Strategies for cell membrane functionalization

The ability to rationally manipulate and augment the cytoplasmic membrane can be used to overcome many of the challenges faced by conventional cellular therapies and provide innovative opportunities when combined with new biotechnologies. The focus of this review is on emerging strategies used in cell functionalization, highlighting both pioneering approaches and recent developments. These will be discussed within the context of future directions in this rapidly evolving field

A mouse model for Luminal epithelial like ER positive subtype of human breast cancer

<p>Abstract</p> <p>Background</p> <p>Generation of novel spontaneous ER positive mammary tumor animal model from heterozygous NIH nude mice.</p> <p>Methods</p> <p>Using brother-sister mating with pedigree expansion system, we derived a colony of heterozygous breeding females showing ER-Positive tumors around the age of 6 months. Complete blood picture, differential leukocyte count, and serum levels of Estrogen, Alanine amino transferase (SGPT), Aspartate amino transferase (SGOT), total protein and albumin were estimated. Aspiration biopsies and microbiology were carried out. Gross pathology of the tumors and their metastatic potential were assessed. The tumors were excised and further characterized using histopathology, cytology, electron microscopy (EM), molecular markers and Mouse mammary Tumor Virus – Long Terminal Repeats (MMTV LTR) specific RT-PCR.</p> <p>Results</p> <p>The tumors originated from 2^ndor 5^thor both the mammary glands and were multi-nodulated with variable central necrosis accompanied with an accumulation of inflammatory exudate. Significant increases in estrogen, SGPT, SGOT and neutrophils levels were noticed. Histopathologically, invasive nodular masses of pleomorphic tubular neoplastic epithelial cells invaded fibro-vascular stroma, adjacent dermis and subcutaneous tissue. Metastatic spread through hematogenous and regional lymph nodes, into liver, lungs, spleen, heart and dermal lymphatics was observed. EM picture revealed no viral particles and MMTV-negativity was confirmed through MMTV LTR-specific RT-PCR. High expression of ER α, moderate to high expression of proliferating cell nuclear antigen (PCNA), moderate expression of vimentin and Cytokeratin 19 (K19) and low expression of p53 were observed in tumor sections, when compared with that of the normal mammary gland.</p> <p>Conclusion</p> <p>Since 75% of human breast cancer were classified ER-positive and as our model mimics (in most of the characteristics, such as histopathology, metastasis, high estrogen levels) the ER-positive luminal epithelial-like human breast cancer, this model will be an attractive tool to understand the biology of estrogen-dependant breast cancer in women. To our knowledge, this is the first report of a spontaneous mammary model displaying regional lymph node involvement with both hematogenous and lymphatic spread to liver, lung, heart, spleen and lymph nodes.</p

Induction of Interferon-Stimulated Genes by Chlamydia pneumoniae in Fibroblasts Is Mediated by Intracellular Nucleotide-Sensing Receptors

BACKGROUND: Recognition of microorganisms by the innate immune system is mediated by pattern recognition receptors, including Toll-like receptors and cytoplasmic RIG-I-like receptors. Chlamydia, which include several human pathogenic species, are obligate intracellular gram-negative bacteria that replicate in cytoplasmic vacuoles. The infection triggers a host response contributing to both bacterial clearance and tissue damage. For instance, type I interferons (IFN)s have been demonstrated to exacerbate the course of Chlamydial lung infections in mice. METHODS/PRINCIPAL FINDINGS: Here we show that Chlamydia pneumoniae induces expression of IFN-stimulated genes (ISG)s dependent on recognition by nucleotide-sensing Toll-like receptors and RIG-I-like receptors, localized in endosomes and the cytoplasm, respectively. The ISG response was induced with a delayed kinetics, compared to virus infections, and was dependent on bacterial replication and the bacterial type III secretion system (T3SS). CONCLUSIONS/SIGNIFICANCE: Activation of the IFN response during C. pneumoniae infection is mediated by intracellular nucleotide-sensing PRRs, which operate through a mechanism dependent on the bacterial T3SS. Strategies to inhibit the chlamydial T3SS may be used to limit the detrimental effects of the type I IFN system in the host response to Chlamydia infection

Improved general regression network for protein domain boundary prediction

Background: Protein domains present some of the most useful information that can be used to understand protein structure and functions. Recent research on protein domain boundary prediction has been mainly based on widely known machine learning techniques, such as Artificial Neural Networks and Support Vector Machines. In this study, we propose a new machine learning model (IGRN) that can achieve accurate and reliable classification, with significantly reduced computations. The IGRN was trained using a PSSM (Position Specific Scoring Matrix), secondary structure, solvent accessibility information and inter-domain linker index to detect possible domain boundaries for a target sequence. Results: The proposed model achieved average prediction accuracy of 67% on the Benchmark_2 dataset for domain boundary identification in multi-domains proteins and showed superior predictive performance and generalisation ability among the most widely used neural network models. With the CASP7 benchmark dataset, it also demonstrated comparable performance to existing domain boundary predictors such as DOMpro, DomPred, DomSSEA, DomCut and DomainDiscovery with 70.10% prediction accuracy. Conclusion: The performance of proposed model has been compared favourably to the performance of other existing machine learning based methods as well as widely known domain boundary predictors on two benchmark datasets and excels in the identification of domain boundaries in terms of model bias, generalisation and computational requirements. © 2008 Yoo et al; licensee BioMed Central Ltd

Influence of sense of coherence on adolescents' self-perceived dental aesthetics:a cross-sectional study

Background Sense of coherence (SOC) is a psychosocial factor capable of influencing perception of health, improving one’s ability to manage life. It is the central construct of salutogenesis. SOC allows for identification and mobilization of resources to effectively manage or solve problems, promoting health and quality of life. Using Wilson-Cleary’s conceptual model we hypothesized that SOC might contribute to self-perception of dental aesthetics. The aim of this study was to investigate whether SOC levels were related to self-perception of dental aesthetics against assessed normative orthodontic treatment need among adolescents. Methods A cross-sectional study was conducted with 615 male and female adolescents aged 12 to 15 years. Data collection comprised socio-demographic and socio-economic characteristics, SOC (SOC 13), self-perceived dental aesthetics (Oral Aesthetic Subjective Impact Scale), and assessment of orthodontic treatment need (Dental Aesthetic Index). Statistical analysis involved Pearson’s chi-square test, Kruskal-Wallis test, Mann-Whitney test and multiple linear regression. Spearman’s correlation coefficient was calculated for the determination of the strength of correlations among the numerical variables. The level of significance was set at 5% (p < 0.05). Results 50.1% of the participants were classified as having a high SOC (≥ median). Overall, SOC was associated with self-perceived dental aesthetics (p = 0.048). In the adolescents with no orthodontic treatment need, those with a low SOC perceived their dental aesthetics more negatively than those with high levels of SOC. The multiple regression analysis demonstrated an inverse relationship between SOC and: 1) age (p = 0.007), SOC being higher in the younger age group; 2) self-perceived dental aesthetics (p = 0.001), a higher SOC being associated with those who had a positive dental self-perception. Conclusions SOC was associated with self-perceived dental aesthetics and adolescents with a high SOC were more likely to perceive their dental aesthetics more positively. SOC did not seem to influence self-perception of dental aesthetics in adolescents who were clinically assessed as having an orthodontic treatment need, however, in those where there was no orthodontic treatment need, a low SOC was associated with a negative self-perception of dental appearance

Efect of maleated anhydride on mechanical properties of rice husk filler reinforced PLA Matrix Polymer Composite

Polylactic acid (PLA) formulated from corn starch has a bright potential to replace the non-renewable petroleum-based plastics. The combination of PLA and natural fbre has gained interest due to its unique performance, as reported in many researches and industries. Meanwhile, rice husk produced as the by-product of rice milling can be utilised, unless it is turned completely into waste. Therefore, in the present study, the rice husk powder (RHP) was used as a fller in the PLA, so to determine the infuence of the fller loading on the mechanical properties of the PLA composite. A coupling agent was selected for treatment from two options, i.e., maleic anhydride polypropylene (MAPP) and maleic anhydride polyethylene (MAPE), by applying the agents with various loading contents, such as 2, 4 and 6 wt%. The composite was fabricated by using the hot compression machine. Both the treated and untreated RHP–PLA composites were characterised via the tensile, fexural and impact strength tests. The increase in the RHP loading content led to the decrease in the tensile and fexural strengths. The applications of the coupling agents (MAPE and MAPP) did not improve the tensile and impact strengths, but the fexural strength was enhanced

Multisensory Perceptual Learning of Temporal Order: Audiovisual Learning Transfers to Vision but Not Audition

Background: An outstanding question in sensory neuroscience is whether the perceived timing of events is mediated by a central supra-modal timing mechanism, or multiple modality-specific systems. We use a perceptual learning paradigm to address this question. Methodology/Principal Findings: Three groups were trained daily for 10 sessions on an auditory, a visual or a combined audiovisual temporal order judgment (TOJ). Groups were pre-tested on a range TOJ tasks within and between their group modality prior to learning so that transfer of any learning from the trained task could be measured by post-testing other tasks. Robust TOJ learning (reduced temporal order discrimination thresholds) occurred for all groups, although auditory learning (dichotic 500/2000 Hz tones) was slightly weaker than visual learning (lateralised grating patches). Crossmodal TOJs also displayed robust learning. Post-testing revealed that improvements in temporal resolution acquired during visual learning transferred within modality to other retinotopic locations and orientations, but not to auditory or crossmodal tasks. Auditory learning did not transfer to visual or crossmodal tasks, and neither did it transfer within audition to another frequency pair. In an interesting asymmetry, crossmodal learning transferred to all visual tasks but not to auditory tasks. Finally, in all conditions, learning to make TOJs for stimulus onsets did not transfer at all to discriminating temporal offsets. These data present a complex picture of timing processes

Natural Killer T Cells Activated by a Lipopeptidophosphoglycan from Entamoeba histolytica Are Critically Important To Control Amebic Liver Abscess

The innate immune response is supposed to play an essential role in the control of amebic liver abscess (ALA), a severe form of invasive amoebiasis due to infection with the protozoan parasite Entamoeba histolytica. In a mouse model for the disease, we previously demonstrated that Jα18-/- mice, lacking invariant natural killer T (iNKT) cells, suffer from more severe abscess development. Here we show that the specific activation of iNKT cells using α-galactosylceramide (α-GalCer) induces a significant reduction in the sizes of ALA lesions, whereas CD1d−/− mice develop more severe abscesses. We identified a lipopeptidophosphoglycan from E. histolytica membranes (EhLPPG) as a possible natural NKT cell ligand and show that the purified phosphoinositol (PI) moiety of this molecule induces protective IFN-γ but not IL-4 production in NKT cells. The main component of EhLPPG responsible for NKT cell activation is a diacylated PI, (1-O-[(28∶0)-lyso-glycero-3-phosphatidyl-]2-O-(C16:0)-Ins). IFN-γ production by NKT cells requires the presence of CD1d and simultaneously TLR receptor signalling through MyD88 and secretion of IL-12. Similar to α-GalCer application, EhLPPG treatment significantly reduces the severity of ALA in ameba-infected mice. Our results suggest that EhLPPG is an amebic molecule that is important for the limitation of ALA development and may explain why the majority of E. histolytica-infected individuals do not develop amebic liver abscess