This article, co-authored by a psoriatic arthritis (PsA) patient and a physician who regularly encounters and treats PsA patients, discusses the patients experience of living with the disease, from diagnosis through living with the disease day-to-day and other peoples reactions to their treatment experiences and responses. The physician adds to this by providing his experiences in treating PsA with biologics, and the importance of patients working together with their rheumatologists to maximize the efficacy of treatments and improve patients quality of life.

Background

Messenger RNA (mRNA) represents a small percentage of RNAs in a cell, with ribosomal RNA (rRNA) making up the bulk of it. To isolate mRNA from eukaryotes, typically poly-A selection is carried out. Recently, a 5´-phosphate-dependent, 5´→3´ processive exonuclease called Terminator has become available. It will digest only RNA that has a 5´-monophosphate end and therefore it is very useful to eliminate most of rRNAs in cell.

Results

We have found that in the pathogenic yeast Candida albicans, while 18S and 25S components isolated from yeast in robust growth phase are easily eliminated by Terminator, those isolated from cells in the nutritionally diminished stationary phase, become resistant to digestion by this enzyme. Additional digestions with alkaline phosphatase, tobacco pyrophosphatase combined with Terminator point toward the 5'-prime end of 18S and 25S as the source of this resistance. Inhibition of TOR by rapamycin also induces resistance by these molecules. We also find that these molecules are incorporated into the ribosome and are not just produced incidentally. Finally, we show that three other yeasts show the same behavior.

Conclusions

Digestion of RNA by Terminator has revealed 18S and 25S rRNA molecules different from the accepted processed ones seen in ribosome generation. The reason for these molecules and the underlying mechanism for their formation is unknown. The preservation of this behavior across these yeasts suggests a useful biological role for it, worthy of further inquiry.

Abstract Background Candida species including Candida krusei have become common pathogens, especially in immune-compromised patients. Pellicle on the surface of incubating nutrient broth extending with an adherent film above the broth has been described as a feature of this organism. We investigated whether this easily observable adherent film could be useful in the identification of this yeast. We also wanted to see if this process involved any morphological changes from the yeast form on the part of C. krusei. Findings Common and less frequently isolated species of Candida were inoculated into YPD broth and observed for pellicle formation. For C. krusei different inoculum sizes and time periods were studied to establish earliest period and the smallest number of organisms needed for this process. A cover-slip assay was established to observe the architecture of the film formed by this organism. Among the clinically common Candida species, only C. krusei formed a visible film, requiring 106 organisms to produce it at 24 hours post inoculation. Film formation also differentiated C. krusei from C. inconspicua usually reported as a complex by carbohydrate assimilation assays. Rarely isolated C. famata and C. norvegensis also formed pellicles and film but less robustly. Microscopic observations of the film showed only yeast forms, no hypha or pseudohypha were seen. Conclusions Pellicle formation following inoculation of a clinical specimen into liquid culture, is a useful alert to the probable presence of C. krusei and likely fluconazole resistance, while awaiting the results of more definitive identification assays. Pellicle and adherence film formation are not a result of polymorphic changes on the part of C. krusei as only yeast forms were present.

Background: According to population-based cohort studies CT coronary calcium score (CTCS), carotid intima-media thickness (cIMT), high-sensitivity C- reactive protein (CRP), and ankle-brachial index (ABI) are promising novel risk markers for improving card

Background: Physicians need to inform asymptomatic individuals about personalized outcomes of statin therapy for primary prevention of cardiovascular disease (CVD). However, current prediction models focus on short-term outcomes and ignore the competing ri

Background

Candida krusei has been known to exhibit communal interactions such as pellicle formation and crawling out of nutritional broth. We noticed another possible interaction on agar surfaces, where C. krusei yeast cells formed mycelia along agar surfaces toward each other. We report here the results of experiments to study this interaction.

Results

When C.krusei yeast cells are plated in parallel streaks, they form mycelia along agar surfaces toward other yeasts. They also detect the presence of Candida albicans and Candida glabrata across agar surfaces, while the latter two react neither to their own kind, nor to C. krusei. Secreted molecule(s) are likely involved as C.krusei does not react to heat killed C. krusei. Timing and rate of mycelia formation across distances suggests that mycelia start forming when a secreted molecule(s) on agar surface reaches a certain concentration. We detected farnesol, tyrosol and tryptophol molecules that may be involved with mycelial formation, on the agar surfaces between yeast streaks. Unexpectedly the amounts detected between streaks were significantly higher than would have expected from additive amounts of two streaks. All three Candida species secreted these molecules. When tested on agar surface however, none of these molecules individually or combined induced mycelia formation by C. krusei.

Conclusions

Our data confirms another communal interaction by C. krusei, manifested by formation of mycelia by yeast cells toward their own kind and other yeasts on agar surfaces. We detected secretion of farnesol, tyrosol and tryptophol by C. krusei but none of these molecules induced this activity on agar surface making it unlikely that they are the ones utilized by this yeast for this activity.

Background

We have previously found that, in the pathogenic yeast Candida albicans, 18S and 25S ribosomal RNA components, containing more than one phosphate on their 5'-end were resistant to 5'-monophosphate requiring 5' → 3″ exonuclease. Several lines of evidence pointed to RNAP II as the enzyme producing them.

Results

We now show the production of such 18S and 25S rRNAs in Saccharomyces cerevisiae that have been permanently switched to RNAP II (due to deletion of part of RNAP I upstream activator alone, or in combination with deletion of one component of RNAP I itself). They contain more than one phosphate at their 5'-end and an anti-cap specific antibody binds to them indicating capping of these molecules. These molecules are found in RNA isolated from nuclei, therefore are unlikely to have been modified in the cytoplasm.

Conclusions

Our data confirm the existence of such molecules and firmly establish RNAP II playing a role in their production. The fact that we see these molecules in wild type Saccharomyces cerevisiae indicates that they are not only a result of mutations but are part of the cells physiology. This adds another way RNAP II is involved in ribosome production in addition to their role in the production of ribosome associated proteins.

Background

Little is known about the opinions of primary care clinicians regarding the newly released 2013 American College of Cardiology/American Heart Association (ACC/AHA) Guidelines for the Prevention of Primary and Secondary Atherosclerotic Disease. This survey was created to assess the awareness, attitudes, and practices of primary care clinicians on adoption of the new guidelines and to explore obstacles to implementation and suggestions for improving shared decision-making.

Methods

Six hundred practicing clinicians within the San Francisco Bay Area Collaborative Research Network were invited to participate in this cross-sectional, Internet-based pilot survey of primary care clinicians. These survey data were collected in March 2014, approximately 4 months after the release of the new guidelines and 1 month after the release of the ACC/AHA risk estimator application.

Results

One hundred eighty-three clinicians responded to the survey. Of those respondents, 176 (96%) were aware of the guidelines. The majority (64%) reported implementing the new guidelines with at least some of their patients, while a minority (25%) reported adopting the guidelines for many of their patients. Disagreeing with the guidelines was the main hindrance to adoption.

Conclusions

While many primary care clinicians are aware of the new guidelines, a substantial proportion has yet to implement them into their clinical practice, and obstacles remain for full adoption. Further understanding of clinicians' views, opinions, and needs is necessary to optimize the approach to lipid management and ensure integration into current practice.