Glycomic analysis of high density lipoprotein shows a highly sialylated particle.

Many of the functional proteins and lipids in high density lipoprotein (HDL) particles are potentially glycosylated, yet very little is known about the glycoconjugates of HDL. In this study, HDL was isolated from plasma by sequential micro-ultracentrifugation, followed by glycoprotein and glycolipid analysis. N-Glycans, glycopeptides, and gangliosides were extracted and purified followed by analysis with nano-HPLC Chip quadrupole time of flight mass spectrometry and MS/MS. HDL particles were found to be highly sialylated. Most of the N-glycans (∼90%) from HDL glycoproteins were sialylated with one or two neuraminic acids (Neu5Ac). The most abundant N-glycan was a biantennary complex type glycan with two sialic acids (Hexose5HexNAc4Neu5Ac2) and was found in multiple glycoproteins using site-specific glycosylation analysis. The observed O-glycans were all sialylated, and most contained a core 1 structure with two Neu5Acs, including those that were associated with apolipoprotein CIII (ApoC-III) and fetuin A. GM3 (monosialoganglioside, NeuAc2-3Gal1-4Glc-Cer) and GD3 (disialoganglioside, NeuAc2-8NeuAc2-3Gal1-4Glc-Cer) were the major gangliosides in HDL. A 60% GM3 and 40% GD3 distribution was observed. Both GM3 and GD3 were composed of heterogeneous ceramide lipid tails, including d18:1/16:0 and d18:1/23:0. This report describes for the first time a glycomic approach for analyzing HDL, highlighting that HDL are highly sialylated particles

EPS-SJ exopolisaccharide produced by the strain Lactobacillus paracasei subsp. paracasei BGSJ2-8 is involved in adhesion to epithelial intestinal cells and decrease on E. coli association to Caco-2 cells

The aim of this study was to determine the role of an exopolysaccharide produced by natural dairy isolate Lactobacillus paracasei subsp. paracasei BGSJ2-8, in the adhesion to intestinal epithelial cells and a decrease in Escherichia coli's association with Caco-2 cells. Annotation of the BGSJ2-8 genome showed the presence of a gene cluster, epsSJ, which encodes the biosynthesis of the strain-specific exopolysaccharide EPS-SJ, detected as two fractions (P1 and P2) by size exclusion chromatography (SEC) coupled with multi-angle laser light scattering (MALLS) detection. SEC-MALLS analysis revealed that an EPS-SJ- mutant (EPS7, obtained by insertion mutagenesis of the glps_2198 gene encoding primary glycosyltransferase) does not produce the P2 fraction of EPS-SJ. Transmission electron microscopy showed that EPS7 mutant has a thinner cell wall compared to the EPS-SJ strain BGSJ2-83 (a plasmid free-derivative of BGSJ2-8). Interestingly, strain BGSJ2-83 showed higher adhesion to Caco-2 epithelial intestinal cell line than the EPS7 mutant. Accordingly, BGSJ2-83 effectively reduced E. coli ATCC25922's association with Caco-2 cells, while EPS7 did not show statistically significant differences. In addition, the effect of EPS-SJ on the proliferation of lymphocytes in gastrointestinal associated lymphoid tissue (GALT) was tested and the results showed that the reduction of GALT lymphocyte proliferation was higher by BGSJ2-83 than by the mutant. To the best of our knowledge this is the first report indicating that the presence of EPS (EPS-SJ) on the surface of lactobacilli can improve communication between bacteria and intestinal epithelium*Implying its possible role in gut colonization.Peer Reviewe

On the ground states of the Bernasconi model

The ground states of the Bernasconi model are binary +1/-1 sequences of length N with low autocorrelations. We introduce the notion of perfect sequences, binary sequences with one-valued off-peak correlations of minimum amount. If they exist, they are ground states. Using results from the mathematical theory of cyclic difference sets, we specify all values of N for which perfect sequences do exist and how to construct them. For other values of N, we investigate almost perfect sequences, i.e. sequences with two-valued off-peak correlations of minimum amount. Numerical and analytical results support the conjecture that almost perfect sequences do exist for all values of N, but that they are not always ground states. We present a construction for low-energy configurations that works if N is the product of two odd primes.Comment: 12 pages, LaTeX2e; extended content, added references; submitted to J.Phys.

Site-Specific Glycoprofiles of HDL-Associated ApoE are Correlated with HDL Functional Capacity and Unaffected by Short-Term Diet.

Since high-density lipoprotein (HDL) glycoprofiles are associated with HDL functional capacity, we set out to determine whether diet can alter the glycoprofiles of key HDL-associated proteins, including ApoE, a potent driver of chronic disease risk. Ten healthy subjects consumed a fast food (FF) and a Mediterranean (Med) diet for 4 days in randomized order, with a 4-day wash-out between treatments. A multiple reaction monitoring method was used to characterize the site-specific glycoprofiles of HDL proteins, and HDL functional capacity was analyzed. We describe for the first time that ApoE has 7 mucin-type O-glycosylation sites, which were not affected by short-term diet. The glycoprofiles of other HDL-associated proteins were also unaffected, except that a disialylated ApoC-III glycan was enriched after Med diet, and a nonsialylated ApoC-III glycan was enriched after FF diet. Twenty-five individual glycopeptides were significantly correlated with cholesterol efflux capacity and 21 glycopeptides were correlated with immunomodulatory capacity. Results from this study indicate that the glycoprofiles of HDL-associated proteins including ApoE are correlated with HDL functional capacity but generally unaffected by diet in the short term, except ApoC-III sialylation. These results suggest that HDL protein glycoprofiles are affected by both acute and long-term factors and may be useful for biomarker discovery

A Geophysical Investigation Of The Northeastern Rim Of The St. Martin Impact Structure, Manitoba, Canada.

The St. Martin impact structure is a 40 Km diameter structure located in Manitoba, Canada lies in featureless, glaciated terrain lacking any surface expression of an impact structure. The age of the structure has been re-determined to range between 224.3 Ma to 241.4 Ma which nullified a previous hypothesis suggesting this impact was part of a multiple impact event. Within the proposed structural boundary two outcrops of Archean granite are present. The first outcrop is located in what has been identified as the central peak of the impact structure. The second outcrop lies along the northeastern boundary and is known locally as Big Rock. The purpose of this investigation was to determine the relationship of Big Rock, if any, to the impact event and to constrain a more accurate diameter of the structure. To accomplish this I conducted two geophysical surveys and used selected data from a previous survey. The two methods I conducted were: a magnetic survey and seismic reflection profiling. Selected data from a previous gravity survey was used to supplement survey results. The magnetic survey was conducted using the total field G-856 Memory-Mag proton precession magnetometer which measures local or regional field strength. The seismic reflection survey was conducted using three Geometrics Geode exploration seismographs. Due to the complexity of seismic data processing I retained an outside seismic data processing company. Previous gravity anomaly data were acquired using a LaCoste and Romberg Model G gravimeter. The results of this geophysical investigation reveal a shallowing of granitic basement rock with exposure near Big Rock. However, a suggested listric fault near Big Rock was not identified via seismic reflection profiling, but was suggested by both the gravity and magnetic surveys. Listric faults that are genetically related to impact structures are also indicative of the structure\u27s outer boundary and therefore can confirm that the St. Martin impact structure is indeed 40 Km in diameter

A Geophysical Investigation of the Northeastern Rim of the St. Martin Impact Structure, Manitoba, Canada

The St. Martin impact structure is a 40 Km diameter structure located in Manitoba, Canada lies in featureless, glaciated terrain lacking any surface expression of an impact structure. The age of the structure has been re-determined to range between 224.3 Ma to 241.4 Ma which nullified a previous hypothesis suggesting this impact was part of a multiple impact event. Within the proposed structural boundary two outcrops of Archean granite are present. The first outcrop is located in what has been identified as the central peak of the impact structure. The second outcrop lies along the northeastern boundary and is known locally as Big Rock. The purpose of this investigation was to determine the relationship of Big Rock, if any, to the impact event and to constrain a more accurate diameter of the structure. To accomplish this I conducted two geophysical surveys and used selected data from a previous survey. The two methods I conducted were: a magnetic survey and seismic reflection profiling. Selected data from a previous gravity survey was used to supplement survey results. The magnetic survey was conducted using the total field G- 856 Memory-Mag proton precession magnetometer which measures local or regional field strength. The seismic reflection survey was conducted using three Geometrics Geode exploration seismographs. Due to the complexity of seismic data processing I retained an outside seismic data processing company. Previous gravity anomaly data were acquired using a LaCoste and Romberg Model G gravimeter. The results of this geophysical investigation reveal a shallowing of granitic basement rock with exposure near Big Rock. However, a suggested listric fault near Big Rock was not identified via seismic reflection profiling, but was suggested by both the gravity and magnetic surveys. Listric faults that are genetically related to impact structures are also indicative of the structure’s outer boundary and therefore can confirm that the St. Martin impact structure is indeed 40 Km in diameter

TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features. Here we studied a novel ALS/FTD family and identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1). Subsequent genetic association analyses showed an increased burden of TIA1 LCD mutations in ALS patients compared to controls (p = 8.7 × 1

Induction of humoral immune response to multiple recombinant Rhipicephalus appendiculatus antigens and their effect on tick feeding success and pathogen transmission

BACKGROUND: Rhipicephalus appendiculatus is the primary vector of Theileria parva, the etiological agent of East Coast fever (ECF), a devastating disease of cattle in sub-Saharan Africa. We hypothesized that a vaccine targeting tick proteins that are involved in attachment and feeding might affect feeding success and possibly reduce tick-borne transmission of T. parva. Here we report the evaluation of a multivalent vaccine cocktail of tick antigens for their ability to reduce R. appendiculatus feeding success and possibly reduce tick-transmission of T. parva in a natural host-tick-parasite challenge model. METHODS: Cattle were inoculated with a multivalent antigen cocktail containing recombinant tick protective antigen subolesin as well as two additional R. appendiculatus saliva antigens: the cement protein TRP64, and three different histamine binding proteins. The cocktail also contained the T. parva sporozoite antigen p67C. The effect of vaccination on the feeding success of nymphal and adult R. appendiculatus ticks was evaluated together with the effect on transmission of T. parva using a tick challenge model. RESULTS: To our knowledge, this is the first evaluation of the anti-tick effects of these antigens in the natural host-tick-parasite combination. In spite of evidence of strong immune responses to all of the antigens in the cocktail, vaccination with this combination of tick and parasite antigens did not appear to effect tick feeding success or reduce transmission of T. parva. CONCLUSION: The results of this study highlight the importance of early evaluation of anti-tick vaccine candidates in biologically relevant challenge systems using the natural tick-host-parasite combination

Measurement of the lifetime of the B_c meson in the semileptonic decay channel

Using approximately 1.3 fb-1 of data collected by the D0 detector between 2002 and 2006, we measure the lifetime of the B_c meson in the B_c -> J/psi mu nu X final state. A simultaneous unbinned likelihood fit to the J/\psi+mu invariant mass and lifetime distributions yields a signal of 881 +/- 80 (stat) candidates and a lifetime measurement of \tau(B_c) = 0.448 +0.038 -0.036 (stat) +/- 0.032 (syst) ps.Comment: 7 pages, 2 figures, submitted to Phys. Rev. Let