The Role of Canids in Ritual and Domestic Contexts: New Ancient DNA Insights from Complex Hunter-Gatherer Sites in Prehistoric Central California

This study explores the interrelationship between the genus Canis and hunter–gatherers through a case study of prehistoric Native Americans in the San Francisco Bay-Sacramento Delta area. A distinctive aspect of the region\u27s prehistoric record is the interment of canids, variously classified as coyotes, dogs, and wolves. Since these species are difficult to distinguish based solely on morphology, ancient DNA analysis was employed to distinguish species. The DNA study results, the first on canids from archaeological sites in California, are entirely represented by domesticated dogs (including both interments and disarticulated samples from midden deposits). These results, buttressed by stable isotope analyses, provide new insight into the complex interrelationship between humans and canids in both ritual and prosaic contexts, and reveal a more prominent role for dogs than previously envisioned

Evidence for ADAR-induced hypermutation of the Drosophila sigma virus (Rhabdoviridae).

BACKGROUND: ADARs are RNA editing enzymes that target double stranded RNA and convert adenosine to inosine, which is read by translation machinery as if it were guanosine. Aside from their role in generating protein diversity in the central nervous system, ADARs have been implicated in the hypermutation of some RNA viruses, although why this hypermutation occurs is not well understood. RESULTS: Here we describe the hypermutation of adenosines to guanosines in the genome of the sigma virus--a negative sense RNA virus that infects Drosophila melanogaster. The clustering of these mutations and the context in which they occur indicates that they have been caused by ADARs. However, ADAR-editing of viral RNA is either rare or edited viral RNA are rapidly degraded, as we only detected evidence for editing in two of the 104 viral isolates we studied. CONCLUSION: This is the first evidence for ADARs targeting viruses outside of mammals, and it raises the possibility that ADARs could play a role in the antiviral defences of insects.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Huntington's disease mouse models online: high-resolution MRI images with stereotaxic templates for computational neuroanatomy.

Magnetic resonance imaging (MRI) has proved to be an ideal modality for non-destructive and highly detailed assessment of structural morphology in biological tissues. Here we used MRI to make a dataset of ex vivo brains from two different rodent models of Huntington's disease (HD), the R6/2 line and the YAC 128 mouse. We are making the whole dataset (399 transgenic HD and wildtype (WT) brains, from mice aged 9-80 weeks) publicly available. These data will be useful, not only to investigators interested in the study of HD, but also to researchers of computational neuroanatomy who may not have access to such large datasets from mouse models. Here we demonstrate a number of uses of such data, for example to produce maps of grey and white matter and cortical thickness. As an example of how the library might provide insights in mouse models of HD, we calculated whole brain grey matter volumes across different age groups with different numbers of cytosine-adenine-guanine (CAG) repeats in a fragment of the gene responsible for HD in humans. (The R6/2 dataset was obtained from an allelic series of R6/2 mice carrying a range of CAG repeat lengths between 109 and 464.) This analysis revealed different trajectories for each fragment length. In particular there was a gradient of decreasing pathology with longer CAG repeat lengths, reflecting our previous findings with behavioural and histological studies. There will be no constraints placed on the use of the datasets included here. The original data will be easily and permanently accessible via the University of Cambridge data repository (http://www.dspace.cam.ac.uk/handle/1810/243361)

Oncology Outpatient and Provider Responses to a Computerized Symptom Assessment System

Purpose/Objectives: To assess patient and provider responses to a computerized symptom assessment system. Design: Descriptive, longitudinal study with retrospective, longitudinal medical records review. Setting: University-based National Cancer Institute-designated outpatient cancer center. Sample: 80 oncology outpatients receiving chemotherapy, 8 providers, and 30 medical records. Methods: Patients completed the computerized assessment during three chemotherapy follow-up clinic appointments (times 1, 2, and 3). Patient usability was recorded via an observer checklist (ease of use) and the computer (completion time). Patient satisfaction and impact were assessed during telephone interviews two to three days after times 1 and 3 only. Provider usability and impact were assessed at the end of the study using a questionnaire and focus groups, whereas effect on provider documentation was assessed through chart audits. Main Research Variables: Patient usability (ease of use, completion time), satisfaction, and impact; provider usability and impact. Findings: Patients reported good usability, high satisfaction, and modest impact on discussions with their providers. Providers reported modest usability, modest impact on discussions with patients, and had varied reactions as to how the system affected practice. Documentation of symptoms was largely absent before and after implementation. Conclusions: This system demonstrated good usability and satisfaction but had only a modest impact on symptom-related discussions and no impact on documentation. Implications for Nursing: A computerized system can help address barriers to symptom assessment but may not improve documentation unless it can be integrated into existing medical records systems

Moodivate: A self-help behavioral activation mobile app for utilization in primary care—Development and clinical considerations

Depressive symptoms are highly prevalent and are associated with considerable functional impairment, significant public health costs, and heightened mortality risk. Individuals experiencing impairment due to depressive symptomatology are most likely to report their symptoms to a primary care provider. As such, national guidelines highlight the need to assess and effectively treat depression via primary care. Despite these guidelines, the dissemination of evidence-based psychotherapy via primary care is limited, likely due to both provider- and patient-level treatment barriers. Mobile health (mHealth) technologies are promising for addressing these barriers and for promoting uptake of evidence-based depression treatment. Among evidence-based psychotherapies for depression, brief Behavioral Activation Treatment for Depression (BATD) has shown great promise and is particularly amenable to mHealth delivery. Herein, we discuss the development of a BATD mobile application, Moodivate, that was developed in order to disseminate BATD via primary care. This paper focuses on description of (1) rationale for Moodivate treatment development, (2) Moodivate treatment components, (3) ongoing clinical trial evaluation of Moodivate, and (4) clinical considerations for incorporating Moodivate into clinical practice

Right Ventricular Dysfunction in the R6/2 Transgenic Mouse Model of Huntington's Disease is Unmasked by Dobutamine

Background: Increasingly, evidence from studies in both animal models and patients suggests that cardiovascular dysfunction is important in HD. Previous studies measuring function of the left ventricle (LV) in the R6/2 mouse model have found a clear cardiac abnormality, albeit with preserved LV systolic function. It was hypothesized that an impairment of RV function might play a role in this condition via mechanisms of ventricular interdependence.Objective: To investigate RV function in the R6/2 mouse model of Huntington's disease (HD).Methods: Cardiac cine- magnetic resonance imaging (MRI) was used to determine functional parameters in R6/2 mice. In a first experiment, these parameters were derived longitudinally to determine deterioration of cardiac function with disease progression. A second experiment compared the response to a stress test (using dobutamine) of wildtype and early-symptomatic R6/2 mice. Results: There was progressive deterioration of RV systolic function with age in R6/2 mice. Furthermore, beta-adrenergic stimulation with dobutamine revealed RV dysfunction in R6/2 mice before any overt symptoms of the disease were apparent.Conclusions: This work adds to accumulating evidence of cardiovascular dysfunction in R6/2 mice, describing for the first time the involvement of the right ventricle. Cardiovascular dysfunction should be considered, both when treatment strategies are being designed, and when searching for biomarkers for HD

Impaired degranulation but enhanced cytokine production after FcɛRI stimulation of diacylglycerol kinase ζ–deficient mast cells

Calcium and diacylglycerol are critical second messengers that together effect mast cell degranulation after allergen cross-linking of immunoglobulin (Ig)E-bound FcɛRI. Diacylglycerol kinase (DGK)ζ is a negative regulator of diacylglycerol-dependent signaling that acts by converting diacylglycerol to phosphatidic acid. We reported previously that DGKζ−/− mice have enhanced in vivo T cell function. Here, we demonstrate that these mice have diminished in vivo mast cell function, as revealed by impaired local anaphylactic responses. Concordantly, DGKζ−/− bone marrow–derived mast cells (BMMCs) demonstrate impaired degranulation after FcɛRI cross-linking, associated with diminished phospholipase Cγ activity, calcium flux, and protein kinase C–βII membrane recruitment. In contrast, Ras-Erk signals and interleukin-6 production are enhanced, both during IgE sensitization and after antigen cross-linking of FcɛRI. Our data demonstrate dissociation between cytokine production and degranulation in mast cells and reveal the importance of DGK activity during IgE sensitization for proper attenuation of FcɛRI signals

An ALMA Survey of H₂CO in Protoplanetary Disks

H₂CO is one of the most abundant organic molecules in protoplanetary disks and can serve as a precursor to more complex organic chemistry. We present an Atacama Large Millimeter/submillimeter Array survey of H₂CO toward 15 disks covering a range of stellar spectral types, stellar ages, and dust continuum morphologies. H₂CO is detected toward 13 disks and tentatively detected toward a fourteenth. We find both centrally peaked and centrally depressed emission morphologies, and half of the disks show ring-like structures at or beyond expected CO snowline locations. Together these morphologies suggest that H₂CO in disks is commonly produced through both gas-phase and CO-ice-regulated grain-surface chemistry. We extract disk-averaged and azimuthally-averaged H₂CO excitation temperatures and column densities for four disks with multiple H₂CO line detections. The temperatures are between 20–50 K, with the exception of colder temperatures in the DM Tau disk. These temperatures suggest that H₂CO emission in disks generally emerges from the warm molecular layer, with some contributions from the colder midplane. Applying the same H₂CO excitation temperatures to all disks in the survey, we find that H₂CO column densities span almost three orders of magnitude (~5 × 10¹¹–5 × 10¹⁴ cm⁻²). The column densities appear uncorrelated with disk size and stellar age, but Herbig Ae disks may have less H₂CO compared to T Tauri disks, possibly because of less CO freeze-out. More H₂CO observations toward Herbig Ae disks are needed to confirm this tentative trend, and to better constrain under which disk conditions H₂CO and other oxygen-bearing organics efficiently form during planet formation