Orientador: Mauro Gonçalves / Banca: Adalgiso Coscrato Cardozo / Banca: Luis Mochizuki / Resumo: O principal objetivo dessa Dissertação foi avaliar o desempenho em contrações isométricas de flexo-extensão do joelho e o padrão da marcha em indivíduos idosos com potencial para sofrerem quedas e avaliar o efeito de um treinamento sobre essas variaveis. Quinze mulheres (71,67+6,60 anos), caidoras, as quais foram divididas aleatoriamente em dois grupos (Grupo Treino - GT; e Grupo Controle - GC) realizaram testes antes e após um período de treinamento de 10 semanas de Facilitação Neuromuscular Proprioceptiva (FNP): i) Aplicação da Escala de Equilíbrio de Berg (EEB), contrações isométricas voluntárias máximas de flexão e extensão do joelho; ii) marcha por vinte minutos na velocidade de preferência; iii) analise da marcha a 2km/h, 3km/h, 4km/h e na velocidade de preferência. Nos testes de contração máxima a Taxa de Desenvolvimento de Força (TDF) e força máxima foram obtidas. O registro eletromiografico (EMG) de Root Mean Square (RMS), freqüência mediana (FM) e Indice de Co-ativação (IC) entre músculos vasto-lateral (VL), vasto-medial (VM), reto-femoral e bíceps femoral (BF) foram determinados. Durante o teste de marcha por 20 minutos foram adquiridos os registros EMG dos VL, RF, VM, BF, tibial anterior (TA), fibular longo (FB), gastrocnêmio medial (GM) e gastrocnêmio lateral (GL) em três diferentes períodos do protocolo (no inicio, no meio e no final do protocolo). Ainda, esses registros foram obtidos em quatro diferentes fases da marcha: pré-contato do calcâneo no solo (Pré), durante o toque do mesmo (Toque), durante a retirada dos dedos (Retirada) e durante todo o ciclo da marcha (Ciclo). Também foram determinadas as seguintes variáveis cinemáticas: freqüência e comprimento de passada, velocidade do calcâneo no momento do seu toque no solo (VEL), sua aceleração mínima prévia ao toque e tempo de apoio. Por fim, no protocolo com quatro... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The main objective of this Dissertation was to evaluate the knee flexion-extension isometric performance and gait pattern in elderly fallers and to evaluate a training course effect on these variables. Fifteen elderly female fallers (71.67+6.60 years), randomly divided into two groups (Training Group - TG, and Control Group - GC), performed a tests battery before and after 10 weeks of Proprioceptive Neuromuscular Facilitation training period, consisting of: i) The Berg Balance Scale (BBS) application, knee extension and flexion isometric contractions, ii) twenty minutes gait at their preferred walking speed, iii) gait analysis at 2km/h, 3 km/h; 4km/h and in their preferred walking speed. In maximum knee flexion and extension contractions the Rate of Development Force (TDF) was achieved in as the maximal force, the electromyography (EMG) Root Mean Square (RMS), median frequency (MF) and Coactivation Index (IC) from vastus-lateralis (VL), vastus-medialis (VM), rectusfemoris (RF) and biceps femoris (BF) muscles. During the 20 minutes walking test the EMG signal from VL, RF, VM, BF, tibialis anterior (TA), fibularis longus (FB), medial gastrocnemius (GM) and lateral gastrocnemius (GL) in three different Protocol periods (at the beginning, medial and at the end). These records were obtained in four different gait phases: Pre-contact (Pre), during the the heel contact (Contact), at the toe-off and throughout the entire gait cycle. The EMG data were also used to determine CI during gait. Also the following kinemetry variables were measured: step length and frequency, heel velocity during its strike on the ground (VEL) and its minimal acceleration previous the heel strike. Finally, during the four speed protocol the VEL, CI around knee and ankle and the RMS and MF were determined at Pre, Contact and Cycle. The results show that during isometric contractions the CI is related significantly with... (Complete abstract click electronic access below) / Mestre

O controle postural em idosos tem sido estudado com o objetivo de melhor entender os fatores que levam esta população a sofrer mais quedas que os indivíduos jovens. A maior variabilidade de força dos músculos flexores plantares (MFP) aparenta estar diretamente associada ao menor controle postural principalmente em adultos jovens. Além disto, o treinamento específico de estabilidade de força dos MFP em baixas intensidades parece diminuir a variabilidade de força destes músculos e também diminuir a oscilação postural de adultos jovens. Entretanto, faltam esclarecimentos sobre a associação entre variabilidade de força dos MFP e oscilação postural na população idosa, bem como os efeitos de um treinamento específico de estabilidade de força destes músculos para esta mesma população. Sendo assim, o objetivo do presente estudo foi analisar a associação entre variabilidade de força dos MFP e a oscilação postural de idosas e examinar os efeitos do treinamento de estabilidade de força na variabilidade da força dos MFP, na coativação muscular dos músculos tibial anterior (TA) e gastrocnêmio medial (GM) e na oscilação corporal destas idosas. Para isto, 40 mulheres idosas foram divididas em quatro grupos: Grupo GT5 (n=10) que realizou treinamentos a 5% da contração isométrica voluntária máxima (CIVM) dos MFP; Grupo GT10 (n=10) que realizou treinamentos a 10% da CIVM dos MFP; Grupo GTLP (n=10) que realizou treinamentos a 10% de uma repetição máxima dos MFP no equipamento Leg Press; Grupo GC (n=10) que não realizou nenhum treinamento específico para os MFP e foi utilizado como controle. Foram avaliadas a oscilação corporal durante a manutenção da postura bipodal ereta, a variabilidade da força dos MFP e a coativação muscular dos músculos TA e GM antes e após o período de treinamento. Este treinamento foi realizado uma vez por semana durante quatro semanas. Em cada sessão de treino a participante realizou cinco séries em que mantinha por 30 segundos a força isométrica de flexão plantar, de acordo com as especificações de seu grupo. Os resultados revelaram que o treinamento de estabilidade de força dos MFP realizado pelos grupos GT5, GT10 e GTLP foi eficiente e diminuiu a variabilidade de força das participantes na condição de 5% da CIVM com feedback visual, além disso, mostrou que o grupo GT5 também diminuiu sua variabilidade de força para a condição 10% da CIVM com feedback visual. Em relação ao controle postural, foi observado que os grupos GT5 e GT10 aumentaram sua amplitude média de oscilação na direção ântero-posterior após o treinamento. Com relação à ativação dos músculos TA e GM, os grupos GT5 e GT10 diminuíram o índice de coativação muscular para as condições 5% e 10% com feedback visual após o treinamento e o grupo GT5 ainda apresentou diminuição da coativação para a condição 5% sem feedback visual. Finalmente, os resultados apontaram que para população idosa não há relação entre a variabilidade de força dos MFP e o controle da postura. Portanto, estes resultados indicam que, na população idosa não existe associação entre controle postural e variabilidade de força dos MFP, e mesmo que não esteja claro o efeito do treinamento no controle da postura, a redução da variabilidade da força e coativação muscular podem ser interpretadas como um ganho em termos de controle motor / Elderly postural control has been studied in order to better understand the factors that lead this population to suffer more falls than young individuals. Greater variability of plantar flexor muscles (PFM) strength appears to be directly associated to lower postural control mainly in young adults. In addition, specific training of PFM strength stability at low intensities seems to decrease force variability of these muscles and also to decrease postural oscillation of young adults. However, there is a lack of clarification about the association between PFM force variability and postural oscillation in elderly population, as well as the effects of specific stability strength training of these muscles for this same population. Thus, the objective of the present study was to analyze the association between PFM force variability and postural oscillation in elderly, and to examine the effects of strength stability training on PFM force variability in the muscle coactivation of anterior tibial muscles (AT) and medial gastrocnemius (MG) and in the body oscillation of these elderly women. For this, 40 elderly women were divided into four groups: Group TG5 (n = 10) who performed training at 5% of maximal voluntary isometric contraction (MVIC) of PFM; TG10 group (n = 10) who performed training at 10% of the MVIC of PFM; TGLP group (n = 10) who underwent training at 10% of a maximum repetition of the PFMs in the Leg Press equipment; Group CG (n = 10) who did not perform any specific training for PFMs and was used as control. Body oscillation was evaluated during maintenance of upright bipodal posture, PFM force variability, and muscle coactivation of AT and MG muscles before and after the training period. This training was performed once a week for four weeks. In each training session participant performed five series in which he maintained for 30 seconds the isometric force of plantar flexion, according to the specifications of his group. The results showed that the PFM force stability training performed by TG5, TG10 and TGLP groups was efficient and decreased the strength variability of the participants in the 5% condition of the MVIC with visual feedback, in addition, showed that the TG5 group also decreased its force variability to the 10% MVIC condition with visual feedback. Regarding the postural control, it was observed that the TG5 and TG10 groups increased their mean amplitude of oscillation in the anteroposterior direction after the training. Regarding the activation of the AT and MG muscles, the TG5 and TG10 groups decreased the muscle activation rate for the 5% and 10% conditions with visual feedback after the training and the TG5 group still showed a decrease of the coactivation for the condition 5% without visual feedback. Finally, the results pointed out that for the elderly population there is no relation between the PFM strength variability and the posture control. Therefore, these results indicate that, in the elderly population, there is no association between postural control and PFM strength variability, and even though the effect of training on posture control is not clear, the reduction in strength variability and muscle coactivation can be interpreted as a gain in terms of motor control

O controle postural em idosos tem sido estudado com o objetivo de melhor entender os fatores que levam esta população a sofrer mais quedas que os indivíduos jovens. A maior variabilidade de força dos músculos flexores plantares (MFP) aparenta estar diretamente associada ao menor controle postural principalmente em adultos jovens. Além disto, o treinamento específico de estabilidade de força dos MFP em baixas intensidades parece diminuir a variabilidade de força destes músculos e também diminuir a oscilação postural de adultos jovens. Entretanto, faltam esclarecimentos sobre a associação entre variabilidade de força dos MFP e oscilação postural na população idosa, bem como os efeitos de um treinamento específico de estabilidade de força destes músculos para esta mesma população. Sendo assim, o objetivo do presente estudo foi analisar a associação entre variabilidade de força dos MFP e a oscilação postural de idosas e examinar os efeitos do treinamento de estabilidade de força na variabilidade da força dos MFP, na coativação muscular dos músculos tibial anterior (TA) e gastrocnêmio medial (GM) e na oscilação corporal destas idosas. Para isto, 40 mulheres idosas foram divididas em quatro grupos: Grupo GT5 (n=10) que realizou treinamentos a 5% da contração isométrica voluntária máxima (CIVM) dos MFP; Grupo GT10 (n=10) que realizou treinamentos a 10% da CIVM dos MFP; Grupo GTLP (n=10) que realizou treinamentos a 10% de uma repetição máxima dos MFP no equipamento Leg Press; Grupo GC (n=10) que não realizou nenhum treinamento específico para os MFP e foi utilizado como controle. Foram avaliadas a oscilação corporal durante a manutenção da postura bipodal ereta, a variabilidade da força dos MFP e a coativação muscular dos músculos TA e GM antes e após o período de treinamento. Este treinamento foi realizado uma vez por semana durante quatro semanas. Em cada sessão de treino a participante realizou cinco séries em que mantinha por 30 segundos a força isométrica de flexão plantar, de acordo com as especificações de seu grupo. Os resultados revelaram que o treinamento de estabilidade de força dos MFP realizado pelos grupos GT5, GT10 e GTLP foi eficiente e diminuiu a variabilidade de força das participantes na condição de 5% da CIVM com feedback visual, além disso, mostrou que o grupo GT5 também diminuiu sua variabilidade de força para a condição 10% da CIVM com feedback visual. Em relação ao controle postural, foi observado que os grupos GT5 e GT10 aumentaram sua amplitude média de oscilação na direção ântero-posterior após o treinamento. Com relação à ativação dos músculos TA e GM, os grupos GT5 e GT10 diminuíram o índice de coativação muscular para as condições 5% e 10% com feedback visual após o treinamento e o grupo GT5 ainda apresentou diminuição da coativação para a condição 5% sem feedback visual. Finalmente, os resultados apontaram que para população idosa não há relação entre a variabilidade de força dos MFP e o controle da postura. Portanto, estes resultados indicam que, na população idosa não existe associação entre controle postural e variabilidade de força dos MFP, e mesmo que não esteja claro o efeito do treinamento no controle da postura, a redução da variabilidade da força e coativação muscular podem ser interpretadas como um ganho em termos de controle motor / Elderly postural control has been studied in order to better understand the factors that lead this population to suffer more falls than young individuals. Greater variability of plantar flexor muscles (PFM) strength appears to be directly associated to lower postural control mainly in young adults. In addition, specific training of PFM strength stability at low intensities seems to decrease force variability of these muscles and also to decrease postural oscillation of young adults. However, there is a lack of clarification about the association between PFM force variability and postural oscillation in elderly population, as well as the effects of specific stability strength training of these muscles for this same population. Thus, the objective of the present study was to analyze the association between PFM force variability and postural oscillation in elderly, and to examine the effects of strength stability training on PFM force variability in the muscle coactivation of anterior tibial muscles (AT) and medial gastrocnemius (MG) and in the body oscillation of these elderly women. For this, 40 elderly women were divided into four groups: Group TG5 (n = 10) who performed training at 5% of maximal voluntary isometric contraction (MVIC) of PFM; TG10 group (n = 10) who performed training at 10% of the MVIC of PFM; TGLP group (n = 10) who underwent training at 10% of a maximum repetition of the PFMs in the Leg Press equipment; Group CG (n = 10) who did not perform any specific training for PFMs and was used as control. Body oscillation was evaluated during maintenance of upright bipodal posture, PFM force variability, and muscle coactivation of AT and MG muscles before and after the training period. This training was performed once a week for four weeks. In each training session participant performed five series in which he maintained for 30 seconds the isometric force of plantar flexion, according to the specifications of his group. The results showed that the PFM force stability training performed by TG5, TG10 and TGLP groups was efficient and decreased the strength variability of the participants in the 5% condition of the MVIC with visual feedback, in addition, showed that the TG5 group also decreased its force variability to the 10% MVIC condition with visual feedback. Regarding the postural control, it was observed that the TG5 and TG10 groups increased their mean amplitude of oscillation in the anteroposterior direction after the training. Regarding the activation of the AT and MG muscles, the TG5 and TG10 groups decreased the muscle activation rate for the 5% and 10% conditions with visual feedback after the training and the TG5 group still showed a decrease of the coactivation for the condition 5% without visual feedback. Finally, the results pointed out that for the elderly population there is no relation between the PFM strength variability and the posture control. Therefore, these results indicate that, in the elderly population, there is no association between postural control and PFM strength variability, and even though the effect of training on posture control is not clear, the reduction in strength variability and muscle coactivation can be interpreted as a gain in terms of motor control

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Title Ways to influence amateur s athletes postural stability Objectives The aim of this study is to describe the selected parameters of body composition and postural stability of the amateur s athletes (floorball players) group and to assess the efficiency of short-term intervention exercise based on senzomotor stimulation, acral coactivation therapy and plyometrics. Methods This work is a descriptive work, one part of it is the intervention. Two groups of amateur s athletes (floorball players) were examined during the study - intervention group(n = 16, average height = 178,23 cm (std 7,18), average weight = 80,04 (std 11,53), average age = 25,15 years (std3,31 )) and control group(n = 8, ave- rage height = 181,48 cm (std 5,59), average weight = 82,29 kg (std 11,20), average age = 27,07 let (2,68)). Each participant underwent the entrance measurement both on Footscan to evaluate the level of postural stability by selected parameters and on InBody 3.0 a Tanita to evaluate the level of body composition by selected parame- ters. Then the intervention group took part in the intervention exercise. After the six week intervention period underwent both groups the second measurement. The results of both measurements were evaluated, compared and statistically analyzed. Results The results showed great...

De l’organisme unicellulaire aux organismes multicellulaires complexes, la spécification cellulaires est un aspect fondamental de la biologie de l'adaptation et du développement. Les cellules souches pluripotentes (CSP) telles que les embryonnaires (CSE) fournissent un modèle approprié pour étudier les mécanismes de régulation et la spécification du sort des cellules chez les mammifères. Les ESC de souris sont connus pour être de nature hétérogènes et sont rapportées comme étant composées de multiples états de cellules souches ressemblant à des stades distincts du développement embryonnaire précoce, tels que totipotentes, pluripotentes, préparées et endoderme primitif. Malgré des études approfondies sur les CSE, les mécanismes moléculaires régulant leur hétérogénéité et l'état totipotent, en particulier, ne sont pas bien compris. Le travail présenté dans cette thèse utilise les CSE de souris comme modèle intéressant pour déterminer les mécanismes de signalisation et de régulation génique qui conduisent à l'hétérogénéité cellulaire et l'état cellulaire totipotent des CSE. Dans une première étude, nous avons utilisé la cytométrie en flux de masse pour analyser simultanément de multiples protéines régulatrices des cellules souches, en mettant l'accent sur les facteurs de transcription clés, les protéines de signalisation et les modificateurs de la chromatine qui régissent les CSE de souris. Les données de cytométrie en flux de masse ont révélé des variations dans les niveaux protéiques cellulaires individuels des régulateurs des cellules souches et ont souligné la vaste coactivation des voies de signalisation cellulaire dans des conditions de culture définies des CSE. De plus, l'application de la cytométrie en flux de masse a facilité l'identification d'états cellulaires distincts et de leurs caractéristiques moléculaires au sein des CSE, offrant des aperçus de leurs variations selon différentes conditions de culture, validant ainsi la présence d'hétérogénéité cellulaire dans les CSE de souris. Dans une deuxième étude, nous avons identifié la signalisation du facteur de croissance des os (BMP) comme inducteur de l'état totipotent. Nous avons également constaté que le rôle du BMP dans la totipotence est réprimé par la coactivation des voies FGF, NODAL et WNT. En inhibant ces voies coactivées, nous démontrons l'amélioration de l'induction de cellules totipotentes et la suppression des états préparés et d'endoderme primitif. Nous avons validé les changements d'état cellulaire au niveau cellulaire unique grâce à un séquençage d'ARNm à cellule unique. De plus, nous avons également démontré que les cellules totipotentes reprogrammées in vitro imitent les cellules totipotentes de l'embryon préimplantatoire avec la capacité de générer des blastocystes in vitro (Blastoïdes) et de s'intégrer dans les lignées embryonnaires et extra-embryonnaires chez la souris. Ensemble, ces résultats ont révélé les mécanismes de signalisation du BMP pour réguler à la fois l'état totipotent et l'hétérogénéité des CSE. Pour la troisième étude, nous avons utilisé les observations clés de nos données de cytométrie en flux de masse (première étude) pour évaluer le rôle des protéines régulatrices clés pour promouvoir l'état cellulaire totipotent. Ici, nous démontrons que NACC1, un régulateur transcriptionnel des CSE, agit également comme un régulateur important des cellules totipotentes. Après avoir identifié NACC1 comme un régulateur potentiel à partir de données de protéines cellulaires à cellule unique et de transcriptome en vrac, nous avons validé sa fonction en utilisant une suppression médiée par CRISPR en combinaison avec des conditions de reprogrammation cellulaire pluripotente à totipotente. Ensuite, nous avons intégré une combinaison d'approches génomiques pour étudier les changements au niveau du système dépendants de NACC1 dans le transcriptome, l'accessibilité à la chromatine et la liaison à l'ADN génomique. Ensemble, ces données ont révélé que NACC1 induit à la fois les programmes d'expression génique codant et de gènes de rétrotransposons pour promouvoir l'état cellulaire totipotent. Enfin, nous avons montré que NACC1 régule les éléments rétrotransposables MERVL-int et MT2_Mm pour moduler l'expression des gènes codants de l'état totipotent. En conclusion, cette thèse révèle la nature hétérogène des CSE de souris au niveau protéique à cellule unique, élucide le rôle significatif et les mécanismes de la voie de signalisation BMP pour réguler l'état totipotent et l'hétérogénéité des CSE, et dévoile les mécanismes de régulation génique dépendants de NACC1 pour promouvoir l'état totipotent. Ces résultats ouvrent la voie à des études ultérieures visant à comprendre la spécification de l'état des cellules souches et leur transition via la modulation des voies de signalisation / facteurs de transcription. De plus, ces mécanismes peuvent réguler l'état cellulaire totipotent chez l'homme, éclairant l'hétérogénéité cellulaire dans les CSE humaines et dans des contextes pathologiques, tels que le cancer. / From unicellular entities to intricate multicellular organisms, the omnipresent process of cell fate specification is a fundamental aspect of adaptation and developmental biology. Pluripotent stem cells (PSCs) such as embryonic stem cells (ESCs) provide a suitable model to study the regulatory mechanisms and cell fate specification in mammals. Intriguingly, mouse ESCs are known to be heterogenous in nature and are reported to consist of multiple stem cell states resembling distinct stages of early embryogenesis, such as totipotent, pluripotent, primed, and primitive endoderm. Despite extensive study of ESCs, the molecular mechanisms regulating their heterogeneity and the totipotent state in particular are not well understood. The work presented in this thesis utilizes mouse ESCs as an attractive model to delineate the signaling and gene regulatory mechanisms driving the cellular heterogeneity and the totipotent cell state of ESCs. In the first study, we utilized mass cytometry (cytometry by time of flight) to concurrently analyse multiple stem cell regulatory proteins, focusing on key transcription factors, signaling proteins, and chromatin modifiers that govern mouse ESCs. Mass cytometry data revealed variations in the single-cell protein levels of stem cell regulators and highlighted the extensive cross-activation of cell signaling pathways across defined culture conditions of ESCs. Furthermore, the application of mass cytometry facilitated the identification of distinct cell states and their molecular features within ESCs, offering insights into their variations across different culture conditions, thereby validating the presence of cellular heterogeneity in mouse ESCs. In the second study, we identified bone morphogenetic protein (BMP) signaling as an inducer of the totipotent state. We also found that, BMP’s role for totipotency is repressed by the cross-activation of FGF, NODAL, and WNT pathways. Through rational inhibition of these cross-activated pathways, we demonstrate the enhancement in the induction of totipotent cells and suppression of primed and primitive endoderm states. We validated the cell state changes at the single-cell level through single-cell mRNA sequencing. Furthermore, we also demonstrate that the in-vitro reprogrammed totipotent cells mimic the totipotent cells of preimplantation embryo with the potency to generate in-vitro blastocyst (Blastoids) and to integrate into both embryonic and extra-embryonic lineages in the mice. Together these results revealed BMP signaling mechanisms to regulate both the totipotent state and the heterogeneity of ESCs. For our third study, we utilized the key observations from our mass cytometry data (first study) to evaluate the role of key regulatory proteins to promote the totipotent cell state. Here, we demonstrate that NACC1, a transcriptional regulator of ESCs, also acts as an important regulator of totipotent cells. Following identification of NACC1 as a potential regulator from both single-cell protein and bulk transcriptome data, we validated its function using CRISPR-mediated knock-out in combination with pluripotent-to-totipotent cell reprogramming conditions. Next, we integrated a combination of genomic approaches to study the NACC1 dependent system’s level changes in the transcriptome, chromatin accessibility and genomic DNA binding. Together, these data revealed that NACC1 induces both the coding gene and retrotransposon gene expression programs to promote the totipotent cell state. Finally, we showed that NACC1 regulates MERVL-int and MT2_Mm retrotransposable elements to modulate the expression of coding genes of the totipotent state. In conclusion, this thesis reveals the heterogeneous nature of mouse ESCs at the single-cell protein level, elucidates the significant role and mechanisms of BMP signaling pathway to regulate the totipotent state and ESC heterogeneity, and unveils NACC1 dependent gene regulatory mechanisms to promote the totipotent state. These findings open the door for subsequent studies aimed at understanding stem cell state specification and their transition occurring via modulation of signaling pathways / transcription factors. Moreover, these mechanisms may regulate the totipotent cell state in humans, shedding light on the cellular heterogeneity in human ESCs and in disease contexts, such as cancer.