Continuous transport of Pacific-derived anthropogenic radionuclides towards the Indian Ocean

Unusually high concentrations of americium and plutonium have been observed in a sediment core collected from the eastern Lombok Basin between Sumba and Sumbawa Islands in the Indonesian Archipelago. Gamma spectrometry and accelerator mass spectrometry data together with radiometric dating of the core provide a high-resolution record of ongoing deposition of anthropogenic radionuclides. A plutonium signature characteristic of the Pacific Proving Grounds (PPG) dominates in the first two decades after the start of the high yield atmospheric tests in 1950’s. Approximately 40–70% of plutonium at this site in the post 1970 period originates from the PPG. This sediment record of transuranic isotopes deposition over the last 55 years provides evidence for the continuous long-distance transport of particle-reactive radionuclides from the Pacific Ocean towards the Indian Ocean

Genetic dissection of a model complex trait using the Drosophila Synthetic Population Resource

Genetic dissection of complex, polygenic trait variation is a key goal of medical and evolutionary genetics. Attempts to identify genetic variants underlying complex traits have been plagued by low mapping resolution in traditional linkage studies, and an inability to identify variants that cumulatively explain the bulk of standing genetic variation in genome-wide association studies (GWAS). Thus, much of the heritability remains unexplained for most complex traits. Here we describe a novel, freely available resource for the Drosophila community consisting of two sets of recombinant inbred lines (RILs), each derived from an advanced generation cross between a different set of eight highly inbred, completely resequenced founders. The Drosophila Synthetic Population Resource (DSPR) has been designed to combine the high mapping resolution offered by multiple generations of recombination, with the high statistical power afforded by a linkage-based design. Here, we detail the properties of the mapping panel of >1600 genotyped RILs, and provide an empirical demonstration of the utility of the approach by genetically dissecting alcohol dehydrogenase (ADH) enzyme activity. We confirm that a large fraction of the variation in this classic quantitative trait is due to allelic variation at the Adh locus, and additionally identify several previously unknown modest-effect trans-acting QTL (quantitative trait loci). Using a unique property of multiparental linkage mapping designs, for each QTL we highlight a relatively small set of candidate causative variants for follow-up work. The DSPR represents an important step toward the ultimate goal of a complete understanding of the genetics of complex traits in the Drosophila model system.This work was supported by the following NIH R01 grants: RR024862 to S.J.M. and A.D.L., GM085260 to S.J.M., GM085251 to A.D.L., GM078338 to S.S., and GM074244 to K.W.B

Phenotype Harmonization in the GLIDE2 Oral Health Genomics Consortium

Genetic risk factors play important roles in the etiology of oral, dental, and craniofacial diseases. Identifying the relevant risk loci and understanding their molecular biology could highlight new prevention and management avenues. Our current understanding of oral health genomics suggests that dental caries and periodontitis are polygenic diseases, and very large sample sizes and informative phenotypic measures are required to discover signals and adequately map associations across the human genome. In this article, we introduce the second wave of the Gene-Lifestyle Interactions and Dental Endpoints consortium (GLIDE2) and discuss relevant data analytics challenges, opportunities, and applications. In this phase, the consortium comprises a diverse, multiethnic sample of over 700,000 participants from 21 studies contributing clinical data on dental caries experience and periodontitis. We outline the methodological challenges of combining data from heterogeneous populations, as well as the data reduction problem in resolving detailed clinical examination records into tractable phenotypes, and describe a strategy that addresses this. Specifically, we propose a 3-tiered phenotyping approach aimed at leveraging both the large sample size in the consortium and the detailed clinical information available in some studies, wherein binary, severity-encompassing, and "precision," data-driven clinical traits are employed. As an illustration of the use of data-driven traits across multiple cohorts, we present an application of dental caries experience data harmonization in 8 participating studies (N = 55,143) using previously developed permanent dentition tooth surface-level dental caries pattern traits. We demonstrate that these clinical patterns are transferable across multiple cohorts, have similar relative contributions within each study, and thus are prime targets for genetic interrogation in the expanded and diverse multiethnic sample of GLIDE2. We anticipate that results from GLIDE2 will decisively advance the knowledge base of mechanisms at play in oral, dental, and craniofacial health and disease and further catalyze international collaboration and data and resource sharing in genomics research.Peer reviewe

The influence of expectation on spinal manipulation induced hypoalgesia: An experimental study in normal subjects

<p>Abstract</p> <p>Background</p> <p>The mechanisms thorough which spinal manipulative therapy (SMT) exerts clinical effects are not established. A prior study has suggested a dorsal horn modulated effect; however, the role of subject expectation was not considered. The purpose of the current study was to determine the effect of subject expectation on hypoalgesia associated with SMT.</p> <p>Methods</p> <p>Sixty healthy subjects agreed to participate and underwent quantitative sensory testing (QST) to their leg and low back. Next, participants were randomly assigned to receive a positive, negative, or neutral expectation instructional set regarding the effects of a specific SMT technique on pain perception. Following the instructional set, all subjects received SMT and underwent repeat QST.</p> <p>Results</p> <p>No interaction (p = 0.38) between group assignment and pain response was present in the lower extremity following SMT; however, a main effect (p < 0.01) for hypoalgesia was present. A significant interaction was present between change in pain perception and group assignment in the low back (p = 0.01) with participants receiving a negative expectation instructional set demonstrating significant hyperalgesia (p < 0.01).</p> <p>Conclusion</p> <p>The current study replicates prior findings of c- fiber mediated hypoalgesia in the lower extremity following SMT and this occurred regardless of expectation. A significant increase in pain perception occurred following SMT in the low back of participants receiving negative expectation suggesting a potential influence of expectation on SMT induced hypoalgesia in the body area to which the expectation is directed.</p

Reversible Disassembly of the Actin Cytoskeleton Improves the Survival Rate and Developmental Competence of Cryopreserved Mouse Oocytes

Effective cryopreservation of oocytes is critically needed in many areas of human reproductive medicine and basic science, such as stem cell research. Currently, oocyte cryopreservation has a low success rate. The goal of this study was to understand the mechanisms associated with oocyte cryopreservation through biophysical means using a mouse model. Specifically, we experimentally investigated the biomechanical properties of the ooplasm prior and after cryopreservation as well as the consequences of reversible dismantling of the F-actin network in mouse oocytes prior to freezing. The study was complemented with the evaluation of post-thaw developmental competence of oocytes after in vitro fertilization. Our results show that the freezing-thawing process markedly alters the physiological viscoelastic properties of the actin cytoskeleton. The reversible depolymerization of the F-actin network prior to freezing preserves normal ooplasm viscoelastic properties, results in high post-thaw survival and significantly improves developmental competence. These findings provide new information on the biophysical characteristics of mammalian oocytes, identify a pathophysiological mechanism underlying cryodamage and suggest a novel cryopreservation method

Predictors of Occurrence and Severity of First Time Low Back Pain Episodes: Findings from a Military Inception Cohort

Primary prevention studies suggest that additional research on identifying risk factors predictive of low back pain (LBP) is necessary before additional interventions can be developed. In the current study we assembled a large military cohort that was initially free of LBP and followed over 2 years. The purposes of this study were to identify baseline variables from demographic, socioeconomic, general health, and psychological domains that were predictive of a) occurrence; b) time; and c) severity for first episode of self-reported LBP. Baseline and outcome measures were collected via web-based surveillance system or phone to capture monthly information over 2 years. The assembled cohort consisted of 1230 Soldiers who provided self-report data with 518 (42.1%) reporting at least one episode of LBP over 2 years. Multivariate logistic regression analysis indicated that gender, active duty status, mental and physical health scores were significant predictors of LBP. Cox regression revealed that the time to first episode of LBP was significantly shorter for Soldiers that were female, active duty, reported previous injury, and had increased BMI. Multivariate linear regression analysis investigated severity of the first episode by identifying baseline predictors of pain intensity, disability, and psychological distress. Education level and physical fitness were consistent predictors of pain intensity, while gender, smoking status, and previous injury status were predictors of disability. Gender, smoking status, physical health scores, and beliefs of back pain were consistent predictors of psychological distress. These results provide additional data to confirm the multi-factorial nature of LBP and suggest future preventative interventions focus on multi-modal approaches that target modifiable risk factors specific to the population of interest

Transcriptome Analysis of Neisseria meningitidis in Human Whole Blood and Mutagenesis Studies Identify Virulence Factors Involved in Blood Survival

During infection Neisseria meningitidis (Nm) encounters multiple environments within the host, which makes rapid adaptation a crucial factor for meningococcal survival. Despite the importance of invasion into the bloodstream in the meningococcal disease process, little is known about how Nm adapts to permit survival and growth in blood. To address this, we performed a time-course transcriptome analysis using an ex vivo model of human whole blood infection. We observed that Nm alters the expression of ≈30% of ORFs of the genome and major dynamic changes were observed in the expression of transcriptional regulators, transport and binding proteins, energy metabolism, and surface-exposed virulence factors. In particular, we found that the gene encoding the regulator Fur, as well as all genes encoding iron uptake systems, were significantly up-regulated. Analysis of regulated genes encoding for surface-exposed proteins involved in Nm pathogenesis allowed us to better understand mechanisms used to circumvent host defenses. During blood infection, Nm activates genes encoding for the factor H binding proteins, fHbp and NspA, genes encoding for detoxifying enzymes such as SodC, Kat and AniA, as well as several less characterized surface-exposed proteins that might have a role in blood survival. Through mutagenesis studies of a subset of up-regulated genes we were able to identify new proteins important for survival in human blood and also to identify additional roles of previously known virulence factors in aiding survival in blood. Nm mutant strains lacking the genes encoding the hypothetical protein NMB1483 and the surface-exposed proteins NalP, Mip and NspA, the Fur regulator, the transferrin binding protein TbpB, and the L-lactate permease LctP were sensitive to killing by human blood. This increased knowledge of how Nm responds to adaptation in blood could also be helpful to develop diagnostic and therapeutic strategies to control the devastating disease cause by this microorganism

The gender specific frequency of risk factor and CHD diagnoses prior to incident MI: A community study

BACKGROUND: CHD is a chronic disease often present years prior to incident AMI. Earlier recognition of CHD may be associated with higher levels of recognition and treatment of CHD risk factors that may delay incident AMI. To assess timing of CHD and CHD risk factor diagnoses prior to incident AMI. METHODS: This is a 10-year population based medical record review study that included all medical care providers in Olmsted County, Minnesota for all women and a sample of men residing in Olmsted County, MN with confirmed incident AMI between 1995 and 2000. RESULTS: All medical care for the 10 years prior to incident AMI was reviewed for 150 women and 148 men (38% sample) in Olmsted County, MN. On average, women were older than men at the time of incident AMI (74.7 versus 65.9 years, p < 0.0001). 30.4% of the men and 52.0% of the women received diagnoses of CHD prior to incident AMI (p = 0.0002). Unrecognized and untreated CHD risk factors were present in both men (45% of men 5 years prior to AMI) and women (22% of women 5 years prior to first AMI), more common in men and those without a diagnosis of CHD prior to incident AMI (p < 0.0001). CONCLUSION: A CHD diagnosis prior to incident AMI is associated with higher rates of recognition and treatment of CHD risk factors suggesting that diagnosing CHD prior to AMI enhances opportunities to lower the risk of future CHD events