Transitions in the morphological features, habitat use, and diet of young-of-the-year goosefish (Lophius americanus)

This study was designed to improve our understanding of transitions in the early life history and the distribution, habitat use, and diets for young-of-the-year (YOY) goosefish (Lophius americanus) and, as a result, their role in northeastern U.S. continental shelf ecosystems. Pelagic juveniles (>12 to ca. 50 mm total length [TL]) were distributed over most portions of the continental shelf in the Middle Atlantic Bight, Georges Bank, and into the Gulf of Maine. Most individuals settled by 50−85 mm TL and reached approximately 60−120 mm TL by one year of age. Pelagic YOY fed on chaetognaths, hyperiid amphipods, calanoid copepods, and ostracods, and benthic YOY had a varied diet of fishes and benthic crustaceans. Goosefish are widely scattered on the continental shelf in the Middle Atlantic Bight during their early life history and once settled, are habitat generalists, and thus play a role in many continental shelf habi

An Evaluation of a Brief School-Based Cognitive Behavioural Therapy Programme for Children with ASD

Autistic Spectrum Disorder (ASD) is characterised by difficulties with\ud social interactions, communication and rigid / stereotyped\ud behaviours, with a prevalence of around 1% within the population.\ud Research has shown that children with ASD also have heightened\ud feelings of anxiety compared to typically developing peers,\ud particularity with social anxiety.\ud Cognitive Behavioural Therapy (CBT) has empirical evidence that\ud demonstrates its efficacy in supporting children with ASD to manage\ud their anxiety. However, these studies have only shown improvements\ud in the children's anxiety using standardised questionnaires. As such,\ud it is difficult to infer whether the gains made using CBT are long-term,\ud or whether it leads to a qualitative improvement in children's\ud interactions with their community. Typically, CBT is typically delivered\ud by Child and Adolescent Mental Health Services, which can be\ud inaccessible to some children and their families.\ud This study employed a mixed methods approach to understand the\ud effectiveness of a six week, group administered, secondary schoolbased\ud CBT programme. 28 children took part in the research, with 14\ud in the treatment-as-usual group and 14 in the experimental group. All\ud children completed the Wechsler Abbreviated Scale of Intelligence,\ud the Social Responsiveness Scale, Spence Children's Anxiety Scale -\ud parent and child versions (SCAS-P/C), the Coping Scale for Children\ud and Youth (CSCY). Qualitative data was also collected through\ud parent and child interviews using a semi-structured technique. Postintervention\ud data consisted of the SCAS-P/C and the CSCY and\ud further parent and child interviews. Follow-up measures were taken\ud six to eight weeks after post-intervention using the SCAS-Parent and\ud child versions and the CSCY.\ud Results suggest children who took part in the intervention had\ud reduced levels of anxiety compared to the TaU group, both at post —\ud intervention and follow-up. However, these improvements were not at a clinically significant level. Interview data, analysed using Thematic\ud Analysis, provided unique insight into the process of cognitive\ud change, the nature of anxiety in children with ASD and highlighted\ud potential barriers to change for these children. Furthermore, the\ud parents identified a lack of post diagnostic support and the view of\ud their child's constantly changing profile of needs.\ud The results are related to their implications for the professional\ud educational psychologist, who is considered to be well placed to\ud respond to the identified needs of this group and to implement CBT\ud programmes in schools. Methodological issues and weaknesses are\ud discussed as well as implications for further study

Nod1 signaling overcomes resistance of S. pneumoniae to opsonophagocytic killing

Airway infection by the Gram-positive pathogen Streptococcus pneumoniae (Sp) leads to recruitment of neutrophils but limited bacterial killing by these cells. Co-colonization by Sp and a Gram-negative species, Haemophilus influenzae (Hi), provides sufficient stimulus to induce neutrophil and complement-mediated clearance of Sp from the mucosal surface in a murine model. Products from Hi, but not Sp, also promote killing of Sp by ex vivo neutrophil-enriched peritoneal exudate cells. Here we identify the stimulus from Hi as its peptidoglycan. Enhancement of opsonophagocytic killing was facilitated by signaling through nucleotide-binding oligomerization domain-1 (Nod1), which is involved in recognition of γ-D-glutamyl-meso-diaminopimelic acid (meso-DAP) contained in cell walls of Hi but not Sp. Neutrophils from mice treated with Hi or compounds containing meso-DAP, including synthetic peptidoglycan fragments, showed increased Sp killing in a Nod1-dependent manner. Moreover, Nod1-/- mice showed reduced Hi-induced clearance of Sp during co-colonization. These observations offer insight into mechanisms of microbial competition and demonstrate the importance of Nod1 in neutrophil-mediated clearance of bacteria in vivo

Absence of p53 in Clara cells favours multinucleation and loss of cell cycle arrest

BACKGROUND: The p53 oncosuppressor protein is a critical mediator of the response to injury in mammalian cells and is mutationally inactivated in the majority of lung malignancies. In this analysis, the effects of p53-deficiency were investigated in short-term primary cultures of murine bronchiolar Clara cells. Clara cells, isolated from gene-targeted p53-deficient mice, were compared to cells derived from wild type littermates. RESULTS: p53 null cultures displayed abnormal morphology; specifically, a high incidence of multinucleation, which increased with time in culture. Multinucleated cells were proficient in S phase DNA synthesis, as determined by BrdU incorporation. However, multinucleation did not reflect altered rates of S phase synthesis, which were similar between wild type and p53-/- cultures. Nucleation defects in p53-/- Clara cells associated with increased centrosome number, as determined by confocal microscopy of pericentrin-stained cultures, and may highlight a novel role of p53 in preserving genomic integrity in lung epithelial cells. Effects of p53-deficiency were also studied following exposure to DNA damage. A p53-dependent reduction in the BrdU index was observed in Clara cells following ionizing radiation. The reduction in BrdU index in wild type cells displayed serum-dependency, and occurred only in the absence of serum. Taken together, these findings demonstrate that in murine primary Clara cell culture, cell cycle arrest is a p53-mediated response to DNA damage, and that extracellular factors, such as serum, influence this response. CONCLUSION: These findings highlight functions of wild type p53 protein in bipolar spindle formation, centrosome regulation, and growth control in bronchiolar Clara cells

Phosphorylation of actopaxin regulates cell spreading and migration

Actopaxin is an actin and paxillin binding protein that localizes to focal adhesions. It regulates cell spreading and is phosphorylated during mitosis. Herein, we identify a role for actopaxin phosphorylation in cell spreading and migration. Stable clones of U2OS cells expressing actopaxin wild-type (WT), nonphosphorylatable, and phosphomimetic mutants were developed to evaluate actopaxin function. All proteins targeted to focal adhesions, however the nonphosphorylatable mutant inhibited spreading whereas the phosphomimetic mutant cells spread more efficiently than WT cells. Endogenous and WT actopaxin, but not the nonphosphorylatable mutant, were phosphorylated in vivo during cell adhesion/spreading. Expression of the nonphosphorylatable actopaxin mutant significantly reduced cell migration, whereas expression of the phosphomimetic increased cell migration in scrape wound and Boyden chamber migration assays. In vitro kinase assays demonstrate that extracellular signal-regulated protein kinase phosphorylates actopaxin, and treatment of U2OS cells with the MEK1 inhibitor UO126 inhibited adhesion-induced phosphorylation of actopaxin and also inhibited cell migration

A data-driven review of thermoelectric materials: Performance and resource considerations

In this review, we describe the creation of a large database of thermoelectric materials prepared by abstracting information from over 100 publications. The database has over 18,000 data points from multiple classes of compounds, whose relevant properties have been measured at several temperatures. Appropriate visualization of the data immediately allows certain insights to be gained with regard to the property space of plausible thermoelectric materials. Of particular note is that any candidate material needs to display an electrical resistivity value that is close to 1 mΩcm at 300 K, i.e., samples should be significantly more conductive than the Mott minimum metallic conductivity. The Herfindahl-Hirschman index, a commonly accepted measure of market concentration, has been calculated from geological data (known elemental reserves) and geopolitical data (elemental production) for much of the periodic table. The visualization strategy employed here allows rapid sorting of thermoelectric compositions with respect to important issues of elemental scarcity and supply risk.Engineering and Applied Science

Interplay between partner and ligand facilitates the folding and binding of an intrinsically disordered protein.

Protein-protein interactions are at the heart of regulatory and signaling processes in the cell. In many interactions, one or both proteins are disordered before association. However, this disorder in the unbound state does not prevent many of these proteins folding to a well-defined, ordered structure in the bound state. Here we examine a typical system, where a small disordered protein (PUMA, p53 upregulated modulator of apoptosis) folds to an α-helix when bound to a groove on the surface of a folded protein (MCL-1, induced myeloid leukemia cell differentiation protein). We follow the association of these proteins using rapid-mixing stopped flow, and examine how the kinetic behavior is perturbed by denaturant and carefully chosen mutations. We demonstrate the utility of methods developed for the study of monomeric protein folding, including β-Tanford values, Leffler α, Φ-value analysis, and coarse-grained simulations, and propose a self-consistent mechanism for binding. Folding of the disordered protein before binding does not appear to be required and few, if any, specific interactions are required to commit to association. The majority of PUMA folding occurs after the transition state, in the presence of MCL-1. We also examine the role of the side chains of folded MCL-1 that make up the binding groove and find that many favor equilibrium binding but, surprisingly, inhibit the association process.This is the final version. It was first published online by PNAS via http://dx.doi.org/10.1073/pnas.140912211

Restriction endonuclease TseI cleaves A:A and T:T mismatches in CAG and CTG repeats.

The type II restriction endonuclease TseI recognizes the DNA target sequence 5'-G^CWGC-3' (where W = A or T) and cleaves after the first G to produce fragments with three-base 5'-overhangs. We have determined that it is a dimeric protein capable of cleaving not only its target sequence but also one containing A:A or T:T mismatches at the central base pair in the target sequence. The cleavage of targets containing these mismatches is as efficient as cleavage of the correct target sequence containing a central A:T base pair. The cleavage mechanism does not apparently use a base flipping mechanism as found for some other type II restriction endonuclease recognizing similarly degenerate target sequences. The ability of TseI to cleave targets with mismatches means that it can cleave the unusual DNA hairpin structures containing A:A or T:T mismatches formed by the repetitive DNA sequences associated with Huntington's disease (CAG repeats) and myotonic dystrophy type 1 (CTG repeats)

Addition of abiraterone to first-line long-term hormone therapy in prostate cancer (STAMPEDE): Model to estimate long-term survival, quality-adjusted survival, and cost-effectiveness

Background: Results from randomised trials show adding abiraterone acetate plus prednisolone (AAP) to standard of care (SOC) improves disease-free and overall survival in men with prostate cancer (PC) starting long-term hormone therapy for first time. Formal assessment is required of whether funding AAP here shows appropriate use of resources. This cost-effectiveness decision model tests if giving AAP to these patients is cost-effective using costs from English National Health Service, the largest nation where STAMPEDE recruited. / Methods: Health outcomes and costs were modelled using patient data from AAP comparison of STAMPEDE (recruitment 2011-14). This included 1917 men with high-risk, locally advanced metastatic or recurrent PC starting 1st-line hormone therapy. SOC was hormone therapy for ≥2 years with radiotherapy in pre-selected patients. If allocated to research group, AAP (AA 1000mg/day, P 5mg/day) was added to SOC. The model makes lifetime predictions of survival, costs and quality-adjusted lifeyears (QALYs), with costs and QALYs discounted at 3.5% annually. Sensitivity analyses were performed. / Results: The model predicted AAP would extend survival (discounted quality-adjusted survival) by 2.68y (1.46 QALYs) for metastatic patients and 0.30y (0.29 QALYs) for non-metastatic. The cost of AAP means it is not currently cost-effective in this setting, including with Patient Access Scheme costs for AAP and enzalutamide and similar reductions for cabazitaxel and Ra. If AAP’s price reduces after patent expiry as expected (90% reduction on BNF cost), it would be cost-effective in both patient groups, with incremental cost-effectiveness ratios below £10,000 (US$12,665) per QALY. AAP could also dominate in non-metastatic patients (i.e. lower costs and higher QALYs than SOC alone). / Conclusions: AAP could be cost-effective for patients with non-metastatic and metastatic disease with expected future pricing and may be cost-saving in the former. Policymakers should encourage license submissions and generic price reductions to facilitate use of AAP given cost-saving potential in addition to improving survival. / Clinical trial information: NCT00268476