Mitochondria clumping vs. mitochondria fusion in CMT2A diseases

Phenotypic variations in Charcot-Marie-Tooth disease type 2A (CMT2A) result from the many mutations in the mitochondrial fusion protein, mitofusin 2 (MFN2). While the GTPase domain mutations of MFN2 lack the ability to hydrolyze GTP and complete mitochondrial fusion, the mechanism of dysfunction in HR1 domain mutations has yet to be explored. Usin

Adapting ASPEN for Orbital Express

By studying the Orbital Express mission, modeling the spacecraft and scenarios, and testing the system, a technique has been developed that uses recursive decomposition to represent procedural actions declaratively, schema-level uncertainty reasoning to make uncertainty reasoning tractable, and lightweight, natural language processing to automatically parse procedures to produce declarative models. Schema-level uncertainty reasoning has, at its core, the basic assumption that certain variables are uncertain, but not independent. Once any are known, then the others become known. This is important where a variable is uncertain for an action and many actions of the same type exist in the plan. For example, if the number of retries to purge pump lines was unknown (but bounded), and each attempt required a sub-plan, then, once the correct number of attempts required for a purge was known, it would likely be the same for all subsequent purges. This greatly reduces the space of plans that needs to be searched to ensure that all executions are feasible. To accommodate changing scenario procedures, each is ingested into a tabular format in temporal order, and a simple natural-language parser is used to read each step and to derive the impact of that step on memory, power, and communications. Then an ASPEN (Activity Scheduling and Planning Environment) model is produced based on this analysis. The model is tested and further changed by hand, if necessary, to reflect the actual procedure. This results in a great savings of time used for modeling procedures. Many processes that need to be modeled in ASPEN (a declarative system) are, in fact, procedural. ASPEN includes the ability to model activities in a hierarchical fashion, but this representation breaks down if there is a practically unbounded number of sub-activities and decomposition topologies. However, if recursive decomposition is allowed, HTN-like encodings are enabled to represent most procedural phenomena. For example, if a switch requires a variable (but known at the time of the attempt) number of attempts to switch on, one can recurse on the number of remaining switch attempts and decompose into either the same switching activity with one less required attempt, or not decompose at all (or decompose into a dummy task), resulting in the end of the decomposition. In fact, any bounded procedural behavior can be modeled using recursive decompositions assuming that the variables impinging the disjunctive decomposition decision are computable at the time that the decision is made. This enables one to represent tasks that are controlled outside of the scheduler, but that the scheduler must accommodate, without requiring one to give a declarative model of the procedural behavior

An In Vitro Pipeline for Screening and Selection of Citrus-Associated Microbiota with Potential Anti-"Candidatus Liberibacter asiaticus" Properties.

Huanglongbing (HLB) is a destructive citrus disease that is lethal to all commercial citrus plants, making it the most serious citrus disease and one of the most serious plant diseases. Because of the severity of HLB and the paucity of effective control measures, we structured this study to encompass the entirety of the citrus microbiome and the chemistries associated with that microbial community. We describe the spatial niche diversity of bacteria and fungi associated with citrus roots, stems, and leaves using traditional microbial culturing integrated with culture-independent methods. Using the culturable sector of the citrus microbiome, we created a microbial repository using a high-throughput bulk culturing and microbial identification pipeline. We integrated an in vitro agar diffusion inhibition bioassay into our culturing pipeline that queried the repository for antimicrobial activity against Liberibacter crescens, a culturable surrogate for the nonculturable "Candidatus Liberibacter asiaticus" bacterium associated with HLB. We identified microbes with robust inhibitory activity against L. crescens that include the fungi Cladosporium cladosporioides and Epicoccum nigrum and bacterial species of Pantoea, Bacillus, and Curtobacterium Purified bioactive natural products with anti-"Ca. Liberibacter asiaticus" activity were identified from the fungus C. cladosporioides Bioassay-guided fractionation of an organic extract of C. cladosporioides yielded the natural products cladosporols A, C, and D as the active agents against L. crescens This work serves as a foundation for unraveling the complex chemistries associated with the citrus microbiome to begin to understand the functional roles of members of the microbiome, with the long-term goal of developing anti-"Ca Liberibacter asiaticus" bioinoculants that thrive in the citrus holosystem.IMPORTANCE Globally, citrus is threatened by huanglongbing (HLB), and the lack of effective control measures is a major concern of farmers, markets, and consumers. There is compelling evidence that plant health is a function of the activities of the plant's associated microbiome. Using Liberibacter crescens, a culturable surrogate for the unculturable HLB-associated bacterium "Candidatus Liberibacter asiaticus," we tested the hypothesis that members of the citrus microbiome produce potential anti-"Ca Liberibacter asiaticus" natural products with potential anti-"Ca Liberibacter asiaticus" activity. A subset of isolates obtained from the microbiome inhibited L. crescens growth in an agar diffusion inhibition assay. Further fractionation experiments linked the inhibitory activity of the fungus Cladosporium cladosporioides to the fungus-produced natural products cladosporols A, C, and D, demonstrating dose-dependent antagonism to L. crescens

Monitoring of oxolinic acid residues in tilapia flesh (Oreochromis niloticus) using a microbiological screening technique and an LC-UV confirmatory method

peer reviewe

A New Analysis of 8 Spitzer Phase Curves and Hot Jupiter Population Trends: Qatar-1b, Qatar-2b, WASP-52b, WASP-34b, and WASP-140b

With over 30 phase curves observed during the warm Spitzer mission, the complete data set provides a wealth of information relating to trends and three-dimensional properties of hot Jupiter atmospheres. In this work we present a comparative study of seven new Spitzer phase curves for four planets with equilibrium temperatures of T$_{eq}\sim$ 1300K: Qatar-2b, WASP-52b, WASP-34b, and WASP-140b, as well as the reanalysis of the 4.5 \micron Qatar-1b phase curve due to the similar equilibrium temperature. In total, five 4.5 \micron phase curves and three 3.6 \micron phase curves are analyzed here with a uniform approach. Using these new results, in combination with literature values for the entire population of published Spitzer phase curves of hot Jupiters, we present evidence for a linear trend of increasing hot spot offset with increasing orbital period, as well as observational evidence for two classes of planets in apparent redistribution vs. equilibrium temperature parameter space, and tentative evidence for a dependence of hot spot offset on planetary surface gravity in our $\sim$ 1300 K sample. We do not find trends in apparent heat redistribution with orbital period or gravity. Non-uniformity in literature Spitzer data analysis techniques precludes a definitive determination of the sources or lack of trends.Comment: 22 pages, 13 figures, 6 tables. Accepted for publication in AAS journal

Mental health recovery for survivors of modern slavery: Grounded theory study protocol

© 2020 Author(s). Published by BMJ. Introduction Slavery and human trafficking are crimes involving the violation of human rights and refer to exploitative situations where an individual cannot refuse or leave due to threats, coercion or abuse of power. Activities involving slavery include forced labour exploitation, forced sexual exploitation, forced marriage and servitude. Epidemiological studies show high levels of mental health need and poor provision of appropriate support for survivors. What mental health recovery means to victims/survivors and how it could be promoted is under-researched. Methods and analysis A grounded theory study based on individual interviews will be undertaken. Survivors across the UK will be identified and recruited from non-governmental organisations and via social media. As per grounded theory methodology, data collection and analysis will be undertaken concurrently and recruitment will continue until theoretical saturation is reached. It is anticipated that approximately 30 participants will be recruited. Interviews will be audio recorded, transcribed verbatim and uploaded to NVivo V.11. The constant comparative method will be used to analyse the data, in order to produce a theoretical framework for mental health recovery that is grounded in the experiences of survivors. Ethics and dissemination Ethical approval has been obtained from the Faculty of Medicine and Health Sciences Ethics Committee at the University of Nottingham. The findings of the study will be disseminated to academic, professional and survivor-based audiences to inform future policy developments and the provision of mental health recovery support to this population

On the benefits of the tryptophan metabolite 3-hydroxyanthranilic acid in Caenorhabditis elegans and mouse aging.

Tryptophan metabolism through the kynurenine pathway influences molecular processes critical to healthy aging including immune signaling, redox homeostasis, and energy production. Aberrant kynurenine metabolism occurs during normal aging and is implicated in many age-associated pathologies including chronic inflammation, atherosclerosis, neurodegeneration, and cancer. We and others previously identified three kynurenine pathway genes-tdo-2, kynu-1, and acsd-1-for which decreasing expression extends lifespan in invertebrates. Here we report that knockdown of haao-1, a fourth gene encoding the enzyme 3-hydroxyanthranilic acid (3HAA) dioxygenase (HAAO), extends lifespan by ~30% and delays age-associated health decline in Caenorhabditis elegans. Lifespan extension is mediated by increased physiological levels of the HAAO substrate 3HAA. 3HAA increases oxidative stress resistance and activates the Nrf2/SKN-1 oxidative stress response. In pilot studies, female Haao knockout mice or aging wild type male mice fed 3HAA supplemented diet were also long-lived. HAAO and 3HAA represent potential therapeutic targets for aging and age-associated disease

Characterizing the Near-infrared Spectra of Flares from TRAPPIST-1 During JWST Transit Spectroscopy Observations

We present the first analysis of JWST near-infrared spectroscopy of stellar flares from TRAPPIST-1 during transits of rocky exoplanets. Four flares were observed from 0.6--2.8 $\mu$m with NIRISS and 0.6--3.5 $\mu$m with NIRSpec during transits of TRAPPIST-1b, f, and g. We discover P$\alpha$ and Br$\beta$ line emission and characterize flare continuum at wavelengths from 1--3.5 $\mu$m for the first time. Observed lines include H$\alpha$, P$\alpha$-P$\epsilon$, Br$\beta$, He I $\lambda$0.7062$\mu$m, two Ca II infrared triplet (IRT) lines, and the He I IRT. We observe a reversed Paschen decrement from P$\alpha$-P$\gamma$ alongside changes in the light curve shapes of these lines. The continuum of all four flares is well-described by blackbody emission with an effective temperature below 5300 K, lower than temperatures typically observed at optical wavelengths. The 0.6--1 $\mu$m spectra were convolved with the TESS response, enabling us to measure the flare rate of TRAPPIST-1 in the TESS bandpass. We find flares of 10$^{30}$ erg large enough to impact transit spectra occur at a rate of 3.6$\substack{+2.1 \\ -1.3}$ flare d$^{-1}$, $\sim$10$\times$ higher than previous predictions from K2. We measure the amount of flare contamination at 2 $\mu$m for the TRAPPIST-1b and f transits to be 500$\pm$450 and 2100$\pm$400 ppm, respectively. We find up to 80% of flare contamination can be removed, with mitigation most effective from 1.0--2.4 $\mu$m. These results suggest transits affected by flares may still be useful for atmospheric characterization efforts.Comment: 29 pages, 17 figures, 3 tables, accepted to The Astrophysical Journa

Smaller than expected bright-spot offsets in Spitzer phase curves of the hot Jupiter Qatar-1b

We present \textit{Spitzer} full-orbit thermal phase curves of the hot Jupiter Qatar-1b, a planet with the same equilibrium temperature---and intermediate surface gravity and orbital period---as the well-studied planets HD 209458b and WASP-43b. We measure secondary eclipse of $0.21 \pm 0.02 \%$ at $3.6~\mu$m and $0.30 \pm 0.02 \%$ at $4.5~\mu$m, corresponding to dayside brightness temperatures of $1542^{+32}_{-31}$~K and $1557^{+35}_{-36}$~K, respectively, consistent with a vertically isothermal dayside. The respective nightside brightness temperatures are $1117^{+76}_{-71}$~K and $1167^{+69}_{-74}$~K, in line with a trend that hot Jupiters all have similar nightside temperatures. We infer a Bond albedo of $0.12_{-0.16}^{+0.14}$ and a moderate day-night heat recirculation efficiency, similar to HD 209458b. General circulation models for HD 209458b and WASP-43b predict that their bright-spots should be shifted east of the substellar point by tens of degrees, and these predictions were previously confirmed with \textit{Spitzer} full-orbit phase curve observations. The phase curves of Qatar-1b are likewise expected to exhibit eastward offsets. Instead, the observed phase curves are consistent with no offset: $11^{\circ}\pm 7^{\circ}$ at $3.6~\mu$m and $-4^{\circ}\pm 7^{\circ}$ at $4.5~\mu$m. The discrepancy in circulation patterns between these three otherwise similar planets points to the importance of secondary parameters like rotation rate and surface gravity, and the presence or absence of clouds, in determining atmospheric conditions on hot Jupiters.Comment: 14 pages, 8 figures. Accepted for publication in A

Transmission Spectroscopy of the Habitable Zone Exoplanet LHS 1140 b with JWST/NIRISS

LHS 1140 b is the second-closest temperate transiting planet to Earth with an equilibrium temperature low enough to support surface liquid water. At 1.730 ± 0.025 R ⊕, LHS 1140 b falls within the radius valley separating H2-rich mini-Neptunes from rocky super-Earths. Recent mass and radius revisions indicate a bulk density significantly lower than expected for an Earth-like rocky interior, suggesting that LHS 1140 b could be either a mini-Neptune with a small envelope of hydrogen (∼0.1% by mass) or a water world (9%–19% water by mass). Atmospheric characterization through transmission spectroscopy can readily discern between these two scenarios. Here we present two JWST/NIRISS transit observations of LHS 1140 b, one of which captures a serendipitous transit of LHS 1140 c. The combined transmission spectrum of LHS 1140 b shows a telltale spectral signature of unocculted faculae (5.8σ), covering ∼20% of the visible stellar surface. Besides faculae, our spectral retrieval analysis reveals tentative evidence of residual spectral features, best fit by Rayleigh scattering from a N2-dominated atmosphere (2.3σ), irrespective of the consideration of atmospheric hazes. We also show through Global Climate Models (GCMs) that H2-rich atmospheres of various compositions (100×, 300×, 1000× solar metallicity) are ruled out to >10σ. The GCM calculations predict that water clouds form below the transit photosphere, limiting their impact on transmission data. Our observations suggest that LHS 1140 b is either airless or, more likely, surrounded by an atmosphere with a high mean molecular weight. Our tentative evidence of a N2-rich atmosphere provides strong motivation for future transmission spectroscopy observations of LHS 1140 b