Host defense at the ocular surface

Microbial infections of the cornea frequently cause painful, blinding and debilitating disease that is often difficult to treat and may require corneal transplantation. In addition, sterile corneal infiltrates that are associated with contact lens wear cause pain, visual impairment and photophobia. In this article, we review the role of Toll-Like Receptors (TLR) in bacterial keratitis and sterile corneal infiltrates, and describe the role of MD-2 regulation in LPS responsiveness by corneal epithelial cells. We conclude that both live bacteria and bacterial products activate Toll-Like Receptors in the cornea, which leads to chemokine production and neutrophil recruitment to the corneal stroma. While neutrophils are essential for bacterial killing, they also cause tissue damage that results in loss of corneal clarity. These disparate outcomes, therefore, represent a spectrum of disease severity based on this pathway, and further indicate that targeting the TLR pathway is a feasible approach to treating inflammation caused by live bacteria and microbial products. Further, as the P. aeruginosa type III secretion system (T3SS) also plays a critical role in disease pathogenesis by inducing neutrophil apoptosis and facilitating bacterial growth in the cornea, T3SS exotoxins are additional targets for therapy for P. aeruginosa keratitis.

Assessing the uncertainties of model estimates of primary productivity in the tropical Pacific Ocean

Depth-integrated primary productivity (PP) estimates obtained from satellite ocean color-based models (SatPPMs) and those generated from biogeochemical ocean general circulation models (BCGCMs) represent a key resource for biogeochemical and ecological studies at global as well as regional scales. Calibration and validation of these PP models are not straightforward, however, and comparative studies show large differences between model estimates. The goal of this paper is to compare PP estimates obtained from 30 different models (21 SatPPMs and 9 BOGCMs) to a tropical Pacific PP database consisting of similar to 1000 C-14 measurements spanning more than a decade (1983-1996). Primary findings include: skill varied significantly between models, but performance was not a function of model complexity or type (i.e. SatPPM vs. BOGCM); nearly all models underestimated the observed variance of PR specifically yielding too few low PP (< 0.2 g Cm-2 d(-1)) values; more than half of the total root-mean-squared model-data differences associated with the satellite-based PP models might be accounted for by uncertainties in the input variables and/or the PP data; and the tropical Pacific database captures a broad scale shift from low biomassnormalized productivity in the 1980s to higher biomass-normalized productivity in the 1990s, which was not successfully captured by any of the models. This latter result suggests that interdecadal and global changes will be a significant challenge for both SatPPMs and BOGCMs. Finally, average root-mean-squared differences between in situ PP data on the equator at 140 degrees W and PP estimates from the satellite-based productivity models were 58% lower than analogous values computed in a previous PP model comparison 6 years ago. The success of these types of comparison exercises is illustrated by the continual modification and improvement of the participating models and the resulting increase in model skill. (C) 2008 Elsevier BY. All rights reserved.

High Levels of Diversity Uncovered in a Widespread Nominal Taxon: Continental Phylogeography of the Neotropical Tree Frog Dendropsophus minutus

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Systematic analysis of protein-detergent complexes applying dynamic light scattering to optimize solutions for crystallization trials

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Sleep patterns and sleepiness of working college students

The double journey (work and study) may result or aggravate health problems, including sleep disturbances, as observed in previous studies with high school students. The aim of this study is to analyze the sleep-wake cycle and perceived sleepiness of working college students during weekdays. Twenty-three healthy college male students, 21-24 years old, working during the day and attending classes in the evening, participated in this study. During five consecutive days, the students filled out daily activities logs and wore actigraphs. Mean sleeping time was lower than 6 hours per night. No significant differences were observed in the sleep-wake cycle during the weekdays. The observed lack of changes in the sleep-wake cycle of these college students might occur as participants were not on a free schedule, but exposed to social constraints, as was the regular attendance to evening college and day work activities. Sleepiness worsened over the evening school hours. Those results show the burden carried by College students who perform double activities - work and study.

Sleep length, working hours and socio-demographic variables are associated with time attending evening classes among working college students

It is the aim of the present study to assess factors associated with time spent in class among working college students. Eighty-two working students from 21 to 26 years old participated in this study. They were enrolled in an evening course of the University of Sao Paulo, Brazil. Participants answered a questionnaire on living and working conditions. During seven consecutive days, they wore an actigraph, filled out daily activity diaries (including time spent in classes) and the Karolinska Sleepiness Scale every three hours from waking until bedtime. Linear regression analyses were performed in order to assess the variables associated with time spent in classes. The results showed that gender, sleep length, excessive sleepiness, alcoholic beverage consumption (during workdays) and working hours were associated factors with time spent in class. Thus, those who spent less time in class were males, slept longer hours, reported excessive sleepiness on Saturdays, worked longer hours, and reported alcohol consumption. The combined effects of long work hours (>40 h/week) and reduced sleep length may affect lifestyles and academic performance. Future studies should aim to look at adverse health effects induced by reduced sleep duration, even among working students who spent more time attending evening classes.

Estimating the monthly pCO2 distribution in the North Atlantic using a self-organizing neural network

[EN] Here we present monthly, basin-wide maps of the partial pressure of carbon dioxide (pCO2) for the North Atlantic on a latitude by longitude grid for years 2004 through 2006 inclusive. The maps have been computed using a neural network technique which reconstructs the non-linear relationships between three biogeochemical parameters and marine pCO2. A self organizing map (SOM) neural network has been trained using 389 000 triplets of the SeaWiFSMODIS chlorophyll-a concentration, the NCEP/NCAR reanalysis sea surface temperature, and the FOAM mixed layer depth. The trained SOM was labelled with 137 000 underway pCO2 measurements collected in situ during 2004, 2005 and 2006 in the North Atlantic, spanning the range of 208 to 437atm. The root mean square error (RMSE) of the neural network fit to the data is 11.6?atm, which equals to just above 3 per cent of an average pCO2 value in the in situ dataset. The seasonal pCO2 cycle as well as estimates of the interannual variability in the major biogeochemical provinces are presented and discussed. High resolution combined with basin-wide coverage makes the maps a useful tool for several applications such as the monitoring of basin-wide air-sea CO2 fluxes or improvement of seasonal and interannual marine CO2 cycles in future model predictions. The method itself is a valuable alternative to traditional statistical modelling techniques used in geosciences.

3D-electron microscopy of different conformations of cephalopod hemocyanins

Die Hämocyanine der Cephalopoden Nautilus pompilius und Sepia officinalis sorgen für den Sauerstofftransport zwischen den Kiemen und den Geweben. Sie bestehen aus einem zylindrischen Dekamer mit interner Kragenstruktur. Während eine Untereinheit (also eine Polypeptidkette) bei NpH aus sieben paralogen funktionellen Domänen (FU-a bis FU-g) besteht, führte ein Genduplikationsereignis der FU-d zu acht FUs in SoH (a, b, c, d, d´, e, f, g). In allen Mollusken Hämocyaninen bilden sechs dieser FUs den äußeren Ring und die restlichen die interne Kragenstruktur. rnrnIn dieser Arbeit wurde ein dreidimensionales Modell des Hämocyanins von Sepia officinalis (SoH) erstellt. Die Rekonstruktion, mit einer Auflösung von 8,8Å (FSC=0,5), erlaubt das Einpassen von Homolologiemodellen und somit das Erstellen eines molekularen Modells mit pseudo atomarer Auflösung. Des Weiteren wurden zwei Rekonstruktionen des Hämocyanins von Nautilus pompilius (NpH) in verschiedenen Oxygenierungszuständen erstellt. Die auf 10 und 8,1Å aufgelösten Modelle zeigen zwei verschiedene Konformationen des Proteins. Daraus ließ sich eine Modellvorstellung über die allosterische Funktionsweise ableiten. Die hier erreichte Auflösung von 8Å ist die momentan höchste eines Molluskenhämocyanins. rnAuf Grundlage des molekularen Modells von SoH konnte die Topologie des Proteins aufgeklärt werden. Es wurde gezeigt, dass die zusätzliche FU-d´ in den Kragen integriert ist und somit die prinzipielle Wandarchitektur aller Mollusken Hämocyanine identisch ist. Wie die Analyse des erstellten molekularen Modells zeigt werden sind die beiden Isoformen (SoH1 und SoH2) in den Bereichen der Interfaces nahezu identisch; auch der Vergleich mit NpH zeigt grosse Übereinstimmungen. Des weiteren konnte eine Fülle von Informationen bezüglich der allosterischen Signalübertragung innerhalb des Moleküls gewonnen werden. rnDer Versuch, NpH in verschiedenen Oxygenierungszuständen zu zeigen, war erfolgreich. Die Datensätze, die unter zwei atmosphärischen Bedingungen präpariert wurden, führten reproduzierbar zu zwei unterschiedlichen Rekonstruktionen. Dies zeigt, daß der hier entwickelte experimentelle Ansatz funktioniert. Er kann nun routinemäßig auf andere Proteine angewandt werden. Wie der strukturelle Vergleich zeigte, verändert sich die Orientierung der FUs durch die Oxygenierung leicht. Dies wiederum beeinflusst die Anordnung innerhalb der Interfaces sowie die Abstände zwischen den beteiligten Aminosäuren. Aus dieser Analyse konnte eine Modellvorstellung zum allosterischen Signaltransfer innerhalb des Moleküls abgeleitet werden, die auf einer Umordnung von Salzbrücken basiert.

Predicting adverse events in children with fever and chemotherapy-induced neutropenia: the prospective multicenter SPOG 2003 FN study

PURPOSE To develop a score predicting the risk of adverse events (AEs) in pediatric patients with cancer who experience fever and neutropenia (FN) and to evaluate its performance. PATIENTS AND METHODS Pediatric patients with cancer presenting with FN induced by nonmyeloablative chemotherapy were observed in a prospective multicenter study. A score predicting the risk of future AEs (ie, serious medical complication, microbiologically defined infection, radiologically confirmed pneumonia) was developed from a multivariate mixed logistic regression model. Its cross-validated predictive performance was compared with that of published risk prediction rules. Results An AE was reported in 122 (29%) of 423 FN episodes. In 57 episodes (13%), the first AE was known only after reassessment after 8 to 24 hours of inpatient management. Predicting AE at reassessment was better than prediction at presentation with FN. A differential leukocyte count did not increase the predictive performance. The score predicting future AE in 358 episodes without known AE at reassessment used the following four variables: preceding chemotherapy more intensive than acute lymphoblastic leukemia maintenance (weight = 4), hemoglobin > or = 90 g/L (weight = 5), leukocyte count less than 0.3 G/L (weight = 3), and platelet count less than 50 G/L (weight = 3). A score (sum of weights) > or = 9 predicted future AEs. The cross-validated performance of this score exceeded the performance of published risk prediction rules. At an overall sensitivity of 92%, 35% of the episodes were classified as low risk, with a specificity of 45% and a negative predictive value of 93%. CONCLUSION This score, based on four routinely accessible characteristics, accurately identifies pediatric patients with cancer with FN at risk for AEs after reassessment.

Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC), after slipped capital femoral epiphysis

OBJECTIVE: The aim of this study was to assess the glycosaminoglycan (GAG) content in hip joint cartilage in mature hips with a history of slipped capital femoral epiphysis (SCFE) using delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). METHODS: 28 young-adult subjects (32 hips) with a mean age of 23.8+/-4.0 years (range: 18.1-30.5 years) who were treated for mild or moderate SCFE in adolescence were included into the study. Hip function and clinical symptoms were evaluated with the Harris hip score (HHS) system at the time of MRI. Plain radiographic evaluation included Tonnis grading, measurement of the minimal joint space width (JSW) and alpha-angle measurement. The alpha-angle values were used to classify three sub-groups: group 1=subjects with normal femoral head-neck offset (alpha-angle <50 degrees ), group 2=subjects with mild offset decrease (alpha-angle 50 degrees -60 degrees ), and group 3=subjects with severe offset decrease (alpha-angle >60 degrees ). RESULTS: There was statistically significant difference noted for the T1(Gd) values, lateral and central, between group 1 and group 3 (p-values=0.038 and 0.041). The T1(Gd) values measured within the lateral portion were slightly lower compared with the T1(Gd) values measured within the central portion that was at a statistically significance level (p-value <0.001). HHS, Tonnis grades and JSW revealed no statistically significant difference. CONCLUSION: By using dGEMRIC in the mid-term follow-up of SCFE we were able to reveal degenerative changes even in the absence of joint space narrowing that seem to be related to the degree of offset pathology. The dGEMRIC technique may be a potential diagnostic modality in the follow-up evaluation of SCFE.

Early bursts of body size and shape evolution are rare in comparative data

George Gaylord Simpson famously postulated that much of life's diversity originated as adaptive radiations-more or less simultaneous divergences of numerous lines from a single ancestral adaptive type. However, identifying adaptive radiations has proven difficult due to a lack of broad-scale comparative datasets. Here, we use phylogenetic comparative data on body size and shape in a diversity of animal clades to test a key model of adaptive radiation, in which initially rapid morphological evolution is followed by relative stasis. We compared the fit of this model to both single selective peak and random walk models. We found little support for the early-burst model of adaptive radiation, whereas both other models, particularly that of selective peaks, were commonly supported. In addition, we found that the net rate of morphological evolution varied inversely with clade age. The youngest clades appear to evolve most rapidly because long-term change typically does not attain the amount of divergence predicted from rates measured over short time scales. Across our entire analysis, the dominant pattern was one of constraints shaping evolution continually through time rather than rapid evolution followed by stasis. We suggest that the classical model of adaptive radiation, where morphological evolution is initially rapid and slows through time, may be rare in comparative data.