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Fusion proteins involving the BRAF serine/threonine kinase occur in many cancers. The oncogenic potential of BRAF fusions has been attributed to the loss of critical N-terminal domains that mediate BRAF autoinhibition. We used whole-exome and RNA sequencing in a patient with glioblastoma multiforme to identify a rearrangement between TTYH3, encoding a membrane-resident, calcium-activated chloride channel, and BRAF intron 1, resulting in a TTYH3–BRAF fusion protein that retained all features essential for BRAF autoinhibition. Accordingly, the BRAF moiety of the fusion protein alone, which represents full-length BRAF without the amino acids encoded by exon 1 (BRAFΔE1), did not induce MEK/ERK phosphorylation or transformation. Likewise, neither the TTYH3 moiety of the fusion protein nor full-length TTYH3 provoked ERK pathway activity or transformation. In contrast, TTYH3–BRAF displayed increased MEK phosphorylation potential and transforming activity, which were caused by TTYH3-mediated tethering of near-full-length BRAF to the (endo)membrane system. Consistent with this mechanism, a synthetic approach, in which BRAFΔE1 was tethered to the membrane by fusing it to the cytoplasmic tail of CD8 also induced transformation. Furthermore, we demonstrate that TTYH3–BRAF signals largely independent of a functional RAS binding domain, but requires an intact BRAF dimer interface and activation loop phosphorylation sites. Cells expressing TTYH3–BRAF exhibited increased MEK/ERK signaling, which was blocked by clinically achievable concentrations of sorafenib, trametinib, and the paradox breaker PLX8394. These data provide the first example of a fully autoinhibited BRAF protein whose oncogenic potential is dictated by a distinct fusion partner and not by a structural change in BRAF itself.

Fusion proteins involving the BRAF serine/threonine kinase occur in many cancers. The oncogenic potential of BRAF fusions has been attributed to the loss of critical N-terminal domains that mediate BRAF autoinhibition. We used whole-exome and RNA sequencing in a patient with glioblastoma multiforme to identify a rearrangement between TTYH3, encoding a membrane-resident, calcium-activated chloride channel, and BRAF intron 1, resulting in a TTYH3-BRAF fusion protein that retained all features essential for BRAF autoinhibition. Accordingly, the BRAF moiety of the fusion protein alone, which represents full-length BRAF without the amino acids encoded by exon 1 (BRAF

Lithium is extensively known to be a good tracer of non-standard mixing processes occurring in stellar interiors. We present the results of a new large Lithium survey in red giant stars and combine it with surveys from the literature to probe the impact of rotation-induced mixing and thermohaline double-diffusive instability along stellar evolution. We determined the surface Li abundance for a sample of 829 giant stars with accurate Gaia parallaxes for a large sub-sample (810 stars) complemented with accurate Hipparcos parallaxes (19 stars). The spectra of our sample of northern and southern giant stars were obtained in three ground-based observatories (OHP, ESO-La Silla, Mc Donald). We determined the atmospheric parameters (Teff, log(g), [Fe/H]), and the Li abundance. We used Gaia parallaxes and photometry to determine the luminosity of our objects and we estimated the mass and evolution status of each sample star with a maximum-likelihood technique using stellar evolution models computed with the STAREVOL code. We compared the observed Li behaviour with predictions from stellar models, including rotation and thermohaline mixing. The same approach was used for stars from selected Li surveys from the literature. Rotation-induced mixing accounts nicely for the lithium behaviour in stars warmer than about 4200K, independently of the mass domain. For stars with masses lower than 2Msun thermohaline mixing leads to further Li depletion below the Teff of the RGB bump (about 4000K), and on the early AGB, as observed. Depending on the definition we adopt, we find between 0.8 and 2.2% of Li-rich giants in our new sample. Gaia puts a new spin on the understanding of mixing processes in stars, and our study confirms the importance of rotation-induced processes and of thermohaline mixing. However asteroseismology is required to definitively pinpoint the actual evolution status of Li-rich giants., Comment: 16 pages, 18 figures, A&A, accepted for publication (new version with an additional reference)

Fusion proteins involving the BRAF serine/threonine kinase occur in many cancers. Oncogenic BRAF fusion proteins usually consist of the BRAF kinase domain and an N-terminal fusion partner that replaces the critical domains required for BRAF autoinhibition. We applied whole-exome and RNA sequencing in a patient with glioblastoma multiforme (GBM) to identify a rearrangement between TTYH3, encoding a membrane-resident, calcium-activated chloride channel, and BRAF intron 1, resulting in a TTYH3-BRAF fusion protein that retained all structural prerequisites for BRAF autoinhibition. Indeed, the BRAF moiety of the fusion protein alone, which represented near-full-length BRAF without the amino acids encoded by exon 1 (BRAFΔE1), did not induce MEK/ERK phosphorylation or cellular transformation. Similarly, neither the TTYH3 moiety of the fusion protein nor full-length TTYH3 provoked ERK pathway activity or transformation. In contrast, TTYH3-BRAF displayed increased MEK phosphorylation potential and transforming activity, which were caused by TTYH3-mediated tethering of BRAFΔE1 to the (endo)membrane system. Consistent with this mechanism, a synthetic approach in which BRAFΔE1 was localized to the membrane by fusing it to the cytoplasmic tail of CD8 also induced transformation. Furthermore, we demonstrate that TTYH3-BRAF signals largely independent of a functional RAS-binding domain, but relies on an intact BRAF dimer interface and forms homo- and heterodimers with RAF1 or ARAF. Moreover, the MEK phosphorylation and transformation potential of TTYH3-BRAF requires the activation loop phosphorylation sites T599 and S602. Various cell line models, including primary human astrocytes and a GBM stem cell line, expressing TTYH3-BRAF exhibited increased MEK/ERK signaling. TTYH3-BRAF-induced MEK/ERK phosphorylation was blocked by clinically achievable concentrations of sorafenib, trametinib, and the paradox breaker PLX8394. These data provide the first example of a fully autoinhibited BRAF protein whose oncogenic potential is dictated by a distinct fusion partner and not by a structural change in BRAF itself. Citation Format: Florian Weinberg, Ricarda Herr, Martina Fröhlich, Christoph Heining, Sandra Braun, Corinna Spohr, Mary Iconomou, Viola Hollek, Michael Röring, Peter Horak, Simon Kreutzfeldt, Gregor Warsow, Barbara Hutter, Sebastian Uhrig, Olaf Neumann, David Reuss, Dieter Hendrik Heiland, Christof von Kalle, Wilko Weichert, Albrecht Stenzinger, Benedikt Brors, Hanno Glimm, Stefan Fröhling, Tilman Brummer. Identification and characterization of an unusual BRAF fusion oncoprotein with retained autoinhibitory domains [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr LB-B08. doi:10.1158/1535-7163.TARG-19-LB-B08

In the faint star KIC 9700322 observed by the Kepler satellite, 76 frequencies with amplitudes from 14 to 29000 ppm were detected. The two dominant frequencies at 9.79 and 12.57 c/d (113.3 and 145.5 \mu Hz), interpreted to be radial modes, are accompanied by a large number of combination frequencies. A small additional modulation with a 0.16 c/d frequency is also seen; this is interpreted to be the rotation frequency of the star. The corresponding prediction of slow rotation is confirmed by a spectrum from which v sin i = 19 \pm 1 km/s is obtained. The analysis of the spectrum shows that the star is one of the coolest {\delta} Sct variables. We also determine Teff = 6700 \pm 100 K and log g = 3.7 \pm 0.1, compatible with the observed frequencies of the radial modes. Normal solar abundances are found. An \ell = 2 frequency quintuplet is also detected with a frequency separation consistent with predictions from the measured rotation rate. A remarkable result is the absence of additional independent frequencies down to an amplitude limit near 14 ppm, suggesting that the star is stable against most forms of nonradial pulsation. The frequency spectrum of this star emphasizes the need for caution in interpreting low frequencies in {\delta} Sct stars as independent gravity modes. A low frequency peak at 2.7763 c/d in KIC 9700322 is, in fact, the frequency difference between the two dominant modes and is repeated over and over in various frequency combinations involving the two dominant modes. The relative phases of the combination frequencies show a strong correlation with frequency, but the physical significance of this result is not clear.

Human malignant melanoma is a highly metastatic tumor with poor prognosis. The majority of metastatic melanomas are resistant to diverse chemotherapeutic agents. Consequently, the search for novel antimelanoma agents continues. In recent years, the interest in plants and their biologically active constituents as a source of novel potential drugs significantly increased. Inositol hexaphosphate (IP6) is a naturally occurring compound that has been shown to inhibit the growth of a wide variety of tumor cells in multiple experimental model systems. The aim of this study was to evaluate the antiproliferative and cytotoxic influence of IP6 on melanotic melanoma cells in vitro. The A2058 cells used as a model of human skin melanoma malignum were exposed to different concentrations of IP6 (0.1-5 mM) for a various period of time and their growth was determined by sulforhodamine B assay after 24, 48 and 72 h. The cytotoxicity of IP6 was measured at 24 and 72 h by XTT assay. IP6 has been found to cause dose-dependent growth suppression of A2058 melanoma cells. At low concentrations (0.1 and 0.5 mM) it did not exert any influence on the cell proliferation as compared to control cultures. Higher concentrations of IP6 (from 1 to 5 mM) had a statistically significant, suppressive effect on cell proliferation after 24 h incubation. When the experimental time period was increased up to 72 h, statistically significant inhibition of cell proliferation was monitored at all IP6 concentrations used. Data obtained from XTT assay indicated that IP6 had dose- and time-dependent cytotoxic effect on melanoma cells. The results demonstrate the antiproliferative and cytotoxic properties of IP6 in a wide range of concentrations on human A2058 melanoma cells. Hence, it can be suggested that IP6 could have a promising therapeutic significance in treating cancer.

Colon cancer has been remaining the second leading cause of cancer mortality in Poland in the last years. Epidemiological, preclinical and clinical studies reveal that dietary phytochemicals may exert chemopreventive and therapeutic effect against colorectal cancer. There is a growing interest in identifying new biologically active agents from dietary sources in this respect. Pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene) is a naturally occurring stilbene, that has been found to have antioxidative, anti-inflammatory and antipro- liferative properties. Compared to other stilbenes, pterostilbene has greater bioavailability, and so, a greater potential for clinical applications. Recent studies showed that pterostilbene exhibits the hallmark characteristics of an anticancer agent. The aim of this study was to analyze antiproliferative and cytotoxic effects of pterostilbene on human colon cancer Caco-2 cells. They were cultured using standard techniques and exposed to increasing doses of pterostilbene (5-100 μM) for 48 and 72 h. Cell proliferation was determined by sulforhodamine B assay. The growth of treated cells was expressed as a percentage of that of untreated control cells. Pterostilbene decreased proliferation rate of Caco-2 cells in a dose- and time-dependent manner. Its concentrations = 25 μM did not affect cell growth after 48 h treatment period. Significant growth inhibition was observed in cultures incubated with higher concentrations of pterostilbene (40-100 μM). Pterostilbene at all concentrations used (5-100 μM) caused significant inhibition of cell proliferation when the experimental time period was elongated to 72 h. The maximum growth reduction was observed at 100 mM pterostilbene. The cytotoxicity of pterostilbene was evaluated in 48 h cultures based on lactate dehydrogenase (LDH) leakage into the culture medium and showed dose-related pattern. The findings of this study showed significant dose-dependent antiproliferative and cytotoxic effects of pterostilbene against human colon cancer cells in vitro.

Isolated non-compaction of the ventricular myocardium (INVM), sometimes referred to as 'spongy myocardium', is a congenital and exceedingly rare cardiomyopathy. Isolated ventricular non-compaction occurs in the absence of other structural heart diseases and, hypothetically, it is due to the arrest of myocardial morphogenesis. Isolated non-compaction of the ventricular myocardium may manifest itself from infancy to young adulthood with a high mortality rate. Both sexes are affected. In our study, we present a case of INVM (left and right ventricles) in a 3-year-old girl, diagnosed by two-dimensional echocardiography. The anomaly presented as a restrictive cardiomyopathy. The girl was admitted to our hospital with heart failure, when she was 10 months old. She was treated with dopamine, digoxin, furosemide, spironolactone, and acenocoumarol and her condition improved. Presently, the girl remains asymptomatic and for 3 years of follow-up, her development has been almost normal. We here describe the genetic background of this disorder (based on a literature review).

Interspecies hybrids between distinct species of the genus Xiphophorus are often used in varied research investigations to identify genomic regions associated with the inheritance of complex traits. There are 24 described Xiphophorus species and a greater number of pedigreed strains; thus, the number of potential interspecies hybrid cross combinations is quite large. Previously, select Xiphophorus experimental crosses have been shown to exhibit differing characteristics between parental species and among the hybrid fishes derived from crossing them, such as widely differing susceptibilities to chemical or physical agents. For instance, genomic regions harboring tumor suppressor and oncogenes have been identified via linkage association of these loci with a small set of established genetic markers. The power of this experimental strategy is related to the number of genetic markers available in the Xiphophorus interspecies cross of interest. Thus, we have undertaken the task of expanding the suite of easily scored markers by characterization of Xiphophorus microsatellite sequences. Using a cross between Xiphophorus maculatus and X. andersi, we report a linkage map predominantly composed of microsatellite markers. All 24 acrocentric chromosome sets of Xiphophorus are represented in the assembled linkage map with an average intergenomic distance of 7.5 cM. Since both male and female F1 hybrids were used to produce backcross progeny, these recombination rates were compared between “male” and “female” maps. Although several genomic regions exhibit differences in map length, male- and female-derived maps are similar. Thus Xiphophorus, in contrast to zebrafish, Danio rerio, and several other vertebrate species, does not show sex-specific differences in recombination. The microsatellite markers we report can be easily adapted to any Xiphophorus interspecies and some intraspecies crosses, and thus provide a means to directly compare results derived from independent experiments.

We describe the clinical and genetic characteristics of the family, in which the diagnosis of LQT1 had been made. The electrocardiogram (ECG) characteristics of this patient indicated the likelihood of LQTS1. Polymorphic ventricular extrasystolies and episodes of polymorphic non-sustained ventricular tachycardia were confirmed by Holter ECG monitoring. On the exertional electrocardiogram polymorphic ventricular tachycardia (torsade de pointes) was recorded. Direct sequencing of both DNA strands revealed the absence of mutations or polymorphisms in the KCNQ1, HERG, and SCN5A genes.

Transforming growth factors-beta (TGF-beta) are multifunctional cytokines involved in the regulation of cell development, differentiation, survival and apoptosis. They are also potent anticancer agents that inhibit uncontrolled proliferation of cells. Incorrect TGF-beta regulation has been implicated in the pathogenesis of many diseases including inflammation and cancer. In humans, the TGF-beta family consists of three members (TGF-beta1, 2, 3) that show high similarity and homology. TGF-betas exert biological activities on various cell types including neoplastic cells via their specific receptors. Inositol hexaphosphate (phytic acid, IP6), a phytochemical has been reported to possess various health benefits. The aim of this study was to examine the effect of IP6 on the expression of genes encoding TGF-beta1, TGF-beta2, TGF-beta3 isoforms and their receptors TbetaRI, TbetaRII, TbetaRIII in human colorectal cancer cell line Caco-2. The cells were treated with 0.5, 1 and 2.5 mM IP6 for 3, 6 and 12 h. The untreated Caco-2 cells were used as the control. Quantification of genes expression was performed by real time QRT-PCR technique with a SYBR Green I chemistry. The experimental data revealed that the TGF-beta1 mRNA was the predominant isoform in Caco-2 cells and that IP6 enhanced transcriptional activity of genes of all three TGF-beta isoforms and their receptors TbetaRI, TbetaRII TbetaRIII in these cells. At concentrations up to 1 mM, IP6 over-expressed the genes in 6 h lasting cultures, and its higher dose (2.5 mM) caused successively increasing transcript level of TGF-beta isoforms and receptors with the duration of experiment up to 12 h. The findings of this study indicate that one of anti-cancer abilities of IP6 can be realized by enhancing the gene expression of TGF-beta isoforms and their receptors at the transcriptional level.

Phytic acid (IP6) is an essential component of high fiber diet physiologically present in human large gut. It has been recognized to possess various significant health benefits effects including chemopreventive and have antineoplastic activity against various types of cancer. Moreover, its role in immune response through modulation of the secretion of proinflammatory cytokines and chemokines has been postulated. One of the signal transduction pathways involved in a variety of inflammatory responses is p38 mitogen-activated protein kinase (MAPK) pathway. The aim of this study was to examine effect of IP6 on human p38alpha MAP kinase activity and the expression of gene encoding p38 MAP kinase in unstimulated and IL-1beta-stimulated Caco-2 cells. Furthermore, the role of signaling pathways involving p38 MAP kinase in IP6-induced down-regulation of IL-8 secretion by unstimulated and IL-1beta-stimulated cells in the presence of p38 MAP kinase activator (anisomycin) and inhibitor (SB 203580) was evaluated. IP6 inhibited activity of recombinant p38 MAPK activity in dose-dependent manner. Treatment of cells with IP6 for 3 h resulted in decreased p38 MAP kinase expression in both unstimulated and stimulated with IL-1beta cells. The similar level of p38alpha mRNA was found in untreated and treated with IP6 cells after 6 and 12 h. Incubation of Caco-2 cells with anisomycin resulted in upregulation of IL-8 secretion and their pretreatment with anisomycin prior to IP6 addition showed down-regulation of IL-8 secretion compared to cells treated with anisomycin alone. The findings of this study show that p38 MAPK could be one of the molecular targets for IP6 in the intestinal epithelial cells and that IP6 inhibitory effect on IL-8 secretion by Caco-2 cells could be mediated by its inhibition of p38 activity.

Intestinal epithelial cells play an important role in the mucosal immune and inflammatory reactions via the expression and secretion of proinflammatory cytokines such as interleukin-6 (IL-6) and interleukin-8 (IL-8). The expression of both interleukins is regulated by nuclear factor KB (NF-kappaB). Phytic acid (IP6) is an essential component of high fiber diet. It is physiologically present in the human large gut at concentrations reaching 4 mM. It exhibits pleiotropic health beneficial effects including anti-oxidant and anti-tumor activities. Recent studies showed that IP6 can modulate immune functions of intestinal epithelium through regulation of proinflammatory cytokines secretion. The aim of this study was to analyze the effect of IP6 on the expression of IL-6 and IL-8 as well as p50 and p65 subunits of NF-kappaB and its inhibitor IkappaBalpha in Caco-2 cells stimulated with IL-1beta. A kinetic study of mRNAs expression in cells was performed after their treatment with 1 and 2.5 mM IP6 for 3, 6 and 12 h. Quantification of the genes expression was carried out using real time QRT-PCR technique. IP6 at all used concentrations had no influence on transcription of p65 gene and modulated expression of p50 and IkappaBalpha genes in Caco-2 cells. Treatment of cells with IP6 resulted in a marked decrease in both IL-6 (at 3 and 6 h) and IL-8 expression (3 h). The results of these studies suggest that IP6 may exert immunoregulatory effects on intestinal epithelium by influencing transcriptional activity of genes encoding p50 subunit of NF-kappaB, its inhibitor IkappaBalpha and proinflammatory cytokines IL-6 and IL-8.

Soluble adhesion molecules such as soluble intercellular adhesion molecules-1 (sICAM-1) and soluble E-cadherin (sE-cadherin) play important role in tumor invasion and the development of metastasis. It was observed that their concentrations in body fluids of patients with colon cancer were elevated. Celecoxib, a selective inhibitor of cyclooxygenase-2 (COX-2) besides its analgesic, anti-inflammatory, and antipyretic activity is able to inhibit development of colon cancer and reduce risk of metastasis. The additional factors, e.g., dietary components in colon cancer, may influence therapeutic effect of drugs, such as cytokines. TNF-alpha (tumor necrosis factor - alpha) is a cytokine, which concentration significantly increases in serum of patients with inflammatory and cancer diseases. The latest studies demonstrate, that phytic acid (IP6), a myo-inositol derivative, abundantly present in high-fiber diets could substantially reduce colon cancer incidence. The aim of the present study was to evaluate the influence of celecoxib on sICAM-1 and sE-cadherin concentrations in transformed epithelial colon cell cultures simultaneously exposed to IP6 and TNF-alpha. Additionally, the adhesion of the exposed cells to collagen I was assessed. HT-29 and Caco-2 cells were cultured in the presence of 50 ng/mL celecoxib, 1.0 mM IP6, and 100 ng/mL TNF-alpha, and their combination: TNF-alpha plus IP6, TNF-alpha plus celecoxib, IP6 plus celecoxib, and TNF-alpha with celecoxib plus IP6, for 96 h. Nonexposed cell line cultures served as controls. Concentrations of sICAM-1 and sE-cadherin were measured in the culture medium by enzyme-linked immunosorbent assay (ELISA) using Quantikine - Human sICAM-1/CD54 Immunoassay and Quantikine-Human sE-Cadherin Immunoassay. All the results obtained were expressed as ng per mL. In the adhesion assay, the cells were incubated with IP6 (0.5, 1.0 and 2.0 mM), TNF-alpha (100 ng/mL), celecoxib (50 ng/mL) and their combination for 90 min. Fluorescence values 480 nm/530 nm reflected concentrations of DNA in cells attached to collagen I. The obtained results indicate that celecoxib (50 ng/mL), the selective COX-2 inhibitor, reduces significantly sICAM-1 and sE-cadherin concentrations in HT-29 and Caco-2 transformed human epithelial colorectal cell line cultures co-treated with IP6 (1.0 mM) and TNF-alpha (100 ng/mL). A decrease of cells adhesion property to collagen I was observed under the influence of 50 ng/mL celecoxib on cell cultures exposed to 1.0 or 2.0 mM IP6 and 1.0 or 2.0 mM IP6 plus 100 ng/mL TNF-alpha.

Inositol hexaphosphate (IP6) is a naturally occurring phytochemical, found in abundance in cereals, legumes and other high-fiber-content diets. IP6 has shown promising efficacy against a wide range of cancers. Its anti-cancer activity involves anti-proliferative, pro-apoptotic and anti-metastatic effects. Both matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), are implicated in tumor growth, metastasis, and angiogenesis. Phorbol-12-myristate 13-acetate (PMA) is a well-known inflammatory stimulator and tumor promoter that activates PKC and increases the invasiveness of various types of cancer cells by activating MMPs. The aim of the present study was to examine the influence of IP6 on the expression of selected MMPs, i.e., MMP-1, -2, -3, -9, 10, -13 and their TIMP-1 and -2 in unstimulated and PMA-stimulated colon cancer cell line Caco-2. Quantification of genes expression in Caco-2 cells treated with 100 ng/mL of PMA, 2.5 mM of IP6 and both for 6 and 12 h was carried out using real time QRT-PCR technique. Stimulation of cells with PMA resulted in an up-expression of MMP-2, MMP-3, MMP-9, MMP-10, MMP-13 and TIMP-1 mRNAs and decrease in MMP-1 gene expression. The quantity of TIMP-2 transcript was reduced by PMA. A significant decrease in MMP-2, MMP-3, MMP-10, MMP-13, and TIMP-1 expression in response to IP6 was observed. IP6 down-regulated MMP-9 transcription induced by PMA and decreased the level of both MMP-2 and MMP-3 mRNAs in PMA-stimulated cells. Caco-2 treated with both PMA and IP6 showed a significant decrease in MMP-1 expression in comparison to PMA-stimulated cells. The results of this study show that PMA can modulate MMP and TIMP genes transcription in colon cancer cells Caco-2. IP6 exerts an influence of basal mRNA expression of some MMPs and their tissue inhibitors and down-regulates MMP-1, MMP-2, MMP-3 and MMP-9 in cells treated with PMA. IP6 could be an effective anti-metastatic agent that suppresses expression of MMP genes at transcription level.

It was found that the yield of thiobarbituric acid reactive substances in UV-irradiated liposome membranes was significantly suppressed in the presence of catecholamine-melanins, indicating their ability to inhibit lipid peroxidation. The extent of inhibition depended on the type and concentration of melanin polymers. Melanin-copper complexes inhibited lecithin photooxidation less effectively than copper-free melanins derived from the same precursor. The antioxidant efficiency of melanins appears to be related to the levels of intrinsic and photo-induced free radical centers in the melanin polymer, as well as to accessibility of these centers for active species formed during irradiation of liposomes.

Arrhythmogenic right ventricular dysplasia (ARVD) is a complex arrhythmogenic cardiomyopathy, characterized by a partial or total replacement of the right ventricular myocytes by fatty and fibrous tissue. In this study, we present a case of ARVD in 17 year old girl, who was admitted to the hospital after syncope with ventricular arrhythmia. The echocardiography did not demonstrate structural cardiac abnormalities but the magnetic resonance recently showed thinning of the right ventricular wall. The girl was treated with the lidocaine, amiodarone and next, after radiofrequency catheter ablation she was receiving metoprolol. The girl has remained asymptomatic for four years of follow-up.

We present a detailed abundance analysis of 23 elements for a newly discovered carbon-enhanced metal-poor (CEMP) star, HE 0414-0343, from the Chemical Abundances of Stars in the Halo (CASH) Project. Its spectroscopic stellar parameters are Teff = 4863 K, log g = 1.25, vmic = 2.20 km/s, and [Fe/H] = -2.24. Radial velocity measurements covering seven years indicate HE 0414-0343 to be a binary. HE 0414-0343 has [C/Fe] = 1.44 and is strongly enhanced in neutron-capture elements but its abundances cannot be reproduced by a solar-type s-process pattern alone. Traditionally, it could be classified as "CEMP-r/s" star. Based on abundance comparisons with AGB star nucleosynthesis models, we suggest a new physically-motivated origin and classification scheme for CEMP-s stars and the still poorly-understood CEMP-r/s. The new scheme describes a continuous transition between these two so-far distinctly treated subgroups: CEMP-sA, CEMP-sB, and CEMP-sC. Possible causes for a continuous transition include the number of thermal pulses the AGB companion underwent, the effect of different AGB star masses on their nucleosynthetic yields, and physics that is not well approximated in 1-D stellar models such as proton ingestion episodes and rotation. Based on a set of detailed AGB models, we suggest the abundance signature of HE 0414-0343 to have arisen from a >1.3 Msun mass AGB star and a late-time mass transfer, that transformed HE 0414-0343 into a CEMP-sC star. We also find the [Y/Ba] ratio well parametrizes the classification and can thus be used to easily classify any future such stars., accepted for publication in ApJ

Interspecies hybrids between distinct species of the genus Xiphophorus are often used in varied research investigations to identify genomic regions associated with the inheritance of complex traits. There are 24 described Xiphophorus species and a greater number of pedigreed strains; thus, the number of potential interspecies hybrid cross combinations is quite large. Previously, select Xiphophorus experimental crosses have been shown to exhibit differing characteristics between parental species and among the hybrid fishes derived from crossing them, such as widely differing susceptibilities to chemical or physical agents. For instance, genomic regions harboring tumor suppressor and oncogenes have been identified via linkage association of these loci with a small set of established genetic markers. The power of this experimental strategy is related to the number of genetic markers available in the Xiphophorus interspecies cross of interest. Thus, we have undertaken the task of expanding the suite of easily scored markers by characterization of Xiphophorus microsatellite sequences. Using a cross between Xiphophorus maculatus and X. andersi, we report a linkage map predominantly composed of microsatellite markers. All 24 acrocentric chromosome sets of Xiphophorus are represented in the assembled linkage map with an average intergenomic distance of 7.5 cM. Since both male and female F1 hybrids were used to produce backcross progeny, these recombination rates were compared between “male” and “female” maps. Although several genomic regions exhibit differences in map length, male- and female-derived maps are similar. Thus Xiphophorus, in contrast to zebrafish, Danio rerio, and several other vertebrate species, does not show sex-specific differences in recombination. The microsatellite markers we report can be easily adapted to any Xiphophorus interspecies and some intraspecies crosses, and thus provide a means to directly compare results derived from independent experiments.

We would like to express our gratitude and appreciation to the authors of the article ‘Genetic background of the left venricular hypertrabeculation/noncompation with stroke’ for fruitful comments of our manuscript.1 We agree with Finsterer et al. that in a single patient ventricular non-compaction is an acquired phenomenon. In our case of a 3-year-old girl with both chambers affected and heart failure, the disorder has not disappeared after treatment. Two-dimensional echocardiograms disclosed numerous prominent trabeculations in both ventricles with deep intertrabecular recesses and thickened endocardium. The echocardiographic images were diagnostic2 of a restrictive filling pattern. Mitral inflow velocities demonstrated a decrease in E/A ratio, consistent with restrictive left ventricular physiology. The left and right atria were enlarged. (LA-20 mm, Ao-14 mm). Left ventricular systolic function was depressed, with an ejection fraction (EF) of 48–50%. During follow-up, the EF of the left ventricle increased to 60–65% and now to 75%. But the ventricular morphology and restrictive filling pattern did …

We present a comprehensive abundance analysis of 20 elements for 16 new low-metallicity stars from the Chemical Abundances of Stars in the Halo (CASH) project. The abundances have been derived from both Hobby-Eberly Telescope High Resolution Spectrograph snapshot spectra (R~15,000) and corresponding high-resolution (R~35,000) Magellan MIKE spectra. The stars span a metallicity range from [Fe/H] from -2.9 to -3.9, including four new stars with [Fe/H]

Melanins synthesized from adrenaline and dopamine in the presence or absence of copper ions were characterized by pyrolysis-gas chromatography-mass spectrometry and by IR and ESR methods. It was shown that Cu2+ are able to induce changes in the melanin structure. Melanins obtained from adrenaline-Cu2+ and dopamine-Cu2+ complexes are composed mainly from monomeric units of the indole type. Melanins synthesized from these catecholamines without Cu2+ contain additionally large amounts of unindolized monomeric units. The structure differences in both types of melanins are reflected in their sorptive abilities and spectroscopic characteristics.

National Optical Astronomy Observatory, Tucson, USAAbstract.Lithium has long been known to be a good tracer of non-standard mixing processesoccurring in stellar interiors. Here we present the results of a large survey aimed at determiningthe surface Li abundance in a sample of about 800 giant (RGB and AGB) stars with accurateHipparcos parallaxes. We compare the observed Li behaviour with that predicted by stellarmodels including rotation and thermohaline mixing.Keywords.Hydrodynamics, instabilities, Stars: abundances, evolution, rotation