A surface plasmon enhanced FLIM-FRET imaging approach based on Au nanoparticles

In this report we have demonstrated a fluorescence resonant energy transfer (FRET)-fluorescence lifetime imaging microscopy (FLIM) combined approach to study the intracellular pathway of gold nanoparticles. The detected energy transfer between gold nanorods (GNRs) and green fluorescence protein (GFP) labeled Hela cell earlyendosomes and the in-depth lifetime distribution analysis on the transfer process suggest an endocytotic uptake process of GNRs. Furthermore, the FRET-FLIM method profits from a surface plasmon enhanced energy transfer mechanism when taking into consideration of GNRs and two photon excitation, and is effective in biological imaging, sensing, and even in single molecular tracing in both in vivo and in vitro studies

Metalloporphyrin-incorporated diphosphine ligands for metal ion-binding

Poster: no. P48Diphosphine ligands have been widely used in organometallic chemistry and catalysis.1 By incorporation of functional units such as metallomacrocycles, the resulting functionalized diphosphines could exhibit unusual properties or binding behavior. In this study, we prepared several examples of ruthenium porphyrin phosphine complexes [RuII(Por)(dppm)2] (1; Por = TTP, 4-MeO-TPP, F20-TPP; dppm = bis(diphenylphosphino)methane) by a similar method to that previously reported for their congeners.2 Reaction of complexes 1 with a number of metal …published_or_final_versio

On Resource-bounded versions of the van Lambalgen theorem

The van Lambalgen theorem is a surprising result in algorithmic information theory concerning the symmetry of relative randomness. It establishes that for any pair of infinite sequences $A$ and $B$, $B$ is Martin-L\"of random and $A$ is Martin-L\"of random relative to $B$ if and only if the interleaved sequence $A \uplus B$ is Martin-L\"of random. This implies that $A$ is relative random to $B$ if and only if $B$ is random relative to $A$ \cite{vanLambalgen}, \cite{Nies09}, \cite{HirschfeldtBook}. This paper studies the validity of this phenomenon for different notions of time-bounded relative randomness. We prove the classical van Lambalgen theorem using martingales and Kolmogorov compressibility. We establish the failure of relative randomness in these settings, for both time-bounded martingales and time-bounded Kolmogorov complexity. We adapt our classical proofs when applicable to the time-bounded setting, and construct counterexamples when they fail. The mode of failure of the theorem may depend on the notion of time-bounded randomness

Elucidation of the RamA Regulon in Klebsiella pneumoniae Reveals a Role in LPS Regulation

Klebsiella pneumoniae is a significant human pathogen, in part due to high rates of multidrug resistance. RamA is an intrinsic regulator in K. pneumoniae established to be important for the bacterial response to antimicrobial challenge; however, little is known about its possible wider regulatory role in this organism during infection. In this work, we demonstrate that RamA is a global transcriptional regulator that significantly perturbs the transcriptional landscape of K. pneumoniae, resulting in altered microbe-drug or microbe-host response. This is largely due to the direct regulation of 68 genes associated with a myriad of cellular functions. Importantly, RamA directly binds and activates the lpxC, lpxL-2 and lpxO genes associated with lipid A biosynthesis, thus resulting in modifications within the lipid A moiety of the lipopolysaccharide. RamA-mediated alterations decrease susceptibility to colistin E, polymyxin B and human cationic antimicrobial peptide LL-37. Increased RamA levels reduce K. pneumoniae adhesion and uptake into macrophages, which is supported by in vivo infection studies, that demonstrate increased systemic dissemination of ramA overexpressing K. pneumoniae. These data establish that RamA-mediated regulation directly perturbs microbial surface properties, including lipid A biosynthesis, which facilitate evasion from the innate host response. This highlights RamA as a global regulator that confers pathoadaptive phenotypes with implications for our understanding of the pathogenesis of Enterobacter, Salmonella and Citrobacter spp. that express orthologous RamA proteins

Spinal disease in myeloma: cohort analysis at a specialist spinal surgery centre indicates benefit of early surgical augmentation or bracing

BACKGROUND: Multiple myeloma osteolytic disease affecting the spine results in vertebral compression fractures. These are painful, result in kyphosis, and impact respiratory function and quality of life. We explore the impact of time to presentation on the efficacy of spinal treatment modalities. METHODS: We retrospectively reviewed 183 patients with spinal myeloma presenting to our service over a 2 year period. RESULTS: Median time from multiple myeloma diagnosis to presentation at our centre was 195 days. Eighty-four patients (45.9 %) were treated with balloon kyphoplasty and the remainder with a thoracolumbar-sacral orthosis as per our published protocol. Patients presenting earlier than 195 days from diagnosis had significant improvements in patient reported outcome measures: EuroQol 5-Dimensions (p < 0.001), Oswestry Disability Index (p < 0.001), and Visual Analogue Pain Score (p < 0.001) at follow-up, regardless of treatment. Patients presenting after 195 days, however, only experienced benefit following balloon kyphoplasty, with no significant benefit from non-operative management. CONCLUSION: Vertebral augmentation and thoracolumbar bracing improve patient reported outcome scores in patients with spinal myeloma. However, delay in treatment negatively impacts clinical outcome, particularly if managed non-operatively. It is important to screen and treat patients with MM and back pain early to prevent deformity and improve quality of life

Temperature dependence of the electronic structure of the J(eff)=12 Mott insulator Sr2IrO4 studied by optical spectroscopy

We investigated the temperature-dependent evolution of the electronic structure of the J(eff)=1/2 Mott insulator Sr2IrO4 using optical spectroscopy. The optical conductivity spectra sigma(omega) of this compound has recently been found to exhibit two d-d transitions associated with the transition between the J(eff)=1/2 and J(eff)=3/2 bands due to the cooperation of the electron correlation and spin-orbit coupling. As the temperature increases, the two peaks show significant changes resulting in a decrease in the Mott gap. The experimental observations are compared with the results of first-principles calculation in consideration of increasing bandwidth. We discuss the effect of the temperature change in the electronic structure of Sr2IrO4 in terms of local lattice distortion, excitonic effect, electron-phonon coupling, and magnetic ordering.open69575

Cryotomography of budding influenza a virus reveals filaments with diverse morphologies that mostly do not bear a genome at their distal end

Influenza viruses exhibit striking variations in particle morphology between strains. Clinical isolates of influenza A virus have been shown to produce long filamentous particles while laboratory-adapted strains are predominantly spherical. However, the role of the filamentous phenotype in the influenza virus infectious cycle remains undetermined. We used cryo-electron tomography to conduct the first three-dimensional study of filamentous virus ultrastructure in particles budding from infected cells. Filaments were often longer than 10 microns and sometimes had bulbous heads at their leading ends, some of which contained tubules we attribute to M1 while none had recognisable ribonucleoprotein (RNP) and hence genome segments. Long filaments that did not have bulbs were infrequently seen to bear an ordered complement of RNPs at their distal ends. Imaging of purified virus also revealed diverse filament morphologies; short rods (bacilliform virions) and longer filaments. Bacilliform virions contained an ordered complement of RNPs while longer filamentous particles were narrower and mostly appeared to lack this feature, but often contained fibrillar material along their entire length. The important ultrastructural differences between these diverse classes of particles raise the possibility of distinct morphogenetic pathways and functions during the infectious process

Mitochondrial DNA Copy Number Is Associated with Breast Cancer Risk

Mitochondrial DNA (mtDNA) copy number in peripheral blood is associated with increased risk of several cancers. However, data from prospective studies on mtDNA copy number and breast cancer risk are lacking. We evaluated the association between mtDNA copy number in peripheral blood and breast cancer risk in a nested case-control study of 183 breast cancer cases with pre-diagnostic blood samples and 529 individually matched controls among participants of the Singapore Chinese Health Study. The mtDNA copy number was measured using real time PCR. Conditional logistic regression analyses showed that there was an overall positive association between mtDNA copy number and breast cancer risk (Ptrend = 0.01). The elevated risk for higher mtDNA copy numbers was primarily seen for women with <3 years between blood draw and cancer diagnosis; ORs (95% CIs) for 2nd, 3rd, 4th, and 5th quintile of mtDNA copy number were 1.52 (0.61, 3.82), 2.52 (1.03, 6.12), 3.12 (1.31, 7.43), and 3.06 (1.25, 7.47), respectively, compared with the 1st quintile (Ptrend = 0.004). There was no association between mtDNA copy number and breast cancer risk among women who donated a blood sample ≥3 years before breast cancer diagnosis (Ptrend = 0.41). This study supports a prospective association between increased mtDNA copy number and breast cancer risk that is dependent on the time interval between blood collection and breast cancer diagnosis. Future studies are warranted to confirm these findings and to elucidate the biological role of mtDNA copy number in breast cancer risk. © 2013 Thyagarajan et al

PI3K/mTORC2 regulates TGF-β/Activin signalling by modulating Smad2/3 activity via linker phosphorylation

Crosstalk between the phosphatidylinositol 3-kinase (PI3K) and the transforming growth factor-β signalling pathways play an important role in regulating many cellular functions. However, the molecular mechanisms underpinning this crosstalk remain unclear. Here, we report that PI3K signalling antagonizes the Activin-induced definitive endoderm (DE) differentiation of human embryonic stem cells by attenuating the duration of Smad2/3 activation via the mechanistic target of rapamycin complex 2 (mTORC2). Activation of mTORC2 regulates the phosphorylation of the Smad2/3-T220/T179 linker residue independent of Akt, CDK and Erk activity. This phosphorylation primes receptor-activated Smad2/3 for recruitment of the E3 ubiquitin ligase Nedd4L, which in turn leads to their degradation. Inhibition of PI3K/mTORC2 reduces this phosphorylation and increases the duration of Smad2/3 activity, promoting a more robust mesendoderm and endoderm differentiation. These findings present a new and direct crosstalk mechanism between these two pathways in which mTORC2 functions as a novel and critical mediator