The emerging role of extracellular vesicle-mediated drug resistance in cancers: Implications in advanced prostate cancer

Emerging evidence has shown that the extracellular vesicles (EVs) regulate various biological processes and can control cell proliferation and survival, as well as being involved in normal cell development and diseases such as cancers. In cancer treatment, development of acquired drug resistance phenotype is a serious issue. Recently it has been shown that the presence of multidrug resistance proteins such as Pgp-1 and enrichment of the lipid ceramide in EVs could have a role in mediating drug resistance. EVs could also mediate multidrug resistance through uptake of drugs in vesicles and thus limit the bioavailability of drugs to treat cancer cells. In this review, we discussed the emerging evidence of the role EVs play in mediating drug resistance in cancers and in particular the role of EVs mediating drug resistance in advanced prostate cancer. The role of EV-associated multidrug resistance proteins, miRNA, mRNA, and lipid as well as the potential interaction(s) among these factors was probed. Lastly, we provide an overview of the current available treatments for advanced prostate cancer, considering where EVs may mediate the development of resistance against these drugs.

Growth hormone resistance and somatomedins in children with end-stage liver disease awaiting transplantation

Background: The success of orthotopic liver transplantation as treatment for end-stage liver disease has prompted investigation of strategies to maintain or improve nutrition and growth in children awaiting transplantation, because malnutrition is an adverse prognostic factor. The purpose of this study was to evaluate the effect of recombinant human growth hormone therapy on body composition and indices of liver function in patients awaiting transplant. Methods: The study was designed as a placebo- controlled, double-blind, crossover trial. Patients received 0.2 U/kg growth hormone, subcutaneously, or placebo daily for 28 days during two treatment periods, separated by a 2-week washout period. Ten patients (mean age, 3.06 ± 1.15 years; range, 0.51-11.65 years, five men), with extrahepatic biliary atresia (n = 8) or two with Alagille's syndrome (n = 2), with end-stage liver disease, completed the trial while awaiting orthotopic liver transplantation. Height, weight, total body potassium, total body fat, resting energy expenditure, respiratory quotient, hematologic and multiple biochemical profile, number of albumin infusions, insulin-like growth factor-1 and 1, growth hormone binding protein (GHBP), and insulin-like growth factor binding protein-1 (IGFBP-1) and insulin-like growth factor binding protein (IGFBP-3) were measured at the beginning and end of each treatment period. Results: Growth hormone treatment was associated with a significant decline in serum bilirubin (-34.6 ± 16.5 μmol/l vs. 18.2 ± 11.59 μmol/l; p < 0.02) but there was no significant effect on any anthropometric or body composition measurements, or on any biochemical or hematologic parameters. Conclusions: These children with end-stage liver disease displayed growth hormone resistance, particularly in relation to the somatomedin axis. Exogenous growth hormone administration may be of limited value in these patients

Electrical Conductivity and Magneto-Resistance Studies on Polyaniline-Pmma Blends at Very Low Temperature

D.C. electrical conductivity of polyaniline (33%,40%) blended with PMMA was measured from 5K to 300mK. The conductivity behaviour is consistent with fluctuation induced tunneling. Magneto-resistance (MR) was measured between 300K and 2K. From 20K to 2K, a large positive MR was observed. At 2K, for low magnetic fields (<1 Tesla), a deviation from the normal H-2 behaviour was observed.

Engineering cellulose nanofibre suspensions to control filtration resistance and sheet permeability

This study examines and quantifies the effect of adding polyelectrolytes to cellulose nanofibre suspensions on the gel point of cellulose nanofibre suspensions, which is the lowest solids concentration at which the suspension forms a continuous network. The lower the gel point, the faster the drainage time to produce a sheet and the higher the porosity of the final sheet formed. Two new techniques were designed to measure the dynamic compressibility and the drainability of nanocellulose–polyelectrolyte suspensions. We developed a master curve which showed that the independent variable controlling the behaviour of nanocellulose suspensions and its composite is the structure of the flocculated suspension which is best quantified as the gel point. This was independent of the type of polyelectrolyte used. At an addition level of 2 mg/g of nanofibre, a reduction in gel point over 50 % was achieved using either a high molecular weight (13 MDa) linear cationic polyacrylamide (CPAM, 40 % charge), a dendrimer polyethylenimine of high molecular weight of 750,000 Da (HPEI) or even a low molecular weight of 2000 Da (LPEI). There was no significant difference in the minimum gel point achieved, despite the difference in polyelectrolyte morphology and molecular weight. In this paper, we show that the gel point controls the flow through the fibre suspension, even when comparing fibre suspensions with solids content above the gel point. A lower gel point makes it easier for water to drain through the fibre network,reducing the pressure required to achieve a given dewatering rate and reducing the filtering time required to form a wet laid sheet. We further show that the lower gel point partially controls the structure of the wet laid sheet after it is dried. Halving the gel point increased the air permeability of the dry sheet by 37, 46 and 25 %, when using CPAM, HPEI and LPEI, respectively. The resistance to liquid flow was reduced by 74 and 90 %, when using CPAM and LPEI. Analysing the paper formed shows that sheet forming process and final sheet properties can be engineered and controlled by adding polyelectrolytes to the nanofibre suspension.

Resistance Noise in Electrically Biased Bilayer Graphene

We demonstrate that the low-frequency resistance uctuations, or noise, in bilayer graphene is strongly connected to its band structure, and displays a minimum when the gap between the conduction and valence band is zero. Using double-gated bilayer graphene devices we have tuned the zero gap and charge neutrality points independently, which oers a versatile mechanism to investigate the low-energy band structure, charge localization and screening properties of bilayer graphene.

Miniature cone tip resistance of sand with fly ash using triaxial setup

In a continuation of the authors' recent work, the ultimate tip resistance of a miniature cone using triaxial equipment was determined for samples of dry sand mixed with dry fly ash. The effect of (i) the proportion of fly ash, (ii) the relative density of samples, and (iii) the vertical overburden pressure was examined. It was noted that an addition of fly ash in sand for the same range of relative density leads to a significant reduction in the ultimate tip resistance of the cone (q(cu)). This occurs due to a decrease in the friction angle (phi) of the sample with an increase in the fly ash content for a given relative density. For phi greater than about 30 degrees, two widely used correlation curves from published literature, providing the relationships between q(cu) and phi for cohesionless soils, were found to provide satisfactory predictions, even for sand - fly ash mixtures. As was expected, the values of qcu increase continuously with an increase in the relative density of the soil mass and the vertical effective ( overburden) stress on the sample.

Resistance Noise in Electrically Biased Bilayer Graphene

We demonstrate that the low-frequency resistance fluctuations, or noise, in bilayer graphene are strongly connected to its band structure and display a minimum when the gap between the conduction and valence band is zero. Using double-gated bilayer graphene devices we have tuned the zero gap and charge neutrality points independently, which offers a versatile mechanism to investigate the low-energy band structure, charge localization, and screening properties of bilayer graphene.

Voice, deliberation, resistance and persuasion through participatory journalism business models

The pervasive use of the World Wide Web by the general population has created a cultural shift throughout the world. It has enabled more people to share more information about more events and issues than was possible before its general use. As a consequence, it has transformed traditional news media’s approach to almost every aspect of journalism, with many organisations restructuring their philosophy and practice to include a variety of participatory spaces/forums where people are free to engage in deliberative dialogue about matters of public importance. This paper draws from an international collective case study that showcases various approaches to participatory online news journalism during the period 1997–2011 (Adams, 2013). The research finds differences in the ways in which public service, commercial, and independent news media give voice to the public, and ultimately in their approach to journalism’s role as the Fourth Estate––one of the key institutions of democracy. The work is framed by the notion that journalism in democratic societies has a crucial role in ensuring citizens are informed and engaged with public affairs. An examination of four media models, OhmyNews International, News Corp Australia (formerly News Limited), the Guardian and the British Broadcasting Corporation (BBC), showcases the various approaches to participatory online news journalism and how each provides different avenues for citizen engagement. Semistructured in-depth interviews with some of the key senior journalists and editors provide specific information on comparisons between the distinctive practices in each of their employer organisations.

Analysis of human immunodeficiency virus type 1 drug resistance in children receiving nucleoside analogue reverse-transcriptase inhibitors plus nevirapine, nelfinavir, or ritonavir (Pediatric AIDS Clinical Trials Group 377)

In Pediatric AIDS Clinical Trials Group 377, antiretroviral therapy-experienced children were randomized to 4 treatment arms that included different combinations of stavudine, lamivudine (3TC), nevirapine (Nvp), nelfinavir (Nfv), and ritonavir (Rtv). Previous treatment with zidovudine (Zdv), didanosine (ddI), or zalcitabine (ddC) was acceptable. Drug resistance ((R)) mutations were assessed before study treatment (baseline) and at virologic failure. Zdv(R), ddI(R), and ddC(R) mutations were detected frequently at baseline but were not associated with virologic failure. Children with drug resistance mutations at baseline had greater reductions in virus load over time than did children who did not. Nvp(R) and 3TC(R) mutations were detected frequently at virologic failure, and Nvp(R) mutations were more common among children receiving 3-drug versus 4-drug Nvp-containing regimens. Children who were maintained on their study regimen after virologic failure accumulated additional Nvp(R) and 3TC(R) mutations plus Rtv(R) and Nfv(R) mutations. However, Rtv(R) and Nfv(R) mutations were detected at unexpectedly low rates.

Induced Resistance: Potential for Control of Postharvest Diseases of Horticultural Crops

Fortunately, plants have developed highly effective mechanisms with which to defend themselves when attacked by potentially disease-causing microorganisms. If not, then they would succumb to the many pathogenic fungi, bacteria, viruses, nematodes and insect pests, and disease would prevail. These natural defence systems of plants can be deliberately activated to provide some protection against the major pathogens responsible for causing severe yield losses in agricultural and horticultural crops. This is the basis of what is known as ‘induced’ or ‘acquired’ disease resistance in plants. Although the phenomenon of induced resistance has been known amongst plant pathologists for over 100 years, its inclusion into pest and disease management programmes has been a relatively recent development, ie. within the last 5 years. This review will discuss very briefly some of the characteristics of the induced resistance phenomenon, outline some of the advantages and limitations to its implementation and provide some examples within a postharvest pathology context. Finally some approaches being investigated by the fruit pathology team at DPI Indooroopilly and collaborators will be outlined.

Studies on the Tracking and Erosion Resistance of RTV Silicone Rubber Nanocomposite

One of the problems associated with outdoor polymeric insulators is tracking and erosion of the weathershed which can directly influence the reliability of the power system. Flame retardants are added to the base material to enhance its tracking and erosion resistance. Hydroxide fillers are regarded as the best flame retardants. This paper deals with studies related to nano - sized magnesium dihydroxide (MDH) and micron-sized Alumina Trihydrate (ATH) fillers as flame retardants in RTV silicone rubber. Tracking and erosion resistance studies were carried out on MDH and ATH silicone rubber composites using an inclined plane tracking and erosion (IPT) resistance tester. The MDH filled (5% by wt) composites performed much better than ATH composites in terms of eroded mass, depth of erosion, width and length of erosion. The eroded mass of MDH composite is 49.8 % that of ATH composite which can be attributed to high surface area and higher thermal stability of MDH nanofillers.

Counter-figures : An Essay on Antimetaphoric Resistance: Paul Celan's Poetry and Poetics at the Limits of Figurality

Titled "An Essay on Antimetaphoric Resistance", the dissertation investigates what is here being called "Counter-figures": a term which has in this context a certain variety of applications. Any other-than-image or other-than-figure, anything that cannot be exhausted by figuration (and that is, more or less, anything at all, except perhaps the reproducible images and figures themselves) can be considered "counter-figurative" with regard to the formation of images and figures, ideas and schemas, "any graven image, or any likeness of any thing". Singularity and radical alterity, as well as temporality and its peculiar mode of uniqueness are key issues here, and an ethical dimension is implied by, or intertwined with, the aesthetic. In terms borrowed from Paul Celan's "Meridian" speech, poetry may "allow the most idiosyncratic quality of the Other, its time, to participate in the dialogue". This connection between singularity, alterity and temporality is one of the reasons why Celan so strongly objects to the application of the traditional concept of metaphor to poetry. As Celan says, "carrying over [übertragen]" by metaphor may imply an unwillingness to "bear with [mittragen]" and to "endure [ertragen]" the poem. The thesis is divided into two main parts. The first consists of five distinct prolegomena which all address the mentioned variety of applications of the term "counter-figures", and especially the rejection or critique of either metaphor (by Aristotle, for instance) or the concept of metaphor (defined by Aristotle, and sometimes deemed "anti-poetic" by both theorists and poets). Even if we restrict ourselves to the traditional rhetorico-poetical terms, we may see how, for instance, metonymy can be a counter-figure for metaphor, allegory for symbol, and irony for any single trope or for any piece of discourse at all. The limits of figurality may indeed be located at these points of intersection between different types of tropes or figures, and even between figures or tropes and the "non-figurative trope" or "pseudo-figure" called catachresis. The second part, following on from the open-ended prolegomena, concentrates on Paul Celan's poetry and poetics. According to Celan, true poetry is "essentially anti-metaphoric". I argue that inasmuch as we are willing to pay attention to the "will" of the poetic images themselves (the tropes and metaphors in a poem) to be "carried ad absurdum", as Celan invites us to do, we may find alternative ways of reading poetry and approaching its "secret of the encounter", precisely when the traditional rhetorical instruments, and especially the notion of metaphor, become inapplicable or suspicious — and even where they still seem to impose themselves.

Developments in phosphine resistance in China and possible implications for Australia

Resistance to phosphine was characterised in strains of rice weevil, Sirophilus oryzae, and the psocids Liposcelis entomophila and L. decolor from China and Australia. Mixed-age cultures (containing all life stages) of insects were tested using a flow-through apparatus. The criterion of response was 'time to population extinction' defined as the exposure period, in days, at which 100% mortality of adults and no live progeny were achieved. Chinese S. oryzae took 11 and 7 days for population extinction at 200 and 700 ppm phosphine, respectively, compared with the Australian strain, which was controlled in 7 and 5 days, respectively. Similarly, the Chinese strains L. Enfornophila and L. decolor were generally more difficult to control than the corresponding Australian strains. The Chinese strains of L. decolor showed resistance levels stronger than any grain storage insect pest species so far detected in Australia. This research allows us to evaluate the likely significance of potential new resistance to the Australian grain industry and to prepare effective fumigation dosages and resistance management strategies to combat new strong resistances before they emerge here.

Genetic analysis of resistance to root-lesion nematode (Pratylenchus thornei) in wheat

The inheritance of resistance to root-lesion nematode was investigated in five synthetic hexaploid wheat lines and two bread wheat lines using a half-diallel design of F1 and F2 crosses. The combining ability of resistance genes in the synthetic hexaploid wheat lines was compared with the performance of the bread wheat line 'GS50a', the source of resistance to Pratylenchus thornei used in Australian wheat breeding programmes. Replicated glasshouse trials identified P. thornei resistance as polygenic and additive in gene action. General combining ability (GCA) of the parents was more important than specific combining ability (SCA) effects in the inheritance of P. thornei resistance in both F1 and F2 populations. The synthetic hexaploid wheat line 'CPI133872' was identified as the best general combiner, however, all five synthetic hexaploid wheat lines possessed better GCA than 'GS50a'. The synthetic hexaploid wheat lines contain novel sources of P. thornei resistance that will provide alternative and more effective sources of resistance to be utilized in wheat breeding programmes

Homologues of the maize rust resistance gene Rp1-D are genetically associated with a major rust resistance QTL in sorghum

As part of a comparative mapping study between sugarcane and sorghum, a sugarcane cDNA clone with homology to the maize Rp1-D rust resistance gene was mapped in sorghum. The cDNA probe hybridised to multiple loci, including one on sorghum linkage group (LG) E in a region where a major rust resistance QTL had been previously mapped. Partial sorghum Rp1-D homologues were isolated from genomic DNA of rust-resistant and -susceptible progeny selected from a sorghum mapping population. Sequencing of the Rp1-D homologues revealed five discrete sequence classes: three from resistant progeny and two from susceptible progeny. PCR primers specific to each sequence class were used to amplify products from the progeny and confirmed that the five sequence classes mapped to the same locus on LG E. Cluster analysis of these sorghum sequences and available sugarcane, maize and sorghum Rp1-D homologue sequences showed that the maize Rp1-D sequence and the partial sugarcane Rp1-D homologue were clustered with one of the sorghum resistant progeny sequence classes, while previously published sorghum Rp1-D homologue sequences clustered with the susceptible progeny sequence classes. Full-length sequence information was obtained for one member of a resistant progeny sequence class ( Rp1-SO) and compared with the maize Rp1-D sequence and a previously identified sorghum Rp1 homologue ( Rph1-2). There was considerable similarity between the two sorghum sequences and less similarity between the sorghum and maize sequences. These results suggest a conservation of function and gene sequence homology at the Rp1 loci of maize and sorghum and provide a basis for convenient PCR-based screening tools for putative rust resistance alleles in sorghum.