403 research outputs found
Morphological and Pathological Evolution of the Brain Microcirculation in Aging and Alzheimer’s Disease
Key pathological hallmarks of Alzheimer’s disease (AD), including amyloid plaques, cerebral amyloid angiopathy (CAA) and neurofibrillary tangles do not completely account for cognitive impairment, therefore other factors such as cardiovascular and cerebrovascular pathologies, may contribute to AD. In order to elucidate the microvascular changes that contribute to aging and disease, direct neuropathological staining and immunohistochemistry, were used to quantify the structural integrity of the microvasculature and its innervation in three oldest-old cohorts: 1) nonagenarians with AD and a high amyloid plaque load; 2) nonagenarians with no dementia and a high amyloid plaque load; 3) nonagenarians without dementia or amyloid plaques. In addition, a non-demented (ND) group (average age 71 years) with no amyloid plaques was included for comparison. While gray matter thickness and overall brain mass were reduced in AD compared to ND control groups, overall capillary density was not different. However, degenerated string capillaries were elevated in AD, potentially suggesting greater microvascular “dysfunction” compared to ND groups. Intriguingly, apolipoprotein ε4 carriers had significantly higher string vessel counts relative to non-ε4 carriers. Taken together, these data suggest a concomitant loss of functional capillaries and brain volume in AD subjects. We also demonstrated a trend of decreasing vesicular acetylcholine transporter staining, a marker of cortical cholinergic afferents that contribute to arteriolar vasoregulation, in AD compared to ND control groups, suggesting impaired control of vasodilation in AD subjects. In addition, tyrosine hydroxylase, a marker of noradrenergic vascular innervation, was reduced which may also contribute to a loss of control of vasoconstriction. The data highlight the importance of the brain microcirculation in the pathogenesis and evolution of AD
Asthma prescribing, ethnicity and risk of hospital admission: an analysis of 35,864 linked primary and secondary care records in East London
This work was partly supported by funding from the Asthma UK Centre for Applied Research
Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set
We report a measurement of the bottom-strange meson mixing phase \beta_s
using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays
in which the quark-flavor content of the bottom-strange meson is identified at
production. This measurement uses the full data set of proton-antiproton
collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment
at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity.
We report confidence regions in the two-dimensional space of \beta_s and the
B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2,
-1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in
agreement with the standard model expectation. Assuming the standard model
value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +-
0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +-
0.009 (syst) ps, which are consistent and competitive with determinations by
other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012
Genes Differentially Expressed in Conidia and Hyphae of Aspergillus fumigatus upon Exposure to Human Neutrophils
Aspergillus fumigatus is the most common etiologic agent of invasive aspergillosis in immunocompromised patients. Several studies have addressed the mechanism involved in host defense but only few have investigated the pathogen's response to attack by the host cells. To our knowledge, this is the first study that investigates the genes differentially expressed in conidia vs hyphae of A. fumigatus in response to neutrophils from healthy donors as well as from those with chronic granulomatous disease (CGD) which are defective in the production of reactive oxygen species.Transcriptional profiles of conidia and hyphae exposed to neutrophils, either from normal donors or from CGD patients, were obtained by using the genome-wide microarray. Upon exposure to either normal or CGD neutrophils, 244 genes were up-regulated in conidia but not in hyphae. Several of these genes are involved in the degradation of fatty acids, peroxisome function and the glyoxylate cycle which suggests that conidia exposed to neutrophils reprogram their metabolism to adjust to the host environment. In addition, the mRNA levels of four genes encoding proteins putatively involved in iron/copper assimilation were found to be higher in conidia and hyphae exposed to normal neutrophils compared to those exposed to CGD neutrophils. Deletants in several of the differentially expressed genes showed phenotypes related to the proposed functions, i.e. deletants of genes involved in fatty acid catabolism showed defective growth on fatty acids and the deletants of iron/copper assimilation showed higher sensitivity to the oxidative agent menadione. None of these deletants, however, showed reduced resistance to neutrophil attack.This work reveals the complex response of the fungus to leukocytes, one of the major host factors involved in antifungal defense, and identifies fungal genes that may be involved in establishing or prolonging infections in humans
The Fitness Cost of Antibiotic Resistance in Streptococcus pneumoniae: Insight from the Field
Laboratory studies have suggested that antibiotic resistance may result in decreased fitness in the bacteria that harbor it. Observational studies have supported this, but due to ethical and practical considerations, it is rare to have experimental control over antibiotic prescription rates.We analyze data from a 54-month longitudinal trial that monitored pneumococcal drug resistance during and after biannual mass distribution of azithromycin for the elimination of the blinding eye disease, trachoma. Prescription of azithromycin and antibiotics that can create cross-resistance to it is rare in this part of the world. As a result, we were able to follow trends in resistance with minimal influence from unmeasured antibiotic use. Using these data, we fit a probabilistic disease transmission model that included two resistant strains, corresponding to the two dominant modes of resistance to macrolide antibiotics. We estimated the relative fitness of these two strains to be 0.86 (95% CI 0.80 to 0.90), and 0.88 (95% CI 0.82 to 0.93), relative to antibiotic-sensitive strains. We then used these estimates to predict that, within 5 years of the last antibiotic treatment, there would be a 95% chance of elimination of macrolide resistance by intra-species competition alone.Although it is quite possible that the fitness cost of macrolide resistance is sufficient to ensure its eventual elimination in the absence of antibiotic selection, this process takes time, and prevention is likely the best policy in the fight against resistance
Enamel-like apatite crown covering amorphous mineral in a crayfish mandible
Carbonated hydroxyapatite is the mineral found in vertebrate bones and teeth, whereas invertebrates utilize calcium carbonate in their mineralized organs. In particular, stable amorphous calcium carbonate is found in many crustaceans. Here we report on an unusual, crystalline enamel-like apatite layer found in the mandibles of the arthropod Cherax quadricarinatus (freshwater crayfish). Despite their very different thermodynamic stabilities, amorphous calcium carbonate, amorphous calcium phosphate, calcite and fluorapatite coexist in well-defined functional layers in close proximity within the mandible. The softer amorphous minerals are found primarily in the bulk of the mandible whereas apatite, the harder and less soluble mineral, forms a wear-resistant, enamel-like coating of the molar tooth. Our findings suggest a unique case of convergent evolution, where similar functional challenges of mastication led to independent developments of structurally and mechanically similar, apatite-based layers in the teeth of genetically remote phyla: vertebrates and crustaceans
How a slow-ovipositing parasitoid can succed as a biological control agent of the invasive mealybug Phenacoccus peruvianus: implications for future classical and conservation biological control programs
[EN] Phenaccocus peruvianus Granara de Willink (Hemiptera: pseudococcidae) is an invasive mealybug that has become a pest of ornamental plants in Europe and has recently been detected in California, USA. In this work, we studied the tritrophic interaction among this mealybug, its main parasitoid Acerophagus n. sp. near coccois (Hymenoptera: Encyrtidae) and tending ants to disclose the success of this parasitoid controlling P. peruvianus. Acerophagus n. sp. near coccois accepted mealybugs for parasitism regardless of their size but did not hostfeed. We recorded three active defenses of P. peruvianus. Host handling time-consuming process that required more than 30 min. Tending ants, Lasius grandis (Hymenoptera: Encyrtidae), reduced the time spent by parasitoids in a patch and disrupted oviposition attempts. The low numbers of ants tending mealybugs colonies in Spain and France could explain why this parasitoid, with a long handling time, is an efficient biological control agent for P. peruvianus.Beltrà Ivars, A.; Soto Sánchez, AI.; Tena Barreda, A. (2015). How a slow-ovipositing parasitoid can succed as a biological control agent of the invasive mealybug Phenacoccus peruvianus: implications for future classical and conservation biological control programs. BioControl. 60(4):473-484. https://doi.org/10.1007/s10526-015-9663-6S473484604Arakelian G (2013) Bougainvillea mealybug (Phenacoccus peruvianus). Factsheet 2013. County of Los Angeles. Department of agricultural commissioner/weights and measures, USABartlett BR (1961) The influence of ants upon parasites, predators, and scale insects. Ann Entomol Soc Am 54:543–551Bartlett BR (1978) Pseudococcidae. In: Clausen CP (ed) Introduced parasites and predators of arthropod pests and weeds: a world review, 1st edn. 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The insecure airway: a comparison of knots and commercial devices for securing endotracheal tubes
BACKGROUND: Endotracheal Tubes (ETTs) are commonly secured using adhesive tape, cloth tape, or commercial devices. The objectives of the study were (1) To compare degrees of movement of ETTs secured with 6 different commercial devices and (2) To compare movement of ETTs secured with cloth tape tied with 3 different knots (hitches). METHODS: A 17 cm diameter PVC tube with 14 mm "mouth" hole in the side served as a mannequin. ETTs were subjected to repeated jerks, using a cable and pulley system. Measurements: (1) Total movement of ETTs relative to "mouth" (measure used for devices) (2) Slippage of ETT through securing knot (measure used for knots). RESULTS: Among commercial devices, the Dale(® )showed less movement than other devices, although some differences between devices did not reach significance. Among knots, Magnus and Clove Hitches produced less slippage than the Cow Hitch, but these differences did not reach statistical significance. CONCLUSION: Among devices tested, the Dale(® )was most secure. Within the scope offered by the small sample sizes, there were no statistically significant differences between the knots in this study
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