Detomidine and butorphanol for standing sedation in a range of zoo-kept ungulate species

General anesthesia poses risks for larger zoo species, like cardiorespiratory depression, myopathy, and hyperthermia. In ruminants, ruminal bloat and regurgitation of rumen contents with potential aspiration pneumonia are added risks. Thus, the use of sedation to perform minor procedures is justified in zoo animals. A combination of detomidine and butorphanol has been routinely used in domestic animals. This drug combination, administered by remote intramuscular injection, can also be applied for standing sedation in a range of zoo animals, allowing a number of minor procedures. The combination was successfully administered in five species of nondomesticated equids (Przewalski horse [Equus ferus przewalskii; n = 1], onager [Equus hemionus onager; n = 4], kiang [Equus kiang; n = 3], Grevy's zebra [Equus grevyi; n = 4], and Somali wild ass [Equus africanus somaliensis; n = 7]), with a mean dose range of 0.10-0.17 mg/kg detomidine and 0.07-0.13 mg/kg butorphanol; the white (Ceratotherium simum simum; n = 12) and greater one-horned rhinoceros (Rhinoceros unicornis; n = 4), with a mean dose of 0.015 mg/kg of both detomidine and butorphanol; and Asiatic elephant bulls (Elephas maximus; n = 2), with a mean dose of 0.018 mg/kg of both detomidine and butorphanol. In addition, the combination was successfully used for standing sedation in six species of artiodactylids: giraffe (Giraffa camelopardalis reticulata; n = 3), western bongo (Tragelaphus eurycerus eurycerus; n = 2), wisent (Bison bonasus; n = 5), yak (Bos grunniens; n = 1), water buffalo (Bubalus bubalis; n = 4) and Bactrian camel (Camelus bactrianus; n = 5). The mean dose range for artiodactylid species except bongo was 0.04-0.06 mg/kg detomidine and 0.03-0.06 mg/kg butorphanol. The dose in bongo, 0.15-0.20 mg/kg detomidine and 0.13-0.15 mg/kg butorphanol, was considerably higher. Times to first effect, approach, and recovery after antidote were short. The use of detomidine and butorphanol has been demonstrated to be a reliable, safe alternative to general anesthesia for a number of large ungulate species

A multidisciplinary approach to the identification of the protein-RNA connectome in double-stranded RNA virus capsids

How multi-segmented double-stranded RNA (dsRNA) viruses correctly incorporate their genomes into their capsids remains unclear for many viruses, including Bluetongue virus (BTV), a Reoviridae member, with a genome of 10 segments. To address this, we used an RNA-cross-linking and peptide-fingerprinting assay (RCAP) to identify RNA binding sites of the inner capsid protein VP3, the viral polymerase VP1 and the capping enzyme VP4. Using a combination of mutagenesis, reverse genetics, recombinant proteins and in vitro assembly, we validated the importance of these regions in virus infectivity. Further, to identify which RNA segments and sequences interact with these proteins, we used viral photo-activatable ribonucleoside crosslinking (vPAR-CL) which revealed that the larger RNA segments (S1-S4) and the smallest segment (S10) have more interactions with viral proteins than the other smaller segments. Additionally, using a sequence enrichment analysis we identified an RNA motif of nine bases that is shared by the larger segments. The importance of this motif for virus replication was confirmed by mutagenesis followed by virus recovery. We further demonstrated that these approaches could be applied to a related Reoviridae member, rotavirus (RV), which has human epidemic impact, offering the possibility of novel intervention strategies for a human pathogen

Spontaneous Self-Assembly of Thermoresponsive Vesicles Using a Zwitterionic and an Anionic Surfactant.

Spontaneous formation of vesicles from the self-assembly of two specific surfactants, one zwitterionic (oleyl amidopropyl betaine, OAPB) and the other anionic (Aerosol-OT, AOT), is explored in water using small-angle scattering techniques. Two factors were found to be critical in the formation of vesicles: surfactant ratio, as AOT concentrations less than equimolar with OAPB result in cylindrical micelles or mixtures of micellar structures, and salt concentration, whereby increasing the amount of NaCl promotes vesicle formation by reducing headgroup repulsions. Small-angle neutron scattering measurements reveal that the vesicles are approximately 30-40 nm in diameter, depending on sample composition. Small-angle X-ray scattering measurements suggest preferential partitioning of OAPB molecules on the vesicle inner layer to support vesicular packing. Heating the vesicles to physiological temperature (37 °C) causes them to collapse into smaller ellipsoidal micelles (2-3 nm), with higher salt concentrations (≥10 mM) inhibiting this transition. These aggregates could serve as responsive carriers for loading or unloading of aqueous cargoes such as drugs and pharmaceuticals, with temperature changes serving as a simple release/uptake mechanism.Australian Research Council Future Fellowship (FT160100191) to Rico Tabor. and a Discovery Early Career Research Award (DE190100531) to Andrew Clulow

Medical Safety and Device Reliability of Active Transcutaneous Middle Ear and Bone Conducting Implants: A Long-Term Multi-Centre Observational Study

Active bone-conducting hearing devices (aBCHD; e.g., MEDEL Bonebridge® (BB)) and active middle ear implants (aMEI; e.g., MEDEL Vibrant Soundbridge® (VSB)) use radio frequency transmission to send information from an external microphone and sound processor to an internally implanted transducer. These devices potentially have an advantage over devices with percutaneous links because the skin is closed over the implantable components, which should reduce the risk of skin problems and infection. On the other hand, surgical procedures are more complex, with a greater risk of damage due to surgery. The objectives of this research were to quantify the reliability and long-term survival of MEDEL VSB and BB devices, determine the adverse and serious adverse device-related complications, and consider associated causes. A multi-center observational retrospective and prospective study was conducted at eleven auditory implant centers in the United Kingdom. Data was collected using a surgical questionnaire and audiological reports. Data were obtained from patient notes or from prospective cases that had a minimum follow-up of one year post-implant. Consecutive patient records were reviewed. Datasets from 109 BB and 163 VSB were reviewed. Of these, 205 were retrospective case note reviews, and 67 were prospective cases. The mean follow-up was 4 and 6 years, respectively, for BB and VSB. Kaplan–Meier Survival analyses indicated that the BB survival was 97% and 93.3% at 1 and 5 years, respectively, and the VSB was 92.1% and 87% at the same time points. This is a large cohort study for the field and has indicated that BB and VSB are safe interventions. Care should be taken to monitor magnet strength in the first few months. For the majority of device-related effects, there was no apparent association with etiology. However, an interesting pattern emerged for individuals who exhibited an inflammatory response, e.g., adhesions or device extrusion, and those with a history of chronic suppurative otitis media. This should be considered in future work and is not surprising given that many VSB recipients have a complicated hearing history, often associated with otitis media

Sensitivity of global soil carbon stocks to combined nutrient enrichment

Soil stores approximately twice as much carbon as the atmosphere and fluctuations in the size of the soil carbon pool directly influence climate conditions. We used the Nutrient Network global change experiment to examine how anthropogenic nutrient enrichment might influence grassland soil carbon storage at a global scale. In isolation, enrichment of nitrogen and phosphorous had minimal impacts on soil carbon storage. However, when these nutrients were added in combination with potassium and micronutrients, soil carbon stocks changed considerably, with an average increase of 0.04 KgCm−2 year−1 (standard deviation 0.18 KgCm−2 year−1). These effects did not correlate with changes in primary productivity, suggesting that soil carbon decomposition may have been restricted. Although nutrient enrichment caused soil carbon gains most dry, sandy regions, considerable absolute losses of soil carbon may occur in high‐latitude regions that store the majority of the world's soil carbon. These mechanistic insights into the sensitivity of grassland carbon stocks to nutrient enrichment can facilitate biochemical modelling efforts to project carbon cycling under future climate scenarios

The incorporation of the novel histone variant H2AL2 confers unusual structural and functional properties of the nucleosome

In this work we have studied the properties of the novel mouse histone variant H2AL2. H2AL2 was used to reconstitute nucleosomes and the structural and functional properties of these particles were studied by a combination of biochemical approaches, atomic force microscopy (AFM) and electron cryo-microscopy. DNase I and hydroxyl radical footprinting as well as micrococcal and exonuclease III digestion demonstrated an altered structure of the H2AL2 nucleosomes all over the nucleosomal DNA length. Restriction nuclease accessibility experiments revealed that the interactions of the H2AL2 histone octamer with the ends of the nucleosomal DNA are highly perturbed. AFM imaging showed that the H2AL2 histone octamer was complexed with only ∼130 bp of DNA. H2AL2 reconstituted trinucleosomes exhibited a type of a ‘beads on a string’ structure, which was quite different from the equilateral triangle 3D organization of conventional H2A trinucleosomes. The presence of H2AL2 affected both the RSC and SWI/SNF remodeling and mobilization of the variant particles. These unusual properties of the H2AL2 nucleosomes suggest a specific role of H2AL2 during mouse spermiogenesis

Microbial interactions in the mosquito gut determineSerratiacolonization and blood-feeding propensity

How microbe–microbe interactions dictate microbial complexity in the mosquito gut is unclear. Previously we found that, Serratia, a gut symbiont that alters vector competence and is being considered for vector control, poorly colonized Aedes aegypti yet was abundant in Culex quinquefasciatus reared under identical conditions. To investigate the incompatibility between Serratia and Ae. aegypti, we characterized two distinct strains of Serratia marcescens from Cx. quinquefasciatus and examined their ability to infect Ae. aegypti. Both Serratia strains poorly infected Ae. aegypti, but when microbiome homeostasis was disrupted, the prevalence and titers of Serratia were similar to the infection in its native host. Examination of multiple genetically diverse Ae. aegypti lines found microbial interference to S. marcescens was commonplace, however, one line of Ae. aegypti was susceptible to infection. Microbiome analysis of resistant and susceptible lines indicated an inverse correlation between Enterobacteriaceae bacteria and Serratia, and experimental co-infections in a gnotobiotic system recapitulated the interference phenotype. Furthermore, we observed an effect on host behavior; Serratia exposure to Ae. aegypti disrupted their feeding behavior, and this phenotype was also reliant on interactions with their native microbiota. Our work highlights the complexity of host–microbe interactions and provides evidence that microbial interactions influence mosquito behavior

Integrated global assessment of the natural forest carbon potential

Forests are a substantial terrestrial carbon sink, but anthropogenic changes in land use and climate have considerably reduced the scale of this system 1. Remote-sensing estimates to quantify carbon losses from global forests 2–5 are characterized by considerable uncertainty and we lack a comprehensive ground-sourced evaluation to benchmark these estimates. Here we combine several ground-sourced 6 and satellite-derived approaches 2,7,8 to evaluate the scale of the global forest carbon potential outside agricultural and urban lands. Despite regional variation, the predictions demonstrated remarkable consistency at a global scale, with only a 12% difference between the ground-sourced and satellite-derived estimates. At present, global forest carbon storage is markedly under the natural potential, with a total deficit of 226 Gt (model range = 151–363 Gt) in areas with low human footprint. Most (61%, 139 Gt C) of this potential is in areas with existing forests, in which ecosystem protection can allow forests to recover to maturity. The remaining 39% (87 Gt C) of potential lies in regions in which forests have been removed or fragmented. Although forests cannot be a substitute for emissions reductions, our results support the idea 2,3,9 that the conservation, restoration and sustainable management of diverse forests offer valuable contributions to meeting global climate and biodiversity targets