Publications by authors named "Aust T"

The physiology of living organisms, such as living plants, is complex and particularly difficult to understand on a macroscopic, organism-holistic level. Among the many options for studying plant physiology, electrical potential and tissue impedance are arguably simple measurement techniques that can be used to gather plant-level information. Despite the many possible uses, our research is exclusively driven by the idea of phytosensing, that is, interpreting living plants' signals to gather information about surrounding environmental conditions.

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The plant cuticle is a multifunctional barrier that separates the organs of the plant from the surrounding environment. Cuticular ridges are microscale wrinkle-like cuticular protrusions that occur on many flower and leaf surfaces. These microscopic ridges can help against pest insects by reducing the frictional forces experienced when they walk on the leaves and might also provide mechanical stability to the growing plant organs.

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 In recent years, new arthroscopic techniques have been introduced to address the irreparable tears of the triangular fibrocartilage complex (TFCC) (Palmer type 1B, Atzei class 4) by replicating the standard Adams-Berger procedure. These techniques, however, show the same limitations of the open procedure in relation to the anatomically defective location of the radial origins of the radioulnar ligaments (RUL) and the risk of neurovascular and/or tendon injury. Aiming to improve the quality of reconstruction and reduce surgical morbidity, a novel arthroscopic technique was developed, with the advantages of reproducing the anatomical origins of the RUL ligaments and providing all-inside tendon graft (TG) deployment and fixation.

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Biosynthesis of glycosylphosphatidylinositol (GPI) is required for anchoring proteins to the plasma membrane, and is essential for the integrity of the fungal cell wall. Here, we use a reporter gene-based screen in Saccharomyces cerevisiae for the discovery of antifungal inhibitors of GPI-anchoring of proteins, and identify the oligocyclopropyl-containing natural product jawsamycin (FR-900848) as a potent hit. The compound targets the catalytic subunit Spt14 (also referred to as Gpi3) of the fungal UDP-glycosyltransferase, the first step in GPI biosynthesis, with good selectivity over the human functional homolog PIG-A.

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Selective and specific inhibitors of Plasmodium falciparum lysyl-tRNA synthetase represent promising therapeutic antimalarial avenues. Cladosporin was identified as a potent P. falciparum lysyl-tRNA synthetase inhibitor, with an activity against parasite lysyl-tRNA synthetase >100-fold more potent than that of the activity registered against the human enzyme.

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Invasive fungal infections are accompanied by high mortality rates that range up to 90%. At present, only three different compound classes are available for use in the clinic, and these often suffer from low bioavailability, toxicity, and drug resistance. These issues emphasize an urgent need for novel antifungal agents.

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Flavivirus infections by Zika and dengue virus impose a significant global healthcare threat with no US Food and Drug Administration (FDA)-approved vaccination or specific antiviral treatment available. Here, we present the discovery of an anti-flaviviral natural product named cavinafungin. Cavinafungin is a potent and selectively active compound against Zika and all four dengue virus serotypes.

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Phenotypic screens are effective starting points to identify compounds with desirable activities. To find novel antifungals, we conducted a phenotypic screen in Saccharomyces cerevisiae and identified two discrete scaffolds with good growth inhibitory characteristics. Lack of broad-spectrum activity against pathogenic fungi called for directed chemical compound optimization requiring knowledge of the molecular target.

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FR171456 is a natural product with cholesterol-lowering properties in animal models, but its molecular target is unknown, which hinders further drug development. Here we show that FR171456 specifically targets the sterol-4-alpha-carboxylate-3-dehydrogenase (Saccharomyces cerevisiae--Erg26p, Homo sapiens--NSDHL (NAD(P) dependent steroid dehydrogenase-like)), an essential enzyme in the ergosterol/cholesterol biosynthesis pathway. FR171456 significantly alters the levels of cholesterol pathway intermediates in human and yeast cells.

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Cultivation of myxobacteria of the Nannocystis genus led to the isolation and structure elucidation of a class of novel cyclic lactone inhibitors of elongation factor 1. Whole genome sequence analysis and annotation enabled identification of the putative biosynthetic cluster and synthesis process. In biological assays the compounds displayed anti-fungal and cytotoxic activity.

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A new cyclic decadepsipeptide was isolated from Chaetosphaeria tulasneorum with potent bioactivity on mammalian and yeast cells. Chemogenomic profiling in S. cerevisiae indicated that the Sec61 translocon complex, the machinery for protein translocation and membrane insertion at the endoplasmic reticulum, is the target.

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Article Synopsis
  • Experimental studies on eukaryotic model organisms, particularly yeast, provide valuable insights into human cellular pathways and physiology through chemogenomic profiling of nearly 1800 small molecules.
  • The resulting data reveals the sensitivity of various biological pathways to specific compounds, helping to identify new inhibitors and mechanisms of action for important processes such as fatty acid synthesis and respiration.
  • This research also includes the identification of background mutations in yeast deletion collections, which enhances the accuracy of future research and contributes to a deeper understanding of eukaryotic biology.
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We report the case of a 37-year-old woman who developed idiopathic brachial plexus neuritis, also referred to as Parsonage-Turner syndrome, after laparoscopic excision of endometriosis. The differential diagnosis between this non-position-related neuritis and brachial plexus injury is discussed. The aim of this report was to raise awareness on this distressing postoperative complication.

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Translation initiation is an emerging target in oncology and neurobiology indications. Naturally derived and synthetic rocaglamide scaffolds have been used to interrogate this pathway; however, there is uncertainty regarding their precise mechanism(s) of action. We exploited the genetic tractability of yeast to define the primary effect of both a natural and a synthetic rocaglamide in a cellular context and characterized the molecular target using biochemical studies and in silico modeling.

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High-throughput phenotypic screening against the yeast Saccharomyces cerevisiae revealed a series of triazolopyrimidine-sulfonamide compounds with broad-spectrum antifungal activity, no significant cytotoxicity, and low protein binding. To elucidate the target of this series, we have applied a chemogenomic profiling approach using the S. cerevisiae deletion collection.

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Article Synopsis
  • * Argyrin B binds to a unique allosteric site on EF-G, presenting a new mechanism of inhibiting protein synthesis, different from established antibiotics like fusidic acid.
  • * In eukaryotic cells, argyrin B disrupts mitochondrial protein synthesis by targeting mitochondrial elongation factor G1 (EF-G1), leading to growth inhibition in yeast and cancer cells, suggesting its potential as a therapeutic agent.
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With renewed calls for malaria eradication, next-generation antimalarials need be active against drug-resistant parasites and efficacious against both liver- and blood-stage infections. We screened a natural product library to identify inhibitors of Plasmodium falciparum blood- and liver-stage proliferation. Cladosporin, a fungal secondary metabolite whose target and mechanism of action are not known for any species, was identified as having potent, nanomolar, antiparasitic activity against both blood and liver stages.

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Article Synopsis
  • The text discusses a surgical technique for uterine artery ligation using an anterior approach during laparoscopic procedures, specifically myomectomy and hysterectomy.
  • The method involves clipping the uterine artery while reducing the risk of complications, and results from a study on 38 myomectomies and 28 hysterectomies are presented.
  • The study noted minimal conversions to open surgery and only one postoperative transfusion, suggesting that this approach is effective for treating large uterine fibroids.
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Objective: To describe a case in which a midline laparotomy for two presumed malignant masses instead revealed parasitic fibroids.

Design: Case report.

Setting: Tertiary-level private hospital.

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Objective: To describe the laparoscopic management of an interstitial gestation of a heterotopic pregnancy.

Design: Case report and technique description.

Setting: Tertiary-level private practice.

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Background: We wanted to test the hypothesis that using abdominal ultrasound at the time of embryo transfer to guide replacement, improved pregnancy rates by at least 5%.

Methods: An RCT in a large assisted conception unit. A pilot study and power calculation suggested that at least 2000 embryo transfers were required to demonstrate a difference of 5%, for a test with 80% power and Type 1 error 0.

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Objective: To design a new method for oral preparation of urine for sperm retrieval after retrograde ejaculation (RE) and to test the motility of sperm exposed to prepared and unprepared urine.

Design: In vitro testing of urine conditions and sperm motility.

Setting: Assisted conception unit at a teaching hospital in the United Kingdom.

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