Adult zebrafish as advanced models of human disease

Modelling adult diseases to understand their aetiology and progression, and to develop new therapies, is a major challenge for medical biology. We are excited by new efforts in the zebrafish community to develop models of adult diseases that range from cancer to heart, infectious and age-related diseases, and those that relate to toxicology and complex social behaviours. Here, we discuss some of the advances in the field of zebrafish models of adult disease, and where we see opportunities and challenges ahead

Trehalose Is A Chemical Attractant In The Establishment Of Coral Symbiosis

Coral reefs have evolved with a crucial symbiosis between photosynthetic dinoflagellates (genus Symbiodinium) and their cnidarian hosts (Scleractinians). Most coral larvae take up Symbiodinium from their environment; however, the earliest steps in this process have been elusive. Here we demonstrate that the disaccharide trehalose may be an important signal from the symbiont to potential larval hosts. Symbiodinium freshly isolated from Fungia scutaria corals constantly released trehalose (but not sucrose, maltose or glucose) into seawater, and released glycerol only in the presence of coral tissue. Spawning Fungia adults increased symbiont number in their immediate area by excreting pellets of Symbiodinium, and when these naturally discharged Symbiodinium were cultured, they also released trehalose. In Y-maze experiments, coral larvae demonstrated chemoattractant and feeding behaviors only towards a chamber with trehalose or glycerol. Concomitantly, coral larvae and adult tissue, but not symbionts, had significant trehalase enzymatic activities, suggesting the capacity to utilize trehalose. Trehalase activity was developmentally regulated in F. scutaria larvae, rising as the time for symbiont uptake occurs. Consistent with the enzymatic assays, gene finding demonstrated the presence of a trehalase enzyme in the genome of a related coral, Acropora digitifera, and a likely trehalase in the transcriptome of F. scutaria. Taken together, these data suggest that adult F. scutaria seed the reef with Symbiodinium during spawning and the exuded Symbiodinium release trehalose into the environment, which acts as a chemoattractant for F. scutaria larvae and as an initiator of feeding behavior- the first stages toward establishing the coral-Symbiodinium relationship. Because trehalose is a fixed carbon compound, this cue would accurately demonstrate to the cnidarian larvae the photosynthetic ability of the potential symbiont in the ambient environment. To our knowledge, this is the first report of a chemical cue attracting the motile coral larvae to the symbiont

Is the observed high-frequency radio luminosity distribution of QSOs bimodal?

The distribution of QSO radio luminosities has long been debated in the literature. Some argue that it is a bimodal distribution, implying that there are two separate QSO populations (normally referred to as 'radio-loud' and 'radio-quiet'), while others claim it forms a more continuous distribution characteristic of a single population. We use deep observations at 20 GHz to investigate whether the distribution is bimodal at high radio frequencies. Carrying out this study at high radio frequencies has an advantage over previous studies as the radio emission comes predominantly from the core of the AGN, hence probes the most recent activity. Studies carried out at lower frequencies are dominated by the large scale lobes where the emission is built up over longer timescales (10^7-10^8 yrs), thereby confusing the sample. Our sample comprises 874 X-ray selected QSOs that were observed as part of the 6dF Galaxy Survey. Of these, 40% were detected down to a 3 sigma detection limit of 0.2-0.5 mJy. No evidence of bimodality is seen in either the 20 GHz luminosity distribution or in the distribution of the R_20 parameter: the ratio of the radio to optical luminosities traditionally used to classify objects as being either radio-loud or radio-quiet. Previous results have claimed that at low radio luminosities, star formation processes can dominate the radio emission observed in QSOs. We attempt to investigate these claims by stacking the undetected sources at 20 GHz and discuss the limitations in carrying out this analysis. However, if the radio emission was solely due to star formation processes, we calculate that this corresponds to star formation rates ranging from ~10 solar masses/yr to ~2300 solar masses/yr.Comment: 13 pages, 11 figures. Accepted for publication in Ap

Lower Postsurgical Mortality for Individuals with Dementia with Better-Educated Hospital Workforce

Surgical patients age 65 and over with Alzheimer’s disease and related dementias (ADRD) were more likely to die within 30 days of admission and to die after a complication than those without ADRD. Having better-educated nurses in the hospital improved the likelihood of good outcomes for all surgical patients, but had a much greater effect in individuals with ADRD. Specifically, a 10% increase in the proportion of nurses with a Bachelor of Science in Nursing (BSN) degree or higher was associated with 10% lower odds of death and 10% lower odds of dying after a complication for surgical patients with ADRD

“All the Men Here Have the Peter Pan Syndrome— They Don’t Want to Grow Up”: Navajo Adolescent Mothers’ Intimate Partner Relationships—A 15-Year Perspective

In 1992 and 1995, data were collected from 29 Navajo Native American adolescent mothers. In 2007 and 2008, data were collected from 21 of the original 29 (72%). Guided by feminist family theory, this investigation sought to (a) examine Navajo adolescent mothers’ intimate partner relationships during the transition to parenthood, (b) identify themes in the young mothers’ intimate partnerships across time, and (c) assess participants’ psychosocial well-being in adulthood. Four themes emerged in the women’s long-term intimate relationships: limited support, substance abuse, infidelity, and intimate partner violence. Implications of the findings and suggestions for future research are discussed

What is the prevalence, and what are the clinical correlates, of insulin resistance in young people presenting for mental health care? A cross-sectional study

Objectives: To report the distribution and predictors of insulin resistance (IR) in young people presenting to primary care-based mental health services. Design: Cross-sectional. Setting: Headspace-linked clinics operated by the Brain and Mind Centre of the University of Sydney. Participants: 768 young people (66% female, mean age 19.7±3.5, range 12–30 years). Main outcome measures: IR was estimated using the updated homeostatic model assessment (HOMA2-IR). Height and weight were collected from direct measurement or self-report for body mass index (BMI). Results: For BMI, 20.6% of the cohort were overweight and 10.2% were obese. However,6.9 mmol/L). By contrast, 9.9% had a HOMA2-IR score \u3e2.0 (suggesting development of IR) and 11.7% (n=90) had a score between 1.5 and 2. Further, there was a positive correlation between BMI and HOMA2-IR (r=0.44, p Conclusions: Emerging IR is evident in a significant subgroup of young people presenting to primary care based mental health services. While the major modifiable risk factor is BMI, a large proportion of the variance is not accounted for by other demographic, clinical or treatment factors. Given the early emergence of IR, secondary prevention interventions may need to commence prior to the development of full-threshold or major mood or psychotic disorders

Measuring the Impact of the Affordable Care Act Medicaid Expansion on Access to Primary Care Using an Interrupted Time Series Approach

BACKGROUND: The Patient Protection and Affordable Care Act of 2010, commonly referred to as the Affordable Care Act (ACA), was created to increase access to primary care, improve quality of care, and decrease healthcare costs. A key provision in the law that mandated expansion of state Medicaid programme changed when states were given the option to voluntarily expand Medicaid. Our study sought to measure the impact of ACA Medicaid expansion on preventable hospitalization (PH) rates, a measure of access to primary care. METHODS: We performed an interrupted time series analysis of quarterly hospitalization rates across eight states from 2012 to 2015. Segmented regression analysis was utilized to determine the impact of policy reform on PH rates. RESULTS: The Affordable Care Act\u27s Medicaid expansion led to decreased rates of PH (improved access to care); however, the finding was not significant (coefficient estimate: -0.0059, CI -0.0225, 0.0107, p = 0.4856). Healthcare system characteristics, such as Medicaid spending per enrollee and Medicaid income eligibility, were associated with a significant decrease in rates of PH (improved access to care). However, the Medicaid-to-Medicare fee index (physician reimbursement) and states with a Democratic state legislature had a significant increase in rates of PH (poor access to care). CONCLUSION: Health policy reform and healthcare delivery characteristics impact access to care. Researchers should continue evaluating such policy changes across more states over longer periods of time. Researchers should translate these findings into cost analysis for state policy-makers to make better-informed decisions for their constituents. CONTRIBUTION TO KNOWLEDGE: Ambulatory care-sensitive conditions are a feasible method for evaluating policy and measuring access to primary care. Policy alone cannot improve access to care. Other factors (trust, communication, policy-makers\u27 motivations and objectives, etc.) must be addressed to improve access

Caspase-3, myogenic transcription factors and cell cycle inhibitors are regulated by leukemia inhibitory factor to mediate inhibition of myogenic differentiation

<p>Abstract</p> <p>Background</p> <p>Leukemia inhibitory factor (LIF) is known to inhibit myogenic differentiation as well as to inhibit apoptosis and caspase-3 activation in non-differentiating myoblasts. In addition caspase-3 activity is required for myogenic differentiation. Therefore the aim of this study was to further investigate mechanisms of the differentiation suppressing effect of LIF in particular the possibility of a caspase-3 mediated inhibition of differentiation.</p> <p>Results</p> <p>LIF dependent inhibition of differentiation appeared to involve several mechanisms. Differentiating myoblasts that were exposed to LIF displayed increased transcripts for c-fos. Transcripts for the cell cycle inhibitor p21 as well as muscle regulatory factors myoD and myogenin were decreased with LIF exposure. However, LIF did not directly induce a proliferative effect under differentiation conditions, but did prevent the proportion of myoblasts that were proliferating from decreasing as differentiation proceeded. LIF stimulation decreased the percentage of cells positive for active caspase-3 occurring during differentiation. Both the effect of LIF inhibiting caspase-3 activation and differentiation appeared dependent on mitogen activated protein kinase and extracellular signal regulated kinase kinase (MEK) signalling. The role of LIF in myogenic differentiation was further refined to demonstrate that myoblasts are unlikely to secrete LIF endogenously.</p> <p>Conclusions</p> <p>Altogether this study provides a more comprehensive view of the role of LIF in myogenic differentiation including LIF and receptor regulation in myoblasts and myotubes, mechanisms of inhibition of differentiation and the link between caspase-3 activation, apoptosis and myogenic differentiation.</p

“I felt really respected and I know she felt respected too”: Using Youth-Adult Partnerships to Promote Positive Youth Development in 4-H Youth

Youth-adult relationships exist on a continuum from adult-led to youth-led collaborations. However, research suggests that quality youth-adult partnerships, which fall in the middle of this continuum, directly contribute to positive youth development. Given this, the current study evaluated the impact of a 4-H Youth Development program, using youth-adult partnerships and a teens as teachers program model, on positive youth development outcomes of participating youth. Qualitative data were collected from 29 youth to evaluate the 4-H Food Smart Families program presented by Washington State University Youth Advocates for Health (YA4-H!). Data analysis identified themes related to the benefits and challenges of the youth-adult partnership and skills gained from being a teen teacher. When looking at results from a positive youth development perspective, it is evident the youth who participated in youth-adult partnerships and as teen teachers experienced beneficial outcomes. Qualitative codes clearly aligned with 4-H Essential Elements of belonging, mastery, independence, and generosity, indicating positive youth development had occurred despite realworld implementation challenges. Based on our experience and lessons learned, we conclude with suggestions for successful implementation of a youth-adult partnership

Modulus variation of composite graphite electrodes in lithium-ion batteries during electrochemical cycling

Graphite is currently the most common anode material used in commercial lithium-ion batteries. During battery charging and discharging processes, lithium ions intercalate into and deintercalate from graphite, forming several distinct stages of graphite-lithium intercalation compounds (G-LICs). Each stage of G-LIC has a unique spacing between graphene layers, with the spacing increasing for increasing lithium content. In graphite-based composite electrodes (graphite particles in a porous polymer matrix), the changing layer spacing leads to stress and strain evolution on the composite length scale. In two separate experiments, we use substrate-curvature measurements to monitor stress changes in a thin electrode constrained on an inert, rigid substrate, and we use digital image correlation to track strain changes in a free-standing, unconstrained electrode. Combining the in-situ stress and strain analyses enables us to extract the change in the apparent modulus of the composite graphite electrode as a function of electrode potential and lithium content. As expected, we found that constrained electrodes develop compressive stress during lithiation (~10 MPa) and that unconstrained electrodes undergo free expansion (~1.5% linear strain). Interestingly, the apparent modulus of the electrode increases the most significantly during the formation of the dilute stage I compound, increases slightly with the formation of the stage IV, dilute stage II, and stage II compounds, and then decreases with the formation of the stage I compound (LiC 6). During delithiation, unconstrained electrodes contract, recovering nearly their original size. In constrained electrodes during delithation, however, the compressive stress is first relaxed, and then a tensile stress develops and is subsequently relaxed. The tensile stress leads to an apparent softening of the composite electrode over a broad range of electrode potential and capacity. At the end of one complete lithiation/delithiation cycle, the apparent modulus returns to approximately its original value. The evolution of stress, strain, and modulus data provides quantitative information on the coupled electro-chemo-mechanical response of battery electrodes and insight on material strategies to increase battery reliability