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

Hundreds of millions of people in the tropics need both wild harvests and other forms of economic development for their well-being

Summary Local access to “wild,” common-pool terrestrial and aquatic resources is being diminished by global resource demand and large-scale conservation interventions. Many theories suggest the well-being of wild harvesters can be supported through transitions to other livelihoods, improved infrastructure, and market access. However, new theories argue that such benefits may not always occur because they are context dependent and vary across dimensions of well-being. We test these theories by comparing how wild harvesting and other livelihoods have been associated with food security and life satisfaction in different contexts across ∼10,800 households in the tropics. Wild harvests coincided with high well-being in remote, asset-poor, and less-transformed landscapes. Yet, overall, well-being increased with electrical infrastructure, proximity to cities, and household capitals. This provides large-scale confirmation of the context dependence of nature’s contributions to people, and suggests a need to maintain local wild resource access while investing in equitable access to infrastructure, markets, and skills

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

A summary of pain and pain-related variables in the Avon Longitudinal Study of Parents and Children

To study pain, data on pain characteristics, possible triggers and consequences - such as the impact of pain on people's lives - need to be available. When not collated, described and/or organised in a systematic manner, it can be difficult to assess how useful an existing dataset may be for one's project. This data note describes and categorises the complex and multi-modal indices of pain available in the Avon Longitudinal Study of Parents and Children (ALSPAC). Data from two generations of the ALSPAC cohort; index child participants (Generation 1, G1), their mothers and fathers/mothers' partners (Generation 0, G0) were used. Search terms such as 'pain', 'ache', 'hurt', 'sore', specific pain conditions, labour pain and methods of pain relief were used to identify pain and pain-related variables. These data were extracted from all waves of data collection. We developed pain categories and subsequently categorised variables in an iterative process. Repeated measurements of the same variables over waves of data collection were also identified. We identified 21 categories of pain variables, which were subsequently grouped into themes: pain characteristics, extended pain characteristics and causes, treatment for pain, pain interference and pain-related to specific events. Pain and pain-related data have been collected from G1 participants, G0 mothers, and G0 partners, although there are fewer data for the partners. There were some repeated measurements, most commonly, of pain location. As is typical with longitudinal birth cohort studies, maternal proxy-reports were used during participants' younger years and self-reports were utilised from adolescence onwards. Researchers interested in studying pain can feasibly do so in two generations of a regional UK population who have been followed up over 30 years. ALSPAC can be used to study pain from the early years through to young adulthood and in mothers from the perinatal period onwards. [Abstract copyright: Copyright: © 2024 Ly A et al.