Associations of the TNF-alpha-308 G/A, IL6-174 G/C and AdipoQ 45 T/G polymorphisms with inflammatory and metabolic responses to lifestyle intervention in Brazilians at high cardiometabolic risk

Background: Cytokines secreted by the adipose tissue influence inflammation and insulin sensitivity, and lead to metabolic disturbances. How certain single-nucleotide polymorphisms (SNPs) interfere on lifestyle interventions is unclear. We assessed associations of selected SNPs with changes induced by a lifestyle intervention. Methods: This 9-month intervention on diet and physical activity included 180 Brazilians at high cardiometabolic risk, genotyped for the TNF-alpha -308 G/A, IL-6 -174 G/C and AdipoQ 45 T/G SNPs. Changes in metabolic and inflammatory variables were analyzed according to these SNPs. Individuals with at least one variant allele were grouped and compared with those with the reference genotype. Results: In the entire sample (66.7% women; mean age 56.5 +/- 11.6 years), intervention resulted in lower energy intake, higher physical activity, and improvement in anthropometry, plasma glucose, HOMA-IR, lipid profile and inflammatory markers, except for IL-6 concentrations. After intervention, only variant allele carriers of the TNF-alpha -308 G/A decreased plasma glucose, after adjusting for age and gender (OR 2.96, p = 0.025). Regarding the IL-6 -174 G/C SNP, carriers of the variant allele had a better response of lipid profile and adiponectin concentration, but only the reference genotype group decreased plasma glucose. In contrast to individuals with the reference genotype, carriers of variant allele of AdipoQ 45 T/G SNP did not change plasma glucose, apolipoprotein B, HDL-c and adiponectin concentrations in response to intervention. Conclusion: The TNF alpha -308 G/A SNP may predispose a better response of glucose metabolism to lifestyle intervention. The IL-6 -174 G/C SNP may confer a beneficial effect on lipid but not on glucose metabolism. Our findings reinforce unfavorable effects of the AdipoQ 45 T/G SNP in lipid profile and glucose metabolism after intervention in Brazilians at cardiometabolic risk. Further studies are needed to direct lifestyle intervention to subsets of individuals at cardiometabolic risk.

Cationic nanoparticles for delivery of amphotericin B: preparation, characterization and activity in vitro

Abstract Background Particulate systems are well known to be able to deliver drugs with high efficiency and fewer adverse side effects, possibly by endocytosis of the drug carriers. On the other hand, cationic compounds and assemblies exhibit a general antimicrobial action. In this work, cationic nanoparticles built from drug, cationic lipid and polyelectrolytes are shown to be excellent and active carriers of amphotericin B against C. albicans. Results Assemblies of amphotericin B and cationic lipid at extreme drug to lipid molar ratios were wrapped by polyelectrolytes forming cationic nanoparticles of high colloid stability and fungicidal activity against Candida albicans. Experimental strategy involved dynamic light scattering for particle sizing, zeta-potential analysis, colloid stability, determination of AmB aggregation state by optical spectra and determination of activity against Candida albicans in vitro from cfu countings. Conclusion Novel and effective cationic particles delivered amphotericin B to C. albicans in vitro with optimal efficiency seldom achieved from drug, cationic lipid or cationic polyelectrolyte in separate. The multiple assembly of antibiotic, cationic lipid and cationic polyelctrolyte, consecutively nanostructured in each particle produced a strategical and effective attack against the fungus cells.

Cocaine induces cell death and activates the transcription nuclear factor kappa-b in pc12 cells

Cocaine is a worldwide used drug and its abuse is associated with physical, psychiatric and social problems. The mechanism by which cocaine causes neurological damage is very complex and involves several neurotransmitter systems. For example, cocaine increases extracellular levels of dopamine and free radicals, and modulates several transcription factors. NF-κB is a transcription factor that regulates gene expression involved in cellular death. Our aim was to investigate the toxicity and modulation of NF-κB activity by cocaine in PC 12 cells. Treatment with cocaine (1 mM) for 24 hours induced DNA fragmentation, cellular membrane rupture and reduction of mitochondrial activity. A decrease in Bcl-2 protein and mRNA levels, and an increase in caspase 3 activity and cleavage were also observed. In addition, cocaine (after 6 hours treatment) activated the p50/p65 subunit of NF-κB complex and the pretreatment of the cells with SCH 23390, a D1 receptor antagonist, attenuated the NF-κB activation. Inhibition of NF-κB activity by using PDTC and Sodium Salicilate increased cell death caused by cocaine. These results suggest that cocaine induces cell death (apoptosis and necrosis) and activates NF-��B in PC12 cells. This activation occurs, at least partially, due to activation of D1 receptors and seems to have an anti-apoptotic effect on these cells.

Associations of the TNF-alpha -308��G/A, IL6 -174���G/C and AdipoQ 45��T/G polymorphisms with inflammatory and metabolic responses to lifestyle intervention in Brazilians at high cardiometabolic risk

Abstract Background Cytokines secreted by the adipose tissue influence inflammation and insulin sensitivity, and lead to metabolic disturbances. How certain single-nucleotide polymorphisms (SNPs) interfere on lifestyle interventions is unclear. We assessed associations of selected SNPs with changes induced by a lifestyle intervention. Methods This 9-month intervention on diet and physical activity included 180 Brazilians at high cardiometabolic risk, genotyped for the TNF-�� -308 G/A, IL-6 -174���G/C and AdipoQ 45��T/G SNPs. Changes in metabolic and inflammatory variables were analyzed according to these SNPs. Individuals with at least one variant allele were grouped and compared with those with the reference genotype. Results In the entire sample (66.7% women; mean age 56.5 ±���11.6 years), intervention resulted in lower energy intake, higher physical activity, and improvement in anthropometry, plasma glucose, HOMA-IR, lipid profile and inflammatory markers, except for IL-6 concentrations. After intervention, only variant allele carriers of the TNF-α -308���G/A decreased plasma glucose, after adjusting for age and gender (OR 2.96, p =��0.025). Regarding the IL6 -174��G/C SNP, carriers of the variant allele had a better response of lipid profile and adiponectin concentration, but only the reference genotype group decreased plasma glucose. In contrast to individuals with the reference genotype, carriers of variant allele of AdipoQ 45���T/G SNP did not change plasma glucose, apolipoprotein B, HDL-c and adiponectin concentrations in response to intervention. Conclusion The TNFα -308���G/A SNP may predispose a better response of glucose metabolism to lifestyle intervention. The IL-6 -174��G/C SNP may confer a beneficial effect on lipid but not on glucose metabolism. Our findings reinforce unfavorable effects of the AdipoQ 45 T/G SNP in lipid profile and glucose metabolism after intervention in Brazilians at cardiometabolic risk. Further studies are needed to direct lifestyle intervention to subsets of individuals at cardiometabolic risk.

The charmed pentaquark ��c(3250) from QCD sum rules.

We study, using the QCD sum rule framework, the possible existence of a charmed pentaquark that we call Θc(3250). In the QCD side we work at leading order in αs and consider condensates up to dimension 10. The mass obtained: mΘc = (3.21��0.13) GeV, is compatible with the mass of the structure seen by BaBar Collaboration in the decay channel B− �� ���p Σ++ c ����π−.

C-clamp and pelvic packing for control of hemorrhage in patients with pelvic ring disruption

Exsanguinating hemorrhage is the major cause of death in patients with pelvic ring disruption.

Search for a light charged Higgs boson in the decay channel H⁺ o c ars in t art events using collisions at sqrts = 7 TeV with the ATLAS detector

A search for a charged Higgs boson (H+) in t (t) over bar decays is presented, where one of the top quarks decays via t -> H(+)b, followed by H+ -> two jets (c (s) over bar). The other top quark decays to Wb, where the W boson then decays into a lepton (e/mu) and a neutrino. The data were recorded in pp collisions at root s = 7 TeV by the ATLAS detector at the LHC in 2011, and correspond to an integrated luminosity of 4.7 fb(-1). With no observation of a signal, 95 % confidence level (CL) upper limits are set on the decay branching ratio of top quarks to charged Higgs bosons varying between 5 % and 1 % for H+ masses between 90 GeV and 150 GeV, assuming B(H+ -> c (s) over bar) = 100 %.

Vom j��dischen Wesen : Vortr., geh. im Isr. Humanitätsverein "Bohemia" B'nai B'rith in Prag am 6. Nov. 1915

von Emil Spiegel

Hinnë woauhel : "Hier ist sie (Mutter Sarah) im Zelte" ; (1. B. M. 18,9) Vorschriften für den jüdischen Haushalt

in popul��rer Form dargest. u. mit kurzen Erklärungen versehen von Ansbacher. Hrsg. vom "Württemberger gesetzestreuen Landesverband"

Abhandlung ��ber den Ursprung der Beschneidung bei wilden und halbwilden V��lkern mit Beziehung auf die Beschneidung der Israeliten : mit e. Kritik von C. Chr. v. Flatt begleitet

verf. von J. H. F. v. Autenrieth

B/Ca ratios of benthic foraminifera

We present modern B/Ca core-top calibrations for the epifaunal benthic foraminifer Nuttallides umbonifera and the infaunal Oridorsalis umbonatus to test whether B/Ca values in these species can be used for the reconstruction of paleo-D[[CO3]2-]. O. umbonatus originated in the Late Cretaceous and remains extant, whereas N. umbonifera originated in the Eocene and is the closest extant relative to Nuttallides truempyi, which ranges from the Late Cretaceous through the Eocene. We measured B/Ca in both species in 35 Holocene sediment samples from the Atlantic, Pacific and Southern Oceans. B/Ca values in epifaunal N. umbonifera (~ 85-175 µmol/mol) are consistently lower than values reported for epifaunal Cibicidoides (Cibicides) wuellerstorfi (130-250 µmol/mol), though the sensitivity of D[[CO3]2-] on B/Ca in N. umbonifera (1.23 �� 0.15) is similar to that in C. wuellerstorfi (1.14 �� 0.048). In addition, we show that B/Ca values of paired N. umbonifera and its extinct ancestor, N. truempyi, from Eocene cores are indistinguishable within error. In contrast, both the B/Ca (35-85 ��mol/mol) and sensitivity to D[[CO3]2-] (0.29 ± 0.20) of core-top O. umbonatus are considerably lower (as in other infaunal species), and this offset extends into the Paleocene. Thus the B/Ca of N. umbonifera and its ancestor can be used to reconstruct bottom water D[[CO3]2?], whereas O. umbonatus B/Ca appears to be buffered by porewater [[CO3]2-] and suited for constraining long-term drift in seawater B/Ca.

Protein kinase C potentiation of N-methyl-d-aspartate receptor activity is not mediated by phosphorylation of N-methyl-d-aspartate receptor subunits

N-methyl-d-aspartate receptors (NMDARs) are Ca2+-permeable glutamate-gated ion channels whose physiological properties in neurons are modulated by protein kinase C (PKC). The present study was undertaken to determine the role in PKC-induced potentiation of the NR1 and NR2A C-terminal tails, which serve as targets of PKC phosphorylation [Tingley, W. G., Ehlers, M. D., Kameyama, K., Doherty, C., Ptak, J. B., Riley, C. T. & Huganir, R. L. (1997) J. Biol. Chem. 272, 5157��5166]. Serine residue 890 in the C1 cassette is a primary target of PKC phosphorylation and a critical residue in receptor clustering at the membrane. We report herein that the presence of the C1 cassette reduces PKC potentiation and that mutation of Ser-890 significantly restores PKC potentiation. Splicing out or deletion of other C-terminal cassettes singly or in combination had little or no effect on PKC potentiation. Moreover, experiments involving truncation mutants reveal the unexpected finding that NMDARs assembled from subunits lacking all known sites of PKC phosphorylation can show PKC potentiation. These results indicate that PKC-induced potentiation of NMDAR activity does not occur by direct phosphorylation of the receptor protein but rather of associated targeting, anchoring, or signaling protein(s). PKC potentiation of NMDAR function is likely to be an important mode of NMDAR regulation in vivo and may play a role in NMDA-dependent long-term potentiation.

In vitro assembly of phytochrome B apoprotein with synthetic analogs of the phytochrome chromophore

Phytochrome B (PhyB), one of the major photosensory chromoproteins in plants, mediates a variety of light-responsive developmental processes in a photoreversible manner. To analyze the structural requirements of the chromophore for the spectral properties of PhyB, we have designed and chemically synthesized 20 analogs of the linear tetrapyrrole (bilin) chromophore and reconstituted them with PhyB apoprotein (PHYB). The A-ring acts mainly as the anchor for ligation to PHYB, because the modification of the side chains at the C2 and C3 positions did not significantly influence the formation or difference spectra of adducts. In contrast, the side chains of the B- and C-rings are crucial to position the chromophore properly in the chromophore pocket of PHYB and for photoreversible spectral changes. The side-chain structure of the D-ring is required for the photoreversible spectral change of the adducts. When methyl and ethyl groups at the C17 and C18 positions are replaced with an n-propyl, n-pentyl, or n-octyl group, respectively, the photoreversible spectral change of the adducts depends on the length of the side chains. From these studies, we conclude that each pyrrole ring of the linear tetrapyrrole chromophore plays a different role in chromophore assembly and the photochromic properties of PhyB.