Telocytes in pleura: two- and three-dimensional imaging by transmission electron microscopy

Information about the ultrastructure of connective (interstitial) cells supporting the pleural mesothelium is scarce. Our aim has been to examine whether telocytes (TCs) are present in pleura, as in epicardium and mesentery. TCs are a distinct type of cell, characterized by specific prolongations named telopodes (Tp). We have used transmission electron microscopy (TEM) and electron tomography (ET) to determine whether ultrastructural diagnostic criteria accepted for TCs are fulfilled by any of the cell subpopulations existing in the sub-mesothelial layer in mouse and human pleura. TCs have been identified with TEM by their characteristic prolongations. Tp appear long and moniliform, because of the alternation of podomeres (thin segments of less than 0.2 μm) and podoms (small dilations accommodating caveolae, mitochondria, and endoplasmic reticulum). Tp ramifications follow a dichotomic pattern and establish specialized cell-to-cell junctional complexes. TCs, via their Tp, seem to form an interstitial network beneath the mesothelium, covering about two-thirds of the abluminal mesothelial layer. ET has revealed complex junctional structures and tight junctions connecting pleural TCs, and small vesicles at this level in Tp. Thus, pleural TCs share significant similarities with TCs described in other serosae. Whether TCs are a (major) player in mesothelial-cell-induced tissue repair remains to be established. Nevertheless, the extremely long thin Tp and complex junctional structures that they form and the release of vesicles (or exosomes) indicate the participation of TCs in long-distance homo- or heterocellular communication

Telocytes and putative stem cells in the lungs: electron microscopy, electron tomography and laser scanning microscopy

This study describes a novel type of interstitial (stromal) cell — telocytes (TCs) — in the human and mouse respiratory tree (terminal and respiratory bronchioles, as well as alveolar ducts). TCs have recently been described in pleura, epicardium, myocardium, endocardium, intestine, uterus, pancreas, mammary gland, etc. (see www.telocytes.com). TCs are cells with specific prolongations called telopodes (Tp), frequently two to three per cell. Tp are very long prolongations (tens up to hundreds of μm) built of alternating thin segments known as podomers (≤ 200 nm, below the resolving power of light microscope) and dilated segments called podoms, which accommodate mitochondria, rough endoplasmic reticulum and caveolae. Tp ramify dichotomously, making a 3-dimensional network with complex homo- and heterocellular junctions. Confocal microscopy reveals that TCs are c-kit- and CD34-positive. Tp release shed vesicles or exosomes, sending macromolecular signals to neighboring cells and eventually modifying their transcriptional activity. At bronchoalveolar junctions, TCs have been observed in close association with putative stem cells (SCs) in the subepithelial stroma. SCs are recognized by their ultrastructure and Sca-1 positivity. Tp surround SCs, forming complex TC-SC niches (TC-SCNs). Electron tomography allows the identification of bridging nanostructures, which connect Tp with SCs. In conclusion, this study shows the presence of TCs in lungs and identifies a TC-SC tandem in subepithelial niches of the bronchiolar tree. In TC-SCNs, the synergy of TCs and SCs may be based on nanocontacts and shed vesicles

Cardiac telocytes — their junctions and functional implications

Telocytes (TCs) form a cardiac network of interstitial cells. Our previous studies have shown that TCs are involved in heterocellular contacts with cardiomyocytes and cardiac stem/progenitor cells. In addition, TCs frequently establish ‘stromal synapses’ with several types of immunoreactive cells in various organs (www.telocytes.com). Using electron microscopy (EM) and electron microscope tomography (ET), we further investigated the interstitial cell network of TCs and found that TCs form ‘atypical’ junctions with virtually all types of cells in the human heart. EM and ET showed different junction types connecting TCs in a network (puncta adhaerentia minima, processus adhaerentes and manubria adhaerentia). The connections between TCs and cardiomyocytes are ‘dot’ junctions with nanocontacts or asymmetric junctions. Junctions between stem cells and TCs are either ‘stromal synapses’ or adhaerens junctions. An unexpected finding was that TCs have direct cell–cell (nano)contacts with Schwann cells, endothelial cells and pericytes. Therefore, ultrastructural analysis proved that the cardiac TC network could integrate the overall ‘information’ from vascular system (endothelial cells and pericytes), nervous system (Schwann cells), immune system (macrophages, mast cells), interstitium (fibroblasts, extracellular matrix), stem cells/progenitors and working cardiomyocytes. Generally, heterocellular contacts occur by means of minute junctions (point contacts, nanocontacts and planar contacts) and the mean intermembrane distance is within the macromolecular interaction range (10–30 nm). In conclusion, TCs make a network in the myocardial interstitium, which is involved in the long-distance intercellular signaling coordination. This integrated interstitial system appears to be composed of large homotropic zones (TC–TC junctions) and limited (distinct) heterotropic zones (heterocellular junctions of TCs)

Quantum Communication

Quantum communication, and indeed quantum information in general, has changed the way we think about quantum physics. In 1984 and 1991, the first protocol for quantum cryptography and the first application of quantum non-locality, respectively, attracted a diverse field of researchers in theoretical and experimental physics, mathematics and computer science. Since then we have seen a fundamental shift in how we understand information when it is encoded in quantum systems. We review the current state of research and future directions in this new field of science with special emphasis on quantum key distribution and quantum networks.Comment: Submitted version, 8 pg (2 cols) 5 fig

Modeling of single mode optical fiber having a complicated refractive index profile by using modified scalar finite element method

A numerical method based on modified scalar finite element method (SC-FEM) is presented and programmed on MATLAB platform for optical fiber modeling purpose. We have estimated the dispersion graph, mode cut off condition, and group delay and waveguide dispersion for highly complicated chirped type refractive index profile fiber. The convergence study of our FEM formulation is carried out with respect to the number of division in core. It has been found that the numerical error becomes less than 2 % when the number of divisions in the core is more then 30. To predict the accurate waveguide dispersion characteristics, we need to compute expression (d^2 (Vb))/(dV^2 ) numerically by the FEM method. For that the normalized propagation constant b (in terms of β) should be an accurate enough up to around 6 decimal points. To achieve this target, we have used 1 million sampling points in our FEM simulations. Further to validate our results we have derived the higher order polynomial expression for each case. Comparison with other methods in calculation of normalized propagation constant is found to be satisfactory. In traditional FEM analysis a spurious solution is generated because the functional does not satisfy the boundary conditions in the original waveguide problem, However in our analysis a new term that compensate the missing boundary condition has been added in the functional to eliminate the spurious solutions. Our study will be useful for the analysis of optical fiber having varying refractive index profile

A combination of gemcitabine and 5-fluorouracil in advanced pancreatic cancer, a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD)

In a randomized clinical trial, gemcitabine (GEM) was more effective than 5-fluorouracil (5-FU) in advanced pancreatic cancer patients. GEM and 5-FU have different mechanisms of action and their combination, from a theoretical point of view, could result in a higher activity. To test activity and feasibility of such a combination, a multi-institutional phase II study was initiated in November 1996 by the Italian Group for the study of Digestive Tract Cancer (GISCAD). Primary objectives of this study were to determine the activity in terms of response rate and clinical benefit, while the secondary objective was toxicity. According to the optimal two-stage phase II design, 54 patients were enrolled. Schedule was: GEM 1000 mg m(-2) intravenous (i.v.), and 5-FU 600 mg m(-2) bolus i.v. weekly for 3 weeks out of every 4. All the 54 patients were symptomatic (pain, weight loss, dyspepsia). A clinical benefit was obtained in 28 patients (51\%) (95\% confidence interval (CI) 38-64\%). Two patients achieved a partial response and 34 a stable disease. Median survival for all the patients was 7 months. Side-effects were mild: no gastrointestinal or haematological grade 3-4 toxicity (WHO) were recorded. We observed only six episodes of grade 2 (WHO) leukopenia and seven episodes of thrombocytopenia. Although the non-randomized design of this study suggests caution in the interpretation of these data, in consideration of the low incidence of toxicity and the favourable results obtained in terms of clinical benefit, it may be worthwhile to test more active schedules of 5-FU (continuous infusion) in combination with gemcitabine

A novel small molecule target in human airway smooth muscle for potential treatment of obstructive lung diseases: a staged high-throughput biophysical screening

<p>Abstract</p> <p>Background</p> <p>A newly identified mechanism of smooth muscle relaxation is the interaction between the small heat shock protein 20 (HSP20) and 14-3-3 proteins. Focusing upon this class of interactions, we describe here a novel drug target screening approach for treating airflow obstruction in asthma.</p> <p>Methods</p> <p>Using a high-throughput fluorescence polarization (FP) assay, we screened a library of compounds that could act as small molecule modulators of HSP20 signals. We then applied two quantitative, cell-based biophysical methods to assess the functional efficacy of these molecules and rank-ordered their abilities to relax isolated human airway smooth muscle (ASM). Scaling up to the level of an intact tissue, we confirmed in a concentration-responsive manner the potency of the cell-based hit compounds.</p> <p>Results</p> <p>Among 58,019 compound tested, 268 compounds caused 20% or more reduction of the polarized emission in the FP assay. A small subset of these primary screen hits, belonging to two scaffolds, caused relaxation of isolated ASM cell <it>in vitro </it>and attenuated active force development of intact tissue <it>ex vivo</it>.</p> <p>Conclusions</p> <p>This staged biophysical screening paradigm provides proof-of-principle for high-throughput and cost-effective discovery of new small molecule therapeutic agents for obstructive lung diseases.</p

Measurement of the Forward-Backward Asymmetry in the B -> K(*) mu+ mu- Decay and First Observation of the Bs -> phi mu+ mu- Decay

We reconstruct the rare decays $B^+ \to K^+\mu^+\mu^-$, $B^0 \to K^{*}(892)^0\mu^+\mu^-$, and $B^0_s \to \phi(1020)\mu^+\mu^-$ in a data sample corresponding to $4.4 {\rm fb^{-1}}$ collected in $p\bar{p}$ collisions at $\sqrt{s}=1.96 {\rm TeV}$ by the CDF II detector at the Fermilab Tevatron Collider. Using $121 \pm 16$ $B^+ \to K^+\mu^+\mu^-$ and $101 \pm 12$ $B^0 \to K^{*0}\mu^+\mu^-$ decays we report the branching ratios. In addition, we report the measurement of the differential branching ratio and the muon forward-backward asymmetry in the $B^+$ and $B^0$ decay modes, and the $K^{*0}$ longitudinal polarization in the $B^0$ decay mode with respect to the squared dimuon mass. These are consistent with the theoretical prediction from the standard model, and most recent determinations from other experiments and of comparable accuracy. We also report the first observation of the $B^0_s \to \phi\mu^+\mu^- decay and measure its branching ratio${\mathcal{B}}(B^0_s \to \phi\mu^+\mu^-) = [1.44 \pm 0.33 \pm 0.46] \times 10^{-6}$using$27 \pm 6$signal events. This is currently the most rare$B^0_s$ decay observed.Comment: 7 pages, 2 figures, 3 tables. Submitted to Phys. Rev. Let

Respiratory maneuvers in echocardiography: a review of clinical applications

During echocardiographic examination, respiration induces cyclic physiological changes of intracardiac haemodynamics, causing normal variations of the right and left ventricle Doppler inflows and outflows and physiological variation of extracardiac flows. The respiration related hemodynamic variation in intra and extracardiac flows may be utilized in the echocardiography laboratory to aid diagnosis in different pathological states. Nevertheless, physiologic respiratory phases can cause excessive translational motion of cardiac structures, lowering 2D image quality and interfering with optimal Doppler interrogation of flows or tissue motion

Synchrotron Radiation X-Ray Microfluorescence Reveals Polarized Distribution of Atomic Elements during Differentiation of Pluripotent Stem Cells

The mechanisms underlying pluripotency and differentiation in embryonic and reprogrammed stem cells are unclear. In this work, we characterized the pluripotent state towards neural differentiated state through analysis of trace elements distribution using the Synchrotron Radiation X-ray Fluorescence Spectroscopy. Naive and neural-stimulated embryoid bodies (EB) derived from embryonic and induced pluripotent stem (ES and iPS) cells were irradiated with a spatial resolution of 20 µm to make elemental maps and qualitative chemical analyses. Results show that these embryo-like aggregates exhibit self-organization at the atomic level. Metallic elements content rises and consistent elemental polarization pattern of P and S in both mouse and human pluripotent stem cells were observed, indicating that neural differentiation and elemental polarization are strongly correlated