Sialylation of campylobacter jejuni lipo-oligosaccharides: impact on phagocytosis and cytokine production in mice

<p>Background: Guillain-Barré syndrome (GBS) is a post-infectious polyradiculoneuropathy, frequently associated with antecedent Campylobacter jejuni (C. jejuni) infection. The presence of sialic acid on C. jejuni lipo-oligosaccharide (LOS) is considered a risk factor for development of GBS as it crucially determines the structural homology between LOS and gangliosides, explaining the induction of cross-reactive neurotoxic antibodies. Sialylated C. jejuni are recognised by TLR4 and sialoadhesin; however, the functional implications of these interactions in vivo are unknown.</p> <p>Methodology/Principal Findings: In this study we investigated the effects of bacterial sialylation on phagocytosis and cytokine secretion by mouse myeloid cells in vitro and in vivo. Using fluorescently labelled GM1a/GD1a ganglioside-mimicking C. jejuni strains and corresponding (Cst-II-mutant) control strains lacking sialic acid, we show that sialylated C. jejuni was more efficiently phagocytosed in vitro by BM-MΦ, but not by BM-DC. In addition, LOS sialylation increased the production of IL-10, IL-6 and IFN-β by both BM-MΦ and BM-DC. Subsequent in vivo experiments revealed that sialylation augmented the deposition of fluorescent bacteria in splenic DC, but not macrophages. In addition, sialylation significantly amplified the production of type I interferons, which was independent of pDC.</p> <p>Conclusions/Significance: These results identify novel immune stimulatory effects of C. jejuni sialylation, which may be important in inducing cross-reactive humoral responses that cause GBS</p&gt

Monitoring sedentary patterns in office employees: validity of an m-health tool (Walk@Work-App) for occupational health.

OBJECTIVE: This study validated the Walk@Work-Application (W@W-App) for measuring occupational sitting and stepping. METHODS: The W@W-App was installed on the smartphones of office-based employees (n=17; 10 women; 26±3 years). A prescribed 1-hour laboratory protocol plus two continuous hours of occupational free-living activities were performed. Intra-class correlation coefficients (ICC) compared mean differences of sitting time and step count measurements between the W@W-App and criterion measures (ActivPAL3TM and SW200Yamax Digi-Walker). RESULTS: During the protocol, agreement between self-paced walking (ICC=0.85) and active working tasks step counts (ICC=0.80) was good. The smallest median difference was for sitting time (1.5seconds). During free-living conditions, sitting time (ICC=0.99) and stepping (ICC=0.92) showed excellent agreement, with a difference of 0.5minutes and 18 steps respectively. CONCLUSIONS: The W@W-App provided valid measures for monitoring occupational sedentary patterns in real life conditions; a key issue for increasing awareness and changing occupational sedentariness

The Sloan Digital Sky Survey Quasar Catalog IV. Fifth Data Release

We present the fourth edition of the Sloan Digital Sky Survey (SDSS) Quasar Catalog. The catalog contains 77,429 objects; this is an increase of over 30,000 entries since the previous edition. The catalog consists of the objects in the SDSS Fifth Data Release that have luminosities larger than M_i = -22.0 (in a cosmology with H_0 = 70 km/s/Mpc, Omega_M = 0.3, and Omega_Lambda = 0.7) have at least one emission line with FWHM larger than 1000 km/s, or have interesting/complex absorption features, are fainter than i=15.0, and have highly reliable redshifts. The area covered by the catalog is 5740 sq. deg. The quasar redshifts range from 0.08 to 5.41, with a median value of 1.48; the catalog includes 891 quasars at redshifts greater than four, of which 36 are at redshifts greater than five. Approximately half of the catalog quasars have i < 19; nearly all have i < 21. For each object the catalog presents positions accurate to better than 0.2 arcsec. rms per coordinate, five-band (ugriz) CCD-based photometry with typical accuracy of 0.03 mag, and information on the morphology and selection method. The catalog also contains basic radio, near-infrared, and X-ray emission properties of the quasars, when available, from other large-area surveys. The calibrated digital spectra cover the wavelength region 3800--9200A at a spectral resolution of ~2000. The spectra can be retrieved from the public database using the information provided in the catalog. The average SDSS colors of quasars as a function of redshift, derived from the catalog entries, are presented in tabular form. Approximately 96% of the objects in the catalog were discovered by the SDSS.Comment: 37 pages, Accepted for publication in A

Identification of domestication-related loci associated with flowering time and seed size in soybean with the RAD-seq genotyping method

Flowering time and seed size are traits related to domestication. However, identification of domestication-related loci/genes of controlling the traits in soybean is rarely reported. In this study, we identified a total of 48 domestication-related loci based on RAD-seq genotyping of a natural population comprising 286 accessions. Among these, four on chromosome 12 and additional two on chromosomes 11 and 15 were associated with flowering time, and four on chromosomes 11 and 16 were associated with seed size. Of the five genes associated with flowering time and the three genes associated with seed size, three genes Glyma11g18720, Glyma11g15480 and Glyma15g35080 were homologous to Arabidopsis genes, additional five genes were found for the first time to be associated with these two traits. Glyma11g18720 and Glyma05g28130 were co-expressed with five genes homologous to flowering time genes in Arabidopsis, and Glyma11g15480 was co-expressed with 24 genes homologous to seed development genes in Arabidopsis. This study indicates that integration of population divergence analysis, genome-wide association study and expression analysis is an efficient approach to identify candidate domestication-related genes

The Search for Gravitational Waves

Experiments aimed at searching for gravitational waves from astrophysical sources have been under development for the last 40 years, but only now are sensitivities reaching the level where there is a real possibility of detections being made within the next five years. In this article a history of detector development will be followed by a description of current detectors such as LIGO, VIRGO, GEO 600, TAMA 300, Nautilus and Auriga. Preliminary results from these detectors will be discussed and related to predicted detection rates for some types of sources. Experimental challenges for detector design are introduced and discussed in the context of detector developments for the future.Comment: 21 pages, 7 figures, accepted J. Phys. B: At. Mol. Opt. Phy

A Phase I Study of Pegylated Arginine Deiminase (Pegargiminase), Cisplatin, and Pemetrexed in Argininosuccinate Synthetase 1-Deficient Recurrent High-grade Glioma.

PURPOSE: Patients with recurrent high-grade gliomas (HGG) are usually managed with alkylating chemotherapy ± bevacizumab. However, prognosis remains very poor. Preclinically, we showed that HGGs are a target for arginine depletion with pegargiminase (ADI-PEG20) due to epimutations of argininosuccinate synthetase (ASS1) and/or argininosuccinate lyase (ASL). Moreover, ADI-PEG20 disrupts pyrimidine pools in ASS1-deficient HGGs, thereby impacting sensitivity to the antifolate, pemetrexed. PATIENTS AND METHODS: We expanded a phase I trial of ADI-PEG20 with pemetrexed and cisplatin (ADIPEMCIS) to patients with ASS1-deficient recurrent HGGs (NCT02029690). Patients were enrolled (01/16-06/17) to receive weekly ADI-PEG20 36 mg/m2 intramuscularly plus pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 intravenously once every 3 weeks for up to 6 cycles. Patients with disease control were allowed ADI-PEG20 maintenance. The primary endpoints were safety, tolerability, and preliminary estimates of efficacy. RESULTS: Ten ASS1-deficient heavily pretreated patients were treated with ADIPEMCIS therapy. Treatment was well tolerated with the majority of adverse events being Common Terminology Criteria for Adverse Events v4.03 grade 1-2. The best overall response was stable disease in 8 patients (80%). Plasma arginine was suppressed significantly below baseline with a reciprocal increase in citrulline during the sampling period. The anti-ADI-PEG20 antibody titer rose during the first 4 weeks of treatment before reaching a plateau. Median progression-free survival (PFS) was 5.2 months (95% confidence interval (CI), 2.5-20.8) and overall survival was 6.3 months (95% CI, 1.8-9.7). CONCLUSIONS: In this recurrent HGG study, ADIPEMCIS was well tolerated and compares favorably to historical controls. Additional trials of ADI-PEG20 in HGG are planned

Subclinical Thyroid Disorders and Cognitive Performance Among Adolescents in the United States

Background: Thyroid hormone plays a crucial role in the growth and function of the central nervous system. The purpose of the study was to examine the relationships between the status of subclinical thyroid conditions and cognition among adolescents in the United States. Methods: Study sample included 1,327 adolescents 13 to 16 years old who participated in the Third National Health and Nutrition Examination Survey (NHANES III). Serum thyroxine (T4) and thyroid stimulating hormone (TSH) were measured and subclinical hypothyroidism, subclinical hyperthyroidism, and euthyroid groups were defined. Cognitive performance was assessed using the subscales of the Wide Range Achievement Test-Revised (WRAT-R) and the Wechsler Intelligence Scale for Children-Revised (WISC-R). The age-corrected scaled scores for arithmetic, reading, block design, and digit span were derived from the cognitive assessments. Results: Subclinical hypothyroidism was found in 1.7% and subclinical hyperthyroidism was found in 2.3% of the adolescents. Cognitive assessment scores on average tended to be lower in adolescents with subclinical hyperthyroidism and higher in those with subclinical hypothyroidism than the score for the euthyroid group. Adolescents with subclinical hypothyroidism had significantly better scores in block design and reading than the euthyroid subjects even after adjustment for a number of variables including sex, age, and family income level. Conclusion: Subclinical hypothyroidism was associated with better performance in some areas of cognitive functions while subclinical hyperthyroidism could be a potential risk factor