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Covid-19, Artificial Intelligence (AI), and Climate Change, have disrupted work education, rendering sustainability of careers and livelihoods a concern. This paper outlines a collaborative response to that challenge, offering opportunities for sustainable livelihoods in a work education cloud collaboration, Project SLiC (Sustainable Livelihoods Collaboration). We have joined forces across nation states in the Global South/North to share cloud resources, focused on teaching a postgraduate course, Sustainable Livelihoods. Online modules are stored in a secure cloud site, from which local courses draw-down, autochthonously, whichever resources fit workforce development in context. We outline modules, and an evaluative process, in a proof-of-concept trial. Finally, we envisage how this initial collaboration may morph into a whole degree, including research supervision. We close with a call to career development professionals to share their unique expertise and experiences at the work education frontline, on how to develop this sustainable careers project, for the greater good. [ABSTRACT FROM AUTHOR]

The evolution of morphinan alkaloid biosynthesis in plants of the genus Papaver includes permutation of several processes including gene duplication, fusion, neofunctionalization, and deletion resulting in the present chemotaxonomy. A critical gene fusion event resulting in the key bifunctional enzyme reticuline epimerase (REPI), which catalyzes the stereochemical inversion of (S)-reticuline, was suggested to precede neofunctionalization of downstream enzymes leading to morphine biosynthesis in opium poppy (Papaver somniferum). The ancestrally related aldo-keto reductases 1,2-dehydroreticuline reductase (DRR), which occurs in some species as a component of REPI, and codeinone reductase (COR) catalyze the second and penultimate steps, respectively, in the pathway converting (S)-reticuline to morphine. Orthologs for each enzyme isolated from the transcriptomes of 12 Papaver species were shown to catalyze their respective reactions in species that capture states of the metabolic pathway prior to key evolutionary events, including the gene fusion event leading to REPI, thus suggesting a patchwork model for pathway evolution. Analysis of the structure and substrate preferences of DRR orthologs in comparison with COR orthologs revealed structure-function relationships underpinning the functional latency of DRR and COR orthologs in the genus Papaver, thus providing insights into the molecular events leading to the evolution of the pathway., (© 2024. The Author(s).)

Several proteins from plant pathogenesis-related family 10 (PR10) are highly abundant in the latex of opium poppy and have recently been shown to play diverse and important roles in the biosynthesis of benzylisoquinoline alkaloids (BIAs). The recent determination of the first crystal structures of PR10-10 showed how large conformational changes in a surface loop and adjacent β-strand are coupled to the binding of BIA compounds to the central hydrophobic binding pocket. A more detailed analysis of these conformational changes is now reported to further clarify how ligand binding is coupled to the formation and cleavage of an intermolecular disulfide bond that is only sterically allowed when the BIA binding pocket is empty. To decouple ligand binding from disulfide-bond formation, each of the two highly conserved cysteine residues (Cys59 and Cys155) in PR10-10 was replaced with serine using site-directed mutagenesis. Crystal structures of the Cys59Ser mutant were determined in the presence of papaverine and in the absence of exogenous BIA compounds. A crystal structure of the Cys155Ser mutant was also determined in the absence of exogenous BIA compounds. All three of these crystal structures reveal conformations similar to that of wild-type PR10-10 with bound BIA compounds. In the absence of exogenous BIA compounds, the Cys59Ser and Cys155Ser mutants appear to bind an unidentified ligand or mixture of ligands that was presumably introduced during expression of the proteins in Escherichia coli. The analysis of conformational changes triggered by the binding of BIA compounds suggests a molecular mechanism coupling ligand binding to the disruption of an intermolecular disulfide bond. This mechanism may be involved in the regulation of biosynthetic reactions in plants and possibly other organisms., (open access.)

Opium poppy accumulates copious amounts of several benzylisoquinoline alkaloids including morphine, noscapine, and papaverine, in the specialized cytoplasm of laticifers, which compose an internal secretory system associated with phloem throughout the plant. The contiguous latex includes an abundance of related proteins belonging to the pathogenesis-related (PR)10 family known collectively as major latex proteins (MLPs) and representing at least 35% of the total cellular protein content. Two latex MLP/PR10 proteins, thebaine synthase and neopione isomerase, have recently been shown to catalyze late steps in morphine biosynthesis previously assigned as spontaneous reactions. Using a combination of sucrose density-gradient fractionation-coupled proteomics, differential scanning fluorimetry, isothermal titration calorimetry, and X-ray crystallography, we show that the major latex proteins are a family of alkaloid-binding proteins that display altered conformation in the presence of certain ligands. Addition of MLP/PR10 proteins to yeast strains engineered with morphine biosynthetic genes from the plant significantly enhanced the conversion of salutaridine to morphinan alkaloids., (© 2022. The Author(s).)

Most developed nations have a statutory minimum wage set at levels insufficient to alleviate poverty. Increased calls for a living wage have generated considerable public controversy. This article draws on 25 interviews and four focus groups with employers, low-pay industry representatives, representatives of chambers of commerce, pay consultants, and unions. The core focus is on how participants use prominent narrative tropes for the living wage and against the living wage to argue their respective perspectives. We also document how both affirmative and negative tropes are often combined by participants to craft their own rhetorical positions on the issue., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hodgetts, Young-Hauser, Arrowsmith, Parker, Carr, Haar and Alefaio.)

Recent pre-pandemic research suggests that living wages can be pivotal for enhancing employee attitudes and subjective wellbeing. This article explores whether or not the present COVID-19 pandemic is impacting pivotal links between living wages and employee attitudes and subjective wellbeing, with replication indicating robustness. Twin cohorts each of 1,000 low-waged workers across New Zealand (NZ), one pre- (2018), and one present-pandemic (2020) were sample surveyed on hourly wage, job attitudes, and subjective wellbeing as linked to changes in the world of work associated with the pandemic (e.g., job security, stress, anxiety, depression, and holistic wellbeing). Using locally estimated scatter-point smoothing, job attitudes and subjective wellbeing scores tended to pivot upward at the living wage level in NZ. These findings replicate earlier findings and extend these into considering subjective wellbeing in the context of a crisis for employee livelihoods and lives more generally. Convergence across multiple measures, constructs, and contexts, suggests the positive impacts of living wages are durable. We draw inspiration from systems dynamics to argue that the present government policy of raising legal minimum wages (as NZ has done) may not protect subjective wellbeing until wages cross the living wage Rubicon. Future research should address this challenge., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Carr, Haar, Hodgetts, Jones, Arrowsmith, Parker, Young-Hauser and Alefaio.)

Benzylisoquinoline alkaloids (BIAs) are a class of specialized metabolites with a diverse range of chemical structures and physiological effects. Codeine and morphine are two closely related BIAs with particularly useful analgesic properties. The aldo-keto reductase (AKR) codeinone reductase (COR) catalyzes the final and penultimate steps in the biosynthesis of codeine and morphine, respectively, in opium poppy (Papaver somniferum). However, the structural determinants that mediate substrate recognition and catalysis are not well defined. Here, we describe the crystal structure of apo-COR determined to a resolution of 2.4 Å by molecular replacement using chalcone reductase as a search model. Structural comparisons of COR to closely related plant AKRs and more distantly related homologues reveal a novel conformation in the β1α1 loop adjacent to the BIA-binding pocket. The proximity of this loop to several highly conserved active-site residues and the expected location of the nicotinamide ring of the NADP(H) cofactor suggest a model for BIA recognition that implies roles for several key residues. Using site-directed mutagenesis, we show that substitutions at Met-28 and His-120 of COR lead to changes in AKR activity for the major and minor substrates codeinone and neopinone, respectively. Our findings provide a framework for understanding the molecular basis of substrate recognition in COR and the closely related 1,2-dehydroreticuline reductase responsible for the second half of a stereochemical inversion that initiates the morphine biosynthesis pathway., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

According to the UN Sustainable Development Goals (SDGs), poverty eradication in the 21st century means everyday access to decent health care, education and livelihoods, political participation, social inclusion, a clean and safe environment, and more. These are aspirational goals that together support a decent quality of life. Crossing monetary, 'poverty thresholds' may enable such goals. Most estimates of 'where' the monetary threshold lies derive the estimates circularly from monetary costs of living. The link to quality of living is thereby made by fiat, untested empirically in everyday human experience. We already know we can measure income independently of middle class quality of life, and probe for relationships between the two. Why not for poverty too? A quantity of money where quality of life changed would mark a genuine threshold required for example to escape from poverty traps. Using this approach, studies in quality of work-life, using multiple indicators, have identified at least three thresholds where quality of life ticked markedly upwards, including inter-threshold ranges where gradients went from zero to positive. The concept of work-life balance suggests that this approach may be usefully extended to include quality health care, education, and other SDGs in sustainability science., (© Springer Japan KK, part of Springer Nature 2020.)

Purpose: Pediatric asthma disproportionately affects low-income and minority children. The HEAL (Head-Off Environmental Asthma in Louisiana), Phase II Project was a collaborative effort with a primary focus to improve pediatric asthma management in New Orleans, Louisiana. The purpose of this article is to report clinical outcomes captured at baseline and 12-month follow-up., Method: HEAL (Head-off Environmental Asthma in Louisiana), Phase II was a pre-post intervention study that enrolled children ages 2 to 18 years of age with a diagnosis of asthma to receive asthma education within the clinic setting. Enrollees received an asthma education intervention, an environmental evaluation, and a 12-month follow-up session. Endpoints included symptom days, level of asthma control, asthma exacerbations, emergency room visits, hospitalizations, and missed school days., Results: The majority of participants were aged 5 years and older, male, Black, and persistent asthmatics. Emergency room visits decreased from 41% to 20% ( p < .001). Improvements in coughing (83% to 62%, p < .001), wheezing (50% to 26%, p < .001), and chest tightness (29% to 18%, p < .001) were also seen., Conclusion: The novel intervention was associated with improved asthma outcomes among pediatric patients receiving care at the clinical sites in the Greater New Orleans area.

There is growing evidence for the role of attachment in psychosis, however, to date there has been no quantitative review of the prevalence of insecure attachment in psychosis. The current study sought to systematically appraise studies investigating the prevalence of insecure attachment and the association with psychosis-spectrum experiences using meta-analytic techniques. A systematic search of studies carried out between January 1980 and 30th November 2015 found 25 papers eligible for inclusion. The meta-analysis showed that the prevalence of insecure attachment style was significantly higher in individuals with psychosis (76%) than in non-clinical samples (38%), with fearful attachment being the most prevalent. Across the continuum, there was a small but significant relationship between positive symptom severity and insecure attachment and a significant relationship between negative symptom severity and insecure attachment in the non-clinical analysis. This relationship was not found in the clinical group. The prevalence of insecure attachment appears to be high in psychosis, however, the relationship between symptom severity and attachment is small. Attachment theory may provide greater understanding of the development of positive symptoms than previously thought, however, research needs to include more at-risk samples and longitudinal research to fully understand the dynamics of this relationship., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: Demonstrate safety and effectiveness of the light-driven contact hearing aid to support FDA clearance., Study Design: A single-arm, open-label investigational-device clinical trial., Setting: Two private-practice and one hospital-based ENT clinics., Patients: Forty-three subjects (86 ears) with mild-to-severe bilateral sensorineural hearing impairment., Intervention: Bilateral amplification delivered via a light-driven contact hearing aid comprising a Tympanic Lens (Lens) with a customized platform to directly drive the umbo and a behind-the-ear sound processor (Processor) that encodes sound into light pulses to wirelessly deliver signal and power to the Lens., Main Outcome Measures: The primary safety endpoint was a determination of "no change" (PTA4 < 10 dB) in residual unaided hearing at the 120-day measurement interval. The primary efficacy endpoint was improvement in word recognition using NU-6 at the 30-day measurement interval over the baseline unaided case. Secondary efficacy endpoints included functional gain from 2 to 10 kHz and speech-in-noise improvement over the baseline unaided case using both omnidirectional and directional microphones., Results: The results for the 86 ears in the study determined a mean change of -0.40 dB in PTA4, indicating no change in residual hearing (p < 0.0001). There were no serious device- or procedure-related adverse events, or unanticipated adverse events. Word recognition aided with the Earlens improved significantly (p < 0.0001) over the unaided performance, by 35% rationalized arcsine units on average. Mean functional gain was 31 dB across 2 to 10 kHz. The average speech-recognition threshold improvement over the unaided case for the Hearing in Noise Test was 0.75 dB (p = 0.028) and 3.14 dB (p < 0.0001) for the omnidirectional and directional microphone modes, respectively., Conclusion: The safety and effectiveness data supported a de novo 510(k) submission that received clearance from the FDA., Competing Interests: and Source of Funding: Bruce Gantz is on the medical advistory board for Earlens, Rodney Perkins is a consultant and chief medical officer, Michael Muray is on the medical advisory board, Suzanne Carr Levy is an employee, Sunil Puria is the Chief Scientist all at Earlens Corporation. The study was funded by Earlens Corporation and work was supported in part by SBIR Phase IIB grant R44 DC08499 from the NIDCD of the NIH.

Objectives: The hypothesis that extending the audible frequency bandwidth beyond the range currently implemented in most hearing aids can improve speech understanding was tested for normal-hearing and hearing-impaired participants using target sentences and spatially separated masking speech., Design: The Hearing In Speech Test (HIST) speech corpus was re-recorded, and four masking talkers were recorded at a sample rate of 44.1 kHz. All talkers were male native speakers of American English. For each subject, the reception threshold for sentences (RTS) was measured in two spatial configurations. In the asymmetric configuration, the target was presented from -45° azimuth and two colocated masking talkers were presented from +45° azimuth. In the diffuse configuration, the target was presented from 0° azimuth and four masking talkers were each presented from a different azimuth: +45°, +135°, -135°, and -45°. The new speech sentences, masking materials, and configurations were presented using low-pass filter cutoff frequencies of 4, 6, 8, and 10 kHz. For the normal-hearing participants, stimuli were presented in the sound field using loudspeakers. For the hearing-impaired participants, the spatial configurations were simulated using earphones, and a multiband wide-dynamic-range compressor with a modified CAM2 fitting algorithm was used to compensate for each participant's hearing loss., Results: For the normal-hearing participants (N = 24, mean age 40 years), the RTS improved significantly by 3.0 dB when the bandwidth was increased from 4 to 10 kHz, and a significant improvement of 1.3 dB was obtained from extending the bandwidth from 6 to 10 kHz, in both spatial configurations. Hearing-impaired participants (N = 25, mean age 71 years) also showed a significant improvement in RTS with extended bandwidth, but the effect was smaller than for the normal-hearing participants. The mean decrease in RTS when the bandwidth was increased from 4 to 10 kHz was 1.3 dB for the asymmetric condition and 0.5 dB for the diffuse condition., Conclusions: Extending bandwidth from 4 to 10 kHz can improve the ability of normal-hearing and hearing-impaired participants to understand target speech in the presence of spatially separated masking speech. Future studies of the benefits of extended high-frequency amplification should investigate other realistic listening situations, masker types, spatial configurations, and room reverberation conditions, to determine added value in overcoming the technical challenges associated with implementing a device capable of providing extended high-frequency amplification.