Strontium incorporated coralline hydroxyapatite for engineering bone

Goniopora was hydrothermally converted to coralline hydroxyapatite (CHA) and incorporated with Sr (Sr-CHA). The pore size of Goniopora was in the range of 40–300 μm with a porosity of about 68%. Surface morphologies of the coral were modified to flake-like hydroxyapatite structures on CHA and the addition of Sr detected on Sr-CHA as confirmed by SEM and EDX. As the first report of incorporating Sr into coral, about 6%–14% Sr was detected on Sr-CHA. The compressive strengths of CHA and Sr-CHA were not compromised due to the hydrothermal treatments. Sr-CHA was studied in vitro using MC3T3-E1 cells and in vivo with an ovariectomized rat model. The proliferation of MC3T3-E1 cells was significantly promoted by Sr-CHA as compared to CHA. Moreover, higher scaffold volume retention (+40%) was reported on the micro-CT analysis of the Sr-CHA scaffold. The results suggest that the incorporation of Sr in CHA can further enhance the osteoconductivity and osteoinductivity of corals. Strontium has been suggested to stimulate bone growth and inhibit bone resorption. In this study, we have successfully incorporated Sr into CHA with the natural porous structure remained and explored the idea of Sr-CHA as a potential scaffolding material for bone regeneration.published_or_final_versio

Was it a pain or a sound? Across-species variability in sensory sensitivity

Natural selection has shaped the physiological properties of sensory systems across species, yielding large variations in their sensitivity. Here, we used laser stimulation of skin nociceptors, a widely used technique to investigate pain in rats and humans, to provide a vivid example of how ignoring these variations can lead to serious misconceptions in sensory neuroscience. In 6 experiments, we characterized and compared the physiological properties of the electrocortical responses elicited by laser stimulation in rats and humans. We recorded the electroencephalogram from the surface of the brain in freely moving rats and from the scalp in healthy humans. Laser stimuli elicited 2 temporally distinct responses, traditionally interpreted as reflecting the concomitant activation of different populations of nociceptors with different conduction velocities: small-myelinated Aδ-fibres and unmyelinated C-fibres. Our results show that this interpretation is valid in humans, but not in rats. Indeed, the early response recorded in rats does not reflect the activation of the somatosensory system, but of the auditory system by laser-generated ultrasounds. These results have wide implications: retrospectively, as they prompt for a reconsideration of a large number of previous interpretations of electrocortical rat recordings in basic, preclinical, and pharmacological research, and prospectively, as they will allow recording truly pain-related cortical responses in rats

Recent Advances in Graph Partitioning

We survey recent trends in practical algorithms for balanced graph partitioning together with applications and future research directions

Effect of growth temperature on the structural, optical and luminescence properties of cadmium telluride nanoparticles

Cadmium telluride (CdTe) has been successfully prepared by a simple wet chemical process at different reaction temperatures. Temperature is one parameter that thermodynamically plays an important role in controlling the growth rate, morphology, size and size distribution of the as-prepared nanoparticles (NPs). Effect of this parameter was investigated on the growth, structural and optical properties of CdTe NPs. It was observed that the Powder X-ray diffraction (XRD) pattern for samples prepared at 50 °C had many impurities from unreacted precursors while those prepared at > 100 °C displayed polycrystalline NPs. The XRD results revealed that the structure of the CdTe NPs was cubic with the planes (111), (220), (311) being the main observed peaks. The crystallite sizes obtained from Scherrer formula increased with the increase in growth temperature (2.86–3.62 nm grown at 50–200 °C respectively). The scanning electron microscopy micrographs showed that the morphology of the nanoparticles possessed spherical-shaped particles over the entire surface. This was further confirmed by high resolution transmission electron microscopy micrographs which also displayed increase in the particle size with an increase in the growth temperature. In the optic study, the photoluminescence (PL) spectra displayed a red shift (540–560 nm) in emission as growth temperature increased from 50 to 200 °C. The highest PL peak intensity was realized at a growth temperature of 150 °C. Absorption band maxima were observed to shift towards longer wavelength for higher growth temperatures. The optical band gap decreased with increase in the growth temperature from 2.67 to 2.08 eV for 50–200 °C respectively

Inducible high-efficiency CRISPR-Cas9-targeted gene editing and precision base editing in African trypanosomes

The Cas9 endonuclease can be programmed by guide RNA to introduce sequence-specific breaks in genomic DNA. Thus, Cas9-based approaches present a range of novel options for genome manipulation and precision editing. African trypanosomes are parasites that cause lethal human and animal diseases. They also serve as models for studies on eukaryotic biology, including 'divergent' biology. Genome modification, exploiting the native homologous recombination machinery, has been important for studies on trypanosomes but often requires multiple rounds of transfection using selectable markers that integrate at low efficiency. We report a system for delivering tetracycline inducible Cas9 and guide RNA to Trypanosoma brucei. In these cells, targeted DNA cleavage and gene disruption can be achieved at close to 100% efficiency without further selection. Disruption of aquaglyceroporin (AQP2) or amino acid transporter genes confers resistance to the clinical drugs pentamidine or eflornithine, respectively, providing simple and robust assays for editing efficiency. We also use the new system for homology-directed, precision base editing; a single-stranded oligodeoxyribonucleotide repair template was delivered to introduce a single AQP2 - T 791G/L 264R mutation in this case. The technology we describe now enables a range of novel programmed genome-editing approaches in T. brucei that would benefit from temporal control, high-efficiency and precision. </p

MicroRNA-377 suppresses initiation and progression of esophageal cancer by inhibiting CD133 and VEGF

published_or_final_versio

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Tumour antigen expression in hepatocellular carcinoma in a low-endemic western area

Background: Identification of tumour antigens is crucial for the development of vaccination strategies against hepatocellular carcinoma (HCC). Most studies come from eastern-Asia, where hepatitis-B is the main cause of HCC. However, tumour antigen expression is poorly studied in low-endemic, western areas where the aetiology of HCC differs. Methods: We constructed tissue microarrays from resected HCC tissue of 133 patients. Expression of a comprehensive panel of cancer-testis (MAGE-A1, MAGE-A3/4, MAGE-A10, MAGE-C1, MAGE-C2, NY-ESO-1, SSX-2, sperm protein 17), onco-fetal (AFP, Glypican-3) and overexpressed tumour antigens (Annexin-A2, Wilms tumor-1, Survivin, Midkine, MUC-1) was determined by immunohistochemistry. Results: A higher prevalence of MAGE antigens was observed in patients with hepatitis-B. Patients with expression of more tumour antigens in general had better HCC-specific survival (P=0.022). The four tumour antigens with high expression in HCC and no, or weak, expression in surrounding tumour-free-liver tissue, were Annexin-A2, GPC-3, MAGE-C1 and MAGE-C2, expressed in 90, 39, 17 and 20% of HCCs, respectively. Ninety-five percent of HCCs expressed at least one of these four tumour antigens. Interestingly, GPC-3 was associated with SALL-4 expression (P=0.001), an oncofetal transcription factor highly expressed in embryonal stem cells. SALL-4 and GPC-3 expression levels were correlated with vascular invasion, poor differentiation and higher AFP levels before surgery. Moreover, patients who co-expressed higher levels of both GPC-3 and SALL-4 had worse HCC-specific survival (P=0.018). Conclusions: We describe a panel of four tumour antigens with excellent coverage and good tumour specificity in a western area, low-endemic for hepatitis-B. The association between GPC-3 and SALL-4 is a novel finding and suggests that GPC-3 targeting may specifically attack the tumour stem-cell compartment

Complexity Variability Assessment of Nonlinear Time-Varying Cardiovascular Control

The application of complex systems theory to physiology and medicine has provided meaningful information about the nonlinear aspects underlying the dynamics of a wide range of biological processes and their disease-related aberrations. However, no studies have investigated whether meaningful information can be extracted by quantifying second-order moments of time-varying cardiovascular complexity. To this extent, we introduce a novel mathematical framework termed complexity variability, in which the variance of instantaneous Lyapunov spectra estimated over time serves as a reference quantifier. We apply the proposed methodology to four exemplary studies involving disorders which stem from cardiology, neurology and psychiatry: Congestive Heart Failure (CHF), Major Depression Disorder (MDD), Parkinson?s Disease (PD), and Post-Traumatic Stress Disorder (PTSD) patients with insomnia under a yoga training regime. We show that complexity assessments derived from simple time-averaging are not able to discern pathology-related changes in autonomic control, and we demonstrate that between-group differences in measures of complexity variability are consistent across pathologies. Pathological states such as CHF, MDD, and PD are associated with an increased complexity variability when compared to healthy controls, whereas wellbeing derived from yoga in PTSD is associated with lower time-variance of complexity

Non-Motor and Motor Features in LRRK2 Transgenic Mice

10.1371/journal.pone.0070249PLoS ONE87-POLN