Lack of Effect of Murine Norovirus Infection on a Mouse Model of Bacteria-Induced Colon Cancer

Murine norovirus (MNV) is endemic in mouse research facilities in the United States and Europe, with a prevalence as high as 58% to 64%. Because of MNV's orofecal route of infection, clinically silent persistent infections in some mouse strains, and proclivity for macrophage and dendritic cells, its presence in mouse colonies has potential to alter phenotypes in experimental mouse models, particularly those involving inflammation and immunologic responses. Although MNV is subclinical, not causing overt disease in immunocompetent mice, we found that MNV infection can accelerate bacteria-induced inflammatory bowel disease (IBD) progression in Mdr1a^(-/-) mice. The studies presented here examined whether MNV infection also affects the phenotype of a bacterially driven mouse model of inflammation-associated colon cancer in genetically susceptible Smad3^(-/-) mice. In vitro culture of bone-marrow—derived macrophages (BMDM) was used to determine whether MNV4 influenced macrophage cytokine production. For in vivo studies, Smad3-/- mice were infected with MNV4 one week prior to infection with Helicobacter. Mice were monitored for 17 to 32 wk for development of IBD and colon cancer, and tissues were analyzed histopathologically. Although in vitro infection of BMDM with MNV4 led to increased inflammatory cytokine production, infection with MNV4 in vivo did not result in any statistically significant differences in survival, IBD scores, tumor incidence, or tumor phenotype in Smad3^(-/-) mice. In addition, MNV infection alone did not result in IBD or colon cancer. Therefore MNV infection alone or in conjunction with Helicobacter does not alter the development or progression of IBD or colon cancer in Smad3^(-/-) mice

Multiple morbidities in companion dogs: a novel model for investigating age-related disease

The proportion of men and women surviving over 65 years has been steadily increasing over the last century. In their later years, many of these individuals are afflicted with multiple chronic conditions, placing increasing pressure on healthcare systems. The accumulation of multiple health problems with advanced age is well documented, yet the causes are poorly understood. Animal models have long been employed in attempts to elucidate these complex mechanisms with limited success. Recently, the domestic dog has been proposed as a promising model of human aging for several reasons. Mean lifespan shows twofold variation across dog breeds. In addition, dogs closely share the environments of their owners, and substantial veterinary resources are dedicated to comprehensive diagnosis of conditions in dogs. However, while dogs are therefore useful for studying multimorbidity, little is known about how aging influences the accumulation of multiple concurrent disease conditions across dog breeds. The current study examines how age, body weight, and breed contribute to variation in multimorbidity in over 2,000 companion dogs visiting private veterinary clinics in England. In common with humans, we find that the number of diagnoses increases significantly with age in dogs. However, we find no significant weight or breed effects on morbidity number. This surprising result reveals that while breeds may vary in their average longevity and causes of death, their age-related trajectories of morbidities differ little, suggesting that age of onset of disease may be the source of variation in lifespan across breeds. Future studies with increased sample sizes and longitudinal monitoring may help us discern more breed-specific patterns in morbidity. Overall, the large increase in multimorbidity seen with age in dogs mirrors that seen in humans and lends even more credence to the value of companion dogs as models for human morbidity and mortality

Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice

The FDA approved drug rapamycin increases lifespan in rodents and delays age-related dysfunction in rodents and humans. Nevertheless, important questions remain regarding the optimal dose, duration, and mechanisms of action in the context of healthy aging. Here we show that 3 months of rapamycin treatment is sufficient to increase life expectancy by up to 60% and improve measures of healthspan in middle-aged mice. This transient treatment is also associated with a remodeling of the microbiome, including dramatically increased prevalence of segmented filamentous bacteria in the small intestine. We also define a dose in female mice that does not extend lifespan, but is associated with a striking shift in cancer prevalence toward aggressive hematopoietic cancers and away from non-hematopoietic malignancies. These data suggest that a short-term rapamycin treatment late in life has persistent effects that can robustly delay aging, influence cancer prevalence, and modulate the microbiome.P30 AG013280 - NIA NIH HHS; T32 AG000057 - NIA NIH HH

Macroinvertebrates online

Macrobenthic invertebrates are important indicators of water quality in many aquatic systems, but accurately identifying these organisms is a challenge, particularly for citizen scientists, due to insufficient funding for training programs and events and a dwindling pool of training personnel. Accurately identifying these organisms is key to the accuracy of the models used to generate the water quality assessments. To help address these issues, this project has developed an interactive online photographic key for macrobenthic invertebrates, designed to improve classification accuracy with minimal training for use by citizen scientists. The online digital photographic field guide was created and tested against a widely used paper key (the Izaac Walton key). Classification exercises and user satisfaction surveys were conducted at different events over two years in order to compare the two identification methods. Results indicate that most participants preferred the online field guide, but that the digital field guide did not necessarily increase classification accuracy within all user groups. The results suggest the need for some basic experience or training in using macrobethic invertebrates for water quality assessment, similar to what high school or college students receive in aquatic ecology or field science courses. Another obstacle to improve water quality assessment is the dissemination of data. A tool currently being developed as part of this project is a digital map and linked database created using ArcGIS 10. This map incorporates spatial data helpful for water quality analyses (e.g. land use/cover) from different sources and has web-enabled links to other water quality databases through hyperlinks built into the map features. This will help account for multiple variables that can affect water quality and to help scientists with outreach, data dissemination, and networking. The map project at this point is still conceptual, but is intended to demonstrate its potential utility

Platelet-like catalyst design for high yield production of multi-walled carbon nanotubes by catalytic chemical vapour deposition

We investigated the effect of catalyst design on the synthesis of multi-walled carbon nanotubes (MWCNTs) by chemical vapor deposition (CVD). A set of highly active supported sol–gel Co–Mo/MgO and Ni–Mo/MgO catalysts was prepared systematically modifying the calcination temperature. First, the evolution of catalysts’ crystallographic phases and their morphology were studied by X-ray diffraction (XRD), Raman spectroscopy, scanning electron (SEM) and transmission electron (TEM) microscopy. Second, the catalysts were used for the CVD growth of MWCNTs. The resulting materials were analysed by SEM and TEM, Raman and XRD to establish a relation between catalyst design and MWCNT yield. We show that our catalyst synthesis route leads to the formation of laminar non-porous catalyst systems, which at a calcination temperature of 800 °C stabilize in a crystallographic phase of MexMg1−xMoO4 (Me = Co or Ni). We give evidence that increased MWCNT yields of more than 3000 wt.% with respect to the catalysts are directly related to the aforementioned crystallographic phase. Finally, we propose a growth model based on the continuous exfoliation of platelet-like catalyst systems. This consistently explains the high catalytic activity towards MWCNT production using a non-porous catalyst. Our findings provide important insights for catalyst design strategies towards large-scale MWCNT production.Peer reviewe

Preschool Social Skills: The Development of Prosocial Interactions.

This study examined differing perceptions of teachers and parents pertaining to frequency and importance of social skills and problem behaviors in preschool children. Specifically, the present investigation considered social skills of preschool children considered to be At-Risk for educationally handicapping conditions as well as a group of Typical preschool children. Both teacher and parent ratings on the Social Skills Rating System (SSRS) (Gresham & Elliott, 1990) and the revised Conners Rating Scales (CRS), (Goyette, Conners, & Ulrich, 1978) were obtained from a sample of 95 preschool children. Fifty-two subjects were enrolled in an at-risk preschool program (i.e., Head Start) and 43 attended a typical preschool program. Both parents and teachers of At-Risk preschool children identified significantly fewer social skills and more problem behaviors than did parents and teachers of Typical preschool children. Teacher ratings of behaviors considered important in the preschool setting (e.g., participates in group activities) did not vary across the two groups and suggested social behaviors related to peer interactions were valued most. Some variation occurred across groups in terms of parent ratings of important social skills, with parents of At-Risk students rating behaviors pertaining to self-control as most important and parents of Typical students stressing compliance behaviors. Interrater correlations indicated low to moderate correlations between teacher and parent ratings, consistent with previous research. Convergent validity was supported by correlations between total factor scores on the SSRS and the CRS. High positive correlations were found between SSRS Problem Behavior factor and CRS teacher ratings (r =.91) and parent ratings (r =.64). Relatively strong negative correlations emerged between SSRS Social Skills factor and CRS teacher (r = $-$.62) and parent ratings (r = $-$.42). Results of discriminant function analysis revealed that 73.51% of subjects were correctly classified based on teacher ratings of social behaviors, and 69.23% based on parent ratings. Findings were discussed with implications for social skills assessment and remediation, as well as the validity of both the SSRS and CRS as viable instruments for the preschool age. These two scales appear to be useful in assessment of social competence in young children

How age, sex and genotype shape the stress response

Exposure to chronic stress is a leading pre-disposing factor for several neuropsychiatric disorders as it often leads to maladaptive responses. The response to stressful events is heterogeneous, underpinning a wide spectrum of distinct changes amongst stress-exposed individuals'. Several factors can underlie a different perception to stressors and the setting of distinct coping strategies that will lead to individual differences on the susceptibility/resistance to stress. Beyond the factors related to the stressor itself, such as intensity, duration or predictability, there are factors intrinsic to the individuals that are relevant to shape the stress response, such as age, sex and genetics. In this review, we examine the contribution of such intrinsic factors to the modulation of the stress response based on experimental rodent models of response to stress and discuss to what extent that knowledge can be potentially translated to humans.FEDER through the Operational Programme Competitiveness Factors - COMPETE and National Funds through FCT - Foundation for Science and Technology under the project POCI-01-0145-FEDER-007038; and by the project NORTE-01-0145-FEDER-000013, supported by Norte Portugal Regional Operational Programme (NORTE, 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). We acknowledge the Portuguese Foundation for Science and Technology (FCT) for providing a post-doctoral fellowship to SR (SFRH/BPD/72710/2010), a doctoral fellowship to SM (SFRH/BD/69311/2010) and a fellowship to AN (ANR/NEU-OSD/0258/2012)info:eu-repo/semantics/publishedVersio

Reproducibility of histopathological findings in experimental pathology of the mouse: a sorry tail

Reproducibility of $\textit{in vivo}$ research using the mouse as a model organism depends on many factors, including experimental design, strain or stock, experimental protocols, and methods of data evaluation. Gross and histopathology are often the endpoints of such research and there is increasing concern about the accuracy and reproducibility of diagnoses in the literature. To reproduce histopathological results, the pathology protocol, including necropsy methods and slide preparation, should be followed by interpretation of the slides by a pathologist familiar with reading mouse slides and familiar with the consensus medical nomenclature used in mouse pathology. Likewise, it is important that pathologists are consulted as reviewers of manuscripts where histopathology is a key part of the investigation. The absence of pathology expertise in planning, executing and reviewing $\textit{in vivo}$ research using mice leads to questionable pathology-based findings and conclusions from studies, even in high-impact journals. We discuss the various aspects of this problem, give some examples from the literature and suggest solutions.This work was supported in part by US National Institutes of Health grants R01 AR049288, CA089713 and R21 AR063781 (to J.P.S.) and by The Warden and Fellows of Robinson College, Cambridge (to P.N.S.)