Engineering biology and climate change mitigation: Policy considerations.

Engineering biology (EngBio) is a dynamic field that uses gene editing, synthesis, assembly, and engineering to design new or modified biological systems. EngBio applications could make a significant contribution to achieving net zero greenhouse gas emissions. Yet, policy support will be needed if EngBio is to fulfil its climate mitigation potential. What form should such policies take, and what EngBio applications should they target? This paper reviews EngBio's potential climate contributions to assist policymakers shape regulations and target resources and, in so doing, to facilitate democratic deliberation on desirable futures.

Visioning synthetic futures for yeast research within the context of current global techno-political trends.

Yeast research is entering into a new period of scholarship, with new scientific tools, new questions to ask and new issues to consider. The politics of emerging and critical technology can no longer be separated from the pursuit of basic science in fields, such as synthetic biology and engineering biology. Given the intensifying race for technological leadership, yeast research is likely to attract significant investment from government, and that it offers huge opportunities to the curious minded from a basic research standpoint. This article provides an overview of new directions in yeast research with a focus on Saccharomyces cerevisiae, and places these trends in their geopolitical context. At the highest level, yeast research is situated within the ongoing convergence of the life sciences with the information sciences. This convergent effect is most strongly pronounced in areas of AI-enabled tools for the life sciences, and the creation of synthetic genomes, minimal genomes, pan-genomes, neochromosomes and metagenomes using computer-assisted design tools and methodologies. Synthetic yeast futures encompass basic and applied science questions that will be of intense interest to government and nongovernment funding sources. It is essential for the yeast research community to map and understand the context of their research to ensure their collaborations turn global challenges into research opportunities.

Advancing preclinical models of psychiatric disorders with human brain organoid cultures.

Psychiatric disorders are often distinguished from neurological disorders in that the former do not have characteristic lesions or findings from cerebrospinal fluid, electroencephalograms (EEGs), or brain imaging, and furthermore do not have commonly recognized convergent mechanisms. Psychiatric disorders commonly involve clinical diagnosis of phenotypic behavioral disturbances of mood and psychosis, often with a poorly understood contribution of environmental factors. As such, psychiatric disease has been challenging to model preclinically for mechanistic understanding and pharmaceutical development. This review compares commonly used animal paradigms of preclinical testing with evolving techniques of induced pluripotent cell culture with a focus on emerging three-dimensional models. Advances in complexity of 3D cultures, recapitulating electrical activity in utero, and disease modeling of psychosis, mood, and environmentally induced disorders are reviewed. Insights from these rapidly expanding technologies are discussed as they pertain to the utility of human organoid and other models in finding novel research directions, validating pharmaceutical action, and recapitulating human disease.

Bioinformational trends in grape and wine biotechnology.

The creative destruction caused by the coronavirus pandemic is yielding immense opportunity for collaborative innovation networks. The confluence of biosciences, information sciences, and the engineering of biology, is unveiling promising bioinformational futures for a vibrant and sustainable bioeconomy. Bioinformational engineering, underpinned by DNA reading, writing, and editing technologies, has become a beacon of opportunity in a world paralysed by uncertainty. This article draws on lessons from the current pandemic and previous agricultural blights, and explores bioinformational research directions aimed at future-proofing the grape and wine industry against biological shocks from global blights and climate change.

Outbreak of SARS-CoV-2 B.1.617.2 (Delta) Variant Infections Among Incarcerated Persons in a Federal Prison - Texas, July-August 2021.

Incarcerated populations have experienced disproportionately higher rates of COVID-19-related illness and death compared with the general U.S. population, due in part to congregate living environments that can facilitate rapid transmission of SARS-CoV-2, the virus that causes COVID-19, and the high prevalence of underlying medical conditions associated with severe COVID-19 (1,2). The SARS-CoV-2 B.1.617.2 (Delta) variant has caused outbreaks among vaccinated and unvaccinated persons in congregate settings and large public gatherings (3,4). During July 2021, a COVID-19 outbreak involving the Delta variant was identified in a federal prison in Texas, infecting 172 of 233 (74%) incarcerated persons in two housing units. The Federal Bureau of Prisons (BOP) partnered with CDC to investigate. CDC analyzed data on infection status, symptom onset date, hospitalizations, and deaths among incarcerated persons. The attack rate was higher among unvaccinated versus fully vaccinated persons (39 of 42, 93% versus 129 of 185, 70%; p = 0.002).† Four persons were hospitalized, three of whom were unvaccinated, and one person died, who was unvaccinated. Among a subset of 70 persons consenting to an embedded serial swabbing protocol, the median interval between symptom onset and last positive reverse transcription-polymerase chain reaction (RT-PCR) test result in fully vaccinated versus unvaccinated persons was similar (9 versus 11 days, p = 0.37). One or more specimens were culture-positive from five of 12 (42%) unvaccinated and 14 of 37 (38%) fully vaccinated persons for whom viral culture was attempted. In settings where physical distancing is challenging, including correctional and detention facilities, vaccination and implementation of multicomponent prevention strategies (e.g., testing, medical isolation, quarantine, and masking) are critical to limiting SARS-CoV-2 transmission (5).

Sensing the future of bio-informational engineering.

The practices of synthetic biology are being integrated into 'multiscale' designs enabling two-way communication across organic and inorganic information substrates in biological, digital and cyber-physical system integrations. Novel applications of 'bio-informational' engineering will arise in environmental monitoring, precision agriculture, precision medicine and next-generation biomanufacturing. Potential developments include sentinel plants for environmental monitoring and autonomous bioreactors that respond to biosensor signaling. As bio-informational understanding progresses, both natural and engineered biological systems will need to be reimagined as cyber-physical architectures. We propose that a multiple length scale taxonomy will assist in rationalizing and enabling this transformative development in engineering biology.

Drawing on the Past to Shape the Future of Synthetic Yeast Research.

Some years inspire more hindsight reflection and future-gazing than others. This is even more so in 2020 with its evocation of perfect vision and the landmark ring to it. However, no futurist can reliably predict what the world will look like the next time that a year's first two digits will match the second two digits-a numerical pattern that only occurs once in a century. As we leap into a new decade, amid uncertainties triggered by unforeseen global events-such as the outbreak of a worldwide pandemic, the accompanying economic hardship, and intensifying geopolitical tensions-it is important to note the blistering pace of 21st century technological developments indicate that while hindsight might be 20/20, foresight is 50/50. The history of science shows us that imaginative ideas, research excellence, and collaborative innovation can, for example, significantly contribute to the economic, cultural, social, and environmental recovery of a post-COVID-19 world. This article reflects on a history of yeast research to indicate the potential that arises from advances in science, and how this can contribute to the ongoing recovery and development of human society. Future breakthroughs in synthetic genomics are likely to unlock new avenues of impactful discoveries and solutions to some of the world's greatest challenges.

Structural interventions and social suffering: Responding to amphetamine-type stimulant use among female entertainment and sex workers in Cambodia.

BACKGROUND: In Cambodia, HIV infection remains high among female entertainment and sex workers (FESW) and the use of amphetamine-type stimulants (ATS) is an independent risk factor for unprotected sex and sexually transmitted infections among this group. For decades public health approaches to HIV prevention in low and middle income countries (LMIC) have attempted to target the macro-power relations that shape risk behaviour with structural interventions. Recent research has highlighted that interventions that combine ATS risk reduction, in the form of financial incentives for abstinence, with existing HIV prevention programmes, may also play an important role. However, whether this approach goes far enough as a response to structural drivers of risk requires further examination. METHODS: Semi-structured in-depth interviews were conducted with 30 FESW (mean age 25 years) from five provinces in Cambodia, as part of formative research for the implementation of the Cambodia Integrated HIV and Drug Prevention (CIPI) trial. The aim was to explore the contexts and drivers of ATS use. Data were analysed using grounded theory. RESULTS: In addition to increasing occupational functionality, ATS were used to control pervasive feelings of 'sadness' in relation to the lived experience of poverty, family and relationship problems. Feeling sad could be viewed as an expression of social suffering, in response to competing priorities and seemingly inescapable constraints imposed by a lack of options for income generation, gender inequalities and stigma. Participants expressed interest in microenterprise (ME) opportunities, particularly vocational training, that could create new work opportunities beyond sex work and ATS use. CONCLUSION: In addition to reducing ATS use, HIV prevention interventions need to target sources of sadness and social suffering as drivers of risk among FESW in this context. The inclusion of ME opportunities in HIV prevention, to alleviate social suffering, warrants further investigation through qualitative and ethnographic research.

Bioinspired Three-Dimensional Human Neuromuscular Junction Development in Suspended Hydrogel Arrays.

The physical connection between motoneurons and skeletal muscle targets is responsible for the creation of neuromuscular junctions (NMJs), which allow electrical signals to be translated to mechanical work. NMJ pathology contributes to the spectrum of neuromuscular, motoneuron, and dystrophic disease. Improving in vitro tools that allow for recapitulation of the physiology of the neuromuscular connection will enable researchers to better understand the development and maturation of NMJs, and will help to decipher mechanisms leading to NMJ degeneration. In this work, we first describe robust differentiation of bungarotoxin-positive human myotubes, as well as a reproducible method for encapsulating and aligning human myoblasts in three-dimensional (3D) suspended culture using bioprinted silk fibroin cantilevers as cell culture supports. Further analysis with coculture of motoneuron-like cells demonstrates feasibility of fully human coculture using two-dimensional and 2.5-dimensional culture methods, with appropriate differentiation of both cell types. Using these coculture differentiation conditions with motoneuron-like cells added to monocultures of 3D suspended human myotubes, we then demonstrate synaptic colocalization in coculture as well as acetylcholine and glutamic acid stimulation of human myocytes. This method represents a unique platform to coculture suspended human myoblast-seeded 3D hydrogels with integrated motoneuron-like cells derived from human induced neural stem cells. The platform described is fully customizable using 3D freeform printing into standard laboratory tissue culture materials, and allows for human myoblast alignment in 3D with precise motoneuron integration into preformed myotubes. The coculture method will ideally be useful in observation and analysis of neurite outgrowth and myogenic differentiation in 3D with quantification of several parameters of muscle innervation and function.

RABDAM: quantifying specific radiation damage in individual protein crystal structures.

Radiation damage remains one of the major limitations to accurate structure determination in protein crystallography (PX). Despite the use of cryo-cooling techniques, it is highly probable that a number of the structures deposited in the Protein Data Bank (PDB) have suffered substantial radiation damage as a result of the high flux densities of third generation synchrotron X-ray sources. Whereas the effects of global damage upon diffraction pattern reflection intensities are readily detectable, traditionally the (earlier onset) site-specific structural changes induced by radiation damage have proven difficult to identify within individual PX structures. More recently, however, development of the BDamage metric has helped to address this problem. BDamage is a quantitative, per-atom metric identifies potential sites of specific damage by comparing the atomic B-factor values of atoms that occupy a similar local packing density environment in the structure. Building upon this past work, this article presents a program, RABDAM, to calculate the BDamage metric for all selected atoms within any standard-format PDB or mmCIF file. RABDAM provides several useful outputs to assess the extent of damage suffered by an input PX structure. This free and open-source software will allow assessment and improvement of the quality of PX structures both previously and newly deposited in the PDB.

3D freeform printing of silk fibroin.

Freeform fabrication has emerged as a key direction in printing biologically-relevant materials and structures. With this emerging technology, complex structures with microscale resolution can be created in arbitrary geometries and without the limitations found in traditional bottom-up or top-down additive manufacturing methods. Recent advances in freeform printing have used the physical properties of microparticle-based granular gels as a medium for the submerged extrusion of bioinks. However, most of these techniques require post-processing or crosslinking for the removal of the printed structures (Miller et al., 2015; Jin et al., 2016) [1,2]. In this communication, we introduce a novel method for the one-step gelation of silk fibroin within a suspension of synthetic nanoclay (Laponite) and polyethylene glycol (PEG). Silk fibroin has been used as a biopolymer for bioprinting in several contexts, but chemical or enzymatic additives or bulking agents are needed to stabilize 3D structures. Our method requires no post-processing of printed structures and allows for in situ physical crosslinking of pure aqueous silk fibroin into arbitrary geometries produced through freeform 3D printing. STATEMENT OF SIGNIFICANCE: 3D bioprinting has emerged as a technology that can produce biologically relevant structures in defined geometries with microscale resolution. Techniques for fabrication of free-standing structures by printing into granular gel media has been demonstrated previously, however, these methods require crosslinking agents and post-processing steps on printed structures. Our method utilizes one-step gelation of silk fibroin within a suspension of synthetic nanoclay (Laponite), with no need for additional crosslinking compounds or post processing of the material. This new method allows for in situ physical crosslinking of pure aqueous silk fibroin into defined geometries produced through freeform 3D printing.

Using back focal plane interferometry to probe the influence of Zernike aberrations in optical tweezers.

We experimentally investigate the influence of geometric aberrations in optical tweezers using back focal plane interferometry. We found that the introduction of coma aberrations causes significant modification to the Brownian motion of the trapped particle, producing an apparent cross-coupling between the in-plane aberrated axis and the weaker propagation axis. This coupling is evidenced by the emergence of a second dominant low frequency Lorentzian feature in the position power spectral density. The effect on Brownian motion was confirmed using a secondary unaberrated probe beam, ruling out the possibility of systematic optical effects related to the detection system.

Examination of traumatic brain injury exposure among veterans with spinal cord injury.

OBJECTIVE: The authors investigated lifetime exposure to traumatic brain injury (TBI) among veterans with spinal cord injury (SCI) in order to describe outcome differences as a function of self-reported TBI history. DESIGN: Cross sectional study, veterans with SCI (N = 857) completed the Ohio State University TBI Identification interview method (OSU-TBI); Veterans RAND 36-Item Health Survey (VR-36); Quick Inventory for Depressive Symptomatology, Self-Report (QIDS-SR); Patient Health Questionnaire-9; Satisfaction with Life Scale; Craig Handicap Assessment and Reporting Technique (CHART; along with clinician-rated Functional Independence Measure (FIM) Total, Motor, and Cognitive scores. RESULTS: Probable TBI exposure was described by 77.6% of participants, with 38% reporting sustaining more than one injury. Self-reported TBIs classified as moderate/severe comprised 49.5% of injuries. Participants with self-reported TBI obtained significantly lower scores on the FIM-Cognitive and CHART Cognitive Independence scales and reported more alcohol use. A history of multiple TBIs was additionally associated with lower mental well-being on the VR-36. CONCLUSIONS: These findings highlight the need to consider more than co-occurring injuries and the potential utility of the OSU-TBI for this purpose. Recognizing lifetime exposure to TBI among veterans with SCI may help identify those with broader impairments and enhance the rehabilitation process. (PsycINFO Database Record

Self-limiting non-medical pharmaceutical opioid use among young people in Sydney, Australia: An exploratory study.

INTRODUCTION AND AIMS: Indicators suggest an escalation in opioid use globally, with recent HIV outbreaks linked to non-medical pharmaceutical opioid (NMPO) use. Little is known about how young Australians engage in NMPO use. DESIGN AND METHODS: During 2015, we conducted qualitative interviews with young people (16-29 years) who reported oral NMPO use at least twice in the past 90 days. The study included a sample of injecting (n = 14) and oral (n = 22) users. This paper focuses on the oral user group. RESULTS: Most participants grew up in affluent areas of Sydney, reported few health problems, rarely accessed health or welfare services and had limited contact with police. NMPO use was part of a repertoire of drug use involving: (i) use to come down from stimulants; (ii) use in conjunction with cannabis and alcohol; and (iii) use by itself. Participants reported limiting their use in order to avoid stigma and dependence. DISCUSSION AND CONCLUSIONS: Results suggest culture of self-limiting NMPO use characterised by stable housing, disposable income and intimate friendship networks. Despite the adverse health outcomes observed in other settings, our data suggest that the patterns and meanings of NMPO use observed in this small sample may help explain the limited nature of problematic use among young Australians to date. Findings indicate a need for epidemiological data, including longitudinal data, to assess possible demographic shifts in NMPO use in Australia, and to address risk factors for dependence and transitions to injecting and heroin use in this population. [Dertadian GC, Dixon TC, Iversen J, Maher L. Self-limiting non-medical pharmaceutical opioid use among young people in Sydney, Australia: An exploratory study. Drug Alcohol Rev 2017;00:000-000].

Pharmaceutical opioid use among oral and intravenous users in Australia: A qualitative comparative study.

BACKGROUND: Between 1992 and 2012 dispensing episodes for pharmaceutical opioids (PO) in Australia increased from 500000 to 7500000. In the US, increases in the prescription of PO have been linked to increases in opioid-related morbidity and mortality and transitions to heroin injection. However, Australian data indicate that morbidity and mortality related to PO are relatively low, particularly when compared to heroin and other drugs. This paper explores the characteristics and patterns of non-medical pharmaceutical opioid (NMPO) use among a sample of young people in Sydney, Australia. METHODS: During 2015, we conducted in-depth qualitative interviews with 34 young people who use PO non-medically by oral (n=22) and intravenous (n=12) routes of administration. RESULTS: Oral NMPO users were a more affluent group who clustered around the Northern, Inner and Eastern suburbs of Sydney, while the intravenous users came from a range of locations including rural/regional areas of NSW and socioeconomically disadvantaged suburbs of South Western Sydney. Oral users were characterised by intermittent and largely self-limiting NMPO use and reported few health and social consequences. Intravenous users reported heavy and frequent drug, including NMPO, use and a range of adverse health and social consequences including overdose, injecting risk behaviour, hepatitis C virus (HCV) infection and residential instability. CONCLUSION: Results highlight the significance of social and structural factors in trajectories of opioid use and related harms. Factors such as stable housing and family relationships, disposable income and close social networks observed in young oral NMPO users may help to explain differences in patterns of NMPO use and related outcomes between the two groups.

Individual Placement and Support in Spinal Cord Injury: A Longitudinal Observational Study of Employment Outcomes.

OBJECTIVE: To determine the effects of a 24-month program of Individual Placement and Support (IPS) supported employment (SE) on employment outcomes for veterans with spinal cord injury (SCI). DESIGN: Longitudinal, observational multisite study of a single-arm, nonrandomized cohort. SETTING: SCI centers in the Veterans Health Administration (n=7). PARTICIPANTS: Veterans with SCI (N=213) enrolled during an episode of either inpatient hospital care (24.4%) or outpatient care (75.6%). More than half the sample (59.2%) had a history of traumatic brain injury (TBI). INTERVENTION: IPS SE for 24 months. MAIN OUTCOME MEASURE: Competitive employment. RESULTS: Over the 24-month period, 92 of 213 IPS participants obtained competitive jobs for an overall employment rate of 43.2%. For the subsample of participants without TBI enrolled as outpatients (n=69), 36 obtained competitive jobs for an overall employment rate of 52.2%. Overall, employed participants averaged 38.2±29.7 weeks of employment, with an average time to first employment of 348.3±220.0 days. Nearly 25% of first jobs occurred within 4 to 6 months of beginning the program. Similar employment characteristics were observed in the subsample without TBI history enrolled as outpatients. CONCLUSIONS: Almost half of the veterans with SCI participating in the 24-month IPS program as part of their ongoing SCI care achieved competitive employment, consistent with their expressed preferences at the start of the study. Among a subsample of veterans without TBI history enrolled as outpatients, employment rates were >50%. Time to first employment was highly variable, but quite long in many instances. These findings support offering continued IPS services as part of ongoing SCI care to achieve positive employment outcomes.