Production study of Fr, Ra and Ac radioactive ion beams at ISOLDE, CERN.

The presented paper discusses the production of radioactive ion beams of francium, radium, and actinium from thick uranium carbide (UC x ) targets at ISOLDE, CERN. This study focuses on the release curves and extractable yields of francium, radium and actinium isotopes. The ion source temperature was varied in order to study the relative contributions of surface and laser ionization to the production of the actinium ion beams. The experimental results are presented in the form of release parameters. Representative extractable yields per µ C are presented for 222 - 231 Ac, several Ra and Fr isotopes in the mass ranges 214 ≤ A ≤ 233 and 205 ≤ A ≤ 231 respectively. The release efficiency for several isotopes of each of the studied elements was calculated by comparing their yields to the estimated in-target production rates modeled by CERN-FLUKA. The maximal extraction efficiency of actinium was calculated to be 2.1(6)% for a combination of surface ionization using a Ta ion source and resonant laser ionization using the two-step 438.58 nm, and 424.69 nm scheme.

EFFECTS OF OMEGA-3 FATTY ACIDS ASSOCIATED WITH ANTIOXIDANT VITAMINS IN OVERWEIGHT AND OBESE CHILDREN.

Introduction: Antioxidants and unsaturated fatty acids have protective effects in obesity. Aim: We investigated the benefits of Omega-3 fatty acids associated with antioxidant vitamins in obese children. Magnesemia and calcemia were observed in relation with other metabolic parameters, before and after the treatment. Materials and methods: 60 obese children were compared with 35 normal weight children. Each obese child received daily, one pill, containing: 130mg docosahexaenoic acid, 25mg of eicosapentaenoic acid, vitamin A 200µg, vitamin D 1,25µg, vitamin E 2,5mg and vitamin C 30mg for three months. All the participants were instructed not to change their lifestyle. Results: The serum values for these minerals and for 25(OH) vitamin D were lower in obese children. The obese children had insulin resistance (HOMA-IR) and an imbalance of serum adipocytokines. In obese children, the body mass index was negatively correlated with calcemia (r=-0.34) and serum 25(OH) vitamin D (r=-0.33). The HOMA-IR was negatively correlated with magnesemia (r=-0.34) and serum adiponectin (r=-0.29). The treatment improved the mineral serum level, the insulin sensitivity and the adipocytokines levels. Conclusion: In obese children, the intake of Omega-3 fatty acids associated with antioxidant vitamins, for three months improved calcemia and magnesemia and increased insulin sensitivity.

Nonquenched Isoscalar Spin-M1 Excitations in sd-Shell Nuclei.

Differential cross sections of isoscalar and isovector spin-M1 (0(+)→1(+)) transitions are measured using high-energy-resolution proton inelastic scattering at E(p)=295 MeV on (24)Mg, (28)Si, (32)S, and (36)Ar at 0°-14°. The squared spin-M1 nuclear transition matrix elements are deduced from the measured differential cross sections by applying empirically determined unit cross sections based on the assumption of isospin symmetry. The ratios of the squared nuclear matrix elements accumulated up to E(x)=16 MeV compared to a shell-model prediction are 1.01(9) for isoscalar and 0.61(6) for isovector spin-M1 transitions, respectively. Thus, no quenching is observed for isoscalar spin-M1 transitions, while the matrix elements for isovector spin-M1 transitions are quenched by an amount comparable with the analogous Gamow-Teller transitions on those target nuclei.

Dynamics of telopodes (telocyte prolongations) in cell culture depends on extracellular matrix protein.

Telocytes (TC) are cells with telopodes (Tp), very long prolongations (up to 100 µm) with an uneven caliber ( www.telocytes.com ). Factors determining the dynamics of cellular prolongations are still unknown, although previous studies showed telopode motility in TC cultures. We comparatively investigated, by time-lapse videomicroscopy, the dynamics of Tp of mouse heart TC seeded on collagen, fibronectin, and laminin. Under our experimental conditions, TC and fibroblasts (cell line L929) behaved differently in terms of adherence, spreading, and prolongation extension. Fibroblasts showed lower spreading on the matrix proteins used. The time needed for spreading was 2-4 h for TC, versus 8-10 h for fibroblasts. The values for final cell surface area after spreading were between 200 and 400 µm(2) for fibroblasts and 800-2,000 µm(2) for TC. TC showed a more than three times higher ability to spread on the tested matrix proteins. An extremely low capacity to extend prolongations with lengths shorter than cell bodies was noted for fibroblasts, while TC extended prolongations longer than the cell body length, with a moniliform appearance. The stronger adherence and spreading were noted for TC seeded on fibronectin, while the lowest were on laminin. Collagen determined an intermediate adherence and spreading for TC, but the highest dynamics in Tp extensions. In conclusion, TC behave differently than fibroblasts in terms of adherence, spreading, and cell prolongation extension when seeded on various matrix proteins in cell culture.

Human cardiac telocytes: 3D imaging by FIB-SEM tomography.

Telocyte (TC) is a newly identified type of cell in the cardiac interstitium (www.telocytes.com). TCs are described by classical transmission electron microscopy as cells with very thin and long telopodes (Tps; cellular prolongations) having podoms (dilations) and podomers (very thin segments). TCs' three-dimensional (3D) morphology is still unknown. Cardiac TCs seem to be particularly involved in long and short distance intercellular signalling and, therefore, their 3D architecture is important for understanding their spatial connections. Using focused ion beam scanning electron microscopy (FIB-SEM) we show, for the first time, the whole ultrastructural anatomy of cardiac TCs. 3D reconstruction of cardiac TCs by FIB-SEM tomography confirms that they have long, narrow but flattened (ribbon-like) telopodes, with humps generated by the podoms. FIB-SEM tomography also confirms the network made by TCs in the cardiac interstitium through adherens junctions. This study provides the first FIB-SEM tomography of a human cell type.

Objective assessment of image quality and dose reduction in CT iterative reconstruction.

PURPOSE: Iterative reconstruction (IR) algorithms have the potential to reduce radiation dose in CT diagnostic imaging. As these algorithms become available on the market, a standardizable method of quantifying the dose reduction that a particular IR method can achieve would be valuable. Such a method would assist manufacturers in making promotional claims about dose reduction, buyers in comparing different devices, physicists in independently validating the claims, and the United States Food and Drug Administration in regulating the labeling of CT devices. However, the nonlinear nature of commercially available IR algorithms poses challenges to objectively assessing image quality, a necessary step in establishing the amount of dose reduction that a given IR algorithm can achieve without compromising that image quality. This review paper seeks to consolidate information relevant to objectively assessing the quality of CT IR images, and thereby measuring the level of dose reduction that a given IR algorithm can achieve. METHODS: The authors discuss task-based methods for assessing the quality of CT IR images and evaluating dose reduction. RESULTS: The authors explain and review recent literature on signal detection and localization tasks in CT IR image quality assessment, the design of an appropriate phantom for these tasks, possible choices of observers (including human and model observers), and methods of evaluating observer performance. CONCLUSIONS: Standardizing the measurement of dose reduction is a problem of broad interest to the CT community and to public health. A necessary step in the process is the objective assessment of CT image quality, for which various task-based methods may be suitable. This paper attempts to consolidate recent literature that is relevant to the development and implementation of task-based methods for the assessment of CT IR image quality.

Observation of the ß-delayed γ-proton decay of (56)Zn and its impact on the Gamow-Teller strength evaluation.

We report the observation of a very exotic decay mode at the proton drip line, the ß-delayed γ-proton decay, clearly seen in the ß decay of the T_{z}=-2 nucleus ^{56}Zn. Three γ-proton sequences have been observed after the ß decay. Here this decay mode, already observed in the sd shell, is seen for the first time in the fp shell. Both γ and proton decays have been taken into account in the estimation of the Fermi and Gamow-Teller strengths. Evidence for fragmentation of the Fermi strength due to strong isospin mixing is found.

Observation of low- and high-energy Gamow-Teller phonon excitations in nuclei.

Gamow-Teller (GT) transitions in atomic nuclei are sensitive to both nuclear shell structure and effective residual interactions. The nuclear GT excitations were studied for the mass number A = 42, 46, 50, and 54 "f-shell" nuclei in ((3)He, t) charge-exchange reactions. In the (42)Ca → (42)Sc reaction, most of the GT strength is concentrated in the lowest excited state at 0.6 MeV, suggesting the existence of a low-energy GT phonon excitation. As A increases, a high-energy GT phonon excitation develops in the 6-11 MeV region. In the (54)Fe → (54)Co reaction, the high-energy GT phonon excitation mainly carries the GT strength. The existence of these two GT phonon excitations are attributed to the 2 fermionic degrees of freedom in nuclei.

Recent advances in synthesis, characterization of hydroxyapatite/polyurethane composites and study of their biocompatible properties.

The development of engineered biomaterials that mimic bone tissues is a promising research area that benefits from a growing interest. Polymers and polymer-ceramic composites are the principle materials investigated for the development of synthetic bone scaffolds thanks to their proven biocompatibility and biostability. Several polymers have been combined with calcium phosphates (mainly hydroxyapatite) to prepare nanocomposites with improved biocompatible and mechanical properties. Here, we report the hydrothermal synthesis in high pressure conditions of nanostructured composites based on hydroxyapatite and polyurethane functionalized with carboxyl and thiol groups. Cell-material interactions were investigated for potential applications of these new types of composites as coating for orthopedic implants. Physical-chemical and morphological characteristics of hydroxyapatite/polyurethane composites were evaluated for different compositions, showing their dependence on synthesis parameters (pressure, temperature). In vitro experiments, performed to verify if these composites are biocompatible cell culture substrates, showed that they are not toxic and do not affect cell viability.

Measurement of the first ionization potential of astatine by laser ionization spectroscopy.

The radioactive element astatine exists only in trace amounts in nature. Its properties can therefore only be explored by study of the minute quantities of artificially produced isotopes or by performing theoretical calculations. One of the most important properties influencing the chemical behaviour is the energy required to remove one electron from the valence shell, referred to as the ionization potential. Here we use laser spectroscopy to probe the optical spectrum of astatine near the ionization threshold. The observed series of Rydberg states enabled the first determination of the ionization potential of the astatine atom, 9.31751(8) eV. New ab initio calculations are performed to support the experimental result. The measured value serves as a benchmark for quantum chemistry calculations of the properties of astatine as well as for the theoretical prediction of the ionization potential of superheavy element 117, the heaviest homologue of astatine.

Genetic comparison of mouse lung telocytes with mesenchymal stem cells and fibroblasts.

Telocytes (TCs) are interstitial cells with telopodes - very long prolongations that establish intercellular contacts with various types of cells. Telocytes have been found in many organs and various species and have been characterized ultrastructurally, immunophenotypically and electrophysiologically (www.telocytes.com). Telocytes are distributed through organ stroma forming a three-dimensional network in close contacts with blood vessels, nerve bundles and cells of the local immune system. Moreover, it has been shown that TCs express a broad range of microRNAs, such as pro-angiogenic and stromal-specific miRs. In this study, the gene expression profile of murine lung TCs is compared with other differentiated interstitial cells (fibroblasts) and with stromal stem/progenitor cells. More than 2000 and 4000 genes were found up- or down-regulated, respectively, in TCs as compared with either MSCs or fibroblasts. Several components or regulators of the vascular basement membrane are highly expressed in TCs, such as Nidogen, Collagen type IV and Tissue Inhibitor of Metalloproteinase 3 (TIMP3). Given that TCs locate in close vicinity of small vessels and capillaries, the data suggest the implication of TCs in vascular branching. Telocytes express also matrix metalloproteases Mmp3 and Mmp10, and thus could regulate extracellular matrix during vascular branching and de novo vessel formation. In conclusion, our data show that TCs are not fibroblasts, as the ultrastructure, immunocytochemistry and microRNA assay previously indicated. Gene expression profile demonstrates that TCs are functionally distinct interstitial cells with specific roles in cell signalling, tissue remodelling and angiogenesis.

Telocytes, a distinct type of cell among the stromal cells present in the lamina propria of jejunum.

Conventionally, cells described in the stroma of the intestinal wall are fibroblasts/fibrocytes, mast cells, plasma cells, eosinophils, macrophages and, interstitial cells of Cajal (ICCs), the latter being considered as the pacemakers of gastrointestinal rhythmicity. Recently, a new type of stromal cell called telocyte (TCs) was found in various cavitary and non-cavitary organs (www.telocytes.com). We show here direct electron microscopical evidence for the presence of TCs in the lamina propria of rat jejunum just beneath the epithelial layer of the mucosal crypts and in between the smooth muscle cells (SMCs) of muscularis mucosae. TCs are characterized by: several very long (tens to hundreds of µm) prolongations called telopodes (Tps). Tps (with caliber below the resolving power of light microscopy) display podomeres (thin segments ≤ 0.2 µm) and podoms (dilations accommodating caveolae, mitochondria, and endoplasmic reticulum). Tps present dichotomous branching and form a three dimensional network close to immune cells, SMCs or nerve bundles. TCs could play a role in intercellular signaling and control of local tissue homeostasis.

Telocytes in human skin--are they involved in skin regeneration?

Telocytes (TCs), a particular interstitial cell type, have been recently described in a wide variety of mammalian organs (www.telocytes.com). The TCs are identified morphologically by a small cell body and extremely long (tens to hundreds of µm), thin prolongations (less than 100 nm in diameter, below the resolving power of light microscopy) called telopodes. Here, we demonstrated with electron microscopy and immunofluorescence that TCs were present in human dermis. In particular, TCs were found in the reticular dermis, around blood vessels, in the perifollicular sheath, outside the glassy membrane and surrounding sebaceous glands, arrector pili muscles and both the secretory and excretory portions of eccrine sweat glands. Immunofluorescence screening and laser scanning confocal microscopy showed two subpopulations of dermal TCs; one expressed c-kit/CD117 and the other was positive for CD34. Both subpopulations were also positive for vimentin. The TCs were connected to each other by homocellular junctions, and they formed an interstitial 3D network. We also found TCs adjoined to stem cells in the bulge region of hair follicles. Moreover, TCs established atypical heterocellular junctions with stem cells (clusters of undifferentiated cells). Given the frequency of allergic skin pathologies, we would like to emphasize the finding that close, planar junctions were frequently observed between TCs and mast cells. In conclusion, based on TC distribution and intercellular connections, our results suggested that TCs might be involved in skin homeostasis, skin remodelling, skin regeneration and skin repair.

Telocytes in meninges and choroid plexus.

Telocytes (TCs) are a recently identified type of interstitial cells present in a wide variety of organs in humans and mammals (www.telocytes.com). They are characterized by a small cell body, but extremely long cell processes - telopodes (Tp), and a specific phenotype. TCs establish close contacts with blood capillaries, nerve fibers and stem cells. We report here identification of TCs by electron microscopy and immunofluorescence in rat meninges and choroid plexus/subventricular zone, in the vicinity of putative stem cells. The presence of TCs in brain areas involved in adult neurogenesis might indicate that they have a role in modulation of neural stem cell fate.

Cardiomyocytes derived from human embryonic and induced pluripotent stem cells: comparative ultrastructure.

Induced pluripotent stem cells (iPSC) are generated from fully differentiated somatic cells that were reprogrammed into a pluripotent state. Human iPSC which can be obtained from various types of somatic cells such as fibroblasts or keratinocytes can differentiate into cardiomyocytes (iPSC-CM), which exhibit cardiac-like transmembrane action potentials, intracellular Ca(2+) transients and contractions. While major features of the excitation-contraction coupling of iPSC-CM have been well-described, very little is known on the ultrastructure of these cardiomyocytes. The ultrastructural features of 31-day-old (post-plating) iPSC-CM generated from human hair follicle keratinocytes (HFKT-iPSC-CM) were analysed by electron microscopy, and compared with those of human embryonic stem-cell-derived cardiomyocytes (hESC-CM). The comparison showed that cardiomyocytes from the two sources share similar proprieties. Specifically, HFKT-iPSC-CM and hESC-CM, displayed ultrastructural features of early and immature phenotype: myofibrils with sarcomeric pattern, large glycogen deposits, lipid droplets, long and slender mitochondria, free ribosomes, rough endoplasmic reticulum, sarcoplasmic reticulum and caveolae. Noteworthy, the SR is less developed in HFKT-iPSC-CM. We also found in both cell types: (1) 'Ca(2+)-release units', which connect the peripheral sarcoplasmic reticulum with plasmalemma; and (2) intercellular junctions, which mimic intercalated disks (desmosomes and fascia adherens). In conclusion, iPSC and hESC differentiate into cardiomyocytes of comparable ultrastructure, thus supporting the notion that iPSC offer a viable option for an autologous cell source for cardiac regenerative therapy.

Experimental acute myocardial infarction: telocytes involvement in neo-angiogenesis.

We used rat experimental myocardial infarction to study the ultrastructural recovery, especially neo-angiogenesis in the infarction border zone. We were interested in the possible role(s) of telocytes (TCs), a novel type of interstitial cell very recently discovered in myocardim (see http://www.telocytes.com). Electron microscopy, immunocytochemistry and analysis of several proangiogenic microRNAs provided evidence for TC involvement in neo-angiogenesis after myocardial infarction. Electron microscopy showed the close spatial association of TCs with neoangiogenetic elements. Higher resolution images provided the following information: (a) the intercellular space between the abluminal face of endothelium and its surrounding TCs is frequently less than 50 nm; (b) TCs establish multiple direct nanocontacts with endothelial cells, where the extracellular space seems obliterated; such nanocontacts have a length of 0.4-1.5 µm; (c) the absence of basal membrane on the abluminal face of endothelial cell. Besides the physical contacts (either nanoscopic or microscopic) TCs presumably contribute to neo-angiognesis via paracrine secretion (as shown by immunocytochemistry for VEGF or NOS2). Last but not least, TCs contain measurable quantities of angiogenic microRNAs (e.g. let-7e, 10a, 21, 27b, 100, 126-3p, 130a, 143, 155, 503). Taken together, the direct (physical) contact of TCs with endothelial tubes, as well as the indirect (chemical) positive influence within the 'angiogenic zones', suggests an important participation of TCs in neo-angiogenesis during the late stage of myocardial infarction.

Complex effects of imatinib on spontaneous and oxytocin-induced contractions in human non-pregnant myometrium.

Human myometrium includes two important cell populations involved in its contractility: smooth muscle fibers and interstitial cells. The pacemaking mechanism is not yet identified, but it is possible that myometrial smooth muscle cells contract in response to a signal generated by c-kit positive interstitial cells. The aim of this study was to investigate the effects of imatinib as a c-kit receptor antagonist on the spontaneous or oxytocin (OT) induced contractions of human non-pregnant myometrium in vitro. Myometrial strips were obtained from non-pregnant women (reproductive age) undergoing hysterectomy for benign indications. The strips were suspended in organ baths for recording of isometric tension. Imatinib effects were assessed on spontaneous contraction and after preexposure to OT.Direct exposure of myometrial strips to imatinib inhibits both amplitude and frequency of contractions (80-320 µM) in a dose dependent manner. Amplitude reverted back to 90% of the baseline amplitude by consequent addition of imatinib (until 480 µM). Total inhibition of myometrial contraction was obtained after addition of OT 60 nM. If myometrium was pre-exposed to OT (320 nM), imatinib 80-160 µm increased amplitude, while decreasing frequency. These data provide evidence that telocytes may be involved as modulators of the spontaneous contractions of the non-pregnant human uterus, via a tyrosine-kinase independent signaling pathway.

Identification of telocytes in skeletal muscle interstitium: implication for muscle regeneration.

Skeletal muscle interstitium is crucial for regulation of blood flow, passage of substances from capillaries to myocytes and muscle regeneration. We show here, probably, for the first time, the presence of telocytes (TCs), a peculiar type of interstitial (stromal) cells, in rat, mouse and human skeletal muscle. TC features include (as already described in other tissues) a small cell body and very long and thin cell prolongations-telopodes (Tps) with moniliform appearance, dichotomous branching and 3D-network distribution. Transmission electron microscopy (TEM) revealed close vicinity of Tps with nerve endings, capillaries, satellite cells and myocytes, suggesting a TC role in intercellular signalling (via shed vesicles or exosomes). In situ immunolabelling showed that skeletal muscle TCs express c-kit, caveolin-1 and secrete VEGF. The same phenotypic profile was demonstrated in cell cultures. These markers and TEM data differentiate TCs from both satellite cells (e.g. TCs are Pax7 negative) and fibroblasts (which are c-kit negative). We also described non-satellite (resident) progenitor cell niche. In culture, TCs (but not satellite cells) emerge from muscle explants and form networks suggesting a key role in muscle regeneration and repair, at least after trauma.

A pirinixic acid derivative (LP105) inhibits murine 5-lipoxygenase activity and attenuates vascular remodelling in a murine model of aortic aneurysm.

BACKGROUND AND PURPOSE Arachidonic acid derivatives play a central role in inflammation processes. Arachidonic acid is metabolized by several enzymes, particularly cyclooxygenases (COX), 5-lipoxygenase (5-LOX) and microsomal prostaglandin E-synthase-1 (mPGES-1) to pro-inflammatory mediators. EXPERIMENTAL APPROACH We determined the effect of LP105, a pirinixic acid derivative which acts as inhibitor of 5-LOX, COX and mPGES-1, on aortic aneurysm development in mice and on 5-LOX activity in murine monocytes. KEY RESULTS In a monocyte cell line (RAW264.7), LP105 inhibited 5-LOX in whole cells (IC(50) : 1-3 µM) and in supernatants (IC(50) : ∼10 µM). Oral administration of LP105 to mice resulted in therapeutic tissue and plasma levels. Aortic aneurysms were induced in ApoE(-/-) mice by angiotensin II (AngII) and LP105 (5 mg·day(-1) per animal) was co-administered to a subgroup. Compared with animals receiving AngII alone, the LP105+AngII group showed a lower heart rate, a trend towards reduced heart to body weight ratio but similar hypertensive responses. AngII alone significantly increased aortic weight and diameter but co-treatment with LP105+AngII prevented these changes. LC/MS-MS studies revealed increased 15-hydroxytetraenoic acid (15-HETE) and 14,15-epoxyeicosatrienoic acid (14,15-EET) plasma levels in LP105-treated animals. In the murine kidney, mRNAs of EET-generating or metabolizing enzymes and of 5-LOX and 15-LOX were unaffected by LP105. LP105 also did not inhibit the EET-metabolizing soluble epoxide hydrolase. CONCLUSIONS AND IMPLICATIONS LP105 was a potent inhibitor of monocyte 5-LOX and reduced AngII-induced vascular remodelling in mice. A shift of arachidonic acid metabolism to the protective EET pathway may contribute to the beneficial effects of LP105.

miR-193 expression differentiates telocytes from other stromal cells.

Telocytes (TCs) are a particular type of interstitial (stromal) cells defined by very long, moniliform telopodes. Their tissue location, between blood vessels and other cells such as cardiomyocytes (CMC) and neurons, suggests a role in intercellular signalling. In order to define a microRNA (miR) signature in cardiac TCs, we have found that miR-193 is differentially expressed between TCs and other interstitial cells. Because miR-193 regulates c-kit, our data support the previous finding that TCs express c-kit in certain circumstances. In addition, the miRs which are specific to CMC and other muscle cells (e.g. miR-133a, miR-208a) are absent in TCs. Overall the data reinforce the view that TCs are a particular type of interstitial (mesenchymal) cells.