Biophotonic Tools in Cell and Tissue Diagnostics.

In order to maintain the rapid advance of biophotonics in the U.S. and enhance our competitiveness worldwide, key measurement tools must be in place. As part of a wide-reaching effort to improve the U.S. technology base, the National Institute of Standards and Technology sponsored a workshop titled "Biophotonic tools for cell and tissue diagnostics." The workshop focused on diagnostic techniques involving the interaction between biological systems and photons. Through invited presentations by industry representatives and panel discussion, near- and far-term measurement needs were evaluated. As a result of this workshop, this document has been prepared on the measurement tools needed for biophotonic cell and tissue diagnostics. This will become a part of the larger measurement road-mapping effort to be presented to the Nation as an assessment of the U.S. Measurement System. The information will be used to highlight measurement needs to the community and to facilitate solutions

High-transition-temperature superconductivity in the absence of the magnetic-resonance mode

The fundamental mechanism that gives rise to high-transition-temperature (high-Tc) superconductivity in the copper oxide materials has been debated since the discovery of the phenomenon. Recent work has focussed on a sharp 'kink' in the kinetic energy spectra of the electrons as a possible signature of the force that creates the superconducting state. The kink has been related to a magnetic resonance and also to phonons. Here we report that infrared spectra of Bi2Sr2CaCu2O(8+d), (Bi-2212) show that this sharp feature can be separated from a broad background and, interestingly, weakens with doping before disappearing completely at a critical doping level of 0.23 holes per copper atom. Superconductivity is still strong in terms of the transition temperature (Tc approx 55 K), so our results rule out both the magnetic resonance peak and phonons as the principal cause of high-Tc superconductivity. The broad background, on the other hand, is a universal property of the copper oxygen plane and a good candidate for the 'glue' that binds the electrons.Comment: 4 pages, 3 figure

Quadricuspid aortic valve not discovered by transthoracic echocardiography

BACKGROUND: Quadricuspid aortic valve is a rare congenital heart defect. Several different anatomical variations of a quadricuspid aortic valve has been described and aortic regurgitation is the predominant valvular dysfunction associated with quadricuspid aortic valve. CASE PRESENTATION: A 68-year-old woman presented with almost a years history of increasing dyspnoea on exertion. The patient have had two previous transthoracic echocardiographic exams in the last six years and they had only documented moderate aortic regurgitation. Transoesophageal echocardiography displayed a rare case of quadricuspid aortic valve with three cusps of equal size and one larger cusp. The malformation was associated with severe aortic regurgitation. CONCLUSION: Liberal use of transoesophageal echocardiography is often warranted if optimal display of valvular morphology is desired

Photoreduction of Shewanella oneidensis Extracellular Cytochromes by Organic Chromophores and Dye-Sensitized TiO2.

The transfer of photoenergized electrons from extracellular photosensitizers across a bacterial cell envelope to drive intracellular chemical transformations represents an attractive way to harness nature's catalytic machinery for solar-assisted chemical synthesis. In $\textit{Shewanella oneidensis}$ MR-1 (MR-1), trans-outer-membrane electron transfer is performed by the extracellular cytochromes MtrC and OmcA acting together with the outer-membrane-spanning porin$\cdot$cytochrome complex (MtrAB). Here we demonstrate photoreduction of solutions of MtrC, OmcA, and the MtrCAB complex by soluble photosensitizers: namely, eosin Y, fluorescein, proflavine, flavin, and adenine dinucleotide, as well as by riboflavin and flavin mononucleotide, two compounds secreted by MR-1. We show photoreduction of MtrC and OmcA adsorbed on Ru$^{\text{II}}$-dye-sensitized TiO$_2$ nanoparticles and that these protein-coated particles perform photocatalytic reduction of solutions of MtrC, OmcA, and MtrCAB. These findings provide a framework for informed development of strategies for using the outer-membrane-associated cytochromes of MR-1 for solar-driven microbial synthesis in natural and engineered bacteria.This work was supported by the UK Biotechnology and Biological Sciences Research Council (grants BB/K009753/1, BB/K010220/1, BB/K009885/1, and BB/K00929X/1), the Engineering and Physical Sciences Research Council (EP/M001989/1, PhD studentship 1307196 to E.V.A.), a Royal Society Leverhulme Trust Senior Research Fellowship to J.N.B., the Christian Doppler Research Association, and OMV group

Drug problems among homeless individuals in Toronto, Canada: prevalence, drugs of choice, and relation to health status

<p>Abstract</p> <p>Background</p> <p>Drug use is believed to be an important factor contributing to the poor health and increased mortality risk that has been widely observed among homeless individuals. The objective of this study was to determine the prevalence and characteristics of drug use among a representative sample of homeless individuals and to examine the association between drug problems and physical and mental health status.</p> <p>Methods</p> <p>Recruitment of 603 single men, 304 single women, and 284 adults with dependent children occurred at homeless shelters and meal programs in Toronto, Canada. Information was collected on demographic characteristics and patterns of drug use. The Addiction Severity Index was used to assess whether participants suffered from drug problems. Associations of drug problems with physical and mental health status (measured by the SF-12 scale) were examined using regression analyses.</p> <p>Results</p> <p>Forty percent of the study sample had drug problems in the last 30 days. These individuals were more likely to be single men and less educated than those without drug problems. They were also more likely to have become homeless at a younger age (mean 24.8 vs. 30.9 years) and for a longer duration (mean 4.8 vs. 2.9 years). Marijuana and cocaine were the most frequently used drugs in the past two years (40% and 27%, respectively). Drug problems within the last 30 days were associated with significantly poorer mental health status (-4.9 points, 95% CI -6.5 to -3.2) but not with poorer physical health status (-0.03 points, 95% CI -1.3 to 1.3)).</p> <p>Conclusions</p> <p>Drug use is common among homeless individuals in Toronto. Current drug problems are associated with poorer mental health status but not with poorer physical health status.</p

A Decaheme Cytochrome as a Molecular Electron Conduit in Dye-Sensitized Photoanodes.

In nature, charge recombination in light-harvesting reaction centers is minimized by efficient charge separation. Here, it is aimed to mimic this by coupling dye-sensitized TiO2 nanocrystals to a decaheme protein, MtrC from Shewanella oneidensis MR-1, where the 10 hemes of MtrC form a ≈7-nm-long molecular wire between the TiO2 and the underlying electrode. The system is assembled by forming a densely packed MtrC film on an ultra-flat gold electrode, followed by the adsorption of approximately 7 nm TiO2 nanocrystals that are modified with a phosphonated bipyridine Ru(II) dye (RuP). The step-by-step construction of the MtrC/TiO2 system is monitored with (photo)electrochemistry, quartz-crystal microbalance with dissipation (QCM-D), and atomic force microscopy (AFM). Photocurrents are dependent on the redox state of the MtrC, confirming that electrons are transferred from the TiO2 nanocrystals to the surface via the MtrC conduit. In other words, in these TiO2/MtrC hybrid photodiodes, MtrC traps the conduction-band electrons from TiO2 before transferring them to the electrode, creating a photobioelectrochemical system in which a redox protein is used to mimic the efficient charge separation found in biological photosystems.This work was supported by the BBSRC (grants BB/K009753/1, BB/K010220/1, and BB/K009885/1), the EPSRC (EP/H00338X/2; PhD studentship to Emma Ainsworth), the Christian Doppler Research Association and the OMV Group. The authors appreciate Dr. Liang Shi (PNNL) and Dr. Marcus Edwards (UEA) for providing the S. oneidensis strain and the protocol allowing for purification of MtrC.This is the final published version of the article. It was originally published in Advanced Functional Materials (Hwang ET, Sheikh K, Orchard KL, Hojo D, Radu V, Lee C-Y, Ainsworth E, Lockwood C, Gross MA, Adschiri T, Reisner E, Butt JN, Jeuken LJC, Advanced Functional Materials 2015, 25, 2308–2315, doi: 10.1002/adfm.201404541) http://dx.doi.org/10.1002/adfm.201404541

Quercetin prevents progression of disease in elastase/LPS-exposed mice by negatively regulating MMP expression

Abstract Background Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis, emphysema and irreversible airflow limitation. These changes are thought to be due to oxidative stress and an imbalance of proteases and antiproteases. Quercetin, a plant flavonoid, is a potent antioxidant and anti-inflammatory agent. We hypothesized that quercetin reduces lung inflammation and improves lung function in elastase/lipopolysaccharide (LPS)-exposed mice which show typical features of COPD, including airways inflammation, goblet cell metaplasia, and emphysema. Methods Mice treated with elastase and LPS once a week for 4 weeks were subsequently administered 0.5 mg of quercetin dihydrate or 50% propylene glycol (vehicle) by gavage for 10 days. Lungs were examined for elastance, oxidative stress, inflammation, and matrix metalloproteinase (MMP) activity. Effects of quercetin on MMP transcription and activity were examined in LPS-exposed murine macrophages. Results Quercetin-treated, elastase/LPS-exposed mice showed improved elastic recoil and decreased alveolar chord length compared to vehicle-treated controls. Quercetin-treated mice showed decreased levels of thiobarbituric acid reactive substances, a measure of lipid peroxidation caused by oxidative stress. Quercetin also reduced lung inflammation, goblet cell metaplasia, and mRNA expression of pro-inflammatory cytokines and muc5AC. Quercetin treatment decreased the expression and activity of MMP9 and MMP12 in vivo and in vitro, while increasing expression of the histone deacetylase Sirt-1 and suppressing MMP promoter H4 acetylation. Finally, co-treatment with the Sirt-1 inhibitor sirtinol blocked the effects of quercetin on the lung phenotype. Conclusions Quercetin prevents progression of emphysema in elastase/LPS-treated mice by reducing oxidative stress, lung inflammation and expression of MMP9 and MMP12.http://deepblue.lib.umich.edu/bitstream/2027.42/78260/1/1465-9921-11-131.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78260/2/1465-9921-11-131.pdfPeer Reviewe

RNA editing signature during myeloid leukemia cell differentiation

Adenosine deaminases acting on RNA (ADARs) are key proteins for hematopoietic stem cell self-renewal and for survival of differentiating progenitor cells. However, their specific role in myeloid cell maturation has been poorly investigated. Here we show that ADAR1 is present at basal level in the primary myeloid leukemia cells obtained from patients at diagnosis as well as in myeloid U-937 and THP1 cell lines and its expression correlates with the editing levels. Upon phorbol-myristate acetate or Vitamin D3/granulocyte macrophage colony-stimulating factor (GM-CSF)-driven differentiation, both ADAR1 and ADAR2 enzymes are upregulated, with a concomitant global increase of A-to-I RNA editing. ADAR1 silencing caused an editing decrease at specific ADAR1 target genes, without, however, interfering with cell differentiation or with ADAR2 activity. Remarkably, ADAR2 is absent in the undifferentiated cell stage, due to its elimination through the ubiquitin–proteasome pathway, being strongly upregulated at the end of the differentiation process. Of note, peripheral blood monocytes display editing events at the selected targets similar to those found in differentiated cell lines. Taken together, the data indicate that ADAR enzymes play important and distinct roles in myeloid cells

Lack of correlation of stem cell markers in breast cancer stem cells

BACKGROUND: Various markers are used to identify the unique sub-population of breast cancer cells with stem cell properties. Whether these markers are expressed in all breast cancers, identify the same population of cells, or equate to therapeutic response is controversial. METHODS: We investigated the expression of multiple cancer stem cell markers in human breast cancer samples and cell lines in vitro and in vivo, comparing across and within samples and relating expression with growth and therapeutic response to doxorubicin, docetaxol and radiotherapy. RESULTS: CD24, CD44, ALDH and SOX2 expression, the ability to form mammospheres and side-population cells are variably present in human cancers and cell lines. Each marker identifies a unique rather than common population of cancer cells. In vivo, cells expressing these markers are not specifically localized to the presumptive stem cell niche at the tumour/stroma interface. Repeated therapy does not consistently enrich cells expressing these markers, although ER-negative cells accumulate. CONCLUSIONS: Commonly employed methods identify different cancer cell sub-populations with no consistent therapeutic implications, rather than a single population of cells. The relationships of breast cancer stem cells to clinical parameters will require identification of specific markers or panels for the individual cancer