Deletion of one SERCA2 allele confers protection against bladder wall hypertrophy in a murine model of partial bladder outlet obstruction

The sarco(endo)plasmic reticulum Ca(2+)-ATPase2 (SERCA2) is downregulated in cardiac hypertrophy with decompensation. We sought to determine whether mice heterozygous for the SERCA2 allele would develop greater bladder hypertrophy and decompensation than their wild-type littermates following partial bladder outlet obstruction (pBOO). We found that following 4 wk of surgically created pBOO, SERCA2 heterozygous murine bladders showed significantly less hypertrophy, improved in vitro cystometry performance, diminished expression of the slow myosin isoform A analyzed by RT-PCR, a significant drop in nuclear translocation of nuclear factor of activated T cells by EMSA, and decreased cell proliferation within the smooth muscle layer following 5-bromo-2'-deoxyuridine labeling compared with their wild-type littermates. Thus, in contrast to cardiac muscle, deletion of a SERCA2 allele confers protection against bladder hypertrophy in a murine model of pBOO. Compensatory mechanisms in heterozygous mice seem to be related to the calcineurin pathway. Further studies are underway to better define the molecular basis of this observation, which has potential clinical applications.     

Association of p53 Arg72Pro polymorphism with bladder cancer: A meta-analysis

Background

p53 tumor suppressor gene Arg72Pro polymorphism has been associated with bladder cancer. However, results were inconsistent. We performed this meta-analysis to estimate the association between p53 Arg72Pro polymorphism and bladder cancer.

Methods

Electronic search of PubMed was conducted to select studies. Studies containing available genotype frequencies of Arg72Pro were chosen, and pooled odds ratio (OR) with 95% confidence interval (CI) was used to assess the association.

Results

The final meta-analysis included 14 published studies with 2176 bladder cancer cases and 2798 controls. The results suggested that the variant genotype was associated with the bladder cancer risk (additive model: OR = 1.72, 95% CI: 1.036–1.325, P = 0.011; dominant model: OR = 1.268, 95% CI: 1.003–1.602, P = 0.047) in Asian subgroup. However, the association was not significant between this polymorphism and bladder cancer risk in Caucasian (additive model: OR = 0.773, 95% CI: 0.564–1.059, P = 0.109; dominant model: OR = 0.685, 95% CI: 0.418–1.124, P = 0.134).

Conclusion

This meta-analysis suggests that p53 Arg72Pro polymorphism is associated with increased risk of bladder cancer in Asians. To validate the association between this polymorphism and bladder cancer, further studies with larger participants worldwide are needed.     

E-cadherin gene promoter hypermethylation may contribute to the risk of bladder cancer among Asian populations

There are increasing scientific evidences suggesting that E-cadherin gene promoter hypermethylation may contribute to the development and progression of bladder cancer, but existing studies have yielded inconclusive results. This meta-analysis aims to assess the role of E-cadherin promoter hypermethylation in bladder carcinogenesis. We conducted an extensive literature search for relevant studies on PubMed, Embase, Web of Science, Cochrane Library, and CBM databases from their inception through May 1st, 2013. This meta-analysis was performed using the STATA 12.0 software. Crude risk ratio (RR) with 95% confidence interval (CI) was calculated. Ten clinical studies were included in this meta-analysis with a total of 620 bladder cancer samples, 199 normal adjacent samples and 131 normal urothelium tissue. Our meta-analysis revealed that the methylation frequencies in bladder cancer tissues were obviously higher than those in normal control tissues (RR = 2.02, 95%CI: 1.00–4.12, P = 0.050). Subgroup analysis by ethnicity indicated that higher methylation frequencies were observed in bladder cancer tissues among Asian populations (RR = 2.35, 95%CI: 1.11–4.95, P = 0.025), but not among Caucasian populations (RR = 1.62, 95%CI: 0.48–5.53, P = 0.439). Univariate and multivariate meta-regression analyses showed that ethnicity may be the major source of heterogeneity (P < 0.05). No publication bias was detected in this meta-analysis (P = 0.358). The present meta-analysis indicates that E-cadherin gene promoter hypermethylation may contribute to increased risk of bladder cancer among Asian populations.     

GnRH treatment at artificial insemination in beef cattle fails to increase plasma progesterone concentrations or pregnancy rates

Treatment with GnRH at the onset of standing estrus increased pregnancy percentages and circulating concentrations of progesterone in repeat breeder dairy cows. The objective of this study was to determine the effect of treatment with GnRH at AI on concentrations of progesterone and conception rates in beef cattle that exhibited estrus. Two hundred ninety-three heifers at four locations were synchronized with the Select Synch plus CIDR protocol (given GnRH and a CIDR was placed into the vagina, and 7 d later, given PGF_2α and CIDR removed; n = 253) or the 14-19 melengestrol acetate (MGA) protocol (MGA fed at 0.5 mg/head/d for 14 d, with PGF_2α 19 d after MGA withdrawal n = 40) and AI was done after detection of estrus. At Location 1, blood samples were collected on Day 2, 4, 6, 10, 15, and 18 after AI (Day 0 = AI). Two hundred and fifty postpartum cows at two locations were synchronized with the Select Synch plus CIDR protocol, and AI was performed after detection of estrus. At AI, cattle were alternately assigned to one of two treatments: (1) treatment with GnRH (100 μg) at AI (n = 127 heifers and n = 108 cows); or (2) non-treated control (n = 120 heifers and n = 119 cows). Concentrations of progesterone tended to be greater in control heifers compared to GnRH-treated heifers on Days 6 (P = 0.08), 10 (P = 0.07), and 15 (P = 0.11). Overall conception rates were 68% and 66% for GnRH treated and control, respectively, and were not different between treatments (P = 0.72). In summary, treatment with GnRH at time of AI had no influence on conception rates in cattle that had exhibited estrus.     

Association of XRCC1 Arg399Gln polymorphism with bladder cancer susceptibility: A meta-analysis

Genetic variations in DNA repair genes are thought to modify DNA repair capacity and may to be related to cancer susceptibility. However, epidemiological study results have been inconsistent. In this meta-analysis, we assessed 24 case–control studies of association between the X-ray repair cross complementing group 1 (XRCC1) Arg399Gln polymorphism and bladder cancer susceptibility in the general population and in Asian and non-Asian subgroups. A moderately significant association with bladder cancer risk was found for AG vs GG (OR = 1.110, 95% CI = 1.018–1.210). No significant associations with bladder cancer risk were found for AA vs GG (OR = 0.942, 95% CI = 0.823–1.077), the dominant model AA/AG vs GG (OR = 1.075, 95% CI = 0.990–1.167) and the recessive model AA vs AG/GG(OR = 0.890, 95% CI = 0.788–1.005). In subgroup analysis, a moderately significant association was also found for AG vs GG (OR = 1.091, 95% CI = 1.008–1.180) in non-Asian subgroup. The analysis suggests that the XRCC1 Arg399Gln polymorphism might be a moderate risk factor for bladder cancer, especially in non-Asian population.     

Impairment of ATP hydrolysis decreases adenosine A1 receptor tonus favoring cholinergic nerve hyperactivity in the obstructed human urinary bladder

This study was designed to investigate whether reduced adenosine formation linked to deficits in extracellular ATP hydrolysis by NTPDases contributes to detrusor neuromodulatory changes associated with bladder outlet obstruction in men with benign prostatic hyperplasia (BPH). The kinetics of ATP catabolism and adenosine formation as well as the role of P1 receptor agonists on muscle tension and nerve-evoked [³H]ACh release were evaluated in mucosal-denuded detrusor strips from BPH patients (n = 31) and control organ donors (n = 23). The neurogenic release of ATP and [³H]ACh was higher (P < 0.05) in detrusor strips from BPH patients. The extracellular hydrolysis of ATP and, subsequent, adenosine formation was slower (t_1/2 73 vs. 36 min, P < 0.05) in BPH detrusor strips. The A₁ receptor-mediated inhibition of evoked [³H]ACh release by adenosine (100 μM), NECA (1 μM), and R-PIA (0.3 μM) was enhanced in BPH bladders. Relaxation of detrusor contractions induced by acetylcholine required 30-fold higher concentrations of adenosine. Despite VAChT-positive cholinergic nerves exhibiting higher A₁ immunoreactivity in BPH bladders, the endogenous adenosine tonus revealed by adenosine deaminase is missing. Restoration of A₁ inhibition was achieved by favoring (1) ATP hydrolysis with apyrase (2 U mL⁻¹) or (2) extracellular adenosine accumulation with dipyridamole or EHNA, as these drugs inhibit adenosine uptake and deamination, respectively. In conclusion, reduced ATP hydrolysis leads to deficient adenosine formation and A₁ receptor-mediated inhibition of cholinergic nerve activity in the obstructed human bladder. Thus, we propose that pharmacological manipulation of endogenous adenosine levels and/or A₁ receptor activation might be useful to control bladder overactivity in BPH patients.     

Synthesis, structures, electrochemistry and properties of dioxo-molybdenum(VI) and -tungsten(VI) complexes with novel asymmetric N2OS, and partially symmetric N2S2, NOS2N-capped tripodal ligands

A new class of asymmetric N-capped (dianionic/trianionic) tripodal proligands [H_x(Lⁿ)] (x = 2, n = 1-6; x = 3, n = 7, 8) which possess pendant arms with N₂OS, N₂S₂ or NOS₂ donor groups and with different chelate ring sizes {5,5,5} or {5,6,5} has been prepared. Treatment of these ligands with [WO₂Cl₂(dme)] (dme = 1,2-dimethoxyethane) in the presence of base (triethylamine or KOH) leads to the formation of cis-dioxotungsten(VI) complexes of the types [WO₂(Lⁿ)] (n = 1-6) and K[WO₂(Lⁿ)] (n = 7, 8). Reaction of these tetradentate ligands with [MoO₂(acac)₂] (acac = acetylacetonate) gives the corresponding Mo(VI) analogues [MoO₂(Lⁿ)] (n = 1-6) and K[MoO₂(Lⁿ)] (n = 7, 8). Moreover, a new five coordinate dioxomolybdenum(VI) complex with an NS₂ tridentate ligand [MoO₂(L⁹)] has been synthesised using similar procedure. All these compounds have been spectroscopically characterised and the molecular structures of [MoO₂(Lⁿ)] (n = 2, 6) and [WO₂(L⁶)] have been established by X-ray diffraction analysis. The electrochemistry and the catalytic activity for oxidation of allylic and benzylic alcohols of these dioxo complexes have also been investigated.     

Water relations of the epidermal bladder cells ofOxalis carnosa Molina

All of the cells of the upper (adaxial) epidermis of the leaves ofOxalis carnosa are transformed into large bladders, while in the lower epidermis the bladder cells are interrupted by “normal” cells with stomata. The epidermal bladders contain a high concentration of free oxalic acid (pH approx. 1). Water-relations parameters of these epidermal bladder cells have been determined using the pressure probe. Original cell turgor (P₀) of the closely packed bladders of theupper epidermis was P₀=0.7 to 2.9 bar ( \(\overline {P_0 } = 1.7 \pm 0.5 bar\) ; mean±SD;N=25 cells) and lower than that in the club-shaped bladders of thelower epidermis (P₀=1.3 to 3.7 bar; \(\overline {P_0 } = 2.5 \pm 0.7 bar\) ;N=25 cells). Large differences in the elastic modulus (ε) and the hydraulic conductivity (Lp) of the two different types of cells were observed. For the lower epidermal bladders, ε=18 to 166 bar and was similar to that of other higher plant cells. Also, for these cells it was found that ε was increasing with both, cell turgor and cell volume. By contrast, ε of the cells of the upper epidermis was by one order of magnitude smaller (ε=1.9 to 17.0 bar) and no dependence of ε on cell volume could be detected. The Lp values of the cell membranes were also different (lower epidermis: \(\overline {Lp} = (2.3 \pm 1.6) \cdot 10^{ - 5} cm s^{ - 1} bar^{ - 1}\) ; upper epidermis: \(\overline {Lp} = (3.8 \pm 2.4) \cdot 10^{ - 6} cm s^{ - 1} bar^{ - 1}\) ). These differences seem to be too large to be caused by errors in determining the exchange area for water (A) between cells and adjacent tissue. The half-times of water exchange between bladders and leaf (T_1/2) were, on average, somewhat longer for the upper than for the lower epidermis (lower epidermis: T_1/2=7 to 38 s; upper epidermis: T_1/2=22 to 213 s), but the differences in the T_1/2 values were not as distinct as for ε and Lp. This is because of the compensatory effects of ε, Lp and the different ratios of volume to exchange area. Since the bladders make up about 75% of the entire volume of the leaf, it is assumed that the rate of response of the leaf to changes in the water potential should be similar to that of the bladder cells. The results are discussed in terms of a possible function of the bladders in the leaf.     

Magic angle spinning NMR spectroscopic metabolic profiling of gall bladder tissues for differentiating malignant from benign disease

Gall bladder tissue specimens obtained from 112 patients were examined by high resolution magic angle spinning (HR-MAS) NMR spectroscopy. Fifty one metabolites were identified by combination of one and two-dimensional NMR spectra. To our knowledge, this is the first report on metabolic profiling of gall bladder tissues using HR-MAS NMR spectroscopy. Metabolic profiles were evaluated for differentiation between benign Chronic Cholecystitis (CC, n = 66) and xantho-granulomatous cholecystitis (XGC, n = 21) and malignant gall bladder cancer (GBC, n = 25). Increase in choline containing compounds, amino acids, taurine, nucleotides and lactate as common metabolites were observed in malignant tissues whereas lipid content was found low as compared to benign tissues. Principal component analysis obtained from the NMR data showed clear distinction between CC and GBC tissue specimens; however, 27 % of XGC tissues were classified with GBC. The partial least square discriminant analysis (PLS-DA) multivariate analysis between benign (CC, XGC) and malignant (GBC) on the training data set (CC; n = 51, XGC; n = 15, GBC; n = 19 tissues specimens) provided 100 % sensitivity and 94.12 % specificity. This PLS-DA model when executed on the spectra of unknown tissue specimens (CC; n = 15, XGC; n = 6, GBC; n = 6) classified them into the three histological categories with more than 95 % of diagnostic accuracy. Non-invasive in vivo MRS technique may be used in future to differentiate between benign (CC and XGC) and malignant (GBC) gall bladder diseases.     

Ionic metallomesogens derived from silver(I) bis-amine complexes: Structure and mesogenic behavior

Complexes [Ag(NH₂R)₂]X, (X = NO₃, R = -C₆H₄-C_nH_2n+1-p, -C₆H₄-O-C_nH_2n+1-p, -CH₂-C₆H₄-O-C_nH_2n+1-p, n = 6, 8, 10, 12, 14; X = BF₄, R = -CH₂-C₆H₄-O-C_nH_2n+1-p, n = 6, 8, 10, 12, 14; X = OAc, R = -CH₂-C₆H₄-O-C₁₀H₂₁-p; X = CF₃SO₃, R = -CH₂-C₆H₄-O-C₁₀H₂₁-p) have been prepared. They all show S_A mesophases corresponding to two kinds of structures, already present in the solid state. The alkylaniline and alkoxyaniline derivatives adopt a bilayered structure where the cation has an extended centrosymmetric conformation. The benzylamine derivatives contain U-shaped cations giving rise to a bilayered structure which allows microsegregation of the organic part of the molecule from the inorganic Ag?(anion) part. Some degree of interdigitation of the terminal chains is observed for all the complexes with aryl containing ligands.     

Pregnancy rates in heifers and cows with cryopreserved sexed sperm: Effects of sperm numbers per inseminate, sorting pressure and sperm storage before sorting

Field trials were conducted to increase fertility with AI of flow-sorted, sexed bovine sperm. In the first trial, a novel competitive fertilization approach was used to compare pressures (30 psi vs 50 psi) for sorting sperm. Both X- and Y-sperm were sorted to approximately 95% purity at 30 and at 50 psi; X-50 + Y-30 (and the converse) were mixed in equal numbers for AI of heifers. Fetal sex divulged which treatment produced the pregnancy; 82% of pregnancies resulted from the 30 psi treatment (P < 0.05). Based on a similar approach, a new-pulsed laser did not damage sperm any more than the previous standard continuous wave laser. In a large field trial, sorting sperm at 40 psi increased pregnancy rates in heifers relative to 50 psi (42.3% vs 34.1%, n = 367/group, P < 0.05). Storing sperm for 20 h before sorting at 40 psi decreased pregnancy rates from 42.3% (n = 367) to 36.8% (n = 368; P < 0.05). Breeding heifers with sexed sperm 55-56 h after CIDR removal and PGF_2α resulted in 34% (n = 32) pregnant, compared to 49% (n = 35) with fixed-time insemination 67-68 h after CIDR removal (P > 0.1). Lactating dairy cows pre-screened for normal reproductive tracts when OvSynch injections (GnRH, prostaglandin, GnRH) were initiated, had similar (P > 0.1) pregnancy rates to timed AI, with 10 × 10⁶ sexed sperm (43.9%, n = 57), 2 × 10⁶ sexed sperm (40.5%, n = 57) and 10 × 10⁶ unsexed control sperm (55.6%, n = 58). A final field trial with unselected, lactating dairy cows resulted in similar pregnancy rates for 2 × 10⁶ sexed sperm in 0.25 mL straws (25.0%, n = 708) and 0.5 mL straws (24.4%, n = 776), but lower (P < 0.05) than unsexed control sperm (37.7%, n = 713). Younger cows and those >84 days in milk had the highest pregnancy rates for both sexed and unsexed sperm. These studies improved sperm sexing procedures, and provided insight into appropriate commercial use of sexed sperm.     

Structure and luminescence of copper(I) cyanide-amine and -sulfide networks

Copper(I) cyanide reacts with various liquid amines and sulfides (L) under solvent-less conditions to form (CuCN)L_n, n = 0.5, 0.57, 0.75, 0.8, 1, 1.25, 1.5, 2. New X-ray structures are reported for L = Py (Py = pyridine, n = 0.57), 2-MePy (n = 1), 3-EtPy (n = 1.5), 2-ClPy (n = 1), 3-ClPy (n = 2), 3-MeOPy (n = 2), 4-^tBuPy (n = 1.5), piperidine (n = 1.25), N-methylmorpholine (n = 1), N,N-dimethylcyclohexylamine (n = 1), 1-methylimidazole (n = 3), Me₂S (n = 1), and tetrahydrothiophene (n = 1). The amine structures (except for the monomeric 1-methylimidazole complex) reveal 1D CuCN chains decorated with 0-2 L per metal atom. Chain structures observed include zigzag, helical and figure-8 helical. The CuCN-sulfide structures show sulfur-bridging of CuCN chains. In some cases (CuCN)L_?1.5 species are transformed to (CuCN)L under vacuum. Thermal analysis shows facile release of ligand, yielding CuCN. Most of the (CuCN)L_n products are photoluminescent, emitting in the visible region. In some cases, coordination of very similar amines results in remarkably different emission spectra.     

Nitrilotris(methylenephosphonates) in aqueous solution and solid state - dilatometric, potentiometric and NMR investigations

Dissociation and alkali complex formation equilibria of nitrilotris(methylenephosphonic acid) (NTMP, H₆L) have been studied by dilatometric, potentiometric and ³¹P NMR-controlled titrations. Dilatometry indicated the formation of alkali complexes ML (M=Li, Na, K, Rb, Cs) at high pH with a stability decreasing from Li to Cs. An efficient combination of potentiometric and NMR methods confirmed two types of alkali metal complexes MHL and ML. Stability constants for the equilibria following M⁺ + HL⁵⁻ ? MHL⁴⁻ and M⁺ + L⁶⁻ ? ML⁵⁻, respectively, were determined: logK_NaHL=1.08(0.07), logK_KHL=0.86(0.08), logK_NaL=2.24(0.03). Systematic errors are introduced by using alkali metal hydroxides as titrants for routine potentiometric determinations of dissociation constants pK_a5^app and pK_a6^app. Correction formulae were derived to convert actual dissociation constants pK_a into apparent dissociation constants pK_a^app (or vice versa). The actual dissociation constants were found: pK_a5(H₂L⁴⁻ ? H⁺ + HL⁵⁻)=7.47(0.03) and pK_a6(HL⁵⁻ ? H⁺ + L⁶⁻)=14.1(0.1). The anisotropy of ³¹P chemical shifts of salts M_nH_6 − nL (M=Li, Na, n=0-5) is more sensitive towards titration (n) than isotropic solution state chemical shifts.     

Strain history and TGF-β1 induce urinary bladder wall smooth muscle remodeling and elastogenesis

Mechanical cues that trigger pathological remodeling in smooth muscle tissues remain largely unknown and are thought to be pivotal triggers for strain-induced remodeling. Thus, an understanding of the effects mechanical stimulation is important to elucidate underlying mechanisms of disease states and in the development of methods for smooth muscle tissue regeneration. For example, the urinary bladder wall (UBW) adaptation to spinal cord injury (SCI) includes extensive hypertrophy as well as increased collagen and elastin, all of which profoundly alter its mechanical response. In addition, the pro-fibrotic growth factor TGF-β1 is upregulated in pathologies of other smooth muscle tissues and may contribute to pathological remodeling outcomes. In the present study, we utilized an ex vivo organ culture system to investigate the response of UBW tissue under various strain-based mechanical stimuli and exogenous TGF-β1 to assess extracellular matrix (ECM) synthesis, mechanical responses, and bladder smooth muscle cell (BSMC) phenotype. Results indicated that a 0.5-Hz strain frequency triangular waveform stimulation at 15% strain resulted in fibrillar elastin production, collagen turnover, and a more compliant ECM. Further, this stretch regime induced changes in cell phenotype while the addition of TGF-β1 altered this phenotype. This phenotypic shift was further confirmed by passive strip biomechanical testing, whereby the bladder groups treated with TGF-β1 were more compliant than all other groups. TGF-β1 increased soluble collagen production in the cultured bladders. Overall, the 0.5-Hz strain-induced remodeling caused increased compliance due to elastogenesis, similar to that seen in early SCI bladders. Thus, organ culture of bladder strips can be used as an experimental model to examine ECM remodeling and cellular phenotypic shift and potentially elucidate BMSCs ability to produce fibrillar elastin using mechanical stretch either alone or in combination with growth factors.     

Effect of osmotic gradient on ADH-induced intramembranous particle aggregates in toad bladder

Summary Paired toad urinary bladders were prepared without or with an osmotic gradient (175 mosm) across them, stimulated for 2.5 (n=6), 5 (n=6), 30 (n=6) or 60 (n=6) min with ADH (20 mU/ml), and studied by freeze-fracture electron microscopy. Water permeability at these times was assessed in additional bladders (n=6 for each case) after tissue fixation according to the technique of Eggena. After both 60 and 30 min of ADH stimulation, the presence of a gradient compared with the absence of one was associated with fewer aggregates (242±35vs. 382±14 ×235 m^–2 at 60 min,P<0.01; 279±36vs. 470±51 ×235 m^–2 at 30 min,P<0.01) and lower water permeability (8.4±1.1vs. 18.8±1.8g×min^–1×cm^–1 ×mosm ^–1 at60min,P<0.005; 9.2±1.0vs. 22.0±2.1 g ×min^–1×cm^–2×mosm ^–1 at 30 min,P<0.001). In addition, with a gradient both maximum water permeability and maximum aggregate frequency were reached nearly together; a similar correspondence occurred without a gradient. We conclude that in the presence of an osmotic gradient both the ADH-associated aggregates and the water permeability response to ADH are prevented from reaching the higher levels observed in bladders not exposed to a gradient.     

Crystal structures of mixed oxonium-cadmium(II) salts with [SbF6]/[Sb2F11] anions: From complex chains to layers and three-dimensional frameworks

Pure H₃OCd(SbF₆)(Sb₂F₁₁)₂ is prepared by the reaction of CdO with nSbF₅ (n ? 5) or by reaction of H₃OSbF₆, Cd(SbF₆)₂ and nSbF₅ (n ? 2) in anhydrous hydrogen fluoride. H₃OCd(SbF₆)(Sb₂F₁₁)₂ crystallizes in the monoclinic space group P2₁/a (No. 14) with a = 986.1(4) pm, b = 1257.3(5) pm, c = 1826.8.4(8) pm, β = 98.062(4)° and Z = 4.Reaction of CdO with SbF₅ (n ? 3) in anhydrous HF yields only a mixture of H₃OSbF₆ and Cd(SbF₆)₂. No reactions were observed also when different ratios of H₃OSbF₆ and Cd(SbF₆)₂ were used as starting materials. However, the re-crystallization of these mixtures yielded single crystals of new phases: (H₃O)₂Cd(SbF₆)₃(Sb₂F₁₁) and (H₃O)₂Cd₂F(SbF₆)₅. The former crystallizes in the orthorhombic Pcca space group (No. 54) with a = 2189(2) pm, b = 1121.2(8) pm, c = 1894(1) pm and Z = 8 and the latter in the monoclinic P2₁/a space group a = 1019(4) pm, b = 1112(1) pm, c = 1147(1) pm, β = 107.81(1)° and Z = 2. The attempt to prepare single crystals of Cd(SbF₆)₂ resulted in the preparation of few single crystals of (H₃O)[Cd(HF)]₄(SbF₆)₉, which crystallizes in the monoclinic space group C2/c (No. 15) with a = 2087(3) pm, b = 1021(5) pm, c = 2112(2) pm, β = 99.36(2)° and Z = 4.     

FGFR3 mutational status and protein expression in patients with bladder cancer in a Jordanian population

Bladder cancer accounts for nearly 5% of all newly diagnosed cancers in Jordan, with a much higher frequency in males. Recent studies have shown that activating mutations in FGFR3 are the most common findings in non-invasive low grade bladder tumors. In this study, we, retrospectively, investigated a cohort of 121 bladder cancer patients with various grades and stages of the tumor for molecular changes in FGFR3. Overexpression of FGFR3 was observed in 49%, 34%, 15%, and 2% of pTa, pT1, pT2, and pT3 cases, respectively. Further, FGFR3 expression was positive in 45%, 26%, and 30% of G1, G2 and G3 cases, respectively. Mutational analysis of exons 7, 10 and 15 of FGFR3 identified four previously reported mutations, namely R248C (n = 4; 10%), S249C (n = 23; 59%), Y375C (n = 7; 18%), G382R (n = 4; 10%), and one novel mutation, G382E (n = 1; 3%). Our results indicate that both mutations and overexpression of FGFR3 are correlated together, and are more prevalent in early stage (pTa and pT1) and low grade (G1 and G2) bladder tumors. Survival analysis showed no contribution of changes in FGFR3 on the patient's survival. Multivariate Cox proportional hazards model analysis of overall survival for the following variables: age, gender, stage and grade of tumor, and FGFR3 (expression and mutation) revealed that age, stage and grade of tumor are independent predictors of overall survival in patients with bladder cancer. Our work is the first to address the molecular status of FGFR3 in Jordanian patients with bladder cancer, and provides further support for FGFR3 as a key player in the initiation of bladder tumors.     

Investigations about dissolution of cellulose in the 1-allyl-3-alkylimidazolium chloride ionic liquids

In this work, the 1-allyl-3-alkylimidazolium chloride ionic liquids were synthesized and characterized by increasing carbon atoms (n ≤ 6) of alkyl chains on a cationic 3-imidazole ring. The results indicated that 1-allyl-3-alkylimidazolium chloride with asymmetrical structure on the two sides of a cationic 3-imidazole ring (i.e., n = 1, 2, 6) exhibited alkalinity and lower thermal stabilities, and showed better solubility to the cellulose samples at 60-120 °C than those with symmetrical structures (n = 3, 4). The cellulose samples treated by 20% (w/w) ethylenediamine solution showed better solubility in 1-allyl-3-ethyl, hexyl-imidazolium chloride ionic liquids than that treated with 20% (w/w) NaOH solution at 5 °C for 72 h. XRD and TG analysis indicated that 0 0 2 plane apparent crystallite size as well as thermal stability of the regenerated cellulose samples from the ionic liquids decreased significantly compared with the untreated cellulose samples.