Innate Recognition of Fungal Cell Walls

The emergence of fungal infections as major causes of morbidity and mortality in immunosuppressed individuals has prompted studies into how the host recognizes fungal pathogens. Fungi are eukaryotes and as such share many similarities with mammalian cells. The most striking difference, though, is the presence of a cell wall that serves to protect the fungus from environmental stresses, particularly osmotic changes [1]. This task is made challenging because the fungus must remodel itself to allow for cell growth and division, including the conversion to different morphotypes, such as occurs during germination of spherical spores into filamentous hyphae. The cell wall also connects the fungus with its environment by triggering intracellular signaling pathways and mediating adhesion to other cells and extracellular matrices. Here, important facts and concepts critical for understanding innate sensing of the fungal cell wall by mammalian pathogens are reviewed

In-reach specialist nursing teams for residential care homes : uptake of services, impact on care provision and cost-effectiveness

Background: A joint NHS-Local Authority initiative in England designed to provide a dedicated nursing and physiotherapy in-reach team (IRT) to four residential care homes has been evaluated.The IRT supported 131 residents and maintained 15 'virtual' beds for specialist nursing in these care homes. Methods: Data captured prospectively (July 2005 to June 2007) included: numbers of referrals; reason for referral; outcome (e.g. admission to IRT bed, short-term IRT support); length of stay in IRT; prevented hospital admissions; early hospital discharges; avoided nursing home transfers; and detection of unrecognised illnesses. An economic analysis was undertaken. Results: 733 referrals were made during the 2 years (range 0.5 to 13.0 per resident per annum)resulting in a total of 6,528 visits. Two thirds of referrals aimed at maintaining the resident's independence in the care home. According to expert panel assessment, 197 hospital admissions were averted over the period; 20 early discharges facilitated; and 28 resident transfers to a nursing home prevented. Detection of previously unrecognised illnesses accounted for a high number of visits. Investment in IRT equalled £44.38 per resident per week. Savings through reduced hospital admissions, early discharges, delayed transfers to nursing homes, and identification of previously unrecognised illnesses are conservatively estimated to produce a final reduction in care cost of £6.33 per resident per week. A sensitivity analysis indicates this figure might range from a weekly overall saving of £36.90 per resident to a 'worst case' estimate of £2.70 extra expenditure per resident per week. Evaluation early in implementation may underestimate some cost-saving activities and greater savings may emerge over a longer time period. Similarly, IRT costs may reduce over time due to the potential for refinement of team without major loss in effectiveness. Conclusion: Introduction of a specialist nursing in-reach team for residential homes is at least cost neutral and, in all probability, cost saving. Further benefits include development of new skills in the care home workforce and enhanced quality of care. Residents are enabled to stay in familiar surroundings rather than unnecessarily spending time in hospital or being transferred to a higher dependency nursing home setting

Macrofossil evidence for a rapid and severe Cretaceous–Paleogene mass extinction in Antarctica

Debate continues about the nature of the Cretaceous–Paleogene (K–Pg) mass extinction event. An abrupt crisis triggered by a bolide impact contrasts with ideas of a more gradual extinction involving flood volcanism or climatic changes. Evidence from high latitudes has also been used to suggest that the severity of the extinction decreased from low latitudes towards the poles. Here we present a record of the K–Pg extinction based on extensive assemblages of marine macrofossils (primarily new data from benthic molluscs) from a highly expanded Cretaceous–Paleogene succession: the López de Bertodano Formation of Seymour Island, Antarctica. We show that the extinction was rapid and severe in Antarctica, with no significant biotic decline during the latest Cretaceous, contrary to previous studies. These data are consistent with a catastrophic driver for the extinction, such as bolide impact, rather than a significant contribution from Deccan Traps volcanism during the late Maastrichtian

Unveiling a novel transient druggable pocket in BACE-1 through molecular simulations: conformational analysis and binding mode of multisite inhibitors

The critical role of BACE-1 in the formation of neurotoxic ß-amyloid peptides in the brain makes it an attractive target for an efficacious treatment of Alzheimer’s disease. However, the development of clinically useful BACE-1 inhibitors has proven to be extremely challeng- ing. In this study we examine the binding mode of a novel potent inhibitor (compound 1, with IC50 80 nM) designed by synergistic combination of two fragments—huprine and rhein— that individually are endowed with very low activity against BACE-1. Examination of crystal structures reveals no appropriate binding site large enough to accommodate 1. Therefore we have examined the conformational flexibility of BACE-1 through extended molecular dynamics simulations, paying attention to the highly flexible region shaped by loops 8–14, 154–169 and 307–318. The analysis of the protein dynamics, together with studies of pocket druggability, has allowed us to detect the transient formation of a secondary binding site, which contains Arg307 as a key residue for the interaction with small molecules, at the edge of the catalytic cleft. The formation of this druggable “floppy” pocket would enable the bind- ing of multisite inhibitors targeting both catalytic and secondary sites. Molecular dynamics simulations of BACE-1 bound to huprine-rhein hybrid compounds support the feasibility of this hypothesis. The results provide a basis to explain the high inhibitory potency of the two enantiomeric forms of 1, together with the large dependence on the length of the oligo- methylenic linker. Furthermore, the multisite hypothesis has allowed us to rationalize the inhibitory potency of a series of tacrine-chromene hybrid compounds, specifically regarding the apparent lack of sensitivity of the inhibition constant to the chemical modifications intro- duced in the chromene unit. Overall, these findings pave the way for the exploration of novel functionalities in the design of optimized BACE-1 multisite inhibitors

Evolutionary Dead End in the Galápagos: Divergence of Sexual Signals in the Rarest of Darwin's Finches

Understanding the mechanisms underlying speciation remains a challenge in evolutionary biology. The adaptive radiation of Darwin's finches is a prime example of species formation, and their study has revealed many important insights into evolutionary processes. Here, we report striking differences in mating signals (songs), morphology and genetics between the two remnant populations of Darwin's mangrove finch Camarhynchus heliobates, one of the rarest species in the world. We also show that territorial males exhibited strong discrimination of sexual signals by locality: in response to foreign songs, males responded weaker than to songs from their own population. Female responses were infrequent and weak but gave approximately similar results. Our findings not only suggest speciation in the mangrove finch, thereby providing strong support for the central role of sexual signals during speciation, but they have also implications for the conservation of this iconic bird. If speciation is complete, the eastern species will face imminent extinction, because it has a population size of only 5–10 individuals

Students’ satisfaction and teaching efficiency of university offer

This study analyses the factors affecting students’ satisfaction with university experience, focusing on the aspects characterising the teaching efficiency of educational offer. For this purpose, organisation of teaching activities, available information, teaching materials, and other facilities offered to students to make their learning experience more successful, are considered as indicators of teaching efficiency. Our interest in this topic is justified by the importance that students’ satisfaction assumes, not only as indicator of the quality of educational services but also for its relationship with overall life satisfaction and subjective well-being. A structural equation model with latent variables is estimated by using survey and administrative data of the University of Pisa. Main findings seem to show that teaching efficiency has a positive effect on satisfaction and suggest that whenever it is inadequate, or at least, considered as such, students are less satisfied for their university experience. The effects of other factors on students’ satisfaction such as studies organisation, social capital and internship experience are also discussed

User-centered virtual environment design for virtual rehabilitation

<p>Abstract</p> <p>Background</p> <p>As physical and cognitive rehabilitation protocols utilizing virtual environments transition from single applications to comprehensive rehabilitation programs there is a need for a new design cycle methodology. Current human-computer interaction designs focus on usability without benchmarking technology within a user-in-the-loop design cycle. The field of virtual rehabilitation is unique in that determining the efficacy of this genre of computer-aided therapies requires prior knowledge of technology issues that may confound patient outcome measures. Benchmarking the technology (e.g., displays or data gloves) using healthy controls may provide a means of characterizing the "normal" performance range of the virtual rehabilitation system. This standard not only allows therapists to select appropriate technology for use with their patient populations, it also allows them to account for technology limitations when assessing treatment efficacy.</p> <p>Methods</p> <p>An overview of the proposed user-centered design cycle is given. Comparisons of two optical see-through head-worn displays provide an example of benchmarking techniques. Benchmarks were obtained using a novel vision test capable of measuring a user's stereoacuity while wearing different types of head-worn displays. Results from healthy participants who performed both virtual and real-world versions of the stereoacuity test are discussed with respect to virtual rehabilitation design.</p> <p>Results</p> <p>The user-centered design cycle argues for benchmarking to precede virtual environment construction, especially for therapeutic applications. Results from real-world testing illustrate the general limitations in stereoacuity attained when viewing content using a head-worn display. Further, the stereoacuity vision benchmark test highlights differences in user performance when utilizing a similar style of head-worn display. These results support the need for including benchmarks as a means of better understanding user outcomes, especially for patient populations.</p> <p>Conclusions</p> <p>The stereoacuity testing confirms that without benchmarking in the design cycle poor user performance could be misconstrued as resulting from the participant's injury state. Thus, a user-centered design cycle that includes benchmarking for the different sensory modalities is recommended for accurate interpretation of the efficacy of the virtual environment based rehabilitation programs.</p

Global Distribution of Polaromonas Phylotypes - Evidence for a Highly Successful Dispersal Capacity

Bacteria from the genus Polaromonas are dominant phylotypes in clone libraries and culture collections from polar and high-elevation environments. Although Polaromonas has been found on six continents, we do not know if the same phylotypes exist in all locations or if they exhibit genetic isolation by distance patterns. To examine their biogeographic distribution, we analyzed all available, long-read 16S rRNA gene sequences of Polaromonas phylotypes from glacial and periglacial environments across the globe. Using genetic isolation by geographic distance analyses, including Mantel tests and Mantel correlograms, we found that Polaromonas phylotypes are globally distributed showing weak isolation by distance patterns at global scales. More focused analyses using discrete, equally sampled distances classes, revealed that only two distance classes (out of 12 total) showed significant spatial structuring. Overall, our analyses show that most Polaromonas phylotypes are truly globally distributed, but that some, as yet unknown, environmental variable may be selecting for unique phylotypes at a minority of our global sites. Analyses of aerobiological and genomic data suggest that Polaromonas phylotypes are globally distributed as dormant cells through high-elevation air currents; Polaromonas phylotypes are common in air and snow samples from high altitudes, and a glacial-ice metagenome and the two sequenced Polaromonas genomes contain the gene hipA, suggesting that Polaromonas can form dormant cells

A review of the benefits and drawbacks to virtual field guides in today’s Geoscience higher education environment

Virtual Field Guides are a way for educators to tackle the growing issue of funding pressures in areas of higher education, such as geography. Virtual Field Guides are however underutilised and can offer students a different way of learning. Virtual Field Guides have many benefits to students, such as being more inclusive, building student skills and confidence in a controlled environment pre fieldtrip and can increase engagement in the topic studied. There are also benefits to the educator, such as reduced cost, more efficient students on fieldwork tasks and the ability to tailor and update their field guides to suit their needs. However there are drawbacks in the challenge of creation and their outcome as educational standalone tools. This paper reviews the literature around the benefits and draw backs to the creation and incorporation of virtual field guides in geoscience education. © 2017, The Author(s)