Polyphosphatases have a polyphosphate-independent influence on the virulence of .

an invasive basidiomycete fungal pathogen, causes one of the most prevalent, life-threatening diseases in immunocompromised individuals and accounts for ~19% of AIDS-associated deaths. Therefore, understanding the pathogenesis of and its interactions with the host immune system is critical for developing therapeutics against cryptococcosis. Previous studies demonstrated that cells lacking polyphosphate (polyP), an immunomodulatory polyanionic storage molecule, display altered cell surface architecture but unimpaired virulence in a murine model of cryptococcosis.

Herbicides as fungicides: Targeting heme biosynthesis in the maize pathogen Ustilago maydis.

Pathogens must efficiently acquire nutrients from host tissue to proliferate, and strategies to block pathogen access therefore hold promise for disease control. In this study, we investigated whether heme biosynthesis is an effective target for ablating the virulence of the phytopathogenic fungus Ustilago maydis on maize plants. We first constructed conditional heme auxotrophs of the fungus by placing the heme biosynthesis gene hem12 encoding uroporphyrinogen decarboxylase (Urod) under the control of nitrogen or carbon source-regulated promoters.

Phosphate availability conditions caspofungin tolerance, capsule attachment and titan cell formation in .

There is an urgent need for new antifungal drugs to treat invasive fungal diseases. Unfortunately, the echinocandin drugs that are fungicidal against other important fungal pathogens are ineffective against , the causative agent of life-threatening meningoencephalitis in immunocompromised people. Contributing mechanisms for echinocandin tolerance are emerging with connections to calcineurin signaling, the cell wall, and membrane composition.

The Monothiol Glutaredoxin Grx4 Influences Iron Homeostasis and Virulence in .

The corn smut fungus, , is an excellent model for studying biotrophic plant-pathogen interactions, including nutritional adaptation to the host environment. Iron acquisition during host colonization is a key aspect of microbial pathogenesis yet less is known about this process for fungal pathogens of plants. Monothiol glutaredoxins are central regulators of key cellular functions in fungi, including iron homeostasis, cell wall integrity, and redox status via interactions with transcription factors, iron-sulfur clusters, and glutathione.

Organic acids and glucose prime late-stage fungal biotrophy in maize.

Many plant-associated fungi are obligate biotrophs that depend on living hosts to proliferate. However, little is known about the molecular basis of the biotrophic lifestyle, despite the impact of fungi on the environment and food security. In this work, we show that combinations of organic acids and glucose trigger phenotypes that are associated with the late stage of biotrophy for the maize pathogen .

The phosphate language of fungi.

Phosphate is an essential macronutrient for fungal proliferation as well as a key mediator of antagonistic, beneficial, and pathogenic interactions between fungi and other organisms. In this review, we summarize recent insights into the integration of phosphate metabolism with mechanisms of fungal adaptation that support growth and survival. In particular, we highlight aspects of phosphate sensing important for responses to stress and regulation of cell-surface changes with an impact on fungal pathogenesis, host immune responses, and disease outcomes.

Chloroplasts and Plant Immunity: Where Are the Fungal Effectors?

Chloroplasts play a central role in plant immunity through the synthesis of secondary metabolites and defense compounds, as well as phytohormones, such as jasmonic acid and salicylic acid. Additionally, chloroplast metabolism results in the production of reactive oxygen species and nitric oxide as defense molecules. The impact of viral and bacterial infections on plastids and chloroplasts has been well documented.

Clinical relevance of metal artefact reduction in computed tomography (iMAR) in the pelvic and head and neck region: Multi-institutional contouring study of gross tumour volumes and organs at risk on clinical cases.

Introduction: Artefacts caused by dental implants and hip replacements may impede target volume definition and dose calculation accuracy. The iterative metal artefact reduction (iMAR) algorithm can provide a solution for this problem. The present study compares delineation of gross tumour volumes (GTVs) and organs at risk (OARs) in the pelvic and the head and neck (H & N) regions using computed tomography (CT) with and without iMAR, and thus the practical applicability of iMAR for routine clinical use.

Transcripts and tumors: regulatory and metabolic programming during biotrophic phytopathogenesis.

Biotrophic fungal pathogens of plants must sense and adapt to the host environment to complete their life cycles. Recent transcriptome studies of the infection of maize by the biotrophic pathogen are providing molecular insights into an ordered program of changes in gene expression and the deployment of effectors as well as key features of nutrient acquisition. In particular, the transcriptome data provide a deeper appreciation of the complexity of the transcription factor network that controls the biotrophic program of invasion, proliferation, and sporulation.

Acetate provokes mitochondrial stress and cell death in Ustilago maydis.

The fungal pathogen Ustilago maydis causes disease on maize by mating to establish an infectious filamentous cell type that invades the host and induces tumours. We previously found that β-oxidation mutants were defective in virulence and did not grow on acetate. Here, we demonstrate that acetate inhibits filamentation during mating and in response to oleic acid.

Impurities in Oligonucleotide Drug Substances and Drug Products.

This white paper, which is the 10th in a series intended to address issues associated with the development of therapeutic oligonucleotides, examines the subject of product-related impurities. The authors consider chemistry and safety aspects and advance arguments in favor of platform approaches to impurity identification and qualification. Reporting, identification, and qualification thresholds suitable for product-related impurities of therapeutic oligonucleotides are proposed.

Planning benchmark study for SBRT of early stage NSCLC : Results of the DEGRO Working Group Stereotactic Radiotherapy.

Purpose: The aim was to evaluate stereotactic body radiation therapy (SBRT) treatment planning variability for early stage nonsmall cell lung cancer (NSCLC) with respect to the published guidelines of the Stereotactic Radiotherapy Working Group of the German Society for Radiation Oncology (DEGRO).

Materials And Methods: Planning computed tomography (CT) scan and the structure sets (planning target volume, PTV; organs at risk, OARs) of 3 patients with early stage NSCLC were sent to 22 radiotherapy departments with SBRT experience: each department was asked to prepare a treatment plan according to the DEGRO guidelines. The prescription dose was 3 fractions of 15 Gy to the 65% isodose.

Phosphorus-rich structures and capsular architecture in Cryptococcus neoformans.

Aim: In this study, we aimed to analyze the relationship of phosphorus-rich structures with surface architecture in Cryptococcus neoformans.

Methods: Phosphorus-rich structures in C. neoformans were analyzed by combining fluorescence microscopy, biochemical extraction, scanning electron microscopy, electron probe x-ray microanalysis and 3D reconstruction of high pressure frozen and freeze substituted cells by focused ion beam-scanning electron microscopy (FIB-SEM).

A P4-ATPase subunit of the Cdc50 family plays a role in iron acquisition and virulence in Cryptococcus neoformans.

The pathogenic fungus Cryptococcus neoformans delivers virulence factors such as capsule polysaccharide to the cell surface to cause disease in vertebrate hosts. In this study, we screened for mutants sensitive to the secretion inhibitor brefeldin A to identify secretory pathway components that contribute to virulence. We identified an ortholog of the cell division control protein 50 (Cdc50) family of the noncatalytic subunit of type IV P-type ATPases (flippases) that establish phospholipid asymmetry in membranes and function in vesicle-mediated trafficking.

Maize susceptibility to Ustilago maydis is influenced by genetic and chemical perturbation of carbohydrate allocation.

The ability of biotrophic fungi to metabolically adapt to the host environment is a critical factor in fungal diseases of crop plants. In this study, we analysed the transcriptome of maize tumours induced by Ustilago maydis to identify key features underlying metabolic shifts during disease. Among other metabolic changes, this analysis highlighted modifications during infection in the transcriptional regulation of carbohydrate allocation and starch metabolism.

Chloroplast-associated metabolic functions influence the susceptibility of maize to Ustilago maydis.

Biotrophic fungal pathogens must evade or suppress plant defence responses to establish a compatible interaction in living host tissue. In addition, metabolic changes during disease reflect both the impact of nutrient acquisition by the fungus to support proliferation and the integration of metabolism with the plant defence response. In this study, we used transcriptome analyses to predict that the chloroplast and associated functions are important for symptom formation by the biotrophic fungus Ustilago maydis on maize.

Treatment of breast cancer with simultaneous integrated boost in hybrid plan technique : Influence of flattening filter-free beams.

Objective: The present study compares in silico treatment plans using hybrid plan technique during hypofractionated radiation of mammary carcinoma with simultaneous integrated boost (SIB). The influence of 6 MV photon radiation in flattening filter free (FFF) mode against the clinical standard flattening filter (FF) mode is to be examined.

Patients And Methods: RT planning took place with FF and FFF radiation plans for 10 left-sided breast cancer patients.

The putative phospholipase Lip2 counteracts oxidative damage and influences the virulence of Ustilago maydis.

Ustilago maydis is an obligate biotrophic fungal pathogen which causes common smut disease of corn. To proliferate in host tissue, U. maydis must gain access to nutrients and overcome plant defence responses, such as the production of reactive oxygen species.

Heart dose reduction in breast cancer treatment with simultaneous integrated boost: Comparison of treatment planning and dosimetry for a novel hybrid technique and 3D-CRT.

Objective: The present study compares in silico treatment plans of clinically established three-dimensional conformal radiotherapy (3D-CRT) with a hybrid technique consisting of intensity-modulated radiotherapy (IMRT) and volumetric modulated arc radiotherapy (VMAT) during normally fractionated radiation of mammary carcinomas with simultaneous integrated boost on the basis of dose-volume histogram (DVH) parameters.

Patients And Methods: Radiation treatment planning was performed with a hybrid and a 3D-CRT treatment plan for 20 patients. Hybrid plans were implemented with two tangential IMRT fields and a VMAT field in the angular range of the tangents.

Defects in phosphate acquisition and storage influence virulence of Cryptococcus neoformans.

Nutrient acquisition and sensing are critical aspects of microbial pathogenesis. Previous transcriptional profiling indicated that the fungal pathogen Cryptococcus neoformans, which causes meningoencephalitis in immunocompromised individuals, encounters phosphate limitation during proliferation in phagocytic cells. We therefore tested the hypothesis that phosphate acquisition and polyphosphate metabolism are important for cryptococcal virulence.

Incidental dose to coronary arteries is higher in prone than in supine whole breast irradiation. A dosimetric comparison in adjuvant radiotherapy of early stage breast cancer.

Purpose: Sparing of normal lung is best achieved in prone whole breast irradiation (WBI). However, exposure of the heart and coronary arteries might increase due to anterior movement of the heart in prone WBI.

Patients And Methods: Treatment plans of 46 patients with large breasts irradiated for mammary cancer after breast-conserving surgery were retrospectively analyzed.

The impact of flattening-filter-free beam technology on 3D conformal RT.

Background: The removal of the flattening filter (FF) leads to non-uniform fluence distribution with a considerable increase in dose rate. It is possible to adapt FFF beams (flattening-filter-free) in 3D conformal radiation therapy (3D CRT) by using field in field techniques (FiF). The aim of this retrospective study is to clarify whether the quality of 3D CRT plans is influenced by the use of FFF beams.

Peroxisomal and mitochondrial β-oxidation pathways influence the virulence of the pathogenic fungus Cryptococcus neoformans.

An understanding of the connections between metabolism and elaboration of virulence factors during host colonization by the human-pathogenic fungus Cryptococcus neoformans is important for developing antifungal therapies. Lipids are abundant in host tissues, and fungal pathogens in the phylum basidiomycota possess both peroxisomal and mitochondrial β-oxidation pathways to utilize this potential carbon source. In addition, lipids are important signaling molecules in both fungi and mammals.

Defects in mitochondrial and peroxisomal β-oxidation influence virulence in the maize pathogen Ustilago maydis.

An understanding of metabolic adaptation during the colonization of plants by phytopathogenic fungi is critical for developing strategies to protect crops. Lipids are abundant in plant tissues, and fungal phytopathogens in the phylum basidiomycota possess both peroxisomal and mitochondrial β-oxidation pathways to utilize this potential carbon source. Previously, we demonstrated a role for the peroxisomal β-oxidation enzyme Mfe2 in the filamentous growth, virulence, and sporulation of the maize pathogen Ustilago maydis.