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In bony fishes, patterning of the vertebral column, or spine, is guided by a metameric blueprint established in the notochord sheath. Notochord segmentation begins days after somitogenesis concludes and can occur in its absence. However, somite patterning defects lead to imprecise notochord segmentation, suggesting that these processes are linked. Here, we identify that interactions between the notochord and the axial musculature ensure precise spatiotemporal segmentation of the zebrafish spine. We demonstrate that myoseptum-notochord linkages drive notochord segment initiation by locally deforming the notochord extracellular matrix and recruiting focal adhesion machinery at these contact points. Irregular somite patterning alters this mechanical signaling, causing non-sequential and dysmorphic notochord segmentation, leading to altered spine development. Using a model that captures myoseptum-notochord interactions, we find that a fixed spatial interval is critical for driving sequential segment initiation. Thus, mechanical coupling of axial tissues facilitates spatiotemporal spine patterning.
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Padronização Corporal , Notocorda , Somitos , Coluna Vertebral , Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Peixe-Zebra/embriologia , Notocorda/embriologia , Notocorda/metabolismo , Somitos/embriologia , Somitos/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Coluna Vertebral/embriologia , Transdução de Sinais , Regulação da Expressão Gênica no Desenvolvimento , Matriz Extracelular/metabolismo , Embrião não Mamífero/metabolismoRESUMO
BACKGROUND: Perinatal running participation has increased recently; however, pregnancy related symptoms can limit activity. Perinatal running biomechanics could inform interventions to help perinatal individuals maintain an active lifestyle. RESEARCH QUESTION: Are perinatal running biomaechanics and muscle activation different compared to nulligravida females? METHODS: Sixteen pregnant participants completed self-selected velocity running during second trimester (2 T), third trimester (3 T), and postpartum (PP) and 16 matched controls completed these procedures once in this case control study. Kinematic, kinetic, and electromyography (EMG) data were collected using a motion capture system, force plates, and EMG electrodes. Peak trunk, pelvis, hip, knee, and ankle kinematics and hip, knee, and ankle moments during stance phase, and average and peak erector spinae (ES), gluteus maximus (GMax), and gluteus medius (GMed) EMG amplitude and duration of activation during stance and swing phases were calculated. Independent t-tests were used to compare 2 T, 3 T, and PP to control participants (α < 0.05). RESULTS: Running velocity was slower during 3 T compared to control participants. At all pregnancy timepoints compared to the control group, peak trunk contralateral rotation was smaller. During 2 T and 3 T peak hip flexor moments were smaller. At 3 T pelvis contralateral rotation was smaller, ES average amplitude was greater during swing, GMax percent duration during stance and GMed percent duration during swing were smaller. At PP trunk flexion was smaller and knee abduction was greater (all p < 0.05). CONCLUSIONS: Decreased running velocity may help offset increased demand during pregnancy. During 3 T, greater ES activation, smaller trunk and pelvis motion, and altered gluteal activation could indicate trunk rigidity combined with modified hip stabilizer muscle utilization. During PP, the rigid trunk combined with greater knee abduction may indicate hip and trunk strength deficits. Altered trunk and hip motion and activation could be relevant to pathologies such as perinatal low back, pelvic girdle, or knee pain.
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Articulação do Quadril , Corrida , Humanos , Feminino , Gravidez , Articulação do Quadril/fisiologia , Fenômenos Biomecânicos , Estudos de Casos e Controles , Músculo Esquelético/fisiologia , Eletromiografia/métodos , NádegasRESUMO
All epidemiological studies on pregnancy fall risk to date have relied on postpartum recall. This study investigated the accuracy of postpartum recall of falls that were reported during pregnancy, including assessment of fall efficacy as a possible reason for recall inaccuracy. Twenty participants reported fall experiences weekly during pregnancy, but one participant was excluded as an outlier. A fall efficacy questionnaire was completed every six weeks during pregnancy. A postpartum survey to mimic previous studies (Dunning, Lemasters, and Bhattacharya 2010; Dunning et al. 2003) was delivered to determine recall accuracy. Postpartum recall of fall events each gestational month matches the previous study (Dunning, Lemasters, and Bhattacharya 2010). However, recall of falls is 16% underestimated and recall of all fall events is 30% overestimated in postpartum survey. There is a slight relationship between fall efficacy and true falls, but not between fall efficacy and fall recall. Our study suggests fall risk needs to be intermittently surveyed throughout pregnancy rather than assessed via postpartum survey.Practitioner summary: This study investigated the accuracy of postpartum survey of fall risk during pregnancy and the possibility of fall efficacy as a covariate. We used three corresponding surveys. We found inaccuracies in postpartum survey, not explain by fall efficacy.
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Wide field of view microscopy that can resolve 3D information at high speed and spatial resolution is highly desirable for studying the behaviour of freely moving model organisms. However, it is challenging to design an optical instrument that optimises all these properties simultaneously. Existing techniques typically require the acquisition of sequential image snapshots to observe large areas or measure 3D information, thus compromising on speed and throughput. Here, we present 3D-RAPID, a computational microscope based on a synchronized array of 54 cameras that can capture high-speed 3D topographic videos over an area of 135 cm2, achieving up to 230 frames per second at spatiotemporal throughputs exceeding 5 gigapixels per second. 3D-RAPID employs a 3D reconstruction algorithm that, for each synchronized snapshot, fuses all 54 images into a composite that includes a co-registered 3D height map. The self-supervised 3D reconstruction algorithm trains a neural network to map raw photometric images to 3D topography using stereo overlap redundancy and ray-propagation physics as the only supervision mechanism. The resulting reconstruction process is thus robust to generalization errors and scales to arbitrarily long videos from arbitrarily sized camera arrays. We demonstrate the broad applicability of 3D-RAPID with collections of several freely behaving organisms, including ants, fruit flies, and zebrafish larvae.
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The vertebrate spine is a metameric structure composed of alternating vertebral bodies (centra) and intervertebral discs.1 Recent studies in zebrafish have shown that the epithelial sheath surrounding the notochord differentiates into alternating cartilage-like (col2a1/col9a2+) and mineralizing (entpd5a+) segments which serve as a blueprint for centra formation.2,3,4,5 This process also defines the trajectories of migrating sclerotomal cells that form the mature vertebral bodies.4 Previous work demonstrated that notochord segmentation is typically sequential and involves the segmented activation of Notch signaling.2 However, it is unclear how Notch is activated in an alternating and sequential fashion. Furthermore, the molecular components that define segment size, regulate segment growth, and produce sharp segment boundaries have not been identified. In this study, we uncover that a BMP signaling wave acts upstream of Notch during zebrafish notochord segmentation. Using genetically encoded reporters of BMP activity and signaling pathway components, we show that BMP signaling is dynamic as axial patterning progresses, leading to the sequential formation of mineralizing domains in the notochord sheath. Genetic manipulations reveal that type I BMP receptor activation is sufficient to ectopically trigger Notch signaling. Moreover, loss of Bmpr1ba and Bmpr1aa or Bmp3 function disrupts ordered segment formation and growth, which is recapitulated by notochord-specific overexpression of the BMP antagonist, Noggin3. Our data suggest that BMP signaling in the notochord sheath precedes Notch activation and instructs segment growth, facilitating proper spine morphogenesis.
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Notocorda , Peixe-Zebra , Animais , Peixe-Zebra/fisiologia , Padronização Corporal/fisiologia , Coluna Vertebral , Transdução de Sinais , Regulação da Expressão Gênica no DesenvolvimentoRESUMO
In bony fishes, formation of the vertebral column, or spine, is guided by a metameric blueprint established in the epithelial sheath of the notochord. Generation of the notochord template begins days after somitogenesis and even occurs in the absence of somite segmentation. However, patterning defects in the somites lead to imprecise notochord segmentation, suggesting these processes are linked. Here, we reveal that spatial coordination between the notochord and the axial musculature is necessary to ensure segmentation of the zebrafish spine both in time and space. We find that the connective tissues that anchor the axial skeletal musculature, known as the myosepta in zebrafish, transmit spatial patterning cues necessary to initiate notochord segment formation, a critical pre-patterning step in spine morphogenesis. When an irregular pattern of muscle segments and myosepta interact with the notochord sheath, segments form non-sequentially, initiate at atypical locations, and eventually display altered morphology later in development. We determine that locations of myoseptum-notochord connections are hubs for mechanical signal transmission, which are characterized by localized sites of deformation of the extracellular matrix (ECM) layer encasing the notochord. The notochord sheath responds to the external mechanical changes by locally augmenting focal adhesion machinery to define the initiation site for segmentation. Using a coarse-grained mathematical model that captures the spatial patterns of myoseptum-notochord interactions, we find that a fixed-length scale of external cues is critical for driving sequential segment patterning in the notochord. Together, this work identifies a robust segmentation mechanism that hinges upon mechanical coupling of adjacent tissues to control patterning dynamics.
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To study the behavior of freely moving model organisms such as zebrafish (Danio rerio) and fruit flies (Drosophila) across multiple spatial scales, it would be ideal to use a light microscope that can resolve 3D information over a wide field of view (FOV) at high speed and high spatial resolution. However, it is challenging to design an optical instrument to achieve all of these properties simultaneously. Existing techniques for large-FOV microscopic imaging and for 3D image measurement typically require many sequential image snapshots, thus compromising speed and throughput. Here, we present 3D-RAPID, a computational microscope based on a synchronized array of 54 cameras that can capture high-speed 3D topographic videos over a 135-cm^2 area, achieving up to 230 frames per second at throughputs exceeding 5 gigapixels (GPs) per second. 3D-RAPID features a 3D reconstruction algorithm that, for each synchronized temporal snapshot, simultaneously fuses all 54 images seamlessly into a globally-consistent composite that includes a coregistered 3D height map. The self-supervised 3D reconstruction algorithm itself trains a spatiotemporally-compressed convolutional neural network (CNN) that maps raw photometric images to 3D topography, using stereo overlap redundancy and ray-propagation physics as the only supervision mechanism. As a result, our end-to-end 3D reconstruction algorithm is robust to generalization errors and scales to arbitrarily long videos from arbitrarily sized camera arrays. The scalable hardware and software design of 3D-RAPID addresses a longstanding problem in the field of behavioral imaging, enabling parallelized 3D observation of large collections of freely moving organisms at high spatiotemporal throughputs, which we demonstrate in ants (Pogonomyrmex barbatus), fruit flies, and zebrafish larvae.
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BACKGROUND: Falls are common during pregnancy and present potential for injury to the pregnant individual and the baby. RESEARCH QUESTION: Do center of pressure characteristics during single leg stance differ between participants during and after pregnancy and nulligravida participants in the presence and absence of visual input? METHODS: Nineteen pregnant participants completed testing during the second trimester, the third trimester, and 4-6 months post-partum. Matched, nulligravida females completed testing once. All participants performed single leg stance on a force platform on each limb for up to 20 s with eyes open and with eyes closed. Center of pressure characteristics were compared between pregnant and nulligravida females using three separate 2 × 2 mixed way ANOVAs, one for each pregnancy time point (second trimester, third trimester, and post-partum) with Bonferroni correction. RESULTS: Pregnant females demonstrated smaller single leg stance time with eyes closed during the third trimester. During the second and third trimester, pregnant participants demonstrated smaller sway and sway velocity across eyes open and eyes closed conditions. During the third trimester and post-partum, pregnant participants demonstrated greater median frequency of the center of pressure data. Pregnant participants also demonstrated smaller sample entropy in the anteroposterior direction during the second and third trimesters and in the mediolateral direction during the second trimester. SIGNIFICANCE: The decreased total sway and sway velocity observed during pregnancy may reflect rigidity or a protective strategy during single limb stance. Additionally, center of pressure data were less smooth and more repetitive during pregnancy indicating robust differences in postural control strategies and potentially increased fall risk. Because single limb stance is a component of many activities of daily living, the single limb stance task may have clinical utility for testing or training balance in this population with a goal of decreasing falls.
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Atividades Cotidianas , Perna (Membro) , Feminino , Humanos , Paridade , Equilíbrio Postural , GravidezRESUMO
BACKGROUND: The purpose of this study was to compare gait kinematics, kinetics, and muscle activation between pregnant females with high and low scores for low back and/or pelvic girdle pain during and after pregnancy. METHODS: Twenty participants tested during second trimester, third trimester, and again post-partum. At each session, motion capture, force plates, and surface electromyography data were captured during self-selected velocity over-ground walking. Participants completed the Quebec Back Pain Disability Scale (QBPDS) and were assigned to high (QBPDS ≥15) or low pain groups (QBPDS <15) based on third trimester scores. Two-way mixed model ANOVAs were used to compare high and low pain groups over time. FINDINGS: Nine participants met the high pain group criteria and 11 were low pain. During second trimester the high pain group compared to the low pain group demonstrated smaller peak hip flexor moments, total hip work, percent hip contribution to work, and larger percent ankle contribution to work. Pregnant females demonstrated greater hip, knee, and ankle moments, ankle work, and gluteus maximus muscle activation third trimester than second trimester. INTERPRETATION: Reduced hip and greater ankle contribution to work in the high pain group during second trimester could indicate decreased hip utilization early in pregnancy and may contribute to disability as pregnancy progresses. It is also possible kinetic differences during second trimester reflect an early strategy to reduce pain by avoiding hip joint loading. Increased moments and work during third trimester indicate a clinical imperative to better prepare pregnant females to accommodate increased joint loading and muscular demand.
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Dor da Cintura Pélvica , Fenômenos Biomecânicos , Feminino , Marcha/fisiologia , Articulação do Quadril/fisiologia , Humanos , Articulação do Joelho/fisiologia , Músculo Esquelético/fisiologia , GravidezRESUMO
BACKGROUND: The biomechanics of the trunk and lower limbs during walking and running gait are frequently assessed in individuals with low back pain (LBP). Despite substantial research, it is still unclear whether consistent and generalizable changes in walking or running gait occur in association with LBP. The purpose of this systematic review was to identify whether there are differences in biomechanics during walking and running gait in individuals with acute and persistent LBP compared with back-healthy controls. METHODS: A search was conducted in PubMed, CINAHL, SPORTDiscus, and PsycINFO in June 2019 and was repeated in December 2020. Studies were included if they reported biomechanical characteristics of individuals with and without LBP during steady-state or perturbed walking and running. Biomechanical data included spatiotemporal, kinematic, kinetic, and electromyography variables. The reporting quality and potential for bias of each study was assessed. Data were pooled where possible to compare the standardized mean differences (SMD) between back pain and back-healthy control groups. RESULTS: Ninety-seven studies were included and reviewed. Two studies investigated acute pain and the rest investigated persistent pain. Nine studies investigated running gait. Of the studies, 20% had high reporting quality/low risk of bias. In comparison with back-healthy controls, individuals with persistent LBP walked slower (SMDâ¯=â¯-0.59, 95% confidence interval (95%CI): -0.77 to -0.42)) and with shorter stride length (SMDâ¯=â¯-0.38, 95%CI: -0.60 to -0.16). There were no differences in the amplitude of motion in the thoracic or lumbar spine, pelvis, or hips in individuals with LBP. During walking, coordination of motion between the thorax and the lumbar spine/pelvis was significantly more in-phase in the persistent LBP groups (SMDâ¯=â¯-0.60, 95%CI: -0.90 to -0.30), and individuals with persistent LBP exhibited greater amplitude of activation in the paraspinal muscles (SMDâ¯=â¯0.52, 95%CI: 0.23-0.80). There were no consistent differences in running biomechanics between groups. CONCLUSION: There is moderate-to-strong evidence that individuals with persistent LBP demonstrate differences in walking gait compared to back-healthy controls.
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Dor Lombar , Corrida , Fenômenos Biomecânicos , Marcha/fisiologia , Humanos , Corrida/fisiologia , CaminhadaRESUMO
Following anterior cruciate ligament (ACL) reconstruction limb dominance for performing tasks is not considered when making rehabilitation progression decisions. The purpose of this study was to determine if strength and functional outcomes differ between individuals who injured their preferred or nonpreferred jumping limb and to determine if these same outcomes differ between individuals who injured their preferred or nonpreferred limb used to kick a ball. A secondary purpose was to determine the association of quadriceps strength and single-leg forward hop performance with patient self-reported function. Forty individuals with ACL reconstruction (age = 20.0 ± 4.6 years, height = 174.2 ± 12.7 cm, mass = 71.2 ± 12.7 kg, time since surgery = 5.3 ± 0.8 months) were included in the study. Primary outcome measures included, International Knee Documentation Committee Subjective Knee Form (IKDC) scores, quadriceps limb symmetry index (LSI) values, and single-leg forward hop LSI values. Limb preference was defined two ways, kicking a ball and performing a unilateral jump. There were no significant differences between groups based on injury to the preferred limb to kick a ball for any of the outcome variables. Individuals who injured their nonpreferred jumping limb demonstrated significantly (p = 0.05, d = 0.77) lower single-leg forward hop LSI values (81.1% ± 19.5%) compared to individuals who injured their preferred jumping limb (94.1% ± 12.6%), but demonstrated no differences in IKDC scores or quadriceps LSI values. Quadriceps LSI and single-leg forward hop LSI explained 73% of the variance in IKDC scores, but quadriceps LSI had the strongest association (r = 0.790). These findings suggests that limb preference influences single forward hop LSI values and should be considered following ACL reconstruction.
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Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Adolescente , Adulto , Lesões do Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior/reabilitação , Humanos , Perna (Membro) , Força Muscular , Músculo Quadríceps , Volta ao Esporte , Adulto JovemRESUMO
BACKGROUND: A comprehensive battery of tests are used to inform return to play decisions following anterior cruciate ligament (ACL) reconstruction. Performance measures contribute to patient function, but it is not clear if achieving symmetrical performance on strength and hop tests is sufficient or if a patient also needs to meet minimum unilateral thresholds. HYPOTHESIS/PURPOSE: To determine the association of quadriceps strength and single-leg forward hop performance with patient-reported function, as measured by the IKDC Subjective Knee Form (IKDC), during late-stage ACL rehabilitation. A secondary purpose was to determine which clinical tests were the most difficult for participants to pass. STUDY DESIGN: Descriptive Laboratory Study. METHODS: Forty-eight individuals with a history of ACL-R (32 female, 16 male; mean±SD age=18.0±2.7 y; height=172.4±7.6 cm; mass=69.6±11.4 kg; time since surgery=7.7±1.8 months; IKDC=86.8±10.6) completed the IKDC survey, quadriceps isometric strength, and single-leg forward hop performance. The relationship between IKDC scores and performance measures (LSI and involved limb) was determined using stepwise linear regression. Frequency counts were used to determine whether participants met clinical thresholds (IKDC ≥ 90%, quadriceps and single-leg forward hop LSI ≥ 90%, quadriceps peak torque ≥ 3.0 Nm/kg, and single-leg forward hop ≥ 80% height for females and ≥ 90% height for males). RESULTS: Quadriceps LSI and involved limb peak torque explained 39% of the variance in IKDC scores while measures of single-leg forward hop performance did not add to the predictive model. Nearly 90% of participants could not meet established clinical thresholds on all five tests and quadriceps strength (LSI and peak torque) was the most common unmet criteria (71% of participants). CONCLUSIONS: During late-stage ACL rehabilitation deficits in quadriceps strength contribute more to patient function and are greater in magnitude compared to hop test performance. LEVEL OF EVIDENCE: Cross-Sectional Study, Level 3.
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BACKGROUND: Low back, pelvic, and lower extremity pain are common during and after pregnancy. Understanding differences in mechanics between pregnant and non-pregnant females is a first step toward identifying potential pathological mechanisms. The primary purpose of this study was to compare joint kinetics and muscle activation during gait between females during and after pregnancy to nulliparous females. METHODS: Twenty pregnant females completed testing on three occasions (second trimester, third trimester, and post-partum), while 20 matched, nulliparous controls were tested once. Motion capture, force data, and surface electromyography were averaged across seven trials during gait. Lower extremity kinematics, lower extremity moments and work normalized to pre-pregnancy body mass, work distribution, and peak and average muscle activation amplitude were calculated. Independent t-tests were conducted between pregnant and nulliparous females at each time point. RESULTS: Compared to controls, peak hip abductor moments were greater throughout and after pregnancy. Females in second trimester also demonstrated greater sagittal negative ankle work and greater percent contribution of the ankle and smaller percent contribution of the hip to negative work. Compared to controls, during third trimester there were greater knee abductor, ankle plantarflexor, and ankle dorsiflexor moments and greater work at the ankle and total work. Several moment and work variables continued to be elevated post-partum compared to controls. Gluteus maximus muscle activation amplitude was smaller in second trimester and post-partum compared to controls. SIGNIFICANCE: While overall joint demands were greater during and after pregnancy, there was a smaller relative sagittal utilization of the hip early in pregnancy and smaller gluteus maximus muscle amplitude during second trimester and post-partum. Because the gluteus maximus muscle contributes to force closure and dynamic stability of the low back and pelvis, relative gluteus maximus disuse, concurrent with increased joint loads, could potentially contribute to pain during and after pregnancy.
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Fenômenos Biomecânicos/fisiologia , Marcha/fisiologia , Extremidade Inferior/fisiologia , Músculo Esquelético/fisiologia , Adulto , Feminino , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Gravidez , Adulto JovemRESUMO
Epithelial cell physiology critically depends on the asymmetric distribution of channels and transporters. However, the mechanisms targeting membrane proteins to the apical surface are still poorly understood. Here, we performed a visual forward genetic screen in the zebrafish intestine and identified mutants with defective apical targeting of membrane proteins. One of these mutants, affecting the vacuolar H+-ATPase gene atp6ap1b, revealed specific requirements for luminal acidification in apical, but not basolateral, membrane protein sorting and transport. Using a low temperature block assay combined with genetic and pharmacologic perturbation of luminal pH, we monitored transport of newly synthesized membrane proteins from the TGN to apical membrane in live zebrafish. We show that vacuolar H+-ATPase activity regulates sorting of O-glycosylated proteins at the TGN, as well as Rab8-dependent post-Golgi trafficking of different classes of apical membrane proteins. Thus, luminal acidification plays distinct and specific roles in apical membrane biogenesis.
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Proteínas de Membrana/metabolismo , Fenobarbital/metabolismo , ATPases Translocadoras de Prótons/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/metabolismo , Animais , Concentração de Íons de Hidrogênio , Proteínas de Membrana/genética , Mutação , Fenobarbital/química , Transporte Proteico , ATPases Translocadoras de Prótons/genética , Proteínas de Peixe-Zebra/genéticaRESUMO
The vertebral column or spine assembles around the notochord rod which contains a core made of large vacuolated cells. Each vacuolated cell possesses a single ï¬uid-ï¬lled vacuole, and loss or fragmentation of these vacuoles in zebrafish leads to spine kinking. Here, we identified a mutation in the kinase gene dstyk that causes fragmentation of notochord vacuoles and a severe congenital scoliosis-like phenotype in zebrafish. Live imaging revealed that Dstyk regulates fusion of membranes with the vacuole. We find that localized disruption of notochord vacuoles causes vertebral malformation and curving of the spine axis at those sites. Accordingly, in dstyk mutants the spine curves increasingly over time as vertebral bone formation compresses the notochord asymmetrically, causing vertebral malformations and kinking of the axis. Together, our data show that notochord vacuoles function as a hydrostatic scaffold that guides symmetrical growth of vertebrae and spine formation.
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Notocorda/metabolismo , Coluna Vertebral/crescimento & desenvolvimento , Vacúolos/metabolismo , Peixe-Zebra/embriologia , Animais , Regulação da Expressão Gênica no Desenvolvimento , Mutação , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Proteínas de Peixe-Zebra/genéticaRESUMO
Enteroendocrine cells (EECs) are specialized sensory cells in the intestinal epithelium that sense and transduce nutrient information. Consumption of dietary fat contributes to metabolic disorders, but EEC adaptations to high fat feeding were unknown. Here, we established a new experimental system to directly investigate EEC activity in vivo using a zebrafish reporter of EEC calcium signaling. Our results reveal that high fat feeding alters EEC morphology and converts them into a nutrient insensitive state that is coupled to endoplasmic reticulum (ER) stress. We called this novel adaptation 'EEC silencing'. Gnotobiotic studies revealed that germ-free zebrafish are resistant to high fat diet induced EEC silencing. High fat feeding altered gut microbiota composition including enrichment of Acinetobacter bacteria, and we identified an Acinetobacter strain sufficient to induce EEC silencing. These results establish a new mechanism by which dietary fat and gut microbiota modulate EEC nutrient sensing and signaling.
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Dieta Hiperlipídica , Células Enteroendócrinas/fisiologia , Microbioma Gastrointestinal/fisiologia , Mucosa Intestinal/fisiologia , Peixe-Zebra/fisiologia , Acinetobacter/fisiologia , Adaptação Fisiológica/fisiologia , Animais , Gorduras na Dieta/administração & dosagem , Estresse do Retículo Endoplasmático/fisiologia , Células Enteroendócrinas/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Vida Livre de Germes , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/microbiologia , Transdução de Sinais/fisiologia , Peixe-Zebra/microbiologiaRESUMO
The guts of neonatal mammals and stomachless fish have a limited capacity for luminal protein digestion, which allows oral acquisition of antibodies and antigens. However, how dietary protein is absorbed during critical developmental stages when the gut is still immature is unknown. Here, we show that specialized intestinal cells, which we call lysosome-rich enterocytes (LREs), internalize dietary protein via receptor-mediated and fluid-phase endocytosis for intracellular digestion and trans-cellular transport. In LREs, we identify a conserved endocytic machinery, composed of the scavenger receptor complex Cubilin/Amnionless and Dab2, that is required for protein uptake by LREs and for growth and survival of larval zebrafish. Moreover, impairing LRE function in suckling mice, via conditional deletion of Dab2, leads to stunted growth and severe protein malnutrition reminiscent of kwashiorkor, a devastating human malnutrition syndrome. These findings identify digestive functions and conserved molecular mechanisms in LREs that are crucial for vertebrate growth and survival.
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Proteínas Alimentares/metabolismo , Enterócitos/metabolismo , Absorção Intestinal , Intestinos/embriologia , Lisossomos/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Modelos Animais de Doenças , Feminino , Microbioma Gastrointestinal , Deleção de Genes , Regulação da Expressão Gênica no Desenvolvimento , Íleo/embriologia , Íleo/metabolismo , Kwashiorkor/metabolismo , Ligantes , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Receptores de Superfície Celular/metabolismo , Peixe-Zebra , Proteínas de Peixe-Zebra/metabolismoRESUMO
BACKGROUND: Previous studies have reported that persons with femoroacetabular impingement syndrome (FAIS) have diminished posterior tilt of the pelvis during functional tasks. It is not known how this movement impairment impacts pelvifemoral coordination during weightbearing and non-weightbearing movements. METHODS: Fifteen persons with a diagnosis of FAIS and 15 matched controls performed a deep squat (weightbearing) and a maximum height stepping task (non-weightbearing). Peak hip flexion, posterior pelvis tilt excursion, and the ratio of sagittal plane pelvis to femur motion during the period of pelvis posterior tilt were calculated for each task. Two factor ANOVAs were used to evaluate differences between groups and tasks. FINDINGS: With regards to peak hip flexion, there were no significant group differences for either task. When averaged across tasks, the FAIS group exhibited significantly less posterior tilt excursion (12.1° (SD 9.1°) vs 20.6° (SD 9.3°)) and smaller pelvifemoral ratios (0.24 (SD 0.14) vs 0.39 (SD 0.16)) compared to the control group. INTERPRETATION: Persons with FAIS exhibit altered pelvifemoral coordination regardless of weightbearing status. This finding suggests that decreased hip and/or lumbopelvic mobility may contribute to altered movement patterns at the hip.
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Impacto Femoroacetabular/fisiopatologia , Fêmur/fisiopatologia , Articulação do Quadril/fisiopatologia , Pelve/fisiopatologia , Suporte de Carga , Adulto , Fenômenos Biomecânicos , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Movimento , Postura , Amplitude de Movimento Articular , Inquéritos e Questionários , Adulto JovemRESUMO
Grindstaff, TL, Palimenio, MR, Franco, M, Anderson, D, Bagwell, JJ, and Katsavelis, D. Optimizing between-session reliability for quadriceps peak torque and rate of torque development measures. J Strength Cond Res 33(7): 1840-1847, 2019-Quadriceps peak torque and rate of torque development (RTD) have relevance for athletic performance and recovery after knee injury. The number of repetitions performed to determine RTD varies between studies, and the associated measurement error has not been established. The purpose of this study was to determine the number of repetitions necessary to optimize the between-session reliability for isometric quadriceps peak torque and RTD measures and to quantify estimates of measurement error. Twenty participants (age = 21.7 ± 1.7 years, height = 172.5 ± 16.0 cm, body mass = 76.0 ± 15.5 kg, and Tegner = 7.1 ± 1.2) volunteered for this study. Quadriceps isometric peak torque and RTD (50, 100, 150, 200, and 250 ms, and maximum torque) were obtained during 2 testing sessions. Between-session reliability was determined using intraclass correlation coefficients (ICC2,k), using the minimal detectable change (MDC) and coefficient of variation (CoV) to quantify measurement error. Between-session reliability was best maximized by using the average of the 3 repetitions with the highest peak torque. Reliability was good for quadriceps peak torque (ICC2,3 = 0.98; MDC = 51.1 N·m; CoV = 38.0%) and ranged from moderate to good for quadriceps RTD measures (ICC2,3 = 0.61 to 0.91; MDC = 264.8 to 738.3 N·m·s; CoV = 38.1-57.9%). Measures of late RTD were less variable and more reliable than early RTD and average RTD measures. These results provide confidence when measuring between-session changes for late RTD measures, but changes in early RTD may be more difficult to distinguish from measurement error. Methods should be used to minimize variability between repetitions and sessions.
Assuntos
Desempenho Atlético/fisiologia , Contração Isométrica/fisiologia , Força Muscular/fisiologia , Músculo Quadríceps/fisiologia , Treinamento Resistido , Torque , Adulto , Fenômenos Biomecânicos , Feminino , Humanos , Masculino , Dinamômetro de Força Muscular , Reprodutibilidade dos TestesRESUMO
The notochord is a conserved axial structure that in vertebrates serves as a hydrostatic scaffold for embryonic axis elongation and, later on, for proper spine assembly. It consists of a core of large fluid-filled vacuolated cells surrounded by an epithelial sheath that is encased in extracellular matrix. During morphogenesis, the vacuolated cells inflate their vacuole and arrange in a stereotypical staircase pattern. We investigated the origin of this pattern and found that it can be achieved purely by simple physical principles. We are able to model the arrangement of vacuolated cells within the zebrafish notochord using a physical model composed of silicone tubes and water-absorbing polymer beads. The biological structure and the physical model can be accurately described by the theory developed for the packing of spheres and foams in cylinders. Our experiments with physical models and numerical simulations generated several predictions on key features of notochord organization that we documented and tested experimentally in zebrafish. Altogether, our data reveal that the organization of the vertebrate notochord is governed by the density of the osmotically swelling vacuolated cells and the aspect ratio of the notochord rod. We therefore conclude that self-organization underlies morphogenesis of the vertebrate notochord.This article is part of the Theo Murphy meeting issue on 'Mechanics of development'.