Dynamic expression of Dab2 in the mouse embryonic central nervous system

<p>Abstract</p> <p>Background</p> <p>Dab2, one of two mammalian orthologs of <it>Drosophila Disabled</it>, has been shown to be involved in cell positioning and formation of visceral endoderm during mouse embryogenesis, but its role in neuronal development is not yet fully understood. In this report, we have examined the localization of the Dab2 protein in the mouse embryonic central nervous system (CNS) at different developmental stages.</p> <p>Results</p> <p>Dab2 protein was transiently expressed in rhombomeres 5 and 6 of the developing hindbrain between E8.5 and E11.5, and in the floor plate of the neural tube from E9.5 to E12.5, following which it was no longer detectable within these regions. Dab2 protein was also identified within circumventricular organs including the choroid plexus, subcommissural organ and pineal gland during their early development. While Dab2 was still strongly expressed in the adult choroid plexus, immunoreactivity within the subcommissural organ and pineal gland was lost after birth. In addition, Dab2 was transiently expressed within a subpopulation of Iba1-positive mononuclear phagocytes (including presumed microglial progenitors) within the neural tube from E10.0 and was lost by E14.5. Dab2 was separately localized to Iba1 positive cells from E9.5 and subsequently to F4/80 positive cells (mature macrophage/myeloid-derived dendritic cells) positioned outside the neural tube from E12.5 onwards, implicating Dab2 expression in early cells of the mononuclear phagocyte lineage. Dab2 did not co-localize with the pan-neuronal marker PGP9.5 at any developmental stage, suggesting that Dab2 positive cells in the developing CNS are unlikely to be differentiating neurons.</p> <p>Conclusion</p> <p>This is the first study to demonstrate the dynamic spatiotemporal expression of Dab2 protein within the CNS during development.</p

Knee stability assessment on anterior cruciate ligament injury: clinical and biomechanical approaches

Anterior cruciate ligament (ACL) injury is common in knee joint accounting for 40% of sports injury. ACL injury leads to knee instability, therefore, understanding knee stability assessments would be useful for diagnosis of ACL injury, comparison between operation treatments and establishing return-to-sport standard. This article firstly introduces a management model for ACL injury and the contribution of knee stability assessment to the corresponding stages of the model. Secondly, standard clinical examination, intra-operative stability measurement and motion analysis for functional assessment are reviewed. Orthopaedic surgeons and scientists with related background are encouraged to understand knee biomechanics and stability assessment for ACL injury patients

A non-invasive biomechanical device to quantify knee rotational laxity: Verification of the device in human cadaveric specimens

Background: Biomechanical measurement tools have been developed and widely used to precisely quantify knee anterior-posterior laxity after anterior cruciate ligament (ACL) injury. However, validated objective device to document knee rotational laxity, though being developed by different researchers, are not yet widely used in the daily clinical practice. A new biomechanical device was developed to quantify knee internal and external rotations. Methods: The reliability of the new biomechanical device which measures knee rotations were tested. Different torques (1-10Nm) were applied by the device to internally and externally rotate human cadaveric knees, which were held in a flexion angle of 30 . The rotations were measured by the device in degrees. There were two independent testers, and each tester carried out three trials. Intra-rater and inter-rater reliability were quantified in terms of intraclass correlation (ICC) coefficient among trials and between testers. The device was verified by the comparison with a computer assisted navigation system. ICC was measured. Mean, standard deviation and 95% confident interval of the difference as well as the root mean square difference were calculated. The correlations were deemed to be reliable if the ICC was above 0.75. Results: The intra-rater and inter-rater reliability achieved high correlation for both internal and external rotation, ranged from 0.959 to 0.992. ICC between the proposed meter and the navigation system for both internal and external rotation was 0.78. The mean differences were 2.3 and 2.5 for internal and external rotation respectively. Conclusions: A new knee rotational laxity meter was proposed in this study. Its reliability was verified by showing high correlation among trials. It also showed good correlation to a gold standard of measurement. It might be used to document knee rotational laxity for various purposes, especially after ACL injury, after further validation of the device in human subject

Comparison of two surgical techniques for reconstructing posterolateral corner of the knee: a cadaveric study evaluated by navigation system

Purpose: This study aimed to evaluate the immediate effect on knee kinematics by 2 different techniques of posterolateral corner (PLC) reconstruction. Methods: Five intact formalin-preserved cadaveric knees were used in this study. A navigation system was used to measure knee kinematics (posterior translation, varus angulation, and external rotation) after application of a constant force and torque to the tibia. Four different conditions of the knee were evaluated during the biomechanical test: intact knee and PLC-sectioned knee and PLC-reconstructed knee by the doublefemoral tunnel technique and singlefemoral tunnel technique. Results: Sectioning of the PLC structures resulted in significant increases in external rotation at 30° of flexion from 11.2° (SD, 2.6) to 24.6° (SD, 6.2), posterior translation at 30° of flexion from 3.4 mm (SD, 1.5) to 7.4 mm (SD, 3.8), and varus angulation at 0° of flexion from 2.3° (SD, 2.1) to 7.9° (SD, 5.1). Both reconstruction techniques significantly restored the varus stability. The external rotation and posterior translation at 30° of flexion after reconstruction with the doublefemoral tunnel technique were 10.2° (SD, 1.3) and 3.4° (SD, 2.7), respectively, which were significantly better than those of the singlefemoral tunnel technique. Conclusions: Both techniques of reconstruction showed improved stability compared with PLC-sectioned knees. The doublefemoral tunnel technique in PLC reconstruction showed better rotational stability and resistance to posterior translation than the singlefemoral tunnel technique without compromising varus stability. Clinical Relevance: PLC reconstruction by a doublefemoral tunnel technique achieves better rotational control and resistance to posterior translation

Discovery of a Novel Prolactin in Non-Mammalian Vertebrates: Evolutionary Perspectives and Its Involvement in Teleost Retina Development

BACKGROUND:The three pituitary hormones, viz. prolactin (PRL), growth hormone (GH) and somatolactin (SL), together with the mammalian placental lactogen (PL), constitute a gene family of hormones with similar gene structure and encoded protein sequences. These hormones are believed to have evolved from a common ancestral gene through several rounds of gene duplication and subsequent divergence. PRINCIPAL FINDINGS:In this study, we have identified a new PRL-like gene in non-mammalian vertebrates through bioinformatics and molecular cloning means. Phylogenetic analyses showed that this novel protein is homologous to the previously identified PRL. A receptor transactivation assay further showed that this novel protein could bind to PRL receptor to trigger the downstream post-receptor event, indicating that it is biologically active. In view of its close phylogenetic relationship with PRL and also its ability to activate PRL receptor, we name it as PRL2 and the previously identified PRL as PRL1. All the newly discovered PRL2 sequences possess three conserved disulfide linkages with the exception of the shark PRL2 which has only two. In sharp contrast to the classical PRL1 which is predominantly expressed in the pituitary, PRL2 was found to be mainly expressed in the eye and brain of the zebrafish but not in the pituitary. A largely reduced inner nuclear layer of the retina was observed after morpholino knockdown of zebrafish PRL2, indicating its role on retina development in teleost. SIGNIFICANCE:The discovery of this novel PRL has revitalized our understanding on the evolution of the GH/PRL/SL/PL gene family. Its unique expression and functions in the zebrafish eye also provide a new avenue of research on the neuroendocrine control of retina development in vertebrates

Demonstrating the validity of the Video Game Functional Assessment-Revised (VGFA-R)

Problematic video play has been well documented over the course of the last decade. So much so the DSM-5 (APA, 2013) has included problematic video gaming as disorder categorized as Internet Gaming Disorder. The field of applied behavior analysis has been utilizing functional assessments for the last 30 years and has showed evidence of effective results across different populations and environments. Therefore, the purpose of this investigation (comprising three studies) was to validate an indirect functional assessment entitled the Video Game Functional Assessment-Revised (VGFA-R). Using academic experts in the field of video game addiction and applied behavioral analysis (n=6), the first study examined the content validity of the VGFA-R and was able to demonstrate the assessment exceeded the criterion for an established assessment. A second study comprising a survey of 467 gamers examined the factorability by using a confirmatory factor analysis, and found that VGFA-R had an overall variance above .60. Within the third laboratory-based study using gamers (n=11), the VGFA-R was examined for construct validity and found the VGFA-R was able to predict 85% of the appropriate function of behavior. Implications of the study are discussed along with the strengths and limitations of the study and future research directions

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Protective Effects of a Rhodiola Crenulata Extract and Salidroside on Hippocampal Neurogenesis against Streptozotocin-Induced Neural Injury in the Rat

Previously we have demonstrated that a Rhodiola crenulata extract (RCE), containing a potent antioxidant salidroside, promotes neurogenesis in the hippocampus of depressive rats. The current study was designed to further investigate the protective effect of the RCE on neurogenesis in a rat model of Alzheimer's disease (AD) induced by an intracerebroventricular injection of streptozotocin (STZ), and to determine whether this neuroprotective effect is induced by the antioxidative activity of salidroside. Our results showed that pretreatment with the RCE significantly improved the impaired neurogenesis and simultaneously reduced the oxidative stress in the hippocampus of AD rats. In vitro studies revealed that (1) exposure of neural stem cells (NSCs) from the hippocampus to STZ strikingly increased intracellular reactive oxygen species (ROS) levels, induced cell death and perturbed cell proliferation and differentiation, (2) hydrogen peroxide induced similar cellular activities as STZ, (3) pre-incubation of STZ-treated NSCs with catalase, an antioxidant, suppressed all these cellular activities induced by STZ, and (4) likewise, pre-incubation of STZ-treated NSCs with salidroside, also an antioxidant, suppressed all these activities as catalase: reduction of ROS levels and NSC death with simultaneous increases in proliferation and differentiation. Our findings indicated that the RCE improved the impaired hippocampal neurogenesis in the rat model of AD through protecting NSCs by its main ingredient salidroside which scavenged intracellular ROS

Human germline heterozygous gain-of-function STAT6 variants cause severe allergic disease

STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti-IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder