Salmonella produce microRNA-like RNA fragment Sal-1 in the infected cells to facilitate intracellular survival.

Salmonella have developed a sophisticated machinery to evade immune clearance and promote survival in the infected cells. Previous studies were mostly focused on either bacteria itself or host cells, the interaction mechanism of host-pathogen awaits further exploration. In the present study, we show that Salmonella can exploit mammalian cell non-classical microRNA processing machinery to further process bacterial small non-coding RNAs into microRNA-like fragments. Sal-1, one such fragment with the highest copy number in the infected cells, is derived from Salmonella 5-leader of the ribosomal RNA transcript and has a stem structure-containing precursor. Processing of Sal-1 precursors to mature Sal-1 is dependent on host cell Argonaute 2 (AGO2) but not Dicer. Functionally, depleting cellular Sal-1 strongly renders the Salmonella bacteria less resistant to the host defenses both in vitro and in vivo. In conclusion, we demonstrate a novel strategy for Salmonella evading the host immune clearance, in which Salmonella produce microRNA-like functional RNA fragments to establish a microenvironment facilitating bacterial survival

Blood eosinophils and inhaled corticosteroid/long-acting β-2 agonist efficacy in COPD

Objective We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels ≥2% were associated with a greater reduction in exacerbation rates with ICS therapy. Methods Three studies of ≥1-year duration met the inclusion criteria. Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs ≥2%). At baseline, 57–75% of patients had ≥2% blood eosinophils. Changes in FEV1 and St George’s Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level. Results For patients with ≥2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001). No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively). In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo). No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ. Discussion Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations

Behavioral Profiles of Genetically Selected Aggressive and Nonaggressive Male Wild House Mice in Two Anxiety Tests

Artificially selected aggressive (SAL) and non-aggressive (LAL) male house mice were tested in a hexagonal tunnel maze and light–dark preference (LD) box to determine if the bidirectional selection for aggressive behavior leads to a coselection for different levels of trait anxiety. The tunnel maze consists of an open, brightly lit central arena surrounded by a complex system of interconnecting tunnels. As in the LD box, animals which spend less time and are less active in the brightly illuminated section of the maze are considered to have higher anxiety levels. In the tunnel maze, the LAL mice showed more exploration and spent more time in the central arena than the SAL animals, but only during the final 2 min of the 6-min test. This reduced preference for the central arena was not due to general inactivity or a failure of the SAL to find the central arena and indicates a higher level of state anxiety in the aggressive animals. In contrast, no “anxiety-like” differences were found in the LD box, either for the percentage of time spent in the light compartment or for the number of crossings. SAL males actually showed higher levels of moving and rearing, and lower levels of freezing, than did LAL males.

Chemical, Biological, and Preliminary In Vitro Studies of Novel Vanadium(IV) Complexes with Schiff Bases and Thiosemicarbazone Ligands

9-Anthraldehyde-N(4)-methylthiosemicarbazone (MeATSC), potassium (E)-2-(2-hydroxybenzylideneamino)-3-(1H-indol-3-yl)propanoate (K[(Sal-L-tryp)] and 2-(2-hydroxybenzylamino)-3-(1H-indol-3-yl)propanoic acid (the reduced Schiff base) were prepared using known synthetic procedures. Two novel thiosemicarbazone ligands, (E)-N-ethyl-2-(4-hydroxy-3-methoxybenzylidene)hydrazinecarbothioamide (N-Ethhymethohcarbthio) and (E)-N-ethyl-2-(1-(thiazol-2-yl)ethylidene)hydrazinecarbothioamide (acetylethTSC), were also prepared. All ligands were characterized by FT IR and electrochemistry. N-Ethhymethohcarbthio were characterized by elemental analysis whereas the reduced Schiff base and K[(Sal-L-tryp)] were characterized by ESI MS. X-ray crystallography was also used to characterize acetylethTSC. The ligands were then reacted with [VO(Sal-L-tryp)(H2O)] (1) (Sal-L-tryp = N-salicylidene-L-tryptophanate) to produce the novel complexes, [VO(Sal-L-tryp)(MeATSC)].1.5C2H5OH (2), [VO(Sal-L-tryp)(N-Ethhymethohcarbthio)].H2O (3), and [VO(Sal-L-tryp)(acetylethTSC)].0.75C2H5OH (4), respectively. All complexes were characterized by elemental analysis, ESI MS, IR, UV-visible, 1H and 13C NMR spectroscopy, and electrochemistry. Oxidized DMSO and DMSO-d6 solutions of each complex were also characterized by ESI MS and 1H NMR spectroscopy. [VO(Sal-L-tryp)(MeATSC)].1.5C2H5OH, [VO(Sal-L-tryp)(N-Ethhymethohcarbthio)].H2O, and [VO(Sal-L-tryp)(acetylethTSC)].0.75C2H5OH were observed to exhibit anti-proliferative activity against three colon cancer cell lines, HTC-116, Caco-2, and HT-29. When the anti-proliferative effects were compared with that of non-cancerous colonic myofibroblasts, less inhibition was observed. The results obtained suggest that these compounds can be used as potential chemotherapeutic agents

Efficacy and Safety of Umeclidinium Added to Fluticasone Propionate/Salmeterol in Patients with COPD : Results of Two Randomized, Double-Blind Studies

Combinations of drugs with distinct and complementary mechanisms of action may offer improved efficacy in the treatment of chronic obstructive pulmonary disease (COPD). In two 12-week, double-blind, parallel-group studies, patients with COPD were randomized 1:1:1 to once-daily umeclidinium (UMEC; 62.5 μg and 125 μg) or placebo (PBO), added to twice-daily fluticasone propionate/salmeterol (FP/SAL; 250/50 μg). In both studies, the primary efficacy measure was trough forced expiratory volume in 1 second (FEV) at Day 85. Secondary endpoints were weighted-mean (WM) FEV over 0-6 hours post-dose (Day 84) and rescue albuterol use. Health-related quality of life outcomes (St. George's Respiratory Questionnaire [SGRQ] and COPD assessment test [CAT]) were also examined. Safety was assessed throughout. Both UMEC+FP/SAL doses provided statistically significant improvements in trough FEV (Day 85: 0.127-0.148 L) versus PBO+FP/SAL. Similarly, both UMEC+FP/SAL doses provided statistically-significant improvements in 0-6 hours post-dose WM FEV versus PBO+FP/SAL (Day 84: 0.144-0.165 L). Rescue use over Weeks 1-12 decreased with UMEC+FP/SAL in both studies versus PBO+FP/SAL (Study 1, 0.3 puffs/day [both doses]; Study 2, 0.5 puffs/day [UMEC 125+FP/SAL]). Decreases from baseline in CAT score were generally larger for both doses of UMEC+FP/SAL versus PBO+FP/SAL (except for Day 84 Study 2). In Study 1, no differences in SGRQ score were observed between UMEC+FP/SAL and PBO+FP/SAL; however, in Study 2, statistically significant improvements were observed with UMEC 62.5+FP/SAL (Day 28) and UMEC 125+FP/SAL (Days 28 and 84) versus PBO+FP/SAL. The incidence of on-treatment adverse events across all treatment groups was 37-41% in Study 1 and 36-38% in Study 2. Overall, these data indicate that the combination of UMEC+FP/SAL can provide additional benefits over FP/SAL alone in patients with COPD

Mononuclear and dinuclear molybdenum(VI) complexes with 2-aminobenzhydrazide derivatives

U ovom diplomskom radu ispitani su uvjeti nastajanja kompleksa molibdena(VI) s derivatima 2-aminobenzhidrazida koji sadrže O i N donorne atome. Provedene su reakcije H2Sal-2- HBNH2 (2-amino-N'-[(2-hidroksifenil)metiliden]benzhidrazid), H2Van-2-HBNH2 (2-amino- N'-(2-hidroksi-3-metoksibenziliden)benzhidrazid) i H24OMeSal-2-HBNH2 (2-amino-N'-(2- hidroksi-4-metoksibenziliden)benzhidrazid) s bis(pentan-2,4-dionato)dioksomolibdenom(VI) pri različitim temperaturama u metanolu i acetontrilu te su priređeni kompleksi [MoO2(Sal-2- HBNH2)(MeOH)], [MoO2(Sal-2-HBNH2)]2 (forma I i forma II), [MoO2(Van-2-HBNH2)]2, [MoO2(4OMeSal-2-HBNH2)(MeOH)], [MoO2(4OMeSal-2-HBNH2)]2 i [MoO2(Sal-2- HBNH2)]2∙2CH3CN. Svi produkti okarakterizirani su IR spektroskopijom, klasičnom kemijskom analizom, termičkom analizom te difrakcijom rentgenskog zračenja na polikristalnom uzorku. Molekulska i kristalna struktura određena je difrakcijom rentgenskog zračenja na monokristalnom uzorku za sve spojeve osim [MoO2(Van-2-HBNH2)]2.In this Diploma Thesis synthesis conditions to obtain molybdenum(VI) complexes with 2- aminobenzhydrazide derivatives containing O and N donor atoms were studied. The reactions of H2Sal-2-HBNH2 (2-amino-N'-[(2-hydroxyphenyl)methylidene]benzhydrazide), H2Van-2- HBNH2 (2-amino-N'-(2-hydroxy-3-methoxybenzylidene)benzhydrazide) and H24OMeSal-2- HBNH2 (2-amino-N'-(2-hydroxy-4-methoxybenzylidene)benzhydrazide) with bis(pentan-2,4- dionato)dioxomolybdenum(VI) were carried out at various temperatures in methanol and acetonitrile, and following complexes were prepared: [MoO2(Sal-2-HBNH2)(MeOH)], [MoO2(Sal-2-HBNH2)]2 (form I i form II), [MoO2(Van-2-HBNH2)]2, [MoO2(4OMeSal-2- HBNH2)(MeOH)], [MoO2(4OMeSal-2-HBNH2)]2 i [MoO2(Sal-2-HBNH2)]2∙2CH3CN. All products were characterized by IR spectroscopy, classic chemical analysis, thermal analysis and X-ray powder diffraction. Molecular and crystal structure was determined by the singlecrystal X-ray diffraction for all compounds except for [MoO2(Van-2-HBNH2)]2

Salvianolic Acid B Prevents Arsenic Trioxide-Induced Cardiotoxicity In Vivo and Enhances Its Anticancer Activity In Vitro

Clinical attempts to reduce the cardiotoxicity of arsenic trioxide (ATO) without compromising its anticancer activities remain to be an unresolved issue. In this study, we determined whether Sal B can protect against ATO-induced cardiac toxicity in vivo and increase the toxicity of ATO toward cancer cells. Combination treatment of Sal B and ATO was investigated using BALB/c mice and human hepatoma (HepG2) cells and human cervical cancer (HeLa) cells. The results showed that the combination treatment significantly improved the ATO-induced loss of cardiac function, attenuated damage of cardiomyocytic structure, and suppressed the ATO-induced release of cardiac enzymes into serum in BALB/c mouse models. The expression levels of Bcl-2 and p-Akt in the mice treated with ATO alone were reduced, whereas those in the mice given the combination treatment were similar to those in the control mice. Moreover, the combination treatment significantly enhanced the ATO-induced cytotoxicity and apoptosis of HepG2 cells and HeLa cells. Increases in apoptotic marker cleaved poly (ADP-ribose) polymerase and decreases in procaspase-3 expressions were observed through western blot. Taken together, these observations indicate that the combination treatment of Sal B and ATO is potentially applicable for treating cancer with reduced cardiotoxic side effects

Spectroscopic studies and thermal analysis of lead(II) and tin(II) solid complexes with bi- , tri- and tetradentate Schiff bases

The Schiff base complexes of Pb(II) and Sn(II) with bidentate (NO), [M(sal-An)2]  (sal-An = aniline salicylideneiminato); tridentate (ONO),  [M(sal-OAP)H2O)] (sal-OAP = ortho- aminophenol salicylideneiminato); and tetradentate (N2O2), [M(sal-o-phdn)] (sal-o-phdn = N,N'-o-phenylene bis(salicylideneiminato) have been synthesized. The infrared spectra were recorded and full assignments of all observed bands have been made. Differential thermal analysis (DTA) and thermogravimetric (TG) for all complexes were also carried out. The data obtained indicate that the complexes of both bi- and tetradentate ligands are decomposed in one stage, but the complexes of tridentate are decomposed in two steps. KEY WORDS: Lead, Tin, Schiff base, Infrared spectra, Thermal analysis  Bull. Chem. Soc. Ethiop. 2004, 18(2), 149-156

CALIPSO Observations of Transatlantic Dust: Vertical Stratification and Effect of Clouds

CALIOP nighttime measurements of lidar backscatter, color and depolarization ratios during the summer of 2007 are used to study transatlantic dust properties downwind of Saharan sources, and to examine the interaction of clouds and dust. We discuss the following findings: (1) while lidar backscatter doesn't change much with altitude in the Saharan Air Layer (SAL), depolarization and color ratios both increase with altitude in the SAL; (2) lidar backscatter and color ratio increase as dust is transported westward in the SAL; (3) the vertical lapse rate of dust depolarization ratio increases within SAL as plumes move westward; (4) nearby clouds barely affect the backscatter and color ratio of dust volumes within SAL but not so below SAL. Finally, (5) the odds of CALIOP finding dust below SAL next to clouds are about 2/3 of those far away from clouds. This feature, together with an apparent increase in depolarization ratio near clouds, indicates that particles in some dusty volumes lose asphericity in the humid air near clouds, and cannot be identified by CALIPSO as dust

Potential of Lignosulphonate of Eucalyptus Lignin from Pulp Plant as Dispersant in Gypsum Paste

AbstractEucalyptus lignin was isolated from kraft black liquor through acidification by using H2SO4. To effectively utilize black liquor waste from pulp plant, lignin was converted into sulphonated hydroxymethylated phenolized sulphuric acid lignin compound (SHP-SAL), which is soluble in water. SHP-SAL was obtained through the sequence of (1) phenolation of sulphuric acid lignin (SAL) into phenolized sulphuric acid lignin (P-SAL), (2) hydroxymethylation of P-SAL into hydroxymethylated phenolized sulphuric acid lignin (HP-SAL), and (3) sulphonation of HP-SAL into SHP-SAL. The derived lignin of SHP-SAL characterized by infrared spectrometry showed a significant absorption at 630 cm-1, which indicates the presence of S−O bond, and absorption at 1118 and 1059 cm-1, which are characteristics of C−O bonds in lignosulphonates. Assessment of SHP-SAL as a dispersant in gypsum paste was done according to C230-90 ASTM standard. The synthesized SHP-SAL has approximately 60% higher dispersability than those of commercial sodium lignosulphonate (comm. SLS) and commercial calcium lignosulphonate (comm. CLS). It is equal to the dispersability of sulphonated naphthalene formaldehyde (SNF), one of the high-performing sulphonate compounds