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1.
Doc Ophthalmol ; 140(1): 31-42, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31512016

RESUMO

PURPOSE: To define the relationship between abnormalities in the activation phase of cone phototransduction and the oscillatory potentials (OPs) of the light-adapted electroretinogram in diabetics who have mild or no retinopathy. METHODS: Subjects included 20 non-diabetic controls and 40 type-2 diabetics (20 had no clinically apparent diabetic retinopathy [NDR] and 20 had mild nonproliferative DR). Single flash responses for a series of stimulus retinal illuminances were measured under light-adapted conditions using conventional techniques. The a-waves of the responses were fit with a delayed Gaussian model to derive Rmp3 (maximum amplitude of the massed photoreceptor response) and S (phototransduction sensitivity). OPs were extracted from the responses by conventional band-pass filtering. RESULTS: Analysis of variance (ANVOA) indicated that both diabetic groups had significant OP amplitude and S reductions compared to the controls, whereas Rmp3 did not differ significantly among the groups. Although log OP amplitude and log Rmp3 were significantly correlated for the control subjects for each flash retinal illuminance (all r > 0.49, p < 0.03), log OP amplitude and log Rmp3 were not correlated for either diabetic group for any flash retinal illuminance (all r ≤ 0.36, p ≥ 0.13). Log OP amplitude and log S were generally not correlated significantly for the control or diabetic groups. CONCLUSION: OP amplitude losses do not appear to be related to reduced cone sensitivity in early-stage diabetic retinopathy. This suggests that diabetes may separately affect cone function, as evidenced by cone phototransduction sensitivity losses, and inner-retina function, as evidenced by OP amplitude losses.

2.
Nutr Metab Cardiovasc Dis ; 30(2): 339-346, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31753784

RESUMO

BACKGROUND AND AIMS: Insulin-like growth factor (IGF)-1 deficiency is associated with a range of metabolic disorders. Cyclic glycine-proline (cGP) is a natural nutrient and regulates the amount of active IGF-1 in plasma. Plasma cGP decreases in hypertensive women whereas increases in obese women, suggesting its involvement in cardio-metabolic function. We therefore examined the effects of cGP on metabolic profiles and blood pressure in high-fat diet (HFD)-induced obese male rats. METHODS: Male rats were fed either a HFD or a standard chow diet (STD) ad-libitum from 3 to 15 weeks of age. Rats were administered either saline or cGP from 11 to 15 weeks of age. At 14 weeks of age, systolic-blood pressure (SBP) was measured by tail-cuff plethysmography and body composition quantified by DEXA. Blood and retroperitoneal fat tissues were collected. Plasma concentrations of insulin, IGF-1, IGF binding protein (IGFBP)-3 and cGP were evaluated using ELISA and HPLC-MS respectively. RESULTS: Compared to STD, HFD feeding increased SBP, total fat mass and fat/lean ratio, retroperitoneal fat weight, fasting plasma insulin and cGP concentrations whereas decreased plasma IGF-1 and IGFBP-3 concentrations. Administration of cGP reduced SBP and retroperitoneal fat weight, but had no effect on body composition and plasma insulin concentrations. CONCLUSION: HFD-associated decreases in IGFBP-3 and increases in cGP represent an autocrine response to normalize IGF-1 function through improving the amount of bioavailable IGF-1 in the circulation of obese male rats. The beneficial effects of cGP on SBP and retroperitoneal fat mass may suggest a therapeutic potential for cGP in HFD-associated cardio-metabolic complications.

3.
Curr Eye Res ; : 1-11, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31847599

RESUMO

Purpose: To evaluate the relationship between microperimetric (MP) sensitivity and retinal thickness measured at co-registered retinal locations in individuals who have mild or no diabetic retinopathy.Methods: Fifty non-diabetic control subjects and 50 type-2 diabetic subjects participated (25 had no clinically apparent DR [NDR] and 25 had mild nonproliferative DR [MDR]). MP sensitivity was measured at 36 retinal locations that were arranged in three concentric rings centered on the fovea (radii of 3°, 6°, and 12°). Optical coherence tomography (OCT) images were obtained, and total retinal thickness (TRT), inner retinal thickness (IRT), and outer retinal thickness (ORT) were quantified from the OCT images at locations that matched the MP measures. Linear quantile mixed models (LQMMs) and linear quantile models (LQMs) were used to compare MP and thickness values for the three subject groups and to quantify structure-function relationships.Results: The statistical models indicated significant TRT and IRT reductions in the NDR and MDR groups, relative to the controls, that were most apparent in the 3° ring. By contrast, ORT was not reduced significantly for either diabetic group. MP sensitivity was reduced significantly within each ring and for both diabetic groups. Despite reductions in both thickness and sensitivity, the structure-function associations were generally weak with borderline statistical significance. For example, a TRT or IRT reduction of approximately 27 µm was predicted to result in approximately 1 dB of MP sensitivity loss for the MDR group (p = .03 and 0.05, respectively)Conclusions: The results support previous findings of early retinal neurodegeneration in diabetics who have NDR or MDR. Interestingly, the structural and functional deficits appear to be only weakly associated, suggesting that mechanisms in addition to retinal thinning underlie the functional defects in early-stage DR.

4.
J Am Acad Dermatol ; 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31884091

RESUMO

BACKGROUND: Cumulative clinical improvement and speed of improvement are important to psoriasis patients. OBJECTIVE: Compare cumulative benefits of biologics over 12-16 weeks in the treatment of moderate-to-severe psoriasis. METHODS: A systematic literature review identified phase III trial data on Psoriasis Area and Severity Index (PASI) responses for biologics during 12 and 16 weeks of treatment. Cumulative clinical benefit, measured by area-under-the-curve (AUC) for PASI 75, PASI 90, and PASI 100, was compared using the network meta-analysis (NMA) and Bayesian methodology on the relative probability of achieving percent of maximum AUC. RESULTS: Among biologics approved for psoriasis treatment, anti-IL-17 biologics demonstrated consistently greater cumulative clinical benefits on PASI 75, PASI 90, and PASI 100 over the 12- or 16-week period than anti-IL-23 and other biologics. For biologics with 12-week data, both ixekizumab and brodalumab showed greater cumulative benefits for PASI 75, PASI 90, and PASI 100 than secukinumab, followed by guselkumab, infliximab, adalimumab, ustekinumab and etanercept. Ixekizumab showed greater cumulative benefits than all other biologics reporting 16-week data . LIMITATIONS: Recently approved biologics were not included. CONCLUSION: Ixekizumab (at 12 weeks and 16 weeks) and brodalumab (at 12 weeks) had greater cumulative clinical benefit than all other biologics studied.

5.
Development ; 146(21)2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31719045

RESUMO

The tongue is a highly specialised muscular organ with a complex anatomy required for normal function. We have utilised multiple genetic approaches to investigate local temporospatial requirements for sonic hedgehog (SHH) signalling during tongue development. Mice lacking a Shh cis-enhancer, MFCS4 (ShhMFCS4/-), with reduced SHH in dorsal tongue epithelium have perturbed lingual septum tendon formation and disrupted intrinsic muscle patterning, with these defects reproduced following global Shh deletion from E10.5 in pCag-CreERTM; Shhflox/flox embryos. SHH responsiveness was diminished in local cranial neural crest cell (CNCC) populations in both mutants, with SHH targeting these cells through the primary cilium. CNCC-specific deletion of orofaciodigital syndrome 1 (Ofd1), which encodes a ciliary protein, in Wnt1-Cre; Ofdfl/Y mice led to a complete loss of normal myotube arrangement and hypoglossia. In contrast, mesoderm-specific deletion of Ofd1 in Mesp1-Cre; Ofdfl/Y embryos resulted in normal intrinsic muscle arrangement. Collectively, these findings suggest key temporospatial requirements for local SHH signalling in tongue development (specifically, lingual tendon differentiation and intrinsic muscle patterning through signalling to CNCCs) and provide further mechanistic insight into the tongue anomalies seen in patients with disrupted hedgehog signalling.

6.
J Vis Exp ; (152)2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31633677

RESUMO

Over the past several decades there has been an increased availability of genetically modified mouse models used to mimic human pathologies. However, the ability to study cell movements and differentiation in vivo is still very difficult. Neurocristopathies, or disorders of the neural crest lineage, are particularly challenging to study due to a lack of accessibility of key embryonic stages and the difficulties in separating out the neural crest mesenchyme from adjacent mesodermal mesenchyme. Here, we set out to establish a well-defined, routine protocol for the culture of primary cranial neural crest cells. In our approach we dissect out the mouse neural plate border during the initial neural crest induction stage. The neural plate border region is explanted and cultured. The neural crest cells form in an epithelial sheet surrounding the neural plate border, and by 24 h after explant, begin to delaminate, undergoing an epithelial-mesenchymal transition (EMT) to become fully motile neural crest cells. Due to our two-dimensional culturing approach, the distinct tissue populations (neural plate versus premigratory and migratory neural crest) can be readily distinguished. Using live imaging approaches, we can then identify changes in neural crest induction, EMT and migratory behaviors. The combination of this technique with genetic mutants will be a very powerful approach for understanding normal and pathological neural crest cell biology.

7.
Acta Ophthalmol ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31517447

RESUMO

PURPOSE: To determine the relationship between contrast sensitivity (CS) and outer-retina thickness (ORT) in diabetics who have minimal or no diabetic retinopathy (DR). METHODS: Twenty non-diabetic control subjects and 40 type-2 diabetic subjects participated (20 had no clinically apparent DR [NDR] and 20 had mild non-proliferative DR [NPDR]). No subject had a history of treatment for macular oedema. Letter CS, microperimetry (MP) sensitivity and visual acuity (VA) were measured. Letter CS and MP measurements were performed over the central 6° of the visual field. Spectral domain optical coherence tomography (SD-OCT) images were obtained at corresponding locations, outer-retina thickness was quantified, and structure-function relationships were evaluated. RESULTS: Analysis of variance indicated significant letter CS differences among the groups (p < 0.001). Letter CS was reduced significantly for the mild NPDR group (p < 0.001; 33% reduction), but not the NDR group (p = 0.08). There were no significant differences in MP sensitivity or ORT among the groups (both p > 0.10). Nevertheless, Hoeffding's D tests indicated significant associations between ORT and letter CS (p < 0.001) and between ORT and MP sensitivity for the mild NPDR group (p = 0.01). VA was not significantly associated with ORT for either diabetic group (both p > 0.49). CONCLUSIONS: Outer-retina thickness is associated with letter CS and MP sensitivity, but not VA, in mild NPDR. This finding highlights the usefulness of simple letter CS measures and suggests neural dysfunction can occur in the absence of marked structural abnormalities in early-stage DR.

8.
Behav Neurol ; 2019: 7536957, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467614

RESUMO

This study examined if imagery ability (i.e., vividness and temporal congruence between imagined and executed knee extensions) and imagery perspective preference were affected by ageing and gender. Ninety-four participants, 31 young, 43 intermediate, and 20 older adults completed the Vividness of Movement Imagery Questionnaire-2 and a knee extension temporal congruence test to reflect on their imagery ability and an imagery perspective preference test. Male participants had a better imagery ability than the female participants (F (4, 85) = 2.84, p = .029, η 2 = .118). However, significant age-related changes in imagery ability were not found in the three age groups. Change in imagery perspective preference with a trend towards an external imagery perspective was observed with ageing (F (3, 89) = 3.16, p = .028, η 2 = .096) but not between male and female. The results suggest that imagery ability may be preserved with ageing. As individuals age, their preference for using an imagery perspective shifts from a more internal to a more external perspective. This understanding is important when designing future imagery research and real-life application or clinical intervention.

9.
Syst Rev ; 8(1): 222, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462306

RESUMO

BACKGROUND: Cognitive changes associated with mild cognitive impairment or mild dementia can lead to difficulties in completing instrumental activities of daily living. The ability to live independently at home and in the community is often compromised due to the inability to complete these activities. Cognitive interventions have been reported as beneficial in maintaining or improving cognitive functions among this group of adults. However, the effectiveness of different types of cognitive interventions on the performance of instrumental activities of daily living in older adults with mild cognitive impairment and mild dementia is not well established. The aim of this paper is to develop a protocol for a systematic review and meta-analysis to investigate the effectiveness of cognitive interventions in maintaining or improving the performance of instrumental activities of daily living in individuals with mild cognitive impairment or mild dementia. METHODS: Randomised control studies which investigate the effectiveness of cognitive interventions on the performance in instrumental activities of daily living for older adults with mild cognitive impairment and mild dementia will be sought. A systematic search will be conducted in five databases: CINAHL, MEDLINE, EMBASE, PsycINFO and Cochrane Central Register of Controlled Trials. The search strategy was developed with assistance from a health science librarian. Two independent reviewers will perform the study selection and data extraction. Quality assessment will be implemented using the Physiotherapy Evidence Database (PEDro) scale. A narrative synthesis of the findings will be used to report outcomes of all included studies. If appropriate, a meta-analysis will combine the results of individual studies. DISCUSSION: This systematic review and meta-analysis will determine the effectiveness of cognitive interventions in maintaining or improving the performance of IADL in individuals with MCI or mild dementia. It is anticipated that the results will inform rehabilitation professionals of the most effective cognitive interventions to be implemented into clinical practice. It will potentially provide substantial benefit to both the persons with MCI or dementia and the health care system by keeping more people out of full-time care and allowing those in full-time care to require less intensive support. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016042364.

10.
Front Mol Neurosci ; 12: 139, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31293383

RESUMO

Neural crest cells arise in the embryo from the neural plate border and migrate throughout the body, giving rise to many different tissue types such as bones and cartilage of the face, smooth muscles, neurons, and melanocytes. While studied extensively in animal models, neural crest development and disease have been poorly described in humans due to the challenges in accessing embryonic tissues. In recent years, patient-derived human induced pluripotent stem cells (hiPSCs) have become easier to generate, and several streamlined protocols have enabled robust differentiation of hiPSCs to the neural crest lineage. Thus, a unique opportunity is offered for modeling neurocristopathies using patient specific stem cell lines. In this work, we make use of hiPSCs derived from patients affected by the Bardet-Biedl Syndrome (BBS) ciliopathy. BBS patients often exhibit subclinical craniofacial dysmorphisms that are likely to be associated with the neural crest-derived facial skeleton. We focus on hiPSCs carrying variants in the BBS10 gene, which encodes a protein forming part of a chaperonin-like complex associated with the cilium. Here, we establish a pipeline for profiling hiPSCs during differentiation toward the neural crest stem cell fate. This can be used to characterize the differentiation properties of the neural crest-like cells. Two different BBS10 mutant lines showed a reduction in expression of the characteristic neural crest gene expression profile. Further analysis of both BBS10 mutant lines highlighted the inability of these mutant lines to differentiate toward a neural crest fate, which was also characterized by a decreased WNT and BMP response. Altogether, our study suggests a requirement for wild-type BBS10 in human neural crest development. In the long term, approaches such as the one we describe will allow direct comparison of disease-specific cell lines. This will provide valuable insights into the relationships between genetic background and heterogeneity in cellular models. The possibility of integrating laboratory data with clinical phenotypes will move us toward precision medicine approaches.

11.
Gene Expr Patterns ; 34: 119057, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31163262

RESUMO

Rap GTPases mediate fundamental cellular processes, including cell adhesion, migration and intracellular signal transduction. The subcellular activity of these GTPases is regulated by dedicated activators (guanine nucleotide exchange factors, GEFs) and deactivators (GTPase-activating proteins, GAPs). RAPGEF5 is a potent activator of Rap proteins and mutations in RAPGEF5 have been linked to both neurological disorders and congenital heart disease. In the frog model, Xenopus tropicalis, Rapgef5 is a critical regulator of the canonical Wnt signalling pathway and is required for normal gastrulation and correct establishment of the left-right body axis. However, requirements for RAPGEF5 in other developmental contexts, and in mammalian embryogenesis in particular, remain undefined. Here, we describe RAPGEF5 mRNA expression patterns during mouse (E9.5 - E16.5) and human (Carnegie stage 21) development, as an initial step towards better understanding its developmental functions.

12.
Neuropeptides ; 76: 101935, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31146894

RESUMO

Childhood metabolic disorders are associated with insulin-like growth factor (IGF)-1 deficiency, which can adversely affect brain development and function. As a neuropeptide, cyclic glycine-proline (cGP) improves IGF-1 function in brain and regulates IGF-1 bioavailability in plasma. Whether such a regulatory process mediates the neurotrophic effects of cGP remains unknown. This study examined the effects cGP treatment on synaptic expression and their association with IGF-1, IGF binding protein (IGFBP)-2 and cGP concentrations in the brain of rats with high fat diet (HFD)-induced obesity. Male rats received either a HFD or a standard chow diet (STD) from weaning and were then treated with either saline or cGP from 11 to 15 weeks of age. The concentrations of cGP, IGF-1 and IGFBP-2 were measured in the brain tissues using ELISA and HPLC-MS. The expressions of synaptic markers were evaluated in the hippocampus, hypothalamus and striatum using immunohistochemical staining. Compared to the STD group, IGF-1 and IGFBP-2, but not cGP concentrations, were lower in the HFD groups. The expression of hippocampal synaptophysin, glutamate receptor-1, GFAP and striatal tyrosine-hydroxylase were also reduced in the HFD groups. While treatment did not alter tissue IGF-1, cGP administration that increased the concentration of cGP in brain tissues, normalized the expression of synaptophysin, GFAP and tyrosine-hydroxylase, but not glutamate receptor-1. IGF-1 concentration in brain tissues correlated with the expression of all synaptic markers. HFD feeding reduced synaptic expression and tissue IGF-1 in brains which were closely associated, thus suggesting IGF-1 in the brain is largely bioavailable. Without increasing IGF-1 in the brain, administration of cGP normalized synaptic expression, possibly be mediated through increasing bioavailable IGF-1, but further studies are required to confirm this.


Assuntos
Obesidade/metabolismo , Peptídeos Cíclicos/administração & dosagem , Sinaptofisina/metabolismo , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Ratos Sprague-Dawley
13.
Vision Res ; 161: 1-11, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31129287

RESUMO

The flicker electroretinogram (ERG) is typically analyzed in terms of peak-to-trough amplitude and implicit time. However, additional important information may be captured by spectral-domain analysis of the ERG harmonics (responses that occur at multiples of the stimulus frequency). This study describes an approach to analyze the harmonic components of the flicker ERG and its application to patients who have early-stage non-proliferative diabetic retinopathy (NPDR). Of particular interest were the sub-harmonic components occurring at 1.5x and 2.5x the stimulus frequency that produce cycle-to-cycle variation in amplitude termed "period doubling." Twenty visually-normal subjects, 20 diabetic subjects who have no clinically-apparent retinopathy (NDR), and 20 diabetic subjects who have mild NPDR participated. ERGs were recorded in response to sinusoidal flicker (27-63 Hz) and Fourier analysis was performed to extract fundamental and harmonic response amplitudes. Linear quantile mixed models (LQMMs) were used to compare the amplitude of the response components among the three subject groups. Results indicated that the maximum sub-harmonic amplitude occurred in the stimulus frequency range of 33-38 Hz for all subjects. The LQMMs showed a significant sub-harmonic amplitude reduction for the mild NPDR subjects compared to the controls; sub-harmonic amplitude for the NDR subjects did not differ significantly from the controls. In contrast, the fundamental response did not differ among the groups for stimulus frequencies between 33 and 38 Hz. Modeling these results indicated that subharmonic amplitude loss in mild NPDR subjects may be attributed to attenuated feedback occurring early in the retina, possibly at the synapse of cone photoreceptors and OFF bipolar cells.

14.
Arch Phys Med Rehabil ; 100(5): 956-979, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31030733

RESUMO

OBJECTIVE: To evaluate the effectiveness of activity-based, nonactivity-based, and combined activity- and nonactivity-based rehabilitative interventions for individuals presenting with unilateral spatial neglect (USN) and hemianopia. DATA SOURCES: We searched CINAHL, Cochrane Library, EMBASE, MEDLINE, and PubMed from 2006 to 2016. STUDY SELECTION: Randomized controlled trials (RCTs) with a score of 6 or more in the Physiotherapy Evidence Database Scale that examined the effects of activity-based and nonactivity-based rehabilitation interventions for people with USN or hemianopia. Two reviewers selected studies independently. DATA EXTRACTION: Extracted data from the published RCTs. Mean differences (MD) or standardized mean differences (SMD), and 95% confidence intervals (CIs) were calculated. Heterogeneity was assessed using the I2 statistic. DATA SYNTHESIS: A total of 20 RCTs for USN and 5 for hemianopia, involving 594 and 206 stroke participants respectively, were identified. Encouraging results were found in relation to activity-based interventions for visual scanning training and compensatory training for hemianopia (MD=5.11; 95% confidence intervals [95% CI], 0.83-9.4; P=.019; I2=25.16% on visual outcomes), and optokinetic stimulation and smooth pursuit training for USN (SMD=0.49; 95% CI, 0.01-0.97; P=.045; I2=49.35%) on functional performance in activities of daily living, (SMD=0.96; 95% CI, 0.09-1.82; P=.031; I2=89.57%) on neglect. CONCLUSIONS: Activity-based interventions are effective and commonly used in the treatment of USN and hemianopia. Nonactivity-based and combined approaches, for both impairments, have not been refuted, because more studies are required for substantiated conclusions to be drawn.


Assuntos
Hemianopsia/reabilitação , Transtornos da Percepção/reabilitação , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/complicações , Hemianopsia/etiologia , Humanos , Transtornos da Percepção/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Biomed Microdevices ; 21(2): 44, 2019 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-30963305

RESUMO

In embryogenesis, mesenchymal condensation is a critical event during the formation of many organ systems, including cartilage and bone. During organ formation, mesenchymal cells aggregate and undergo compaction while activating developmental programmes. The final three-dimensional form of the organ, as well as cell fates, can be influenced by the size and shape of the forming condensation. This process is hypothesized to result from multiscale cell interactions within mesenchymal microenvironments; however, these are complex to investigate in vivo. Three-dimensional in vitro models that recapitulate key phenotypes can contribute to our understanding of the microenvironment interactions regulating this fundamental developmental process. Here we devise such models by using image analysis to guide the design of polydimethylsiloxane 3D microstructures as cell culture substrates. These microstructures establish geometrically constrained micromass cultures of mouse embryonic skeletal progenitor cells which influence the development of condensations. We first identify key phenotypes differentiating face and limb bud micromass cultures by linear discriminant analysis of the shape descriptors for condensation morphology, which are used to guide the rational design of a micropatterned polydimethylsiloxane substrate. High-content imaging analysis highlights that the geometry of the microenvironment affects the establishment and growth of condensations. Further, cells commit to establish condensations within the first 5 h; condensations reach their full size within 17 h; following which they increase cell density while maintaining size for at least 7 days. These findings elucidate the value of our model in dissecting key aspects of mesenchymal condensation development.


Assuntos
Técnicas de Cultura de Células/métodos , Células-Tronco Mesenquimais/citologia , Animais , Adesão Celular , Dimetilpolisiloxanos/química , Células-Tronco Embrionárias/citologia , Fibronectinas/química , Camundongos , Imagem Molecular , Nylons/química , Propilaminas/química , Silanos/química
16.
Mol Syndromol ; 10(1-2): 48-57, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30976279

RESUMO

The craniofacial skeleton is formed from the neural crest and mesodermal lineages, both of which contribute mesenchymal precursors during formation of the skull bones. The large majority of cranial sutures also includes a proportion of neural crest-derived mesenchyme. While some studies have addressed the relative healing abilities of neural crest and mesodermal bone, relatively little attention has been paid to differences in intrinsic osteogenic potential. Here, we use mouse models to compare neural crest osteoblasts (from frontal bones or dura mater) to mesodermal osteoblasts (from parietal bones). Using in vitro culture approaches, we find that neural crest-derived osteoblasts readily generate bony nodules, while mesodermal osteoblasts do so less efficiently. Furthermore, we find that co-culture of neural crest-derived osteoblasts with mesodermal osteoblasts is sufficient to nucleate ossification centres. Altogether, this suggests that the intrinsic osteogenic abilities of neural crest-derived mesenchyme may be a primary driver behind craniosynostosis.

17.
Zoological Lett ; 5: 6, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30788138

RESUMO

Background: The pharyngeal arches are a series of bulges found on the lateral surface of the head of vertebrate embryos, and it is within these segments that components of the later anatomy are laid down. In most vertebrates, the post-otic pharyngeal arches will form the branchial apparatus, while in amniotes these segments are believed to generate the larynx. It has been unclear how the development of these segments has been altered with the emergence of the amniotes. Results: In this study, we examined the development of pharyngeal arches in amniotes and show that the post-otic pharyngeal arches in this clade are greatly diminished. We find that the post-otic segments do not undergo myogenesis or skeletogenesis, but are remodelled before these processes occur. We also find that nested DLX expression, which is a feature of all the pharyngeal arches in anamniotes, is associated with the anterior segments but less so with the posterior arches in amniotes. We further show that the posterior arches of the mouse embryo fail to properly delineate, which demonstrates the lack of function of these posterior segments in later development. Conclusion: In amniotes, there has been a loss of the ancestral "branchial" developmental programme that is a general feature of gnathostomes; myogenesis and skeletogenesis This is likely to have facilitated the emergence of the larynx as a new structure not constrained by the segmental organisation of the posterior pharyngeal region.

18.
Medicine (Baltimore) ; 98(2): e14134, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30633230

RESUMO

In this study, balance performance, agility, eye-hand coordination, and sports performance were compared between amateur badminton players and active controls.Thirty young adult badminton players and 33 active controls participated in the study. Static single-leg standing balance (with eyes closed) was measured using a force platform, and dynamic balance was measured using the Y Balance Test (lower quarter). Agility was measured using a hexagon agility test, and eye-hand coordination was measured using a computerized finger-pointing task. Sports performance was quantified by the number of times a shuttlecock fell in a designated area following a badminton serve.The badminton players had superior accuracy in badminton serving (P < .001) relative to the active controls. However, no significant between-group differences were noted in all other outcome variables (P > .05).Amateur badminton players had more favorable sports performance, but not balance performance, agility, or eye-hand coordination, than controls.


Assuntos
Desempenho Atlético/fisiologia , Movimento/fisiologia , Equilíbrio Postural/fisiologia , Desempenho Psicomotor/fisiologia , Esportes com Raquete/fisiologia , Adulto , Estudos de Casos e Controles , Estudos Transversais , Feminino , Voluntários Saudáveis , Humanos , Masculino
19.
Semin Cell Dev Biol ; 91: 45-54, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-29784581

RESUMO

The vertebrate tongue is a complex muscular organ situated in the oral cavity and involved in multiple functions including mastication, taste sensation, articulation and the maintenance of oral health. Although the gross embryological contributions to tongue formation have been known for many years, it is only relatively recently that the molecular pathways regulating these processes have begun to be discovered. In particular, there is now evidence that the Hedgehog, TGF-Beta, Wnt and Notch signaling pathways all play an important role in mediating appropriate signaling interactions between the epithelial, cranial neural crest and mesodermal cell populations that are required to form the tongue. In humans, a number of congenital abnormalities that affect gross morphology of the tongue have also been described, occurring in isolation or as part of a developmental syndrome, which can greatly impact on the health and well-being of affected individuals. These anomalies can range from an absence of tongue formation (aglossia) through to diminutive (microglossia), enlarged (macroglossia) or bifid tongue. Here, we present an overview of the gross anatomy and embryology of mammalian tongue development, focusing on the molecular processes underlying formation of the musculature and connective tissues within this organ. We also survey the clinical presentation of tongue anomalies seen in human populations, whilst considering their developmental and genetic etiology.

20.
EMBO J ; 38(2)2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30523147

RESUMO

Proper temporal and spatial activation of stem cells relies on highly coordinated cell signaling. The primary cilium is the sensory organelle that is responsible for transmitting extracellular signals into a cell. Primary cilium size, architecture, and assembly-disassembly dynamics are under rigid cell cycle-dependent control. Using mouse incisor tooth epithelia as a model, we show that ciliary dynamics in stem cells require the proper functions of a cholesterol-binding membrane glycoprotein, Prominin-1 (Prom1/CD133), which controls sequential recruitment of ciliary membrane components, histone deacetylase, and transcription factors. Nuclear translocation of Prom1 and these molecules is particularly evident in transit amplifying cells, the immediate derivatives of stem cells. The absence of Prom1 impairs ciliary dynamics and abolishes the growth stimulation effects of sonic hedgehog (SHH) treatment, resulting in the disruption of stem cell quiescence maintenance and activation. We propose that Prom1 is a key regulator ensuring appropriate response of stem cells to extracellular signals, with important implications for development, regeneration, and diseases.


Assuntos
Antígeno AC133/metabolismo , Cílios/metabolismo , Incisivo/citologia , Antígeno AC133/genética , Animais , Núcleo Celular/metabolismo , Células Cultivadas , Humanos , Incisivo/metabolismo , Camundongos , Modelos Biológicos , Mutagênese Sítio-Dirigida , Transporte Proteico , Transdução de Sinais , Células-Tronco/citologia , Células-Tronco/metabolismo
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