Post-genomic approaches to understanding interactions between fungi and their environment

Fungi inhabit every natural and anthropogenic environment on Earth. They have highly varied life-styles including saprobes (using only dead biomass as a nutrient source), pathogens (feeding on living biomass), and symbionts (co-existing with other organisms). These distinctions are not absolute as many species employ several life styles (e.g. saprobe and opportunistic pathogen, saprobe and mycorrhiza). To efficiently survive in these different and often changing environments, fungi need to be able to modify their physiology and in some cases will even modify their local environment. Understanding the interaction between fungi and their environments has been a topic of study for many decades. However, recently these studies have reached a new dimension. The availability of fungal genomes and development of post-genomic technologies for fungi, such as transcriptomics, proteomics and metabolomics, have enabled more detailed studies into this topic resulting in new insights. Based on a Special Interest Group session held during IMC9, this paper provides examples of the recent advances in using (post-)genomic approaches to better understand fungal interactions with their environments

Thoracic spine pain in the general population: Prevalence, incidence and associated factors in children, adolescents and adults. A systematic review

<p>Abstract</p> <p>Background</p> <p>Thoracic spine pain (TSP) is experienced across the lifespan by healthy individuals and is a common presentation in primary healthcare clinical practice. However, the epidemiological characteristics of TSP are not well documented compared to neck and low back pain. A rigorous evaluation of the prevalence, incidence, correlates and risk factors needs to be undertaken in order for epidemiologic data to be meaningfully used to develop evidence-based prevention and treatment recommendations for TSP.</p> <p>Methods</p> <p>A systematic review method was followed to report the evidence describing prevalence, incidence, associated factors and risk factors for TSP among the general population. Nine electronic databases were systematically searched to identify studies that reported either prevalence, incidence, associated factors (cross-sectional study) or risk factors (prospective study) for TSP in healthy children, adolescents or adults. Studies were evaluated for level of evidence and method quality.</p> <p>Results</p> <p>Of the 1389 studies identified in the literature, 33 met the inclusion criteria for this systematic review. The mean (SD) quality score (out of 15) for the included studies was 10.5 (2.0). TSP prevalence data ranged from 4.0–72.0% (point), 0.5–51.4% (7-day), 1.4–34.8% (1-month), 4.8–7.0% (3-month), 3.5–34.8% (1-year) and 15.6–19.5% (lifetime). TSP prevalence varied according to the operational definition of TSP. Prevalence for any TSP ranged from 0.5–23.0%, 15.8–34.8%, 15.0–27.5% and 12.0–31.2% for 7-day, 1-month, 1-year and lifetime periods, respectively. TSP associated with backpack use varied from 6.0–72.0% and 22.9–51.4% for point and 7-day periods, respectively. TSP interfering with school or leisure ranged from 3.5–9.7% for 1-year prevalence. Generally, studies reported a higher prevalence for TSP in child and adolescent populations, and particularly for females. The 1 month, 6 month, 1 year and 25 year incidences were 0–0.9%, 10.3%, 3.8–35.3% and 9.8% respectively. TSP was significantly associated with: concurrent musculoskeletal pain; growth and physical; lifestyle and social; backpack; postural; psychological; and environmental factors. Risk factors identified for TSP in adolescents included age (being older) and poorer mental health.</p> <p>Conclusion</p> <p>TSP is a common condition in the general population. While there is some evidence for biopsychosocial associations it is limited and further prospectively designed research is required to inform prevention and management strategies.</p

A Systematic Analysis of the Clinical Outcome Associated with Multiple Reclassified Desmosomal Gene Variants in Arrhythmogenic Right Ventricular Cardiomyopathy Patients

The presence of multiple pathogenic variants in desmosomal genes (DSC2, DSG2, DSP, JUP, and PKP2) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been linked to a severe phenotype. However, the pathogenicity of variants is reclassified frequently, which may result in a changed clinical risk prediction. Here, we present the collection, reclassification, and clinical outcome correlation for the largest series of ARVC patients carrying multiple desmosomal pathogenic variants to date (n = 331). After reclassification, only 29% of patients remained carriers of two (likely) pathogenic variants. They reached the composite endpoint (ventricular arrhythmias, heart failure, and death) significantly earlier than patients with one or no remaining reclassified variant (hazard ratios of 1.9 and 1.8, respectively). Periodic reclassification of variants contributes to more accurate risk stratification and subsequent clinical management strategy. [Figure not available: see fulltext.]

The cardiac troponin C mutation Leu29Gln found in a patient with hypertrophic cardiomyopathy does not alter contractile parameters in skinned murine myocardium

The present study investigates the effects of the first mutation of troponin C (hcTnCL29Q) found in a patient with hypertrophic cardiomyopathy (HCM) on force–pCa relations and the interplay with phosphorylation of sarcomeric PKA substrates. In triton-skinned murine cardiac fibers, the endogenous mcTnC was extracted and the fibers were subsequently reconstituted with recombinant wild-type and mutant hcTnC. Force–pCa relations of preparations containing hcTnCL29Q or hcTnCWT were similar. Incubation of fibers reconstituted with the recombinant proteins with phosphatase to dephosphorylate sarcomeric PKA substrates induced an increase in Ca2+ sensitivity, slightly more pronounced (0.04 pCa units) in hcTnCL29Q-containing fibers. Incubation of the dephosphorylated fibers with PKA induced significant rightward shifts of force–pCa relations of similar magnitude with both, hcTnCL29Q and hcTnCWT. No significant effects of hcTnCL29Q on the velocity of unloaded shortening were observed. In conclusion, no major differences in contractile parameters of preparations containing hcTnCL29Q compared to hcTnCWT were observed. Therefore, it appears unlikely that hcTnCL29Q induces the development of HCM by affecting the regulation of Ca2+-activated force and interference with PKA-mediated modulation of the Ca2+ sensitivity of contraction

Retinal Muller Glia Initiate Innate Response to Infectious Stimuli via Toll-Like Receptor Signaling

Ocular surgeries and trauma predispose the eye to develop infectious endophthalmitis, which often leads to vision loss. The mechanisms of initiation of innate defense in this disease are not well understood but are presumed to involve retinal glial cells. We hypothesize that retinal Muller glia can recognize and respond to invading pathogens via TLRs, which are key regulators of the innate immune system. Using the mouse retinal sections, human retinal Muller cell line (MIO-M1), and primary mouse retinal Muller cells, we show that they express known human TLR1-10, adaptor molecules MyD88, TRIF, TRAM, and TRAF6, and co-receptors MD2 and CD14. Consistent with the gene expression, protein levels were also detected for the TLRs. Moreover, stimulation of the Muller glia with TLR 2, 3, 4, 5, 7 and 9 agonists resulted in an increased TLR expression as assayed by Western blot and flow cytometry. Furthermore, TLR agonists or live pathogen (S. aureus, P. aeruginosa, & C. albicans)-challenged Muller glia produced significantly higher levels of inflammatory mediators (TNF-α, IL-1β, IL-6 and IL-8), concomitantly with the activation of NF-κB, p38 and Erk signaling. This data suggests that Muller glia directly contributes to retinal innate defense by recognizing microbial patterns under infectious conditions; such as those in endophthalmitis

Modeling Within-Host Dynamics of Influenza Virus Infection Including Immune Responses

Influenza virus infection remains a public health problem worldwide. The mechanisms underlying viral control during an uncomplicated influenza virus infection are not fully understood. Here, we developed a mathematical model including both innate and adaptive immune responses to study the within-host dynamics of equine influenza virus infection in horses. By comparing modeling predictions with both interferon and viral kinetic data, we examined the relative roles of target cell availability, and innate and adaptive immune responses in controlling the virus. Our results show that the rapid and substantial viral decline (about 2 to 4 logs within 1 day) after the peak can be explained by the killing of infected cells mediated by interferon activated cells, such as natural killer cells, during the innate immune response. After the viral load declines to a lower level, the loss of interferon-induced antiviral effect and an increased availability of target cells due to loss of the antiviral state can explain the observed short phase of viral plateau in which the viral level remains unchanged or even experiences a minor second peak in some animals. An adaptive immune response is needed in our model to explain the eventual viral clearance. This study provides a quantitative understanding of the biological factors that can explain the viral and interferon kinetics during a typical influenza virus infection

Thoracic spine pain in the general population: Prevalence, incidence and associated factors in children, adolescents and adults. A systematic review

<p>Abstract</p> <p>Background</p> <p>Thoracic spine pain (TSP) is experienced across the lifespan by healthy individuals and is a common presentation in primary healthcare clinical practice. However, the epidemiological characteristics of TSP are not well documented compared to neck and low back pain. A rigorous evaluation of the prevalence, incidence, correlates and risk factors needs to be undertaken in order for epidemiologic data to be meaningfully used to develop evidence-based prevention and treatment recommendations for TSP.</p> <p>Methods</p> <p>A systematic review method was followed to report the evidence describing prevalence, incidence, associated factors and risk factors for TSP among the general population. Nine electronic databases were systematically searched to identify studies that reported either prevalence, incidence, associated factors (cross-sectional study) or risk factors (prospective study) for TSP in healthy children, adolescents or adults. Studies were evaluated for level of evidence and method quality.</p> <p>Results</p> <p>Of the 1389 studies identified in the literature, 33 met the inclusion criteria for this systematic review. The mean (SD) quality score (out of 15) for the included studies was 10.5 (2.0). TSP prevalence data ranged from 4.0–72.0% (point), 0.5–51.4% (7-day), 1.4–34.8% (1-month), 4.8–7.0% (3-month), 3.5–34.8% (1-year) and 15.6–19.5% (lifetime). TSP prevalence varied according to the operational definition of TSP. Prevalence for any TSP ranged from 0.5–23.0%, 15.8–34.8%, 15.0–27.5% and 12.0–31.2% for 7-day, 1-month, 1-year and lifetime periods, respectively. TSP associated with backpack use varied from 6.0–72.0% and 22.9–51.4% for point and 7-day periods, respectively. TSP interfering with school or leisure ranged from 3.5–9.7% for 1-year prevalence. Generally, studies reported a higher prevalence for TSP in child and adolescent populations, and particularly for females. The 1 month, 6 month, 1 year and 25 year incidences were 0–0.9%, 10.3%, 3.8–35.3% and 9.8% respectively. TSP was significantly associated with: concurrent musculoskeletal pain; growth and physical; lifestyle and social; backpack; postural; psychological; and environmental factors. Risk factors identified for TSP in adolescents included age (being older) and poorer mental health.</p> <p>Conclusion</p> <p>TSP is a common condition in the general population. While there is some evidence for biopsychosocial associations it is limited and further prospectively designed research is required to inform prevention and management strategies.</p

Albumin-derived peptides efficiently reduce renal uptake of radiolabelled peptides

Contains fulltext : 88022.pdf (publisher's version ) (Closed access)PURPOSE: In peptide-receptor radionuclide therapy (PRRT), the maximum activity dose that can safely be administered is limited by high renal uptake and retention of radiolabelled peptides. The kidney radiation dose can be reduced by coinfusion of agents that competitively inhibit the reabsorption of radiolabelled peptides, such as positively charged amino acids, Gelofusine, or trypsinised albumin. The aim of this study was to identify more specific and potent inhibitors of the kidney reabsorption of radiolabelled peptides, based on albumin. METHODS: Albumin was fragmented using cyanogen bromide and six albumin-derived peptides with different numbers of electric charges were selected and synthesised. The effect of albumin fragments (FRALB-C) and selected albumin-derived peptides on the internalisation of (111)In-albumin, (111)In-minigastrin, (111)In-exendin and (111)In-octreotide by megalin-expressing cells was assessed. In rats, the effect of Gelofusine and albumin-derived peptides on the renal uptake and biodistribution of (111)In-minigastrin, (111)In-exendin and (111)In-octreotide was determined. RESULTS: FRALB-C significantly reduced the uptake of all radiolabelled peptides in vitro. The albumin-derived peptides showed different potencies in reducing the uptake of (111)In-albumin, (111)In-exendin and (111)In-minigastrin in vitro. The most efficient albumin-derived peptide (peptide #6), was selected for in vivo testing. In rats, 5 mg of peptide #6 very efficiently inhibited the renal uptake of (111)In-minigastrin, by 88%. Uptake of (111)In-exendin and (111)In-octreotide was reduced by 26 and 33%, respectively. CONCLUSIONS: The albumin-derived peptide #6 efficiently inhibited the renal reabsorption of (111)In-minigastrin, (111)In-exendin and (111)In-octreotide and is a promising candidate for kidney protection in PRRT.1 februari 201

Comparative genomic analysis reveals independent expansion of a lineage-specific gene family in vertebrates: The class II cytokine receptors and their ligands in mammals and fish

BACKGROUND: The high degree of sequence conservation between coding regions in fish and mammals can be exploited to identify genes in mammalian genomes by comparison with the sequence of similar genes in fish. Conversely, experimentally characterized mammalian genes may be used to annotate fish genomes. However, gene families that escape this principle include the rapidly diverging cytokines that regulate the immune system, and their receptors. A classic example is the class II helical cytokines (HCII) including type I, type II and lambda interferons, IL10 related cytokines (IL10, IL19, IL20, IL22, IL24 and IL26) and their receptors (HCRII). Despite the report of a near complete pufferfish (Takifugu rubripes) genome sequence, these genes remain undescribed in fish. RESULTS: We have used an original strategy based both on conserved amino acid sequence and gene structure to identify HCII and HCRII in the genome of another pufferfish, Tetraodon nigroviridis that is amenable to laboratory experiments. The 15 genes that were identified are highly divergent and include a single interferon molecule, three IL10 related cytokines and their potential receptors together with two Tissue Factor (TF). Some of these genes form tandem clusters on the Tetraodon genome. Their expression pattern was determined in different tissues. Most importantly, Tetraodon interferon was identified and we show that the recombinant protein can induce antiviral MX gene expression in Tetraodon primary kidney cells. Similar results were obtained in Zebrafish which has 7 MX genes. CONCLUSION: We propose a scheme for the evolution of HCII and their receptors during the radiation of bony vertebrates and suggest that the diversification that played an important role in the fine-tuning of the ancestral mechanism for host defense against infections probably followed different pathways in amniotes and fish