ALBERT

Beschreibung: The modeling of the atmospheric boundary layer over sea ice is still challenging because of the complex interaction between clouds, radiation and turbulence over the often inhomogeneous sea ice cover. There is still much uncertainty concerning sea ice roughness, near-surface thermal stability and related processes, and their accurate parameterization. Here, a regional Arctic climate model forced by ERA-interim data was used to test the sensitivity of climate simulations to a modified surface flux parameterization for wintertime conditions over the Arctic. The reference parameterization as well as the modified one is based on Monin–Obukhov similarity theory, but different roughness lengths were prescribed and the stability dependence of the transfer coefficients for momentum, heat and moisture differed from each other. The modified parameterization accounts for the most compre- hensive observations that are presently available over sea ice in the inner Arctic. Independent of the parameterization used, the model was able to reproduce the two observed dominant winter states with respect to cloud cover and longwave radiation. A stepwise use of the different parameterization assumptions showed that modifications of both surface roughness and stability dependence had a considerable impact on quantities such as air pressure, wind and near-surface turbulent fluxes. However, the reduction of surface roughness to values agreeing with those observed during t he Surface Heat Budget of the Arctic Ocean campaign led to an improvement in the western Arctic, while the modified stability parameteri- zation had only a minor impact. The latter could be traced back to the model's underestimation of the strength of stability over sea ice. Future work should concentrate on possible reasons for this underestimation and on the question of generality of the results for other climate models

Beschreibung: Globally, mesoscale processes create a rich and filamented pattern in biological productivity. Despite of remoteness and a harsh environment, observations likewise show an impact of mesoscale processes on phytoplankton growth in the Arctic. Observations of sufficiently high resolution are, however, difficult to carry out. Large-scale models are another way to gain knowledge about the system. In the current study, we use a global sea ice-ocean biogeochemical model, which is eddy resolving in Fram Strait, to show that the mesoscale dynamics has a strong effect on shaping phytoplankton growth. For the year 2009, we demonstrate that the growth season in the West Spitzbergen Current can be divided into two regimes; during Regime I, which takes place in May and June before and during the spring bloom, high chlorophyll concentrations are associated with areas of positive vorticity and a shallow mixed layer, pointing toward light limitation controlling growth. During Regime II, which occurs after the bloom from mid-July to late August, the highest chlorophyll concentration is found in areas of negative vorticity. Here, upwelling of nutrient-rich water occurs, through doming isopycnals, acting to raise the nutricline, may also play a role in alleviating nutrient limitation in the surface water. The study suggests that the mesoscale eddy environment locally modulates the seasonal cycle of light and nutrient limitation. Knowledge of the eddy field should be taken into consideration for making conclusions from point-wise measurements in Fram Strait.

Beschreibung: Predicting the implications of ongoing ocean climate warming demands a better understanding of how short-term thermal variability impacts marine ectotherms, particularly at beyond-optimal average conditions during summer heatwaves. Using a globally important model species, the blue mussel Mytilus, in a 5-week-long experiment, we (a) assessed growth performance traits under 12 scenarios, consisting of four thermal averages (18.5, 21, 23.5 and 26℃) imposed as constant or daily fluctuating regimes with amplitudes of 2 or 4℃. Additionally, we conducted a short-term assay using different mussel individuals to (b) test for the species capacity for suppression and recovery of metabolic performance traits (feeding and aerobic respiration) when exposed to a 1-day thermal fluctuation regime (16.8–30.5℃). Using this high-resolution data, we (c) generated short-term thermal metabolic performance curves to predict and explain growth responses observed in the long-term experiment. We found that daily high-amplitude thermal cycles (4℃) improved mussel growth when fluctuations were imposed around an extreme average temperature of 26℃, representing end-of-century heatwaves. In contrast, thermal cycles negatively affected mussel growth at a less extreme average temperature of 23.5℃, resembling current peak summer temperature scenarios. These results suggest that fluctuations ameliorate heat stress impacts only at critically high average temperatures. The short-term assay demonstrated that during the warming phase, animals stopped feeding between 24 and 30℃ while gradually suppressing respiration. In the subsequent cooling phase, feeding and respiration partially and fully recovered to pre-heating rates respectively. Furthermore, nonlinear averaging of short-term feeding responses (upscaling) well-predicted longer term growth responses to fluctuations. Our findings suggest that fluctuations can be beneficial to or detrimental for the long-term performance of ectothermic animals, depending on the fluctuations' average and amplitude. Furthermore, the observed effects can be linked to fluctuation-mediated metabolic suppression and recovery. In a general framework, we propose various hypothetical scenarios of fluctuation impacts on ectotherm performance considering inter- or intra-species variability in heat sensitivity. Our research highlights the need for studying metabolic performance in relation to cyclic abiotic fluctuations to advance the understanding of climate change impacts on aquatic systems. A free Plain Language Summary can be found within the Supporting Information of this article

Beschreibung: The Bransfield Basin is a young (∼4 Ma) back-arc basin related to the remnant subduction of the Phoenix Plate that once existed along the entire Pacific margin of the Antarctic Peninsula. Based on a recently deployed amphibious seismic network, we use ambient noise tomography to obtain the S-wave velocity structure in the Central Bransfield Basin (CBB). Combining with the stress field inverted from focal mechanisms, our images reveal that the CBB suffers a significant extension in the northwest-southeast direction. The extension is strongest in the northeastern CBB with associated mantle exhumation and weakens to the southwest with decoupled deformations between the upper crust and lithospheric mantle. Such an along-strike variation of extension can be explained by slab window formation and forearc rotation, which are associated with the Phoenix Plate detachment during the ridge–trench collisions at the southwest of the Hero Fracture Zone.

Beschreibung: Physical activity is important for health. However, there is a lack of literature related to the physical activity levels of adults living in urban villagers, which is a vulnerable population in China. The aim of this study is to compare the physical activity and sedentary behavior engagements between urban villagers and non-urban villagers using the 2019 Luohu Shenzhen, China Community Diagnosis Questionnaire. A total of 1205 adults living in urban villages and non-urban villages were included in the analysis. Unadjusted and multiple multivariate logistic regression were conducted for the dependent variable of engagement in recreational physical activity, frequency of recreational physical activity per week, and hours spent in sedentary behaviors per day. Descriptive analysis was conducted to identify the reasons for not engaging in physical activity among urban villagers and non-urban villagers. Across the included sample, 29.05% were urban villagers and 70.95% were non-urban villagers. The results suggested that urban villagers are more likely to engage in physical activity than non-urban villager (OR = 1.90, 95% CI [1.40, 2.59], p 〈 0.001). However, it was also found that urban village status had no significant association for frequency in engaging in physical activity and average hours spent in sedentary behaviors. Both urban villagers and non-urban villages indicated that lack of time, lack of safe and appropriate environment, and working in labor intensive occupations as some of the reasons for not engaging in physical activity. There is a need for tailed interventions and policies for promoting physical activity among urban villagers and non-urban villagers. Additional studies are needed to further our understanding of the physical activity behaviors among urban villagers in China.

Beschreibung: Adherent-invasive Escherichia coli (AIEC) is a pathovar linked to inflammatory bowel diseases (IBD), especially Crohn’s disease, and colorectal cancer. AIEC are genetically diverse, and in the absence of a universal molecular signature, are defined by in vitro functional attributes. The relative ability of difference AIEC strains to colonize, persist, and induce inflammation in an IBD-susceptible host is unresolved. To evaluate strain-level variation among tissue-associated E. coli in the intestines, we develop a long-read sequencing approach to identify AIEC by strain that excludes host DNA. We use this approach to distinguish genetically similar strains and assess their fitness in colonizing the intestine. Here we have assembled complete genomes using long-read nanopore sequencing for a model AIEC strain, NC101, and seven strains isolated from the intestinal mucosa of Crohn’s disease and non-Crohn’s tissues. We show these strains can colonize the intestine of IBD susceptible mice and induce inflammatory cytokines from cultured macrophages. We demonstrate that these strains can be quantified and distinguished in the presence of 99.5% mammalian DNA and from within a fecal population. Analysis of global genomic structure and specific sequence variation within the ribosomal RNA operon provides a framework for efficiently tracking strain-level variation of closely-related E. coli and likely other commensal/pathogenic bacteria impacting intestinal inflammation in experimental settings and IBD patients.

Beschreibung: Gene Set Enrichment Analysis (GSEA) is a powerful algorithm to determine biased pathways between groups based on expression profiling. However, for fruit fly, a popular animal model, gene matrixes for GSEA are unavailable. This study provides the pathway-targeting gene matrixes based on Reactome and KEGG database for fruit fly. An expression profiling containing neurons or glia of fruit fly was used to validate the feasibility of the generated gene matrixes. We validated the gene matrixes and identified characteristic neuronal and glial pathways, including mRNA splicing and endocytosis. In conclusion, we generated and validated the feasibility of Reactome and KEGG gene matrix files, which may benefit future profiling studies using Drosophila.

Beschreibung: This paper establishes a compartment model describing the propagation of injurious information among a well-mixed population. We define the information’s injuriousness as the people practicing the information being injured and leaving the system. Some informed people practice the information and are active, while others do not practice and are inactive. With the recovery resources fixed, the two groups of informed people’s recovering rates are normalized considering the information features. The stability of the nonlinear system is thoroughly studied. Analyzing the reproduction number of the injurious information, we find that in general parameter space, when there are people in an informed compartment, it is not always necessary to consider their recovery resource allocation. Instead, only when their proportion reaches a critical point should it be allocated. Unless the people in an informed compartment form a certain proportion, we can take a laissez-faire attitude towards them. In a more realistic parameter space, once inactive informed people exist, they should be allocated recovery resources. On the one hand, when the recovering rate rises, the focus on both groups of informed people is necessary for more situations. On the other hand, when the rate of active informed people leaving the system rises, ignoring active informed people benefits removing the injurious information in more cases. The model provides qualitative ways in the scenarios of removing injurious information.

Beschreibung: Homozygous nonsense mutations in CEP55 are associated with several congenital malformations that lead to perinatal lethality suggesting that it plays a critical role in regulation of embryonic development. CEP55 has previously been studied as a crucial regulator of cytokinesis, predominantly in transformed cells, and its dysregulation is linked to carcinogenesis. However, its molecular functions during embryonic development in mammals require further investigation. We have generated a Cep55 knockout (Cep55-/-) mouse model which demonstrated preweaning lethality associated with a wide range of neural defects. Focusing our analysis on the neocortex, we show that Cep55-/- embryos exhibited depleted neural stem/progenitor cells in the ventricular zone as a result of significantly increased cellular apoptosis. Mechanistically, we demonstrated that Cep55-loss downregulates the pGsk3β/β-Catenin/Myc axis in an Akt-dependent manner. The elevated apoptosis of neural stem/progenitors was recapitulated using Cep55-deficient human cerebral organoids and we could rescue the phenotype by inhibiting active Gsk3β. Additionally, we show that Cep55-loss leads to a significant reduction of ciliated cells, highlighting a novel role in regulating ciliogenesis. Collectively, our findings demonstrate a critical role of Cep55 during brain development and provide mechanistic insights that may have important implications for genetic syndromes associated with Cep55-loss.

Beschreibung: Objective To examine the main and interactive effects of the amount of daily television exposure and frequency of parent conversation during shared television viewing on parent ratings of curiosity at kindergarten, and to test for moderation by socioeconomic status (SES). Study design Sample included 5100 children from the Early Childhood Longitudinal Study, Birth Cohort. Hours of daily television exposure and frequency of parent screen-time conversation were assessed from a parent interview at preschool, and the outcome of early childhood curiosity was derived from a child behavior questionnaire at kindergarten. Multivariate linear regression examined the main and interactive effects of television exposure and parent screen-time conversation on kindergarten curiosity and tested for moderation by SES. Results In adjusted models, greater number of hours of daily television viewing at preschool was associated with lower curiosity at kindergarten (B = -0.14, p = .008). More frequent parent conversation during shared screen-time was associated with higher parent-reported curiosity at kindergarten with evidence of moderation by SES. The magnitude of association between frequency of parent conversation during television viewing and curiosity was greater for children from low SES environments, compared to children from high SES environments: (SES ≤ median): B = 0.29, p 〈 .001; (SES 〉 median): B = 0.11, p 〈 .001. Conclusions Higher curiosity at kindergarten was associated with greater frequency of parent conversation during shared television viewing, with a greater magnitude of association in low-SES families. While the study could not include measures of television program content, digital media use and non-screen time conversation, our results suggest the importance of parent conversation to promote early childhood curiosity, especially for children with socioeconomic disadvantage.

Beschreibung: Background The Substance Abuse and Mental Health Administration awarded State Targeted Response grants to support states’ efforts to address the opioid epidemic. In Nevada, one component of this grant was mobile recovery outreach teams (MROTs) that utilized peer recovery support specialists to provide care for qualifying patients in emergency departments (EDs). The Mobile Emergency Recovery Intervention Trial (MERIT) is a mixed methods study to assess the feasibility/acceptability and effectiveness of the MROT intervention. This protocol mainly describes the R33 research activities and outcomes. The full protocol can be found protocols.io. Methods Data will be derived from state-level data sets containing de-identified emergency department visits, substance use disorder treatment records, and mortality files; in-person mixed methods interviews; participant observation; and self-report process evaluation forms. Primary outcomes include Medication Assisted Treatment (MAT) initiation and non-fatal overdose; secondary outcomes include MAT retention and fatal overdose. Quantitative hypotheses will be tested using generalized linear mixed effects models, Bayesian hierarchical models, and marginal Cox models. Qualitative interview data will be analyzed using an inductive thematic analysis procedure. Discussion It is impossible to conduct a randomized controlled trial of the effectiveness of the MROTs, given the ethical and logistical considerations of this intervention. This study’s innovative design employs a mixed methods formative phase to examine feasibility and acceptability, and a quasi-experimental outcomes evaluation phase employing advanced statistical methods to mitigate bias and suggest causal inference regarding the effectiveness of the MROTs. Innovative interventions have been deployed in many states; evidence regarding their effectiveness is lacking, but critical to informing an effective public health response to the opioid epidemic.

Beschreibung: Stay-at-home orders and shutdowns of non-essential businesses are powerful, but socially costly, tools to control the pandemic spread of SARS-CoV-2. Mass testing strategies, which rely on widely administered frequent and rapid diagnostics to identify and isolate infected individuals, could be a potentially less disruptive management strategy, particularly where vaccine access is limited. In this paper, we assess the extent to which mass testing and isolation strategies can reduce reliance on socially costly non-pharmaceutical interventions, such as distancing and shutdowns. We develop a multi-compartmental model of SARS-CoV-2 transmission incorporating both preventative non-pharmaceutical interventions (NPIs) and testing and isolation to evaluate their combined effect on public health outcomes. Our model is designed to be a policy-guiding tool that captures important realities of the testing system, including constraints on test administration and non-random testing allocation. We show how strategic changes in the characteristics of the testing system, including test administration, test delays, and test sensitivity, can reduce reliance on preventative NPIs without compromising public health outcomes in the future. The lowest NPI levels are possible only when many tests are administered and test delays are short, given limited immunity in the population. Reducing reliance on NPIs is highly dependent on the ability of a testing program to identify and isolate unreported, asymptomatic infections. Changes in NPIs, including the intensity of lockdowns and stay at home orders, should be coordinated with increases in testing to ensure epidemic control; otherwise small additional lifting of these NPIs can lead to dramatic increases in infections, hospitalizations and deaths. Importantly, our results can be used to guide ramp-up of testing capacity in outbreak settings, allow for the flexible design of combined interventions based on social context, and inform future cost-benefit analyses to identify efficient pandemic management strategies.

Beschreibung: Aims Impaired renal function is a major contributor to the low proportion of mineralocorticoid receptor antagonist (MRA) treatment in patients with heart failure with reduced ejection fraction (HFrEF). Our aims were to investigate the impact of MRA treatment on all-cause mortality and worsening renal function (WRF) in patients with HFrEF and moderately impaired renal function. Methods Retrospective data between 2010–2018 on HFrEF patients from a single-centre hospital with estimated glomerular renal function (eGFR) 〈 60 ml/min/1.73 m2 were analysed. WRF was defined as a decline of by eGFR ≥ 20%. Results 416 patients were included, 131 patients on MRA and 285 without MRA, mean age was 77 years (SD ± 9) and 82 years (SD ± 9), respectively. Median follow-up was 2 years. 128 patients (32%) experienced WRF, 25% in the MRA group and 30% in patients without MRA (p = 0.293). In multivariable analysis, hospitalization for heart failure and systolic blood pressure were associated with WRF (p = 0.015 and p =

Beschreibung: Background Pharmaceuticals wastes are drugs and medicines that can no longer be used. The improper disposal of unused medicines is a growing problem throughout the world. This study assessed the pharmaceutical wastage rate and pharmaceutical waste management for the year 2015 to 2017 in the public health facility of Dessie, Ethiopia. Methodology A cross-section study design was used to review logistic data retrospectively from health commodity management information systems and manual records in 8 health facilities. Health professionals’ (135) pharmaceutical waste management practices were assessed using the world health organization waste management checklist. Descriptive and inferential statistics were made using a statistical package for social sciences version 20. Result Supplies were the leading class of pharmaceuticals with an overall wastage rate of 37.1%. Tablet and injectable constituted the highest class of pharmaceuticals dosage form with the overall wastage rate of 20.78% and 16.49%. The overall pharmaceutical wastage rate was 3.68% amounting to USD 159,762.66 and expiry (92.05%) was the major reason for wastage. The pharmaceutical wastage rate of health centers was nearly twofold higher than hospitals. Pharmaceutical waste management was practiced by 105 (77%; 95% CI; 69.9%, 84.9%) health professionals. Determinants of pharmaceutical waste management were being male (P value = 0.08, AOR = 3.72), receiving training (P value = 0.01, AOR = 4.34), writing label (P value = 0.02, AOR = 5.04), storage of segregated waste in dispensing unit (P value = 0.01, AOR = 0.72) and the presence of disposal plan (P value = 0.002, AOR = 16.93). Conclusions Supplies and tablets constituted the highest wastage class of pharmaceuticals and dosage form. The pharmaceutical wastage rate was higher than the standard and increasing in successive years. Pharmaceutical waste management was not fully practiced. Appropriate inventory control and waste management are recommended.

Beschreibung: Wilms tumor-1-interacting protein (Wtip) is a LIM-domain-containing adaptor that links cell junctions with actomyosin complexes and modulates actomyosin contractility and ciliogenesis in Xenopus embryos. The Wtip C-terminus with three LIM domains associates with the actin-binding protein Shroom3 and modulates Shroom3-induced apical constriction in ectoderm cells. By contrast, the N-terminal domain localizes to apical junctions in the ectoderm and basal bodies in skin multiciliated cells, but its interacting partners remain largely unknown. Targeted proximity biotinylation (TPB) using anti-GFP antibody fused to the biotin ligase BirA identified SSX2IP as a candidate protein that binds GFP-WtipN. SSX2IP, also known as Msd1 or ADIP, is a component of cell junctions, centriolar satellite protein and a targeting factor for ciliary membrane proteins. WtipN physically associated with SSX2IP and the two proteins readily formed mixed aggregates in overexpressing cells. By contrast, we observed only partial colocalization of full length Wtip and SSX2IP, suggesting that Wtip adopts a ‘closed’ conformation in the cell. Furthermore, the double depletion of Wtip and SSX2IP in early embryos uncovered the functional interaction of the two proteins during neural tube closure. Our results suggest that the association of SSX2IP and Wtip is essential for cell junction remodeling and morphogenetic processes that accompany neurulation. We propose that TPB can be a general approach that is applicable to other GFP-tagged proteins.