Assimilation to the Unmarked

Steel, JC ORCiD: 0000-0003-3608-7542Intravitreal injection of recombinant adeno-associated virus (AAV) might be an alternative approach for retinal gene therapy for certain applications. Although the jelly-like substance consists mainly of water, anti-viral antibodies against various viruses such as HIV or HSV have been observed in the human vitreous and anti-AAV neutralising antibodies (NAbs) in rhesus macaque vitreous have also been detected. In this study, the human vitreous humour was obtained from 70 post mortem unpaired eye cups and 10 paired eye cups from the Queensland Eye Bank. The transduction efficiency of 1-3 · 108 vcg of recombinant AAV-2, -5, -6 and -8 expressing secreted nanoluciferase was measured following transduction of ARPE-19 and Cos-7 cells at vitreous humour dilutions from 1:2 to 1:10 000. At vitreous humour dilution of 1:2, a reduction in transduction of over 50% was observed for AAV2 in 50.5% of samples and for AAV6 in 66.2% of samples. Only 23.2% of tested samples showed similar reduction in transduction efficiency for AAV5, and for AAV8 only 2.5% of samples inhibited transduction by 50% at 1:2 dilution. Differences in serum antibody levels have been previously observed in a similar Australian population, but low transduction inhibition at vitreous humour dilutions of 1:100 suggests that the concentration of NAbs within the vitreous humour is lower than in human serum. In addition, this study also reported an increase in transduction efficiency for AAV8 at highest vitreous humour concentrations, supporting previous reports that human albumin can increase AAV transduction but only in some serotypes

High Levels of Genetic Divergence Detected in Sacramento Perch Suggests Two Divergent Translocation Sources

Translocation has been used to conserve imperiled fishes and create new fisheries. One species for which translocation has played a significant role is the Sacramento Perch Archoplites interruptus. Extirpated from its native range, the Sacramento Perch has been introduced throughout California and Nevada through multiple translocation events, though historical records are incomplete. Recent assessments of eight previously uncharacterized Sacramento Perch populations have prompted reevaluation of range-wide population structure to inform a genetic management plan for long-term resiliency of this species. We examined Sacramento Perch genetic diversity and population structure across the current range of the species using 12 microsatellite markers. We analyzed samples from the eight uncharacterized populations and seven populations previously studied by Schwartz and May (2008). Bayesian clustering supported two distinct clusters of Sacramento Perch herein designated as A and B. Within these two clusters we detected hierarchical substructure, likely due to genetic drift after population founding. Genetic differentiation among populations within the same cluster was relatively low (FST = 0.023–0.176), while differentiation among populations from different clusters was higher (FST = 0.190–0.320). The existence of two strongly divergent genetic clusters in Sacramento Perch suggests two distinct translocation sources, and we recommend that these clusters be treated as genetic management units (GMUs). The B GMU populations had fairly low levels of genetic diversity relative to the A GMU populations. All populations showed evidence of past bottlenecks, and most had effective population sizes placing them at risk for inbreeding depression. Human-facilitated gene flow is recommended to prevent further genetic diversity loss. Due to uncertainty surrounding Sacramento Perch translocation history and strong levels of divergence between the two GMUs, translocations should be facilitated only between populations within the same GMU

Covariation Among Vowel Height Effects on Acoustic Measures

Covariation among vowel height effects on vowel intrinsic fundamental frequency (IF0), voice onset time (VOT), and voiceless interval duration (VID) is analyzed to assess the plausibility of a common physiological mechanism underlying variation in these measures. Phrases spoken by 20 young adults, containing words composed of initial voiceless stops or /s/ and high or low vowels, were produced in habitual and voluntarily increased F0 conditions. High vowels were associated with increased IF0 and longer VIDs. VOT and VID exhibited significant covariation with IF0 only for males at habitua

Monte Carlo investigation of the effect of blood volume and oxygen saturation on optical path in reflectance pulse oximetry

Despite the clinical importance of pulse oximetry, the precise nature of the interaction of light with tissue, which underlies the technique, is not yet fully understood. The limitations of the method with regard toits accuracy inconditions of compromised perfusion and/or low blood oxygen saturations are well documented but have only partly been resolved. Results from a static monolayer Monte Carlo modelof optical path and reflectance attwo wavelengths most commonly usedinpulse-oximetry (660 and 940 nm) through skin tissue, containing different volume fractions of blood witharange of oxygen saturations, are presented. Results exhibited differences in mean optical path (MOP) between the two wavelengths, with differences generally increasing with increasing tissue oxygen saturation and decreasing blood volume.As anexample, inatypical sensor configuration, the MOP of red light traveling through skin containing 7.5% blood volume fraction with mean oxygen saturationof60% was 58% higher than that for infrared. The results presented should contribute to further understandingofthe effectofphysiological conditions suchasanemia, ischemia and hypoxemia on the accuracy of pulse oximetry readings

Dynamic Habitat Disturbance and Ecological Resilience (DyHDER): Modeling Population Responses to Habitat Condition

Understanding how populations respond to spatially heterogeneous habitat disturbance is as critical to conservation as it is challenging. Here, we present a new, free, and open‐source metapopulation model: Dynamic Habitat Disturbance and Ecological Resilience (DyHDER), which incorporates subpopulation habitat condition and connectivity into a population viability analysis framework. Modeling temporally dynamic and spatially explicit habitat disturbance of varying magnitude and duration is accomplished through the use of habitat time‐series data and a mechanistic approach to adjusting subpopulation vital rates. Additionally, DyHDER uses a probabilistic dispersal model driven by site‐specific habitat suitability, density dependence, and directionally dependent connectivity. In the first application of DyHDER, we explore how fragmentation and projected climate change are predicted to impact a well‐studied Bonneville cutthroat trout metapopulation in the Logan River (Utah, USA). The DyHDER model predicts which subpopulations are most susceptible to disturbance, as well as the potential interactions between stressors. Further, the model predicts how populations may be expected to redistribute following disturbance. This information is valuable to conservationists and managers faced with protecting populations of conservation concern across landscapes undergoing changing disturbance regimes. The DyHDER model provides a valuable and generalizable new tool to explore metapopulation resilience to spatially and temporally dynamic stressors for a diverse range of taxa and ecosystems

The Importance of Time Congruity in the Organisation.

In 1991 Kaufman, Lane, and Lindquist proposed that time congruity in terms of an individual's time preferences and the time use methods of an organisation would lead to satisfactory performance and enhancement of quality of work and general life. The research reported here presents a study which uses commensurate person and job measures of time personality in an organisational setting to assess the effects of time congruity on one aspect of work life, job-related affective well-being. Results show that time personality and time congruity were found to have direct effects on well-being and the influence of time congruity was found to be mediated through time personality, thus contributing to the person–job (P–J) fit literature which suggests that direct effects are often more important than indirect effects. The study also provides some practical examples of ways to address some of the previously cited methodological issues in P–J fit research

Three-Dimensional Human iPSC-Derived Artificial Skeletal Muscles Model Muscular Dystrophies and Enable Multilineage Tissue Engineering

Summary: Generating human skeletal muscle models is instrumental for investigating muscle pathology and therapy. Here, we report the generation of three-dimensional (3D) artificial skeletal muscle tissue from human pluripotent stem cells, including induced pluripotent stem cells (iPSCs) from patients with Duchenne, limb-girdle, and congenital muscular dystrophies. 3D skeletal myogenic differentiation of pluripotent cells was induced within hydrogels under tension to provide myofiber alignment. Artificial muscles recapitulated characteristics of human skeletal muscle tissue and could be implanted into immunodeficient mice. Pathological cellular hallmarks of incurable forms of severe muscular dystrophy could be modeled with high fidelity using this 3D platform. Finally, we show generation of fully human iPSC-derived, complex, multilineage muscle models containing key isogenic cellular constituents of skeletal muscle, including vascular endothelial cells, pericytes, and motor neurons. These results lay the foundation for a human skeletal muscle organoid-like platform for disease modeling, regenerative medicine, and therapy development. : Maffioletti et al. generate human 3D artificial skeletal muscles from healthy donors and patient-specific pluripotent stem cells. These human artificial muscles accurately model severe genetic muscle diseases. They can be engineered to include other cell types present in skeletal muscle, such as vascular cells and motor neurons. Keywords: skeletal muscle, pluripotent stem cells, iPS cells, myogenic differentiation, tissue engineering, disease modeling, muscular dystrophy, organoid

The steady-state pharmacokinetics of efavirenz and nevirapine when used in combination in human immunodeficiency virus type 1-infected persons

The steady-state pharmacokinetics of efavirenz and nevirapine, when used in combination to treat human immunodeficiency virus type 1 (HIV-1)-infected subjects, were investigated. HIV-1-infected persons who had used efavirenz (600 mg once daily) for > or =2 weeks were eligible for study inclusion. The plasma pharmacokinetics of efavirenz were determined over 24 h. Subsequently, nevirapine (400 mg once daily) was added to the regimen. After 4 weeks, the pharmacokinetics of efavirenz and nevirapine were assessed over 24 h. The differences between the pharmacokinetic parameters of efavirenz with and without nevirapine were analyzed, and the pharmacokinetics of nevirapine were compared with those in historical control patients. The exposure to efavirenz when combined with nevirapine was significantly decreased by 22% (area under the plasma concentration vs. time curve), 36% (minimum plasma concentration), and 17% (maximum plasma concentration). Nevirapine pharmacokinetics appear to be unaffected by coadministration of efavirenz, compared with data from historical control patient