amb un TCR òptim seleccionat.

Implication of Nerve Growth Factor in intestinal mucosal mast cell activity and colonic motor alterations in a model of ovalbumin-induced gut dysfunction in rats

We determined NGF involvement in MMCs and colonic motor alterations in an ovalbumin (OVA)-induced gut dysfunction model in rats. Animals received OVA (6 weeks), with/without simultaneous K252a (TrkA antagonist) treatment. MMCs, rat mast cell protease II (RMCPII) levels and colonic contractility in vitro were assessed. OVA increased MMC density and RMCPII concentration. Spontaneous contractility was similar in both groups and inhibited by K252a. Carbachol responses were increased by OVA in a K252a-independent manner. NO-synthase inhibition increased spontaneous activity in OVA-treated animals in a K252a-dependent manner. These observations support an involvement of NGF in the functional changes observed in this model.

Determination of vibrational polarizabilities and hyperpolarizabilities using field-induced coordinates

An analytical set of field-induced coordinates is defined and is used to show that the vibrational degrees of freedom required to completely describe nuclear relaxation polarizabilities and hyperpolarizabilities is reduced from 3N-6 to a relatively small number. As this number does not depend upon the size of the molecule, the process provides computational advantages. A method is provided to separate anharmonic contributions from harmonic contributions as well as effective mechanical from electrical anharmonicity. The procedures are illustrated by Hartree-Fock calculations, indicating that anharmonicity can be very important

Field-induced coordinates for the determination of dynamic vibrational nonlinear optical properties

Three conjugated organic molecules that span a range of polarity and valence-bond/charge transfer characteristics were studied. It was found that dispersion can be insignificant, and that adequate treatment can be achieved with frequency-dependent field-induced vibrational coordinates (FD-FICs)

A comparative analysis of two methods for the calculation of electric-field-induced perturbations to molecular vibration

Two common methods of accounting for electric-field-induced perturbations to molecular vibration are analyzed and compared. The first method is based on a perturbation-theoretic treatment and the second on a finite-field treatment. The relationship between the two, which is not immediately apparent, is made by developing an algebraic formalism for the latter. Some of the higher-order terms in this development are documented here for the first time. As well as considering vibrational dipole polarizabilities and hyperpolarizabilities, we also make mention of the vibrational Stark effec

Role of the cannabinoid system in the effects induced by nicotine on anxiety-like behaviour in mice

Rationale: Acute behavioural effects and motivational responses induced by nicotine can be modulated by the endocannabinoid system supporting the existence of a physiological interaction between these two systems. Objectives: The present study was designed to examine the possible involvement of the cannabinoid system in the anxiolytic- and anxiogenic-like responses induced by nicotine in mice. Methods: Animals were only exposed once to nicotine. The acute administration of low (0.05, sc) or high (0.8 mg/kg, sc) doses of nicotine produced opposite effects in the elevated plus-maze, i.e., anxiolytic- and anxiogenic-like responses, respectively. The effects of the pretreatment with the CB1 cannabinoid receptor antagonist, rimonabant (0.25, 0.5 and 1 mg/kg, ip), and the cannabinoid agonist, 9-tetrahydrocannabinol (0.1 mg/kg, ip), were evaluated on the anxiolytic- and anxiogenic-like responses induced by nicotine. Results: Rimonabant completely abolished nicotine-induced anxiolytic-like effects and increased the anxiogenic-like responses of nicotine, suggesting an involvement of CB1 receptors in these behavioural responses. On the other hand, 9-tetrahydrocannabinol failed to modify nicotine anxiolytic-like responses, but attenuated its anxiogenic-like effects. In addition the association of non-effective doses of 9-tetrahydrocannabinol and nicotine produced clear anxiolytic-like responses. Conclusions: These results demonstrate that the endogenous cannabinoid system is involved in the regulation of nicotine anxiety-like behaviour in mice, and provide new findings to support the use of cannabinoid antagonists in the treatment of tobacco addiction.

Attenuation of nicotine-induced antinociception, rewarding effects, and dependence in mu-opioid receptor knock-out mice

The involvement of μ-opioid receptors in different behavioral responses elicited by nicotine was explored by using μ-opioid receptor knock-out mice. The acute antinociceptive responses induced by nicotine in the tail-immersion and hot-plate tests were reduced in the mutant mice, whereas no difference between genotypes was observed in the locomotor responses. The rewarding effects induced by nicotine were then investigated using the conditioning place-preference paradigm. Nicotine produced rewarding responses in wild-type mice but failed to produce place preference in knock-out mice, indicating the inability of this drug to induce rewarding effects in the absence of μ-opioid receptors. Finally, the somatic expression of the nicotine withdrawal syndrome, precipitated in dependent mice by the injection of mecamylamine, was evaluated. Nicotine withdrawal was significantly attenuated in knock-out mutants when compared with wild-type mice. In summary, the present results show that μ-opioid receptors are involved in the rewarding responses induced by nicotine and participate in its antinociceptive responses and the expression of nicotine physical dependence.

Vitamin E but not 17B-estradiol protect against vascular toxicity induced by B-amyloid wild type and the Dutch amyploid variant

Amyloid β-peptide (Aβ) fibril deposition on cerebral vessels produces cerebral amyloid angiopathy that appears in the majority of Alzheimer's disease patients. An early onset of a cerebral amyloid angiopathy variant called hereditary cerebral hemorrhage with amyloidosis of the Dutch type is caused by a point mutation in Aβ yielding AβGlu22→Gln. The present study addresses the effect of amyloid fibrils from both wild-type and mutated Aβ on vascular cells, as well as the putative protective role of antioxidants on amyloid angiopathy. For this purpose, we studied the cytotoxicity induced by Aβ1–40 Glu22→Gln and Aβ1–40 wild-type fibrils on human venule endothelial cells and rat aorta smooth muscle cells. We observed that AβGlu22→Gln fibrils are more toxic for vascular cells than the wild-type fibrils. We also evaluated the cytotoxicity of Aβ fibrils bound with acetylcholinesterase (AChE), a common component of amyloid deposits. Aβ1–40 wild-type–AChE fibrillar complexes, similar to neuronal cells, resulted in an increased toxicity on vascular cells. Previous reports showing that antioxidants are able to reduce the toxicity of Aβ fibrils on neuronal cells prompted us to test the effect of vitamin E, vitamin C, and 17β-estradiol on vascular damage induced by Aβwild-type and AβGlu22→Gln. Our data indicate that vitamin E attenuated significantly the Aβ-mediated cytotoxicity on vascular cells, although 17β-estradiol and vitamin C failed to inhibit the cytotoxicity induced by Aβ fibrils.

Disease-corrected haematopoietic progenitors from Fanconi anemia induced pluripotent stem cells

The generation of induced pluripotent stem (iPS) cells has enabled the derivation of patient-specific pluripotent cells andprovided valuable experimental platforms to model human disease. Patient-specific iPS cells are also thought to hold greattherapeutic potential, although direct evidence for this is still lacking. Here we show that, on correction of the genetic defect,somatic cells from Fanconi anaemia patients can be reprogrammed to pluripotency to generate patient-specific iPS cells. These cell lines appear indistinguishable from human embryonic stem cells and iPS cells from healthy individuals. Most importantly, we show that corrected Fanconi-anaemia-specific iPS cells can give rise to haematopoietic progenitors of the myeloid and erythroid lineages that are phenotypically normal, that is, disease-free. These data offer proof-of-concept that iPS cell technology can be used for the generation of disease-corrected, patient-specific cells with potential value for cell therapy applications.

Generation of mouse-induced pluripotent stem cells by transient expression of a single nonviral polycistronic vector

Induced pluripotent stem (iPS) cells have generated keen interestdue to their potential use in regenerative medicine. They havebeen obtained from various cell types of both mice and humans byexogenous delivery of different combinations of Oct4, Sox2, Klf4,c-Myc, Nanog, and Lin28. The delivery of these transcription factorshas mostly entailed the use of integrating viral vectors (retrovirusesor lentiviruses), carrying the risk of both insertional mutagenesisand oncogenesis due to misexpression of these exogenousfactors. Therefore, obtaining iPS cells that do not carry integratedtransgene sequences is an important prerequisite for their eventualtherapeutic use. Here we report the generation of iPS cell linesfrom mouse embryonic fibroblasts with no evidence of integrationof the reprogramming vector in their genome, achieved by nucleofectionof a polycistronic construct coexpressing Oct4, Sox2, Klf4,and c-Myc