Ana Silva - Academia.edu (original) (raw)
Papers by Ana Silva
Physics Letters B, 2015
The calculated position resolutions for X-ray photons (1-60 keV) in pure noble gases at atmospher... more The calculated position resolutions for X-ray photons (1-60 keV) in pure noble gases at atmospheric pressure are presented. In this work we show the influence of the atomic shells and the detector dimensions on the intrinsic position resolution of the used noble gas. The calculated results were obtained by using a new software tool, Degrad, and compared to the available experimental data.
Hormones and Behavior, 2015
The neuroendocrine control of intraspecific aggression is a matter of current debate. Although ag... more The neuroendocrine control of intraspecific aggression is a matter of current debate. Although aggression in a reproductive context has been associated with high levels of circulating androgens in a broad range of species, it has also been shown to occur during the non-breeding season when gonads are regressed and plasma steroid hormone levels are low. In mammals and birds the aromatization of androgens into estrogens plays a key role in the regulation of aggression in both the breeding and non-breeding seasons. This is the first study in a teleost fish to explore the role of steroids in the modulation of non-breeding aggression. Gymnotus omarorum is a highly aggressive teleost fish that exhibits aggression all year-round. We analyzed male-male non-breeding agonistic behavior, compared circulating 11-Ketotestosterone (11-KT) levels between dominants and isolated males, assessed the regulatory role of aromatization of androgens into estrogens, and evaluated the gonads as a source of these sex steroids. We found that high levels of aggression occurred in the non-breeding season despite low plasma 11-KT levels, and that there was no difference in 11-KT levels between dominant and isolated males. We demonstrated that acute aromatase inhibition decreased aggression, distorted contest dynamics, and affected expected outcome. We also found that castrated individuals displayed aggressive behavior indistinguishable from non-castrated males. Our results show, for the first time in teleost fish, that territorial aggression of G. omarorum during the non-breeding season depends on a non-gonadal estrogenic pathway.
International Journal of Migration, Health and Social Care, 2009
The paper addresses diversity, multi‐culturalism and mental health. It reports qualitative data f... more The paper addresses diversity, multi‐culturalism and mental health. It reports qualitative data from a larger project on multi‐cultural counselling competencies in Portugal which sought to meet the needs identified by specific minority groups by developing integrative, responsive and culturally sensitive treatments. A qualitative study is presented, with the aim of exploring the representations of mental health and illness held by ethnic minority groups in Portugal, as well as their specific needs and obstacles encountered in their interactions with health professionals. Semi‐structured interviews were conducted, and the results indicate that the meanings of health and mental health varied. Meanings of psychological health were related to general well‐being. Help‐seeking behaviours were associated with providing and receiving family and social support, mainly among participants of African descent. Although the great majority of participants had had no experience of counselling or ps...
Frontiers in behavioral neuroscience, 2010
Social behavior diversity is correlated with distinctively distributed patterns of a conserved br... more Social behavior diversity is correlated with distinctively distributed patterns of a conserved brain network, which depend on the action of neuroendocrine messengers that integrate extrinsic and intrinsic cues. Arginine vasotocin (AVT) is a key integrator underlying differences in behavior across vertebrate taxa. Weakly electric fish use their electric organ discharges (EODs) as social behavioral displays. We examined the effect of AVT on EOD rate in two species of Gymnotiformes with different social strategies: Gymnotus omarorum, territorial and highly aggressive, and Brachyhypopomus gauderio, gregarious and aggressive only between breeding males. AVT induced a long-lasting and progressive increase of EOD rate in isolated B. gauderio, partially blocked by the V1a AVT receptor antagonist (Manning compound, MC), and had no effects in G. omarorum. AVT also induced a long-lasting increase in the firing rate (prevented by MC) of the isolated medullary pacemaker nucleus (PN) of B. gauder...
Journal of Experimental Biology, 2004
SUMMARYIn contrast to most of the previous studies in gymnotiform reproduction,which have been co... more SUMMARYIn contrast to most of the previous studies in gymnotiform reproduction,which have been conducted in the tropical region, this study examines a gymnotid from the temperate region in both the natural habitat and the laboratory. The gonadal histology of Brachyhypopomus pinnicaudatus is described for the first time. The male had a paired, lobular testis of the unrestricted spermatogonial type, and females a paired saccular cystovary. Analysis of gonads and their annual cycle enabled us to confirm the breeding season and to conclude that this species is a multiple spawner. Water temperature and photoperiod showed the expected annual cycles for the region. High temperature and a 14 h:10 h L:D photoperiod in the natural habitat coincided with (1) mature gonadal stages, (2) electrophysiological sexual dimorphism: males present a lengthened negative phase in their electric organ discharge (EOD) and (3) decreased temperature sensitivity of the EOD: the waveform does not change when te...
Synlett, 2009
Abstract Condensation adducts of the Ni (II) and Cu (II) complexes of β-amino-meso-tetraphenylpor... more Abstract Condensation adducts of the Ni (II) and Cu (II) complexes of β-amino-meso-tetraphenylporphyrin with dimethyl acetylenedicarboxylate (DMAD) and diethyl ethoxymethylenemalonate were converted into the corresponding esters of pyridinone-...
Proceedings of the National Academy of Sciences, 2014
Significance Interleukin (IL)-7 is critical for the maintenance of the peripheral T-cell compartm... more Significance Interleukin (IL)-7 is critical for the maintenance of the peripheral T-cell compartment of the adaptive immune system. Our study identifies a role for the Nuclear Factor κ-B (NF-κB) signalling pathway in the control of IL-7 receptor expression by T cells. Following thymic selection, new T cells specifically up-regulate IL-7R even as they leave the thymus, and we reveal that this expression is strictly NF-κB dependent. NF-κB signaling was only required transiently, however, and once fully mature, naive T cells did not require NF-κB signaling to maintain IL-7R expression. Therefore, we reveal a developmental role for NF-κB signaling for the normal maturation and function of new T cells.
Physiology & Behavior, 2007
The electric organ discharge (EOD) of weakly electric fish encodes information about species, sex... more The electric organ discharge (EOD) of weakly electric fish encodes information about species, sex, behavioral, and physiological states throughout the lifetime. Its central command is crucial for sensory-motor coordination, and is therefore the target of plastic mechanisms that adapt fish to environmental and social challenges. The EOD waveform of Brachyhypopomus pinnicaudatus is modulated by environmental factors and the neuroendocrine system. In this study we investigate the effects of water temperature and day-night cycle upon EOD rate in this species during the breeding and non-breeding seasons. During the non-breeding season, EOD rate is a linear function of water temperature and exhibits counterclockwise hysteresis. During breeding, a thermal resistance strategy prevents the decrease of EOD rate to cooling. A nocturnal increase of EOD basal rate independent of water temperature and locomotor activity was demonstrated in isolated non-breeding adults and in male-female dyads all year round. An additional increase of nocturnal EOD rate, probably acting as a social courtship signal, was found in breeding dyads. This additional increase of nocturnal EOD rate could not be fully explained by gonadal maturation and was modulated by social stimuli. This study provides novel data on the complex interactions between environment, reproductive cycle, social behavior, and electromotor output in an advantageous model of the vertebrate central nervous system.
New England Journal of Medicine, 2013
Background Transthyretin amyloidosis is caused by the deposition of hepatocyte-derived transthyre... more Background Transthyretin amyloidosis is caused by the deposition of hepatocyte-derived transthyretin amyloid in peripheral nerves and the heart. A therapeutic approach mediated by RNA interference (RNAi) could reduce the production of transthyretin. Methods We identified a potent antitransthyretin small interfering RNA, which was encapsulated in two distinct first-and second-generation formulations of lipid nanoparticles, generating ALN-TTR01 and ALN-TTR02, respectively. Each formulation was studied in a single-dose, placebo-controlled phase 1 trial to assess safety and effect on transthyretin levels. We first evaluated ALN-TTR01 (at doses of 0.01 to 1.0 mg per kilogram of body weight) in 32 patients with transthyretin amyloidosis and then evaluated ALN-TTR02 (at doses of 0.01 to 0.5 mg per kilogram) in 17 healthy volunteers. Results Rapid, dose-dependent, and durable lowering of transthyretin levels was observed in the two trials. At a dose of 1.0 mg per kilogram, ALN-TTR01 suppressed transthyretin, with a mean reduction at day 7 of 38%, as compared with placebo (P = 0.01); levels of mutant and nonmutant forms of transthyretin were lowered to a similar extent. For ALN-TTR02, the mean reductions in transthyretin levels at doses of 0.15 to 0.3 mg per kilogram ranged from 82.3 to 86.8%, with reductions of 56.6 to 67.1% at 28 days (P<0.001 for all comparisons). These reductions were shown to be RNAimediated. Mild-to-moderate infusion-related reactions occurred in 20.8% and 7.7% of participants receiving ALN-TTR01 and ALN-TTR02, respectively. Conclusions ALN-TTR01 and ALN-TTR02 suppressed the production of both mutant and nonmutant forms of transthyretin, establishing proof of concept for RNAi therapy targeting messenger RNA transcribed from a disease-causing gene.
Journal of Physiology-Paris, 2002
Temperature is a major variable that affects all biological systems. Environmental temperature de... more Temperature is a major variable that affects all biological systems. Environmental temperature determines animal geographical distribution and activity, and influences their reproductive cycle, particularly within the temperate zone. Temperature, as a physical parameter, also strongly affects excitable tissues. The hypothesis of temperature as the most important environmental cue for the onset of breeding in gymnotiform pulse fish of the temperate zone is supported by: (a) a clear temporal correlation that was observed in the wild between water temperature and sexual maturity, and (b) the induction of gonadal maturation and sexual differences after acclimation at high temperature (28 C) in the laboratory. Temperature sensitivity of EOD waveform (described in Brachyhypopomus pinnicaudatus and Gymnotus carapo) is characterized by the decrease of the EOD's late head-negative phase as temperature increases. This phenomenon depends on electrocyte properties since: (a) experimentally induced changes of discharge rate at constant temperature generate smaller EOD distortion, and (b) the effect of temperature upon EOD also depends on water conductivity. Temperature sensitivity of EOD waveform is negatively correlated with gonadal maturity in Brachyhypopomus pinnicaudatus. High temperature sensitivity was observed during the non-breeding season, whereas low temperature sensitivity was recorded during the breeding season. Temperature sensitivity of EOD waveform in both Brachyhypopomus pinnicaudatus and Gymnotus carapo was modulated by: (a) testosterone treatment (100 mg/g) that decreased temperature sensitivity, and (b) acclimation at high temperature (28 C, 1 month) that also decreased temperature sensitivity. Temperature is probably acting through the neuroendocrine system, and ultimately interacting with steroid hormones in their effects upon EOD waveform.
Journal of Physiology-Paris, 2008
Behavior in electric fish includes modulations of a stereotyped electric organ discharge (EOD) in... more Behavior in electric fish includes modulations of a stereotyped electric organ discharge (EOD) in addition to locomotor displays. Gymnotiformes can modulate the EOD rate to produce signals that participate in different behaviors. We studied the reproductive behavior of Brachyhypopomus pinnicaudatus both in the wild and laboratory settings. During the breeding season, fish produce sexually dimorphic social electric signals (SES): males emit three types of chirps (distinguished by their duration and internal structure), and accelerations, whereas females interrupt their EOD. Since these SES imply EOD frequency modulations, the pacemaker nucleus (PN) is involved in their generation and constitutes the main target organ to explore seasonal and sexual plasticity of the CNS. The PN has two types of neurons, pacemakers and relays, which receive modulatory inputs from pre-pacemaker structures. These neurons show an anisotropic rostro-caudal and dorso-ventral distribution that is paralleled by different field potential waveforms in distinct portions of the PN. In vivo glutamate injections in different areas of the PN provoke different kinds of EOD rate modulations. Ventral injections produce chirp-like responses in breeding males and EOD interruptions in breeding females, whereas dorsal injections provoke EOD frequency rises in both sexes. In the non-breeding season, males and females respond with interruptions when stimulated ventrally and frequency rises when injected dorsally. Our results show that changes of glutamate effects in the PN could explain the seasonal and sexual differences in the generation of SES. By means of behavioral recordings both in the wild and in laboratory settings, and by electrophysiological and pharmacological experiments, we have identified sexual and seasonal plasticity of the CNS and explored its underlying mechanisms.
Journal of Neuroimmunology, 2007
Journal of Inorganic Biochemistry, 2011
Results from an investigation in an in vivo model of STZ-induced diabetic rats demonstrate that c... more Results from an investigation in an in vivo model of STZ-induced diabetic rats demonstrate that compound bis(1,2-dimethyl-3-hydroxy-4(1H)-pyridinonate)zinc(II), Zn(dmpp)(2), significantly lowers the blood glucose levels of individuals, thus showing evidence of glucose lowering activity. The compound was selected from a set of eight zinc(II) complexes of 3-hydroxy-4-pyridinones with diverse lipophilicity that were prepared and characterized in our laboratory. Assessment of insulin-like activity of the complexes was firstly performed in vitro by measuring the inhibition of FFA release in isolated rat adipocytes. The results indicate that compounds bis(2-methyl-3-hydroxy-4-pyridinonate)zinc(II), Zn(mpp)(2) and Zn(dmpp)(2) display significantly higher activity than that of the respective positive control thus suggesting its selection for in vivo tests. Safety evaluation of the active zinc(II) compounds was performed in freshly isolated rat hepatocytes. The results support that cell viability is not significantly different from the control set after 1 and 2h of incubation with both zinc(II) complexes.
Proceedings. Biological sciences / The Royal Society, Jan 22, 2009
Animal conflicts are influenced by social experience such that a previous winning experience incr... more Animal conflicts are influenced by social experience such that a previous winning experience increases the probability of winning the next agonistic interaction, whereas a previous losing experience has the opposite effect. Since androgens respond to social interactions, increasing in winners and decreasing in losers, we hypothesized that socially induced transient changes in androgen levels could be a causal mediator of winner/loser effects. To test this hypothesis, we staged fights between dyads of size-matched males of the Mozambique tilapia (Oreochromis mossambicus). After the first contest, winners were treated with the anti-androgen cyproterone acetate and losers were supplemented with 11-ketotestosterone. Two hours after the end of the first fight, two contests were staged simultaneously between the winner of the first fight and a naive male and between the loser of first fight and another naive male. The majority (88%) of control winners also won the second interaction, wher...
Frontiers in Neuroscience, 2009
Emotion, 2008
The Experience Sampling Method was used to explore emotions to music as they naturally occurred i... more The Experience Sampling Method was used to explore emotions to music as they naturally occurred in everyday life, with a focus on the prevalence of different musical emotions and how such emotions are related to various factors in the listener, the music, and the situation. Thirty-two college students, 20 to 31 years old, carried a palmtop that emitted a sound signal seven times per day at random intervals for 2 weeks. When signaled, participants were required to complete a questionnaire on the palmtop. Results showed that music occurred in 37% of the episodes, and in 64% of the music episodes, the participants reported that the music affected how they felt. Comparisons showed that happiness-elation and nostalgia-longing were more frequent in episodes with musical emotions, whereas anger-irritation, boredom-indifference, and anxiety-fear were more frequent in episodes with nonmusical emotions. The prevalence of specific musical emotions correlated with personality measures and also varied depending on the situation (e.g., current activity, other people present), thus highlighting the need to use representative samples of situations to obtain valid estimates of prevalence.
Electronic Notes in Discrete Mathematics, 2009
HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Electronic Notes in Discrete Mathematics, 2008
The class of planar graphs has unbounded treewidth, since the k × k grid, ∀k ∈ N, is planar and h... more The class of planar graphs has unbounded treewidth, since the k × k grid, ∀k ∈ N, is planar and has treewidth k. So, it is of interest to determine subclasses of planar graphs which have bounded treewidth. In this paper, we show that if G is an evenhole-free planar graph, then it does not contain a 9 × 9 grid minor. As a result, we have that even-hole-free planar graphs have treewidth at most 44.
Clinical Cancer Research, 2007
Purpose: Epidermal growth factor (EGF) plays a critical role in cancer. A polymorphism in the EGF... more Purpose: Epidermal growth factor (EGF) plays a critical role in cancer. A polymorphism in the EGF gene (EGF+61) may influence its expression and contribute to cancer predisposition and aggressiveness. In the present study, we aimed to elucidate the role of EGF+61 in glioma susceptibility and prognosis. Experimental Design: A case-control study involving 197 glioma patients and 570 controls was done. Univariate and multivariate logistic regression analyses were used to calculate odds ratio (OR) and 95% confidence intervals (95% CI). False-positive report probability was also assessed. The luciferase reporter gene assay was used to ascertain the functional consequences of this polymorphism. Results: Corroborating the univariate analysis, the multivariate model showed that the G allele conferred higher risks for gliomas (OR, 1.32; 95% CI, 1.04-1.67), glioblastomas (OR, 1.47; 95% CI, 1.02-2.10), and oligodendrogliomas (OR, 1.55; 95% CI, 1.07-2.23). The GG genotypes were associated with ...
Physics Letters B, 2015
The calculated position resolutions for X-ray photons (1-60 keV) in pure noble gases at atmospher... more The calculated position resolutions for X-ray photons (1-60 keV) in pure noble gases at atmospheric pressure are presented. In this work we show the influence of the atomic shells and the detector dimensions on the intrinsic position resolution of the used noble gas. The calculated results were obtained by using a new software tool, Degrad, and compared to the available experimental data.
Hormones and Behavior, 2015
The neuroendocrine control of intraspecific aggression is a matter of current debate. Although ag... more The neuroendocrine control of intraspecific aggression is a matter of current debate. Although aggression in a reproductive context has been associated with high levels of circulating androgens in a broad range of species, it has also been shown to occur during the non-breeding season when gonads are regressed and plasma steroid hormone levels are low. In mammals and birds the aromatization of androgens into estrogens plays a key role in the regulation of aggression in both the breeding and non-breeding seasons. This is the first study in a teleost fish to explore the role of steroids in the modulation of non-breeding aggression. Gymnotus omarorum is a highly aggressive teleost fish that exhibits aggression all year-round. We analyzed male-male non-breeding agonistic behavior, compared circulating 11-Ketotestosterone (11-KT) levels between dominants and isolated males, assessed the regulatory role of aromatization of androgens into estrogens, and evaluated the gonads as a source of these sex steroids. We found that high levels of aggression occurred in the non-breeding season despite low plasma 11-KT levels, and that there was no difference in 11-KT levels between dominant and isolated males. We demonstrated that acute aromatase inhibition decreased aggression, distorted contest dynamics, and affected expected outcome. We also found that castrated individuals displayed aggressive behavior indistinguishable from non-castrated males. Our results show, for the first time in teleost fish, that territorial aggression of G. omarorum during the non-breeding season depends on a non-gonadal estrogenic pathway.
International Journal of Migration, Health and Social Care, 2009
The paper addresses diversity, multi‐culturalism and mental health. It reports qualitative data f... more The paper addresses diversity, multi‐culturalism and mental health. It reports qualitative data from a larger project on multi‐cultural counselling competencies in Portugal which sought to meet the needs identified by specific minority groups by developing integrative, responsive and culturally sensitive treatments. A qualitative study is presented, with the aim of exploring the representations of mental health and illness held by ethnic minority groups in Portugal, as well as their specific needs and obstacles encountered in their interactions with health professionals. Semi‐structured interviews were conducted, and the results indicate that the meanings of health and mental health varied. Meanings of psychological health were related to general well‐being. Help‐seeking behaviours were associated with providing and receiving family and social support, mainly among participants of African descent. Although the great majority of participants had had no experience of counselling or ps...
Frontiers in behavioral neuroscience, 2010
Social behavior diversity is correlated with distinctively distributed patterns of a conserved br... more Social behavior diversity is correlated with distinctively distributed patterns of a conserved brain network, which depend on the action of neuroendocrine messengers that integrate extrinsic and intrinsic cues. Arginine vasotocin (AVT) is a key integrator underlying differences in behavior across vertebrate taxa. Weakly electric fish use their electric organ discharges (EODs) as social behavioral displays. We examined the effect of AVT on EOD rate in two species of Gymnotiformes with different social strategies: Gymnotus omarorum, territorial and highly aggressive, and Brachyhypopomus gauderio, gregarious and aggressive only between breeding males. AVT induced a long-lasting and progressive increase of EOD rate in isolated B. gauderio, partially blocked by the V1a AVT receptor antagonist (Manning compound, MC), and had no effects in G. omarorum. AVT also induced a long-lasting increase in the firing rate (prevented by MC) of the isolated medullary pacemaker nucleus (PN) of B. gauder...
Journal of Experimental Biology, 2004
SUMMARYIn contrast to most of the previous studies in gymnotiform reproduction,which have been co... more SUMMARYIn contrast to most of the previous studies in gymnotiform reproduction,which have been conducted in the tropical region, this study examines a gymnotid from the temperate region in both the natural habitat and the laboratory. The gonadal histology of Brachyhypopomus pinnicaudatus is described for the first time. The male had a paired, lobular testis of the unrestricted spermatogonial type, and females a paired saccular cystovary. Analysis of gonads and their annual cycle enabled us to confirm the breeding season and to conclude that this species is a multiple spawner. Water temperature and photoperiod showed the expected annual cycles for the region. High temperature and a 14 h:10 h L:D photoperiod in the natural habitat coincided with (1) mature gonadal stages, (2) electrophysiological sexual dimorphism: males present a lengthened negative phase in their electric organ discharge (EOD) and (3) decreased temperature sensitivity of the EOD: the waveform does not change when te...
Synlett, 2009
Abstract Condensation adducts of the Ni (II) and Cu (II) complexes of β-amino-meso-tetraphenylpor... more Abstract Condensation adducts of the Ni (II) and Cu (II) complexes of β-amino-meso-tetraphenylporphyrin with dimethyl acetylenedicarboxylate (DMAD) and diethyl ethoxymethylenemalonate were converted into the corresponding esters of pyridinone-...
Proceedings of the National Academy of Sciences, 2014
Significance Interleukin (IL)-7 is critical for the maintenance of the peripheral T-cell compartm... more Significance Interleukin (IL)-7 is critical for the maintenance of the peripheral T-cell compartment of the adaptive immune system. Our study identifies a role for the Nuclear Factor κ-B (NF-κB) signalling pathway in the control of IL-7 receptor expression by T cells. Following thymic selection, new T cells specifically up-regulate IL-7R even as they leave the thymus, and we reveal that this expression is strictly NF-κB dependent. NF-κB signaling was only required transiently, however, and once fully mature, naive T cells did not require NF-κB signaling to maintain IL-7R expression. Therefore, we reveal a developmental role for NF-κB signaling for the normal maturation and function of new T cells.
Physiology & Behavior, 2007
The electric organ discharge (EOD) of weakly electric fish encodes information about species, sex... more The electric organ discharge (EOD) of weakly electric fish encodes information about species, sex, behavioral, and physiological states throughout the lifetime. Its central command is crucial for sensory-motor coordination, and is therefore the target of plastic mechanisms that adapt fish to environmental and social challenges. The EOD waveform of Brachyhypopomus pinnicaudatus is modulated by environmental factors and the neuroendocrine system. In this study we investigate the effects of water temperature and day-night cycle upon EOD rate in this species during the breeding and non-breeding seasons. During the non-breeding season, EOD rate is a linear function of water temperature and exhibits counterclockwise hysteresis. During breeding, a thermal resistance strategy prevents the decrease of EOD rate to cooling. A nocturnal increase of EOD basal rate independent of water temperature and locomotor activity was demonstrated in isolated non-breeding adults and in male-female dyads all year round. An additional increase of nocturnal EOD rate, probably acting as a social courtship signal, was found in breeding dyads. This additional increase of nocturnal EOD rate could not be fully explained by gonadal maturation and was modulated by social stimuli. This study provides novel data on the complex interactions between environment, reproductive cycle, social behavior, and electromotor output in an advantageous model of the vertebrate central nervous system.
New England Journal of Medicine, 2013
Background Transthyretin amyloidosis is caused by the deposition of hepatocyte-derived transthyre... more Background Transthyretin amyloidosis is caused by the deposition of hepatocyte-derived transthyretin amyloid in peripheral nerves and the heart. A therapeutic approach mediated by RNA interference (RNAi) could reduce the production of transthyretin. Methods We identified a potent antitransthyretin small interfering RNA, which was encapsulated in two distinct first-and second-generation formulations of lipid nanoparticles, generating ALN-TTR01 and ALN-TTR02, respectively. Each formulation was studied in a single-dose, placebo-controlled phase 1 trial to assess safety and effect on transthyretin levels. We first evaluated ALN-TTR01 (at doses of 0.01 to 1.0 mg per kilogram of body weight) in 32 patients with transthyretin amyloidosis and then evaluated ALN-TTR02 (at doses of 0.01 to 0.5 mg per kilogram) in 17 healthy volunteers. Results Rapid, dose-dependent, and durable lowering of transthyretin levels was observed in the two trials. At a dose of 1.0 mg per kilogram, ALN-TTR01 suppressed transthyretin, with a mean reduction at day 7 of 38%, as compared with placebo (P = 0.01); levels of mutant and nonmutant forms of transthyretin were lowered to a similar extent. For ALN-TTR02, the mean reductions in transthyretin levels at doses of 0.15 to 0.3 mg per kilogram ranged from 82.3 to 86.8%, with reductions of 56.6 to 67.1% at 28 days (P<0.001 for all comparisons). These reductions were shown to be RNAimediated. Mild-to-moderate infusion-related reactions occurred in 20.8% and 7.7% of participants receiving ALN-TTR01 and ALN-TTR02, respectively. Conclusions ALN-TTR01 and ALN-TTR02 suppressed the production of both mutant and nonmutant forms of transthyretin, establishing proof of concept for RNAi therapy targeting messenger RNA transcribed from a disease-causing gene.
Journal of Physiology-Paris, 2002
Temperature is a major variable that affects all biological systems. Environmental temperature de... more Temperature is a major variable that affects all biological systems. Environmental temperature determines animal geographical distribution and activity, and influences their reproductive cycle, particularly within the temperate zone. Temperature, as a physical parameter, also strongly affects excitable tissues. The hypothesis of temperature as the most important environmental cue for the onset of breeding in gymnotiform pulse fish of the temperate zone is supported by: (a) a clear temporal correlation that was observed in the wild between water temperature and sexual maturity, and (b) the induction of gonadal maturation and sexual differences after acclimation at high temperature (28 C) in the laboratory. Temperature sensitivity of EOD waveform (described in Brachyhypopomus pinnicaudatus and Gymnotus carapo) is characterized by the decrease of the EOD's late head-negative phase as temperature increases. This phenomenon depends on electrocyte properties since: (a) experimentally induced changes of discharge rate at constant temperature generate smaller EOD distortion, and (b) the effect of temperature upon EOD also depends on water conductivity. Temperature sensitivity of EOD waveform is negatively correlated with gonadal maturity in Brachyhypopomus pinnicaudatus. High temperature sensitivity was observed during the non-breeding season, whereas low temperature sensitivity was recorded during the breeding season. Temperature sensitivity of EOD waveform in both Brachyhypopomus pinnicaudatus and Gymnotus carapo was modulated by: (a) testosterone treatment (100 mg/g) that decreased temperature sensitivity, and (b) acclimation at high temperature (28 C, 1 month) that also decreased temperature sensitivity. Temperature is probably acting through the neuroendocrine system, and ultimately interacting with steroid hormones in their effects upon EOD waveform.
Journal of Physiology-Paris, 2008
Behavior in electric fish includes modulations of a stereotyped electric organ discharge (EOD) in... more Behavior in electric fish includes modulations of a stereotyped electric organ discharge (EOD) in addition to locomotor displays. Gymnotiformes can modulate the EOD rate to produce signals that participate in different behaviors. We studied the reproductive behavior of Brachyhypopomus pinnicaudatus both in the wild and laboratory settings. During the breeding season, fish produce sexually dimorphic social electric signals (SES): males emit three types of chirps (distinguished by their duration and internal structure), and accelerations, whereas females interrupt their EOD. Since these SES imply EOD frequency modulations, the pacemaker nucleus (PN) is involved in their generation and constitutes the main target organ to explore seasonal and sexual plasticity of the CNS. The PN has two types of neurons, pacemakers and relays, which receive modulatory inputs from pre-pacemaker structures. These neurons show an anisotropic rostro-caudal and dorso-ventral distribution that is paralleled by different field potential waveforms in distinct portions of the PN. In vivo glutamate injections in different areas of the PN provoke different kinds of EOD rate modulations. Ventral injections produce chirp-like responses in breeding males and EOD interruptions in breeding females, whereas dorsal injections provoke EOD frequency rises in both sexes. In the non-breeding season, males and females respond with interruptions when stimulated ventrally and frequency rises when injected dorsally. Our results show that changes of glutamate effects in the PN could explain the seasonal and sexual differences in the generation of SES. By means of behavioral recordings both in the wild and in laboratory settings, and by electrophysiological and pharmacological experiments, we have identified sexual and seasonal plasticity of the CNS and explored its underlying mechanisms.
Journal of Neuroimmunology, 2007
Journal of Inorganic Biochemistry, 2011
Results from an investigation in an in vivo model of STZ-induced diabetic rats demonstrate that c... more Results from an investigation in an in vivo model of STZ-induced diabetic rats demonstrate that compound bis(1,2-dimethyl-3-hydroxy-4(1H)-pyridinonate)zinc(II), Zn(dmpp)(2), significantly lowers the blood glucose levels of individuals, thus showing evidence of glucose lowering activity. The compound was selected from a set of eight zinc(II) complexes of 3-hydroxy-4-pyridinones with diverse lipophilicity that were prepared and characterized in our laboratory. Assessment of insulin-like activity of the complexes was firstly performed in vitro by measuring the inhibition of FFA release in isolated rat adipocytes. The results indicate that compounds bis(2-methyl-3-hydroxy-4-pyridinonate)zinc(II), Zn(mpp)(2) and Zn(dmpp)(2) display significantly higher activity than that of the respective positive control thus suggesting its selection for in vivo tests. Safety evaluation of the active zinc(II) compounds was performed in freshly isolated rat hepatocytes. The results support that cell viability is not significantly different from the control set after 1 and 2h of incubation with both zinc(II) complexes.
Proceedings. Biological sciences / The Royal Society, Jan 22, 2009
Animal conflicts are influenced by social experience such that a previous winning experience incr... more Animal conflicts are influenced by social experience such that a previous winning experience increases the probability of winning the next agonistic interaction, whereas a previous losing experience has the opposite effect. Since androgens respond to social interactions, increasing in winners and decreasing in losers, we hypothesized that socially induced transient changes in androgen levels could be a causal mediator of winner/loser effects. To test this hypothesis, we staged fights between dyads of size-matched males of the Mozambique tilapia (Oreochromis mossambicus). After the first contest, winners were treated with the anti-androgen cyproterone acetate and losers were supplemented with 11-ketotestosterone. Two hours after the end of the first fight, two contests were staged simultaneously between the winner of the first fight and a naive male and between the loser of first fight and another naive male. The majority (88%) of control winners also won the second interaction, wher...
Frontiers in Neuroscience, 2009
Emotion, 2008
The Experience Sampling Method was used to explore emotions to music as they naturally occurred i... more The Experience Sampling Method was used to explore emotions to music as they naturally occurred in everyday life, with a focus on the prevalence of different musical emotions and how such emotions are related to various factors in the listener, the music, and the situation. Thirty-two college students, 20 to 31 years old, carried a palmtop that emitted a sound signal seven times per day at random intervals for 2 weeks. When signaled, participants were required to complete a questionnaire on the palmtop. Results showed that music occurred in 37% of the episodes, and in 64% of the music episodes, the participants reported that the music affected how they felt. Comparisons showed that happiness-elation and nostalgia-longing were more frequent in episodes with musical emotions, whereas anger-irritation, boredom-indifference, and anxiety-fear were more frequent in episodes with nonmusical emotions. The prevalence of specific musical emotions correlated with personality measures and also varied depending on the situation (e.g., current activity, other people present), thus highlighting the need to use representative samples of situations to obtain valid estimates of prevalence.
Electronic Notes in Discrete Mathematics, 2009
HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Electronic Notes in Discrete Mathematics, 2008
The class of planar graphs has unbounded treewidth, since the k × k grid, ∀k ∈ N, is planar and h... more The class of planar graphs has unbounded treewidth, since the k × k grid, ∀k ∈ N, is planar and has treewidth k. So, it is of interest to determine subclasses of planar graphs which have bounded treewidth. In this paper, we show that if G is an evenhole-free planar graph, then it does not contain a 9 × 9 grid minor. As a result, we have that even-hole-free planar graphs have treewidth at most 44.
Clinical Cancer Research, 2007
Purpose: Epidermal growth factor (EGF) plays a critical role in cancer. A polymorphism in the EGF... more Purpose: Epidermal growth factor (EGF) plays a critical role in cancer. A polymorphism in the EGF gene (EGF+61) may influence its expression and contribute to cancer predisposition and aggressiveness. In the present study, we aimed to elucidate the role of EGF+61 in glioma susceptibility and prognosis. Experimental Design: A case-control study involving 197 glioma patients and 570 controls was done. Univariate and multivariate logistic regression analyses were used to calculate odds ratio (OR) and 95% confidence intervals (95% CI). False-positive report probability was also assessed. The luciferase reporter gene assay was used to ascertain the functional consequences of this polymorphism. Results: Corroborating the univariate analysis, the multivariate model showed that the G allele conferred higher risks for gliomas (OR, 1.32; 95% CI, 1.04-1.67), glioblastomas (OR, 1.47; 95% CI, 1.02-2.10), and oligodendrogliomas (OR, 1.55; 95% CI, 1.07-2.23). The GG genotypes were associated with ...