Functional analysis of yeast snoRNA and snRNA 3' end formation mediated by uncoupling of cleavage and polyadenylation

Many nuclear and nucleolar small RNAs are accumulated as nonpolyadenylated species and require 3′-end processing for maturation. Here, we show that several genes coding for box C/D and H/ACA snoRNAs and for the U5 and U2 snRNAs contain sequences in their 3′ portions which direct cleavage of primary transcripts without being polyadenylated. Genetic analysis of yeasts with mutations in different components of the pre-mRNA cleavage and polyadenylation machinery suggests that this mechanism of 3"-end formation requires cleavage factor IA (CF IA) but not cleavage and polyadenylation factor activity. However, in vitro results indicate that other factors participate in the reaction besides CF IA. Sequence analysis of snoRNA genes indicated that they contain conserved motifs in their 3" noncoding regions, and mutational studies demonstrated their essential role in 3"-end formation. We propose a model in which CF IA functions in cleavage and polyadenylation of pre-mRNAs and, in combination with a different set of factors, in 3"-end formation of nonpolyadenylated polymerase II transcripts.

Painful nipples in nursing mothers: fungal or staphylococcal?

Painful nipples, or ‘breast thrush’, in nursing mothers is a well recognised condition. It is a clinical diagnosis characterised by intense nipple pain often radiating into the breast, especially during breastfeeding. Between feeds it may cause a burning sensation and tenderness; breastfeeding may be abandoned because of it.

Self-assembly of functional, amphipathic amyloid monolayers by the fungal hydrophobin EAS

The hydrophobin EAS from the fungus Neurospora crassa forms functional amyloid fibrils called rodlets that facilitate spore formation and dispersal. Self-assembly of EAS into fibrillar rodlets occurs spontaneously at hydrophobic:hydrophilic interfaces and the rodlets further associate laterally to form amphipathic monolayers. We have used site-directed mutagenesis and peptide experiments to identify the region of EAS that drives intermolecular association and formation of the cross-β rodlet structure. Transplanting this region into a nonamyloidogenic hydrophobin enables it to form rodlets. We have also determined the structure and dynamics of an EAS variant with reduced rodlet-forming ability. Taken together, these data allow us to pinpoint the conformational changes that take place when hydrophobins self-assemble at an interface and to propose a model for the amphipathic EAS rodlet structure.

Fungal Mastoiditis in immunocompromised children

The immunocompromised host is subject to a variety of opportunistic infections. Mycotic infections, including invasive fungal sinusitis, are a dreaded complication in immune deficient children. Fungal mastoiditis has rarely been described in this population. Our experience with 2 cases of fungal mastoiditis in immunocompromised children is reviewed. Case histories describing aggressive medical management with and without surgical intervention and a review of the literature are presented.Fungal mastoiditis is a rare entity described in isolated case reports in the adult literature. It is seen almost entirely in immunocompromised patients, particularly those lacking cell-mediated immunity. The first case of Aspergillus mastoiditis was described in 1985.1 Reports of fungal mastoiditis have been primarily of patients with leukemia, and, more recently, of patients with acquired immunodeficiency syndrome.2,3 Using a computerized search of the MEDLINE database, we identified 1 report (in a non–English language journal) of fungal mastoiditis in a pediatric patient.4 We report 2 cases of fungal mastoiditis in immunosuppressed children.

Consensus guidelines for implementation of quality processes to prevent invasive fungal disease and enhanced surveillance measures during hospital building works, 2014

Healthcare-associated fungal outbreaks impose a substantial economic burden on the health system and typically result in high patient morbidity and mortality, particularly in the immunocompromised host. As the population at risk of invasive fungal infection continues to grow due to the increased burden of cancer and related factors, the need for hospitals to employ preventative measures has become increasingly important. These guidelines outline the standard quality processes hospitals need to accommodate into everyday practice and at times of healthcare-associated outbreak, including the role of antifungal stewardship programmes and best practice environmental sampling. Specific recommendations are also provided to help guide the planning and implementation of quality processes and enhanced surveillance before, during and after high-risk activities, such as hospital building works. Areas in which information is still lacking and further research is required are also highlighted.

The putative role of viruses, bacteria, and chronic fungal biotoxin exposure in the genesis of intractable fatigue accompanied by cognitive and physical disability

Patients who present with severe intractable apparently idiopathic fatigue accompanied by profound physical and or cognitive disability present a significant therapeutic challenge. The effect of psychological counseling is limited, with significant but very slight improvements in psychometric measures of fatigue and disability but no improvement on scientific measures of physical impairment compared to controls. Similarly, exercise regimes either produce significant, but practically unimportant, benefit or provoke symptom exacerbation. Many such patients are afforded the exclusionary, non-specific diagnosis of chronic fatigue syndrome if rudimentary testing fails to discover the cause of their symptoms. More sophisticated investigations often reveal the presence of a range of pathogens capable of establishing life-long infections with sophisticated immune evasion strategies, including Parvoviruses, HHV6, variants of Epstein-Barr, Cytomegalovirus, Mycoplasma, and Borrelia burgdorferi. Other patients have a history of chronic fungal or other biotoxin exposure. Herein, we explain the epigenetic factors that may render such individuals susceptible to the chronic pathology induced by such agents, how such agents induce pathology, and, indeed, how such pathology can persist and even amplify even when infections have cleared or when biotoxin exposure has ceased. The presence of active, reactivated, or even latent Herpes virus could be a potential source of intractable fatigue accompanied by profound physical and or cognitive disability in some patients, and the same may be true of persistent Parvovirus B12 and mycoplasma infection. A history of chronic mold exposure is a feasible explanation for such symptoms, as is the presence of B. burgdorferi. The complex tropism, life cycles, genetic variability, and low titer of many of these pathogens makes their detection in blood a challenge. Examination of lymphoid tissue or CSF in such circumstances may be warranted.

Diversity of root-associated arbuscular mycorrhizal fungal communities in a rubber tree plantation chronosequence in Northeast Thailand

Rubber tree (Hevea brasiliensis) is of major economic importance in Southeast Asia and for small land holders in Thailand in particular. Due to the high value of latex, plantations are expanding into unsuitable areas, such as the northeast province of Thailand where soil fertility is very low and therefore appropriate management practices are of primary importance. Arbuscular mycorrhizal fungi (AMF) contribute to plant growth through a range of mechanisms and could play a key role in a more sustainable management of the rubber plantations. We described the diversity of AMF associated with rubber tree roots in Northeast Thailand in relation to tree age and soil parameters along a chronosequence of rubber tree plantations. Cassava fields were included for comparison. Rubber tree and cassava roots harbored high diversity of AMF (111 Virtual Taxa, VT), including 20 novel VT. AMF VT richness per sample was consistently high (per site mean 16 to 21 VT per sample) along the chronosequence and was not related to soil properties. The composition of AMF communities differed between cassava and rubber tree plantations and was influenced by soil texture and nutrient content (sand, K, P, Ca). AMF community composition gradually shifted with the age of the trees. Our results suggest that the high diversity of AMF in this region is potentially significant for maintaining high functionality of AMF communities.

Associations between outdoor fungal spores and childhood and adolescent asthma hospitalisations.

BACKGROUND: Childhood asthma is a significant public health problem and severe exacerbations can result in diminished quality of life and hospitalisation. OBJECTIVE: To examine the contribution of outdoor fungi to childhood and adolescent asthma hospitalisations. METHODS: The Melbourne Air Pollen Children and Adolescent (MAPCAH) study is a case-crossover study of 644 children and adolescents (aged 2-17 years) hospitalised for asthma. MAPCAH collected individual data on human rhinovirus (HRV) infection and sensitisation to Alternaria and Cladosporium; and daily counts of ambient concentrations of fungal spores, pollen and air pollutants. Conditional logistic regression models were used to assess associations with increases in spore counts while controlling for potential confounding and testing interactions. RESULTS: Exposure to Alternaria (aOR=1.07, 95%CI 1.03-1.11), Leptosphaeria (aOR=1.05, 95%CI 1.02-1.07), Coprinus (aOR=1.04, 95%CI 1.01-1.07), Drechslera (aOR=1.03, 95%CI1.00-1.05) and total spores (aOR=1.05, 95%CI 1.01-1.09) were significantly associated with child asthma hospitalisations independent of HRV infection. There were significant lagged effects up to 3-days with Alternaria, Leptosphaeria, Cladosporium, Sporormiella, Coprinus, and Drechslera. Some of these associations were significantly greater in participants with Cladosporium sensitisation. CONCLUSION: Exposures to several outdoor fungal spore taxa, including some not reported in previous research, are associated with the risk of child and adolescent asthma hospitalisation, particularly in individuals sensitised to Cladosporium. We need further studies to examine cross-reactivity causing asthma exacerbations. Identifying sensitisation to multiple fungal allergens in asthmatic children could support the design and implementation of more effective strategies to prevent asthma exacerbations.