Apolipoprotein E polymorphism and serum concentration in Alzheimer's disease in nine European centres:the ApoEurope study. ApoEurope group

As part of the ApoEurope Project, apolipoprotein E (apo E) common polymorphism and serum concentration were determined in 489 Alzheimer's disease patients and 429 controls. Patients and controls were recruited through nine centres in eight European countries. Age, sex ratios and education levels of both case and control populations were similar, although discrete differences appeared between centres. The prevalence of the epsilon4 allele was higher in Alzheimer's disease than in controls (increased by 140%), while serum apo E concentration was lower by 11.2% (p

What are RBC-transfusion-dependence and -independence?

The term RBC-transfusion-dependence is widely-used by hematologists to describe a condition of severe anemia typically arising when erythropoiesis is reduced such that a person continuously requires =1 RBC-transfusions over a specified interval. Defining a person as RBC-transfusion-dependent has important implications in diverse hematological disorders especially because it strongly-correlated with decreased survival. Conversely, becoming RBC-transfusion-independent or receiving fewer RBC-transfusions over a specified interval is defined as improvement or response in many disease- and/or therapy-setting. Whether this correlates with improved survival is controversial. We used a structured expert-panel consensus panel process to define RBC-transfusion-dependence and -independence or improvement. We suggest these definitions may prove useful to persons studying or treating these diseases.

Two new mutations in the HIF2A gene associated with erythrocytosis

Congenital or familial erythrocytosis/polycythemia can have many causes, and an emerging cause is genetic disruption of the oxygen-sensing pathway that regulates the Erythropoietin (EPO) gene. More specifically, recent studies have identified erythrocytosis-associated mutations in the HIF2A gene, which encodes for Hypoxia Inducible Factor-2a (HIF-2a), as well as in two genes that encode for proteins that regulate it, Prolyl Hydroxylase Domain protein 2 (PHD2) and the von Hippel Lindau tumor suppressor protein (VHL). We report here the identification of two new heterozygous HIF2A missense mutations, M535T, and F540L, both associated with erythrocytosis. Met-535 has previously been identified as a residue mutated in other patients with erythrocytosis; although, the mutation of this particular residue to Thr has not been reported. In contrast, Phe-540 has not been reported as a residue mutated in erythrocytosis, and we present evidence here that this mutation impairs interaction of HIF-2a with both VHL and PHD2. © 2012 Wiley Periodicals, Inc.

Phosphotungstic Acid Encapsulated in Metal-Organic Framework as Catalysts for Carbohydrate Dehydration to 5-Hydroxymethylfurfural

MIL-101, a chromium-based metal-organic framework, is known for its very large pore size, large surface area and good stability. However, applications of this material in catalysis are still limited. 5-Hydroxymethylfurfural (HMF) has been considered a renewable chemical platform for the production of liquid fuels and fine chemicals. Phosphotungstic acid, H3PW12O40 (PTA), encapsulated in MIL-101 is evaluated as a potential catalyst for the selective dehydration of fructose and glucose to 5-hydroxymethylfurfural. The results demonstrate that PTA/MIL-101 is effective for HMF production from fructose in DMSO and can be reused. This is the first example of the application of a metal-organic framework in carbohydrate dehydration.

Late Quaternary tephrostratigraphy, Ahklun Mountains, SW Alaska

Radiocarbon-dated sediment cores from six lakes in the Ahklun Mountains, south-western Alaska, were used to interpolate the ages of late Quaternary tephra beds ranging in age from 25.4 to 0.4ka. The lakes are located downwind of the Aleutian Arc and Alaska Peninsula volcanoes in the northern Bristol Bay area between 159° and 161°W at around 60°N. Sedimentation-rate age models for each lake were based on a published spline-fit procedure that uses Monte Carlo simulation to determine age model uncertainty. In all, 62 C ages were used to construct the six age models, including 23 ages presented here for the first time. The age model from Lone Spruce Pond is based on 18 ages, and is currently the best-resolved Holocene age model available from the region, with an average 2s age uncertainty of about±109 years over the past 14.5ka. The sedimentary sequence from Lone Spruce Pond contains seven tephra beds, more than previously found in any other lake in the area. Of the 26 radiocarbon-dated tephra beds at the six lakes and from a soil pit, seven are correlated between two or more sites based on their ages. The major-element geochemistry of glass shards from most of these tephra beds supports the age-based correlations. The remaining tephra beds appear to be present at only one site based on their unique geochemistry or age. The 5.8ka tephra is similar to the widespread Aniakchak tephra [3.7±0.2 (1s) ka], but can be distinguished conclusively based on its trace-element geochemistry. The 3.1 and 0.4ka tephras have glass major- and trace-element geochemical compositions indistinguishable from prominent Aniakchak tephra, and might represent redeposited beds. Only two tephra beds are found in all lakes: the Aniakchak tephra (3.7±0.2ka) and Tephra B (6.1±0.3ka). The tephra beds can be used as chronostratigraphic markers for other sedimentary sequences in the region, including cores from Cascade and Sunday lakes, which were previously undated and were analyzed in this study to correlate with the new regional tephrostratigraphy. © 2012 John Wiley & Sons, Ltd.

Northern peatland initiation lagged abrupt increases in deglacial atmospheric CH4

Peatlands are a key component of the global carbon cycle. Chronologies of peatland initiation are typically based on compiled basal peat radiocarbon (14C) dates and frequency histograms of binned calibrated age ranges. However, such compilations are problematic because poor quality 14C dates are commonly included and because frequency histograms of binned age ranges introduce chronological artefacts that bias the record of peatland initiation. Using a published compilation of 274 basal 14C dates from Alaska as a case study, we show that nearly half the 14C dates are inappropriate for reconstructing peatland initiation, and that the temporal structure of peatland initiation is sensitive to sampling biases and treatment of calibrated14C dates. We present revised chronologies of peatland initiation for Alaska and the circumpolar Arctic based on summed probability distributions of calibrated 14C dates. These revised chronologies reveal that northern peatland initiation lagged abrupt increases in atmospheric CH4 concentration at the start of the Bølling–Allerød interstadial (Termination 1A) and the end of the Younger Dryas chronozone (Termination 1B), suggesting that northern peatlands were not the primary drivers of the rapid increases in atmospheric CH4. Our results demonstrate that subtle methodological changes in the synthesis of basal 14C ages lead to substantially different interpretations of temporal trends in peatland initiation, with direct implications for the role of peatlands in the global carbon cycle.

Judging pain in newborns:facial and cry determinants

Explored the facial and cry characteristics that adults use when judging an infant's pain. Sixteen women viewed videotaped reactions of 36 newborns subjected to noninvasive thigh rubs and vitamin K injections in the course of routine care and rated discomfort. The group mean interrater reliability was high. Detailed descriptions of the infants' facial reactions and cry sounds permitted specification of the determinants of distress judgments. Several facial variables (a brow bulge, eyes squeezed shut, and deepened nasolabial fold constellation, and taut tongue) accounted for 49% of the variance in ratings of affective discomfort after controlling for ratings of discomfort during a noninvasive event. In a separate analysis not including facial activity, several cry variables (formant frequency, latency to cry) also accounted for variance (38%) in ratings. When the facial and cry variables were considered together, cry variables added little to the prediction of ratings in comparison to facial variables. Cry would seem to command attention, but facial activity, rather than cry, can account for the major variations in adults' judgments of neonatal pain.

Neonatal facial and cry responses to invasive and non-invasive procedures

Evaluation of pain in neonates is difficult due to their limited means of communication. The aim was to determine whether behavioural reactions of cry and facial activity provoked by an invasive procedure could be discriminated from responses to non-invasive tactile events. Thirty-six healthy full-term infants (mean age 2.2 h) received 3 procedures in counterbalanced order: intramuscular injection, application of triple dye to the umbilical stub, and rubbing thigh with alcohol. Significant effects of procedure were found for total face activity and latency to face movement. A cluster of facial actions comprised of brow bulging, eyes squeezed shut, deepening of the naso-labial furrow and open mouth was associated most frequently with the invasive procedure. Comparisons between the 2 non-invasive procedures showed more facial activity to thigh swabbing and least to application of triple dye to the umbilical cord. Acoustic analysis of cry showed statistically significant differences across procedures only for latency to cry and cry duration for the group as a whole. However, babies who cried to two procedures showed higher pitch and greater intensity to the injection. There were no significant differences in melody, dysphonation, or jitter. Methodological difficulties for investigators in this area were examined, including criteria for the selection of cries for analysis, and the logical and statistical challenges of contrasting cries induced by different conditions when some babies do not always cry. It was concluded that facial expression, in combination with short latency to onset of cry and long duration of first cry cycle typifies reaction to acute invasive procedures.

Expression of Toll-Like Receptors 2 and 4 is Upregulated During Hospital Admission in Traumatic Patients:Lack of Correlation with Blunted Innate Immune Responses

Background: There are reports with conflicting results on the expression of toll-like receptors (TLRs) in trauma patients. In addition, these studies analyzed TLR expression only at patients hospital admission but not later when complications usually arise. Objectives: To analyze the surface expression of TLR2 and TLR4 on circulating monocytes from trauma patients during the hospitalization period and to correlate this with cytokine production after stimulation with TLR2 and TLR4 agonists. The phagocytic capacity of monocytes was analyzed at the same time points of TLR expression analysis; to correlate these molecular findings with the presence or absence of infections. Methods: Prospective and observational study from June 2005 to June 2007. In all analysis, a control group composed of healthy subjects was included. Results: We studied 70 trauma patients admitted to the intensive care unit (ICU) of a tertiary hospital, and 30 healthy volunteers. Blood samples were collected at hospital admission, on day 7 and 14. Forty-four patients (63%) developed at least one episode of infection. Monocytes from trauma patients expressed higher levels of TLR2 and TLR4 than monocytes from control subjects at all time points. Expression of TLR2 and TLR4 in monocytes from those patients who developed any infection was significantly lower than in those patients without infection but still significantly higher than in control subjects. Cellular responses to TLR4 agonist were impaired. Monocytes from traumatic patients phagocytosized less efficiently than monocytes from control subjects. Conclusions: These results indicate that trauma patients present a dysregulation of the innate immune system that persists during the first 14 days after hospital admission. Copyright © 2010 by Lippincott Williams & Wilkins.

Evidence for a non-replicative intracellular stage of nontypable Haemophilus influenzae in epithelial cells

Nontypable Haemophilus influenzae (NTHi) is a Gram-negative, non-capsulated human bacterial pathogen, a major cause of a repertoire of respiratory infections, and intimately associated with persistent lung bacterial colonization in patients suffering from chronic obstructive pulmonary disease (COPD). Despite its medical relevance, relatively little is known about its mechanisms of pathogenicity. In this study, we found that NTHi invades the airway epithelium by a distinct mechanism, requiring microtubule assembly, lipid rafts integrity, and activation of phosphatidylinositol 3-kinase (PI3K) signalling. We found that the majority of intracellular bacteria are located inside an acidic subcellular compartment, in a metabolically active and non-proliferative state. This NTHi-containing vacuole (NTHi-CV) is endowed with late endosome features, co-localizing with LysoTracker, lamp-1, lamp-2, CD63 and Rab7. The NTHi-CV does not acquire Golgi- or autophagy-related markers. These observations were extended to immortalized and primary human airway epithelial cells. By using NTHi clinical isolates expressing different amounts of phosphocholine (PCho), a major modification of NTHi lipooligosaccharide, on their surfaces, and an isogenic lic1BC mutant strain lacking PCho, we showed that PCho is not responsible for NTHi intracellular location. In sum, this study indicates that NTHi can survive inside airway epithelial cells.

Expression of Toll-like receptor 2 is up-regulated in monocytes from patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is characterised by pulmonary and systemic inflammation which flare-up during episodes of acute exacerbation (AECOPD). Given the role of Toll-like receptors (TLRs) in the induction of inflammatory responses we investigated the involvement of TLRs in COPD pathogenesis.

Capsule polysaccharide mediates bacterial resistance to antimicrobial peptides

The innate immune system plays a critical role in the defense of areas exposed to microorganisms. There is an increasing body of evidence indicating that antimicrobial peptides and proteins (APs) are one of the most important weapons of this system and that they make up the protective front for the respiratory tract. On the other hand, it is known that pathogenic organisms have developed countermeasures to resist these agents such as reducing the net negative charge of the bacterial membranes. Here we report the characterization of a novel mechanism of resistance to APs that is dependent on the bacterial capsule polysaccharide (CPS). Klebsiella pneumoniae CPS mutant was more sensitive than the wild type to human neutrophil defensin 1, beta-defensin 1, lactoferrin, protamine sulfate, and polymyxin B. K. pneumoniae lipopolysaccharide O antigen did not play an important role in AP resistance, and CPS was the only factor conferring protection against polymyxin B in strains lacking O antigen. In addition, we found a significant correlation between the amount of CPS expressed by a given strain and the resistance to polymyxin B. We also showed that K. pneumoniae CPS mutant bound more polymyxin B than the wild-type strain with a concomitant increased in the self-promoted pathway. Taken together, our results suggest that CPS protects bacteria by limiting the interaction of APs with the surface. Finally, we report that K. pneumoniae increased the amount of CPS and upregulated cps transcription when grown in the presence of polymyxin B and lactoferrin.

Ferroelectricity in Strain-Free SrTiO3 Thin Films

Biaxial strain is known to induce ferroelectricity in thin films of nominally nonferroelectric materials such as SrTiO3. By a direct comparison of the strained and strain-free SrTiO3 films using dielectric, ferroelectric, Raman, nonlinear optical and nanoscale piezoelectric property measurements, we conclude that all SrTiO3 films and bulk crystals are relaxor ferroelectrics, and the role of strain is to stabilize longerrange correlation of preexisting nanopolar regions, likely originating from minute amounts of unintentional Sr deficiency in nominally stoichiometric samples. These findings highlight the sensitive role of stoichiometry when exploring strain and epitaxy-induced electronic phenomena in oxide films, heterostructures, and interfaces.