Brain edema : a valid endpoint for measuring hepatic encephalopathy?

Hepatic encephalopathy (HE) is a major complication of liver failure/disease which frequently develops during the progression of end-stage liver disease. This metabolic neuropsychiatric syndrome involves a spectrum of symptoms, including cognition impairment, attention deficits and motor dysfunction which eventually can progress to coma and death. Pathologically, HE is characterized by swelling of the astrocytes which consequently leads to brain edema, a common feature found in patients with acute liver failure (ALF) as well as in cirrhotic patients suffering from HE. The pathogenic factors involved in the onset of astrocyte swelling and brain edema in HE are unresolved. However, the role of astrocyte swelling/brain edema in the development of HE remains ambiguous and therefore measuring brain edema as an endpoint to evaluate HE is questioned. The following review will determine the effect of astrocyte swelling and brain edema on neurological function, discuss the various possible techniques to measure brain edema and lastly to propose a number of neurobehavioral tests to evaluate HE

High-frequency oscillatory ventilation in pediatric acute hypoxemic respiratory failure: disease-specific morbidity survival analysis.

BackgroundMultiple ventilatory strategies for acute hypoxemic respiratory failure (AHRF) in children have been advocated, including high-frequency oscillatory ventilation (HFOV). Despite the frequent deployment of HFOV, randomized controlled trials remain elusive and currently there are no pediatric trials looking at its use. Our longitudinal study analyzed the predictive clinical outcome of HFOV in pediatric AHRF given disease-specific morbidity.MethodsA retrospective 8-year review on pediatric intensive care unit admissions with AHRF ventilated by HFOV was performed. Primary outcomes included survival, morbidity, length of stay (LOS), and factors associated with survival or mortality.ResultsA total of 102 patients underwent HFOV with a 66 % overall survival rate. Survivors had a greater LOS than nonsurvivors (p = 0.001). Mortality odds ratio (OR) for patients without bronchiolitis was 8.19 (CI = 1.02, 65.43), and without pneumonia it was 3.07 (CI = 1.12, 8.39). A lower oxygenation index (OI) after HFOV commencement and at subsequent time points analyzed predicted survival. After 24 h, mortality was associated with an OI > 35 [OR = 31.11 (CI = 3.25, 297.98)]. Sepsis-related mortality was associated with a higher baseline FiO(2) (0.88 vs. 0.65), higher OI (42 vs. 22), and augmented metabolic acidosis (pH of 7.25 vs. 7.32) evaluated 4 h on HFOV (p < 0.05).ConclusionHigh-frequency oscillatory ventilation may be safely utilized. It has a 66 % overall survival rate in pediatric AHRF of various etiologies. Patients with morbidity limited to the respiratory system and optimized oxygenation indices are most likely to survive on HFOV

Structural insights into the function of ZRANB3 in replication stress response

Strategies to resolve replication blocks are critical for the maintenance of genome stability. Among the factors implicated in the replication stress response is the ATP-dependent endonuclease ZRANB3. Here, we present the structure of the ZRANB3 HNH (His-Asn-His) endonuclease domain and provide a detailed analysis of its activity. We further define PCNA as a key regulator of ZRANB3 function, which recruits ZRANB3 to stalled replication forks and stimulates its endonuclease activity. Finally, we present the co-crystal structures of PCNA with two specific motifs in ZRANB3: the PIP box and the APIM motif. Our data provide important structural insights into the PCNA-APIM interaction, and reveal unexpected similarities between the PIP box and the APIM motif. We propose that PCNA and ATP-dependency serve as a multi-layered regulatory mechanism that modulates ZRANB3 activity at replication forks. Importantly, our findings allow us to interpret the functional significance of cancer associated ZRANB3 mutations

Differential Roles of Communal and Agentic Narcissism in Affective and Cognitive Responses to Intelligence Feedback

This experimental study explored the role of agentic and communal narcissism in response to positive, negative, or neutral feedback on a difficult task. Results revealed that those scoring high in communal narcissism responded differently than those scoring high in agentic narcissism, further illustrating the applied distinction between the two constructs. Implications are discussed

Groups of two galaxies in SDSS: implications of colours on star formation quenching time-scales

We have devised a method to select galaxies that are isolated in their dark matter halo (N=1 systems) and galaxies that reside in a group of exactly two (N=2 systems). Our N=2 systems are widely-separated (up to $\sim$\,200\,$h^{-1}$\,kpc), where close galaxy-galaxy interactions are not dominant. We apply our selection criteria to two volume-limited samples of galaxies from SDSS DR6 with $M_{r}-5 \log_{10} h \leq$ -19 and -20 to study the effects of the environment of very sparse groups on galaxy colour. For satellite galaxies in a group of two, we find a red excess attributed to star formation quenching of 0.15\,$\pm$\,0.01 and 0.14\,$\pm$\,0.01 for the -19 and -20 samples, respectively, relative to isolated galaxies of the same stellar mass. Assuming N=1 systems are the progenitors of N=2 systems, an immediate-rapid star formation quenching scenario is inconsistent with these observations. A delayed-then-rapid star formation quenching scenario with a delay time of 3.3 and 3.7\,Gyr for the -19 and -20 samples, respectively, yields a red excess prediction in agreement with the observations. The observations also reveal that central galaxies in a group of two have a slight blue excess of 0.06\,$\pm$\,0.02 and 0.02\,$\pm$\,0.01 for the -19 and -20 samples, respectively, relative to N=1 populations of the same stellar mass. Our results demonstrate that even the environment of very sparse groups of luminous galaxies influence galaxy evolution and in-depth studies of these simple systems are an essential step towards understanding galaxy evolution in general.Comment: 17 pages, 11 figures, accepted to MNRA

SLoMo: automated site localization of modifications from ETD/ECD mass spectra

Recently, software has become available to automate localization of phosphorylation sites from CID data and to assign associated confidence scores. We present an algorithm, SLoMo (Site Localization of Modifications), which extends this capability to ETD/ECD mass spectra. Furthermore, SLoMo caters for both high and low resolution data and allows for site-localization of any UniMod post-translational modification. SLoMo accepts input data from a variety of formats (e.g., Sequest, OMSSA). We validate SLoMo with high and low resolution ETD, ECD, and CID data

The Plant Ontology facilitates comparisons of plant development stages across species

The Plant Ontology (PO) is a community resource consisting of standardized terms, definitions, and logical relations describing plant structures and development stages, augmented by a large database of annotations from genomic and phenomic studies. This paper describes the structure of the ontology and the design principles we used in constructing PO terms for plant development stages. It also provides details of the methodology and rationale behind our revision and expansion of the PO to cover development stages for all plants, particularly the land plants (bryophytes through angiosperms). As a case study to illustrate the general approach, we examine variation in gene expression across embryo development stages in Arabidopsis and maize, demonstrating how the PO can be used to compare patterns of expression across stages and in developmentally different species. Although many genes appear to be active throughout embryo development, we identified a small set of uniquely expressed genes for each stage of embryo development and also between the two species. Evaluating the different sets of genes expressed during embryo development in Arabidopsis or maize may inform future studies of the divergent developmental pathways observed in monocotyledonous versus dicotyledonous species. The PO and its annotation databasemake plant data for any species more discoverable and accessible through common formats, thus providing support for applications in plant pathology, image analysis, and comparative development and evolution

Structures of Two Melanoma-Associated Antigens Suggest Allosteric Regulation of Effector Binding

The MAGE (melanoma associated antigen) protein family are tumour-associated proteins normally present only in reproductive tissues such as germ cells of the testis. The human genome encodes over 60 MAGE genes of which one class (containing MAGE-A3 and MAGE-A4) are exclusively expressed in tumours, making them an attractive target for the development of targeted and immunotherapeutic cancer treatments. Some MAGE proteins are thought to play an active role in driving cancer, modulating the activity of E3 ubiquitin ligases on targets related to apoptosis. Here we determined the crystal structures of MAGE- A3 and MAGE-A4. Both proteins crystallized with a terminal peptide bound in a deep cleft between two tandem-arranged winged helix domains. MAGE-A3 (but not MAGE-A4), is pre- dominantly dimeric in solution. Comparison of MAGE-A3 and MAGE-A3 with a structure of an effector-bound MAGE-G1 suggests that a major conformational rearrangement is required for binding, and that this conformational plasticity may be targeted by allosteric binders

A comparison study of the blower door and novel pulse technique on measuring enclosure airtightness in a controlled environment

This paper introduces a comparison study of measuring the airtightness of a house sized test chamber using the novel pulse technique and the standard blower door method in a controlled environment. Eight different testing plates have been applied to the improvised envelope of the chamber to establish different leakage characteristics. Each testing plate has a unique opening in the centre of the plate, achieved by obtaining a different combination of shape and thickness of the opening. By using the controlled environment, the vagaries of the natural condition when testing within buildings have been reduced providing a more robust testing environment. This investigation focuses on how the air leakage rate calculated from the measurements made by both techniques compare with each other. Comparable results (within 3 %) under most scenarios have been obtained. Additionally, other aspects such as usability of the equipment used for the pulse testing have also been appraised