Posttranslational modifications of proteins in the pathobiology of medically relevant fungi

Peer reviewedPublisher PD

Modelling the regulation of thermal adaptation in Candida albicans, a major fungal pathogen of humans

Peer reviewedPublisher PD

Role of the heat shock transcription factor, Hsf1, in a major fungal pathogen that is obligately associated with warm-blooded animals

Peer reviewedPublisher PD

Treatment for Anogenital Molluscum Contagiosum

There is no evidence from comparative trials to suggest a single best treatment method for anogenital molluscum contagiosum. Randomized controlled trials suggest self-administered topical imiquimod or podophyllotoxin cream is effective for resolving lesions. (Strength of Recommendation: B, based on inconsistent or limited quality patient-oriented evidence). There are no comparative trials of other commonly used treatments, such as carbon dioxide laser, cryotherapy, or curettage

The SOX11 transcription factor is a critical regulator of basal-like breast cancer growth, invasion, and basal-like gene expression.

Basal-like breast cancers (BLBCs) are aggressive breast cancers associated with poor survival. Defining the key drivers of BLBC growth will allow identification of molecules for targeted therapy. In this study, we performed a primary screen integrating multiple assays that compare transcription factor expression and activity in BLBC and non-BLBC at the RNA, DNA, and protein levels. This integrated screen identified 33 transcription factors that were elevated in BLBC in multiple assays comparing mRNA expression, DNA cis-element sequences, or protein DNA-binding activity. In a secondary screen to identify transcription factors critical for BLBC cell growth, 8 of the 33 candidate transcription factors (TFs) were found to be necessary for growth in at least two of three BLBC cell lines. Of these 8 transcription factors, SOX11 was the only transcription factor required for BLBC growth, but not for growth of non-BLBC cells. Our studies demonstrate that SOX11 is a critical regulator of multiple BLBC phenotypes, including growth, migration, invasion, and expression of signature BLBC genes. High SOX11 expression was also found to be an independent prognostic indicator of poor survival in women with breast cancer. These results identify SOX11 as a potential target for the treatment of BLBC, the most aggressive form of breast cancer

Solution structure of a bacterial microcompartment targeting peptide and its application in the construction of an ethanol bioreactor

Targeting of proteins to bacterial microcompartments (BMCs) is mediated by an 18-amino-acid peptide sequence. Herein, we report the solution structure of the N-terminal targeting peptide (P18) of PduP, the aldehyde dehydrogenase associated with the 1,2-propanediol utilization metabolosome from Citrobacter freundii. The solution structure reveals the peptide to have a well-defined helical conformation along its whole length. Saturation transfer difference and transferred NOE NMR has highlighted the observed interaction surface on the peptide with its main interacting shell protein, PduK. By tagging both a pyruvate decarboxylase and an alcohol dehydrogenase with targeting peptides, it has been possible to direct these enzymes to empty BMCs in vivo and to generate an ethanol bioreactor. Not only are the purified, redesigned BMCs able to transform pyruvate into ethanol efficiently, but the strains containing the modified BMCs produce elevated levels of alcohol

p53 null Fluorescent Yellow Direct Repeat (FYDR) mice have normal levels of homologous recombination

The tumor suppressor p53 is a transcription factor whose function is critical for maintaining genomic stability in mammalian cells. In response to DNA damage, p53 initiates a signaling cascade that results in cell cycle arrest, DNA repair or, if the damage is severe, programmed cell death. In addition, p53 interacts with repair proteins involved in homologous recombination. Mitotic homologous recombination (HR) plays an essential role in the repair of double-strand breaks (DSBs) and broken replication forks. Loss of function of either p53 or HR leads to an increased risk of cancer. Given the importance of both p53 and HR in maintaining genomic integrity, we analyzed the effect of p53 on HR in vivo using Fluorescent Yellow Direct Repeat (FYDR) mice as well as with the sister chromatid exchange (SCE) assay. FYDR mice carry a direct repeat substrate in which an HR event can yield a fluorescent phenotype. Here, we show that p53 status does not significantly affect spontaneous HR in adult pancreatic cells in vivo or in primary fibroblasts in vitro when assessed using the FYDR substrate and SCEs. In addition, primary fibroblasts from p53 null mice do not show increased susceptibility to DNA damage-induced HR when challenged with mitomycin C. Taken together, the FYDR assay and SCE analysis indicate that, for some tissues and cell types, p53 status does not greatly impact HR.National Institute of Environmental Health Sciences (ES02109)National Cancer Institute (U.S.) (R33CA112151)National Cancer Institute (U.S.) (R01CA79827)United States. Dept. of Energy (DE-FG01-04ER04-21)National Institute of Environmental Health Sciences (T32 ES007020, NIEHS Training Grant in Environmental Toxicology)National Science Foundation (U.S.) (Fellowship

Clinical simulation in Australia and New Zealand: Through the lens of an advisory group

Across Australia, innovations in simulation to enhance learning in nursing have been occurring for three decades and nursing is, and needs to be, a leading player in simulation knowledge diffusion. However, expertise is unevenly distributed across health services and education providers. Rather than build on the expertise and achievements of others, there is a tendency for resource duplication and for trial and error problem solving, in part related to a failure to communicate achievements for the benefits of the professional collective. For nursing to become a leader in the use of simulation and drive ongoing development, as well as conducting high quality research and evaluation, academics need to collaborate, aggregate best practice in simulation learning, and disseminate that knowledge to educators working in health services and higher education sectors across the whole of Australia and New Zealand. To achieve this strategic intent, capacity development principles and committed action are necessary. In mid 2010 the opportunity to bring together nurse educators with simulation learning expertise within Australia and New Zealand became a reality. The Council of Deans of Nursing and Midwifery (CDNM) Australia and New Zealand decided to establish an expert reference group to reflect on the state of Australian nursing simulation, to pool expertise and to plan ways to share best practice knowledge on simulation more widely. This paper reflects on the achievements of the first 18 months since the group's establishment and considers future directions for the enhancement of simulation learning practice, research and development in Australian nursing

People with aphasia’s perspectives of the therapeutic alliance during speech-language intervention: A Q methodological approach

Purpose: To identify which elements of the therapeutic alliance are important to people with aphasia (PWA) attending speech-language pathology post-stroke. Method: A Q methodology design was adopted to explore which elements of the therapeutic alliance were valued by PWA. Statements (n = 453) relevant to the research question were extrapolated from the literature and qualitative interviews. A representative sample of statements (n = 38) was identified from the expansive data set. PWA (n = 23) sorted statements hierarchically according to whether they thought the statement was important or unimportant. Completed Q sorts were analysed using a by-person factor analysis. Result: Analysis yielded a five-factor solution, representing five distinct viewpoints: (1) acknowledge me, help me to understand; (2) respect me, listen to me; (3) challenge me, direct me; (4) understand me, laugh with me; and (5) hear me, encourage me. Conclusion: The findings highlight the need for clinicians to adopt a flexible and idiosyncratic approach to therapeutic alliance construction in order to meet the relational needs of a heterogeneous population. This is the first study to use Q methodology with PWA, demonstrating that Q methodology is an effective and viable method for investigating subjectivity in this population

Relocation risky for bumblebee colonies

Climate change impacts on bumblebees converge across continentsFil: Lozier, Jeffrey. University of Alabama; Estados UnidosFil: Cameron, Sydney. University of Illinois; Estados UnidosFil: Duennes, Michelle. University of Illinois; Estados UnidosFil: Strange, James. State University of Utah; Estados UnidosFil: Williams, Paul. Natural History Museum; Reino UnidoFil: Goulson, David. University of Sussex; Reino UnidoFil: Brown, Mark. University of London; Reino UnidoFil: Morales, Carolina Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Jepsen, Sarina. Xerces Society; Estados Unido