Carbohydrate and protein contents of grain dusts in relation to dust morphology.

Grain dusts contain a variety of materials which are potentially hazardous to the health of workers in the grain industry. Because the characterization of grain dusts is incomplete, we are defining the botanical, chemical, and microbial contents of several grain dusts collected from grain elevators in the Duluth-Superior regions of the U.S. Here, we report certain of the carbohydrate and protein contents of dusts in relation to dust morphology. Examination of the gross morphologies of the dusts revealed that, except for corn, each dust contained either husk or pericarp (seed coat in the case of flax) fragments in addition to respirable particles. When viewed with the light microscope, the fragments appeared as elongated, pointed structures. The possibility that certain of the fragments within corn, settled, and spring wheat were derived from cell walls was suggested by the detection of pentoses following colorimetric assay of neutralized 2 N trifluoroacetic acid hydrolyzates of these dusts. The presence of pentoses together with the occurrence of proteins within water washings of grain dusts suggests that glycoproteins may be present within the dusts. With scanning electron microscopy, each dust was found to consist of a distinct assortment of particles in addition to respirable particles. Small husk fragments and "trichome-like" objects were common to all but corn dust

Chronic Lung Function Decline in Cotton Textile Workers: Roles of Historical and Recent Exposures to Endotoxin

BackgroundLong-term occupational exposure to cotton dust that contains endotoxin is associated with chronic respiratory symptoms and excessive decline in forced expiratory volume in 1 sec (FEV1), but the mechanisms of endotoxin-related chronic airflow obstruction remain unclear.ObjectiveIn the current study, we examined temporal aspects of the exposure-response relationship between airborne endotoxin exposure, longitudinal change in FEV1, and respiratory symptoms in a cohort of Chinese cotton textile workers.MethodsThis prospective cohort study followed 447 cotton textile workers from 1981 to 2006. at approximately 5-year intervals. We used a generalized estimating equations approach to model FEV1 level and respiratory symptoms as a function of past exposure (cumulative exposure up to the start of the most recent 5-year survey interval) and cumulative exposure (within the most recent interval) to endotoxins, after adjusting for other covariates. Models were stratified by active versus retired work status and by years employed before the baseline survey (< 5 and > or = 5 years).Results and conclusionsPast exposure to endotoxin was associated with reduced FEV1 level among retired cotton workers. Among all cotton workers, past exposure was more strongly associated with reduced FEV1 for those hired < 5 years before baseline than for those who were hired > or = 5 years after baseline. Recent endotoxin exposure was significantly associated with byssinosis, chronic bronchitis, and chronic cough

Essential Role of Neuron-Enriched Diacylglycerol Kinase (DGK), DGKβ in Neurite Spine Formation, Contributing to Cognitive Function

BACKGROUND: Diacylglycerol (DG) kinase (DGK) phosphorylates DG to produce phosphatidic acid (PA). Of the 10 subtypes of mammalian DGKs, DGKbeta is a membrane-localized subtype and abundantly expressed in the cerebral cortex, hippocampus, and caudate-putamen. However, its physiological roles in neurons and higher brain function have not been elucidated. METHODOLOGY/PRINCIPAL FINDINGS: We, therefore, developed DGKbeta KO mice using the Sleeping Beauty transposon system, and found that its long-term potentiation in the hippocampal CA1 region was reduced, causing impairment of cognitive functions including spatial and long-term memories in Y-maze and Morris water-maze tests. The primary cultured hippocampal neurons from KO mice had less branches and spines compared to the wild type. This morphological impairment was rescued by overexpression of DGKbeta. In addition, overexpression of DGKbeta in SH-SY5Y cells or primary cultured mouse hippocampal neurons resulted in branch- and spine-formation, while a splice variant form of DGKbeta, which has kinase activity but loses membrane localization, did not induce branches and spines. In the cells overexpressing DGKbeta but not the splice variant form, DGK product, PA, was increased and the substrate, DG, was decreased on the plasma membrane. Importantly, lower spine density and abnormality of PA and DG contents in the CA1 region of the KO mice were confirmed. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that membrane-localized DGKbeta regulates spine formation by regulation of lipids, contributing to the maintenance of neural networks in synaptic transmission of cognitive processes including memory

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Cyanobacterial lipopolysaccharides and human health – a review

Cyanobacterial lipopolysaccharide/s (LPS) are frequently cited in the cyanobacteria literature as toxins responsible for a variety of heath effects in humans, from skin rashes to gastrointestinal, respiratory and allergic reactions. The attribution of toxic properties to cyanobacterial LPS dates from the 1970s, when it was thought that lipid A, the toxic moiety of LPS, was structurally and functionally conserved across all Gram-negative bacteria. However, more recent research has shown that this is not the case, and lipid A structures are now known to be very different, expressing properties ranging from LPS agonists, through weak endotoxicity to LPS antagonists. Although cyanobacterial LPS is widely cited as a putative toxin, most of the small number of formal research reports describe cyanobacterial LPS as weakly toxic compared to LPS from the Enterobacteriaceae. We systematically reviewed the literature on cyanobacterial LPS, and also examined the much lager body of literature relating to heterotrophic bacterial LPS and the atypical lipid A structures of some photosynthetic bacteria. While the literature on the biological activity of heterotrophic bacterial LPS is overwhelmingly large and therefore difficult to review for the purposes of exclusion, we were unable to find a convincing body of evidence to suggest that heterotrophic bacterial LPS, in the absence of other virulence factors, is responsible for acute gastrointestinal, dermatological or allergic reactions via natural exposure routes in humans. There is a danger that initial speculation about cyanobacterial LPS may evolve into orthodoxy without basis in research findings. No cyanobacterial lipid A structures have been described and published to date, so a recommendation is made that cyanobacteriologists should not continue to attribute such a diverse range of clinical symptoms to cyanobacterial LPS without research confirmation

Histone H3 lysine 9 methylation and HP1γ are associated with transcription elongation through mammalian chromatin

Methylation of histones modulates chromatin structure and function. Whereas methylation of histone H3 on lysines 4, 36, and 79 has been linked with gene activation, methylation of H3 on lysines 9 and 27 and histone H4 on lysine 20 is associated with heterochromatin and some repressed genes within euchromatin. Here, we show that H3K9 di- and trimethylation occur in the transcribed region of active genes in mammalian chromatin. This modification is dynamic, as it increases during activation of transcription and is rapidly removed upon gene repression. Heterochromatin Protein 1γ (HP1γ), a protein containing a chromo-domain that recognizes H3K9 methylation, is also present in the transcribed region of all active genes examined. Both the presence of HP1γ and H3K9 methylation are dependent upon elongation by RNA polymerase II. These findings demonstrate novel roles for H3K9 methylation and HP1γ in transcription activation. Copyright ©2005 by Elsevier Inc