Sialic acid isomers attached in either α2,3 or α2,6 linkage to glycan termini confer distinct chemical, biological, and pathological properties, but they cannot be distinguished by mass differences ...in traditional mass spectrometry experiments. Multiple derivatization strategies have been developed to stabilize and facilitate the analysis of sialic acid isomers and their glycoconjugate carriers by high-performance liquid chromatography, capillary electrophoresis, and mass spectrometry workflows. Herein, a set of novel derivatization schemes are described that result in the introduction of bioorthogonal click chemistry alkyne or azide groups into α2,3- and α2,8-linked sialic acids. These chemical modifications were validated and structurally characterized using model isomeric sialic acid conjugates and model protein carriers. Use of an alkyne-amine, propargylamine, as the second amidation reagent effectively introduces an alkyne functional group into α2,3-linked sialic acid glycoproteins. In tissues, serum, and cultured cells, this allows for the detection and visualization of
-linked glycan sialic acid isomers by imaging mass spectrometry approaches. Formalin-fixed paraffin-embedded prostate cancer tissues and pancreatic cancer cell lines were used to characterize the numbers and distribution of alkyne-modified α2,3-linked sialic acid
-glycans. An azide-amine compound with a poly(ethylene glycol) linker was evaluated for use in histochemical staining. Formalin-fixed pancreatic cancer tissues were amidated with the azide amine, reacted with biotin-alkyne and copper catalyst, and sialic acid isomers detected by streptavidin-peroxidase staining. The direct chemical introduction of bioorthogonal click chemistry reagents into sialic acid-containing glycans and glycoproteins provides a new glycomic tool set to expand approaches for their detection, labeling, visualization, and enrichment.
Physical activity (PA) can protect against depression, but few studies have assessed whether meeting PA guidelines is sufficient, or if benefits can be derived from greater volumes of PA. The present ...study examines cross-sectional and prospective associations between different volumes of moderate-to-vigorous PA (MVPA) and walking, and depressive symptoms and status. Participants (n = 4556; 56.7% female) aged ≥ 50 years completed the International PA Questionnaire (IPAQ) at baseline and the Center for Epidemiological Studies Depression Scale at baseline and two years later. Prevalence and incidence of depression were 9.0% (n = 410) and 5.0% (n = 207), respectively. After full adjustment, odds of prevalent depression were: 40% (OR = 0.60, 95%CI: 0.48–0.76) lower among those meeting PA guidelines; 23% (OR = 0.77, 0.49–1.21) and 43% (OR = 0.57, 0.45–0.73) lower among those in moderate and high categories, respectively; and, 22% (OR = 0.78, 0.61–1.01) and 44.0% (OR = 0.56, 0.42–0.74) lower among those in moderate and high walking tertiles, respectively. Odds of incident depression were: 23% (OR = 0.77, 0.58–1.04) lower among those meeting PA guidelines; 37% (OR = 0.63, 0.32–1.22) and 20.0% (OR = 0.80, 0.59–1.09) lower among those in moderate and high categories, respectively; and, 21% (OR = 0.79, 0.56–1.12) and 25% (OR = 0.75, 0.52–1.07) lower among those in moderate and high walking tertiles, respectively. Moderate and high volumes of MVPA were significantly associated with lower odds of concurrent depression, and significantly and non-significantly associated with reduced odds of incident depression, respectively. Meeting recommended levels of MVPA and walking were associated with significantly lower odds of concurrent depression, and non-significantly reduced odds of the development of depression over two years.
•A greater proportion of respondents who reported depression were aged 80+ years, female, and current smokers.•A dose-response was observed for moderate-to-vigorous physical activity (PA) and walking in cross-sectional analyses.•Meeting PA guidelines was significantly and non-significantly associated with lower odds of prevalent and incident depression.
Exposure to methyl mercury, a risk factor for neurodevelopmental toxicity, was assessed in U.S. children 1-5 years of age (n = 838) and women 16-49 years of age (n = 1,726) using hair mercury ...analysis during the 1999-2000 National Health and Nutrition Examination Survey (NHANES). The data are nationally representative and are based on analysis of cross-sectional data for the non-institutionalized, U.S. household population. The survey consisted of interviews conducted in participants' homes and standardized health examinations conducted in mobile examination centers. Distributions of total hair mercury levels expressed as micrograms per gram hair Hg and the association of hair Hg levels with sociodemographic characteristics and fish consumption are reported. Geometric mean (standard error of the geometric mean) hair mercury was 0.12 μg/g (0.01 μg/g) in children, and 0.20 μg/g (0.02 μg/g) in women. Among frequent fish consumers, geometric mean hair mercury levels were 3-fold higher for women (0.38 vs. 0.11 μg/g) and 2-fold higher for children (0.16 vs. 0.08 μg/g) compared with nonconsumers. The NHANES 1999-2000 data provide population-based data on hair mercury concentrations for women and children in the United States. Hair mercury levels were associated with age and fish consumption frequency.
N-glycan imaging mass spectrometry (IMS) can rapidly and reproducibly identify changes in disease-associated N-linked glycosylation that are linked with histopathology features in standard ...formalin-fixed paraffin-embedded tissue samples. It can detect multiple N-glycans simultaneously and has been used to identify specific N-glycans and carbohydrate structural motifs as possible cancer biomarkers. Recent advancements in instrumentation and sample preparation are also discussed. The tissue N-glycan IMS workflow has been adapted to new glass slide-based assays for effective and rapid analysis of clinical biofluids, cultured cells, and immunoarray-captured glycoproteins for detection of changes in glycosylation associated with disease.
The protein-protein interaction between leukocyte functional antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) is critical to lymphocyte and immune system function. Here, we report on ...the transfer of the contiguous, nonlinear epitope of ICAM-1, responsible for its association with LFA-1, to a small-molecule framework. These LFA-1 antagonists bound LFA-1, blocked binding of ICAM-1, and inhibited a mixed lymphocyte reaction (MLR) with potency significantly greater than that of cyclosporine A. Furthermore, in comparison to an antibody to LFA-1, they exhibited significant anti-inflammatory effects in vivo. These results demonstrate the utility of small-molecule mimics of nonlinear protein epitopes and the protein epitopes themselves as leads in the identification of novel pharmaceutical agents.
Humans are exposed to methylmercury, a well-established neurotoxin, through fish consumption. The fetus is most sensitive to the adverse effects of exposure. The extent of exposure to methylmercury ...in US women of reproductive age is not known.
To describe the distribution of blood mercury levels in US children and women of childbearing age and the association with sociodemographic characteristics and fish consumption.
The 1999-2000 data from the National Health and Nutrition Examination Survey, a cross-sectional survey of the noninstitutionalized US population.
In 1999-2000, 1250 children aged 1 to 5 years and 2314 women aged 16 to 49 years were selected to participate in the survey. Household interviews, physical examinations, and blood mercury levels assessments were performed on 705 children (56% response rate) and 1709 women (74% response rate).
Blood concentration of total mercury.
Blood mercury levels were approximately 3-fold higher in women compared with children. The geometric mean concentration of total blood mercury was 0.34 micro g/L (95% confidence interval CI, 0.30-0.39 microg/L) in children and 1.02 microg/L (95% CI, 0.85-1.20 microg/L) in women. Geometric mean mercury levels were almost 4-fold higher among women who ate 3 or more servings of fish in the past 30 days compared with women who ate no fish in that period (1.94 microg/L vs 0.51 microg/L; P<.001).
Measures of mercury exposure in women of childbearing age and young children generally fall below levels of concern. However, approximately 8% of women had concentrations higher than the US Environmental Protection Agency's recommended reference dose (5.8 microg/L), below which exposures are considered to be without adverse effects. Women who are pregnant or who intend to become pregnant should follow federal and state advisories on consumption of fish.
State and local health departments established the California Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Respiratory Virus Sentinel Surveillance System to conduct enhanced ...surveillance for SARS-CoV-2 and other respiratory pathogens at sentinel outpatient testing sites in 10 counties throughout California, USA. We describe results obtained during May 10, 2020‒June 12, 2021, and compare persons with positive and negative SARS-CoV-2 PCR results by using Poisson regression. We detected SARS-CoV-2 in 1,696 (19.6%) of 8,662 specimens. Among 7,851 specimens tested by respiratory panel, rhinovirus/enterovirus was detected in 906 (11.5%) specimens and other respiratory pathogens in 136 (1.7%) specimens. We also detected 23 co-infections with SARS-CoV-2 and another pathogen. SARS-CoV-2 positivity was associated with male participants, an age of 35-49 years, Latino race/ethnicity, obesity, and work in transportation occupations. Sentinel surveillance can provide useful virologic and epidemiologic data to supplement other disease monitoring activities and might become increasingly useful as routine testing decreases.
As important vectors of human disease, phlebotomine sand flies are of global significance to human health, transmitting several emerging and re‐emerging infectious diseases. The most devastating of ...the sand fly transmitted infections are the leishmaniases, causing significant mortality and morbidity in both the Old and New World. Here we present the first global transcriptome analysis of the Old World vector of cutaneous leishmaniasis, Phlebotomus papatasi (Scopoli) and compare this transcriptome to that of the New World vector of visceral leishmaniasis, Lutzomyia longipalpis. A normalized cDNA library was constructed using pooled mRNA from Phlebotomus papatasi larvae, pupae, adult males and females fed sugar, blood, or blood infected with Leishmania major. A total of 47 615 generated sequences was cleaned and assembled into 17 120 unique transcripts. Of the assembled sequences, 50% (8837 sequences) were classified using Gene Ontology (GO) terms. This collection of transcripts is comprehensive, as demonstrated by the high number of different GO categories. An in‐depth analysis revealed 245 sequences with putative homology to proteins involved in blood and sugar digestion, immune response and peritrophic matrix formation. Twelve of the novel genes, including one trypsin, two peptidoglycan recognition proteins (PGRP) and nine chymotrypsins, have a higher expression level during larval stages. Two novel chymotrypsins and one novel PGRP are abundantly expressed upon blood feeding. This study will greatly improve the available genomic resources for P. papatasi and will provide essential information for annotation of the full genome.
Generalized anxiety disorder (GAD) is prevalent and costly. Physical activity (PA) may protect against other mental health disorders, including depression, but its protective effect on GAD remains ...under-studied in the general population and unstudied among older adults. Therefore, the present study examines associations between meeting World Health Organization PA guidelines (i.e. ≥150 min of moderate PA, ≥75 min of vigorous PA or ≥600MET min of moderate and vigorous PA weekly) and the prevalence of probable GAD and incidence of GAD.
Participants (n = 3950; 56.2% female) aged ≥50 years completed the short-form International Physical Activity Questionnaire and the abbreviated Penn State Worry Questionnaire at baseline and the Composite International Diagnostic Interview - Short Form to clinically assess GAD 2 years later. Prospective analyses included participants without probable GAD at baseline (n = 3236).
Prevalence and incidence of GAD were 18.1% (n = 714) and 0.9% (n = 29), respectively. More respondents with GAD were female (72.2% vs 52.7%), aged 50-59 years (51.7% vs 38.7%), had normal waist circumference (52.7% vs 47.8) and smoked (20.4% vs 13.3%; all P <0.05). Meeting PA guidelines was associated with 25% and 63% lower odds of prevalent odds ratio (OR) = 0.75, 95% confidence interval: 0.64 to 0.88 and incident (OR = 0.37, 0.17 to 0.85) GAD, respectively, in crude models, and 17% and 57% lower odds of prevalent (OR = 0.83, 0.70 to 0.98) and incident (OR = 0.43, 0.19 to 0.99) GAD, respectively, following adjustment for age, sex, waist circumference, social class and smoking.
In addition to established physical health benefits of PA, the present findings support the importance of increasing PA at the population-level for mental health.
Applications of SELDI‐MS technology in oncology Whelan, L. C.; Power, K. A. R.; McDowell, D. T. ...
Journal of cellular and molecular medicine,
September/October 2008, Letnik:
12, Številka:
5a
Journal Article
Recenzirano
Odprti dostop
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Introduction
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Surface enhanced laser desorption/ionisation‐mass spectrometry
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Sampling
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Clinical applications
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Detection and diagnosis
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Pre‐operative staging of disease
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Predicting ...response to therapy
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Metastasis and disease progression
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Drug resistance
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In vitro applications
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Cell culture models
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Protein interactions
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Advantages over conventional technologies
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Limitations
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Conclusions
Considerable interest, speculation and controversy have been generated utilising surface‐enhanced laser desorption/ionization in conjunction with mass spectrometry (SELDI‐MS) for the diagnosis, prognosis and therapeutic monitoring of cancer and offers an attractive approach to cancer biomarker discovery from tissues and biological fluids. This technology utilises a combination of mass spectrometry and chromatography to facilitate protein profiling of complex biological mixtures. Compared to some other more traditional proteomic platforms, such as 2D polyacrylamide gel electrophoresis, it has a high‐throughput capability and can resolve low‐mass proteins. However, a considerable number of challenging issues related to the design of studies, including reproducibility, sensitivity, specificity, variation in sample collection, processing and storage, have been reported as problematic with this technology; albeit some of these concerns could perhaps also be lauded against other proteomic approaches that have attempted to address complex protein mixtures, such as plasma. Applications, successes and limitations of SELDI‐MS in both clinical and basic science arenas will be reviewed in this article.
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