The role of Olig2 regulation in ventral neural tube patterning

In the developing spinal cord, a ventral to dorsal gradient of Sonic Hedgehog (Shh) protein directs spatial organisation of neural progenitor domains that subsequently di erentiate to molecularly distinct neurons. Graded Shh signalling is interpreted by a gene regulatory network (GRN) that restricts expression of di erent transcription factors to progenitor domains delimited by sharp boundaries. This GRN, comprising of four key transcription factors, has been modelled in a deterministic mathematical model. To explore how this GRN ensures robustness in patterning, the interactions between nodes of the network required further investigation. In this study, we investigate interactions at a particular node, Olig2, expressed in the ventral neural tube in the motor neuron progenitor (pMN) domain. We fo- cused on the -33 kb enhancer of Olig2 that has binding sites for all major inputs in the GRN. CRISPR/Cas9-mediated excision of this enhancer in vitro severely disrupted Olig2 expression in mouse ES cells directly di erentiated towards spinal cord progenitors. Remaining Olig2 expression highlighted a second regulatory re- gion, +75 kb, that became accessible at later stages. Deletion of both -33 and +75 kb enhancers led to a complete loss of Olig2 expression in vitro. Excision of the -33 kb enhancer in vivo resulted in embryos having reduced Olig2 expression in a smaller pMN domain which was more severe when combined with deletion of the +75 kb enhancer. In addition to reduced Olig2 expression, a loss of precision was observed at the p3/pMN boundary in the developing neural tube. In collaboration with Edgar Herrera Delgado, we modelled this loss of precision in silico and have been able to uncover a mechanism encoded within GRN structure that drives precision in patterning even in the presence of noisy gene expression. Through analyses of Olig2 enhancers both in vitro and in vivo, we demonstrate how enhancers contribute to robustness in gene regulatory networks driving patterning

A RISK-BASED APPROACH TO BLENDED LEARNING DESIGN FOR HEALTHCARE WORKPLACE TRAINING

New employee orientation and ongoing compliance training ensure that healthcare staff are competent and confident to perform their duties and provide safe patient care. There is no industry standard or evidence-informed decision framework that determines when to use in-person, face-to-face, online, or blended learning for healthcare workplace training. This research aims to answer the question: Is there a relationship between perceived risk of the learning content, delivery modes, and interaction techniques in health care workplace training? An online survey and correlation analysis were used to rank the preferences of healthcare workplace instructional designers. Quantitative analysis found statistically significant preferences for: 1) learner-instructor and learner-content interaction for high-risk content, 2) in-person face-to-face delivery via learner-content interaction for high-risk learning content, and 3) learner-content interaction for medium-risk learning content. This study enabled a proposed risk-based training and orientation planning support (RB-TOPS) matrix for instructional design decision-making that aids healthcare operational readiness.202

The use of Instagram for travel planning and destination selection

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Precision of tissue patterning is controlled by dynamical properties of gene regulatory networks

During development, gene regulatory networks allocate cell fates by partitioning tissues into spatially organised domains of gene expression. How the sharp boundaries that delineate these gene expression patterns arise, despite the stochasticity associated with gene regulation, is poorly understood. We show, in the vertebrate neural tube, using perturbations of coding and regulatory regions, that the structure of the regulatory network contributes to boundary precision. This is achieved, not by reducing noise in individual genes, but by the configuration of the network modulating the ability of stochastic fluctuations to initiate gene expression changes. We use a computational screen to identify network properties that influence boundary precision, revealing two dynamical mechanisms by which small gene circuits attenuate the effect of noise in order to increase patterning precision. These results highlight design principles of gene regulatory networks that produce precise patterns of gene expression.</p

Species-specific pace of development is associated with differences in protein stability

Although many molecular mechanisms controlling developmental processes are evolutionarily conserved, the speed at which the embryo develops can vary substantially between species. For example, the same genetic program, comprising sequential changes in transcriptional states, governs the differentiation of motor neurons in mouse and human, but the tempo at which it operates differs between species. Using in vitro directed differentiation of embryonic stem cells to motor neurons, we show that the program runs more than twice as fast in mouse as in human. This is not due to differences in signaling, nor the genomic sequence of genes or their regulatory elements. Instead, there is an approximately two-fold increase in protein stability and cell cycle duration in human cells compared with mouse cells. This can account for the slower pace of human development and suggests that differences in protein turnover play a role in interspecies differences in developmental tempo

Trisomy 18 and hepatic neoplasia

A 2 9/12-year-old girl with trisomy 18 presented with a 3-week history of low grade fever, abdominal distention, and hepatosplenomegaly. Abdominal cytotomography (CT) scan showed hepatic infiltration with a tumor mass presumed to be hepatoblastoma. She deteriorated rapidly and died 3 weeks later. No autopsy and/or biopsy could be done.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38245/1/1320270122_ftp.pd

The immediate effects of two manual therapy techniques on ankle musculoarticular stiffness and dorsiflexion range of motion in people with chronic ankle rigidity: A randomized clinical trial

OBJECTIVE: Ankle rigidity is a common musculoskeletal disorder affecting the talocrural joint, which can impair weight-bearing ankle dorsiflexion (WBADF) and daily-life in people with or without history of ankle injuries. Our objective was to compare the immediate effects of efficacy of Mulligan Mobilization with Movement (MWM) and Osteopathic Mobilization (OM) for improving ankle dorsiflexion range of motion (ROM) and musculoarticular stiffness (MAS) in people with chronic ankle dorsiflexion rigidity. DESIGN: A randomized clinical trial with two arms. METHODS: Patients were recruited by word of mouth and via social network as well as posters, and analyzed in the neuro musculoskeletal laboratory of the “Université Catholique de Louvain-la-Neuve”, Brussels, Belgium. PARTICIPANTS: 67 men (aged 18–40 years) presenting with potential chronic non-specific and unilateral ankle mobility deficit during WBDF were assessed for eligibility and finally 40 men were included and randomly allocated to single session of either MWM or OM. INTERVENTIONS: Two modalities of manual therapy indicated for hypothetic immediate effects in chronic ankle dorsiflexion stiffness, i.e. MWM and OM, were applied during a single session on included patients. MAIN OUTCOME MEASURES: Comprised blinding measures of MAS with a specific electromechanical device (namely: Lehmann’s device) producing passive oscillatory ankle joint dorsiflexion and with clinical measures of WBADF-ROM as well. RESULTS: A two-way ANOVA revealed a non-significant interaction between both techniques and time for all outcome measures. For measures of MAS: elastic-stiffness (p= 0.37), viscous-stiffness (p= 0.83), total-stiffness (p= 0.58). For WBADF-ROM: toe-wall distance (p= 0.58) and angular ROM (p= 0.68). Small effect sizes between groups were determined with Cohen’s d ranging from 0.05 to 0.29. One-way ANOVA demonstrated non-significant difference and small to moderate effects sizes (d= 0.003–0.58) on all outcome measures before and after interventions within both groups. A second two-way ANOVA analyzed the effect of each intervention on the sample categorized according to injury history status, and demonstrated a significant interaction between groups and time only for viscous stiffness (p= 0.04, d=-0.55). CONCLUSION: A single session of MWM and OM targeting the talocrural joint failed to immediately improve all measures in subjects with chronic ankle dorsiflexion stiffness. Despite this, there was an increase in viscous stiffness in people with history of ankle injury following both manual techniques, the value of which remains unclear even if it might help to prevent future abnormal ankle joint movements

The comparison of grey-scale ultrasonic and clinical features of hepatoblastoma and hepatocellular carcinoma in children: a retrospective study for ten years

<p>Abstract</p> <p>Background</p> <p>Hepatoblastoma (HBL) and hepatocellular carcinoma (HCC) are respectively the first and the second most common pediatric malignant liver tumors. The purpose of this study was to evaluate the combined use of the ultrasound examination and the assessment of the patients' clinical features for differentiating HBL from HCC in children.</p> <p>Methods</p> <p>Thirty cases of the confirmed HBL and 12 cases of the confirmed HCC in children under the age of 15 years were enrolled into our study. They were divided into the HBL group and the HCC group according to the histological types of the tumors. The ultrasonic features and the clinical manifestations of the two groups were retrospectively analyzed, with an emphasis on the following parameters: onset age, gender (male/female) ratio, positive epatitis-B-surface-antigen (HBV), alpha-fetoprotein increase, and echo features including septa, calcification and liquefaction within the tumors.</p> <p>Results</p> <p>Compared with the children with HCC, the children with HBL had a significantly younger onset age (8.2 years vs. 3.9 years, P < 0.001) and a significantly smaller frequency of positive HBV (66.7% vs. 13.3%, P < 0.001). The septa and liquefaction were more frequently found in HBL than in HCC (25/30, 83.3% vs. 2/12, 16.7%, P < 0.001; 17/30, 56.7% vs. 3/12, 25%, P = 0.02). When a combination of the liquefaction, septa, negative HBV and onset age smaller than 5 years was used in the evaluation, the sensitivity was raised to 90%, the accuracy was raised to 88%, and the negative predictive value was raised to 73%.</p> <p>Conclusion</p> <p>Ultrasonic features combined with clinical manifestations are valuable for differentiating HBL from HCC in children.</p