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1.
Artigo em Inglês | MEDLINE | ID: mdl-33069817

RESUMO

Psychobiotics are considered among potential avenues for modulating the bidirectional communication between the gastrointestinal tract and central nervous system, defined as the microbiota-gut-brain axis (MGBA). Even though causality has not yet been established, intestinal dysbiosis has emerged as a hallmark of several diseases, including neuropsychiatric disorders (NPDs). The fact that the microbiota and central nervous system are co-developing during the first years of life has provided a paradigm suggesting a potential role of psychobiotics for earlier interventions. Studies in animal models of early-life stress (ELS) have shown that they can counteract the pervasive effects of stress during this crucial developmental period, and rescue behavioral symptoms related to anxiety and depression later in life. In humans, evidence from clinical studies on the efficacy of psychobiotics at improving mental outcomes in most NPDs remain limited, except for major depressive disorder for which more studies are available. Consequently, the beneficial effect of psychobiotics on depression-related outcomes in adults are becoming clearer. While the specific mechanisms at play remain elusive, the effect of psychobiotics are generally considered to involve the hypothalamic-pituitary-adrenal axis, intestinal permeability, and inflammation. It is anticipated that future clinical studies will explore the potential role of psychobiotics at mitigating the risk developing NPDs in vulnerable individuals or in the context of childhood adversity. However, such studies remain challenging at present in terms of design and target populations; the profound impact of stress on the proper development of the MGBA during the first year of life is becoming increasingly recognized, but the trajectories post-ELS in humans and the mechanisms by which stress affects the susceptibility to various NPDs are still ill-defined. As psychobiotics are likely to exert both shared and specific mechanisms, a better definition of target subpopulations would allow to tailor psychobiotics selection by aligning mechanistic properties with known pathophysiological mechanisms or risk factors. Here we review the available evidence from clinical and preclinical studies supporting a role for psychobiotics at ameliorating depression-related outcomes, highlighting the knowledge gaps and challenges associated with conducting longitudinal studies to address outstanding key questions in the field.

2.
Front Microbiol ; 11: 1662, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32793153

RESUMO

Still relevant after 19 years, the FAO/WHO definition of probiotics can be translated into four simple and pragmatic criteria allowing one to conclude if specific strains of microorganisms qualify as a probiotic for use in foods and dietary supplements. Probiotic strains must be (i) sufficiently characterized; (ii) safe for the intended use; (iii) supported by at least one positive human clinical trial conducted according to generally accepted scientific standards or as per recommendations and provisions of local/national authorities when applicable; and (iv) alive in the product at an efficacious dose throughout shelf life. We provide clarity and detail how each of these four criteria can be assessed. The wide adoption of these criteria is necessary to ensure the proper use of the word probiotic in scientific publications, on product labels, and in communications with regulators and the general public.

3.
J Diet Suppl ; : 1-21, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32306803

RESUMO

Few studies have focused on dose-response analyses of multi-strain probiotics in the general adult population. This study aimed at comparing how a low- and high-dose of a multi-strain probiotic supplement (containing Lactobacillus helveticus R0052, Lactobacillus rhamnosus R0011, Lactobacillus casei R0215, Pediococcus acidilactici R1001, Bifidobacterium breve R0070, Bifidobacterium longum ssp. longum BB536, Lactobacillus plantarum R1012, Lactococcus lactis ssp. lactis R1058) affected microbiota composition, transit persistence and safety in adults. After a 7-d baseline, participants were randomized to receive capsules containing 5 or 25 billion CFU, or placebo daily for 28 days, followed by a 7-d washout. Digestive health and general wellness were assessed. Fecal microbiota composition was analyzed using 16S rRNA gene amplicon sequencing and strain persistence, by qPCR. Participants' gastrointestinal and general wellbeing were unaffected. No adverse events were associated with either dose. Supplemented strains contributed to the Lactobacillus and Bifidobacterium genera detected in stool, with 0.40 ± 0.11% and 0.51 ± 0.26%, respectively, in the high-dose group. Strain-specific qPCR assays revealed variable levels of post-intervention persistence between strains. Sequencing and composition analyses using the 16S V4 region revealed a decrease in Holdemania and increase in Bacteroidales. The formulation was well tolerated in this sample of the general adult population, even at the higher dose. The strains appear to have influenced microbiota composition minimally, as expected in the absence of dysbiosis, and consistently with the dose administered. Overall, the results provide a rationale to study the effects this formulation on microbiota composition in individuals exhibiting dysbiosis associated with metabolic disorders or obesity.

4.
PLoS One ; 14(4): e0215101, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31009477

RESUMO

Caspase-3 activation in the limbic system and depressive-like symptoms are observed after an acute myocardial infarction (MI) and studies suggest that inflammation may play a significant role. Combined treatment with the probiotic strains Bifidobacterium longum and Lactobacillus helveticus in rats has been shown to attenuate caspase-3 activation and depressive-like behaviour together with a reduction in pro-inflammatory cytokines. The present study was designed to determine the respective contribution of these two strains on caspase-3 activity in the limbic system and on depressive-like behaviour. Sprague-Dawley rats were assigned to one of four groups: Vehicle, L. helveticus R0052, B. longum R0175 and L. salivarius HA-118, administered orally for 14 days (109CFU daily) before inducing MI by occlusion of the left anterior descending artery for 40 min followed by 14 days of reperfusion. Animals were then tested for socialisation, passive avoidance and forced swim test to assess depressive-like behaviour. At day 18 the animals were sacrificed; infarct size was estimated, plasma C-reactive protein concentration and brain caspase-3 activity were measured. Results indicated that infarct size did not vary across the different treatments. Rats treated with B. longum spent more time socializing, learned more rapidly the passive avoidance test and spent less time immobile in the forced swim test compared to the vehicle groups. Caspase-3 activity and plasma C-reactive protein concentrations were reduced in the lateral and medial amygdala as well as in the dentate gyrus of B. longum-supplemented animals. The only significant effect in the two groups receiving Lactobacilli compared to vehicle was that rats receiving L. salivarius learned more rapidly in the step-down passive avoidance test. In conclusion, most of the beneficial effects that we previously reported with the combination of two probiotic strains in our experimentation regarding post-myocardial infarction depression are related to Bifidobacterium longum.


Assuntos
Comportamento Animal/efeitos dos fármacos , Bifidobacterium longum/fisiologia , Transtorno Depressivo/prevenção & controle , Infarto do Miocárdio/complicações , Probióticos/administração & dosagem , Animais , Transtorno Depressivo/etiologia , Transtorno Depressivo/psicologia , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley
5.
Lang Speech ; 61(4): 615-631, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30249146

RESUMO

This study investigates whether syntactic cues take precedence over distributional cues in native and non-native speech segmentation by examining native and non-native speech segmentation in potential French-liaison contexts. Native French listeners and English-speaking second-language learners of French completed a visual-world eye-tracking experiment. Half the stimuli contained the pivotal consonant /t/, a frequent word onset but infrequent liaison consonant, and half contained /z/, a frequent liaison consonant but rare word onset. In the adjective-noun condition (permitting liaison), participants heard a consonant-initial target (e.g., le petit tatoué; le fameux zélé) that was temporarily ambiguous at the segmental level with a vowel-initial competitor (e.g., le petit [t]athée; le fameux [z]élu); in the noun-adjective condition (not permitting liaison), they heard a consonant-initial target (e.g., le client tatoué; le Français zélé) that was not temporarily ambiguous with a vowel-initial competitor (e.g., le client [*t]athée; le Français [*z]élu). Growth-curve analyses revealed that syntactic context modulated both groups' fixations (noun-adjective > adjective-noun), and pivotal consonant modulated both groups' fixations (/t/ > /z/) only in the adjective-noun condition, with the effect of the consonant decreasing in more proficient French learners. These results suggest that syntactic cues override distributional cues in the segmentation of French words in potential liaison contexts.


Assuntos
Sinais (Psicologia) , Multilinguismo , Fonética , Semântica , Percepção da Fala , Feminino , França , Humanos , Idioma , Aprendizagem , Masculino , Adulto Jovem
6.
PLoS One ; 12(7): e0181709, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28738093

RESUMO

This study investigates whether listeners' experience with a second language learned later in life affects their use of fundamental frequency (F0) as a cue to word boundaries in the segmentation of an artificial language (AL), particularly when the cues to word boundaries conflict between the first language (L1) and second language (L2). F0 signals phrase-final (and thus word-final) boundaries in French but word-initial boundaries in English. Participants were functionally monolingual French listeners, functionally monolingual English listeners, bilingual L1-English L2-French listeners, and bilingual L1-French L2-English listeners. They completed the AL-segmentation task with F0 signaling word-final boundaries or without prosodic cues to word boundaries (monolingual groups only). After listening to the AL, participants completed a forced-choice word-identification task in which the foils were either non-words or part-words. The results show that the monolingual French listeners, but not the monolingual English listeners, performed better in the presence of F0 cues than in the absence of such cues. Moreover, bilingual status modulated listeners' use of F0 cues to word-final boundaries, with bilingual French listeners performing less accurately than monolingual French listeners on both word types but with bilingual English listeners performing more accurately than monolingual English listeners on non-words. These findings not only confirm that speech segmentation is modulated by the L1, but also newly demonstrate that listeners' experience with the L2 (French or English) affects their use of F0 cues in speech segmentation. This suggests that listeners' use of prosodic cues to word boundaries is adaptive and non-selective, and can change as a function of language experience.


Assuntos
Multilinguismo , Percepção da Fala/fisiologia , Fala/fisiologia , Estimulação Acústica/métodos , Adulto , Percepção Auditiva/fisiologia , Sinais (Psicologia) , Feminino , Humanos , Idioma , Masculino , Fonética , Espectrografia do Som/métodos , Acústica da Fala , Adulto Jovem
7.
Stem Cells ; 35(8): 1958-1972, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28589555

RESUMO

Hippo pathway downstream effectors Yap and Taz play key roles in cell proliferation and regeneration, regulating gene expression especially via Tead transcription factors. To investigate their role in skeletal muscle stem cells, we analyzed Taz in vivo and ex vivo in comparison with Yap. Small interfering RNA knockdown or retroviral-mediated expression of wild-type human or constitutively active TAZ mutants in satellite cells showed that TAZ promoted proliferation, a function shared with YAP. However, at later stages of myogenesis, TAZ also enhanced myogenic differentiation of myoblasts, whereas YAP inhibits such differentiation. Functionally, while muscle growth was mildly affected in Taz (gene Wwtr1-/- ) knockout mice, there were no overt effects on regeneration. Conversely, conditional knockout of Yap in satellite cells of Pax7Cre-ERT2/+ : Yapfl °x/fl °x :Rosa26Lacz mice produced a regeneration deficit. To identify potential mechanisms, microarray analysis showed many common TAZ/YAP target genes, but TAZ also regulates some genes independently of YAP, including myogenic genes such as Pax7, Myf5, and Myod1 (ArrayExpress-E-MTAB-5395). Proteomic analysis revealed many novel binding partners of TAZ/YAP in myogenic cells, but TAZ also interacts with proteins distinct from YAP that are often involved in myogenesis and aspects of cytoskeleton organization (ProteomeXchange-PXD005751). Neither TAZ nor YAP bind members of the Wnt destruction complex but both regulated expression of Wnt and Wnt-cross talking genes with known roles in myogenesis. Finally, TAZ operates through Tead4 to enhance myogenic differentiation. In summary, Taz and Yap have overlapping functions in promoting myoblast proliferation but Taz then switches to enhance myogenic differentiation. Stem Cells 2017;35:1958-1972.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Músculo Esquelético/citologia , Fosfoproteínas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Células-Tronco/metabolismo , Animais , Proteínas de Ciclo Celular , Diferenciação Celular/genética , Fusão Celular , Proliferação de Células , Retroalimentação Fisiológica , Regulação da Expressão Gênica , Camundongos Knockout , Desenvolvimento Muscular/genética , Fibras Musculares Esqueléticas/citologia , Fibras Musculares Esqueléticas/metabolismo , Mioblastos/citologia , Mioblastos/metabolismo , Regeneração/genética , Células Satélites de Músculo Esquelético/citologia , Células Satélites de Músculo Esquelético/metabolismo , Células-Tronco/citologia , Transativadores , Via de Sinalização Wnt/genética
9.
Front Psychol ; 7: 985, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27445943

RESUMO

This study investigates whether the learning of prosodic cues to word boundaries in speech segmentation is more difficult if the native and second/foreign languages (L1 and L2) have similar (though non-identical) prosodies than if they have markedly different prosodies (Prosodic-Learning Interference Hypothesis). It does so by comparing French, Korean, and English listeners' use of fundamental-frequency (F0) rise as a cue to word-final boundaries in French. F0 rise signals phrase-final boundaries in French and Korean but word-initial boundaries in English. Korean-speaking and English-speaking L2 learners of French, who were matched in their French proficiency and French experience, and native French listeners completed a visual-world eye-tracking experiment in which they recognized words whose final boundary was or was not cued by an increase in F0. The results showed that Korean listeners had greater difficulty using F0 rise as a cue to word-final boundaries in French than French and English listeners. This suggests that L1-L2 prosodic similarity can make the learning of an L2 segmentation cue difficult, in line with the proposed Prosodic-Learning Interference Hypothesis. We consider mechanisms that may underlie this difficulty and discuss the implications of our findings for understanding listeners' phonological encoding of L2 words.

10.
J Appl Physiol (1985) ; 120(10): 1105-17, 2016 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-26940657

RESUMO

The ubiquitous transcriptional coactivators Yap (gene symbol Yap1) and Taz (gene symbol Wwtr1) regulate gene expression mainly by coactivating the Tead transcription factors. Being at the center of the Hippo signaling network, Yap and Taz are regulated by the Hippo kinase cassette and additionally by a plethora of exercise-associated signals and signaling modules. These include mechanotransduction, the AKT-mTORC1 network, the SMAD transcription factors, hypoxia, glucose homeostasis, AMPK, adrenaline/epinephrine and angiotensin II through G protein-coupled receptors, and IL-6. Consequently, exercise should alter Hippo signaling in several organs to mediate at least some aspects of the organ-specific adaptations to exercise. Indeed, Tead1 overexpression in muscle fibers has been shown to promote a fast-to-slow fiber type switch, whereas Yap in muscle fibers and cardiomyocytes promotes skeletal muscle hypertrophy and cardiomyocyte adaptations, respectively. Finally, genome-wide association studies in humans have linked the Hippo pathway members LATS2, TEAD1, YAP1, VGLL2, VGLL3, and VGLL4 to body height, which is a key factor in sports.


Assuntos
Exercício Físico/fisiologia , Condicionamento Físico Animal/fisiologia , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/fisiologia , Animais , Humanos , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiologia , Fatores de Transcrição/metabolismo
11.
Biochim Biophys Acta ; 1856(1): 121-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26050962

RESUMO

Sarcomas are rare cancers (≈1% of all solid tumours) usually of mesenchymal origin. Here, we review evidence implicating the Hippo pathway in soft tissue sarcomas. Several transgenic mouse models of Hippo pathway members (Nf2, Mob1, LATS1 and YAP1 mutants) develop various types of sarcoma. Despite that, Hippo member genes are rarely point mutated in human sarcomas. Instead, WWTR1-CAMTA1 and YAP1-TFE3 fusion genes are found in almost all cases of epithelioid haemangioendothelioma. Also copy number gains of YAP1 and other Hippo members occur at low frequencies but the most likely cause of perturbed Hippo signalling in sarcoma is the cross-talk with commonly mutated cancer genes such as KRAS, PIK3CA, CTNNB1 or FBXW7. Current Hippo pathway-targeting drugs include compounds that target the interaction between YAP and TEAD G protein-coupled receptors (GPCR) and the mevalonate pathway (e.g. statins). Given that many Hippo pathway-modulating drugs are already used in patients, this could lead to early clinical trials testing their efficacy in different types of sarcoma.


Assuntos
Proteínas Serina-Treonina Quinases/metabolismo , Sarcoma/metabolismo , Transdução de Sinais , Animais , Modelos Animais de Doenças , Humanos , Camundongos , Sarcoma/genética , Sarcoma/patologia
12.
Cancer Cell ; 26(2): 273-87, 2014 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-25087979

RESUMO

The role of the Hippo pathway effector YAP1 in soft tissue sarcomas is poorly defined. Here we report that YAP1 activity is elevated in human embryonal rhabdomyosarcoma (ERMS). In mice, sustained YAP1 hyperactivity in activated, but not quiescent, satellite cells induces ERMS with high penetrance and short latency. Via its transcriptional program with TEAD1, YAP1 directly regulates several major hallmarks of ERMS. YAP1-TEAD1 upregulate pro-proliferative and oncogenic genes and maintain the ERMS differentiation block by interfering with MYOD1 and MEF2 pro-differentiation activities. Normalization of YAP1 expression reduces tumor burden in human ERMS xenografts and allows YAP1-driven ERMS to differentiate in situ. Collectively, our results identify YAP1 as a potent ERMS oncogenic driver and a promising target for differentiation therapy.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Transformação Celular Neoplásica/metabolismo , Neoplasias Musculares/metabolismo , Fosfoproteínas/fisiologia , Rabdomiossarcoma Embrionário/metabolismo , Células Satélites de Músculo Esquelético/patologia , Animais , Diferenciação Celular/genética , Proliferação de Células , Proteínas de Ligação a DNA/metabolismo , Dosagem de Genes , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Camundongos Transgênicos , Neoplasias Musculares/mortalidade , Neoplasias Musculares/patologia , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Proteína MyoD , Transplante de Neoplasias , Proteínas Nucleares/metabolismo , Oncogenes , Rabdomiossarcoma Embrionário/mortalidade , Rabdomiossarcoma Embrionário/patologia , Fatores de Transcrição/metabolismo
13.
Palliat Support Care ; 12(1): 25-38, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23905694

RESUMO

OBJECTIVE: Implementation of routine Screening for Distress constitutes a major change in cancer care, with the aim of achieving person-centered care. METHOD: Using a cross-sectional descriptive design within a University Tertiary Care Hospital setting, 911 patients from all cancer sites were screened at the time of their first meeting with a nurse navigator who administered a paper questionnaire that included: the Distress Thermometer (DT), the Canadian Problem Checklist (CPC), and the Edmonton Symptom Assessment System (ESAS). RESULTS: Results showed a mean score of 3.9 on the DT. Fears/worries, coping with the disease, and sleep were the most common problems reported on the CPC. Tiredness was the most prevalent symptom on the ESAS. A final regression model that included anxiety, the total number of problems on the CPC, well-being, and tiredness accounted for almost 50% of the variance of distress. A cutoff score of 5 on the DT together with a cutoff of 5 on the ESAS items represents the best combination of specificity and sensitivity to orient patients on the basis of their reported distress. SIGNIFICANCE OF RESULTS: These descriptive data will provide valuable feedback to answer practical questions for the purpose of effectively implementing and managing routine screening in cancer care.


Assuntos
Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/enfermagem , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/enfermagem , Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Programas de Rastreamento/enfermagem , Neoplasias/enfermagem , Neoplasias/psicologia , Avaliação em Enfermagem/estatística & dados numéricos , Assistência Centrada no Paciente , Papel do Doente , Inquéritos e Questionários , Adaptação Psicológica , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos de Ansiedade/psicologia , Estudos Transversais , Transtorno Depressivo/psicologia , Fadiga/diagnóstico , Fadiga/enfermagem , Fadiga/psicologia , Feminino , Necessidades e Demandas de Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria/estatística & dados numéricos , Quebeque , Reprodutibilidade dos Testes , Centros de Atenção Terciária , Adulto Jovem
14.
J Mem Lang ; 69(3): 349-367, 2013 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-24014935

RESUMO

Although foreign accents can be highly dissimilar to native speech, existing research suggests that listeners readily adapt to foreign accents after minimal exposure. However, listeners often report difficulty understanding non-native accents, and the time-course and specificity of adaptation remain unclear. Across five experiments, we examined whether listeners could use a newly learned feature of a foreign accent to eliminate lexical competitors during online speech perception. Participants heard the speech of a native English speaker and a native speaker of Québec French who, in English, pronounces /i/ as [i] (e.g., weak as wick) before all consonants except voiced fricatives. We examined whether listeners could learn to eliminate a shifted /i/-competitor (e.g., weak) when interpreting the accented talker produce an unshifted word (e.g., wheeze). In four experiments, adaptation was strikingly limited, though improvement across the course of the experiment and with stimulus variations indicates learning was possible. In a fifth experiment, adaptation was not improved when a native English talker produced the critical vowel shift, demonstrating that the limitation is not simply due to the fact the accented talker was non-native. These findings suggest that although listeners can arrive at the correct interpretation of a foreign accent, this process can pose significant difficulty.

15.
J Cell Sci ; 125(Pt 24): 6009-19, 2012 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-23038772

RESUMO

Satellite cells are the resident stem cells of skeletal muscle. Mitotically quiescent in mature muscle, they can be activated to proliferate and generate myoblasts to supply further myonuclei to hypertrophying or regenerating muscle fibres, or self-renew to maintain the resident stem cell pool. Here, we identify the transcriptional co-factor Yap as a novel regulator of satellite cell fate decisions. Yap expression increases during satellite cell activation and Yap remains highly expressed until after the differentiation versus self-renewal decision is made. Constitutive expression of Yap maintains Pax7(+) and MyoD(+) satellite cells and satellite cell-derived myoblasts, promotes proliferation but prevents differentiation. In contrast, Yap knockdown reduces the proliferation of satellite cell-derived myoblasts by ≈40%. Consistent with the cellular phenotype, microarrays show that Yap increases expression of genes associated with Yap inhibition, the cell cycle, ribosome biogenesis and that it represses several genes associated with angiotensin signalling. We also identify known regulators of satellite cell function such as BMP4, CD34 and Myf6 (Mrf4) as genes whose expression is dependent on Yap activity. Finally, we confirm in myoblasts that Yap binds to Tead transcription factors and co-activates MCAT elements which are enriched in the proximal promoters of Yap-responsive genes.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Fosfoproteínas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Células Satélites de Músculo Esquelético/citologia , Células Satélites de Músculo Esquelético/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Proteínas de Ciclo Celular , Processos de Crescimento Celular/fisiologia , Núcleo Celular/metabolismo , Embrião de Galinha , Cavalos , Camundongos , Fosfoproteínas/genética , Transdução de Sinais , Transfecção
16.
Semin Cell Dev Biol ; 23(7): 818-26, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23034192

RESUMO

Over the past decade, the Hippo signaling cascade has been linked to organ size regulation in mammals. Indeed, modulation of the Hippo pathway can have potent effects on cellular proliferation and/or apoptosis and a deregulation of the pathway often leads to tumor development. Importantly, emerging evidence indicates that the Hippo pathway can modulate its effects on tissue size by the regulation of stem and progenitor cell activity. This role has recently been associated with the central position of the pathway in sensing spatiotemporal or mechanical cues, and translating them into specific cellular outputs. These results provide an attractive model for how the Hippo cascade might sense and transduce cellular 'neighborhood' cues into activation of tissue-specific stem or progenitors cells. A further understanding of this process could allow the development of new therapies for various degenerative diseases and cancers. Here, we review current and emerging data linking Hippo signaling to progenitor cell function.


Assuntos
Transdução de Sinais , Células-Tronco/metabolismo , Animais , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Mamíferos , Especificidade de Órgãos , Proteínas Serina-Treonina Quinases/metabolismo
17.
Acta Psychol (Amst) ; 140(3): 187-95, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22664316

RESUMO

Previous research showed that handwriting production is mediated by linguistically oriented processing units such as syllables and graphemes. The goal of this study was to investigate whether French adults also activate another kind of unit that is more related to semantics than phonology, namely morphemes. Experiment 1 revealed that letter duration and inter-letter intervals were longer for suffixed words than for pseudo-suffixed words. These results suggest that the handwriting production system chunks the letter components of the root and suffix into morpheme-sized units. Experiment 2 compared the production of prefixed and pseudo-prefixed words. The results did not yield significant differences. This asymmetry between suffix and prefix processing has also been observed in other linguistic tasks. In suffixed words, the suffix would be processed on-line during the production of the root, in an analytic fashion. Prefixed words, in contrast, seem to be processed without decomposition, as pseudo-affixed words.


Assuntos
Escrita Manual , Idioma , Semântica , Adulto , França , Humanos , Processos Mentais
18.
Int J Telerehabil ; 4(1): 7-14, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-25945192

RESUMO

The purpose of this pilot study was to investigate the efficacy of in-home telerehabilitation for people with Chronic Obstructive Pulmonary Disease (COPD). Three community-living elders with COPD were recruited in a rehabilitation outpatient group and by direct referrals from pneumologists with outpatients who have COPD. A pre/post-test design without a control group was used for this pilot study. Telerehabilitation sessions (15 sessions) were conducted by two trained physiotherapists from a service center to the patient's home. Locomotor function (walking performance) and quality of life were measured in person prior to and at the end of the treatment by an independent assessor. Clinical outcomes improved for all subjects except for locomotor function in the first participant. In-home telerehabilitation for people with COPD is a realistic alternative to dispense rehabilitation services for patients requiring physical therapy follow-up.

20.
Mol Endocrinol ; 24(7): 1349-58, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20484414

RESUMO

Posttranslational modifications are instrumental to achieve gene- and tissue-specific regulatory outcomes by transcription factors. Nuclear receptors are dynamically modulated by several types of posttranslational modifications including phosphorylation, methylation, acetylation, ubiquitination, and sumoylation. The estrogen-related receptor alpha (ERRalpha, NR3B1) is phosphorylated on multiple sites, and sumoylated in the amino-terminal region in a phosphorylation-dependent manner. Here we demonstrate that ERRalpha interacts with and is acetylated by p300 coactivator associated factor (PCAF) in vitro and in mouse liver. Purified PCAF acetylated the DNA-binding domain of ERRalpha on four highly-conserved lysines. In addition, coexpression of PCAF reduced the transcriptional activity of ERRalpha and, reciprocally, a deacetylase screen identified histone deacetylase 8 (HDAC8) and sirtuin 1 homolog (Sirt1) as independent enhancers of ERRalpha transcriptional function. HDAC8 and Sirt1 were also demonstrated to interact directly with ERRalpha in vivo and to deacetylate and increase the DNA binding affinity of ERRalpha in vitro. The removal of PCAF increases the DNA binding of ERRalpha in vivo, whereas the removal of Sirt1 and HDAC8 decreases it as assessed by chromatin immunoprecipitation assay. Altogether, our results show that ERRalpha is an acetylated protein and imply the existence of a dynamic acetylation/deacetylation switch involved in the control of ERRalpha transcriptional activity.


Assuntos
Receptores Estrogênicos/genética , Receptores Estrogênicos/metabolismo , Transcrição Genética/genética , Fatores de Transcrição de p300-CBP/metabolismo , Acetilação , Animais , Células COS , Linhagem Celular , Chlorocebus aethiops , Imunoprecipitação da Cromatina , Ensaio de Desvio de Mobilidade Eletroforética , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Humanos , Immunoblotting , Imunoprecipitação , Espectrometria de Massas , Camundongos , Ligação Proteica , Sirtuína 1/genética , Sirtuína 1/metabolismo , Fatores de Transcrição de p300-CBP/genética
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