Case Study: An Individual with Autism and an Intellectual Disability

The proposed study is a single-subject case study. For this study, we will be measuring the academic level of an individual with autism and an intellectual disability as compared to typically developing peers. This individual is in a self-contained classroom for students with intellectual disabilities for reading, math, and social skills. We will interview his special education teachers and also will be observing or administering a test to him a total of 5 times. There will be three standardized tests administered: Woodcock Reading Mastery Tests-Revised, Kaufman Test of Educational Achievement-3, and KeyMath-3. These three standardized tests measure the participant’s overall level of academic achievement, as well as breakdown his strengths and weaknesses in specific areas of reading and math. We will analyze the scores from these standardized tests to gain understanding of the student’s academic ability in order to provide recommendations for the instructional level in which the student should be taught

Evolution of Morphological Integration: Developmental Accommodation of Stress-Induced Variation

Extreme environmental change during growth often results in an increase in developmental abnormalities in the morphology of an organism. The evolutionary significance of such stress-induced variation depends on the recurrence of a stressor and on the degree to which developmental errors can be accommodated by an organism\u27s ontogeny without significant loss of function. We subjected populations of four species of soricid shrews to an extreme environment during growth and measured changes in the patterns of integration and accommodation of stress-induced developmental errors in a complex of mandibular traits. Adults that grew under an extreme environment had lower integration of morphological variation among mandibular traits and highly elevated fluctuating asymmetry in these traits, compared to individuals that grew under the control conditions. However, traits differed strongly in the magnitude of response to a stressor - traits within attachments of the same muscle (functionally integrated traits) had lower response and changed their integration less than other traits. Cohesiveness in functionally integrated complexes of traits under stress was maintained by close covariation of their developmental variation. Such developmental accommodation of stress-induced variation might enable the individual\u27s functioning and persistence under extreme environmental conditions and thus provides a link between individual adaptation to stress and the evolution of stress resistance

17beta-estradiol suppresses TLR3-induced cytokine and chemokine production in endometrial epithelial cells

BACKGROUND: The human endometrium is an important site for contact between the host and pathogens ascending the reproductive tract, and thus plays an important role in female reproductive tract immunity. Previous work in our laboratory has suggested that Toll-like receptors (TLRs) are involved in endometrial epithelial recognition of pathogens and that ligation of endometrial TLRs results in the production of cytokines and chemokines important for both immune and reproductive functions of the endometrium. We have also demonstrated cyclic regulation of TLR3 mRNA and protein expression in human endometrium, suggesting that steroid hormones might play a role in the expression and function of TLR3. In this study, the effects of 17beta-estradiol (E2) and progesterone (P) on TLR3 expression and function in endometrial cell lines were investigated. METHODS: Endometrial epithelial cell lines were cultured and examined for the presence of TLR3 and hormone receptors by endpoint RT-PCR. For hormonal studies, cells were pre-treated with ethanol vehicle, 10^(-8) M E2, and/or 10^(-7) M P. For antagonist assays, cells were treated with the ER antagonist, ICI 182, 780, or the PR antagonist, RU486, for two hours prior to treatment with hormones. Following hormone or hormone/antagonist pre-treatment, cells were stimulated with vehicle, the synthetic TLR3 ligand, polyinosinic-polycytidylic acid (Poly I:C), a negative dsDNA control, or a positive control. Cytokine and chemokine production post-stimulation was measured by ELISA. The effects of E2 and P on TLR3 mRNA and protein expression were measured using Real Time RT-PCR and FACS analysis, respectively. RESULTS: Stimulation of TLR3-expressing cells with the synthetic TLR3 ligand, Poly I:C, resulted in the production of cytokines and chemokines important for endometrial function and regulation. Suppression of Poly I:C-induced cytokine and chemokine production by cells treated with 10^(-8) M E2, but not cells treated with 10^(-7) M P, was observed in endometrial epithelial cell lines expressing TLR3 and estrogen receptor alpha (ERalpha). The effects of E2 were not observed on cells which did not express ERalpha or in cells pre-treated with the ER antagonist, ICI 182, 780. Treatment with E2 did not affect TLR3 mRNA or protein expression. However, treatment with E2 did suppress cytokine and chemokine production resulting from TLR3 stimulation with Poly I:C, suggesting that E2 modulates TLR3 function. CONCLUSION: The data presented in this study are the first indication that E2 can markedly alter the innate immune response to dsRNA, providing a previously unreported process by which E2 can alter immune responses

Interphotoreceptor matrix-poly(ϵ-caprolactone) composite scaffolds for human photoreceptor differentiation

Tissue engineering has been widely applied in different areas of regenerative medicine, including retinal regeneration. Typically, artificial biopolymers require additional surface modification (e.g. with arginine–glycine–aspartate-containing peptides or adsorption of protein, such as fibronectin), before cell seeding. Here, we describe an alternative approach for scaffold design: the manufacture of hybrid interphotoreceptor matrix-poly (ϵ-caprolactone) scaffolds, in which the insoluble extracellular matrix of the retina is incorporated into a biodegradable polymer well suited for transplantation. The incorporation of interphotoreceptor matrix did not change the topography of polycaprolactone film, although it led to a slight increase in hydrophilic properties (water contact angle measurements). This hybrid scaffold provided sufficient stimuli for human retinal progenitor cell adhesion and inhibited proliferation, leading to differentiation toward photoreceptor cells (expression of Crx, Nrl, rhodopsin, ROM1). This scaffold may be used for transplantation of retinal progenitor cells and their progeny to treat retinal degenerative disorders

The adenovirus E4-ORF3 protein stimulates SUMOylation of general transcription factor TFII-I to direct proteasomal degradation

Modulation of host cell transcription, translation, and posttranslational modification processes is critical for the ability of many viruses to replicate efficiently within host cells. The human adenovirus (Ad) early region 4 open reading frame 3 (E4-ORF3) protein forms unique inclusions throughout the nuclei of infected cells and inhibits the antiviral Mre11-Rad50-Nbs1 DNA repair complex through relocalization. E4-ORF3 also induces SUMOylation of Mre11 and Nbs1. We recently identified additional cellular targets of E4-ORF3 and found that E4-ORF3 stimulates ubiquitin-like modification of 41 cellular proteins involved in a wide variety of processes. Among the proteins most abundantly modified in an E4-ORF3-dependent manner was the general transcription factor II–I (TFII-I). Analysis of Ad-infected cells revealed that E4-ORF3 induces TFII-I relocalization and SUMOylation early during infection. In the present study, we explored the relationship between E4-ORF3 and TFII-I. We found that Ad infection or ectopic E4-ORF3 expression leads to SUMOylation of TFII-I that precedes a rapid decline in TFII-I protein levels. We also show that E4-ORF3 is required for ubiquitination of TFII-I and subsequent proteasomal degradation. This is the first evidence that E4-ORF3 regulates ubiquitination. Interestingly, we found that E4-ORF3 modulation of TFII-I occurs in diverse cell types but only E4-ORF3 of Ad species C regulates TFII-I, providing critical insight into the mechanism by which E4-ORF3 targets TFII-I. Finally, we show that E4-ORF3 stimulates the activity of a TFII-I-repressed viral promoter during infection. Our results characterize a novel mechanism of TFII-I regulation by Ad and highlight how a viral protein can modulate a critical cellular transcription factor during infection

Large Scale Nanoparticle Screening for Small Molecule Analysis in Laser Desorption Ionization Mass Spectrometry

Nanoparticles (NPs) have been suggested as efficient matrixes for small molecule profiling and imaging by laser-desorption ionization mass spectrometry (LDI-MS), but so far there has been no systematic study comparing different NPs in the analysis of various classes of small molecules. Here, we present a large scale screening of 13 NPs for the analysis of two dozen small metabolite molecules. Many NPs showed much higher LDI efficiency than organic matrixes in positive mode and some NPs showed comparable efficiencies for selected analytes in negative mode. Our results suggest that a thermally driven desorption process is a key factor for metal oxide NPs, but chemical interactions are also very important, especially for other NPs. The screening results provide a useful guideline for the selection of NPs in the LDI-MS analysis of small molecules

A protocol for a feasibility randomised controlled trial to assess the difference between functional bracing and plaster cast for the treatment of ankle fractures

Background: UK Hospital Episode Statistics 2013–2014 recorded 57,286 fractures of the lower limb including the ankle. This figure is expected to continue to increase due to a greater population of older adults. Following an ankle fracture, patients usually have their ankle immobilised with a plaster cast. This provides maximum support for the healing ankle but is associated with stiffness and muscle wasting. A Cochrane Review has concluded that functional bracing may reduce muscle wasting and speed recovery of ankle movement. The aim of this study is to determine the feasibility of conducting a full randomised controlled trial in adults with an ankle fracture followed by functional bracing and exercises versus standard plaster cast care. Methods: This is a single-centre feasibility randomised controlled trial. All patients with a fractured ankle are potentially eligible. The trial will employ 1:1 random allocation, stratified by age and non-operative/operative management. Baseline demographic and pre-injury functional data, the Manchester-Oxford Foot and Ankle Questionnaire (MOXFQ) and Olerud and Molander Ankle Score (OMAS) will be collected alongside the EuroQol EQ-5D-5 L health-related quality of life questionnaire. A research associate will perform a clinical assessment and obtain X-rays in 6 weeks and 6 months post randomisation to record complications. Functional outcome and health-related quality of life will be collected in 6 weeks, 3 and 6 months post randomisation. Discussion: This feasibility trial will provide authoritative high-quality evidence to inform the design of a definitive trial in this important area