Long-distance early endosome motility in Aspergillus fumigatus promotes normal hyphal growth behaviors in controlled microenvironments but is dispensable for virulence

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordIn filamentous fungi, early endosomes are continuously trafficked to, and from, the growing hyphal tip by microtubule-based motor proteins, serving as platforms for the long-distance transport of diverse cargos including mRNA, signaling molecules, and other organelles which hitchhike on them. While the cellular machinery for early endosome motility in filamentous fungi are fairly well characterized, the broader physiological significance of this process remains less well understood. We set out to determine the importance of long-distance early endosome trafficking in Aspergillus fumigatus, an opportunistic human pathogenic fungus that can cause devastating pulmonary infections in immunocompromised individuals. We first characterized normal early endosome motile behavior in A. fumigatus, then generated a mutant in which early endosome motility is severely perturbed through targeted deletion of the gene encoding for FtsA, one of a complex of proteins that links early endosomes to their motor proteins. Using a microfluidics-based approach we show that contact-induced hyphal branching behaviors are impaired in ΔftsA mutants, but that FtsA-mediated early endosome motility is dispensable for virulence in an invertebrate infection model. Overall, our study provides new insight into early endosome motility in an important human pathogenic fungus.Arkansas Biosciences Institut

In Situ Ambient Pressure X-ray Photoelectron Spectroscopy Studies of Lithium-Oxygen Redox Reactions

The lack of fundamental understanding of the oxygen reduction and oxygen evolution in nonaqueous electrolytes significantly hinders the development of rechargeable lithium-air batteries. Here we employ a solid-state Li4+xTi5O12/LiPON/LixV2O5 cell and examine in situ the chemistry of Li-O2 reaction products on LixV2O5 as a function of applied voltage under ultra high vacuum (UHV) and at 500 mtorr of oxygen pressure using ambient pressure X-ray photoelectron spectroscopy (APXPS). Under UHV, lithium intercalated into LixV2O5 while molecular oxygen was reduced to form lithium peroxide on LixV2O5 in the presence of oxygen upon discharge. Interestingly, the oxidation of Li2O2 began at much lower overpotentials (~240 mV) than the charge overpotentials of conventional Li-O2 cells with aprotic electrolytes (~1000 mV). Our study provides the first evidence of reversible lithium peroxide formation and decomposition in situ on an oxide surface using a solid-state cell, and new insights into the reaction mechanism of Li-O2 chemistry.National Science Foundation (U.S.) (Materials Research Science and Engineering Center (MRSEC) Program, Award DMR-0819762)United States. Dept. of Energy (Assistant Secretary for Energy Efficiency and Renewable Energy, Office of FreedomCAR and Vehicle Technologies of the U. S. Department of Energy under contract no. DE-AC03-76SF00098)Lawrence Berkeley National LaboratoryUnited States. Dept. of Energy (Office of Basic Energy Sciences, Materials Sciences and Engineering

Intravenous Infusion Administration: A Comparative Study of Practices and Errors Between the United States and England and Their Implications for Patient Safety

Introduction Intravenous medication administration is widely reported to be error prone. Technologies such as smart pumps have been introduced with a view to reducing these errors. An international comparison could provide evidence of their effectiveness, including consideration of contextual factors such as regulatory systems and local cultures. Objectives The aim of this study was to investigate similarities and differences in practices and error types involving intravenous medication administration in the United States and England, and summarise methodological differences necessary to perform these parallel studies. Methods We drew on findings of separate point prevalence studies conducted across hospitals in each country. In these, we compared what was being administered at the time of observation with the prescription and relevant policies, errors were classified by type and severity, and proportions of infusions featuring each error type were calculated. We also reviewed what adaptations to the US protocol were needed for England. Authors independently reviewed findings from both studies and proposed themes for comparison. In online meetings, each country’s research team clarified assumptions and explained their findings. Results Key themes included commonalities and contrasts in methods, findings, practices and policies. Although US sites made greater use of smart infusion devices, and had more precisely defined requirements around infusion device use, patterns of errors were similar. Differences among clinical contexts within each country were as marked as differences across countries. Regulatory and quality control systems shape practices, but causal relationships are complex. Conclusion Infusion administration is a complex adaptive system with multiple interacting agents (professionals, patients, software systems, etc.) that respond in rich ways to their environments; safety depends on complex, interrelated factors

Non-extremal Black Hole Microstates: Fuzzballs of Fire or Fuzzballs of Fuzz ?

We construct the first family of microstate geometries of near-extremal black holes, by placing metastable supertubes inside certain scaling supersymmetric smooth microstate geometries. These fuzzballs differ from the classical black hole solution macroscopically at the horizon scale, and for certain probes the fluctuations between various fuzzballs will be visible as thermal noise far away from the horizon. We discuss whether these fuzzballs appear to infalling observers as fuzzballs of fuzz or as fuzzballs of fire. The existence of these solutions suggests that the singularity of non-extremal black holes is resolved all the way to the outer horizon and this "backwards in time" singularity resolution can shed light on the resolution of spacelike cosmological singularities.Comment: 34 pages, 10 figure

Size constancy in bat biosonar?

Perception and encoding of object size is an important feature of sensory systems. In the visual system object size is encoded by the visual angle (visual aperture) on the retina, but the aperture depends on the distance of the object. As object distance is not unambiguously encoded in the visual system, higher computational mechanisms are needed. This phenomenon is termed "size constancy". It is assumed to reflect an automatic re-scaling of visual aperture with perceived object distance. Recently, it was found that in echolocating bats, the 'sonar aperture', i.e., the range of angles from which sound is reflected from an object back to the bat, is unambiguously perceived and neurally encoded. Moreover, it is well known that object distance is accurately perceived and explicitly encoded in bat sonar. Here, we addressed size constancy in bat biosonar, recruiting virtual-object techniques. Bats of the species Phyllostomus discolor learned to discriminate two simple virtual objects that only differed in sonar aperture. Upon successful discrimination, test trials were randomly interspersed using virtual objects that differed in both aperture and distance. It was tested whether the bats spontaneously assigned absolute width information to these objects by combining distance and aperture. The results showed that while the isolated perceptual cues encoding object width, aperture, and distance were all perceptually well resolved by the bats, the animals did not assign absolute width information to the test objects. This lack of sonar size constancy may result from the bats relying on different modalities to extract size information at different distances. Alternatively, it is conceivable that familiarity with a behaviorally relevant, conspicuous object is required for sonar size constancy, as it has been argued for visual size constancy. Based on the current data, it appears that size constancy is not necessarily an essential feature of sonar perception in bats

Wolbachia in the flesh: symbiont intensities in germ-line and somatic tissues challenge the conventional view of Wolbachia transmission routes

Symbionts can substantially affect the evolution and ecology of their hosts. The investigation of the tissue-specific distribution of symbionts (tissue tropism) can provide important insight into host-symbiont interactions. Among other things, it can help to discern the importance of specific transmission routes and potential phenotypic effects. The intracellular bacterial symbiont Wolbachia has been described as the greatest ever panzootic, due to the wide array of arthropods that it infects. Being primarily vertically transmitted, it is expected that the transmission of Wolbachia would be enhanced by focusing infection in the reproductive tissues. In social insect hosts, this tropism would logically extend to reproductive rather than sterile castes, since the latter constitute a dead-end for vertically transmission. Here, we show that Wolbachia are not focused on reproductive tissues of eusocial insects, and that non-reproductive tissues of queens and workers of the ant Acromyrmex echinatior, harbour substantial infections. In particular, the comparatively high intensities of Wolbachia in the haemolymph, fat body, and faeces, suggest potential for horizontal transmission via parasitoids and the faecal-oral route, or a role for Wolbachia modulating the immune response of this host. It may be that somatic tissues and castes are not the evolutionary dead-end for Wolbachia that is commonly thought

A Biometric Model for Mineralization of Type-I Collagen Fibrils

The bone and dentin mainly consist of type-I collagen fibrils mineralized by hydroxyapatite (HAP) nanocrystals. In vitro biomimetic models based on self-assembled collagen fibrils have been widely used in studying the mineralization mechanism of type-I collagen. In this chapter, the protocol we used to build a biomimetic model for the mechanistic study of type-I collagen mineralization is described. Type-I collagen extracted from rat tail tendon or horse tendon is self-assembled into fibrils and mineralized by HAP in vitro. The mineralization process is monitored by cryoTEM in combination with two-dimensional (2D) and three-dimensional (3D) stochastic optical reconstruction microscopy (STORM), which enables in situ and high-resolution visualization of the process

New instability of non-extremal black holes: spitting out supertubes

We search for stable bound states of non-extremal rotating three-charge black holes in five dimensions (Cvetic-Youm black holes) and supertubes. We do this by studying the potential of supertube probes in the non-extremal black hole background and find that generically the marginally bound state of the supersymmetric limit becomes metastable and disappears with non-extremality (higher temperature). However near extremality there is a range of parameters allowing for stable bound states, which have lower energy than the supertube-black hole merger. Angular momentum is crucial for this effect. We use this setup in the D1-D5 decoupling limit to map a thermodynamic instability of the CFT (a new phase which is entropically dominant over the black hole phase) to a tunneling instability of the black hole towards the supertube-black hole bound state. This generalizes the results of ArXiv:1108.0411 [hep-th], which mapped an entropy enigma in the bulk to the dual CFT in a supersymmetric setup.Comment: 28 pages + appendix, 15 figures, v2: References added, typos corrected. Version published in JHE

Does the implementation of an electronic prescribing system create unintended medication errors? A study of the sociotechnical context through the analysis of reported medication incidents

<p>Abstract</p> <p>Background</p> <p>Even though electronic prescribing systems are widely advocated as one of the most effective means of improving patient safety, they may also introduce new risks that are not immediately obvious. Through the study of specific incidents related to the processes involved in the administration of medication, we sought to find out if the prescribing system had unintended consequences in creating new errors. The focus of this study was a large acute hospital in the Midlands in the United Kingdom, which implemented a Prescribing, Information and Communication System (PICS).</p> <p>Methods</p> <p>This exploratory study was based on a survey of routinely collected medication incidents over five months. Data were independently reviewed by two of the investigators with a clinical pharmacology and nursing background respectively, and grouped into broad types: sociotechnical incidents (related to human interactions with the system) and non-sociotechnical incidents. Sociotechnical incidents were distinguished from the others because they occurred at the point where the system and the professional intersected and would not have occurred in the absence of the system. The day of the week and time of day that an incident occurred were tested using univariable and multivariable analyses. We acknowledge the limitations of conducting analyses of data extracted from incident reports as it is widely recognised that most medication errors are not reported and may contain inaccurate data. Interpretation of results must therefore be tentative.</p> <p>Results</p> <p>Out of a total of 485 incidents, a modest 15% (n = 73) were distinguished as sociotechnical issues and thus may be unique to hospitals that have such systems in place. These incidents were further analysed and subdivided into categories in order to identify aspects of the context which gave rise to adverse situations and possible risks to patient safety. The analysis of sociotechnical incidents by time of day and day of week indicated a trend for increased proportions of these types of incidents occurring on Sundays.</p> <p>Conclusion</p> <p>Introducing an electronic prescribing system has the potential to give rise to new types of risks to patient safety. Being aware of these types of errors is important to the clinical and technical implementers of such systems in order to, where possible, design out unintended problems, highlight training requirements, and revise clinical practice protocols.</p

Holographic Vitrification

We establish the existence of stable and metastable stationary black hole bound states at finite temperature and chemical potentials in global and planar four-dimensional asymptotically anti-de Sitter space. We determine a number of features of their holographic duals and argue they represent structural glasses. We map out their thermodynamic landscape in the probe approximation, and show their relaxation dynamics exhibits logarithmic aging, with aging rates determined by the distribution of barriers.Comment: 100 pages, 25 figure