Analysis of acute vascular damage after photodynamic therapy using benzoporphyrin derivative (BPD)

Benzoporphyrin derivative monoacid ring A (BPD-MA, verteporfin) is currently under investigation as a photosensitizer for photodynamic therapy (PDT). Since BPD exhibits rapid pharmacokinetics in plasma and tissues, we assessed damage to tumour and muscle microvasculature when light treatment for PDT was given at short times after injection of photosensitizer. Groups of rats with chondrosarcoma were given 2 mg kg−1 of BPD intravenously 5 min to 180 min before light treatment of 150 J cm−2 690 nm. Vascular response was monitored using intravital microscopy and tumour cure was monitored by following regrowth over 42 days. For treatment at 5 or 30 min after BPD injection, blood flow stasis was limited to tumour microvasculature with lesser response in the surrounding normal microvasculature, indicating selective targeting for damage. No acute changes were observed in vessels when light was given 180 min after BPD injection. Tumour regression after light treatment occurred in all animals given PDT with BPD. Long-term tumour regression was greater in animals treated 5 min after BPD injection and least in animals given treatment 180 min after drug injection. The correlation between the timing for vascular damage and cure implies that blood flow stasis plays a significant role in PDT-induced tumour destruction. © 1999 Cancer Research Campaig

On stable higher spin states in Heterotic String Theories

We study properties of 1/2 BPS Higher Spin states in heterotic compactifications with extended supersymmetry. We also analyze non BPS Higher Spin states and give explicit expressions for physical vertex operators of the first two massive levels. We then study on-shell tri-linear couplings of these Higher Spin states and confirm that BPS states with arbitrary spin cannot decay into lower spin states in perturbation theory. Finally, we consider scattering of vector bosons off higher spin BPS states and extract form factors and polarization effects in various limits.Comment: 38 page

The Winter Worries of Bats : Past and Present Perspectives on Winter Habitat and Management of Cave Hibernating Bats

Winter is a time of fascinating changes in biology for cave-hibernating bats, but it is also a time of vulnerability. Unsurprisingly, assessments of winter habitat for these mammals and how it can be managed have been a focus of many researchers involved with the North American Society for Bat Research over the last 50 years. Over this time, a paradigm shift has occurred in the way scientists think about factors driving selection of winter habitat, especially temperature. To illustrate this change, we review three hypotheses seeking to explain microclimate selection in cavernicolous bats. The first, which we call the “Colder is Better Hypothesis,” posits that bats should select cold microclimates that minimize energy expenditure. The “Hibernation Optimization Hypothesis” suggests that bats should select microclimates that reduce expression of torpor to balance energy conservation against non-energetic costs of hibernation. Finally, the “Thrifty Female Hypothesis” asserts that females should select colder microclimates than males to conserve energy for reproduction. We discuss these hypotheses and the shift from viewing hibernation as a phenomenon driven solely by the need to conserve energy in the context of hibernacula management in North America. We focus on both historical and recent conservation threats, most notably alteration of thermal regimes and the disease white-nose syndrome. We urge against returning to an over-simplified view of winter habitat selection in response to our current conservation challenges.Peer reviewe

RNA secondary structure prediction from multi-aligned sequences

It has been well accepted that the RNA secondary structures of most functional non-coding RNAs (ncRNAs) are closely related to their functions and are conserved during evolution. Hence, prediction of conserved secondary structures from evolutionarily related sequences is one important task in RNA bioinformatics; the methods are useful not only to further functional analyses of ncRNAs but also to improve the accuracy of secondary structure predictions and to find novel functional RNAs from the genome. In this review, I focus on common secondary structure prediction from a given aligned RNA sequence, in which one secondary structure whose length is equal to that of the input alignment is predicted. I systematically review and classify existing tools and algorithms for the problem, by utilizing the information employed in the tools and by adopting a unified viewpoint based on maximum expected gain (MEG) estimators. I believe that this classification will allow a deeper understanding of each tool and provide users with useful information for selecting tools for common secondary structure predictions.Comment: A preprint of an invited review manuscript that will be published in a chapter of the book `Methods in Molecular Biology'. Note that this version of the manuscript may differ from the published versio

Microbial Functional Capacity Is Preserved Within Engineered Soil Formulations Used In Mine Site Restoration

Mining of mineral resources produces substantial volumes of crushed rock based wastes that are characterised by poor physical structure and hydrology, unstable geochemistry and potentially toxic chemical conditions. Recycling of these substrates is desirable and can be achieved by blending waste with native soil to form a 'novel substrate' which may be used in future landscape restoration. However, these post-mining substrate based 'soils' are likely to contain significant abiotic constraints for both plant and microbial growth. Effective use of these novel substrates for ecosystem restoration will depend on the efficacy of stored topsoil as a potential microbial inoculum as well as the subsequent generation of key microbial soil functions originally apparent in local pristine sites. Here, using both marker gene and shotgun metagenome sequencing, we show that topsoil storage and the blending of soil and waste substrates to form planting substrates gives rise to variable bacterial and archaeal phylogenetic composition but a high degree of metabolic conservation at the community metagenome level. Our data indicates that whilst low phylogenetic conservation is apparent across substrate blends we observe high functional redundancy in relation to key soil microbial pathways, allowing the potential for functional recovery of key belowground pathways under targeted management

Geographic distribution at subspecies resolution level: closely related Rhodopirellula species in European coastal sediments.

Members of the marine genus Rhodopirellula are attached living bacteria and studies based on cultured Rhodopirellula strains suggested that three closely related species R. baltica, 'R. europaea' and 'R. islandica' have a limited geographic distribution in Europe. To address this hypothesis, we developed a nested PCR for a single gene copy detection of a partial acetyl CoA synthetase (acsA) from intertidal sediments collected all around Europe. Furthermore, we performed growth experiments in a range of temperature, salinity and light conditions. A combination of Basic Local Alignment Search Tool (BLAST) and Minimum Entropy Decomposition (MED) was used to analyze the sequences with the aim to explore the geographical distribution of the species and subspecies. MED has been mainly used for the analysis of the 16S rRNA gene and here we propose a protocol for the analysis of protein-coding genes taking into account the degeneracy of the codons and a possible overestimation of functional diversity. The high-resolution analysis revealed differences in the intraspecies community structure in different geographic regions. However, we found all three species present in all regions sampled and in agreement with growth experiments we demonstrated that Rhodopirellula species do not have a limited geographic distribution in Europe

Kinematics of the Local Group gas and galaxies in the hestia simulations

We investigate the kinematic properties of gas and galaxies in the Local Group (LG) using high-resolution simulations performed by the hestia (High-resolution Environmental Simulations of The Immediate Area) collaboration. Our simulations include the correct cosmography surrounding LG-like regions consisting of two main spiral galaxies of ∼1012 M⊙, their satellites and minor isolated galaxies, all sharing the same large-scale motion within a volume of a few Mpc. We characterize the gas and galaxy kinematics within the simulated LGs, from the perspective of the Sun, to compare with observed trends from recent HST/COS absorption-line observations and LG galaxy data. To analyse the velocity pattern of LG gas and galaxies seen in the observational data, we build sky maps from the local standard of rest, and the Galactic and LG barycentre frames. Our findings show that the establishment of a radial velocity dipole at low/high latitudes, near the preferred barycentre direction, is a natural outcome of simulation kinematics for material outside the Milky Way virial radius after removing Galaxy rotation when the two main LG galaxies are approaching. Our results favour a scenario where gas and galaxies stream towards the LG barycentre producing a velocity dipole resembling observations. While our study shows in a qualitative way the global matter kinematics in the LG as part of its ongoing assembly, quantitative estimates of gas-flow rates and physical conditions of the LG gas have to await a more detailed modelling of the ionization conditions, which will be presented in a follow-up paper

Effect of Acyl Chain Length on Hydrophobized Cashew Gum Self-Assembling Nanoparticles: Colloidal Properties and Amphotericin B Delivery

Given its many potential applications, cashew gum hydrophobic derivatives have gained increasing attraction in recent years. We report here the effect of acyl chain length on hydrophobized cashew gum derivatives, using acetic, propionic, and butyric anhydrides on self-assembly nanoparticle properties and amphotericin B delivery. Nanoparticles with unimodal particle size distribution, highly negative zeta potential, and low PDI were produced. Butyrate cashew gum nanoparticles presented smaller size (<~100 nm) than acetylated and propionate cashew gum nanoparticles and no cytotoxicity in murine fibroblast cells was observed up to 100 µg/mL for loaded and unloaded nanoparticles. As a proof of concept of the potential use of the developed nanoparticle as a drug carrier formulation, amphotericin B (AmB) was encapsulated and fully characterized in their physicochemical, AmB association and release, stability, and biological aspects. They exhibited average hydrodynamic diameter lower than ~200 nm, high AmB efficiency encapsulations (up to 94.9%), and controlled release. A decrease in AmB release with the increasing of the anhydride chain length was observed, which explains the differences in antifungal activity against Candida albicans strains. An excellent storage colloidal stability was observed for unloaded and loaded AmB without use of surfactant. Considering the AmB delivery, the acyl derivative with low chain length is shown to be the best one, as it has high drug loading and AmB release, as well as low minimum inhibitory concentration against Candida albicans strains