Depositional environment of the Middle Pennsylvanian granite wash: Lambert 1, Hryhor, and Sundance fields, northern Palo Duro basin, Oldham County, Texas

Due to the character of the original source materials and the nature of batch digitization, quality control issues may be present in this document. Please report any quality issues you encounter to [email protected], referencing the URI of the item.Bibliography: leaves 105-108.Not availabl

Car Cabin Filters as Sampling Devices to Study Bioaerosols Using eDNA and Microbiological Methods

The aim of this study was to examine whether bioaerosols could be isolated and quantified from used car cabin filters. Car cabin filters are widely available and can provide a vast untapped resource for sampling of bioaerosols in areas with enhanced air pollution. We developed a test system where we exposed car cabin filters to birch pollen under compressed air to represent airflow onto the filter. The flow of pollen within the test system was confirmed by microscopy and real-time PCR. Testing of extraction methods was performed on the most prevalent types of filters in UK cars and confirmed it was possible to extract and quantify viable fungi, birch pollen or proteins from car filters. The main challenge of their use is envisaged to be the lack of temporal resolution as car cabin filters are not routinely changed at intervals greater than 1 year; however, the systematic recording of the different routes driven during the sampling interval has been enabled through the common use of GPS, smartphones or similar technologies. Car filters therefore provide substantial possibilities to monitor exposure of harmful bioaerosols in the polluted traffic regions defined by the road network. This method could also be applied to studying allergen exposure associated with bioaerosols and their delivery into the human respiratory system. These findings demonstrate that car cabin filters have the potential to be used to isolate and quantify a range of bioaerosols including pollen and fungi, as well as fractions of bioaerosols, such as proteins

Vaccine safety issues at the turn of the 21st century

Global gains in vaccination coverage during the early 21st century have been threatened by the emergence of antivaccination groups that have questioned the effectiveness of vaccines to generate public distrust of vaccines and immunisation programmes. This manuscript summarises six key topics that have been at the centre of global discussions on vaccine safety during the early 21st century: thiomersal in multi-dose non-live vaccines, aluminium adjuvants used with several non-live vaccines, autism and auto-immune conditions as possible consequences of vaccination, a risk of immune overload with increasing numbers of vaccinations, and detrimental non-specific effects (NSEs) of vaccination. For each topic, we describe the hypothesis behind the public concern, the evidence reviewed by the WHO's Global Advisory Committee for Vaccine Safety (GACVS) during 1999-2019, and any significant new data that has emerged since GACVS conclusions were made. Although the scientific evidence on these issues overwhelmingly supports the safety of vaccines, communication messages to caregivers and providers need to condense and convey scientific information in an appropriate way to address concerns contributing to vaccine distrust. In addition, there is need for further studies specifically designed to address both positive and negative NSE of vaccination. The role of GACVS will be increasingly important in evaluating the evidence and engaging the global community in promoting and assuring the safety of vaccines in the decades to come as we move into an era in which we use new vaccination platforms, antigens and formulations

Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS)

Background: Amyotrophic lateral sclerosis (ALS), a common late-onset neurodegenerative disease, is associated with fronto-temporal dementia (FTD) in 3-10% of patients. A mutation in CHMP2B was recently identified in a Danish pedigree with autosomal dominant FTD. Subsequently, two unrelated patients with familial ALS, one of whom also showed features of FTD, were shown to carry missense mutations in CHMP2B. The initial aim of this study was to determine whether mutations in CHMP2B contribute more broadly to ALS pathogenesis. Methodology/Principal Findings: Sequencing of CHMP2B in 433 ALS cases from the North of England identified 4 cases carrying 3 missense mutations, including one novel mutation, p. Thr104Asn, none of which were present in 500 neurologically normal controls. Analysis of clinical and neuropathological data of these 4 cases showed a phenotype consistent with the lower motor neuron predominant (progressive muscular atrophy (PMA)) variant of ALS. Only one had a recognised family history of ALS and none had clinically apparent dementia. Microarray analysis of motor neurons from CHMP2B cases, compared to controls, showed a distinct gene expression signature with significant differential expression predicting disassembly of cell structure; increased calcium concentration in the ER lumen; decrease in the availability of ATP; down-regulation of the classical and p38 MAPK signalling pathways, reduction in autophagy initiation and a global repression of translation. Transfection of mutant CHMP2B into HEK-293 and COS-7 cells resulted in the formation of large cytoplasmic vacuoles, aberrant lysosomal localisation demonstrated by CD63 staining and impairment of autophagy indicated by increased levels of LC3-II protein. These changes were absent in control cells transfected with wild-type CHMP2B. Conclusions/Significance: We conclude that in a population drawn from North of England pathogenic CHMP2B mutations are found in approximately 1% of cases of ALS and 10% of those with lower motor neuron predominant ALS. We provide a body of evidence indicating the likely pathogenicity of the reported gene alterations. However, absolute confirmation of pathogenicity requires further evidence, including documentation of familial transmission in ALS pedigrees which might be most fruitfully explored in cases with a LMN predominant phenotype

The Host Galaxy and Redshift of the Repeating Fast Radio Burst FRB 121102

The precise localization of the repeating fast radio burst (FRB 121102) has provided the first unambiguous association (chance coincidence probability $p\lesssim3\times10^{-4}$) of an FRB with an optical and persistent radio counterpart. We report on optical imaging and spectroscopy of the counterpart and find that it is an extended ($0.6^{\prime\prime}-0.8^{\prime\prime}$) object displaying prominent Balmer and [OIII] emission lines. Based on the spectrum and emission line ratios, we classify the counterpart as a low-metallicity, star-forming, $m_{r^\prime} = 25.1$ AB mag dwarf galaxy at a redshift of $z=0.19273(8)$, corresponding to a luminosity distance of 972 Mpc. From the angular size, the redshift, and luminosity, we estimate the host galaxy to have a diameter $\lesssim4$ kpc and a stellar mass of $M_*\sim4-7\times 10^{7}\,M_\odot$, assuming a mass-to-light ratio between 2 to 3$\,M_\odot\,L_\odot^{-1}$. Based on the H$\alpha$ flux, we estimate the star formation rate of the host to be $0.4\,M_\odot\,\mathrm{yr^{-1}}$ and a substantial host dispersion measure depth $\lesssim 324\,\mathrm{pc\,cm^{-3}}$. The net dispersion measure contribution of the host galaxy to FRB 121102 is likely to be lower than this value depending on geometrical factors. We show that the persistent radio source at FRB 121102's location reported by Marcote et al (2017) is offset from the galaxy's center of light by $\sim$200 mas and the host galaxy does not show optical signatures for AGN activity. If FRB 121102 is typical of the wider FRB population and if future interferometric localizations preferentially find them in dwarf galaxies with low metallicities and prominent emission lines, they would share such a preference with long gamma ray bursts and superluminous supernovae.Comment: 12 pages, 3 figures, Published in ApJ Letters. V2: Corrected mistake in author lis

Dissociable rate-dependent effects of oral methylphenidate on impulsivity and D2/3 receptor availability in the striatum.

We have previously shown that impulsivity in rats is linked to decreased dopamine D2/3 receptor availability in the ventral striatum. In the present study, we investigated, using longitudinal positron emission tomography (PET), the effects of orally administered methylphenidate (MPH), a first-line treatment for attention deficit hyperactivity disorder, on D2/3 receptor availability in the dorsal and ventral striatum and related these changes to impulsivity. Rats were screened for impulsive behavior on a five-choice serial reaction time task. After a baseline PET scan with the D2/3 ligand [(18)F]fallypride, rats received 6 mg/kg MPH, orally, twice each day for 28 d. Rats were then reassessed for impulsivity and underwent a second [(18)F]fallypride PET scan. Before MPH treatment, we found that D2/3 receptor availability was significantly decreased in the left but not the right ventral striatum of high-impulse (HI) rats compared with low-impulse (LI) rats. MPH treatment increased impulsivity in LI rats, and modulated impulsivity and D2/3 receptor availability in the dorsal and ventral striatum of HI rats through inverse relationships with baseline levels of impulsivity and D2/3 receptor availability, respectively. However, we found no relationship between the effects of MPH on impulsivity and D2/3 receptor availability in any of the striatal subregions investigated. These findings indicate that trait-like impulsivity is associated with decreased D2/3 receptor availability in the left ventral striatum, and that stimulant drugs modulate impulsivity and striatal D2/3 receptor availability through independent mechanisms.This work was funded by Medical Research Council Grant G0701500, and by a joint award from the Medical Research Council (Grant G1000183) and the Wellcome Trust (Grant 093875/Z/10/Z) in support of the Behavioural and Clinical Neuroscience Institute at the University of Cambridge. We also acknowledge funding from the Medical Research Council in support of the ICCAM addiction cluster in the United Kingdom (G1000018). B.J. is supported by grants from the AXA Research Fund and the Australian National Health and Medical Research Council (Grant 1016313).This is the author accepted manuscript. The final version is available from Society for Neuroscience via http://doi.org/10.1523/JNEUROSCI.3890-14.201

Effect of Plain Versus Sugar-Sweetened Breakfast on Energy Balance and Metabolic Health : A Randomized Crossover Trial

We would like to thank Pippa Heath for her help with randomization, our participants, and Dr. Graham Horgan for statistical advice. Funding Information Economic and Social Research Council. Grant Number: ES/J50015X/1 Biotechnology and Biological Sciences Research Council (BBSRC) GlaxoSmithKline Lucozade Ribena Suntory Kellogg’s Nestlé PepsiCo Sugar Nutrition UK Danone Baby Nutrition the Alpro Foundation Kellogg Europe Unilever Volac International The Collagen Research Institute British Summer FruitsPeer reviewedPublisher PD

Neuronal DNA damage response-associated dysregulation of signalling pathways and cholesterol metabolism at the earliest stages of Alzheimer-type pathology.

AIMS: Oxidative damage and an associated DNA damage response (DDR) are evident in mild cognitive impairment and early Alzheimer's disease, suggesting that neuronal dysfunction resulting from oxidative DNA damage may account for some of the cognitive impairment not fully explained by Alzheimer-type pathology. METHODS: Frontal cortex (Braak stage 0-II) was obtained from the Medical Research Council's Cognitive Function and Ageing Study cohort. Neurones were isolated from eight cases (four high and four low DDR) by laser capture microdissection and changes in the transcriptome identified by microarray analysis. RESULTS: Two thousand three hundred seventy-eight genes were significantly differentially expressed (1690 up-regulated, 688 down-regulated, P < 0.001) in cases with a high neuronal DDR. Functional grouping identified dysregulation of cholesterol biosynthesis, insulin and Wnt signalling, and up-regulation of glycogen synthase kinase 3β. Candidate genes were validated by quantitative real-time polymerase chain reaction. Cerebrospinal fluid levels of 24(S)-hydroxycholesterol associated with neuronal DDR across all Braak stages (rs  = 0.30, P = 0.03). CONCLUSIONS: A persistent neuronal DDR may result in increased cholesterol biosynthesis, impaired insulin and Wnt signalling, and increased GSK3β, thereby contributing to neuronal dysfunction independent of Alzheimer-type pathology in the ageing brain

Phosphatase and tensin homologue/protein kinase B pathway linked to motor neuron survival in human superoxide dismutase 1-related amyotrophic lateral sclerosis

Gene expression profiling has been used previously with spinal cord homogenates and laser capture microdissected motor neurons to determine the mechanisms involved in neurodegeneration in amyotrophic lateral sclerosis. However, while cellular and animal model work has focused on superoxide dismutase 1-related amyotrophic lateral sclerosis, the transcriptional profile of human mutant superoxide dismutase 1 motor neurons has remained undiscovered. The aim of this study was to apply gene expression profiling to laser captured motor neurons from human superoxide dismutase 1-related amyotrophic lateral sclerosis and neurologically normal control cases, in order to determine those pathways dysregulated in human superoxide dismutase 1-related neurodegeneration and to establish potential pathways suitable for therapeutic intervention. Identified targets were then validated in cultured cell models using lentiviral vectors to manipulate the expression of key genes. Microarray analysis identified 1170 differentially expressed genes in spinal cord motor neurons from superoxide dismutase 1-related amyotrophic lateral sclerosis, compared with controls. These genes encoded for proteins in multiple functional categories, including those involved in cell survival and cell death. Further analysis determined that multiple genes involved in the phosphatidylinositol-3 kinase signalling cascade were differentially expressed in motor neurons that survived the disease process. Functional experiments in cultured cells and primary motor neurons demonstrate that manipulating this pathway by reducing the expression of a single upstream target, the negative phosphatidylinositol-3 kinase regulator phosphatase and tensin homology, promotes a marked pro-survival effect. Therefore, these data indicate that proteins in the phosphatidylinositol-3 kinase pathway could represent a target for therapeutic manipulation in motor neuron degeneration