Confirmation of correct tracheal tube placement in newborn infants

Tracheal intubation remains a common procedure during neonatal intensive care. Rapid confirmation of correct tube placement is important because tube malposition is associated with serious adverse outcomes. The current gold standard test to confirm tube position is a chest radiograph, however this is often delayed until after ventilation has commenced. Hence, point of care methods to confirm correct tube placement have been developed. The aim of this article is to review the available literature on tube placement in newborn infants. We reviewed books, resuscitation manuals and articles from 1830 to the present with the search terms “Infant, Newborn”, “Endotracheal intubation”, “Resuscitation”, “Clinical signs”, “Radiography”, “Respiratory Function Tests”, “Laryngoscopy”, “Ultrasonography”, and “Bronchoscopy”. Various techniques have been studied to help clinicians assess tube placement. However, despite 85 years of clinical practice, the search for higher success rates and quicker intubation continues. Currently, chest radiography remains the gold standard test to confirm tube position. However, rigorous evaluation of new techniques is required to ensure the safety of newborn infants.     

Fusing landscape accuracy-dependent SRTM elevation data with NGDC and LiDAR data for the Florida coastline

Extended coverage digital elevation models (DEMs) including topographic and bathymetric area at moderate resolution are needed for regional-scale hazard modelling. Shuttle Radar Topography Mission (SRTM) provides important intermediate-scale information between coarse resolution data sets of wide area and high-resolution data sets of limited area. Although there are many anthropogenic structures that cause errors in the height of SRTM data, the measurement error is given as a single value for the entire area. The filter residuals in an adaptive multi-scale fusion algorithm were used to evaluate the landscape-dependent accuracy of SRTM elevations over the Florida coastal urban area. With accuracy and employing a stochastic framework to optimally fuse National Geophysical Data Center (NGDC) data, SRTM data and high-resolution light detection and ranging data, single seamless fused DEMs at multiple scales were derived for the coastal area and improved DEM quality at 30 m scale for coastal flood prediction was demonstrated.     

Signal transduction by the platelet Fc receptor

We have evaluated the mechanism by which crosslinking human platelet Fc receptor (FcR) for IgG triggers platelet aggregation and the platelet release reaction. Platelet FcR was crosslinked by incubating purified human platelets with anti-FcRII monoclonal antibody and F(ab')2 anti- mouse Ig. The resultant [Ca2+]i increase, monitored by Fura-2 and measured in the absence of extracellular Ca2+, reached a peak of 750 +/- 50 nmol/L. The effects of cyclooxygenase inhibitors, aspirin and indomethacin, and a phospholipase A2 inhibitor, dibromoacetophenone, were examined. Regardless of the inhibitor, at least 25% of the [Ca2+]i increase remained. Thrombin (0.2 U/mL) stimulated an immediate [Ca2+]i increase that reached 1.95 +/- 0.8 mumol/L. The [Ca2+]i increase generated by thrombin was only slightly reduced by these inhibitors. Crosslinking the FcRII of platelets resulted in a fivefold increase in the production of [3H]inositol phosphates, (IP) which, in the absence of extracellular Ca2+ was insensitive to aspirin. The activation of a [Ca2+]i increase along with the measured increases in IP indicate that FcRII crosslinking leads to the activation of phospholipase C (PLC). In contrast to thrombin, platelet activation via FcRII depends to a large extent on arachidonic acid metabolites. However, neither cyclooxygenase nor phospholipase A2 inhibitors completely blocked FcRII-stimulated [Ca2+]i increase. These observations led us to propose that crosslinking of platelet FcRII initially activates PLC.     

Treatment with atorvastatin ameliorates hepatic very-low-density lipoprotein overproduction in an animal model of insulin resistance, the fructose-fed Syrian golden hamster: evidence that reduced hypertriglyceridemia is accompanied by improved hepatic insulin sensitivity

A novel animal model of insulin resistance, the fructose-fed Syrian golden hamster has been previously documented to exhibit considerable hepatic very-low-density lipoprotein (VLDL) overproduction concomitant with the development of whole body insulin resistance. Here, we investigated whether hepatic lipoprotein overproduction can be ameliorated by treatment with a hydroxymethyl glutaryl conenzyme A (HMG-CoA) reductase inhibitor, atorvastatin, using a series of ex vivo experiments. Hamsters were fed a fructose-enriched diet for 14 days to induce a state of insulin resistance, and then continued on a fructose-enriched diet supplemented with or without 40 mg/kg atorvastatin per day for 14 days. Fructose feeding in the first 2 weeks caused a significant increase in plasma total cholesterol and triglyceride levels. There was a significant decline in plasma triglyceride levels following supplementation with the inhibitor (50% to 59%; P <.05). Experiments with primary hepatocytes revealed a decreased VLDL-apolipoprotein B (apoB) production (37.4% +/- 10.4%; P <.05) in hamsters treated with atorvastatin. Interestingly, atorvastatin treatment partially attenuated (by 23%) the elevated hepatic level of microsomal triglyceride transfer protein (MTP) induced by fructose feeding. There was molecular evidence of improved hepatic insulin sensitivity with atorvastatin treatment based on assessment of the phosphorylation status of the insulin receptor and the expression of protein tyrosine phosphatase-1B. The improvement in insulin signaling was not mediated by a change in hepatic triglyceride accumulation as no significant difference was observed in liver triglyceride levels. Taken together, these data suggest that statins can ameliorate the VLDL-apoB overproduction state observed in a fructose-fed, insulin-resistant hamster model, and may potentially contribute to an enhanced hepatic insulin sensitivity.     

A unique AtSar1D-AtRabD2a nexus modulates autophagosome biogenesis in Arabidopsis thaliana

In eukaryotes, secretory proteins traffic from the endoplasmic reticulum (ER) to the Golgi apparatus via coat protein complex II (COPII) vesicles. Intriguingly, during nutrient starvation, the COPII machinery acts constructively as a membrane source for autophagosomes during autophagy to maintain cellular homeostasis by recycling intermediate metabolites. In higher plants, essential roles of autophagy have been implicated in plant development and stress responses. Nonetheless, the membrane sources of autophagosomes, especially the participation of the COPII machinery in the autophagic pathway and autophagosome biogenesis, remains elusive in plants. Here, we provided evidence in support of a novel role of a specific Sar1 homolog AtSar1d in plant autophagy in concert with a unique Rab1/Ypt1 homolog AtRabD2a. First, proteomic analysis of the plant ATG (autophagy-related gene) interactome uncovered the mechanistic connections between ATG machinery and specific COPII components including AtSar1d and Sec23s, while a dominant negative mutant of AtSar1d exhibited distinct inhibition on YFP-ATG8 vacuolar degradation upon autophagic induction. Second, a transfer DNA insertion mutant of AtSar1d displayed starvation-related phenotypes. Third, AtSar1d regulated autophagosome progression through specific recognition of ATG8e by a noncanonical motif. Fourth, we demonstrated that a plant-unique Rab1/Ypt1 homolog AtRabD2a coordinates with AtSar1d to function as the molecular switch in mediating the COPII functions in the autophagy pathway. AtRabD2a appears to be essential for bridging the specific AtSar1d-positive COPII vesicles to the autophagy initiation complex and therefore contributes to autophagosome formation in plants. Taken together, we identified a plant-specific nexus of AtSar1d-AtRabD2a in regulating autophagosome biogenesis.

Autophagy is a conserved catabolic process characterized by the de novo generation of a double-membrane structure called an autophagosome with a fundamental function in the bulk turnover of cytoplasmic components, including proteins, RNAs, and organelles. Genetic studies in yeast have elucidated the molecular machinery of autophagy, whereby 42 autophagy-related (ATG) genes have been identified (1–3). These ATG genes are highly conserved among eukaryotes but often have multiple isoforms in other higher organisms, in particular in sessile plants. Albeit increasing understanding on the molecular function of Atg proteins in acting hierarchically on the phagophore assembly site (PAS) to produce autophagosomes, the origin of the autophagosomal membrane remains unclear in higher eukaryotes. Furthermore, the dedication of other membranes and machineries in the autophagy pathway remains under investigation.Plant autophagy is known to play important roles in the sessile lifestyle of plants, participating in seed germination, seedling establishment, plant development, hormone responses, lipid metabolism, and reproductive development (4). Plant autophagy research is advancing with findings not only on the counterparts of the yeast/mammalian Atg proteins but also dealing with some plant-unique factors functioning in different steps of autophagosome biogenesis, thereby uncovering novel mechanisms that might or might not be conserved in nonplant species (5). More interestingly, higher plants possess multiple protein isoforms of ATG machinery, whose functional heterogeneity in the autophagy pathway has only recently been unveiled (6).The coat protein complex II (COPII) machinery consists of five cytosolic components: the small GTPase Sar1, the inner coat protein dimer Sec23-Sec24, and the outer coat proteins Sec13-Sec31. These proteins are essential for COPII-coated vesicle formation, which buds from specialized regions of the ER, namely ER exit sites (ERESs) (7). Under nutrient-rich conditions, COPII vesicles mediate anterograde ER to Golgi transport. However, increasing evidence from yeast and mammals suggests that the COPII machinery or even COPII vesicles themselves may contribute to autophagosome formation when cells are starved for nutrients (8–16). Gene duplication events have occurred substantially in sessile plants during evolution, and the importance of distinct paralogs in environmental stress adaptation during plant development has been implied (17). Arabidopsis encodes multiple COPII paralogs in its genome, including five Sar1s, seven Sec23s, three Sec24s, two Sec13s, and two Sec31s (17). Increasing numbers of studies have pinpointed the functional diversity and importance of distinct COPII paralogs in ER protein export (18–23). Nonetheless, the mechanism by which COPII vesicles are redirected to the autophagy pathway upon nutrient starvation, and their roles in autophagosome biogenesis, remains unclear. Furthermore, the participation of specific COPII paralogs in autophagy regulation remains unknown in plants.Here, we report on a role of a specific Sar1 homolog, AtSar1d, that modulates plant autophagosome biogenesis in concert with AtRabD2a. Large-scale proteomic analysis of the ATG interactome has revealed possible mechanistic connections between the ATG machinery and specific COPII components in plants. Cellular and biochemical analyses have shown that the dominant negative (DN) mutant of AtSar1d (AtSar1dDN) specifically perturbs YFP-ATG8 vacuolar degradation upon autophagic induction. Consistently, a transfer DNA (T-DNA) insertion mutant of AtSar1d exhibited starvation-related phenotypes. Notably, AtSar1d regulates autophagosome progression through specific recognition of ATG8e by a previously uncharacterized noncanonical motif. We further identify a plant-unique Rab1/Ypt1 homolog AtRabD2a that colocalizes with AtSar1d and ATG8 upon starvation by transient expression in Arabidopsis protoplasts. A DN mutant of AtRabD2a (AtRabD2aNI) perturbs autophagy flux, while AtRabD2a is indispensable for bridging the AtSar1d-positive COPII vesicles with the ATG1 complex, thus contributing to autophagosome biogenesis in plants. Our study therefore unequivocally demonstrates that the plant-specific COPII machinery regulates autophagosome biogenesis and sheds light on the evolutionary importance of gene duplication events in the plant autophagy pathway.     

Niche adaptation and genome expansion in the chlorophyll d-producing cyanobacterium Acaryochloris marina

Acaryochloris marina is a unique cyanobacterium that is able to produce chlorophyll d as its primary photosynthetic pigment and thus efficiently use far-red light for photosynthesis. Acaryochloris species have been isolated from marine environments in association with other oxygenic phototrophs, which may have driven the niche-filling introduction of chlorophyll d. To investigate these unique adaptations, we have sequenced the complete genome of A. marina. The DNA content of A. marina is composed of 8.3 million base pairs, which is among the largest bacterial genomes sequenced thus far. This large array of genomic data is distributed into nine single-copy plasmids that code for >25% of the putative ORFs. Heavy duplication of genes related to DNA repair and recombination (primarily recA) and transposable elements could account for genetic mobility and genome expansion. We discuss points of interest for the biosynthesis of the unusual pigments chlorophyll d and α-carotene and genes responsible for previously studied phycobilin aggregates. Our analysis also reveals that A. marina carries a unique complement of genes for these phycobiliproteins in relation to those coding for antenna proteins related to those in Prochlorococcus species. The global replacement of major photosynthetic pigments appears to have incurred only minimal specializations in reaction center proteins to accommodate these alternate pigments. These features clearly show that the genus Acaryochloris is a fitting candidate for understanding genome expansion, gene acquisition, ecological adaptation, and photosystem modification in the cyanobacteria.     

Detection of inadvertent catheter movement into a pulmonary vein during radiofrequency catheter ablation by real-time impedance monitoring

Introduction: During radiofrequency ablation to encircle or isolate the pulmonary veins (PVs), applications of radiofrequency energy within a PV may result in stenosis. The aim of this study was to determine whether monitoring of real-time impedance facilitates detection of inadvertent catheter movement into a PV.
Methods and Results: In 30 consecutive patients (mean age 53 ± 11 years) who underwent a left atrial ablation procedure, the three-dimensional geometry of the left atrium, the PVs, and their ostia were reconstructed using an electroanatomic mapping system. The PV ostia were identified based on venography, changes in electrogram morphology, and manual and fluoroscopic feedback as the catheter was withdrawn from the PV into the left atrium. Real-time impedance was measured at the ostium, inside the PV at approximately 1 and 3 cm from the ostium, in the left atrial appendage, and at the posterior left atrial wall. There was an impedance gradient from the distal PV (127 ± 30 Ω) to the proximal PV (108 ± 15 Ω) to the ostium (98 ± 11 Ω) in each PV (P < 0.01). There was no significant impedance difference between the ostial and left atrial sites. During applications of radiofrequency energy, movement of the ablation catheter into a PV was accurately detected in 80% of the cases (20) when there was an abrupt increase of ≥4 Ω in real-time impedance.
Conclusion: There is a significant impedance gradient from the distal PV to the left atrium. Continuous monitoring of the real-time impedance facilitates detection of inadvertent catheter movement into a PV during applications of radiofrequency energy. (J Cardiovasc Electrophysiol, Vol. 15, pp. 1-5, June 2004)     

The Role of Serotonin (5-HT) in Behavioral Control: Findings from Animal Research and Clinical Implications

The neurotransmitters serotonin and dopamine both have a critical role in the underlying neurobiology of different behaviors. With focus on the interplay between dopamine and serotonin, it has been proposed that dopamine biases behavior towards habitual responding, and with serotonin offsetting this phenomenon and directing the balance toward more flexible, goal-directed responding. The present focus paper stands in close relationship to the publication by Worbe et al. (2015), which deals with the effects of acute tryptophan depletion, a neurodietary physiological method to decrease central nervous serotonin synthesis in humans for a short period of time, on the balance between hypothetical goal-directed and habitual systems. In that research, acute tryptophan depletion challenge administration and a following short-term reduction in central nervous serotonin synthesis were associated with a shift of behavioral performance towards habitual responding, providing further evidence that central nervous serotonin function modulates the balance between goal-directed and stimulus-response habitual systems of behavioral control. In the present focus paper, we discuss the findings by Worbe and colleagues in light of animal experiments as well as clinical implications and discuss potential future avenues for related research.