Hsp90 governs dispersion and drug resistance of fungal biofilms

Fungal biofilms are a major cause of human mortality and are recalcitrant to most treatments due to intrinsic drug resistance. These complex communities of multiple cell types form on indwelling medical devices and their eradication often requires surgical removal of infected devices. Here we implicate the molecular chaperone Hsp90 as a key regulator of biofilm dispersion and drug resistance. We previously established that in the leading human fungal pathogen, Candida albicans, Hsp90 enables the emergence and maintenance of drug resistance in planktonic conditions by stabilizing the protein phosphatase calcineurin and MAPK Mkc1. Hsp90 also regulates temperature-dependent C. albicans morphogenesis through repression of cAMP-PKA signalling. Here we demonstrate that genetic depletion of Hsp90 reduced C. albicans biofilm growth and maturation in vitro and impaired dispersal of biofilm cells. Further, compromising Hsp90 function in vitro abrogated resistance of C. albicans biofilms to the most widely deployed class of antifungal drugs, the azoles. Depletion of Hsp90 led to reduction of calcineurin and Mkc1 in planktonic but not biofilm conditions, suggesting that Hsp90 regulates drug resistance through different mechanisms in these distinct cellular states. Reduction of Hsp90 levels led to a marked decrease in matrix glucan levels, providing a compelling mechanism through which Hsp90 might regulate biofilm azole resistance. Impairment of Hsp90 function genetically or pharmacologically transformed fluconazole from ineffectual to highly effective in eradicating biofilms in a rat venous catheter infection model. Finally, inhibition of Hsp90 reduced resistance of biofilms of the most lethal mould, Aspergillus fumigatus, to the newest class of antifungals to reach the clinic, the echinocandins. Thus, we establish a novel mechanism regulating biofilm drug resistance and dispersion and that targeting Hsp90 provides a much-needed strategy for improving clinical outcome in the treatment of biofilm infections

Workplace Health Promotion and Mental Health: Three-Year Findings from Partnering Healthy@Work

This study aimed to investigate the association between mental health and comprehensive workplace health promotion (WHP) delivered to an entire state public service workforce (~28,000 employees) over a three-year period. Government departments in a state public service were supported to design and deliver a comprehensive, multi-component health promotion program, Healthy@Work, which targeted modifiable health risks including unhealthy lifestyles and stress. Repeated cross-sectional surveys compared self-reported psychological distress (Kessler-10; K10) at commencement (N = 3406) and after 3 years (N = 3228). WHP availability and participation over time was assessed, and associations between the K10 and exposure to programs estimated. Analyses were repeated for a cohort subgroup (N = 580). Data were weighted for non-response. Participation in any mental health and lifestyle programs approximately doubled after 3 years. Both male and female employees with poorer mental health participated more often over time. Women's psychological distress decreased over time but this change was only partially attributable to participation in WHP, and only to lifestyle interventions. Average psychological distress did not change over time for men. Unexpectedly, program components directly targeting mental health were not associated with distress for either men or women. Cohort results corroborated findings. Healthy@Work was successful in increasing participation across a range of program types, including for men and women with poorer mental health. A small positive association of participation in lifestyle programs with mental health was observed for women but not men. The lack of association of mental health programs may have reflected program quality, its universality of application or other contextual factors

Влияние фосфатных связующих на физико-механические свойства периклазохромитовых огнеупоров

У данній статті наведено та порівняно фізико-механічні властивості периклазо-хромітових матеріалів в залежності від різних типів фосфатних зв’язуючих та введення різних домішок. Визначено, що найбільш раціональним є введення триполіфосфату натрію.In given clause are resulted and the physycal-mechanical properties periclase-cgromite of materials are compared depending on different of types phosphate binding and introduction of the various additives. Is determined, that most rational is the introduction treepolyphosphate sodume

Perceived control over condom use among sex workers in Madagascar: a cohort study

<p>Abstract</p> <p>Background</p> <p>Women's perceived control over condom use has been found to be an important determinant of actual condom use in some studies. However, many existing analyses used cross-sectional data and little quantitative information exists to characterize the relationships between perceived control and actual condom use among sex worker populations.</p> <p>Methods</p> <p>We assessed the association between measures of perceived condom use control and self-reported use of male condoms employing data from a longitudinal pilot study among 192 sex workers in Madagascar.</p> <p>Results</p> <p>In multivariable models, a lack of perceived control over condom use with a main partner and having a main partner ever refuse to use a condom when asked were both associated with an increased number of sex acts unprotected by condoms in the past week with a main partner (RR 1.86; 95% CI 1.21-2.85; RR 1.34; 95% CI 1.03-1.73, respectively). Conversely, no measure of condom use control was significantly associated with condom use with clients.</p> <p>Conclusion</p> <p>Perceived control over condom use was an important determinant of condom use with main partners, but not clients, among sex workers in Madagascar. Programs working with sex workers should reach out to main and commercial partners of sex workers to increase male condom use.</p

Salmonella in Broiler Litter and Properties of Soil at Farm Location

Contamination of litter in a broiler grow-out house with Salmonella prior to placement of a new flock has been shown to be a precursor of the flock's Salmonella contamination further down the production continuum. In the southern USA, broiler grow-out houses are primarily built on dirt pad foundations that are placed directly on top of the native soil surface. Broiler litter is placed directly on the dirt pad. Multiple grow-out flocks are reared on a single litter batch, and the litter is kept in the houses during downtime between flocks. The effects of environmental determinants on conditions in broiler litter, hence Salmonella ecology within it, has received limited attention. In a field study that included broiler farms in the states of Alabama, Mississippi and Texas we assessed Salmonella in broiler litter at the end of downtime between flocks, i.e. at the time of placement of a new flock for rearing. Here we utilized these results and the U.S. General Soil Map (STATSGO) data to test if properties of soil at farm location impacted the probability of Salmonella detection in the litter. The significance of soil properties as risk factors was tested in multilevel regression models after accounting for possible confounding differences among the farms, the participating broiler complexes and companies, and the farms' geographical positioning. Significant associations were observed between infiltration and drainage capabilities of soil at farm location and probability of Salmonella detection in the litter

Accounting for Ecosystem Alteration Doubles Estimates of Conservation Risk in the Conterminous United States

Previous national and global conservation assessments have relied on habitat conversion data to quantify conservation risk. However, in addition to habitat conversion to crop production or urban uses, ecosystem alteration (e.g., from logging, conversion to plantations, biological invasion, or fire suppression) is a large source of conservation risk. We add data quantifying ecosystem alteration on unconverted lands to arrive at a more accurate depiction of conservation risk for the conterminous United States. We quantify ecosystem alteration using a recent national assessment based on remote sensing of current vegetation compared with modeled reference natural vegetation conditions. Highly altered (but not converted) ecosystems comprise 23% of the conterminous United States, such that the number of critically endangered ecoregions in the United States is 156% higher than when calculated using habitat conversion data alone. Increased attention to natural resource management will be essential to address widespread ecosystem alteration and reduce conservation risk

Dispersion as an Important Step in the Candida albicans Biofilm Developmental Cycle

Biofilms are dynamic microbial communities in which transitions between planktonic and sessile modes of growth occur interchangeably in response to different environmental cues. In the last decade, early events associated with C. albicans biofilm formation have received considerable attention. However, very little is known about C. albicans biofilm dispersion or the mechanisms and signals that trigger it. This is important because it is precisely C. albicans cells dispersed from biofilms that are the main culprits associated with candidemia and establishment of disseminated invasive disease, two of the gravest forms of candidiasis. Using a simple flow biofilm model recently developed by our group, we have performed initial investigations into the phenomenon of C. albicans biofilm dispersion, as well as the phenotypic characteristics associated with dispersed cells. Our results indicate that C. albicans biofilm dispersion is dependent on growing conditions, including carbon source and pH of the media used for biofilm development. C. albicans dispersed cells are mostly in the yeast form and display distinct phenotypic properties compared to their planktonic counterparts, including enhanced adherence, filamentation, biofilm formation and, perhaps most importantly, increased pathogenicity in a murine model of hematogenously disseminated candidiasis, thus indicating that dispersed cells are armed with a complete arsenal of “virulence factors” important for seeding and establishing new foci of infection. In addition, utilizing genetically engineered strains of C. albicans (tetO-UME6 and tetO-PES1) we demonstrate that C. albicans biofilm dispersion can be regulated by manipulating levels of expression of these key genes, further supporting the evidence for a strong link between biofilms and morphogenetic conversions at different stages of the C. albicans biofilm developmental cycle. Overall, our results offer novel and important insight into the phenomenon of C. albicans biofilm dispersion, a key part of the biofilm developmental cycle, and provide the basis for its more detailed analysis

Spectral hole burning: examples from photosynthesis

The optical spectra of photosynthetic pigment–protein complexes usually show broad absorption bands, often consisting of a number of overlapping, ‘hidden’ bands belonging to different species. Spectral hole burning is an ideal technique to unravel the optical and dynamic properties of such hidden species. Here, the principles of spectral hole burning (HB) and the experimental set-up used in its continuous wave (CW) and time-resolved versions are described. Examples from photosynthesis studied with hole burning, obtained in our laboratory, are then presented. These examples have been classified into three groups according to the parameters that were measured: (1) hole widths as a function of temperature, (2) hole widths as a function of delay time and (3) hole depths as a function of wavelength. Two examples from light-harvesting (LH) 2 complexes of purple bacteria are given within the first group: (a) the determination of energy-transfer times from the chromophores in the B800 ring to the B850 ring, and (b) optical dephasing in the B850 absorption band. One example from photosystem II (PSII) sub-core complexes of higher plants is given within the second group: it shows that the size of the complex determines the amount of spectral diffusion measured. Within the third group, two examples from (green) plants and purple bacteria have been chosen for: (a) the identification of ‘traps’ for energy transfer in PSII sub-core complexes of green plants, and (b) the uncovering of the lowest k = 0 exciton-state distribution within the B850 band of LH2 complexes of purple bacteria. The results prove the potential of spectral hole burning measurements for getting quantitative insight into dynamic processes in photosynthetic systems at low temperature, in particular, when individual bands are hidden within broad absorption bands. Because of its high-resolution wavelength selectivity, HB is a technique that is complementary to ultrafast pump–probe methods. In this review, we have provided an extensive bibliography for the benefit of scientists who plan to make use of this valuable technique in their future research

Analysis of arterial intimal hyperplasia: review and hypothesis

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Despite a prodigious investment of funds, we cannot treat or prevent arteriosclerosis and restenosis, particularly its major pathology, arterial intimal hyperplasia. A cornerstone question lies behind all approaches to the disease: what causes the pathology? Hypothesis: I argue that the question itself is misplaced because it implies that intimal hyperplasia is a novel pathological phenomenon caused by new mechanisms. A simple inquiry into arterial morphology shows the opposite is true. The normal multi-layer cellular organization of the tunica intima is identical to that of diseased hyperplasia; it is the standard arterial system design in all placentals at least as large as rabbits, including humans. Formed initially as one-layer endothelium lining, this phenotype can either be maintained or differentiate into a normal multi-layer cellular lining, so striking in its resemblance to diseased hyperplasia that we have to name it &quot;benign intimal hyperplasia&quot;. However, normal or &quot;benign &quot; intimal hyperplasia, although microscopically identical to pathology, is a controllable phenotype that rarely compromises blood supply. It is remarkable that each human heart has coronary arteries in which a single-layer endothelium differentiates earl

Jet modification via π 0 -hadron correlations in Au+Au collisions at √sNN = 200 GeV

High-momentum two-particle correlations are a useful tool for studying jet-quenching effects in the quark-gluon plasma. Angular correlations between neutral-pion triggers and charged hadrons with transverse momenta in the range 4–12 GeV/c and 0.5–7 GeV/c, respectively, have been measured by the PHENIX experiment in 2014 for Au+Au collisions at √sNN = 200 GeV. Suppression is observed in the yield of high-momentum jet fragments opposite the trigger particle, which indicates jet suppression stemming from in-medium partonic energy loss, while enhancement is observed for low-momentum particles. The ratio and differences between the yield in Au+Au collisions and p+p collisions, IAA and ∆AA, as a function of the trigger-hadron azimuthal separation, ∆ϕ, are measured for the first time at the Relativistic Heavy Ion Collider. These results better quantify how the yield of low-pT associated hadrons is enhanced at wide angle, which is crucial for studying energy loss as well as medium-response effects