Spaceflight Induces Strength Decline in Caenorhabditis elegans

This is the final version. Available on open access from MDPI via the DOI in this recordData Availability Statement: Raw RNA sequencing data are deposited in the NCBI Sequence Read Archive with links to BioProject ID PRJNA1026503 (https://www.ncbi.nlm.nih.gov/bioproject/).Background: Understanding and countering the well-established negative health consequences of spaceflight remains a primary challenge preventing safe deep space exploration. Targeted/personalized therapeutics are at the forefront of space medicine strategies, and cross-species molecular signatures now define the 'typical' spaceflight response. However, a lack of direct genotype-phenotype associations currently limits the robustness and, therefore, the therapeutic utility of putative mechanisms underpinning pathological changes in flight. Methods: We employed the worm Caenorhabditis elegans as a validated model of space biology, combined with 'NemaFlex-S' microfluidic devices for assessing animal strength production as one of the most reproducible physiological responses to spaceflight. Wild-type and dys-1 (BZ33) strains (a Duchenne muscular dystrophy (DMD) model for comparing predisposed muscle weak animals) were cultured on the International Space Station in chemically defined media before loading second-generation gravid adults into NemaFlex-S devices to assess individual animal strength. These same cultures were then frozen on orbit before returning to Earth for next-generation sequencing transcriptomic analysis. Results: Neuromuscular strength was lower in flight versus ground controls (16.6% decline, p < 0.05), with dys-1 significantly more (23% less strength, p < 0.01) affected than wild types. The transcriptional gene ontology signatures characterizing both strains of weaker animals in flight strongly corroborate previous results across species, enriched for upregulated stress response pathways and downregulated mitochondrial and cytoskeletal processes. Functional gene cluster analysis extended this to implicate decreased neuronal function, including abnormal calcium handling and acetylcholine signaling, in space-induced strength declines under the predicted control of UNC-89 and DAF-19 transcription factors. Finally, gene modules specifically altered in dys-1 animals in flight again cluster to neuronal/neuromuscular pathways, suggesting strength loss in DMD comprises a strong neuronal component that predisposes these animals to exacerbated strength loss in space. Conclusions: Highly reproducible gene signatures are strongly associated with space-induced neuromuscular strength loss across species and neuronal changes in calcium/acetylcholine signaling require further study. These results promote targeted medical efforts towards and provide an in vivo model for safely sending animals and people into deep space in the near future.NASABiotechnology and Biological Sciences Research Council (BBSRC)Engineering and Physical Sciences Research Council (EPSRC)Osteopathic Heritage Foundatio

On-site primary care and mental health services in outpatient drug abuse treatment units

Providing health services to drug abuse treatment clients improves their outcomes. Using data from a 1995 national survey of 597 outpatient drug abuse treatment units, this article examines the relationship between these units' organizational features and the degree to which they provided onsite primary care and mental health services. In two-stage models, Joint Commission on Accreditation of Healthcare Organizations-certified and methadone programs delivered more on-site primary care services. Units affiliated with mental health centers provided more on-site mental health services but less direct medical care. Units with more dual-diagnosis clients provided more on-site mental health but fewer on-site HIV/AIDS treatment services. Organizational features appear to influence the degree to which health services are incorporated into drug abuse treatment. Fully integrated care might be an unattainable ideal for many such organizations, but quality improvement across the treatment system might increase the reliability of clients' access to health services.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45768/1/11414_2005_Article_BF02287796.pd

Learning from Practical Experience: Implementation Epistemic Communities in the European Union

Contains fulltext : 192390.pdf (publisher's version ) (Closed access

Southern Ocean carbon sink enhanced by sea-ice feedbacks at the Antarctic Cold Reversal

The Southern Ocean occupies 14% of the Earth’s surface and plays a fundamental role in the global carbon cycle and climate. It provides a direct connection to the deep ocean carbon reservoir through biogeochemical processes that include surface primary productivity, remineralization at depth and the upwelling of carbon-rich water masses. However, the role of these different processes in modulating past and future air–sea carbon flux remains poorly understood. A key period in this regard is the Antarctic Cold Reversal (ACR, 14.6–12.7 kyr bp), when mid- to high-latitude Southern Hemisphere cooling coincided with a sustained plateau in the global deglacial increase in atmospheric CO2. Here we reconstruct high-latitude Southern Ocean surface productivity from marine-derived aerosols captured in a highly resolved horizontal ice core. Our multiproxy reconstruction reveals a sustained signal of enhanced marine productivity across the ACR. Transient climate modelling indicates this period coincided with maximum seasonal variability in sea-ice extent, implying that sea-ice biological feedbacks enhanced CO2 sequestration and created a substantial regional marine carbon sink, which contributed to the plateau in CO2 during the ACR. Our results highlight the role Antarctic sea ice plays in controlling global CO2, and demonstrate the need to incorporate such feedbacks into climate–carbon models

The temporal dimension of knowledge and the limits of policy appraisal: biofuels policy in the UK

Biofuels, Chief Scientific Advisers, Learning, New institutional economics, Policy appraisal, Positive feedback, Time,