In-vivo optical detection of cancer using chlorin e6 – polyvinylpyrrolidone induced fluorescence imaging and spectroscopy

<p>Abstract</p> <p>Background</p> <p>Photosensitizer based fluorescence imaging and spectroscopy is fast becoming a promising approach for cancer detection. The purpose of this study was to examine the use of the photosensitizer chlorin e6 (Ce6) formulated in polyvinylpyrrolidone (PVP) as a potential exogenous fluorophore for fluorescence imaging and spectroscopic detection of human cancer tissue xenografted in preclinical models as well as in a patient.</p> <p>Methods</p> <p>Fluorescence imaging was performed on MGH human bladder tumor xenografted on both the chick chorioallantoic membrane (CAM) and the murine model using a fluorescence endoscopy imaging system. In addition, fiber optic based fluorescence spectroscopy was performed on tumors and various normal organs in the same mice to validate the macroscopic images. In one patient, fluorescence imaging was performed on angiosarcoma lesions and normal skin in conjunction with fluorescence spectroscopy to validate Ce6-PVP induced fluorescence visual assessment of the lesions.</p> <p>Results</p> <p>Margins of tumor xenografts in the CAM model were clearly outlined under fluorescence imaging. Ce6-PVP-induced fluorescence imaging yielded a specificity of 83% on the CAM model. In mice, fluorescence intensity of Ce6-PVP was higher in bladder tumor compared to adjacent muscle and normal bladder. Clinical results confirmed that fluorescence imaging clearly captured the fluorescence of Ce6-PVP in angiosarcoma lesions and good correlation was found between fluorescence imaging and spectral measurement in the patient.</p> <p>Conclusion</p> <p>Combination of Ce6-PVP induced fluorescence imaging and spectroscopy could allow for optical detection and discrimination between cancer and the surrounding normal tissues. Ce6-PVP seems to be a promising fluorophore for fluorescence diagnosis of cancer.</p

PDADMAC/Alginate-Coated Gold Nanorod For Eradication of Staphylococcus Aureus Biofilms

Malarmugila Manimaran,1,&ast; Yin Yin Teo,2 James Chen Yong Kah,3 Adilet Beishenaliev,1 Yean Leng Loke,2 Yiing Yee Foo,1 Shiow-Fern Ng,4 Chin Fei Chee,5 Sek Peng Chin,6 Farid Nazer Faruqu,1 Chia-Yu Chang,7 Misni Misran,2 Lip Yong Chung,6 Bey Fen Leo,8,&ast; Shih-Hwa Chiou,9,10 Chia-Ching Chang,7,11– 13 Sun Tee Tay,14 Lik Voon Kiew1,7 1Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia; 2Department of Chemistry, Faculty of Science, Universiti Malaya, Kuala Lumpur, Malaysia; 3Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, Singapore, Singapore; 4Centre for Drug Delivery Technology and Vaccine, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia; 5Nanotechnology Catalysis Research Centre, Universiti Malaya, Kuala Lumpur, Malaysia; 6Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universiti Malaya, Kuala Lumpur, Malaysia; 7Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, Republic of China; 8Department of Molecular Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia; 9Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China; 10Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan, Republic of China; 11Department of Electrophysics, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, Republic of China; 12Center for Intelligent Drug Systems and Smart Bio-devices, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, Republic of China; 13Institute of Physics, Academia Sinica, Nankang, Taipei, Taiwan, Republic of China; 14Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia&ast;These authors contributed equally to this workCorrespondence: Chia-Ching Chang; Lik Voon Kiew, Email [email protected]; [email protected]: Over 75% of clinical microbiological infections are caused by bacterial biofilms that grow on wounds or implantable medical devices. This work describes the development of a new poly(diallyldimethylammonium chloride) (PDADMAC)/alginate-coated gold nanorod (GNR/Alg/PDADMAC) that effectively disintegrates the biofilms of Staphylococcus aureus (S. aureus), a prominent pathogen responsible for hospital-acquired infections.Methods: GNR was synthesised via seed-mediated growth method, and the resulting nanoparticles were coated first with Alg and then PDADMAC. FTIR, zeta potential, transmission electron microscopy, and UV–Vis spectrophotometry analysis were performed to characterise the nanoparticles. The efficacy and speed of the non-coated GNR and GNR/Alg/PDADMAC in disintegrating S. aureus-preformed biofilms, as well as their in vitro biocompatibility (L929 murine fibroblast) were then studied.Results: The synthesised GNR/Alg/PDADMAC (mean length: 55.71 ± 1.15 nm, mean width: 23.70 ± 1.13 nm, aspect ratio: 2.35) was biocompatible and potent in eradicating preformed biofilms of methicillin-resistant (MRSA) and methicillin-susceptible S. aureus (MSSA) when compared to triclosan, an antiseptic used for disinfecting S. aureus colonisation on abiotic surfaces in the hospital. The minimum biofilm eradication concentrations of GNR/Alg/PDADMAC (MBEC50 for MRSA biofilm = 0.029 nM; MBEC50 for MSSA biofilm = 0.032 nM) were significantly lower than those of triclosan (MBEC50 for MRSA biofilm = 10,784 nM; MBEC50 for MRSA biofilm 5967 nM). Moreover, GNR/Alg/PDADMAC was effective in eradicating 50% of MRSA and MSSA biofilms within 17 min when used at a low concentration (0.15 nM), similar to triclosan at a much higher concentration (50 μM). Disintegration of MRSA and MSSA biofilms was confirmed by field emission scanning electron microscopy and confocal laser scanning microscopy.Conclusion: These findings support the potential application of GNR/Alg/PDADMAC as an alternative agent to conventional antiseptics and antibiotics for the eradication of medically important MRSA and MSSA biofilms.Keywords: biofilm, gold nanorod, S. aureus, PDADMAC, MRSA, MSS

Sleep Loss Produces False Memories

People sometimes claim with high confidence to remember events that in fact never happened, typically due to strong semantic associations with actually encoded events. Sleep is known to provide optimal neurobiological conditions for consolidation of memories for long-term storage, whereas sleep deprivation acutely impairs retrieval of stored memories. Here, focusing on the role of sleep-related memory processes, we tested whether false memories can be created (a) as enduring memory representations due to a consolidation-associated reorganization of new memory representations during post-learning sleep and/or (b) as an acute retrieval-related phenomenon induced by sleep deprivation at memory testing. According to the Deese, Roediger, McDermott (DRM) false memory paradigm, subjects learned lists of semantically associated words (e.g., “night”, “dark”, “coal”,…), lacking the strongest common associate or theme word (here: “black”). Subjects either slept or stayed awake immediately after learning, and they were either sleep deprived or not at recognition testing 9, 33, or 44 hours after learning. Sleep deprivation at retrieval, but not sleep following learning, critically enhanced false memories of theme words. This effect was abolished by caffeine administration prior to retrieval, indicating that adenosinergic mechanisms can contribute to the generation of false memories associated with sleep loss

An efficient algorithm for the stochastic simulation of the hybridization of DNA to microarrays

<p>Abstract</p> <p>Background</p> <p>Although oligonucleotide microarray technology is ubiquitous in genomic research, reproducibility and standardization of expression measurements still concern many researchers. Cross-hybridization between microarray probes and non-target ssDNA has been implicated as a primary factor in sensitivity and selectivity loss. Since hybridization is a chemical process, it may be modeled at a population-level using a combination of material balance equations and thermodynamics. However, the hybridization reaction network may be exceptionally large for commercial arrays, which often possess at least one reporter per transcript. Quantification of the kinetics and equilibrium of exceptionally large chemical systems of this type is numerically infeasible with customary approaches.</p> <p>Results</p> <p>In this paper, we present a robust and computationally efficient algorithm for the simulation of hybridization processes underlying microarray assays. Our method may be utilized to identify the extent to which nucleic acid targets (e.g. cDNA) will cross-hybridize with probes, and by extension, characterize probe robustnessusing the information specified by MAGE-TAB. Using this algorithm, we characterize cross-hybridization in a modified commercial microarray assay.</p> <p>Conclusions</p> <p>By integrating stochastic simulation with thermodynamic prediction tools for DNA hybridization, one may robustly and rapidly characterize of the selectivity of a proposed microarray design at the probe and "system" levels. Our code is available at <url>http://www.laurenzi.net</url>.</p

Circadian Preference Modulates the Neural Substrate of Conflict Processing across the Day

Human morning and evening chronotypes differ in their preferred timing for sleep and wakefulness, as well as in optimal daytime periods to cope with cognitive challenges. Recent evidence suggests that these preferences are not a simple by-product of socio-professional timing constraints, but can be driven by inter-individual differences in the expression of circadian and homeostatic sleep-wake promoting signals. Chronotypes thus constitute a unique tool to access the interplay between those processes under normally entrained day-night conditions, and to investigate how they impinge onto higher cognitive control processes. Using functional magnetic resonance imaging (fMRI), we assessed the influence of chronotype and time-of-day on conflict processing-related cerebral activity throughout a normal waking day. Sixteen morning and 15 evening types were recorded at two individually adapted time points (1.5 versus 10.5 hours spent awake) while performing the Stroop paradigm. Results show that interference-related hemodynamic responses are maintained or even increased in evening types from the subjective morning to the subjective evening in a set of brain areas playing a pivotal role in successful inhibitory functioning, whereas they decreased in morning types under the same conditions. Furthermore, during the evening hours, activity in a posterior hypothalamic region putatively involved in sleep-wake regulation correlated in a chronotype-specific manner with slow wave activity at the beginning of the night, an index of accumulated homeostatic sleep pressure. These results shed light into the cerebral mechanisms underlying inter-individual differences of higher-order cognitive state maintenance under normally entrained day-night conditions

The Chromatin Remodeling Factor SMARCB1 Forms a Complex with Human Cytomegalovirus Proteins UL114 and UL44

Background: Human cytomegalovirus (HCMV) uracil DNA glycosylase, UL114, is required for efficient viral DNA replication. Presumably, UL114 functions as a structural partner to other factors of the DNA-replication machinery and not as a DNA repair protein. UL114 binds UL44 (HCMV processivity factor) and UL54 (HCMV-DNA-polymerase). In the present study we have searched for cellular partners of UL114. Methodology/Principal Findings: In a yeast two-hybrid screen SMARCB1, a factor of the SWI/SNF chromatin remodeling complex, was found to be an interacting partner of UL114. This interaction was confirmed in vitro by coimmunoprecipitation and pull-down. Immunofluorescence microscopy revealed that SMARCB1 along with BRG-1, BAF170 and BAF155, which are the core SWI/SNF components required for efficient chromatin remodeling, were present in virus replication foci 24–48 hours post infection (hpi). Furthermore a direct interaction was also demonstrated for SMARCB1 and UL44. Conclusions/Significance: The core SWI/SNF factors required for efficient chromatin remodeling are present in the HCMV replication foci throughout infection. The proteins UL44 and UL114 interact with SMARCB1 and may participate in the recruitment of the SWI/SNF complex to the chromatinized virus DNA. Thus, the presence of the SWI/SNF chromatin remodeling complex in replication foci and its association with UL114 and with UL44 might imply its involvement i

Transcriptome characterization of the South African abalone Haliotis midae using sequencing-by-synthesis

<p>Abstract</p> <p>Background</p> <p>Worldwide, the genus <it>Haliotis </it>is represented by 56 extant species and several of these are commercially cultured. Among the six abalone species found in South Africa, <it>Haliotis midae </it>is the only aquacultured species. Despite its economic importance, genomic sequence resources for <it>H. midae</it>, and for abalone in general, are still scarce. Next generation sequencing technologies provide a fast and efficient tool to generate large sequence collections that can be used to characterize the transcriptome and identify expressed genes associated with economically important traits like growth and disease resistance.</p> <p>Results</p> <p>More than 25 million short reads generated by the Illumina Genome Analyzer were <it>de novo </it>assembled in 22,761 contigs with an average size of 260 bp. With a stringent <it>E</it>-value threshold of 10^-10, 3,841 contigs (16.8%) had a BLAST homologous match against the Genbank non-redundant (NR) protein database. Most of these sequences were annotated using the gene ontology (GO) and eukaryotic orthologous groups of proteins (KOG) databases and assigned to various functional categories. According to annotation results, many gene families involved in immune response were identified. Thousands of simple sequence repeats (SSR) and single nucleotide polymorphisms (SNP) were detected. Setting stringent parameters to ensure a high probability of amplification, 420 primer pairs in 181 contigs containing SSR loci were designed.</p> <p>Conclusion</p> <p>This data represents the most comprehensive genomic resource for the South African abalone <it>H. midae </it>to date. The amount of assembled sequences demonstrated the utility of the Illumina sequencing technology in the transcriptome characterization of a non-model species. It allowed the development of several markers and the identification of promising candidate genes for future studies on population and functional genomics in <it>H. midae </it>and in other abalone species.</p

Applications of microarray technology in breast cancer research

Microarrays provide a versatile platform for utilizing information from the Human Genome Project to benefit human health. This article reviews the ways in which microarray technology may be used in breast cancer research. Its diverse applications include monitoring chromosome gains and losses, tumour classification, drug discovery and development, DNA resequencing, mutation detection and investigating the mechanism of tumour development