Matrix Metalloproteinases and Minocycline: Therapeutic Avenues for Fragile X Syndrome

Fragile X syndrome (FXS) is the most common known genetic form of intellectual disability and autism spectrum disorders. FXS patients suffer a broad range of other neurological symptoms, including hyperactivity, disrupted circadian activity cycles, obsessive-compulsive behavior, and childhood seizures. The high incidence and devastating effects of this disease state make finding effective pharmacological treatments imperative. Recently, reports in both mouse and Drosophila FXS disease models have indicated that the tetracycline derivative minocycline may hold great therapeutic promise for FXS patients. Both models strongly suggest that minocycline acts on the FXS disease state via inhibition of matrix metalloproteinases (MMPs), a class of zinc-dependent extracellular proteases important in tissue remodeling and cell-cell signaling. Recent FXS clinical trials indicate that minocycline may be effective in treating human patients. In this paper, we summarize the recent studies in Drosophila and mouse FXS disease models and human FXS patients, which indicate that minocycline may be an effective FXS therapeutic treatment, and discuss the data forming the basis for the proposed minocycline mechanism of action as an MMP inhibitor

Standardisation of Parameters during Endovenous Laser Therapy of Truncal Varicose Veins - Experimental Ex-vivo Study

BackgroundVein shrinkage is a surrogate marker for successful laser treatment of varicose veins. However, many controversies still remain concerning the best laser parameters to use. The aim of this study was standardisation of intraoperative energy dosages and pull-back rates to achieve optimal clinical results.DesignEx-vivo study in surgically removed saphenous trunks.Material and methodsGreat saphenous veins were removed by Babcock stripping and irradiated with laser energy delivered by a laser diode emitting at 980nm. In total, 279 vein segments (5cm long) were treated using powers from 5–15W. Vein segments were opened longitudinally and the circumference measured in the treated and untreated regions to assess thermal shrinkage.ResultsThe greatest shrinkage and minimum number of perforations was achieved using lower or medium power (8 to 12W) with longer exposure to administer laser energy. The median percentage vein shrinkage was 50% (power 5W), 45% (8W), 40% (10W), 45% (12W) and 59% (15W). When a higher power was used (15W), the perforations were more frequent and carbonisation was marked.ConclusionsOur data suggests that similar efficacy with fewer vein perforations may be obtained with low or medium power settings and increased exposure when undertaking laser obliteration of saphenous trunks. This may result in fewer adverse events such as ecchymosis following treatment in patients

Development of a rapid screen for the endodermal differentiation potential of human pluripotent stem cell lines.

A challenge facing the human pluripotent stem cell (hPSC) field is the variability observed in differentiation potential of hPSCs. Variability can lead to time consuming and costly optimisation to yield the cell type of interest. This is especially relevant for the differentiation of hPSCs towards the endodermal lineages. Endodermal cells have the potential to yield promising new knowledge and therapies for diseases affecting multiple organ systems, including lung, thymus, intestine, pancreas and liver, as well as applications in regenerative medicine and toxicology. Providing a means to rapidly, cheaply and efficiently assess the differentiation potential of multiple hPSCs is of great interest. To this end, we have developed a rapid small molecule based screen to assess the endodermal potential (EP) of hPSCs, based solely on definitive endoderm (DE) morphology. This drastically reduces the cost and time to identify lines suitable for use in deriving endodermal lineages. We demonstrate the efficacy of this screen using 10 different hPSCs, including 4 human embryonic stem cell lines (hESCs) and 6 human induced pluripotent stem cell lines (hiPSCs). The screen clearly revealed lines amenable to endodermal differentiation, and only lines that passed our morphological assessment were capable of further differentiation to hepatocyte like cells (HLCs)

Taking the Mentoring of New Teacher Educators Seriously: Lessons From a Clinically-Intensive Teacher Preparation Program

The challenges facing teacher educators entering their first faculty position in a clinically intensive teacher preparation program reflect similar difficulties that novice teachers encounter upon entry to their own classroom. Just as new teachers must learn the ropes while performing the work of teaching (Feiman-Nemser, 2001; Wildman, Niles, Magliaro, & McLaughlin, 1989), so, too, must novice teacher educators learn to create clinically based learning opportunities for teacher candidates (American Association of Colleges for Teacher Education, 2018; Grossman, Hammerness & McDonald, 2009) while learning to navigate the university system, establish their practice as field-based practitioners, earn strong student/course evaluations (Ramsden, 2003) and address the realities of publish or perish (Russell & Korthagen, 1995)

The transition between hole-pairs and four-hole clusters in four-leg tJ ladders

Holes weakly doped into a four-leg \tj ladder bind in pairs. At dopings exceeding a critical doping of $\delta_c\simeq {1/8}$ four hole clusters are observed to form in DMRG calculations. The symmetry of the ground state wavefunction does not change and we are able to reproduce this behavior qualitatively with an effective bosonic model in which the four-leg ladder is represented as two coupled two-leg ladders and hole-pairs are mapped on hard core bosons moving along and between these ladders. At lower dopings, $\delta<\delta_c$, a one dimensional bosonic representation for hole-pairs works and allows us to calculate accurately the Luttinger liquid parameter \krho, which takes the universal value \krho=1 as half-filling is approached

Charge density correlations in t-J ladders investigated by the CORE method

Using 4-site plaquette or rung basis decomposition, the CORE method is applied to 2-leg and 4-leg t-J ladders and cylinders. Resulting range-2 effective hamiltonians are studied numerically on periodic rings taking full advantage of the translation symmetry as well as the drastic reduction of the Hilbert space. We investigate the role of magnetic and fermionic degrees of freedom to obtain the most reliable representation of the underlying model. Spin gaps, pair binding energies and charge correlations are computed and compared to available ED and DMRG data for the full Hamiltonian. Strong evidences for short-range diagonal stripe correlations are found in periodic 4-leg t-J ladders.Comment: Computation of Luttinger liquid parameters (charge velocity and charge correlation exponent) adde

Superconductivity and antiferromagnetism in a hard-core boson spin-1 model in two dimensions

A model of hard-core bosons and spin-1 sites with single-ion anisotropy is proposed to approximately describe hole pairs moving in a background of singlets and triplets with the aim of exploring the relationship between superconductivity and antiferromagnetism. The properties of this model at zero temperature were investigated using quantum Monte Carlo techniques. The most important feature found is the suppression of superconductivity, as long range coherence of preformed pairs, due to the presence of both antiferromagnetism and $S^z=\pm 1$ excitations. Indications of charge ordered and other phases are also discussed.Comment: One figure, one reference, adde

A comparison of the shear strength of strucutral composite lumber using torsion and shear block tests

The objective of this study was to compare the shear strength of structural composite lumber (SCL) based on shear block to that of shear strength based on torsion test. Shear blocks in two diflcrent orientations fom laminated veneer lumber, parallel strand lumber, and laminated strand lumber (LSL) were tested and their shear strengths were compared to the shear strengths or full-sized specimens based on torsion tests from the literature. The results showed that the shear strength based on torsion is 12 to 39 percent lower than the shear strength based on shear block. The failure mode of LSL using shear blocks is predominantly compression parallel. The study concluded that the shear block is not an appropriate test method to determine the shear strength of SCL