Sleep and Circadian Rhythm Regulation in Early Parkinson Disease

Importance: Sleep disturbances are recognized as a common nonmotor complaint in Parkinson disease but their etiology is poorly understood. Objective: To define the sleep and circadian phenotype of patients with early-stage Parkinson disease. Design, Setting, and Participants: Initial assessment of sleep characteristics in a large population-representative incident Parkinson disease cohort (N=239) at the University of Cambridge, England, followed by further comprehensive case-control sleep assessments in a subgroup of these patients (n=30) and matched controls (n=15). Main Outcomes and Measures: Sleep diagnoses and sleep architecture based on polysomnography studies, actigraphy assessment, and 24-hour analyses of serum cortisol, melatonin, and peripheral clock gene expression (Bmal1, Per2, and Rev-Erbα). Results: Subjective sleep complaints were present in almost half of newly diagnosed patients and correlated significantly with poorer quality of life. Patients with Parkinson disease exhibited increased sleep latency (P = .04), reduced sleep efficiency (P = .008), and reduced rapid eye movement sleep (P = .02). In addition, there was a sustained elevation of serum cortisol levels, reduced circulating melatonin levels, and altered Bmal1 expression in patients with Parkinson disease compared with controls. Conclusions and Relevance: Sleep dysfunction seen in early Parkinson disease may reflect a more fundamental pathology in the molecular clock underlying circadian rhythms

Targeted SERS nanosensors measure physicochemical gradients and free energy changes in live 3D tumor spheroids.

Use of multicellular tumor spheroids (MTS) to investigate therapies has gained impetus because they have potential to mimic factors including zonation, hypoxia and drug-resistance. However, analysis remains difficult and often destroys 3D integrity. Here we report an optical technique using targeted nanosensors that allows in situ 3D mapping of redox potential gradients whilst retaining MTS morphology and function. The magnitude of the redox potential gradient can be quantified as a free energy difference (ΔG) and used as a measurement of MTS viability. We found that by delivering different doses of radiotherapy to MTS we could correlate loss of ΔG with increasing therapeutic dose. In addition, we found that resistance to drug therapy was indicated by an increase in ΔG. This robust and reproducible technique allows interrogation of an in vitro tumor-model's bioenergetic response to therapy, indicating its potential as a tool for therapy development.Leverhulme Trust (Grant ID: RPG-2012-680), Jamie King Cancer Research FundThis is the final version of the article. It first appeared from the Royal Society of Chemistry via http://dx.doi.org/10.1039/C6NR06031

Nocardia kroppenstedtii sp. nov., a novel actinomycete isolated from a lung transplant patient with a pulmonary infection

An actinomycete, strain N1286T, isolated from a lung transplant patient with a pulmonary infection, was provisionally assigned to the genus Nocardia. The strain had chemotaxonomic and morphological properties typical of members of the genus Nocardia and formed a distinct phyletic line in the Nocardia 16S rRNA gene tree. It was most closely related to Nocardia farcinica DSM 43665T (99.8% gene similarity) but was distinguished from the latter by a low level of DNA:DNA relatedness. These strains were also distinguished by a broad range of phenotypic properties. On the basis of these data, it is proposed that isolate N1286T (=DSM 45810T = NCTC 13617T) should be classified as the type strain of a new Nocardia species for which the name Nocardia kroppenstedtii is proposed

Wolbachia and DNA barcoding insects: patterns, potential and problems

Wolbachia is a genus of bacterial endosymbionts that impacts the breeding systems of their hosts. Wolbachia can confuse the patterns of mitochondrial variation, including DNA barcodes, because it influences the pathways through which mitochondria are inherited. We examined the extent to which these endosymbionts are detected in routine DNA barcoding, assessed their impact upon the insect sequence divergence and identification accuracy, and considered the variation present in Wolbachia COI. Using both standard PCR assays (Wolbachia surface coding protein – wsp), and bacterial COI fragments we found evidence of Wolbachia in insect total genomic extracts created for DNA barcoding library construction. When >2 million insect COI trace files were examined on the Barcode of Life Datasystem (BOLD) Wolbachia COI was present in 0.16% of the cases. It is possible to generate Wolbachia COI using standard insect primers; however, that amplicon was never confused with the COI of the host. Wolbachia alleles recovered were predominantly Supergroup A and were broadly distributed geographically and phylogenetically. We conclude that the presence of the Wolbachia DNA in total genomic extracts made from insects is unlikely to compromise the accuracy of the DNA barcode library; in fact, the ability to query this DNA library (the database and the extracts) for endosymbionts is one of the ancillary benefits of such a large scale endeavor – for which we provide several examples. It is our conclusion that regular assays for Wolbachia presence and type can, and should, be adopted by large scale insect barcoding initiatives. While COI is one of the five multi-locus sequence typing (MLST) genes used for categorizing Wolbachia, there is limited overlap with the eukaryotic DNA barcode region

Geological Storage of CO\u3csub\u3e2\u3c/sub\u3e in Sub-Seafloor Basalt: The CarbonSAFE Pre-Feasibility Study Offshore Washington State and British Columbia

The CarbonSAFE Cascadia project team is conducting a pre-feasibility study to evaluate technical and nontechnical aspects of collecting and storing 50 MMT of CO2 in a safe, ocean basalt reservoir offshore from Washington State and British Columbia. Sub-seafloor basalts are very common on Earth and enable CO2 mineralization as a long-term storage mechanism, permanently sequestering the carbon in solid rock form. Our project goals include the evaluation of this reservoir as an industrial-scale CO2 storage complex, developing potential source/transport scenarios, conducting laboratory and modeling studies to determine the potential capacity of the reservoir, and completing an assessment of economic, regulatory and project management risks. Potential scenarios include sources and transport options in the USA and in Canada. The overall project network consists of a coordination team of researchers from collaborating academic institutions, subcontractors, and external participants. Lessons learned from this study at the Cascadia Basin location may be transferrable elsewhere around the globe

Geological Storage of CO2 in Sub-Seafloor Basalt: The CarbonSAFE Pre-Feasibility Study Offshore Washington State and British Columbia

The CarbonSAFE Cascadia project team is conducting a pre-feasibility study to evaluate technical and nontechnical aspects of collecting and storing 50 MMT of CO2 in a safe, ocean basalt reservoir offshore from Washington State and British Columbia. Sub-seafloor basalts are very common on Earth and enable CO2 mineralization as a long-term storage mechanism, permanently sequestering the carbon in solid rock form. Our project goals include the evaluation of this reservoir as an industrial-scale CO2 storage complex, developing potential source/transport scenarios, conducting laboratory and modeling studies to determine the potential capacity of the reservoir, and completing an assessment of economic, regulatory and project management risks. Potential scenarios include sources and transport options in the USA and in Canada. The overall project network consists of a coordination team of researchers from collaborating academic institutions, subcontractors, and external participants. Lessons learned from this study at the Cascadia Basin location may be transferrable elsewhere around the globe

Context-dependent conservation responses to emerging wildlife diseases

Emerging infectious diseases pose an important threat to wildlife. While established protocols exist for combating outbreaks of human and agricultural pathogens, appropriate management actions before, during, and after the invasion of wildlife pathogens have not been developed. We describe stage-specific goals and management actions that minimize disease impacts on wildlife, and the research required to implement them. Before pathogen arrival, reducing the probability of introduction through quarantine and trade restrictions is key because prevention is more cost effective than subsequent responses. On the invasion front, the main goals are limiting pathogen spread and preventing establishment. In locations experiencing an epidemic, management should focus on reducing transmission and disease, and promoting the development of resistance or tolerance. Finally, if pathogen and host populations reach a stable stage, then recovery of host populations in the face of new threats is paramount. Successful management of wildlife disease requires risk-taking, rapid implementation, and an adaptive approach."Funding was provided by the US National Science Foundation (grants EF-0914866, DGE-0741448, DEB-1115069, DEB-1336290) and the National Institutes of Health (grant 1R010AI090159)."https://esajournals.onlinelibrary.wiley.com/doi/abs/10.1890/14024

Lenticel hydration alters the susceptibility of apple fruit to infection by Phlyctema vagabunda

Bull’s eye rot, caused by Phlyctema vagabunda, is an important postharvest rot of apples. A combination of laboratory and field trials were conducted to examine the relationship between infection and status of apple lenticels. Fruit were hydrated and then inoculated, and climatic factors were compared with inoculations and natural infections in the field. In laboratory trials it was shown that increased lenticel density and size led to more infections. Hydration distended lenticel diameter, and dehydration contracted lenticels. A strong relationship with wind run, leaf wetness and temperature were shown to be important for laboratory inoculations of monthly harvested fruit, natural infections in trap fruit experiments, and monthly field inoculations. It was hypothesised that high wind run (> c. 240 km/day) reduced fruit susceptibility by promoting lenticel closure, and when lenticels were open, temperature limited the formation of an infection stroma. If the stroma did not form, postharvest expression of disease was negligible. Leaf wetness over 28 days was also an important factor for infection, probably because of the effect on micro-crack formation and resealing of lenticels during maturation by components of the cuticle. From these results, pre-harvest application of compounds that close lenticels could provide some control of bull’s eye rot without the need for fungicides

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal