Similarities and Differences in the Cohesinopathies of Roberts Syndrome and Cornelia de Lange Syndrome

Cohesins were first identified based on their role in chromosome segregation. The products of chromosome replication must be identified from S phase until anaphase onset in mitosis to ensure high fidelity chromosome segregation. Cohesin complexes tether together sister chromatids to maintain identity over time. More recently, cohesins were found to play numerous roles in transcription regulation and other forms of DNA metabolism, including the firing of clustered DNA replication forks, insulator function, and replication fork restart. Genetic mapping that revealed cohesin mutations are responsible for severe developmental defects spurred intense research regarding which role of cohesins was crucial to proper development. Cohesinopathies are a group of developmental disorders caused by disruption in cohesin function. Cornelia de Lange Syndrome (CdLS) and Roberts Syndrome (RBS) are two examples of cohesinopathies that exhibit a similar suite of phenotypes but are thought to arise through very different cellular mechanisms. This review investigates the similarities and differences between these two disorders to formulate a hypothesis unifying the relationship of these disorders as a possible continuum of manifestations caused by the same underlying mechanism

Exploring the Milky Way Circumgalactic Medium in a Cosmological Context with a Semi-Analytic Model

We combine the Santa-Cruz Semi-Analytic Model (SAM) for galaxy formation and evolution with the circumgalactic medium (CGM) model presented in Faerman et al. (2020) to explore the CGM properties of $L^{*}$ galaxies. We use the SAM to generate a sample of galaxies with halo masses similar to the Milky Way (MW) halo, $M_{\rm vir} \approx 10^{12}~{\rm M_{sun}}$, and find that the CGM mass and mean metallicity in the sample are correlated. We use the CGM masses and metallicities of the SAM galaxies as inputs for the FSM20 model, and vary the amount of non-thermal support. The density profiles in our models can be approximated by power-law functions with slopes in the range of $0.75 < a_n < 1.25$, with higher non-thermal pressure resulting in flatter distributions. We explore how the gas pressure, dispersion measure, OVI-OVIII column densities, and cooling rates behave with the gas distribution and total mass. We show that for CGM masses below $\sim 3 \times 10^{10}~{\rm M_{sun}}$, photoionization has a significant effect on the column densities of OVI and OVIII. The combination of different MW CGM observations favors models with similar fractions in thermal pressure, magnetic fields/cosmic rays, and turbulent support, and with $M_{\rm gas} \sim 3-10 \times 10^{10}~{\rm M_{sun}}$. The MW OVI column requires $t_{\rm cool}/t_{\rm dyn} \sim 4$, independent of the gas distribution. The AGN jet-driven heating rates in the SAM are enough to offset the CGM cooling, although exact balance is not required in star-forming galaxies. We provide predictions for the columns densities of additional metal ions - NV, NeVIII, and MgX.Comment: Submitted to ApJ. 19 pages, 15 figures (+ appendix

Dissemination of Resistant Escherichia coli Among Wild Birds, Rodents, Flies, and Calves on Dairy Farms

Antimicrobial resistance (AMR) in bacteria in the livestock is a growing problem, partly due to inappropriate use of antimicrobial drugs. Antimicrobial use (AMU) occurs in Swedish dairy farming but is restricted to the treatment of sick animals based on prescription by a veterinary practitioner. Despite these strict rules, calves shedding antimicrobial resistant Enterobacteriaceae have been recorded both in dairy farms and in slaughterhouses. Yet, not much is known how these bacteria disseminate into the local environment around dairy farms. In this study, we collected samples from four animal sources (fecal samples from calves, birds and rodents, and whole flies) and two environmental sources (cow manure drains and manure pits). From the samples, Escherichia coli was isolated and antimicrobial susceptibility testing performed. A subset of isolates was whole genome sequenced to evaluate relatedness between sources and genomic determinants such as antimicrobial resistance genes (ARGs) and the presence of plasmids were assessed. We detected both ARGs, mobile genetic elements and low rates of AMR. In particular, we observed four potential instances of bacterial clonal sharing in two different animal sources. This demonstrates resistant E. coli dissemination potential within the dairy farm, between calves and scavenger animals (rodents and flies). AMR dissemination and the zoonotic AMR risk is generally low in countries with low and restricted AMU. However, we show that interspecies dissemination does occur, and in countries that have little to no AMU restrictions this risk could be under-estimated

Effect of inhaled glucocorticoids in childhood on adult height

BACKGROUND: The use of inhaled glucocorticoids for persistent asthma causes a temporary reduction in growth velocity in prepubertal children. The resulting decrease in attained height 1 to 4 years after the initiation of inhaled glucocorticoids is thought not to decrease attained adult height. METHODS: We measured adult height in 943 of 1041 participants (90.6%) in the Childhood Asthma Management Program; adult height was determined at a mean (±SD) age of 24.9±2.7 years. Starting at the age of 5 to 13 years, the participants had been randomly assigned to receive 400 μg of budesonide, 16 mg of nedocromil, or placebo daily for 4 to 6 years. We calculated differences in adult height for each active treatment group, as compared with placebo, using multiple linear regression with adjustment for demographic characteristics, asthma features, and height at trial entry. RESULTS: Mean adult height was 1.2 cm lower (95% confidence interval [CI], -1.9 to -0.5) in the budesonide group than in the placebo group (P=0.001) and was 0.2 cm lower (95% CI, -0.9 to 0.5) in the nedocromil group than in the placebo group (P=0.61). A larger daily dose of inhaled glucocorticoid in the first 2 years was associated with a lower adult height (-0.1 cm for each microgram per kilogram of body weight) (P=0.007). The reduction in adult height in the budesonide group as compared with the placebo group was similar to that seen after 2 years of treatment (-1.3 cm; 95% CI, -1.7 to -0.9). During the first 2 years, decreased growth velocity in the budesonide group occurred primarily in prepubertal participants. CONCLUSIONS: The initial decrease in attained height associated with the use of inhaled glucocorticoids in prepubertal children persisted as a reduction in adult height, although the decrease was not progressive or cumulative. (Funded by the National Heart, Lung, and Blood Institute and the National Center for Research Resources; CAMP ClinicalTrials.gov number, NCT00000575.)

Communal Innovations : Inspiring Neighborhoods of Hope and Advocacy

Innovations promise a better future, which may generate feelings of hope and inspire advocacy. Some innovations are more communal in nature: attempting to address a social problem, through community engagement and wide-spread adoption. For such innovations, the social processes that involve collective aspects of community life may play important roles in fostering hope and interpersonal advocacy. This study uses communication infrastructure theory and discrete emotions theory to investigate hope and advocacy within a field trial for a salient, visible, community-bound innovation to reduce transmission of malaria. Heads of households in one community (N = 119) in West Africa were interviewed. Results showed that innovation hope was predicted by appraisals of innovation attributes. Better appraisals of the innovation's attributes, greater perceived collective efficacy, and recent malaria illness predicted more innovation advocacy. The spatial analysis showed that innovation advocacy was geographically clustered within the community, but hope was not. The implications for theory and practice are discussed

Integrating Models of Diffusion and Behavior to Predict Innovation Adoption, Maintenance, and Social Diffusion

This study documents an investigation into the adoption and diffusion of eave tubes, a novel mosquito vector control, during a large-scale scientific field trial in West Africa. The diffusion of innovations (DOI) and the integrated model of behavior (IMB) were integrated (i.e., innovation attributes with attitudes and social pressures with norms) to predict participants’ (N = 329) diffusion intentions. The findings showed that positive attitudes about the innovation’s attributes were a consistent positive predictor of diffusion intentions: adopting it, maintaining it, and talking with others about it. As expected by the DOI and the IMB, the social pressure created by a descriptive norm positively predicted intentions to adopt and maintain the innovation. Drawing upon sharing research, we argued that the descriptive norm may dampen future talk about the innovation, because it may no longer be seen as a novel, useful topic to discuss. As predicted, the results showed that as the descriptive norm increased, the intention to talk about the innovation decreased. These results provide broad support for integrating the DOI and the IMB to predict diffusion and for efforts to draw on other research to understand motivations for social diffusion

Evaluating the impact of screening plus eave tubes on malaria transmission compared to current best practice in central Côte d'Ivoire : A two armed cluster randomized controlled trial

Background: Access to long-lasting insecticidal nets (LLINs) has increased and malaria has decreased globally, but malaria transmission remains high in parts of sub-Saharan Africa and insecticide resistance threatens current progress. Eave tubes are a new tool for the targeted delivery of insecticides against mosquitoes attempting to enter houses. The primary objective of this trial is to test whether screening plus eave tubes (SET) provides protection against malaria, on top of universal coverage with LLINs in an area of intense pyrethroid resistance. The trial will also assess acceptability and cost-effectiveness of the intervention. Methods/design: A two-armed, cluster randomized controlled trial will be conducted to evaluate the effect of SET on clinical malaria incidence in children living in central Côte d'Ivoire. Forty villages will be selected based on population size and the proportion of houses suitable for modification with SET. Using restricted randomization, half the villages will be assigned to the treatment arm (SET + LLINs) and the remainder will be assigned to the control arm (LLINs only). In both arms, LLINs will be distributed and in the treatment arm, householders will be offered SET. Fifty children aged six months to eight years old will be enrolled from randomly selected households in each of the 40 villages. Cohorts will be cleared of malaria parasites at the start of the study and one year after recruitment, and will be monitored for clinical malaria case incidence by active case detection over two years. Mosquito densities will be assessed using CDC light traps and human landing catches and a subset of Anopheles mosquitoes will be examined for parity status and tested for sporozoite infection. Acceptability of SET will be monitored using surveys and focus groups. Cost-effectiveness analysis will measure the incremental cost per case averted and per disability-adjusted life year (DALY) averted of adding SET to LLINs. Economic and financial costs will be estimated from societal and provider perspective using standard economic evaluation methods. Discussion: This study will be the first evaluation of the epidemiological impact of SET. Trial findings will show whether SET is a viable, cost-effective technology for malaria control in Côte d'Ivoire and possibly elsewhere. Trial registration: ISRCTN18145556, registered on 01 February 2017 - retrospectively registered