A water-soluble form of porin from the mitochondrial outer membrane of Neurospora crassa

Mitochondrial porin, the outer membrane pore-forming protein, was isolated in the presence of detergents and converted into a water- soluble form. This water-soluble porin existed under nondenaturing conditions as a mixture of dimers and oligomers. The proportion of dimers increased with decreasing porin concentration during conversion. Water-soluble porin inserted spontaneously into artificial bilayers as did detergent-solubilized porin. Whereas the latter form had no specific requirements for the lipid composition of the bilayer, water- soluble porin inserted only into membranes containing a sterol, and only in the presence of very low concentrations of Triton X-100 (0.001% w/v) in the solution bathing the bilayer. The channels formed by water- soluble porin were indistinguishable from those formed by detergent- purified porin with respect to specific conductance and voltage dependence of conductance. Water-soluble porin bound tightly in a saturable fashion to isolated mitochondria. The bound form was readily accessible to added protease, indicating its presence on the mitochondrial surface. The number of binding sites was in the range of 5-10 pmol/mg of mitochondrial protein. Water-soluble porin apparently binds to a site on the assembly pathway of the porin precursor, since mitochondria whose binding sites were saturated with the water-soluble form did not import porin precursor synthesized in a cell-free system

Patient Perspectives on Osseointegration: A National Survey of Veterans with Upper Limb Amputation

INTRODUCTION: Osseointegrated (OI) prostheses have a unique benefit-risk profile among prosthetic alternatives and have been marketed in the United States under a Humanitarian Device Exemption since 2015. Information about upper limb prosthesis user perspectives on benefits and risks, prosthesis-user subpopulations for whom OI is most acceptable, and outcomes that matter most to patients could help inform clinical and regulatory decision-making. Recent 21st Century Cures legislation expanded the role of patient experience data in the decision-making process of the U.S. Food and Drug Administration, recognizing that patient perspectives may be informative to regulators. OBJECTIVE: To better understand prosthesis user perspectives about the benefits and risks associated with upper limb OI prostheses. DESIGN: Patient perspective survey. SETTING: Telephone administration. PARTICIPANTS: National sample of veterans with upper limb loss. INTERVENTIONS: NA MAIN OUTCOME MEASURES: Benefit-risk survey developed for this study. RESULTS: Twenty-eight percent of unilateral and 13% of bilateral amputees were willing to consider osseointegration surgery. Multivariate logistic regression models [OR; 95% CI] showed that transhumeral amputation level [OR 1.40; 1.01-1.98] was associated with greater willingness to consider surgery, whereas older age [OR 0.17; 0.09-0.32] and higher VR-12 Mental Component Summary [OR 0.53; 0.35-0.81] were associated with less willingness. Having a durable/reliable device, the ability to do more activities, and having a comfortable device were rated as very important or somewhat important by 98% or more for every risk condition. CONCLUSIONS: Persons who were older, had transradial amputation (compared to transhumeral), and those who had better mental functioning were less willing to consider this surgery. Respondents who were willing to consider surgery indicated that the most important potential benefits were obtaining a durable/reliable device, the ability to do more activities, and having a comfortable device. Most were willing to accept one or more risks of surgery, with long-term risks including chronic pain, loss of nerve function, or device failure considered the most unacceptable. LEVEL OF EVIDENCE: III. has been contributed to by US Government employees and their work is in the public domain in the USA

Collapse of a molecular cloud core to stellar densities: the radiative impact of stellar core formation on the circumstellar disc

We present results from the first three-dimensional radiation hydrodynamical calculations to follow the collapse of a molecular cloud core beyond the formation of the stellar core. We find the energy released by the formation of the stellar core, within the optically-thick first hydrostatic core, is comparable to the binding energy of the disc-like first core. This heats the inner regions of the disc, drives a shock wave through the disc, dramatically decreases the accretion rate on to the stellar core, and launches a temporary bipolar outflow perpendicular to the rotation axis that travels in excess of 50 AU into the infalling envelope. This outburst may assist the young protostar in launching a conventional magnetic jet. Furthermore, if these events are cyclic, they may provide a mechanism for intense bursts of accretion separated by long periods of relatively quiescent accretion which can potentially solve both the protostellar luminosity problem and the apparent age spread of stars in young clusters. Such outbursts may also provide a formation mechanism for the chondrules found in meteorites, with the outflow transporting them to large distances in the circumstellar disc.Comment: Accepted by MNRAS Letters. 6 pages, 4 figures. Animations can be found at http://www.astro.ex.ac.uk/people/mbate/Animations/Stellar

Advancing academic careers through formal professional mentorship: The Research Scholars Mentorship Program (RSMP)

Mentorship is an essential component of professional development for young and emerging scholars. In partnership with the Kellogg Health Scholars Program, the American Academy of Health Behavior (AAHB) developed the 12-month Research Scholars Mentorship Program (RSMP) as a mechanism to facilitate high-quality mentorship interactions among junior and seasoned investigators within the Academy. This article provides a rationale, history, and description of the RSMP, as well as the collective scholarly achievements of the Cohorts and future directions. To date, 44 Pairs have initiated or completed the program. Products written and submitted by the Pairs during the 12-month mentorship period have included grants (n = 21), peer-reviewed manuscripts (n = 64), and book chapters (n = 2). Additionally, Pairs have collaborated to initiate new studies (n = 10) and develop new courses (n = 1). AAHB’s commitment to mentorship and professional development fueled the development of the RSMP to foster inclusive scholarship, expand membership, and promote productivity. The 12-month RSMP is a model for formal mentorship within professional organizations in that it facilitates Mentee-Mentor Pairs to enhance their professional and research trajectories through the execution of processes and development of products

The growth and hydrodynamic collapse of a protoplanet envelope

We have conducted three-dimensional self-gravitating radiation hydrodynamical models of gas accretion onto high mass cores (15-33 Earth masses) over hundreds of orbits. Of these models, one case accretes more than a third of a Jupiter mass of gas, before eventually undergoing a hydrodynamic collapse. This collapse causes the density near the core to increase by more than an order of magnitude, and the outer envelope to evolve into a circumplanetary disc. A small reduction in the mass within the Hill radius (R_H) accompanies this collapse as a shock propagates outwards. This collapse leads to a new hydrostatic equilibrium for the protoplanetary envelope, at which point 97 per cent of the mass contained within the Hill radius is within the inner 0.03 R_H which had previously contained less than 40 per cent. Following this collapse the protoplanet resumes accretion at its prior rate. The net flow of mass towards this dense protoplanet is predominantly from high latitudes, whilst at the outer edge of the circumplanetary disc there is net outflow of gas along the midplane. We also find a turnover of gas deep within the bound envelope that may be caused by the establishment of convection cells.Comment: 16 pages, 16 figures. Accepted for publication in MNRA

On the fragmentation criteria of self-gravitating protoplanetary discs

We investigate the fragmentation criterion in massive self-gravitating discs. We present new analysis of the fragmentation conditions which we test by carrying out global three-dimensional numerical simulations. Whilst previous work has placed emphasis on the cooling timescale in units of the orbital timescale, \beta , we find that at a given radius the surface mass density (i.e. disc mass and profile) and star mass also play a crucial role in determining whether a disc fragments or not as well as where in the disc fragments form. We find that for shallow surface mass density profiles (p<2, where \Sigma \propto R^{-p}), fragments form in the outer regions of the disc. However for steep surface mass density profiles (p \gtrsim 2), fragments form in the inner regions of a disc. In addition, we also find that the critical value of the cooling timescale in units of the orbital timescale found in previous simulations is only applicable to certain disc surface mass density profiles and for particular disc radii and is not a general rule for all discs. We find an empirical fragmentation criteria between the cooling timescale in units of the orbital timescale, \beta , the surface mass density, the star mass and the radius.Comment: Accepted for publication by MNRAS. 15 pages, 18 figure

The regulatory and transcriptional landscape associated with carbon utilization in a filamentous fungus.

Filamentous fungi, such as Neurospora crassa, are very efficient in deconstructing plant biomass by the secretion of an arsenal of plant cell wall-degrading enzymes, by remodeling metabolism to accommodate production of secreted enzymes, and by enabling transport and intracellular utilization of plant biomass components. Although a number of enzymes and transcriptional regulators involved in plant biomass utilization have been identified, how filamentous fungi sense and integrate nutritional information encoded in the plant cell wall into a regulatory hierarchy for optimal utilization of complex carbon sources is not understood. Here, we performed transcriptional profiling of N. crassa on 40 different carbon sources, including plant biomass, to provide data on how fungi sense simple to complex carbohydrates. From these data, we identified regulatory factors in N. crassa and characterized one (PDR-2) associated with pectin utilization and one with pectin/hemicellulose utilization (ARA-1). Using in vitro DNA affinity purification sequencing (DAP-seq), we identified direct targets of transcription factors involved in regulating genes encoding plant cell wall-degrading enzymes. In particular, our data clarified the role of the transcription factor VIB-1 in the regulation of genes encoding plant cell wall-degrading enzymes and nutrient scavenging and revealed a major role of the carbon catabolite repressor CRE-1 in regulating the expression of major facilitator transporter genes. These data contribute to a more complete understanding of cross talk between transcription factors and their target genes, which are involved in regulating nutrient sensing and plant biomass utilization on a global level

On the convergence of the critical cooling timescale for the fragmentation of self-gravitating discs

We carry out simulations of gravitationally unstable discs using a Smoothed Particle Hydrodynamics (SPH) code and a grid-based hydrodynamics code, FARGO, to understand the previous non-convergent results reported by Meru & Bate (2011a). We obtain evidence that convergence with increasing resolution occurs with both SPH and FARGO and in both cases we find that the critical cooling timescale is larger than previously thought. We show that SPH has a first-order convergence rate while FARGO converges with a second-order rate. We show that the convergence of the critical cooling timescale for fragmentation depends largely on the numerical viscosity employed in both SPH and FARGO. With SPH, particle velocity dispersion may also play a role. We show that reducing the dissipation from the numerical viscosity leads to larger values of the critical cooling time at a given resolution. For SPH, we find that the effect of the dissipation due to the numerical viscosity is somewhat larger than had previously been appreciated. In particular, we show that using a quadratic term in the SPH artificial viscosity (beta_{SPH}) that is too low appears to lead to excess dissipation in gravitationally unstable discs, which may affect any results that sensitively depend on the thermodynamics, such as disc fragmentation. We show that the two codes converge to values of the critical cooling timescale, beta_{crit} > 20 (for a ratio of specific heats of gamma=5/3), and perhaps even as large as beta_{crit} \approx 30. These are approximately 3-5 times larger than has been found by most previous studies. This is equivalent to a maximum gravitational stress that a disc can withstand without fragmenting of alpha_{GI,crit} \approx 0.013-0.02, which is much smaller than the values typically used in the literature. It is therefore easier for self-gravitating discs to fragment than has been concluded from most past studies.Comment: Accepted for publication by MNRAS. 26 pages, 17 figure

On the accumulation of planetesimals near disc gaps created by protoplanets

We have performed three-dimensional two-fluid (gas-dust) hydrodynamical models of circumstellar discs with embedded protoplanets (3 - 333 M\oplu) and small solid bodies (radii 10cm to 10m). We find that high mass planets (\gtrsim Saturn mass) open sufficiently deep gaps in the gas disc such that the density maximum at the outer edge of the gap can very efficiently trap metre-sized solid bodies. This allows the accumulation of solids at the outer edge of the gap as solids from large radii spiral inwards to the trapping region. This process of accumulation occurs fastest for those bodies that spiral inwards most rapidly, typically metre-sized boulders, whilst smaller and larger objects will not migrate sufficiently rapidly in the discs lifetime to benefit from the process. Around a Jupiter mass planet we find that bound clumps of solid material, as large as several Earth masses, may form, potentially collapsing under self-gravity to form planets or planetesimals. These results are in agreement with Lyra et al. (2009), supporting their finding that the formation of a second generation of planetesimals or of terrestrial mass planets may be triggered by the presence of a high mass planet.Comment: 14 pages, 10 figures. Accepted for publication in MNRA