Learning to Swim: What Influences Success?

Swimming and water safety skills are important life skills, particularly in Australia, where aquatic activities are regularly enjoyed. Little research has been undertaken exploring children’s swimming and water safety skills, what level they can achieve, and what factors impact their ability to learn these skills. This study explores children aged 5-12 years who participated in the Australian Capital Territory Primary Schools Swim and Survive Program, 2009-2011. Children who were more likely to achieve higher levels were older, were female, attended private school, swam at least once a fortnight, had a swimming pool at home, or visited a public swimming pool. Those who were less likely were Aboriginal or Torres Strait Islander, had a negative experience, and swam less than once a fortnight

Probing Star Formation at Low Metallicity: The Radio Emission of Super Star Clusters in SBS0335-052

We present high-resolution radio continuum observations of the nascent starburst in the metal-poor galaxy SBS 0335-052. These radio data were taken with the Very Large Array and include observations at 0.7cm, 1.3cm, 2cm, 3.6cm, and 6cm. These observations enable us to probe the thermal radio nebulae associated with the extremely young star-forming regions in this galaxy. Two discrete and luminous star-forming regions are detected in the south of the galaxy that appear to be associated with massive star clusters previously identified at optical wavelengths. However, the remaining optically-identified massive star clusters are not clearly associated with radio emission (either thermal or non-thermal) down to the sensitivity limits of these radio data. The spectral energy distributions of the two radio-detected clusters are consistent with being purely thermal, and the entire region has an inferred ionizing flux of ~1.2 x 10^ 53 s^-1, which is equivalent to ~12,000 "typical" O-type stars (type O7.5 V). The observations presented here have resolved out a significant contribution from diffuse non-thermal emission detected previously, implying a previous episode of significant star formation. The current star formation rate (SFR) for this southern region alone is ~1.3 M_sun yr^-1, or ~ 23M_sun yr^-1 kpc^-2. This SFR derived from thermal radio emission also suggests that previous optical recombination line studies are not detecting a significant fraction of the current star formation in SBS 0335-052. From model fits to the radio spectral energy distribution, we infer a global mean density in the two youngest clusters of n_e > 10^3-10^4 cm^-3. In addition, a comparison between the compact and diffuse radio emission indicates that up to ~50% of the ionizing flux could be leaking out of the compact HII regions.Comment: accepted AJ, 14 pages, 5 figure

Increased Expression of Cytotoxic T-Lymphocyte-Associated Protein 4 by T Cells, Induced by B7 in Sera, Reduces Adaptive Immunity in Patients With Acute Liver Failure.

BACKGROUND & AIMS: Patients with acute liver failure (ALF) have defects in innate immune responses to microbes (immune paresis) and are susceptible to sepsis. Cytotoxic T-lymphocyte-associated protein 4 (CTLA4), which interacts with the membrane receptor B7 (also called CD80 and CD86), is a negative regulator of T-cell activation. We collected T cells from patients with ALF and investigated whether inhibitory signals down-regulate adaptive immune responses in patients with ALF. METHODS: We collected peripheral blood mononuclear cells from patients with ALF and controls from September 2013 through September 2015 (45 patients with ALF, 20 patients with acute-on-chronic liver failure, 15 patients with cirrhosis with no evidence of acute decompensation, 20 patients with septic shock but no cirrhosis or liver disease, and 20 healthy individuals). Circulating CD4+ T cells were isolated and analyzed by flow cytometry. CD4+ T cells were incubated with antigen, or agonist to CD3 and dendritic cells, with or without antibody against CTLA4; T-cell proliferation and protein expression were quantified. We measured levels of soluble B7 molecules in supernatants of isolated primary hepatocytes, hepatic sinusoidal endothelial cells, and biliary epithelial cells from healthy or diseased liver tissues. We also measured levels of soluble B7 serum samples from patients and controls, and mice with acetaminophen-induced liver injury using enzyme-linked immunosorbent assays. RESULTS: Peripheral blood samples from patients with ALF had a higher proportion of CD4+ CTLA4+ T cells than controls; patients with infections had the highest proportions. CD4+ T cells from patients with ALF had a reduced proliferative response to antigen or CD3 stimulation compared to cells from controls; incubation of CD4+ T cells from patients with ALF with an antibody against CTLA4 increased their proliferative response to antigen and to CD3 stimulation, to the same levels as cells from controls. CD4+ T cells from controls up-regulated expression of CTLA4 after 24-48 hours culture with sera from patients with ALF; these sera were found to have increased concentrations of soluble B7 compared to sera from controls. Necrotic human primary hepatocytes exposed to acetaminophen, but not hepatic sinusoidal endothelial cells and biliary epithelial cells from patients with ALF, secreted high levels of soluble B7. Sera from mice with acetaminophen-induced liver injury contained high levels of soluble B7 compared to sera from mice without liver injury. Plasma exchange reduced circulating levels of soluble B7 in patients with ALF and expression of CTLA4 on T cells. CONCLUSIONS: Peripheral CD4+ T cells from patients with ALF have increased expression of CTLA4 compared to individuals without ALF; these cells have a reduced response to antigen and CD3 stimulation. We found sera of patients with ALF and from mice with liver injury to have high concentrations of soluble B7, which up-regulates CTLA4 expression by T cells and reduces their response to antigen. Plasma exchange reduces levels of B7 in sera from patients with ALF and might be used to restore antimicrobial responses to patients

Exercise training results in depot-specific adaptations to adipose tissue mitochondrial function

We assessed differences in mitochondrial function in gluteal (gSAT) and abdominal subcutaneous adipose tissue (aSAT) at baseline and in response to 12-weeks of exercise training; and examined depot-specific associations with body fat distribution and insulin sensitivity (S-I). Obese, black South African women (n = 45) were randomized into exercise (n = 23) or control (n = 22) groups. Exercise group completed 12-weeks of aerobic and resistance training (n = 20), while the control group (n = 15) continued usual behaviours. Mitochondrial function (high-resolution respirometry and fluorometry) in gSAT and aSAT, SI (frequently sampled intravenous glucose tolerance test), body composition (dual-energy X-ray absorptiometry), and ectopic fat (MRI) were assessed pre- and post-intervention. At baseline, gSAT had higher mitochondrial respiratory capacity and hydrogen peroxide (H2O2) production than aSAT (p < 0.05). Higher gSAT respiration was associated with higher gynoid fat (p < 0.05). Higher gSAT H2O2 production and lower aSAT mitochondrial respiration were independently associated with lower SI (p < 0.05). In response to training, S-I improved and gynoid fat decreased (p < 0.05), while H2O2 production reduced in both depots, and mtDNA decreased in gSAT (p < 0.05). Mitochondrial respiration increased in aSAT and correlated with a decrease in body fat and an increase in soleus and hepatic fat content (p < 0.05). This study highlights the importance of understanding the differences in mitochondrial function in multiple SAT depots when investigating the pathophysiology of insulin resistance and associated risk factors such as body fat distribution and ectopic lipid deposition. Furthermore, we highlight the benefits of exercise training in stimulating positive adaptations in mitochondrial function in gluteal and abdominal SAT depots

Emerging Massive Star Clusters Revealed: High Resolution Imaging of NGC 4449 from the Radio to the Ultraviolet

We present a multi-wavelength study of embedded massive clusters in the nearby (3.9 Mpc) starburst galaxy NGC 4449 in an effort to uncover the earliest phases of massive cluster evolution. By combining high resolution imaging from the radio to the ultraviolet, we reveal these clusters in the process of emerging from their gaseous and dusty birth cocoons. We use Very Large Array (VLA) observations at centimeter wavelengths to identify young clusters surrounded by ultra-dense HII regions, detectable via their production of thermal free-free radio continuum. Ultraviolet, optical and infrared observations are obtained from the Hubble and Spitzer Space Telescope archives for comparison. We detect 39 compact radio sources towards NGC 4449 at 3.6 cm using the highest resolution (1.3") and sensitivity (RMS ~ 12 uJy) VLA image of the galaxy to date. We reliably identify 13 thermal radio sources and their physical properties are derived using both nebular emission from the HII regions and SED fitting to the stellar continuum. These radio detected clusters have ages < 5 Myr and stellar masses of order 10^4 Msun. The measured extinctions are quite low: 12 of the 13 thermal radio sources have Av < 1.5, while the most obscured source has Av ~ 4.3. By combining results from the nebular and stellar emission, we find an I-band excess that is anti-correlated with cluster age and an apparent mass-age correlation. Additionally, we find evidence that local processes such as supernovae and stellar winds are likely playing an important role in triggering the current bursts of star formation within NGC 4449.Comment: Accepted for publication in the Astronomical Journal. 20 pages, 14 figure

Effects of conjugated linoleic acid on myogenic and inflammatory responses in a human primary muscle and tumor coculture model

The antiproliferative and anti-inflammatory properties of conjugated linoleic acid (CLA) make it a potentially novel treatment in chronic inflammatory muscle wasting disease, particularly cancer cachexia. Human primary muscle cells were grown in coculture with MIA PaCa-2 pancreatic tumor cells and exposed to varying concentrations of c9,t11 and t10,c12 CLA. Expression of myogenic (Myf5, MyoD, myogenin, and myostatin) and inflammatory genes (CCL-2, COX-2, IL-8, and TNF-) were measured by real-time PCR. The t10,c12 CLA isomer, but not the c9,t11 isomer, significantly decreased MIA PaCa-2 proliferation by between 15% and 19%. There was a marked decrease in muscle MyoD and myogenin expression (78% and 62%, respectively), but no change in either Myf5 or myostatin, in myotubes grown in coculture with MIA PaCa-2 cells. CLA had limited influence on these responses. A similar pattern of myogenic gene expression changes was observed in myotubes treated with TNF- alone. Several-fold significant increases in CCL-2, COX-2, IL-8, and TNF- expression in myotubes were observed with MIA PaCa-2 coculture. The c9,t11 CLA isomer significantly decreased basal expression of TNF- in myotubes and could ameliorate its tumor-induced rise. The study provides insight into the anti-inflammatory and antiproliferative actions of CLA and its application as a therapeutic agent in inflammatory disease states.<br /

Development of a New Vaccine for the Prevention of Lassa Fever

BACKGROUND: Recent importation of Lassa fever into Germany, the Netherlands, the United Kingdom, and the United States by travelers on commercial airlines from Africa underscores the public health challenge of emerging viruses. Currently, there are no licensed vaccines for Lassa fever, and no experimental vaccine has completely protected nonhuman primates against a lethal challenge. METHODS AND FINDINGS: We developed a replication-competent vaccine against Lassa virus based on attenuated recombinant vesicular stomatitis virus vectors expressing the Lassa viral glycoprotein. A single intramuscular vaccination of the Lassa vaccine elicited a protective immune response in nonhuman primates against a lethal Lassa virus challenge. Vaccine shedding was not detected in the monkeys, and none of the animals developed fever or other symptoms of illness associated with vaccination. The Lassa vaccine induced strong humoral and cellular immune responses in the four vaccinated and challenged monkeys. Despite a transient Lassa viremia in vaccinated animals 7 d after challenge, the vaccinated animals showed no evidence of clinical disease. In contrast, the two control animals developed severe symptoms including rashes, facial edema, and elevated liver enzymes, and ultimately succumbed to the Lassa infection. CONCLUSION: Our data suggest that the Lassa vaccine candidate based on recombinant vesicular stomatitis virus is safe and highly efficacious in a relevant animal model that faithfully reproduces human disease

The Splicing Efficiency of Activating HRAS Mutations Can Determine Costello Syndrome Phenotype and Frequency in Cancer

Costello syndrome (CS) may be caused by activating mutations in codon 12/13 of the HRAS proto-oncogene. HRAS p.Gly12Val mutations have the highest transforming activity, are very frequent in cancers, but very rare in CS, where they are reported to cause a severe, early lethal, phenotype. We identified an unusual, new germline p.Gly12Val mutation, c.35_36GC>TG, in a 12-year-old boy with attenuated CS. Analysis of his HRAS cDNA showed high levels of exon 2 skipping. Using wild type and mutant HRAS minigenes, we confirmed that c.35_36GC>TG results in exon 2 skipping by simultaneously disrupting the function of a critical Exonic Splicing Enhancer (ESE) and creation of an Exonic Splicing Silencer (ESS). We show that this vulnerability of HRAS exon 2 is caused by a weak 3' splice site, which makes exon 2 inclusion dependent on binding of splicing stimulatory proteins, like SRSF2, to the critical ESE. Because the majority of cancer- and CS- causing mutations are located here, they affect splicing differently. Therefore, our results also demonstrate that the phenotype in CS and somatic cancers is not only determined by the different transforming potentials of mutant HRAS proteins, but also by the efficiency of exon 2 inclusion resulting from the different HRAS mutations. Finally, we show that a splice switching oligonucleotide (SSO) that blocks access to the critical ESE causes exon 2 skipping and halts proliferation of cancer cells. This unravels a potential for development of new anti-cancer therapies based on SSO-mediated HRAS exon 2 skipping