Programmed cell death in pathogenic fungi.

addresses: School of Biosciences, University of Exeter, Geoffrey Pope Building, Exeter, UK. [email protected]: Journal Article; Research Support, Non-U.S. Gov't; ReviewCopyright © 2008 Elsevier. NOTICE: this is the author’s version of a work that was accepted for publication in Biochimica et Biophysica Acta. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Biochimica et Biophysica Acta, 2008, Vol. 1783, Issue 7, pp. 1369 – 1380 DOI: 10.1016/j.bbamcr.2008.01.021Greater understanding of programmed cell death (PCD) responses in pathogenic fungi may offer a chance of exploiting the fungal molecular death machinery to control fungal infections. Clearly identifiable differences between the death machineries of pathogens and their hosts, make this a feasible target. Evidence for PCD in a range of pathogenic fungi is discussed alongside an evaluation of the capacity of existing antifungal agents to promote apoptosis and other forms of cell death. Information about death related signalling pathways that have been examined in pathogens as diverse as Candida albicans, Aspergillus fumigatus, Magnaporthe grisea and Colletotrichum trifolii are discussed

Proteases and caspase-like activity in the yeast Saccharomyces cerevisiae.

addresses: Biosciences, University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter EX4 4QD, UK.types: Journal Article; Research Support, Non-U.S. Gov't; ReviewAuthor's post-print versionThe final version of record is available at http://www.biochemsoctrans.org/bst/039/bst0391502.htm© The Authors Journal compilation © 2011 Biochemical SocietyA variety of proteases have been implicated in yeast PCD (programmed cell death) including the metacaspase Mca1 and the separase Esp1, the HtrA-like serine protease Nma111, the cathepsin-like serine carboxypeptideases and a range of vacuolar proteases. Proteasomal activity is also shown to have an important role in determining cell fate, with both pro- and anti-apoptotic roles. Caspase 3-, 6- and 8-like activities are detected upon stimulation of yeast PCD, but not all of this activity is associated with Mca1, implicating other proteases with caspase-like activity in the yeast cell death response. Global proteolytic events that accompany PCD are discussed alongside a consideration of the conservation of the death-related degradome (both at the level of substrate choice and cleavage site). The importance of both gain-of-function changes in the degradome as well as loss-of-function changes are highlighted. Better understanding of both death-related proteases and their substrates may facilitate the design of future antifungal drugs or the manipulation of industrial yeasts for commercial exploitation

Teaching Competencies for the Online Environment

The goals of this study are to identify key competency areas that lead to success in online instruction and to develop a framework that supports professional development and self- assessment. To identify the key competency areas, skills and behaviours presented within current literature were analyzed. Secondly, gaps were identified and levels of competence were determined within each key competency area. The resulting analysis produced the Online Teaching Competency (OTC) Matrix including five competency areas: Community & Netiquette, Active Teaching/Facilitating, Instructional Design, Tools & Technology, and Leadership & Instruction. This leveled competency matrix can be used to inform professional development in the online teaching environment and is also a useful guide in the areas of self- assessment, portfolio design, and the development and evaluation of professional development opportunities

Discovery of new 19.9-GHz methanol masers in star-forming regions

We have used the NASA Tidbinbilla 70-m antenna to search for emission from the 21-30 E (19.9-GHz) transition of methanol. The search was targeted towards 22 star formation regions that exhibit maser emission in the 107.0-GHz 31-40 A+ methanol transition, and in the 6.6-GHz 51-60 A+ transition characteristic of class II methanol maser sources. A total of seven sources were detected in the 21-30 E transition, six of these being new detections. Many of the new detections are weak (≳0.5 Jy), however, they appear to be weak masers rather than thermal or quasi-thermal emission. We find a strong correlation between sources that exhibit 19.9-GHz methanol masers and those that both have the class II methanol masers projected against radio continuum emission and have associated 6035-MHz OH masers. This suggests that the 19.9-GHz methanol masers arise in very specific physical conditions, probably associated with a particular evolutionary phase. In the model of Cragg, Sobolev & Godfrey these observations are consistent with gas temperatures of 50 K, dust temperatures of 150-200 K and gas densities of 106.5-107.5 cm-3

Gridmapping the northern plains of Mars: Geomorphological, Radar and Water-Equivalent Hydrogen results from Arcadia Plantia

A project of mapping ice-related landforms was undertaken to understand the role of sub-surface ice in the northern plains. This work is the first continuous regional mapping from CTX (“ConTeXt Camera”, 6 m/pixel; Malin et al., 2007) imagery in Arcadia Planitia along a strip 300 km across stretching from 30°N to 80°N centred on the 170° West line of longitude. The distribution and morphotypes of these landforms were used to understand the permafrost cryolithology. The mantled and textured signatures occur almost ubiquitously between 35° N and 78° N and have a positive spatial correlation with inferred ice stability based on thermal modelling, neutron spectroscopy and radar data. The degradational features into the LDM (Latitude Dependent Mantle) include pits, scallops and 100 m polygons and provide supporting evidence for sub-surface ice and volatile loss between 35-70° N in Arcadia with the mantle between 70-78° N appearing much more intact. Pitted terrain appears to be much more pervasive in Arcadia than in Acidalia and Utopia suggesting that the Arcadia study area had more wide-spread near-surface sub-surface ice, and thus was more susceptible to pitting, or that the ice was less well-buried by sediments. Correlations with ice stability models suggest that lack of pits north of 65-70° N could indicate a relatively young age (~1Ma), however this could also be explained through regional variations in degradation rates. The deposition of the LDM is consistent with an airfall hypothesis however there appears to be substantial evidence for fluvial processes in southern Arcadia with older, underlying processes being equally dominant with the LDM and degradation thereof in shaping the landscape

Modelling the properties of a difunctional epoxy resin cured with aromatic diamine isomers

Group Interaction Modelling has been extended to predict a range of thermo-mechanical properties of diglycidyl ether of bisphenol A cured with two isomers of diaminodiphenyl sulphone. The meta-meta and para-para positions of the substituents on the phenylene rings in the curing agent cause differences in packing efficiency, reaction kinetics and conformational freedom. Experimental data in the form of dynamic mechanical, static mechanical and density measurements are acquired in order to provide validation for the model. The model has proven capable of accurately reproducing the experimental measurements to well within experimental errors in most cases. Both the experimental measurements and model predictions have highlighted a number of subtle differences in behaviour of the resins cured with the two diamine isomers. In particular, variation of the amine/epoxy ratio has revealed how the secondary phase transitions of the resins are influenced. Variation of the glass and beta transitions in amine rich, stoichiometric or epoxy rich mixtures is described in terms of the molecular motions responsible for the transitions and the underlying network structural differences between the meta and para isomers

Associations of Polypharmacy and Inappropriate Medications with Adverse Outcomes in Older Adults with Cancer: A Systematic Review and Meta-Analysis

© AlphaMed Press 2019 Background: Polypharmacy (PP) and potentially inappropriate medications (PIM) are highly prevalent in older adults with cancer. This study systematically reviews the associations of PP and/or PIM with outcomes and, through a meta-analysis, obtains estimates of postoperative outcomes associated with PP in this population. Materials and Methods: We searched PubMed, Embase, Web of Science, and Cochrane Register of Clinical Trials using standardized terms for concepts of PP, PIM, and cancer. Eligible studies included cohort studies, cross-sectional studies, meta-analyses, and clinical trials which examined outcomes associated with PP and/or PIM and included older adults with cancer. A random effects model included studies in which definitions of PP were consistent to examine the association of PP with postoperative complications. Results: Forty-seven articles met the inclusion criteria. PP was defined as five or more medications in 57% of the studies. Commonly examined outcomes included chemotherapy toxicities, postoperative complications, functional decline, hospitalization, and overall survival. PP was associated with chemotherapy toxicities (4/9 studies), falls (3/3 studies), functional decline (3/3 studies), and overall survival (2/11 studies). A meta-analysis of four studies indicated an association between PP (≥5 medications) and postoperative complications (overall odds ratio, 1.3; 95% confidence interval [1.3–2.8]). PIM was associated with adverse outcomes in 3 of 11 studies. Conclusion: PP is associated with postoperative complications, chemotherapy toxicities, and physical and functional decline. Only three studies showed an association between PIM and outcomes. However, because of inconsistent definitions, heterogeneous populations, and variable study designs, these associations should be further investigated in prospective studies. Implications for Practice: Polypharmacy and potentially inappropriate medications (PIM) are prevalent in older adults with cancer. This systematic review summarizes the associations of polypharmacy and PIM with health outcomes in older patients with cancer. Polypharmacy and PIM have been associated with postoperative complications, frailty, falls, medication nonadherence, chemotherapy toxicity, and mortality. These findings emphasize the prognostic importance of careful medication review and identification of PIM by oncology teams. They also underscore the need to develop and test interventions to address polypharmacy and PIM in older patients with cancer, with the goal of improving outcomes in these patients

Interconnections of Reactive Oxygen Species Homeostasis and Circadian Rhythm in Neurospora crassa.

Abstract Significance: Both circadian rhythm and the production of reactive oxygen species (ROS) are fundamental features of aerobic eukaryotic cells. The circadian clock enhances the fitness of organisms by enabling them to anticipate cycling changes in the surroundings. ROS generation in the cell is often altered in response to environmental changes, but oscillations in ROS levels may also reflect endogenous metabolic fluctuations governed by the circadian clock. On the other hand, an effective regulation and timing of antioxidant mechanisms may be crucial in the defense of cellular integrity. Thus, an interaction between the circadian timekeeping machinery and ROS homeostasis or signaling in both directions may be of advantage at all phylogenetic levels. Recent Advances: The Frequency-White Collar-1 and White Collar-2 oscillator (FWO) of the filamentous fungus Neurospora crassa is well characterized at the molecular level. Several members of the ROS homeostasis were found to be controlled by the circadian clock, and ROS levels display circadian rhythm in Neurospora. On the other hand, multiple data indicate that ROS affect the molecular oscillator. Critical Issues: Increasing evidence suggests the interplay between ROS homeostasis and oscillators that may be partially or fully independent of the FWO. In addition, ROS may be part of a complex cellular network synchronizing non-transcriptional oscillators with timekeeping machineries based on the classical transcription-translation feedback mechanism. Future Directions: Further investigations are needed to clarify how the different layers of the bidirectional interactions between ROS homeostasis and circadian regulation are interconnected. Antioxid. Redox Signal. 00, 000-000

Hsp21potentiates antifungal drug tolerance in Candida albicans

Peer reviewedPublisher PD