Testing quantum electrodynamics in extreme fields using helium-like uranium.

Quantum electrodynamics (QED), the quantum field theory that describes the interaction between light and matter, is commonly regarded as the best-tested quantum theory in modern physics. However, this claim is mostly based on extremely precise studies performed in the domain of relatively low field strengths and light atoms and ions1-6. In the realm of very strong electromagnetic fields such as in the heaviest highly charged ions (with nuclear charge Z ≫ 1), QED calculations enter a qualitatively different, non-perturbative regime. Yet, the corresponding experimental studies are very challenging, and theoretical predictions are only partially tested. Here we present an experiment sensitive to higher-order QED effects and electron-electron interactions in the high-Z regime. This is achieved by using a multi-reference method based on Doppler-tuned X-ray emission from stored relativistic uranium ions with different charge states. The energy of the 1s1/22p3/2 J = 2 → 1s1/22s1/2 J = 1 intrashell transition in the heaviest two-electron ion (U90+) is obtained with an accuracy of 37 ppm. Furthermore, a comparison of uranium ions with different numbers of bound electrons enables us to disentangle and to test separately the one-electron higher-order QED effects and the bound electron-electron interaction terms without the uncertainty related to the nuclear radius. Moreover, our experimental result can discriminate between several state-of-the-art theoretical approaches and provides an important benchmark for calculations in the strong-field domain.

Properties of polycapillary optics dedicated to low-energy parallel-beam wavelength-dispersive spectrometers for synchrotron-based X-ray fluorescence study.

The main advantage of wavelength-dispersive spectrometers applied in X-ray study is their high energy resolution. The design and construction of spectrometer, usually dedicated to the specific experimental systems, for example synchrotron based setups, need information about the characteristics of the main elements of the spectrometer such as X-ray optics elements, crystals and detectors. Such information can be obtained using Monte-Carlo simulations. In this paper, the Monte-Carlo simulations of X-ray tracing in parallel-beam wavelength-dispersive spectrometer (PBWDS), equipped with polycapillary optics, are presented and discussed. The study concentrates on the description of the polycapillary model, simulations of the properties of X-ray polycapillary optics and, finally, on the simulations of X-ray track in the spectrometer designed and installed at the ID21 beamline at the European Synchrotron Radiation Facility (ESRF, Grenoble, France). The results of simulations were compared with experimental data obtained for different registered X-ray energies and spectrometer crystals, showing good agreement. The obtained results showed that the X-ray transmission in the tested polycapillary optics is at the level of 15%, while the divergence of the outgoing beam changes from 8 mrad to 3 mrad with an increase of photon energy from 2 keV to 10 keV. The spectrometer provides an energy resolution of 5 eV and 33 eV in the energy range of 1.4 keV - 6.5 keV. The developed simulation program can be successfully used for the construction of spectrometers dedicated to the different experimental conditions.

Common variants in DLG1 locus are associated with non-syndromic cleft lip with or without cleft palate.

Non-syndromic cleft lip with or without cleft palate (nsCL/P) is a common craniofacial anomaly with a complex and heterogeneous aetiology. Knowledge regarding specific genetic factors underlying this birth defect is still not well understood. Therefore, we conducted an independent replication analysis for the top-associated variants located within the DLG1 locus at chromosome 3q29, which was identified as a novel cleft-susceptibility locus in our genome-wide association study (GWAS). Mega-analysis of the pooled individual data from the GWAS and replication study confirmed that common DLG1 variants are associated with the risk of nsCL/P. Two single nucleotide polymorphisms (SNPs), rs338217 and rs7649443, were statistically significant even at the genome-wide level (Ptrend = 9.70E-10 and Ptrend = 8.96E-09, respectively). Three other SNPs, rs9826379, rs6805920 and rs6583202, reached a suggestive genome-wide significance threshold (Ptrend < 1.00E-05). The location of the strongest individual SNP in the intronic sequence of the gene encoding DLG1 antisense RNA suggests that the true causal variant implicated in the risk of nsCL/P may affect the DLG1 gene expression level rather than structure of the encoded protein. In conclusion, we identified a novel cleft-susceptibility locus at chromosome 3q29 with a DLG1 as a novel candidate gene for this common craniofacial anomaly.

GREM2 nucleotide variants and the risk of tooth agenesis.

OBJECTIVE: The etiology of tooth agenesis (TA) is multifactorial and still not fully understood. The aim of the study was to test whether variants of GREM2, encoding a bone morphogenetic protein (BMP) antagonist, are associated with the risk of this common dental anomaly in a Polish population. SUBJECTS AND METHODS: Direct sequencing of the GREM2 coding sequence including exon/intron boundaries was performed in 95 patients with both hypodontia and oligodontia. All identified GREM2 variants were then further tested in an independent group of patients (n = 163) and controls (n = 184). RESULTS: The previously described, functional GREM2 mutation (c.226C > G, p.Gln76Glu) was identified in two patients with hypodontia and associated dental anomalies, including taurodontism and microdontia. This mutation generating an allele with increased inhibitory activity was not detected in the control group. The second identified GREM2 variant, c.-1-21C > T (rs11806449), was not associated with the risk TA. The polymorphism allele frequency in both patients and controls was 0.21 (OR = 1.0, 95%CI: 0.76-1.46). The rs11806449 did not correlate either with the overall TA phenotype or hypodontia/oligodontia phenotypes. CONCLUSION: Our study confirmed that GREM2 is a candidate gene for tooth agenesis, which mutations can explain, however, only a small fraction of the genetic contribution to the pathogenesis of this anomaly.

Genetic Variants in IL-12B and IL-27 in the Polish Patients with Systemic Lupus Erythematosus.

To investigate the potential association between IL-12B and IL-27 gene polymorphisms and systemic lupus erythematosus (SLE), we performed a case-control study based on the Polish population. Patients with SLE and healthy individuals were examined for -6415 CTCTAA/GC (rs17860508) and +1188A/C (rs3212227) in IL-12B and -924A/G (rs153109) and 4730T/C (rs181206) in IL-27 gene polymorphisms using the high-resolution melting method, PCR-RFLP method and TaqMan SNP genotyping assay, respectively. An increased frequency of GC/GC genotype as well as GC allele of the IL-12B rs17860508 was found in patients with SLE, as compared with healthy subjects (P < 0.001). We did not find differences in genotype and allele frequencies of the IL-12B rs3212227 and IL-27 rs153109 and rs181206 variants between patients with SLE and controls. IL-27 haplotype rs181206C/rs153109G indicated higher risk for SLE (P = 0.002), whereas haplotype rs181206T/rs153109G indicated reduced risk for SLE (P = 0.005). The IL-12B rs3212227 A/C polymorphism was associated with the mean value of the platelets (PLT), urea and complement C3 level. Furthermore, IL-12B rs17860508 genetic variant showed correlation with PLT, prothrombin time, international normalized ratio and alkaline phosphatase. Our results revealed that IL-12B rs17860508 and IL-27 haplotype CG are genetic risk factors for SLE and that both IL-12B rs17860508 and rs3212227 predict disease phenotype.

The genetic background of climacteric symptoms in women during menopause.

The subject of the study is the evaluation of the correlation between the polymorphism of candidate genes in the etiology of depression and the occurrence of the symptoms of the climacteric syndrome in women during menopause. The group subjected to the study comprised of 203 women aged between 42-65 years: 71 of them still menstruated (premenopausal group) and 132 at least one year after the last period (postmenopausal group), admitted to the Department of Gynecological Endocrinology at the University of Medical Sciences in Poznan with symptoms of the climacteric syndrome All the examined women were evaluated according to the degree of severity of the climacteric syndrome symptoms using the Kupperman index and the concentration of FSH, LH hormones, 17ß-estradiol, PRL, total testosterone, and DHEAS in peripheral blood serum. Among the candidate genes in the aetiology of depression the following were selected for the research: the serotonergic system receptor genes: 5HTR2A, 5HTR1B, 5HTR2C, TPH 1, TPH2, and MAO-A; the genes of noradrenergic and dopaminergic systems (COMT, NET), the genes of the GABAergic (GABRBl) system, a gene of the estrogen receptor (ESR1), and the genes of the enzymes crucial in the methyl cycle (MTHRF, MTR, and MTHFD1). With regards to the correlation between the examined polymorphisms and the occurrence of the symptoms of the climacteric syndrome, the associations analysis indicated a connection between GABRBl.TaqI polymorphism and the occurrence of vertigo in premenopausal women (0.0198; after correction: 0.0497 CC to CA). The correlation was also found regarding the examined polymorphisms and the concentration of the examined hormones in blood serum: TPH1.MaeI polymorphism and the LH concentration in the postmenopausal group (0.004; after correction: 0.014 CC to CA), NET.Eco1471 polymorphism, and the 17ß-estradiol concentration in the postmenopausal group (0.0208; after correction: 0.048 GG to GA) and HTR2AMspI polymorphism and PRL concentration in all examined women (0.03; after correction: 0.038 TT to CT).

JHDM1D and HDAC1-3 mRNA expression levels in peripheral blood mononuclear cells of patients with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic relapsing autoimmune disease characterized by production of autoantibodies against a series of nuclear antigens and by chronic inflammation. The etiology of SLE is the result of interactions between genetic, epigenetic, hormonal, and environmental factors. Changes in histone acetylation and methylation contribute to structural chromatin modifications. OBJECTIVE: We studied the histone demethylase JHDM1D and histone deacetylases HDAC1, HDAC2, and HDAC3 transcript levels in peripheral blood mononuclear cells (PBMCs) from patients diagnosed with systemic lupus erythematosus (SLE). Furthermore, the association of JHDM1D, HDAC1, HDAC2, and HDAC3 transcript levels with gender, age, and major clinical manifestations were analyzed. MATERIALS AND METHODS: Real-time quantitative polymerase chain reaction (RQ-PCR) analysis was used to determine JHDM1D, HDAC1, HDAC2, and HDAC3 mRNA expression levels in peripheral blood mononuclear cells (PBMCs) from 30 patients with SLE and 36 healthy controls. RESULTS: Significantly lower HDAC2 transcript levels (p = 0.006785) and significantly higher JHDM1D (p = 0.0000002) and HDAC1 (p = 0.010581) transcript levels in SLE patients were observed compared with healthy controls. Higher JHDM1D mRNA expression was detected in active SLE patients when compared with inactive patients (p = 0.005). Furthermore, the JHDM1D transcript levels were positively correlated with disease activity (r(s) = 0.368, p = 0.045), while HDAC2 mRNA expression was positively correlated with disease duration (r(s) = 0.502, p = 0.0047). CONCLUSION: Our analyses confirmed the importance of epigenetic alterations (histone demethylation and acetylation) in SLE etiology. Moreover, our results suggest that the presence of some clinical manifestations, like hematological disease and anti-Ro antibody, might be associated with the dysregulation of histone demethylase and deacetylases mRNA expression levels.

Variations in the interferon and TLR3 genes may be associated with susceptibility to systemic lupus erythematosus and its clinical presentation.

The study aimed to explore the pontential impact of 10 polymorphisms within IFN-α, IFN-ß1, IFN-γ and TLR3 genes on SLE phenotype and susceptibility and to study the relationship between specific genotypes and clinics. Whole blood samples from SLE patients and healthy controls was obtained. DNA was extracted from the peripheral blood by the QIAamp DNA Blood Mini Kit (Qiagen). The quality and quantity of isolated DNA was estimated by the Quawell Q5000 spectrophotometer. We genotyped SLE patients and healthy subjects using real-time PCR (QuantStudio 5 thermocycler). The study suggests that IFN-γ rs2069705, IFN-γ rs2069718 and IFN-α rs3758236 polymorphisms have a protective role in SLE. We observed relations between TLR3 rs3775292, IFN-ß1 rs7873167, IFN-γ rs2069705, TLR3 rs3775291 and TLR3 rs5743305 polymorphisms and clinical picture of SLE patients. We found associations between the IFN-α rs3758236, IFN-γ rs2069705, IFN-γ rs2069718, IFN-γ rs1861493 and IFN-ß1 rs10964831 polymorphisms and the clinical manifestation of the SLE and/or its comorbidities. We perceived links between IFN-γ rs2069705, IFN-γ rs2069718, IFN-γ rs1861493, TLR3 rs3775291, TLR3 rs3775292 and TLR3 rs5743305 polymorphisms and the occurrence of autoantibodies. Our study presented the relationship between IFN and TLR gene polymorphisms with SLE susceptibility, phenotype and autoantibodies profile. This study propose that polymorphisms within interferons and TLR3 genes can be engaged in the SLE pathogenesis and course.

Nucleotide variants of genes encoding components of the Wnt signalling pathway and the risk of non-syndromic tooth agenesis.

Tooth agenesis is one of the most common dental anomalies, with a complex and not yet fully elucidated aetiology. Given the crucial role of the Wnt signalling pathway during tooth development, the purpose of this study was to determine whether nucleotide variants of genes encoding components of this signalling pathway might be associated with hypodontia and oligodontia in the Polish population. A set of 34 single nucleotide polymorphism (SNPs) in 13 WNT and WNT-related genes were analyzed in a group of 157 patients with tooth agenesis and a properly matched control group (n = 430). In addition, direct sequencing was performed to detect mutations in the MSX1, PAX9 and WNT10A genes. Both single-marker and haplotype analyses showed highly significant association between SNPs in the WNT10A gene and the risk for tooth agenesis. Moreover, nine pathogenic mutations within the coding region of the WNT10A gene were identified in 26 out of 42 (62%) tested patients. One novel heterozygous mutation was identified in the PAX9 gene. Borderline association with the risk of non-syndromic tooth agenesis was also observed for the APC, CTNNB1, DVL2 and WNT11 polymorphisms. In conclusion, nucleotide variants of genes encoding important components of the Wnt signalling pathway might influence the risk of tooth agenesis.

Single nucleotide polymorphism of CD40 region and the risk of systemic lupus erythematosus.

There is one study on the association of the CD40 G > T (rs4810485) single nucleotide polymorphism (SNP) as a risk factor of systemic lupus erythematosus (SLE). Therefore, we studied the prevalence of the CD40 G > T SNP in patients with SLE (n = 261) and controls (n = 545) in a Polish population. We did not find significant differences between the CD40 G > T genotype and allele frequency in patients with SLE and healthy individuals. However, the frequency of the CD40 TT and GT genotypes was statistically different between patients with arthritis and neurologic manifestations and patients without these symptoms (OR = 0.2009 (95% CI = 0.07547-0.5348, p = 0.0004, p (corr) = 0.0068) and OR = 0.2876 (95% CI = 0.1371-0.6031, p = 0.0005, p (corr) = 0.0085) respectively). Our observations indicate that the CD40 T variant might be negatively associated with some clinical disease manifestations in patients with SLE.

Hymenolepis diminuta: analysis of the expression of Toll-like receptor genes (TLR2 and TLR4) in the small and large intestines of rats. Part II.

Toll-like receptors in the gastrointestinal tract can influence intestinal homeostasis and play a role in the repair and restitution of intestinal epithelium following tissue damage. In our previous study a statistically significant increase in the level of TLR4 and TLR2 gene expression was observed in rats in early stages of hymenolepidosis. Moreover, the immunopositive cell number and the intensity of immunohistochemical staining (indicating the presence of TLRs within intestinal epithelial cells) increased over the infection period. In this paper, we determined changes in the expression of TLR2 and TLR4 and the number of anaerobic intestinal commensal bacteria in Hymenolepis diminuta infected rats. In the isolated jejunum of infected rats at 16 days post infection (dpi), the expression of TLR4 and TLR2 was significantly higher than uninfected rats. In the colon, a statistically significantly increased expression of TLR2 was observed from 16 to 40 dpi, and TLR4 from 16 to 60 dpi. The jejunum and colon of infected rats contained Gram-negative bacteria (Escherichia coli), Gram-positive bacteria (Enterococcus, Streptococcus, Staphylococcus, Bacillus, Lactobacillus) and Candida. The total number of intestinal bacteria was higher in H. diminuta infected rats, but the observed microbiota had only minor effects on the expression of TLR2 and TLR4. Toll-like receptors play a role in maintaining epithelial barrier function in response to enteric pathogens and parasites. In our study, the alteration of TLR2 and TLR4 expression in the infected rats indicates the potential role of the innate immune system in the pathomechanism of this infection.

Hymenolepis diminuta: analysis of the expression of Toll-like receptor genes (TLR2 and TLR4) in the small and large intestines of rats.

Toll receptors play a critical role in the rapid activation of innate immune responses to a variety of pathogens. In mammals, Toll-like receptors (TLR) have been found in both immune related cells and other cells. At present little is known about the participation of TLR in host defense mechanisms during parasitic infections. The aim of this study was to determine the expression of TLR2 and TLR4 genes in rat intestines during experimental hymenolepidosis. There is difference in expression of TLR2 and TLR4 genes in the colon and jejunum in uninfected rats: in the colon, mRNA of the examined TLR is present in much higher amounts than the jejunum, while the protein of the TLR also had a segmented specific distribution. In the jejunum isolated rats infected with Hymeolepis diminuta 6 and 8 days post infection (dpi), mRNA for TLR4 and TLR2 were significantly more strongly expressed in comparison with the uninfected controls. In the colon, a statistically significantly increased expression of TLR4 gene was observed only at 6 dpi, and at 8 dpi for the TLR2 gene. Moreover, we observed that during inflammation, the immunopositive cell number and the intensity of immunohistochemical staining (indicating the presence of TLR within intestinal epithelial cells), increased together with the duration of the infection period.

The c.1460C>T polymorphism of MAO-A is associated with the risk of depression in postmenopausal women.

OBJECTIVE: The aim of the study was an evaluation of possible relationships between polymorphisms of serotoninergic system genes and the risk of depression in postmenopausal women. METHODS: We studied 332 women admitted to our department because of climacteric symptoms. The study group included 113 women with a diagnosis of depressive disorder according to the Hamilton rating scale for depression; the controls consisted of 219 women without depression. Serum 17ß-estradiol concentrations were evaluated using radioimmunoassay, while polymorphisms in serotoninergic system genes: serotonin receptors 2A (HTR2A), 1B (HTR1B), and 2C (HTR2C); tryptophan hydroxylase 1 (TPH1) and 2 (TPH2), and monoamine oxidase A (MAO-A) were evaluated using polymerase chain reaction-restriction. RESULTS: We found that the 1460T allele of MAO-A c.1460C>T (SNP 1137070) appeared with a significantly higher frequency in depressed female patients than in the control group (P = 0.011) and the combined c.1460CT + TT genotypes were associated with a higher risk of depression (P = 0.0198). Patients with the 1460TT genotype had a significantly higher 17ß-estradiol concentration than patients with the 1460CT genotype (P = 0.0065) and 1460CC genotype (P = 0.0018). CONCLUSIONS: We concluded that depression in postmenopausal women is closely related to the genetic contribution of MAO-A.

First observation of two-electron one-photon transitions in single-photon K-shell double ionization.

Experimental evidence for the correlated two-electron one-photon transitions (1s(-2)→2s(-1)2p(-1)) following single-photon K-shell double ionization is reported. The double K-shell vacancy states in solid Mg, Al, and Si were produced by means of monochromatized synchrotron radiation, and the two-electron one-photon radiative transitions were observed by using a wavelength dispersive spectrometer. The two-electron one-photon transition energies and the branching ratios of the radiative one-electron to two-electron transitions were determined and compared to available perturbation theory predictions and configuration interaction calculations.

Differential association of juvenile and adult systemic lupus erythematosus with genetic variants of oestrogen receptors alpha and beta.

Oestrogens acting via nuclear receptors (encoded by ESR1 or ESR2) are important for pathogenesis of systemic lupus erythematosus (SLE). rs2234693 and rs4986938 are two single nucleotide polymorphisms (SNPs) whose C and A variants increase transcription of ESR1 and ESR2, respectively. The T allele of rs2234693 was associated with early onset SLE, whereas the role of rs4986938 in SLE was not reported. Our aim was to examine the role of rs2234693 and rs4986938 in conferring susceptibility to juvenile and adult SLE (jSLE and aSLE). Genotype distribution of both SNPs was analysed in 84 jSLE, 112 aSLE patients and 1001 controls. Allele C of rs2234693 was associated with jSLE (OR = 1.87, p = 0.006, p(corrected) = 0.02), whereas allele A of rs4986938 showed an association with aSLE (OR = 1.46, p = 0.008, p(corrected) = 0.03). In jSLE, rs2234693 C had lower frequency in patients with central nervous system involvement (OR = 0.39, p = 0.005, p(corrected) = 0.04) and showed a trend for increase among males, patients with renal involvement and those without DR2/3 (p < 0.05, p(corrected) > 0.05). Whereas our results are consistent with a role of ESR1 variation in jSLE, more studies are needed since the direction of association was the opposite of that reported previously. The association between rs4986938 (ESR2) and aSLE is a novel finding, consistent with our recent report associating this variant with Graves' disease.

Interleukin-18 promoter polymorphisms in patients with systemic lupus erythematosus.

OBJECTIVES: The role of various polymorphisms located in the IL-18 promoter has not yet been defined with regards to patient susceptibility to SLE, and occurrence of clinical manifestations of the disease remains inconsistent. METHODS: Using PCR-RFLP and DNA sequencing analysis we studied the frequency of -137 G/C (rs187238), -607 C/A (rs1946518) and -1297C/T (rs360719) polymorphisms in IL-18 promoter in patients with SLE from a sample of the Polish population. RESULTS: We observed that patients with SLE bearing the IL-18 -1297CC genotype exhibited a 2.536-fold increased risk of SLE incidence (95% CI=1.333-4.826, p=0.0035). We also found a significantly higher frequency of the IL-18 -1297C allele in patients than in controls, with odds ratio (OR) for the IL-18 -1297C allele in patients with SLE being 1.558 (95% CI=1.189-2.041, p=0.0013). Moreover, there was an association between the IL-18 -1297CC genotype and renal manifestations of SLE, OR=3.792 (1.446-9.947, p=0.0051). However, we did not find any contribution of the IL-18 -607 C/A and -137 G/C polymorphisms to SLE incidence or occurrence of the studied SLE manifestations. CONCLUSIONS: Our findings confirmed that the IL-18 -1297C gene variant may contribute to the risk of SLE incidence. Moreover, IL-18 -1297CC might be associated with renal manifestations of SLE.

Wavelength-dispersive spectrometer for X-ray microfluorescence analysis at the X-ray Microscopy beamline ID21 (ESRF).

The development of a wavelength-dispersive spectrometer for microfluorescence analysis at the X-ray Microscopy ID21 beamline of the European Synchrotron Radiation Facility (ESRF) is reported. The spectrometer is based on a polycapillary optic for X-ray fluorescence collection and is operated in a flat-crystal geometry. The design considerations as well as operation characteristics of the spectrometer are presented. The achieved performances, in particular the energy resolution, are compared with the results of Monte Carlo simulations. Further improvement in the energy resolution, down to approximately eV range, by employing a double-crystal geometry is examined. Finally, examples of applications requiring both spatial and spectral resolutions are presented.

CD24 Ala57Val gene polymorphism and the risk of systemic lupus erythematosus.

It was recently shown that the CD24 Ala57Val (rs 52812045) polymorphism plays a significant role in susceptibility to systemic lupus erythematosus (SLE) in a Spanish population, which has not been confirmed in other ethnic groups. We investigated the distribution of the CD24 Ala57Val polymorphism in patients with SLE (n = 250) and controls (n = 350) in Poland. The odds ratio (OR) for patients with SLE with the Ala/Val genotype compared with Ala/Ala genotype was 1.490 [95% confidence interval (CI) = 1.052-2.111, P = 0.0275], and OR for the Val/Val genotype compared with Ala/Ala genotypes was 2.001 (95% CI = 1.154-3.467, P = 0.0154). Moreover, we observed a significant association between the CD24 Val allele and the presence of anti-Scl-70 antibody (Ab) OR = 2.155 (1.438-3.229, P = 0.0002). There was also an association of Val allele with the presence of anti-snRNP Ab OR = 1.984 (1.266-3.110, P = 0.0034) in patients with SLE. We also found that the CD24 Val/Val and Ala/Val genotypes contribute to immunologic manifestations OR = 2.244 (1.323-3.806, P = 0.0037). Our observations indicate that the CD24 Ala57Val polymorphism may predispose to SLE incidence and can be linked to immunologic manifestations and production of autoantibodies in this disease.

Spectral shape of the two-photon decay of the 2 1S0 state in he-like tin.

The spectral distribution of the 1s2s {1}S{0}-->1s{2} 1S0 two-photon decay of He-like tin was measured using a novel approach at the gas-jet target of the ESR storage ring. Relativistic collisions of Li-like projectiles with low-density gaseous matter have been exploited to selectively populate the desired 1s2s state. Compared to conventional techniques, this approach results in a substantial gain in statistical and systematic accuracy, which allowed us to achieve for the first time a sensitivity to relativistic effects on the two-photon decay spectral shape as well as to discriminate the measured spectrum for Sn from theoretical shapes for different elements along the He-isoelectronic sequence.

Butyrate increases the formation of anti-angiogenic vascular endothelial growth factor variants in human lung microvascular endothelial cells.

The primary transcript of vascular endothelial growth factor (VEGF) can be alternatively spliced and translated to pro-angiogenic and anti-angiogenic VEGF variants. We investigated the effect of sodium butyrate (NaB) on pro-angiogenic and anti-angiogenic VEGF variants production in immortalized human lung microvascular endothelial cells (HLMEC). These cells were cultured in the absence or in the presence of NaB, followed by total RNA and protein isolation. The transcript and protein levels of pro-angiogenic and anti-angiogenic VEGF variants were evaluated by reverse transcription, real-time quantitative PCR and western blot analysis. We found that NaB significantly increased the anti-angiogenic transcript and protein levels of the VEGF 121b, VEGF165b and VEGF189b variants in HLMEC cells. We did not find the pro-angiogenic VEGF189a transcript variant either in control or NaB treated cells. By contrast, the pro-angiogenic VEGF121a and VEGF165a transcript variants were present in HLMEC cells, but their levels were slightly modulated in the cells treated with NaB compared to controls. Since anti-angiogenic VEGF variants inhibit angiogenesis and tumour progression, and NaB is considered an anticancer drug, our findings may have clinical significance.