Measurement of the B0 anti-B0 oscillation frequency using l- D*+ pairs and lepton flavor tags

The oscillation frequency Delta-md of B0 anti-B0 mixing is measured using the partially reconstructed semileptonic decay anti-B0 -> l- nubar D*+ X. The data sample was collected with the CDF detector at the Fermilab Tevatron collider during 1992 - 1995 by triggering on the existence of two lepton candidates in an event, and corresponds to about 110 pb-1 of pbar p collisions at sqrt(s) = 1.8 TeV. We estimate the proper decay time of the anti-B0 meson from the measured decay length and reconstructed momentum of the l- D*+ system. The charge of the lepton in the final state identifies the flavor of the anti-B0 meson at its decay. The second lepton in the event is used to infer the flavor of the anti-B0 meson at production. We measure the oscillation frequency to be Delta-md = 0.516 +/- 0.099 +0.029 -0.035 ps-1, where the first uncertainty is statistical and the second is systematic.Comment: 30 pages, 7 figures. Submitted to Physical Review

Comparative 3D analyses and palaeoecology of giant early amphibians (Temnospondyli: Stereospondyli)

Macroevolutionary, palaeoecological and biomechanical analyses in deep time offer the possibility to decipher the structural constraints, ecomorphological patterns and evolutionary history of extinct groups. Here, 3D comparative biomechanical analyses of the extinct giant early amphibian group of stereospondyls together with living lissamphibians and crocodiles, shows that: i) stereospondyls had peculiar palaeoecological niches with proper bites and stress patterns very different than those of giant salamanders and crocodiles; ii) their extinction may be correlated with the appearance of neosuchians, which display morphofunctional innovations. Stereospondyls weathered the end-Permian mass extinction, re-radiated, acquired gigantic sizes and dominated (semi) aquatic ecosystems during the Triassic. Because these ecosystems are today occupied by crocodilians, and stereospondyls are extinct amphibians, their palaeobiology is a matter of an intensive debate: stereospondyls were a priori compared with putative living analogous such as giant salamanders and/or crocodilians and our new results try to close this debate.Peer ReviewedPostprint (published version

Identifying chondroprotective diet-derived bioactives and investigating their synergism

Osteoarthritis (OA) is a multifactorial disease and nutrition is a modifiable factor that may contribute to disease onset or progression. A detailed understanding of mechanisms through which diet-derived bioactive molecules function and interact in OA is needed. We profiled 96 diet-derived, mainly plant-based bioactives using an in vitro model in chondrocytes, selecting four candidates for further study. We aimed to determine synergistic interactions between bioactives that affected the expression of key genes in OA. Selected bioactives, sulforaphane, apigenin, isoliquiritigenin and luteolin, inhibited one or more interleukin-1-induced metalloproteinases implicated in OA (MMP1, MMP13, ADAMTS4, ADAMTS5). Isoliquiritigenin and luteolin showed reactive oxygen species scavenging activity in chondrocytes whereas sulforaphane had no effect and apigenin showed only a weak trend. Sulforaphane inhibited the IL-1/NFκB and Wnt3a/TCF/Lef pathways and increased TGFβ/Smad2/3 and BMP6/Smad1/5/8 signalling. Apigenin showed potent inhibition of the IL-1/NFκB and TGFβ/Smad2/3 pathways, whereas luteolin showed only weak inhibition of the IL-1/NFκB pathway. All four bioactives inhibited cytokine-induced aggrecan loss from cartilage tissue explants. The combination of sulforaphane and isoliquiritigenin was synergistic for inhibiting MMP13 gene expression in chondrocytes. We conclude that dietary-derived bioactives may be important modulators of cartilage homeostasis and synergistic relationships between bioactives may have an anti-inflammatory and chondroprotective role

Functional Improvement of Regulatory T Cells From Rheumatoid Arthritis Subjects Induced by Capsular Polysaccharide Glucuronoxylomannogalactan

Objective: Regulatory T cells (Treg) play a critical role in the prevention of autoimmunity, and the suppressive activity of these cells is impaired in rheumatoid arthritis (RA). The aim of the present study was to investigate function and properties of Treg of RA patients in response to purified polysaccharide glucuronoxylomannogalactan (GXMGal). Methods: Flow cytometry and western blot analysis were used to investigate the frequency, function and properties of Treg cells. Results: GXMGal was able to: i) induce strong increase of FOXP3 on CD4+ T cells without affecting the number of CD4+CD25+FOXP3+ Treg cells with parallel increase in the percentage of non-conventional CD4+CD25-FOXP3+ Treg cells; ii) increase intracellular levels of TGF-beta1 in CD4+CD25-FOXP3+ Treg cells and of IL-10 in both CD4+CD25+FOXP3+ and CD4+CD25-FOXP3+ Treg cells; iii) enhance the suppressive activity of CD4+CD25+FOXP3+ and CD4+CD25-FOXP3+ Treg cells in terms of inhibition of effector T cell activity and increased secretion of IL-10; iv) decrease Th1 response as demonstrated by inhibition of T-bet activation and down-regulation of IFN-gamma and IL-12p70 production; v) decrease Th17 differentiation by down-regulating pSTAT3 activation and IL-17A, IL-23, IL-21, IL-22 and IL-6 production. Conclusion: These data show that GXMGal improves Treg functions and increases the number and function of CD4+CD25-FOXP3+ Treg cells of RA patients. It is suggested that GXMGal may be potentially useful for restoring impaired Treg functions in autoimmune disorders and for developing Treg cell-based strategies for the treatment of these diseases

Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption.

Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91 462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P<5 × 10-8).Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee

Recent trends in breast cancer incidence in US white women by county-level urban/rural and poverty status

<p>Abstract</p> <p>Background</p> <p>Unprecedented declines in invasive breast cancer rates occurred in the United States between 2001 and 2004, particularly for estrogen receptor-positive tumors among non-Hispanic white women over 50 years. To understand the broader public health import of these reductions among previously unstudied populations, we utilized the largest available US cancer registry resource to describe age-adjusted invasive and <it>in situ </it>breast cancer incidence trends for non-Hispanic white women aged 50 to 74 years overall and by county-level rural/urban and poverty status.</p> <p>Methods</p> <p>We obtained invasive and <it>in situ </it>breast cancer incidence data for the years 1997 to 2004 from 29 population-based cancer registries participating in the North American Association of Central Cancer Registries resource. Annual age-adjusted rates were examined overall and by rural/urban and poverty of patients' counties of residence at diagnosis. Joinpoint regression was used to assess trends by annual quarter of diagnosis.</p> <p>Results</p> <p>Between 2001 and 2004, overall invasive breast cancer incidence fell 13.2%, with greater reductions among women living in urban (-13.8%) versus rural (-7.5%) and low- (-13.0%) or middle- (-13.8%) versus high- (-9.6%) poverty counties. Most incidence rates peaked around 1999 then declined after second quarter 2002, although in rural counties, rates decreased monotonically after 1999. Similar but more attenuated patterns were seen for <it>in situ </it>cancers.</p> <p>Conclusion</p> <p>Breast cancer rates fell more substantially in urban and low-poverty, affluent counties than in rural or high-poverty counties. These patterns likely reflect a major influence of reductions in hormone therapy use after July 2002 but cannot exclude possible effects due to screening patterns, particularly among rural populations where hormone therapy use was probably less prevalent.</p

Putative Nanobacteria Represent Physiological Remnants and Culture By-Products of Normal Calcium Homeostasis

Putative living entities called nanobacteria (NB) are unusual for their small sizes (50–500 nm), pleomorphic nature, and accumulation of hydroxyapatite (HAP), and have been implicated in numerous diseases involving extraskeletal calcification. By adding precipitating ions to cell culture medium containing serum, mineral nanoparticles are generated that are morphologically and chemically identical to the so-called NB. These nanoparticles are shown here to be formed of amorphous mineral complexes containing calcium as well as other ions like carbonate, which then rapidly acquire phosphate, forming HAP. The main constituent proteins of serum-derived NB are albumin, fetuin-A, and apolipoprotein A1, but their involvement appears circumstantial since so-called NB from different body fluids harbor other proteins. Accordingly, by passage through various culture media, the protein composition of these particles can be modulated. Immunoblotting experiments reveal that antibodies deemed specific for NB react in fact with either albumin, fetuin-A, or both, indicating that previous studies using these reagents may have detected these serum proteins from the same as well as different species, with human tissue nanoparticles presumably absorbing bovine serum antigens from the culture medium. Both fetal bovine serum and human serum, used earlier by other investigators as sources of NB, paradoxically inhibit the formation of these entities, and this inhibition is trypsin-sensitive, indicating a role for proteins in this inhibitory process. Fetuin-A, and to a lesser degree albumin, inhibit nanoparticle formation, an inhibition that is overcome with time, ending with formation of the so-called NB. Together, these data demonstrate that NB are most likely formed by calcium or apatite crystallization inhibitors that are somehow overwhelmed by excess calcium or calcium phosphate found in culture medium or in body fluids, thereby becoming seeds for calcification. The structures described earlier as NB may thus represent remnants and by-products of physiological mechanisms used for calcium homeostasis, a concept which explains the vast body of NB literature as well as explains the true origin of NB as lifeless protein-mineralo entities with questionable role in pathogenesis

Quantitative nucleolar proteomics reveals nuclear re-organization during stress- induced senescence in mouse fibroblast

<p>Abstract</p> <p>Background</p> <p>Nucleolus is the most prominent mammalian organelle within the nucleus which is also the site for ribosomal biogenesis. There have been many reports indicating the involvement of nucleolus in the process of aging. Several proteins related to aging have been shown to localize in the nucleolus, which suggests the role of this organelle in senescence.</p> <p>Results</p> <p>In this study, we used quantitative mass spectrometry to map the flux of proteins into and out of the nucleolus during the induction of senescence in cultured mammalian cells. Changes in the abundance of 344 nucleolar proteins in sodium butyrate-induced senescence in NIH3T3 cells were studied by SILAC (stable isotope labeling by amino acids in cell culture)-based mass spectrometry. Biochemically, we have validated the proteomic results and confirmed that B23 (nucleophosmin) protein was down-regulated, while poly (ADP-ribose) polymerase (PARP) and nuclear DNA helicase II (NDH II/DHX9/RHA) were up-regulated in the nucleolus upon treatment with sodium butyrate. Accumulation of chromatin in the nucleolus was also observed, by both proteomics and microscopy, in sodium butyrate-treated cells. Similar observations were found in other models of senescence, namely, in mitoxantrone- (MTX) treated cells and primary fibroblasts from the Lamin A knockout mice.</p> <p>Conclusion</p> <p>Our data indicate an extensive nuclear organization during senescence and suggest that the redistribution of B23 protein and chromatin can be used as an important marker for senescence.</p

Biocontrol of larval mosquitoes by Acilius sulcatus (Coleoptera: Dytiscidae)

<p>Abstract</p> <p>Background</p> <p>Problems associated with resistant mosquitoes and the effects on non-target species by chemicals, evoke a reason to find alternative methods to control mosquitoes, like the use of natural predators. In this regard, aquatic coleopterans have been explored less compared to other insect predators. In the present study, an evaluation of the role of the larvae of <it>Acilius sulcatus </it>Linnaeus 1758 (Coleoptera: Dytiscidae) as predator of mosquito immatures was made in the laboratory. Its efficacy under field condition was also determined to emphasize its potential as bio-control agent of mosquitoes.</p> <p>Methods</p> <p>In the laboratory, the predation potential of the larvae of <it>A. sulcatus </it>was assessed using the larvae of <it>Culex quinquefasciatus </it>Say 1823 (Diptera: Culicidae) as prey at varying predator and prey densities and available space. Under field conditions, the effectiveness of the larvae of <it>A. sulcatus </it>was evaluated through augmentative release in ten cemented tanks hosting immatures of different mosquito species at varying density. The dip density changes in the mosquito immatures were used as indicator for the effectiveness of <it>A. sulcatus </it>larvae.</p> <p>Results</p> <p>A single larva of <it>A. sulcatus </it>consumed on an average 34 IV instar larvae of <it>Cx. quinquefasciatus </it>in a 24 h period. It was observed that feeding rate of <it>A. sulcatus </it>did not differ between the light-on (6 a.m. – 6 p.m.), and dark (6 p.m. – 6 a.m.) phases, but decreased with the volume of water i.e., space availability. The prey consumption of the larvae of <it>A. sulcatus </it>differed significantly (P < 0.05) with different prey, predator and volume combinations, revealed through univariate ANOVA. The field study revealed a significant decrease (p < 0.05) in larval density of different species of mosquitoes after 30 days from the introduction of <it>A. sulcatus </it>larvae, while with the withdrawal, a significant increase (p < 0.05) in larval density was noted indicating the efficacy of <it>A. sulcatus </it>in regulating mosquito immatures. In the control tanks, mean larval density did not differ (p > 0.05) throughout the study period.</p> <p>Conclusion</p> <p>the larvae of the dytiscid beetle <it>A. sulcatus </it>proved to be an efficient predator of mosquito immatures and may be useful in biocontrol of medically important mosquitoes.</p